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last updated: 2026-03-10_105728
file_name: _archive-combined-files_fda-policy_308k.md
category: regulatory
subcategory: fda-policy
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CONTENT

# _archive-combined-files_fda-policy_308k (48 files, 308,051 tokens)

# 1,795  _context-commentary_regulatory-fda-policy.md
METADATA
last updated: 2026-03-01 RT
file_name: _context-commentary_regulatory-fda-policy.md
category: regulatory
subcategory: fda-policy
words: 1160
tokens: 1795


CONTENT

## Context
This subcategory contains 47 documents spanning 2020–2023 that trace the evolution of FDA's regulatory policy for COVID-19 diagnostic testing. The collection includes seven versions of FDA's overarching COVID test policy guidance, EUA letters and amendment letters, review templates (molecular, antigen, home-use, pooling), fact sheet templates, FDA press announcements, and transition planning documents. Together they form a detailed record of how FDA managed the regulatory environment for COVID-19 tests from the earliest emergency through the end of the Public Health Emergency.
This collection is not complete and are mostly the documents that we downloaded and reviewed at FloodLAMP. There are almost certainly other important documents that are not included here.

#### AI Summary of FDA Policy
Below is an AI (ChatGPT 5.2 Pro and Claude Opus 4.6) generated summary, which may contain errors.

The FDA policy COVID-19 testing policy evolved through three broad phases:

- **Emergency expansion (early 2020):** FDA used enforcement discretion to allow CLIA high-complexity labs to develop, validate, and begin using molecular tests before EUA issuance, provided labs notified FDA and submitted an EUA within a set timeframe. Guidance versions 1–4 (Feb–May 2020) progressively broadened these pathways to include state authorization, commercial manufacturers, and serology.
- **Standardization and new use cases (mid-2020–2021):** FDA tightened quality oversight (notably revoking the serology umbrella EUA pathway), introduced standardized templates, and expanded authorized intended uses from "suspected COVID-19" into explicit asymptomatic screening and pooled testing. Serial testing emerged as a formal authorization strategy, and variant monitoring became a standard EUA condition.
- **Narrowing and wind-down (2022–2023):** FDA reduced the scope of new EUA reviews, encouraged developers toward traditional marketing pathways (510(k)/De Novo), standardized repeat-testing labeling for consumer antigen tests, and published transition plans for returning to normal device regulation. The COVID-19 PHE expired May 11, 2023, but FDA clarified that existing EUAs remain in effect as long as the underlying EUA declaration persists.

Key points of variation across the seven guidance versions:

| Version | Date | Key Change |
| --- | --- | --- |
| v1 | Feb 29, 2020 | Initial accelerated policy for CLIA high-complexity lab molecular LDTs |
| v2 | Mar 16, 2020 | Expanded pathways: state authorization, commercial distribution prior to EUA, serology policy |
| v3 | May 4, 2020 | Additional templates, clearer timelines, tightened oversight |
| v4 | May 11, 2020 | Further template and oversight refinements |
| v5 | Nov 15, 2021 | Major reset: umbrella EUAs for serial testing, reissued/narrowed molecular LDT umbrella EUA, FDA signals that newly offered tests should generally have EUA or traditional authorization before clinical use |
| v6 | Sep 27, 2022 | Narrowed EUA review priorities; encouraged traditional marketing pathways |
| v7 | Jan 12, 2023 | Final revision of the overarching COVID test policy guidance |

Three policy innovations are specifically documented in this subcategory:

##### Serial screening (Mar 2021 onward)
FDA authorized screening claims based on strong symptomatic performance combined with a repeat-testing regimen, rather than requiring standalone evidence in asymptomatic populations. This treated the testing algorithm and frequency as part of the risk-control package. By Nov 2022, serial testing instructions were standardized into enforceable antigen test labeling (two tests over three days if symptomatic; three tests over five days if asymptomatic, at least 48 hours apart). Key archive files include:
- `2021-03-16_FDA Website - FDA takes steps to streamline path for COVID-19 screening tools.md`
- `2021-03-16_FDA Template - Supplemental Template for Developers...for Screening with Serial Testing.md`
- `2021-03-13_FDA Fact Sheet - Screening for COVID-19 Deciding Which Test to Use When Establishing Testing Programs.md`
- `2021-10-25_FDA Template - Supplemental Template for Developers...for Screening with Serial Testing.md` (updated version)
- `2022-11-01_FDA Letter - Repeat Testing Revision Letter.md`
- `2022-11-01_FDA Website - Antigen EUA Revisions for Serial Repeat Testing.md`
- `2022-11-17_FDA Website - At Home COVID-19 Antigen Tests-Take Steps.md`

##### Asymptomatic/screening testing (Jul 2020 onward)
FDA distinguished between testing asymptomatic individuals under clinical "suspicion" (provider judgment) and broad population screening (no symptoms, no known exposure). The Jul 24, 2020 LabCorp reissuance was the first EUA explicitly authorizing screening of people without known or suspected infection, establishing screening as a distinct intended use with its own evidence and labeling requirements. Key archive files include:
- `2020-08-24_FDA Policy IVD - Pooled Sample Testing and Screening Testing for COVID-19.md`
- `2021-03-13_FDA Fact Sheet - Screening for COVID-19 Deciding Which Test to Use When Establishing Testing Programs.md`
- `2020-10-26_FDA Template - Antigen Template for Test Developers.md`
- `2021-10-06_FDA Template - For Developers of Molecular Diagnostic Tests.md`

##### Pooled testing (Jul 2020 onward)
FDA authorized sample pooling to conserve reagents and increase throughput, but constrained it through validation requirements (replicate detection thresholds, Ct shift limits, invalid-rate caps), restriction to CLIA high-complexity labs, and behavioral controls (reflex individual testing for positive/invalid pools, specific fact-sheet language). The Apr 20, 2021 amendment letter tied pooled screening specifically to serial testing programs operating at least weekly, treating serial frequency as a mitigation for the sensitivity loss inherent in pooling. FDA distinguished swab pooling from media pooling and provided different validation pathways for each. Key archive files include:
- `2020-08-24_FDA Policy IVD - Pooled Sample Testing and Screening Testing for COVID-19.md`
- `2021-04-20_FDA Letter - Amendment Letter.md`
- `2021-04-20_FDA Website - Pooling and Serial Testing Amendment.md`
- `2021-04-20_FDA Fact Sheet - Sample Updated Fact Sheet for Health Care Providers.md`
- `2021-04-20_FDA Fact Sheet - Sample Updated Fact Sheet for Patients.md`

An important distinction throughout the archive is between FDA's two regulatory levers: **EUA issuance** (test-specific, enforceable conditions, required fact sheets) and **enforcement discretion** (FDA choosing not to enforce certain requirements for a period, with conditions). The early guidances relied heavily on enforcement discretion to expand access; later guidances progressively moved back toward requiring EUA or traditional authorization before clinical use.

Related subcategories include `regulatory/open-euas` (the open EUA submissions FloodLAMP prepared), `regulatory/fda-townhalls` (a RAG demo over 100 FDA townhall transcripts for COVID-19 test developers), and `regulatory/ldts` (laboratory-developed test policy context).


## Commentary
For the primary commentary on FDA policy and the Open EUAs, see `regulatory/open-euas/_context-commentary_regulatory-open-euas.md`.

There remains a need for significant progress in FDA policy as it relates to pandemic preparedness and response. The complexity of the regulatory environment documented in this subcategory, with seven guidance versions, multiple overlapping enforcement mechanisms, and evolving intended-use distinctions, illustrates both the scale of the challenge and the difficulty of navigating it in real time as a small developer.

AI tools offer substantial potential for making this kind of dense regulatory material more accessible and navigable. As a related effort within this archive project, we built a demo RAG (Retrieval Augmented Generation) tool over a corpus of 100 FDA townhall meeting transcripts for COVID-19 diagnostic test developers (see `regulatory/fda-townhalls`). That tool takes natural language queries and returns the closest matching quoted FDA authority responses along with an AI-generated summary, demonstrating one approach to making regulatory guidance more searchable and usable. Feel free to try it at [FDA COVID-19 Diagnostics Townhalls - QRAG Demo](https://www.focusonfoundations.org/fda-town-halls-qrag-demo).


# 2,610  2020-02-29_FDA Guidance - COVID IVD Test Developers v1.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-02-29_FDA Guidance - COVID IVD Test Developers v1.md
file_date: 2020-02-29
title: FDA Guidance - COVID IVD Test Developers v1
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summary_short: The FDA Guidance for COVID-19 IVD Test Developers v1 establishes an accelerated policy allowing CLIA-certified high-complexity laboratories to develop, validate, and use SARS-CoV-2 molecular diagnostic tests prior to Emergency Use Authorization during the early public health emergency. It outlines minimum expectations for validation, FDA notification, result reporting, and EUA submission while permitting temporary clinical use to rapidly expand testing capacity. This guidance shaped early laboratory testing practices by balancing speed with basic analytical and clinical safeguards.


CONTENT

***INTERNAL TITLE:*** Policy for Diagnostics Testing in Laboratories Certified to Perform High Complexity Testing under CLIA prior to Emergency Use Authorization for Coronavirus Disease-2019 during the Public Health Emergency
Immediately in Effect Guidance for Clinical Laboratories and Food and Drug Administration Staff

**Document issued on the web on February 29, 2020.**

**Document announced in the Federal Register on March 6, 2020.**

For questions about this document, contact OHT7 at 301-796-7692 or OHT7/Division of Microbiology Devices at 301-348-1778 or CDRH-EUA-Templates@fda.hhs.gov.

U.S. Department of Health and Human Services  
Food and Drug Administration  
Center for Devices and Radiological Health  

## Preface
### Public Comment

You may submit electronic comments and suggestions at any time for Agency consideration to https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. Identify all comments with the docket number FDA-2020-D-0987. Comments may not be acted upon by the Agency until the document is next revised or updated.

### Additional Copies
Additional copies are available from the Internet. You may also send an e-mail request to CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 20010 and complete title of the guidance in the request.

## Table of Contents
| | | | |
|-|-|-|-|
| I. | Introduction | | 1 |
| II. | Background | | 2 |
| III. | Scope | | 3 |
| IV. | Policy | | 3 |
| A. | Validation | | 3 |
| (1) | Limit of Detection | | 3 |
| (2) | Clinical Evaluation | | 4 |
| (3) | Inclusivity | | 4 |
| (4) | Cross-reactivity | | 4 |
| B. | FDA Notification | | 4 |
| C. | Reporting of Results | | 4 |
| D. | EUA Request | | 5 |
| E. | Clinical Testing | | 5 | 
||

## I. Introduction
The Food and Drug Administration (FDA or Agency) is issuing this guidance to provide a policy for novel coronavirus (COVID-19) molecular diagnostics tests developed and used in laboratories certified to perform high-complexity testing under the Clinical Laboratory Improvement Amendments (CLIA) prior to issuance of emergency use authorizations (EUA) for such tests.

On February 4, 2020, the Secretary of Health and Human Services determined that there is a public health emergency and that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the novel coronavirus (2019-nCoV). Rapid detection of COVID-19 cases in the United States requires wide availability of diagnostic testing to control the emergence of this rapidly spreading, severe illness. This guidance describes an accelerated policy enabling laboratories to use tests they develop faster in order to achieve more rapid testing capacity in the United States.

In light of this public health emergency, this guidance is being implemented without prior public comment because the FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is immediately in effect, but it remains subject to comment in accordance with the Agency's good guidance practices.

FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.

## II. Background
There is currently an outbreak of respiratory disease caused by a novel coronavirus that was first detected in Wuhan City, Hubei Province, China and which has now been detected in 50 locations internationally, including cases in the United States. The virus has been named "SARS-CoV-2" and the disease it causes has been named "Coronavirus Disease 2019" (COVID-19). SARS-CoV-2 has demonstrated the capability to rapidly spread, leading to significant impacts on healthcare systems and causing societal disruption. The potential public health threat posed by COVID-19 is high, both globally and to the United States. To effectively respond to the COVID-19 outbreak, rapid detection of cases and contacts, appropriate clinical management and infection control, and implementation of community mitigation efforts are critical. FDA believes the policy set forth in this guidance will help address these urgent public health concerns by helping to expand available testing capabilities in healthcare settings, and reference and commercial laboratories.

The Centers for Disease Control and Prevention (CDC) laboratories have supported the COVID-19 response, including development of a diagnostic assay that was issued an EUA on February 4, 2020. Since authorizing CDC's EUA, FDA has been actively working with other SARS-CoV-2 diagnostic developers to help accelerate development programs and respond to requests for in vitro diagnostic EUAs. However, the severity and scope of the current COVID-19 situation around the globe necessitates greater testing capacity for the virus than is currently available.

The EUA authorities allow FDA to help strengthen the nation's public health protections against chemical, biological, radiological, and nuclear (CBRN) threats by facilitating the availability and use of medical countermeasures initiatives (MCMs) needed during certain public health emergencies. Under section 564 of the FD&C Act, the FDA Commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in certain emergency circumstances, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use, to diagnose, treat, or prevent serious or life-threatening disease or conditions caused by CBRN threat agents when certain criteria are met.

FDA understands that some laboratories certified to perform high-complexity testing under CLIA are developing diagnostic tests to detect the SARS-CoV-2 virus and pursue EUA authorization for those tests. For a reasonable period of time after validation and while they are preparing their EUA requests, FDA does not intend to object to the use of these tests for specimen testing, as described below. FDA believes 15 days is a reasonable period of time to prepare an EUA submission for test that has already been validated.

This guidance is intended to help rapidly expand testing capacity by facilitating the development of molecular SARS-CoV-2 diagnostic assays. The accelerated approach discussed below should be considered for initial testing of patient specimens, with subsequent confirmatory testing performed as appropriate.

## III. Scope
The policy described in this guidance applies to laboratories certified to perform high-complexity testing under CLIA, that comply with CLIA requirements, that have developed and are using their own validated diagnostic test, and are pursuing an EUA.

## IV. Policy
FDA anticipates that clinical laboratories may need to design and manufacture the individual test kit components (e.g., primers, probes, etc.), or to purchase research use only (RUO) components from third party manufacturers for the development of their assays.

### A. Validation
All clinical tests should be validated prior to use; however, in the context of a public health emergency, it is especially important that tests are validated as false results can have broad public health impact beyond that to the individual patient. Below, FDA has provided recommendations regarding the minimum testing to be performed to ensure analytical and clinical validity of these tests, and FDA encourages laboratories to discuss any alternative testing with FDA that they would like to conduct.

#### (1) Limit of Detection
FDA recommends that laboratories document the limit of detection (LoD) of their SARS-CoV-2 assay. FDA generally does not have concerns with spiking RNA or inactivated virus into artificial or real clinical matrix (e.g., BAL fluid, sputum, etc.) for LoD determination.

FDA recommends that laboratories test a dilution series of three replicates per concentration, and then confirm the final concentration with 20 replicates. FDA defines LoD as the lowest concentration at which 19/20 replicates are positive. If multiple clinical matrices are intended for clinical testing, FDA recommends that laboratories submit in their EUA requests the results from the most challenging clinical matrix to FDA. For example, if testing respiratory specimens (e.g., sputum, BAL, nasophayngeal (NP) swabs, etc.), laboratories should include only results from sputum in their EUA request.

#### (2) Clinical Evaluation
In the absence of known positive samples for testing, FDA recommends that laboratories confirm performance of their assay with a series of contrived clinical specimens by testing a minimum of 30 contrived reactive specimens and 30 non-reactive specimens. Contrived reactive specimens can be created by spiking RNA or inactivated virus into leftover clinical specimens, of which the majority can be leftover upper respiratory specimens such as NP swabs, or lower respiratory tract specimens such as sputum, etc. Twenty of the contrived clinical specimens should be spiked at a concentration of 1x-2x LoD, with the remainder of specimens spanning the assay testing range. FDA defines the acceptance criteria for the performance as 95% agreement at 1x-2x LoD, and 100% agreement at all other concentrations and for negative specimens.

#### (3) Inclusivity
Laboratories should document the results of an in silico analysis indicating the percent identity matches against publicly available SARS-CoV-2 sequences that can be detected by the proposed molecular assay. FDA anticipates that 100% of published SARS-CoV-2 sequences will be detectable with the selected primers and probes.

#### (4) Cross-reactivity
At an minimum, FDA believes an in silico analysis of the assay primer and probes compared to common respiratory flora and other viral pathogens is sufficient for initial clinical use. FDA defines in silico cross-reactivity as greater than 80% homology between one of the primers/probes and any sequence present in the targeted microorganism. In addition, FDA recommends that laboratories should follow recognized laboratory procedures in the context of the sample types intended for testing for any additional cross-reactivity testing.

### B. FDA Notification
Following completion of assay validation, laboratories should notify FDA (e.g., e-mail to CDRH-EUA-Templates@fda.hhs.gov) that their assay has been validated. This notification should include the name of the laboratory, name of the lab director, address, and contact person in this email. FDA will acknowledge receipt of this notification via auto-reply. As noted above, FDA recommends that laboratories submit a completed EUA request within 15 business days of the initial communication to FDA that the assay has been successfully validated.

### C. Reporting of Results
In order to provide transparency, FDA recommends that test reports include a general statement that the test has been validated but FDA's independent review of this validation is pending.

Laboratories should immediately notify appropriate Federal, State, or local public health agencies of all positive results.

### D. EUA Request
The COVID-19 specific EUA template can be obtained by contacting FDA (CDRH-EUA-Templates@fda.hhs.gov), or downloading the template available on the FDA website. FDA will communicate any questions or concerns regarding the completed EUA request or EUA template to the clinical laboratory. FDA will also work collaboratively to address any potential concerns or safety considerations raised in the request and will contact the laboratory regarding a final determination on the EUA request.

If FDA is not able to authorize an EUA, FDA will notify the laboratory. FDA believes it would be important for the laboratory to terminate testing patient specimens and issue a corrected test report that indicates the prior test result may not be valid.

### E. Clinical Testing
While awaiting FDA determination on the EUA request, FDA recommends that clinical laboratories obtain confirmation of the first five positive and the first five negative clinical specimens using an EUA-authorized assay, which may involve sending these ten specimens to another laboratory for confirmation. If any of these results cannot be confirmed, the laboratory should notify FDA at CDRH-EUA-Templates@fda.hhs.gov, and take other appropriate actions such as terminating testing patient specimens, and issuing a corrected test report that indicates the prior test result may not be valid.


# 5,900  2020-03-16_FDA Guidance - COVID IVD Test Developers v2.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-03-16_FDA Guidance - COVID IVD Test Developers v2.md
file_date: 2020-03-16
title: FDA Guidance - COVID IVD Test Developers v2
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summary_short: The FDA Guidance for COVID IVD Test Developers v2 expands the February 29, 2020 policy by covering not only CLIA high-complexity laboratory-developed molecular tests but also state-authorized testing pathways, commercial manufacturer test distribution prior to EUA, and serology testing policies during the public health emergency. It provides validation study recommendations by test type (molecular, antigen, serology) and sets expectations for notification, transparency in reporting, and EUA submission timelines while allowing limited use during review. The guidance helped scale U.S. testing capacity by defining flexible, risk-managed routes for labs and manufacturers to deploy validated tests quickly.


CONTENT

***INTERNAL TITLE:*** Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency
Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff

**Document issued on the web on March 16, 2020.**

**This document supersedes "Policy for Diagnostics Testing in Laboratories Certified to Perform High-Complexity Testing under Clinical Laboratory Improvement Amendments (CLIA) prior to Emergency Use Authorization for Coronavirus Disease-2019 during the Public Health Emergency" issued February 29, 2020.**

For questions about this document, contact CDRH-EUA-Templates@fda.hhs.gov.

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health

## Preface
### Public Comment
You may submit electronic comments and suggestions at any time for Agency consideration to https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. Identify all comments with the docket number FDA-2020-D-0987. Comments may not be acted upon by the Agency until the document is next revised or updated.

### Additional Copies
Additional copies are available from the Internet. You may also send an e-mail request to CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 20010 and complete title of the guidance in the request.

### Table of Contents
|  |  |  |
|---------|-------|------|
| I. | Introduction | 1 |
| II. | Background | 2 |
| III. | Scope | 3 |
| IV. | Policy | 3 |
| A. | Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing Using Their Validated Tests Prior to EUA Submission | 3 |
| 1. | Validation | 4 |
| 2. | FDA Notification | 4 |
| 4. | EUA Request | 5 |
| 5. | Clinical Testing | 5 |
| B. | State Authorization of Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing | 6 |
| C. | Commercial Manufacturer Development and Distribution of Tests Prior to EUA Submission | 7 |
| 1. | Validation | 7 |
| 2. | FDA Notification | 7 |
| 4. | EUA Request | 8 |
| 5. | Clinical Testing | 8 |
| D. | Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Without an EUA | 9 |
| V. | Validation Study Recommendations Based on the Technological Principles of Diagnostic Tests | 9 |
| A. | Molecular Diagnostics | 9 |
| (1) | Limit of Detection | 9 |
| (2) | Clinical Evaluation | 10 |
| (3) | Inclusivity | 10 |
| (4) | Cross-reactivity | 10 |
| B. | Antigen Detection Diagnostics | 10 |
| C. | Serological Diagnostics | 11 |
||

## I. Introduction
The Food and Drug Administration (FDA or Agency) is issuing this guidance to provide a policy to help accelerate the availability of novel coronavirus (COVID-19) diagnostic tests developed by laboratories and commercial manufacturers during the public health emergency.

On February 4, 2020, the Secretary of Health and Human Services (HHS) determined that there is a public health emergency and that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the novel coronavirus (2019-nCoV). Rapid detection of COVID-19 cases in the United States requires wide availability of diagnostic testing to control the emergence of this rapidly spreading, severe illness. This guidance describes a policy for laboratories and commercial manufacturers to help accelerate the use of tests they develop in order to achieve more rapid and widespread testing capacity in the United States.

In light of this public health emergency, this guidance is being implemented without prior public comment because the FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is immediately in effect, but it remains subject to comment in accordance with the Agency's good guidance practices.

FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.

## II. Background
There is currently an outbreak of respiratory disease caused by a novel coronavirus that was first detected in Wuhan City, Hubei Province, China, which has now been designated a pandemic by the World Health Organization (WHO) and which has been detected internationally, including cases in the United States. The virus has been named "SARS-CoV-2" and the disease it causes has been named "Coronavirus Disease 2019" (COVID-19). SARS-CoV-2 has demonstrated the capability to spread rapidly, leading to significant impacts on healthcare systems and causing societal disruption. The potential public health threat posed by COVID-19 is high, both globally and to the United States. To respond effectively to the COVID-19 outbreak, rapid detection of cases and contacts, appropriate clinical management and infection control, and implementation of community mitigation efforts are critical. FDA believes the policy set forth in this guidance will help address these urgent public health concerns by helping to expand the number and variety of diagnostic tests, as well as available testing capabilities in reference and commercial laboratories and healthcare settings.

The Centers for Disease Control and Prevention (CDC) laboratories have supported the COVID-19 response, including development of a diagnostic assay that was issued an Emergency Use Authorization (EUA) on February 4, 2020. Since authorizing CDC's EUA, FDA has been actively working with other SARS-CoV-2 diagnostic test developers to help accelerate development programs and respond to requests for in vitro diagnostic EUAs. However, the severity and scope of the current COVID-19 situation around the globe necessitates greater testing capacity for the virus than is currently available.

The EUA authorities allow FDA to help strengthen the nation's public health protections against chemical, biological, radiological, and nuclear (CBRN) threats by facilitating the availability and use of medical countermeasures initiatives (MCMs) needed during certain public health emergencies. Under section 564 of the FD&C Act, the FDA Commissioner may authorize the use of unapproved medical products, or unapproved uses of approved medical products, in certain emergency circumstances, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use, to diagnose, treat, or prevent serious or life-threatening disease or conditions caused by CBRN threat agents when certain criteria are met.

## III. Scope
The policies described in this guidance for accelerated availability of testing for COVID-19 applies to certain laboratories and commercial manufacturers developing SARS-CoV-2 diagnostic tests during the public health emergency, as described below.

## IV. Policy
This guidance describes policies intended to help rapidly expand testing capacity by facilitating the development and use of SARS-CoV-2 diagnostic tests during the public health emergency.

This guidance describes two policies for accelerating the development of certain laboratory tests for COVID-19 – one leading to an EUA submission to FDA, and the other not leading to an EUA submission when the test is developed under the authorities of the State in which the lab resides and the State takes responsibility for COVID-19 testing by laboratories in its State. The policy leading to an EUA remains unchanged from the initial publication of this guidance on February 29, 2020.

In addition, this guidance describes a policy for commercial manufacturers to more rapidly distribute their SARS-CoV-2 diagnostics to laboratories for specimen testing after validation while an EUA is being prepared for submission to FDA.

This guidance also describes a policy regarding the use of serological testing without an EUA.

In the context of a public health emergency involving pandemic infectious disease, it is critically important that tests are validated as false results can have broad public health impact beyond that to the individual patient. In this guidance, FDA provides recommendations regarding validation of COVID-19 tests. FDA encourages test developers to discuss any alternative approaches to validation with FDA.

### A. Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High Complexity Testing Using Their Validated Tests Prior to EUA Submission
The policy described in this subsection applies to laboratories certified under Clinical Laboratory Improvement Amendments (CLIA) that meet the CLIA regulatory requirements to perform high-complexity testing and that seek to develop and perform diagnostic tests to detect the SARS-CoV-2 virus and pursue EUA authorization from FDA for those tests.

FDA anticipates that clinical laboratories may need to design and manufacture the individual test kit components (e.g., primers, probes, etc.), or to purchase research use only (RUO) components from third party manufacturers, for the development of their assays.

In light of the increasing numbers of COVID-19 cases throughout the country and the urgent need to expand the nation's capacity for COVID-19 testing during the public health emergency, for a reasonable period of time after validation and while they are preparing their EUA requests, FDA does not intend to object to the use of these SARS-CoV-2 tests for specimen testing, as described below. FDA believes that 15 business days is a reasonable period of time to prepare an EUA submission for a test that has already been validated.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is especially important that tests are validated as false results can have broad public health impact beyond that to the individual patient. FDA has provided recommendations regarding the minimum testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages laboratories to discuss any alternative testing with FDA that they would like to conduct.

#### 2. FDA Notification
Following completion of assay validation, laboratories should notify FDA (e.g., e-mail to CDRH-EUA-Templates@FDA.HHS.GOV) that their assay has been validated. This notification should include the name of the laboratory, name of the lab director, address, and contact person in this email. FDA will acknowledge receipt of this notification via auto-reply. As noted above, FDA recommends that laboratories submit a completed EUA request within 15 business days of the initial communication to FDA that the assay has been successfully validated.

It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Reporting of Results
In order to provide transparency, FDA recommends that test reports include a general statement that the test has been validated but FDA's independent review of this validation is pending.

Additionally, reporting of results from serological testing under this policy should include the limitations outlined in section D below unless and until data is submitted and an EUA is authorized for any claims outside those described in section D below.

Laboratories should immediately notify appropriate Federal, State, and local public health agencies of all positive results.

#### 4. EUA Request
FDA has made available, through download from our website, a template that laboratories may choose to use to facilitate the preparation, submission, and authorization of an EUA. Laboratories that intend to use alternative approaches should consider seeking FDA's feedback or advice to help them through the pre-EUA and EUA process. FDA encourages laboratories to discuss any alternative technological approaches with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

Soon after receiving the EUA request, FDA intends to perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the laboratory to address the problem (e.g., through labeling or bench testing). If any problems are significant and cannot be addressed in a timely manner, FDA would expect the laboratory to stop testing and issue corrected test reports indicating prior results may not be accurate.

If FDA is not able to authorize an EUA, FDA will notify the laboratory. FDA would expect the laboratory to stop testing and issue corrected test reports indicating prior test results may not be accurate. FDA does not intend to object to the use of a test, without a new or amended EUA, where the test is validated using a bridging study to an EUA-authorized test. One way to bridge to a new component is to establish equivalent performance between parallel testing of the same specimens with the new and original components. We recommend testing 3-fold serial dilutions of SARS-CoV-2 viral materials (e.g., whole genomic viral RNA or inactivated virus, etc.) in pooled respiratory sample matrix in triplicate.

FDA would like to see your validation data informally through an email to CDRH-EUA-Templates@FDA.HHS.GOV. If FDA's review of validation data indicates that it could be applicable to modifications of other tests with an authorized EUA, and the laboratory agrees to FDA sharing that information on our website for use by other laboratories, FDA intends to update our FAQs so other laboratories can refer to the validation for their testing, without conducting their own bridging study for the same modification.

#### 5. Clinical Testing
While awaiting FDA determination on the EUA request, FDA recommends that clinical laboratories obtain confirmation of the first five positive and the first five negative clinical specimens using an EUA-authorized assay, which may involve sending these ten specimens to another laboratory for confirmation. If any of these results cannot be confirmed, the laboratory should notify FDA at CDRH-EUA-Templates@FDA.HHS.GOV, and take other appropriate actions such as terminating testing patient specimens, and issuing a corrected test report that indicates the prior test result may not be valid.

### B. State Authorization of Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High Complexity Testing
On March 12, 2020, FDA issued enforcement discretion and stated that it was not objecting to the Wadsworth Center authorizing certain laboratories in the State of New York to begin patient testing under certain circumstances to increase availability of COVID-19 testing in response to a request from the Wadsworth Center of the New York State Department of Health (Wadsworth). Wadsworth had informed FDA that it would be willing to have clinical laboratories that currently hold a New York State Department of Health clinical laboratory permit to notify Wadsworth that they have validated a test for COVID-19, and to submit validation studies to Wadsworth. Wadsworth likewise said it would notify the laboratory if it identified any concerns, and request that the laboratory terminate testing patient specimens and issue a corrected test report that indicates the prior test result might not be valid.

On March 13, 2020, the President issued a "Memorandum on Expanding State-Approved Diagnostic Tests" (Memorandum), which refers to the flexibility that FDA allowed New York State and states as follows:

"Should additional States request flexibility to authorize laboratories within the State to develop and perform tests used to detect COVID-19, the Secretary shall take appropriate action, consistent with law, to facilitate the request."

In accordance with the Memorandum, FDA describes below its policy regarding States and territories that authorize laboratories within their State or territory to develop their own COVID-19 tests and perform specimen testing, where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA.

A State or territory choosing to authorize laboratories within that State or territory to develop and perform a test for COVID-19 would do so under authority of its own State law, and under a process that it establishes. FDA does not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA, and where instead the State or territory takes responsibility for COVID-19 testing by laboratories in its State during the COVID-19 outbreak.

FDA requests that the State or territory notify us if they choose to use this flexibility to expedite COVID-19 testing. FDA will not be reviewing the process adopted by the State or territory, which we understand may be different than the process adopted by New York State. FDA expects that such states as part of their oversight process will require laboratories developing SARS-CoV-2 tests to validate those tests prior to use. FDA encourages laboratories that develop and perform a test for COVID-19 under this policy to notify FDA that they have started clinical testing by sending an email to that effect to CDRH-EUA-Templates@FDA.HHS.GOV. It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

### C. Commercial Manufacturer Development and Distribution of Tests Prior to EUA Submission
The policy described in this subsection applies to commercial manufacturers that seek to develop and distribute diagnostic test kits to detect the SARS-CoV-2 virus to clinical laboratories or to healthcare workers for point-of-care testing. This policy does not apply to at home testing.

In light of the increasing numbers of COVID-19 cases throughout the country and the urgent need to expand the nation's capacity for COVID-19 testing during the public health emergency, FDA does not intend to object to a commercial manufacturer's development and distribution of SARS-CoV-2 test kits for specimen testing for a reasonable period of time after the manufacturer's validation of the test and while the manufacturer is preparing its EUA request where the manufacturer provides instructions for use of the test and posts data about the test's performance characteristics on the manufacturer's website. Transparency can help mitigate potential adverse impacts from a poorly designed test by facilitating better informed decisions by potential purchasers and users.

FDA believes that 15 business days is a reasonable period of time to prepare an EUA submission for a test whose performance characteristics have already been validated. Soon after receiving the EUA request, FDA will perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the manufacturer to address the problem (e.g., through labeling or bench testing). If the problem is significant and cannot be addressed in a timely manner, and the manufacturer has already distributed the device, FDA would expect the manufacturer to suspend distribution and conduct a recall of the test.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is especially important that tests are validated as false results can have broad public health impact beyond that to the individual patient. FDA has provided recommendations regarding the minimum testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages laboratories to discuss any alternative testing with FDA that they would like to conduct.

#### 2. FDA Notification
Following completion of assay validation, manufacturers should notify FDA (e.g., e-mail to CDRH-EUA-Templates@FDA.HHS.GOV) that their assay has been validated and they intend to begin distribution. This notification should include the name of the manufacturer, address, contact person, and a copy of the instructions for use including summary of assay performance. FDA will acknowledge receipt of this notification via auto-reply. As noted above, FDA recommends that manufacturers submit a completed EUA request within 15 business days of the initial communication to FDA that the assay has been successfully validated.

It would be helpful to FDA if manufacturers provide information on testing capacity, as well as the number of laboratories in the U.S. with the required platforms installed. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Reporting of Results
In order to provide transparency, FDA recommends that test reports include a general statement that the test has been validated but FDA's independent review of this validation is pending.

#### 4. EUA Request
FDA has made available, through download from our website, a template for test kit manufacturers that is intended to facilitate the preparation, submission and authorization of an EUA. Manufacturers can use alternative approaches. Manufacturers who intend to use alternative approaches should consider seeking FDA's feedback or advice to help them through the pre-EUA and EUA process. FDA encourages manufacturers to discuss any alternative technological approaches with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

FDA will communicate any questions or concerns regarding the completed EUA request or EUA template to the manufacturer. FDA will also work collaboratively to address any potential concerns or safety considerations raised in the request and will contact the manufacturer regarding a final determination on the EUA request.

If FDA is not able to authorize an EUA, FDA intends to notify the manufacturer. FDA would expect the manufacturer to suspend distribution and conduct a recall of the test.

Modifications to a manufacturer's EUA-authorized test are submitted as an amendment to the EUA. Where validation data supporting the modification has been submitted in the amendment, FDA does not intend to object to implementation of the modification while FDA conducts its review.

#### 5. Clinical Testing
While awaiting FDA determination on the EUA request, FDA recommends that manufacturers make publicly available on their website the instructions for use, including a summary of assay performance.

### D. Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Without an EUA
The policy described in this subsection applies to developers of serology tests that identify antibodies (e.g., IgM, IgG) to SARS-CoV-2 from clinical specimens. This policy is limited to such testing in laboratories or by healthcare workers at the point-of-care. This policy does not apply to at home testing.

Considering that serology tests are less complex than molecular tests and are solely used to identify antibodies to the virus, FDA does not intend to object to the development and distribution by commercial manufacturers or development and use by laboratories of serology tests to identify antibodies to SARS-CoV-2, where the test has been validated, notification is provided to FDA, and information along the lines of the following is included in the test reports:

- This test has not been reviewed by the FDA.
- Negative results do not rule out SARS-CoV-2 infection, particularly in those who have been in contact with the virus. Follow-up testing with a molecular diagnostic should be considered to rule out infection in these individuals.
- Results from antibody testing should not be used as the sole basis to diagnose or exclude SARS-CoV-2 infection or to inform infection status.
- Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

FDA recommends that developers planning to submit an EUA for serological testing as the sole basis to diagnose or inform infection status, include information along the lines of the statements above in their test reports until data is submitted and an EUA is authorized for additional uses.

## V. Validation Study Recommendations Based on the Technological Principles of Diagnostic Tests
In this section, FDA provides recommendations for developers regarding the minimum testing that should be performed for SARS-CoV-2 diagnostics based upon the underlying technological principles of the test. Depending on the characteristics of your test, additional validation studies may be recommended. FDA encourages test developers to discuss any alternative technological approaches with FDA through CDRH-EUA-templates@FDA.HHS.GOV.

### A. Molecular Diagnostics
FDA defines SARS-CoV-2 molecular diagnostic tests as tests that detect SARS-CoV-2 nucleic acids from human specimens. FDA recommends that the following validation studies be conducted for a molecular SARS-CoV-2 diagnostic:

#### (1) Limit of Detection
FDA recommends that laboratories document the limit of detection (LoD) of their SARS-CoV-2 assay. FDA generally does not have concerns with spiking RNA or inactivated virus into artificial or real clinical matrix (e.g., Bronchoalveolar lavage [BAL] fluid, sputum, etc.) for LoD determination.

FDA recommends that laboratories test a dilution series of three replicates per concentration, and then confirm the final concentration with 20 replicates. For this guidance, FDA defines LoD as the lowest concentration at which 19/20 replicates are positive. If multiple clinical matrices are intended for clinical testing, FDA recommends that laboratories submit in their EUA requests the results from the most challenging clinical matrix to FDA. For example, if testing respiratory specimens (e.g., sputum, BAL, nasopharyngeal (NP) swabs, etc.), laboratories should include only results from sputum in their EUA request.

#### (2) Clinical Evaluation
In the absence of known positive samples for testing, FDA recommends that laboratories confirm performance of their assay with a series of contrived clinical specimens by testing a minimum of 30 contrived reactive specimens and 30 non-reactive specimens. Contrived reactive specimens can be created by spiking RNA or inactivated virus into leftover clinical specimens, of which the majority can be leftover upper respiratory specimens such as NP swabs, or lower respiratory tract specimens such as sputum, etc. We recommend that twenty of the contrived clinical specimens be spiked at a concentration of 1x-2x LoD, with the remainder of specimens spanning the assay testing range. For this guidance, FDA defines the acceptance criteria for the performance as 95% agreement at 1x-2x LoD, and 100% agreement at all other concentrations and for negative specimens.

#### (3) Inclusivity
Laboratories should document the results of an in silico analysis indicating the percent identity matches against publicly available SARS-CoV-2 sequences that can be detected by the proposed molecular assay. FDA anticipates that 100% of published SARS-CoV-2 sequences will be detectable with the selected primers and probes.

#### (4) Cross-reactivity
At a minimum, FDA believes an in silico analysis of the assay primer and probes compared to common respiratory flora and other viral pathogens is sufficient for initial clinical use. For this guidance, FDA defines in silico cross-reactivity as greater than 80% homology between one of the primers/probes and any sequence present in the targeted microorganism. In addition, FDA recommends that laboratories follow recognized laboratory procedures in the context of the sample types intended for testing for any additional cross-reactivity testing.

Additional information for the validation of molecular diagnostics is included in the manufacturer and laboratory EUA templates available for download on our website.

### B. Antigen Detection Diagnostics
FDA defines SARS-CoV-2 antigen diagnostic tests as those that detect SARS-CoV-2 antigens directly from clinical specimens. FDA recommends that the following validation studies be conducted for a SARS-CoV-2 antigen test:

- Limit of Detection/Analytical Sensitivity
- Cross-reactivity/Analytical Specificity
- Microbial Interference
- Clinical Agreement Study

The clinical agreement study is intended to establish the performance characteristics (e.g., sensitivity/PPA, specificity/NPA) of the test. FDA believes that clinical agreement should be established on human specimens, preferably leftover specimens from patients with or without SARS-CoV-2 infection. If SARS-CoV-2 positive clinical specimens cannot be obtained, it is acceptable to spike leftover specimens with SARS-CoV-2 materials. For devices claiming multiple clinical matrices, the most challenging matrix should be used in your validation studies.

### C. Serological Diagnostics
FDA defines SARS-CoV-2 serological diagnostic tests as tests that identify antibodies (e.g., IgM, IgG) to SARS-CoV-2 from clinical specimens. FDA recommends that the following validation studies be conducted for a SARS-CoV-2 serological assay:

- Cross-reactivity/Analytical Specificity
- Class Specificity
- Clinical Agreement Study

The clinical agreement study is intended to establish the performance characteristics (e.g., sensitivity/PPA, specificity/NPA) of the test. FDA recommends that clinical accuracy should be established on human specimens from patients with microbiologically confirmed COVID-19 infection.


# 285  2020-03-31_FDA Website - EUA for Molecular Diagnostic Tests.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-03-31_FDA Website - EUA for Molecular Diagnostic Tests.md
file_date: 2020-03-31
title: FDA Website - EUA for Molecular Diagnostic Tests
category: regulatory
subcategory: fda-policy
tags: 
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web_url: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2#umbrella-molecular
summary_short: The FDA umbrella EUA for molecular laboratory-developed tests (LDTs) for SARS-CoV-2 outlines eligibility criteria, including CLIA high-complexity certification and use limited to the single developing laboratory, with authorized tests listed in Appendix A. It also notes the November 15, 2021 reissuance that limited authorization to tests already in Appendix A and provides links to the authorization letter and provider/patient fact sheets.


CONTENT

On March 31, 2020, the FDA issued an umbrella EUA for molecular laboratory developed tests (LDTs) for detection of SARS-CoV-2 that meet certain criteria for eligibility described in the EUA. Under this EUA, authorized tests are authorized for use in the single laboratory that developed the authorized test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet requirements to perform high complexity tests.  Tests authorized under this umbrella EUA were added to Appendix A in the table below. 

On November 15, 2021, the FDA reissued this EUA such that only tests that are listed in Appendix A are authorized for use as described in the EUA, and no additional tests will be authorized by this EUA.  The reissued EUA also includes updated Conditions of Authorization and Fact Sheets to reflect the most up-to-date information.

EUA Letter of Authorization - [Laboratories Who Have Developed a Molecular-Based Test (LDTs) for Coronavirus Disease 2019 (COVID-19)](https://www.fda.gov/media/136598/download?attachment)
Fact Sheet for [Healthcare Providers](https://www.fda.gov/media/136599/download?attachment)
Fact Sheet for [Patients](https://www.fda.gov/media/136600/download?attachment)


# 271  2020-04-28_FDA Website - Umbrella EUA for Independently Validated Serology Tests.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-04-28_FDA Website - Umbrella EUA for Independently Validated Serology Tests.md
file_date: 2020-04-28
title: FDA Website - Umbrella EUA for Independently Validated Serology Tests
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: website
xfile_type: NA
gfile_url: NA
xfile_github_download_url: NA
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pdf_github_url: NA
conversion_input_file_type: docx
conversion: manual cut and paste
license: Public Domain
tokens: 271
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notes: date converted 2024-04-05
web_url: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-emergency-use-authorizations-euas-serology-and-other-adaptive-immune-response#umbrella-serological
summary_short: The Umbrella EUA for Independently Validated SARS-CoV-2 Serology Tests describes FDA’s April 28, 2020 authorization pathway for antibody tests validated through designated government studies such as NIH/NCI. It explains that no tests were ultimately authorized under this umbrella and that FDA revoked the EUA on July 21, 2020 in favor of issuing individual EUAs with test-specific conditions and broader, more flexible scopes of authorization.


CONTENT

On April 28, 2020, FDA issued an umbrella EUA for SARS-CoV-2 Antibody Tests (Lateral flow or Enzyme-linked immunosorbent assay (ELISA) tests) that have been evaluated in an independent validation study performed at the National Institutes of Health's (NIH) National Cancer Institute (NCI), or by another government agency designated by the FDA, and are confirmed by the FDA to meet the criteria set forth in the Scope of Authorization of the EUA.  To date, however, no device has been added to the list of authorized devices in Appendix A of the letter of authorization.

On July 21, 2020, FDA determined, based on information and experience since issuing this EUA, that circumstances support revocation of this umbrella EUA so that FDA may issue individual EUAs. Individual EUAs will allow for broader indications and scopes of authorization, individualized conditions of authorization to address any issue unique to a specific test, and more streamlined EUA amendments, such as additional uses that would not fall under this umbrella EUA.

Accordingly, [the EUA was revoked](https://www.fda.gov/media/140351/download?attachment) under Section 564(g)(2)(C) of the Federal Food, Drug, and Cosmetic (FD&C) Act.


# 18,972  2020-05-04_FDA Guidance - COVID IVD Test Developers v3.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-05-04_FDA Guidance - COVID IVD Test Developers v3.md
file_date: 2020-05-04
title: FDA Guidance - COVID IVD Test Developers v3
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: pdf
xfile_type: docx
gfile_url: https://docs.google.com/document/d/1znZ6frcoKUCeafYZdDkTZ1S2r9uklCrH
xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fda-policy/2020-05-04_FDA%20Guidance%20-%20COVID%20IVD%20Test%20Developers%20v3.docx
pdf_gdrive_url: https://drive.google.com/file/d/1gH7xdIi7L0hRx97Eob9oEUcMSend_7f7
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2020-05-04_FDA%20Guidance%20-%20COVID%20IVD%20Test%20Developers%20v3.pdf
conversion_input_file_type: pdf
conversion: claude
license: Public Domain
tokens: 18972
words: 14273
notes: 
summary_short: The FDA Guidance for COVID IVD Test Developers v3 revises the March 16, 2020 policy to further scale pandemic testing while tightening oversight, especially for commercial serology tests, and adding streamlined EUA templates and pathways (including NIH/NCI-evaluated serology under an umbrella EUA). It keeps the core CLIA lab and commercial manufacturer “validate + notify + submit EUA within a set window” approach but adds clearer enforcement levers like FDA website listing/removal if submissions aren’t timely and more explicit rules for modifications and bridging studies. The guidance provides updated validation recommendations by test type and reflects the shift from early flexibility toward stronger performance and labeling controls as more data and market experience accumulated.


CONTENT

***INTERNAL TITLE:*** Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)
Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff

**Document issued on the web on May 4, 2020.**

**This document supersedes "Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency: Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff" issued March 16, 2020.**

U.S. Department of Health and Human Services  
Food and Drug Administration  
Center for Devices and Radiological Health

## Preface
### Public Comment
This guidance is being issued to address the Coronavirus Disease 2019 (COVID-19) public health emergency. This guidance is being implemented without prior public comment because the Food and Drug Administration (FDA or Agency) has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency's good guidance practices.

Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov. All comments should be identified with the docket number FDA-2020-D-0987 and complete title of the guidance in the request.

### Additional Copies
Additional copies are available from the FDA webpage titled "COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders," available at https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders, and the FDA webpage titled "Search for FDA Guidance Documents," available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. You may also send an e-mail request to CDRH-Guidance@fda.hhs.gov to receive an additional copy of the guidance. Please include the document number 20010-R2 and complete title of the guidance in the request.

### Questions
For questions about this document, contact CDRH-EUA-Templates@fda.hhs.gov.

## Table of Contents
Here's the content from the screenshot converted to a Markdown pipe table:

|  |  |  |
|---------|-------|------|
| I. | Introduction | 4 |
| II. | Background | 5 |
| III. | Scope | 6 |
| IV. | Policy | 6 |
| A. | Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing Using Their Validated Diagnostic Tests Prior to EUA Submission | 8 |
| 1. | Validation | 8 |
| 2. | FDA Notification | 8 |
| 4. | EUA Request | 9 |
| 5. | Clinical Testing | 10 |
| B. | State Authorization of Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing | 10 |
| C. | Commercial Manufacturer Development and Distribution of Diagnostic Tests Prior to EUA Submission | 11 |
| 1. | Validation | 12 |
| 2. | FDA Notification | 12 |
| 4. | EUA Request | 13 |
| 5. | Clinical Testing | 14 |
| D. | Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Without or Prior to an EUA | 14 |
| 1. | Validation | 15 |
| 2. | FDA Notification | 15 |
| 4. | EUA Request | 17 |
| V. | Validation Study Recommendations Based on the Technological Principles of Tests | 17 |
| A. | Molecular Diagnostics | 17 |
| (1) | Limit of Detection | 18 |
| (2) | Clinical Evaluation | 18 |
| (3) | Inclusivity | 18 |
| (4) | Cross-reactivity | 18 |
| B. | Antigen Detection Diagnostics | 19 |
| C. | Serological Tests | 19 |
||

## I. Introduction
FDA plays a critical role in protecting the United States from threats such as emerging infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support response efforts to this pandemic.

FDA is issuing this guidance to provide a policy to help accelerate the availability of novel coronavirus (COVID-19) tests developed by laboratories and commercial manufacturers for the duration of the public health emergency. Rapid detection of COVID-19 cases in the United States requires wide availability of testing to control the emergence of this rapidly spreading, severe illness. This guidance describes a policy for laboratories and commercial manufacturers to help accelerate the use of tests they develop in order to achieve more rapid and widespread testing capacity in the United States.

This policy is intended to remain in effect only for the duration of the public health emergency related to COVID-19 declared by the Secretary of Health and Human Services (HHS) on January 31, 2020, effective January 27, 2020, including any renewals made by the HHS Secretary in accordance with section 319(a)(2) of the Public Health Service Act (PHS Act).

Given this public health emergency, and as discussed in the Notice in the Federal Register of March 25, 2020, titled "Process for Making Available Guidance Documents Related to Coronavirus Disease 2019," available at https://www.govinfo.gov/content/pkg/FR-2020-03-25/pdf/2020-06222.pdf, this guidance is being implemented without prior public comment because FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency's good guidance practices.

In general, FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.

## II. Background
There is currently a pandemic of respiratory disease caused by a novel coronavirus. The virus has been named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) and the disease it causes has been named "Coronavirus Disease 2019" (COVID-19). On January 31, 2020, HHS issued a declaration of a public health emergency related to COVID-19 and mobilized the Operating Divisions of HHS. In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19.

SARS-CoV-2 has demonstrated the capability to spread rapidly, leading to significant impacts on healthcare systems and causing societal disruption. The potential public health threat posed by COVID-19 is high, both globally and to the United States. To respond effectively to the COVID-19 outbreak, rapid detection of cases and contacts, appropriate clinical management and infection control, and implementation of community mitigation efforts are critical. FDA believes the policies set forth in this guidance will help address these urgent public health concerns by helping to expand the number and variety of tests, as well as available testing capabilities in reference and commercial laboratories and healthcare settings, while helping ensure these tests are accurate and reliable.

The Centers for Disease Control and Prevention (CDC) laboratories have supported the COVID-19 response, including development of a diagnostic assay that was issued an Emergency Use Authorization (EUA) on February 4, 2020. Since authorizing CDC's EUA, FDA has been actively working with other SARS-CoV-2 diagnostic test developers to help accelerate development programs and respond to requests for in vitro diagnostic EUAs. However, the severity and scope of the current COVID-19 situation around the globe necessitates greater testing capacity for the virus than is currently available.

The EUA authorities allow FDA to help strengthen the nation's public health protections against chemical, biological, radiological, and nuclear (CBRN) threats by facilitating the availability and use of medical countermeasures initiatives (MCMs) needed during certain public health emergencies. Under section 564 of the FD&C Act, the FDA Commissioner may authorize the use of unapproved medical products, or unapproved uses of approved medical products, in certain emergency circumstances, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use, to diagnose, treat, or prevent serious or life-threatening disease or conditions caused by CBRN threat agents when certain criteria are met.

## III. Scope
The policies described in this guidance for accelerating availability of testing for COVID-19 apply to certain laboratories and commercial manufacturers developing SARS-CoV-2 tests during the public health emergency, as described below.

## IV. Policy
This guidance describes policies intended to help rapidly expand testing capacity by facilitating the development and use of SARS-CoV-2 tests during the public health emergency.

This guidance describes two policies for accelerating the development of certain laboratory-developed diagnostic tests for COVID-19 – one leading to an EUA submission to FDA, and the other not leading to an EUA submission when the test is developed under the authorities of the State in which the laboratory resides and the State takes responsibility for COVID-19 testing by laboratories in its State. The policy leading to an EUA remains unchanged from the initial publication of this guidance on February 29, 2020, though some process updates and clarifications have been made as discussed further below. The policy for State oversight remains unchanged from the second publication of this guidance on March 16, 2020.

In addition, this guidance describes a policy for commercial manufacturers to more rapidly distribute their SARS-CoV-2 diagnostic tests to laboratories for specimen testing after validation, while an EUA is being prepared for submission to FDA. This policy remains unchanged from the second publication of this guidance on March 16, 2020, though some process updates and clarification have been made as discussed further below.

This guidance also describes a policy regarding SARS-CoV-2 serological testing, which is modified from the policy included in the March 16, 2020 guidance as it pertains to commercial manufacturers but not laboratories. At the time of previous issuance, FDA provided flexibility for serology tests to be marketed with notification to FDA and certain labeling information, but without submission of an EUA. FDA's policy was based on the considerations that serology tests are not meant to diagnose active SARS-CoV-2 infection and that early availability and use of these tests could help answer critical questions about the prevalence of COVID-19 infections in different communities, whether the presence of antibodies conveys immunity, and, if so, for how long. That policy succeeded in encouraging development of serology tests.

Since that policy was issued, FDA has authorized several serology tests under individual EUAs and has issued an umbrella EUA providing a streamlined approach for EUA authorization of serology tests that are evaluated by the National Institutes of Health's National Cancer Institute (NIH/NCI). The umbrella EUA for NIH-evaluated tests has provided a streamlined pathway for EUA authorization of commercial serology tests. Also since that time, FDA has become aware that a concerning number of commercial serology tests are being promoted inappropriately, including for diagnostic use, or are performing poorly based on an independent evaluation by the NIH, indicating that greater FDA oversight of commercial serology tests is important to protect the public health.

Under the modified policy, FDA does not intend to object as described below where commercial manufacturers develop and distribute their serology tests after validation, for a limited period of time, while an EUA is being prepared for submission to FDA. Appendices with templates for such submissions have been added to facilitate and streamline the EUA process.

The policy for serological tests developed and used by laboratories that are certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing has not changed from the March 16, 2020 guidance, though FDA continues to encourage such laboratories to submit EUAs for their laboratory developed tests.

In the context of a public health emergency involving pandemic infectious disease, it is critically important that tests are validated because false results not only can negatively impact the individual patient but also can have broad public health impact. In this guidance, FDA provides recommendations regarding validation of COVID-19 tests based on the available information. FDA encourages test developers to discuss any alternative technological approaches to validating their test with FDA.

### A. Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing Using Their Validated Diagnostic Tests Prior to EUA Submission
The policy described in this subsection applies to laboratories certified under CLIA that meet the CLIA regulatory requirements to perform high-complexity testing and that seek to develop and perform diagnostic tests to detect the SARS-CoV-2 virus and pursue an EUA from FDA for those tests. This policy does not apply to home collection of specimens to be sent for testing at a laboratory certified under CLIA for high-complexity testing.

FDA anticipates that clinical laboratories may need to design and manufacture the individual test kit components (e.g., primers, probes, etc.), or to purchase research use only (RUO) components from third party manufacturers, for the development of their assays.

In light of the increasing numbers of COVID-19 cases throughout the country and the urgent need to expand the nation's capacity for COVID-19 testing during the public health emergency, FDA does not intend to object to the use of these SARS-CoV-2 tests for specimen testing for a reasonable period of time, where the test has been validated and while the laboratory is preparing their EUA request, and where the laboratory gives notification of validation to FDA, as described below. FDA believes that 15 business days is a reasonable period of time to prepare an EUA submission for a test that has already been validated.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is critically important that tests are validated because false results can negatively impact not only the individual patient but also can have broad public health impact. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages laboratories to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

#### 2. FDA Notification
Following completion of assay validation, laboratories should notify FDA (e.g., email to CDRH-EUA-Templates@FDA.HHS.GOV) that their assay has been validated. This notification should include the name of the laboratory, name of the laboratory director, laboratory address, and contact person in this email. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the laboratory name to FDA's website listing. As noted above, FDA recommends that laboratories submit a completed EUA request within 15 business days of the notification to FDA that the assay has been successfully validated. If an EUA request is not submitted within this timeframe, FDA intends to remove the laboratory from its website listing of laboratories that have notified FDA and may take additional actions as appropriate.

It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Reporting of Results
In order to provide transparency, FDA recommends that test reports include a general statement that the test has been validated but FDA's independent review of this validation is pending.

Laboratories should immediately notify appropriate Federal, State, and local public health agencies of all positive results.

#### 4. EUA Request
FDA has made available, through download from our website, a template that laboratories may choose to use to facilitate the preparation, submission, and authorization of an EUA for a molecular diagnostic test. Laboratories that intend to use alternative approaches should consider seeking FDA's feedback or recommendation to help them through the pre-EUA and EUA process. FDA encourages laboratories to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

Soon after receiving the EUA request, FDA intends to perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the laboratory to address the problem (e.g., through labeling or bench testing). If any problems are significant and cannot be addressed in a timely manner, FDA would expect the laboratory to stop testing and issue corrected test reports indicating prior results may not be accurate. In such circumstances, FDA intends to remove the laboratory from the website listing of notifications.

Issued EUAs are posted on FDA's website.

When a laboratory makes a modification to an EUA authorized test for use of a new specimen type, FDA does not intend to object to the use of such a modified test without notification to FDA or a new or amended EUA where the new specimen type has been previously authorized for another test of the same technology and where the EUA authorized test is validated for the new specimen type. Modifications to an EUA authorized test for use of a new specimen type that has not been previously authorized for another test of the same technology must be authorized under a new or amended EUA prior to clinical use.

For all other types of modifications, FDA does not intend to object to the use of a test, without notification to FDA or a new or amended EUA, where the test is a modification of an EUA-authorized test and the modified test is validated using a bridging study to the EUA-authorized test. One way to bridge to a new component is to establish equivalent performance between parallel testing of the same specimens with the new and original components. We recommend testing 3-fold serial dilutions of SARS-CoV-2 viral materials (e.g., whole genomic viral RNA or inactivated virus, etc.) in a pooled respiratory sample matrix in triplicate until you achieve a hit rate of <100%. If the resultant Limit of Detection (LoD) is the same as the LoD for the unmodified authorized test (i.e., ≤3xLOD), then FDA believes the two tests can be considered to have equivalent performance.

When validating through a bridging study and not pursuing an EUA amendment for the modification, FDA would like to see the laboratory's validation data informally through an email to CDRH-EUA-Templates@FDA.HHS.GOV. If FDA's review of the bridged validation data indicates that it could be applicable to modifications of other tests with an EUA, or to other laboratories modifying the same authorized test, and the laboratory agrees to FDA sharing that information on our website for use by other laboratories, FDA intends to update our FAQs so other laboratories can refer to the validation for their testing, without conducting their own bridging study for the same modification. This informal sharing of data would not be considered to be a notification, as discussed above, or an EUA request.

#### 5. Clinical Testing
While awaiting an FDA determination on the EUA request, FDA recommends that clinical laboratories obtain confirmation of the first five positive and the first five negative clinical specimens using an EUA-authorized assay. This testing may be performed within the same laboratory using an EUA-authorized assay or may involve sending these ten specimens to another laboratory for confirmation. If any of these results cannot be confirmed, the laboratory should notify FDA at CDRH-EUA-Templates@FDA.HHS.GOV, and take other appropriate actions such as terminating testing patient specimens, and issuing corrected test reports indicating prior test results may not be accurate.

### B. State Authorization of Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing
On March 12, 2020, FDA issued enforcement discretion and stated that it was not objecting to the Wadsworth Center authorizing certain laboratories in the State of New York to begin patient testing under certain circumstances to increase availability of COVID-19 testing in response to a request from the Wadsworth Center of the New York State Department of Health (Wadsworth). Wadsworth had informed FDA that it would be willing to have clinical laboratories that currently hold a New York State Department of Health clinical laboratory permit to notify Wadsworth that they have validated a test for COVID-19, and to submit validation studies to Wadsworth. Wadsworth likewise said it would notify the laboratory if it identified any concerns, and request that the laboratory terminate testing patient specimens and issue corrected test reports indicating prior test results might not be accurate.

On March 13, 2020, the President issued a "Memorandum on Expanding State-Approved Diagnostic Tests" (Memorandum), which refers to the flexibility that FDA allowed New York State and states as follows:

"Should additional States request flexibility to authorize laboratories within the State to develop and perform tests used to detect COVID-19, the Secretary shall take appropriate action, consistent with law, to facilitate the request."

In accordance with the Memorandum, FDA describes below its policy regarding States and territories that authorize laboratories within their State or territory to develop their own COVID-19 tests and perform specimen testing, where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA.

A State or territory choosing to authorize laboratories within that State or territory to develop and perform a test for COVID-19 would do so under authority of its own State law, and under a process that it establishes. FDA does not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA, and where instead the State or territory takes responsibility for COVID-19 testing by laboratories in its State during the COVID-19 outbreak.

FDA requests that the State or territory notify us if they choose to use this flexibility to expedite COVID-19 testing. FDA will not be reviewing the process adopted by the State or territory, which we understand may be different than the process adopted by New York State. FDA expects that such states as part of their oversight process will require laboratories developing SARS-CoV-2 tests to validate those tests prior to use. FDA encourages laboratories that develop and perform a test for COVID-19 under this policy to notify FDA that they have started clinical testing by sending an email to that effect to CDRH-EUA-Templates@FDA.HHS.GOV. It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

### C. Commercial Manufacturer Development and Distribution of Diagnostic Tests Prior to EUA Submission
The policy described in this subsection applies to commercial manufacturers that seek to develop and distribute diagnostic test kits to detect the SARS-CoV-2 virus to clinical laboratories or to healthcare workers for point-of-care testing. Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to laboratories certified to perform high complexity testing, including testing at the point-of-care when the site is covered by the laboratory's CLIA certificate for high-complexity testing.

This policy does not apply to at-home testing, including at-home specimen collection.

In light of the increasing numbers of COVID-19 cases throughout the country and the urgent need to expand the nation's capacity for COVID-19 testing during the public health emergency, FDA does not intend to object to a commercial manufacturer's development and distribution of SARS-CoV-2 test kits for specimen testing for a reasonable period of time, where the test has been validated and while the manufacturer is preparing its EUA request, where the manufacturer gives notification of validation to FDA as described below, and where the manufacturer provides instructions for use of the test and posts data about the test's performance characteristics on the manufacturer's website. Transparency can help mitigate potential adverse impacts from a poorly designed test by facilitating better informed decisions by potential purchasers and users.

FDA believes that 15 business days is a reasonable period of time to prepare an EUA submission for a test that has already been validated. Soon after receiving the EUA request, FDA will perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the manufacturer to address the problem (e.g., through labeling or bench testing). If the problem is significant and cannot be addressed in a timely manner, and the manufacturer has already distributed the device, FDA would expect the manufacturer to suspend distribution and conduct a recall of the test.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is critically important that tests are validated because false results can negatively impact not only the individual patient but also can have broad public health impact. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages manufacturers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

#### 2. FDA Notification
Following completion of assay validation, manufacturers should notify FDA (e.g., e-mail to CDRH-EUA-Templates@FDA.HHS.GOV) that their assay has been validated and they intend to begin distribution. This notification should include the name of the manufacturer, address, contact person, a website link, and a copy of the instructions for use including a summary of assay performance. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the name of the manufacturer and test to FDA's website listing.

In circumstances where manufacturers use distributor(s) for their product, the manufacturers should identify the names of all distributors in their notification. Distributors and laboratories using these tests should not provide separate notification. As noted above, FDA recommends that manufacturers submit a completed EUA request within 15 business days of the notification to FDA that the assay has been successfully validated. If an EUA request is not submitted within this timeframe, FDA intends to remove the manufacturer/test from its website listing of notified tests and may take additional actions as appropriate.

It would be helpful to FDA if manufacturers provide information on testing capacity, as well as the number of laboratories in the U.S. with the required platforms installed. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Reporting of Results
In order to provide transparency, FDA recommends that instructions for use and test reports include a general statement that the test has been validated but FDA's independent review of this validation is pending.

#### 4. EUA Request
FDA has made available, through download from our website, a template that test kit manufacturers may choose to use to facilitate the preparation, submission, and authorization of an EUA for a molecular diagnostic. Manufacturers can use alternative approaches. Manufacturers who intend to use alternative approaches should consider seeking FDA's feedback or recommendations to help them through the pre-EUA and EUA process. FDA encourages manufacturers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

Soon after receiving the EUA request, FDA intends to perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the manufacturer to address the problem (e.g., through labeling or bench testing). If any problems are significant and cannot be addressed in a timely manner, FDA would expect the manufacturer to suspend distribution and conduct a recall of the test, which should include a notification concerning corrected test reports indicating prior test results may not be accurate. In such circumstances, FDA intends to remove the manufacturer/test from the website listing of notifications.

Issued EUAs are posted on FDA's website.

A manufacturer may request certain modifications to its EUA-authorized test as an amendment to the EUA as specified in the EUA's Conditions of Authorization. Where validation data supporting the modification have been submitted in the amendment, FDA does not intend to object to implementation of the modification while FDA conducts its review, except for modifications to add specimen types that have not been previously authorized with another test of the same technology.

#### 5. Clinical Testing
While awaiting FDA determination on the EUA request, FDA recommends that manufacturers make publicly available on their website the instructions for use, including a summary of assay performance.

### D. Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Prior to or Without an EUA
The policy described in this subsection applies to developers of serology tests that identify antibodies (e.g., IgG, IgM) to SARS-CoV-2 from clinical specimens. Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to laboratories certified to perform high complexity testing, and at the point-of-care when covered by the laboratory's CLIA certificate for high-complexity testing. This policy does not apply to at-home testing, including at-home specimen collection, due to additional considerations that require FDA review.

FDA does not intend to object to a commercial manufacturer's development and distribution of serology tests to identify antibodies to SARS-CoV-2 for a reasonable period of time, where the test has been validated and while the manufacturer is preparing its EUA request, where the manufacturer gives notification of validation to FDA as described in subsection D.2 below, and where the manufacturer includes information in the instructions for use as described in subsection D.3 below. FDA provided early market access through its March 16, 2020, updated guidance, but that access was premised on the understanding that tests should be validated before being marketed to fall under the enforcement discretion policy. Given that any test on the market under the March 16 enforcement discretion policy or this policy should already be validated by the manufacturer before being marketed, FDA believes that 10 business days (from the date of notification or the date of publication of this guidance, whichever is later) is a reasonable period of time to prepare an EUA submission for a test whose performance characteristics have already been validated.

If FDA becomes aware of questions or concerns about a test after notification, such as poor performance or misleading statements about the test, FDA will communicate those concerns to the manufacturer and provide the manufacturer an opportunity to address the questions or concerns. If the concerns cannot be or have not been addressed in a timely manner, and the manufacturer has already distributed the test, FDA would expect the manufacturer to suspend distribution of the test. FDA also intends to remove the test from the website listing of notifications and may take additional actions as appropriate.

While laboratories are encouraged to submit EUA requests for serology tests, FDA does not intend to object to the development and use of serology tests to identify antibodies to SARS-CoV-2 by laboratories that are certified under CLIA to perform high-complexity testing, where the test has been validated, notification is provided to FDA, and information is included in the test reports as described in subsection D.3 below. At this time, we believe it is most beneficial to focus our EUA review and authorization efforts on tests from commercial manufacturers, which have the potential to be distributed more broadly, rather than laboratory-developed serology tests that are not for diagnostic purposes, are being performed at one laboratory that is CLIA-certified to perform high-complexity testing, and that are validated in-house. However, if FDA becomes aware of questions or concerns about a laboratory-developed serology test, such as poor performance or misleading statements about the test, FDA will communicate those concerns to the laboratory and provide the laboratory an opportunity to address the questions or concerns. If the concerns cannot be or have not been addressed in a timely manner, FDA intends to remove the laboratory from the website listing of notifications and may take additional actions as appropriate.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is critically important that tests are validated because false results can negatively impact not only the individual patient but also can have broad public health impact. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV and additionally encourages developers to refer to the templates provided as examples in the Appendices to this guidance for serology test manufacturers and laboratories.

#### 2. FDA Notification
Following completion of assay validation, developers should notify FDA by email to CDRH-EUA-Templates@FDA.HHS.GOV that their assay has been validated and they intend to begin distribution or testing.

a. For tests developed and used by laboratories certified under CLIA that meet the CLIA regulatory requirements to perform high-complexity testing, this notification should include the name of the laboratory, name of the laboratory director, laboratory address, and contact person in this email. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the laboratory name to FDA's website listing.

It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

b. For tests developed and distributed by commercial manufacturers, this notification should include the name of the manufacturer, address, contact person, and a copy of the instructions for use that includes a summary of assay performance. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the name of the manufacturer and test to FDA's website listing. As noted above, FDA recommends that manufacturers submit a completed EUA request within 10 business days of the notification to FDA that the assay has been successfully validated, or the date of publication of this guidance, whichever is later. If an EUA request is not submitted within this timeframe, FDA intends to remove the manufacturer/test from its website listing of notified tests and may take additional actions as appropriate.

In circumstances where manufacturers use distributor(s) for their test, the manufacturer should identify the names of all distributors in their notification. Distributors should not provide separate notification.

It would be helpful to FDA if manufacturers provide information on test production capacity, the number of laboratories in the U.S. with the required platforms installed. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Labeling and Reporting of Results
In order to provide important information about the intended use of the test and its limitations, FDA recommends that instructions for use and patient test reports include information that helps users and patients understand the test results, such as the following:

- This test has not been reviewed by the FDA.
- Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct testing for SARS-CoV-2 is necessary.
- Results from antibody testing should not be used to diagnose or exclude acute SARS-CoV-2 infection.
- Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

#### 4. EUA Request
Templates for commercial manufacturers and laboratories are provided in Appendices A and B to facilitate the preparation, submission, and authorization of an EUA. Developers can use alternative approaches. Developers who intend to use alternative approaches should consider seeking FDA's feedback or recommendations to help them through the EUA process. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

FDA may leverage data from testing at the National Institutes of Health's National Cancer Institute (NIH/NCI), or at another federal government laboratory designated by FDA, to inform decisions on EUA requests and other actions. FDA has issued an EUA for certain serology tests evaluated in the NIH/NCI independent validation study, or by another government agency designated by FDA, that are confirmed by FDA to meet certain specific performance and other criteria, and added to the EUA.

FDA will communicate any questions or concerns regarding a pre-EUA or EUA submission to the developer. FDA will also work collaboratively to address any potential concerns or safety considerations raised in the pre-EUA submission or EUA request and will contact the developer regarding a final determination on the EUA request.

Issued EUAs are posted on FDA's website.

If FDA is not able to issue an EUA, FDA intends to notify the manufacturer. Where the manufacturer has distributed tests, FDA also would expect the manufacturer to suspend distribution of the test, which should include a notification indicating that prior test results may not be accurate. FDA intends to remove the manufacturer/test from the website listing of notifications. FDA may also take other action as may be appropriate in the circumstances.

## V. Validation Study Recommendations Based on the Technological Principles of Tests
In this section, FDA provides recommendations for developers regarding testing that should be performed to demonstrate that a SARS-CoV-2 test is validated based upon the underlying technological principles of the test. Depending on the characteristics of your test, additional validation studies may be recommended. FDA encourages test developers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-templates@FDA.HHS.GOV.

### A. Molecular Diagnostic Tests
FDA defines SARS-CoV-2 molecular diagnostic tests as tests that detect SARS-CoV-2 nucleic acids from human specimens. FDA recommends that the following validation studies be conducted for molecular SARS-CoV-2 diagnostic tests:

#### (1) Limit of Detection
FDA recommends that developers document the limit of detection (LoD) of their SARS-CoV-2 assay. FDA generally does not have concerns with spiking RNA or inactivated virus into artificial or real clinical matrix (e.g., Bronchoalveolar lavage [BAL] fluid, sputum, etc.) for LoD determination.

FDA recommends that developers test a dilution series of three replicates per concentration with inactivated virus on actual patient specimen, and then confirm the final concentration with 20 replicates. For this guidance, FDA defines LoD as the lowest concentration at which 19/20 replicates are positive. If multiple clinical matrices are intended for clinical testing, FDA recommends that developers submit in their EUA requests the results from the most challenging clinical matrix to FDA. For example, if testing respiratory specimens (e.g., sputum, BAL, nasopharyngeal (NP) swabs, etc.), laboratories should include only results from sputum in their EUA request.

#### (2) Clinical Evaluation
The availability of positive samples has increased as the pandemic has progressed. As such, FDA now recommends that developers use positive clinical samples for clinical validation. Moreover, due to the increased availability of clinical samples, FDA recommends that developers confirm performance of their assay by testing a minimum of 30 positive specimens and 30 negative specimens as determined by an authorized assay. If you do not have access to clinical samples as determined by an authorized assay, contrived clinical specimens may be considered. Contrived reactive specimens can be created by spiking RNA or inactivated virus into leftover clinical specimens, of which the majority can be leftover upper respiratory specimens such as NP swabs, or lower respiratory tract specimens such as sputum, etc. If contrived samples are used, FDA recommends that twenty of the contrived clinical specimens be spiked at a concentration of 1x-2x LoD, with the remainder of specimens spanning the assay testing range. For this guidance, FDA defines the acceptance criteria for the performance as 95% agreement at 1x-2x LoD, and 100% agreement at all other concentrations and for negative specimens.

#### (3) Inclusivity
Developers should document the results of an in silico analysis indicating the percent identity matches against publicly available SARS-CoV-2 sequences that can be detected by the proposed molecular assay. FDA anticipates that 100% of published SARS-CoV-2 sequences will be detectable with the selected primers and probes.

#### (4) Cross-reactivity
FDA recommends cross-reactivity wet testing on common respiratory flora and other viral pathogens at concentrations of 10^6 CFU/ml or higher for bacteria and 10^5 pfu/ml or higher for viruses, except for SARS-Coronavirus and MERS-Coronavirus, which can be accomplished by in silico analysis. As an alternative, FDA believes an in silico analysis of the assay primer and probes compared to common respiratory flora and other viral pathogens can be performed. For this guidance, FDA defines in silico cross-reactivity as greater than 80% homology between one of the primers/probes and any sequence present in the targeted microorganism. In addition, FDA recommends that developers follow recognized laboratory procedures in the context of the sample types intended for testing for any additional cross-reactivity testing.

Additional information for the validation of molecular diagnostics is included in the manufacturer and developers EUA templates available for download on our website.

### B. Antigen Detection Tests
FDA defines SARS-CoV-2 antigen tests as those that detect proteins that are part of the SARS-CoV-2 virus directly from clinical specimens. FDA recommends that the following validation studies be conducted for a SARS-CoV-2 antigen test:

- Limit of Detection/Analytical Sensitivity
- Cross-reactivity/Analytical Specificity
- Microbial Interference
- Clinical Agreement Study

The clinical agreement study is intended to establish the performance characteristics (e.g., sensitivity/PPA, specificity/NPA) of the test. FDA believes that clinical agreement should be established on human specimens, preferably leftover specimens from patients with or without SARS-CoV-2 infection.

### C. Serological Tests
FDA defines SARS-CoV-2 serological tests as tests that identify antibodies (e.g., IgG, IgM) to SARS-CoV-2 from clinical specimens. FDA recommends that the following validation studies be conducted for a SARS-CoV-2 serological assay:

- Cross-reactivity/Analytical Specificity
- Class Specificity
- Clinical Agreement Study

The clinical agreement study is intended to establish the performance characteristics (e.g., sensitivity/PPA, specificity/NPA) of the test. FDA recommends that clinical accuracy should be established on human specimens from patients with microbiologically confirmed COVID-19 infection.

EUA templates for serology tests for manufacturers and laboratories are provided in Appendices A and B, respectively, to facilitate pre-EUA/EUA submissions. These templates include further recommendations concerning the above validation studies and make additional recommendations about other information that should be provided to FDA as part of the pre-EUA/EUA submission process. Developers can use alternative approaches. FDA encourages developers to discuss any alternative approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

## Appendix A: Serology Template for Manufacturers
This template (the "template") provides FDA's current recommendations concerning what data and information should be submitted to FDA in support of a pre-EUA/EUA submission for a SARS-CoV-2 antibody test. As outlined in Section V.C. of this guidance, FDA recommends that the following validation studies be conducted for a SARS-CoV-2 serological assay: Cross-reactivity/Analytical Specificity, Class Specificity, and Clinical Agreement Study. This template is intended to help manufacturers provide these validation data and other recommended information to FDA, but alternative approaches can be used. For more information about EUAs in general, please see the FDA Guidance document: [Emergency Use Authorization of Medical Products and Related Authorities](https://www.fda.gov/media/97321/download).

### GENERAL INFORMATION ABOUT THIS TEMPLATE
- Text highlighted in yellow [Text] should be completed by the test manufacturer (sponsor) as applicable to their specific test. Text in bold outlines the Food and Drug Administration's (FDA) additional recommendations for the sponsors' consideration when completing the suggested information in each section.
- Please be reminded that tests for the detection of antibodies against SARS-CoV-2 must not be distributed and/or used for clinical diagnoses.
- This is an EUA interactive review template for Pre-EUA/EUA submissions. The template is subject to change as we learn more about the COVID-19 disease and its risk-benefit profile.
- A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.
- The EUA is not a pathway to permanent marketing of your device. Therefore, we strongly recommend that you consider, in addition to an EUA, a traditional premarket submission for your IVD so that your device can still be legally marketed after termination of the public health emergency declaration. We recommend that you identify as soon as possible in the Pre-EUA review process any consideration of moving your product forward towards De Novo/510(k) clearance.

### EXAMPLE TEMPLATE:
#### A. PURPOSE FOR SUBMISSION
Emergency Use Authorization (EUA) request for distribution of the [test name] in [indicate labs e.g., U.S. laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform moderate complexity and high complexity tests, and U.S. laboratories certified under CLIA to perform high complexity tests, and as applicable, for near patient testing, or point of care use], for the detection of [specify types of antibodies e.g., IgM, IgG, total] antibodies to SARS-CoV-2 in [specify matrices] from individuals with current or prior COVID-19 infection.

#### B. MEASURAND
[Specify what the test detects and whether it can differentiate between IgM and IgG or if it detects total antibody without differentiation.]

#### C. APPLICANT
[Official name, address and contact information of applicant]

#### D. PROPRIETARY AND ESTABLISHED NAMES
Proprietary Name: [test name]
Established Name - [test name]

#### E. REGULATORY INFORMATION
Approval/Clearance Status:
The [test name] is not cleared, CLIA waived, approved, or subject to an approved investigational device exemption.

Product Code:
QKO

#### F. PROPOSED INTENDED USE
1\) Intended Use:
The proposed IU will be finalized based on the data provided at the time of authorization.

The [test name] is a [specify technology e.g., Enzyme-Linked Immunosorbent Assay (ELISA)] intended for qualitative [or semi-quantitative or quantitative tests, if appropriate validation data is provided. Performance evaluations beyond what is currently described in the template may be necessary] detection of [specify the antibody class or classes that are being detected, or indicate whether the test only detects total antibodies] antibodies to SARS-CoV-2 in human [specify matrices including anticoagulants]. The [test name] is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. Testing is limited to [laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C 263a, to perform moderate or high complexity tests and as applicable, Point of Care (POC) testing].

Results are for the detection of SARS CoV-2 antibodies. [Specify antibodies detected] antibodies to SARS-CoV-2 are generally detectable in blood several days after initial infection, although the duration of time antibodies are present post-infection is not well characterized. Individuals may have detectable virus present for several weeks following seroconversion.

Laboratories within the United States and its territories are required to report all positive results to the appropriate public health authorities.

[As applicable, the sensitivity of [test name] early after infection is unknown.] Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct testing for SARS-CoV-2 is necessary.

False positive results for [test name] may occur due to cross-reactivity from pre-existing antibodies or other possible causes. [For lateral flow devices: Due to the risk of false positive results, confirmation of positive results should be considered using second, different [as appropriate, IgG or IgM] assay].

The [test name] is only for use under the Food and Drug Administration's Emergency Use Authorization.

2\) Special Conditions for Use Statements:
For prescription use only
For in vitro diagnostic use only
For Emergency Use Authorization only

3\) Special Instrument Requirements:
The [test name] test is to be used with the [list all instruments, software requirements, other applicable instrumentation, etc.].

#### G. DEVICE DESCRIPTION AND TEST PRINCIPLE
1\) Product Overview/Test Principle:
[Describe the technology of the test and how this technology works to identify measurand (i.e., the test principle), the instruments/reader employed/required to perform the test from sample collection to result, and the specimen types for which you claim to have performance characteristics as described below]
The [test name] uses the following:
[List the antigen(s) and antibodies used in the assay to detect the antibodies in human specimens]

2\) Description of Test Steps: [Describe in order the steps of the test from specimen collection to result output.]

3\) Control Material
[List all control materials (provided with the test kit and/or required but not provided with the test kit) and describe what they are, how they are expected to work, where in the testing process they are used, and the frequency of use. If a control is commercially available, provide supplier's name and catalog number or other identifier; if your device relies on external controls that are manufactured by a third party please note that these controls should also be validated within your analytical and clinical studies described below in Section J.]

Controls that will be provided with the test kit include:

a) An external positive control for each antibody class claimed (e.g., IgG, IgM) is needed to [describe need] and is used [describe use – please specify the concentration of the positive control relative to the cut-off of your test (note that ideally the positive control concentration should be such that it is close to the cut-off of your test) and specify frequency of use.]

b) An external negative control is needed to [describe need] and is used [describe use – please specify the composition of the negative control and specify frequency of use.]

c) A [other (e.g., sample adequacy, internal, etc.)] control is needed to [describe need] and is used [describe use – please specify the composition of the control and specify frequency of use.]

Controls that are required but not provided with the test kit include [describe control – provide recommended sources of the control materials – either a separate control kit for purchase that you develop and market or a control material that can be purchased from a third party]. This/these control(s) is/are needed to [describe need] and is/are used [describe use – please also specify frequency of use].

#### H. INTERPRETATION OF RESULTS
Assessment of [test name] results should be performed after the positive and negative controls have been examined and determined to be valid and acceptable. If the controls are not valid, the patient results cannot be interpreted.

[Clearly describe how results are to be interpreted. If applicable, clearly indicate how to interpret numeric test values as positive or negative for the presence of antibodies against SARS-CoV-2. Indicate how to identify indeterminate/equivocal results (if applicable) and how the user should resolve them. Also describe if and when repeat testing may be required.

If your test is a lateral flow, please describe the results interpretation for each of the test lines. You could consider reporting the results in the form of a table as shown below for a test that detects and differentiates between IgG and IgM:

**Table 1. Interpretation of Results**
| C Line | M Line | G Line | Test Result Interpretation |
|--------|--------|--------|---------------------------|
| not present | Any | Any | Invalid Test. The specimen must be retested with another device |
| + | - | - | Valid Test, Negative for antibodies for SARS-CoV-2 |
| + | + | - | Valid Test, IgM positive for antibodies for SARS-CoV-2 |
| + | + | + | Valid Test, IgM and IgG positive for antibodies for SARS-CoV-2 |
| + | - | + | Valid Test, IgG positive for antibodies for SARS-CoV-2 |
||

If you have a lateral flow device, please include a schematic/picture showing the location of the sample well, buffer well, and control and test lines]

#### I. PRODUCT MANUFACTURING
1\) Overview of Manufacturing and Distribution
The product will be manufactured at [manufacturer's name and FDA registration number (if applicable)] by [manufacturer name] personnel consistent with practices for the production of [types of devices] based on [type of quality system*]. Material manufactured by [manufacturer's name] may be bottled and kitted by [packager name] manufacturing facility.

The current manufacturing capabilities include the ability to manufacture approximately [insert the approximate number of units/products that can currently be manufactured per week at the manufacturing facility] products per week, however in the event of a surge in demand this could be increased to [please insert the approximate maximum number of units/products that could potentially be manufactured per week at the manufacturing facility if there was a surge in demand] product per week within a [please specify in weeks/months the expected timeframe required to increase product production if required] timeframe.

2\) Component Included with the Test: Components manufactured by [manufacturer's name and FDA registration number (if applicable)] and supplied with the test include:

[List all components and reagents provided for your test, including volumes, concentrations, quantities, etc.]

**Example: Table Kit Components**
| Kit components (example) | Manufacturer |
|--------------------------|--------------|
| Test Cassette with test strip | |
| Negative control | |
| Positive control | |
| Sample buffer (bottle) | |
| Transfer pipette | |
| Lancet (for fingerstick only) | |
| Instructions for Use leaflet | |
| Packing materials | |
||

3\) Components required but not included with the test:
[List all components (e.g., timer, analyzer/reader) and reagents not included with the test that must be supplied by the user to perform the test, with specific supplier names and catalog numbers or other identifiers for obtaining these components and reagents. Please include here all specific consumables that were validated for use with your device, that are not interchangeable with other products and that are needed to guarantee device performance as established in the EUA validation studies listed in section J below].

4\) The [test name] has been validated using only the components referenced above. The [test name] was developed using [briefly describe the capture antigens and antibodies used in the test, how they were designed and purified (e.g., are monoclonal antibodies used, are they manufactured in house or purchased commercially, what species they derive from, what epitope is targeted by the antibodies used in the assay, and if commercial products is there a certificate of analysis, etc.).

5\) Testing Capabilities: [Briefly describe current sample throughput capacity, total time required to perform the test (from clinical specimen collection to result), and number of tests that can be performed. Please provide the number of kits you can manufacture per day/week.]

6\) Distribution Plan
[Describe if you will partner with other companies for the distribution of the device]

7\) Reagent Stability
[Describe the information that supports the stability claims for your device. Please indicate if the test is already in use in other parts of the world.]

#### J. PERFORMANCE EVALUATION
1\) Analytical Sensitivity and Specificity

a) Reactivity/lnclusivity:
Although mutations in the SARS-CoV-2 genome have been identified as the virus has spread, no serologically unique strains have been described relative to the originally isolated virus (this research is exceptionally limited at present).

b) Cross-Reactivity:
If a large number of known negative samples (e.g., ≥75 samples collected in the US prior to December 2019) are tested from a population with a high prevalence of vaccination against, and/or infection with, the following viruses, and specificity >98% is observed, cross-reactivity testing for the following viruses would not be expected at this time:

- anti-influenza A (IgG and IgM)
- anti-influenza B (IgG and IgM)
- anti-HCV (IgG and IgM)
- anti-HBV (IgG and IgM)
- anti-Haemophilus influenzae (IgG and IgM)
- anti-229E (alpha coronavirus)
- anti-NL63 (alpha coronavirus)
- anti-OC43 (beta coronavirus)
- anti-HKU1 (beta coronavirus)
- ANA
- anti-respiratory syncytial virus (IgG and IgM)
- anti-HIV

[If a large number of known negative samples are not evaluated, or lower than 95% specificity is observed, describe the cross-reactivity testing performed to evaluate the cross-reactants in the table above. Please include in your description the number of samples tested and how samples were prepared.]

If testing of the cross-reactants is needed to demonstrate cross-reactivity of the test, FDA believes testing a minimum of 5 individual samples for each disease/infectious agent/antibody class listed above may be acceptable.

If natural specimens are used, it is important to assess cross reactivity using sera from patients with the underlying diseases in the acute or convalescent stages of infection in order to obtain high levels of IgM or IgG for the underlying condition. If spiked samples with the IgM or IgG antibodies for the underlying conditions are prepared for this study, it is important to confirm that "negative samples" are SARS-CoV-2 IgM and IgG seronegative with the candidate assay prior to spiking. Additionally, commercially available IgM or IgG antibodies for the underlying conditions panels may be acceptable if collected prior to the COVID-19 pandemic to ensure the panels are SARS-CoV-2 antibody negative.

We recommend you present your results in the following suggested table and calculate agreement between the candidate test result and the expected result.

**Table Cross-Reactivity: [test name] example table for wet tested organisms below:**
| Virus/Bacteria/Parasite | Antibody positive | Source/ Sample type | Results* |
|-------------------------|--------------------|--------------------|----------|
| | | | |
||

*If applicable, please include the signal output for your test's technology.

[If your test exhibits significant cross-reactivity that would produce false positive results for any virus evaluated, please describe a plan to address this risk.]

2\) Class Specificity:
If your test is intended for the detection of total antibody with no differentiation between different immunoglobulins, then this study does not apply. [In this case, please indicate that this study is not applicable.]

[If your test is intended for the detection of total antibody with no differentiation between different immunoglobulins, then this study does not apply. Please indicate not applicable.

If your test is intended to differentiate between different immunoglobulins, describe the approach used to evaluate class specificity.]

[If class specificity testing is needed for your test, please describe the study, or studies, performed to demonstrate that the assay accurately detects each antibody class (e.g., IgG and IgM). This should include a description of the studies performed to evaluate the potential for human IgM to cross react and therefore produce false positive results for IgG, and the reverse, and the potential for IgM to compete with IgG and produce false negative results. Please indicate the number of samples, and the number of replicates per sample, tested. FDA believes that evaluating at least 5 samples positive for both antibody classes (IgM positive while also IgG positive), in duplicate, may be acceptable.]

Approaches to evaluate class specificity depend on the assay format. If you have well-characterized the anti-IgG and anti-IgM reagents, used in your test class specificity testing may not be needed. In this case, please describe how the reagents were characterized and such characterization supports class specificity. One recommended approach includes treating the specimen with dithiothreitol (DTT) where the final IgG result will remain unaffected and the final IgM signal will decrease or be negative. A positive control should also be included that confirms DTT activity.

[Please provide the protocol and results, including line data, from any class specificity testing.]

FDA believes that 100% agreement with expected result would establish antibody class specificity.

**If a DTT Treatment approach is followed, below is an example table for IgM and IgG:**
| Sample ID | Replicates | Result NO DTT Treatment (IgM/IgG) | Result DTT Treatment (IgM/IgG) | Expected result with DTT treatment (IgM/IgG) | Result Agreement |
|-----------|------------|-----------------------------------|--------------------------------|----------------------------------------------|-------------------|
| 1 | 1 | +/+ | -/+ | -/+ | yes |
| | 2 | +/+ | -/+ | -/+ | yes |
| 2 | 1 | +/+ | -/+ | -/+ | yes |
| | 2 | +/+ | -/+ | -/+ | yes |
| 3 | 1 | +/+ | -/+ | -/+ | yes |
| | 2 | +/+ | -/+ | -/+ | yes |
| 4 | 1 | +/+ | -/+ | -/+ | yes |
| | 2 | +/+ | -/+ | -/+ | yes |
| 5 | 1 | +/+ | -/+ | -/+ | yes |
| | 2 | +/+ | -/+ | -/+ | yes |
||

3\) Clinical Agreement Study:
[Please describe the clinical study used to evaluate the clinical performance of the test. Please note that the exact requirements for the clinical evaluation depend on access to COVID-19 disease clinical specimens at the time of the studies and the nature of the emergency.]

Initial clinical agreement trials typically evaluate all matrices that the sponsor intends to claim in their EUA submission.

The comparator method used to establish clinical truth for the patient at this time is a PCR based assay. Results from the comparator PCR method are obtained using specimens that have been validated for use with the comparator method. Consider collecting nasal swab samples from a patient for PCR and then follow with a fingerstick or blood draw from the same patient. [Please identify the PCR comparator that was used. If the PCR comparator is not an EUA-authorized test, please provide Limit of Detection (LoD) and cross-reactivity validation data. If it is an EUA-authorized test, then no validation is needed.]

Ideally, performance characteristics are established in a clinical study with prospective samples. If a prospective study is not feasible, an acceptable alternative would be to test retrospectively collected SARS-CoV-2 antibody positive specimens from patients that have been previously confirmed infected by SARS-CoV-2 RT PCR, accompanied by basic information such as the population from which the sample was drawn and the comparator method, specimen collection date, date of onset of symptoms (if present/known), and comparator method to confirm patients as SARS-CoV-2 infected or not infected (see above).

Clinical agreement data should be provided using at least 30 antibody positive samples for each immunoglobulin claimed and 75 antibody negative samples from patients tested for SARS-CoV-2 and confirmed as negative and the data should demonstrate a minimum overall 90.0% positive percent agreement and overall 95.0% negative percent agreement, and for tests that report specifically IgM and IgG results, a minimum positive percent agreement for IgM of 70% and a minimum positive percent agreement for IgG of 90%. Point estimates not lower than 93% for combined NPA, not lower than 90% for combined PPA, and for tests that specifically report IgG or IgG and IgM, PPA for IgG not lower than 87%, and PPA for IgM not lower than 67% may be acceptable if a larger number of samples are evaluated and the lower bounds of the 95% confidence intervals are higher than would be demonstrated in a clinical agreement study with 30 antibody positive and 75 antibody negative samples.

For visually read tests, blinding and randomization should be included in the experimental design

If a claim for fingerstick is desired, we believe evaluating a minimum of 30 positive and 30 negative fingerstick whole blood samples may be acceptable to demonstrate clinical performance in fingerstick samples. If a claim for near patient testing, or point-of-care (POC) is desired, please see the section specific to POC below.

[Please specify how the samples were generated, collected, and sourced. Please also specify if the samples were fully prospective, mix of prospective, retrospective and/or contrived. Please specify inclusion/exclusion criteria, collection and testing sites, number of samples collected and tested, and number of operators performing the testing, as available.]

[Please clearly describe the data analysis methods used and provide the results from the study, including line data. We suggest calculating positive and negative percent agreement between the candidate device and the comparator method results separately for each claimed matrix, using 2 x 2 tables as follows:

| |  | Comparator method/Clinical truth ||
|:-:|:-----------:|:--------------------------------:|:----------:|
| | | Positive | Negative |
| Your Device | Positive | A | B |
| | Negative | C | D |
||

Percent Positive Agreement = A/(A + C) or
True Positives/(True Positives + False Negatives)

Negative Percent Agreement = D/(B + D) or
True Negatives/(True Negatives + False positives)

If you claim that your test can differentiate between IgG and IgM, PPA and NPA for IgG and IgM separately should be calculated separately.]

4\) Matrix Equivalency
[Please describe the protocol and provide the results from any matrix equivalency studies performed to support the performance of the assay in claimed sample matrices (serum, EDTA plasma, venipuncture whole blood, different anticoagulants, etc.) that were not evaluated in the initial clinical agreement study.] Please note: Fingerstick whole blood is not considered to be the same sample type as venipuncture whole blood and clinical agreement against PCR should be evaluated (please see Section J.3 above).

Matrix equivalency studies are performed to evaluate specimen matrices for which clinical agreement isn't initially assessed. In these studies, the matrix in which the clinical study(ies) are conducted is the comparator matrix/specimen type and each matrix set (whole blood, plasma, serum) comes from the same donor (i.e., paired samples).

Typically, negative, low positive (e.g., for lateral flow tests, faint test line), and moderate positive (e.g., for lateral flow tests, strong test line) are evaluated. We believe five samples, run in duplicate for each concentration, for a total of 30 results per matrix (assuming 3 concentrations were evaluated) may be acceptable. To allow for comparison, negative samples for each claimed specimen type/matrix are spiked with the same amount of analyte (SARS-CoV-2 IgG and IgM). We believe confirming samples are antibody seronegative with the candidate assay before spiking with SARS-CoV-2 IgG and IgM antibodies is important. For visually read tests, blinding and randomization are important considerations for the experimental design.

For these types of studies, typically, each sample is assayed with the candidate device, and the results obtained for the comparator matrix are compared to the results obtained for each additional matrix under evaluation for each subject. Positive percent agreement and negative percent agreement for each matrix with respect to the comparator matrix are calculated. We believe that at least 95% agreement across all matrices/subject may be acceptable to demonstrate that performance between the matrices can be considered equivalent.

5\) Studies to support Point of Care claim, as applicable.
[If the device is intended for near patient testing or Point of Care (POC), please provide data to demonstrate that non-laboratory personnel can perform the test accurately in the intended use environment (i.e. a non-laboratorian healthcare provider accuracy study). Please also provide data to demonstrate robust use of your device for near patient testing (e.g., as applicable, studies to demonstrate the impact of adding different volumes of sample, different volumes of reagents, incorrect order of sample or reagent application).]

#### K. UNMET NEED ADDRESSED BY THE PRODUCT
This section will be completed by FDA.

#### L. APPROVED/CLEARED ALTERNATIVE PRODUCTS
Currently no methods for the qualitative detection of SARS-CoV-2 IgM or IgG antibodies have been approved or cleared by FDA.

#### M. RISKS AND BENEFITS:
This section will be completed by FDA.

#### N. FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:
[Include proposed Fact Sheets for Patients and Healthcare Providers] - see examples for authorized EUA tests on our website. During review, FDA will make available Fact Sheet templates.

#### O. INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:
[Include Instructions for Use, Box Labels, Vial Labels and any other proposed labeling.]

#### P. RECORD KEEPING AND REPORTING INFORMATION TO FDA:
[Manufacturer Name] will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report on adverse events, and this website is referenced in the Fact Sheet for Health Care providers as well as through the [Manufacturer Name] Product Support website: [link to Manufacturer's website]. Each report of an adverse event will be processed according to [Manufacturer Name]'s Non-Conformance Reporting Requirements, and Medical Device Reports will be filed with the FDA as required. Through a process of inventory control, [Manufacturer Name] will also maintain records of device usage/purchase. [Manufacturer Name] will collect information on the performance of the test, and report to FDA any suspected occurrence of false positive or false negative results of which [Manufacturer Name] becomes aware. [Manufacturer Name] will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

## Appendix B: Serology Template for Laboratories
This template (the "template") includes FDA's current recommendations for laboratories concerning what data and information they should submit to support an EUA request for a SARS-CoV-2 antibody test developed for use in a single CLIA certified high-complexity laboratory. As outlined in Section V.C. of this guidance, FDA recommends that the following validation studies be conducted for a SARS-CoV-2 serological assay: Cross-reactivity/Analytical Specificity, Class Specificity, and Clinical Agreement Study. This template provides one example of how a laboratory can submit these validation data and other recommended information to FDA, but alternative approaches can be used. For more information about EUAs in general, please see the FDA Guidance document: [Emergency Use Authorization of Medical Products and Related Authorities](https://www.fda.gov/media/97321/download).

### GENERAL INFORMATION ABOUT THIS TEMPLATE
- This EUA review template (EUA template) is only intended for use by CLIA certified high-complexity laboratories who intend to submit a pre-EUA or EUA to FDA for a SARS-CoV-2 antibody test.
- Text highlighted in yellow [Text] should be completed by the laboratory (sponsor) as applicable to their specific test. Text in bold outlines the Food and Drug Administration's (FDA) recommendations for the sponsors' consideration when providing the suggested information in a specific section. Text in regular font is recommended language provided by FDA as an example. As explained throughout, this template is intended to be a helpful aid that provides FDA's recommendations to help facilitate the pre-EUA/EUA submission process.
- This is an EUA interactive review template for Pre-EUA/EUA submissions. The template is subject to change as we learn more about the COVID-19 disease and its risk-benefit profile.
- Please be reminded that tests for the detection of antibodies against SARS-CoV-2 must not be distributed and/or used for clinical diagnoses.

### EXAMPLE TEMPLATE
#### A. PURPOSE OF SUBMISSION
Emergency Use Authorization (EUA) request for [test name] to be performed for the detection of [specify types of antibodies e.g., IgG, IgG/IgM or total] antibodies to SARS-CoV-2 in [specify matrices] from individuals with current or prior COVID-19 infection. The test will be performed in CLIA certified high-complexity laboratories. Additional testing and confirmation procedures should be performed in consultation with public health and/or other authorities to whom reporting is required. Positive results should also be reported in accordance with local, state, and federal regulations.

#### B. MEASURAND
[Specify what the test detects and whether it can differentiate between IgM and IgG or if the test detects total antibody without differentiation]

#### C. LABORATORY/SPONSOR
[Include the following information: Official name, address and contact information of applicant and all locations where specimen testing will be performed]

#### D. REGULATORY INFORMATION
D. Approval/Clearance Status:
The [test name] is not cleared, CLIA waived, approved, or subject to an approved investigational device exemption.

#### E. PROPOSED INTENDED USE
1\) Intended Use (IU):
The proposed IU will be finalized based on the data provided at the time of authorization. An example IU is provided below.

The [test name] is a [specify technology e.g., Enzyme-Linked Immunosorbent Assay (ELISA)] intended for qualitative [or semi-quantitative or quantitative tests, if appropriate validation data is provided. Performance evaluations beyond what is currently described in the template may be necessary] detection of [specify the antibody class or classes that are being detected, or indicate whether the test only detects total antibodies] antibodies to SARS-CoV-2 in human [specify matrices including anticoagulants]. The [test name] is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. The [test name] should not be used to diagnose acute SARS-CoV-2 infection. Testing is limited to [Name of Clinical Laboratory(s)] that are Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a certified high-complexity laboratories.

Results are for the detection of SARS CoV-2 antibodies. [Specify antibodies detected] antibodies to SARS-CoV-2 are generally detectable in blood several days after initial infection, although the duration of time antibodies are present post-infection is not well characterized. Individuals may have detectable virus present for several weeks following seroconversion.

Laboratories within the United States and its territories are required to report all positive results to the appropriate public health authorities.

[As applicable, the sensitivity of [test name] early after infection is unknown.] Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct testing for SARS-CoV-2 is necessary.

False positive results for [test name] may occur due to cross-reactivity from pre-existing antibodies or other possible causes.

The [test name] is only for use under the Food and Drug Administration's Emergency Use Authorization.

2\) Special Conditions for Use Statements:
For prescription use only
For in vitro diagnostic use only
For Emergency Use Authorization only

3\) Instruments Used:
The [test name] test is to be used with the [list all instruments, software requirements, other applicable instrumentation, etc.].

#### F. DEVICE DESCRIPTION AND TEST PRINCIPLE
1\) Product Overview/Test Principle:
[Briefly describe the technology of the test and how this technology identifies the measurand (i.e., the test principle), and the instruments/reader employed/required to perform the test from sample collection to result and the specimen types for which you claim to have performance characteristics as described below.]

The [test name] uses the following: [List the antigen(s) and antibodies used in the assay to detect the antibodies in human specimens]

2\) Description of Test Steps: [Describe in order the steps of the test from specimen collection to result output.]

3\) Control Material
[Please describe the assay controls to be performed in the laboratory, including the positive control for each antibody class the test is intended to detect, the negative control, and any other necessary controls. Please also describe the frequency with which controls will be performed.]

#### G. INTERPRETATION OF RESULTS
Assessment of [test name] results should be performed after the positive and negative controls have been examined and determined to be valid and acceptable. If the controls are not valid, the patient results cannot be interpreted.

[Clearly indicate how to interpret numeric test values as positive or negative for the presence of antibodies against SARS-CoV-2. If applicable, indicate how to identify indeterminate/equivocal results and how the user should resolve them. Also describe if and when repeat testing may be required.]

#### H. PERFORMANCE EVALUATION
1\) Analytical Sensitivity and Specificity
a) Reactivity/lnclusivity:
Although mutations in the SARS-CoV-2 genome have been identified as the virus has spread, no serologically unique strains have been described relative to the originally isolated virus (this research is exceptionally limited at present).

b) Cross-Reactivity:
If a large number of known negative samples (e.g., ≥75 samples collected in the US prior to December 2019) are tested from a population with a high prevalence of vaccination against, and/or infection with, the following viruses, and specificity >98% is observed, cross-reactivity testing for the following viruses would not be expected at this time:

- anti-influenza A (IgG and IgM)
- anti-influenza B (IgG and IgM)
- anti-HCV (IgG and IgM)
- anti-HBV (IgG and IgM)
- anti-Haemophilus influenzae (IgG and IgM)
- anti-229E (alpha coronavirus)
- anti-NL63 (alpha coronavirus)
- anti-OC43 (beta coronavirus)
- anti-HKU1 (beta coronavirus)
- ANA
- anti-respiratory syncytial virus (IgG and IgM)
- anti-HIV

[If a large number of known negative samples are not evaluated, or lower than 95% specificity is observed, describe the cross-reactivity testing performed to evaluate the cross-reactants in the table above.]

If testing of the cross-reactants on above is needed to demonstrate cross-reactivity for the test, FDA believes testing a minimum of 5 individual samples for each disease/infectious agent/antibody class listed above may be acceptable.

If natural specimens are used, it is important to assess cross reactivity using sera from patients with the underlying diseases in the acute or convalescent stages of infection in order to obtain high levels of IgM or IgG for the underlying condition. If spiked samples with the IgM or IgG antibodies for the underlying conditions are prepared for this study, it is important to confirm that "negative samples" are SARS-CoV-2 IgM and IgG seronegative with the candidate assay prior to spiking. Additionally, commercially available IgM or IgG antibodies for the underlying conditions panels may be acceptable if collected prior to the COVID-19 pandemic to ensure the panels are SARS-CoV-2 antibody negative.

We recommend you present your results in the following suggested table and calculate agreement between the candidate test result and the expected result.

**Cross-Reactivity: [test name] example table for wet tested organisms below:**
| Virus/Bacteria/Parasite Antibody positive | Source/ Sample type | Results* |
|-------------------------|--------------------|--------------------|
|                         |                    |                    |      
||

*If applicable, please include the signal output for your test's technology.

[If your test exhibits significant cross-reactivity that would produce false positive results for any virus evaluated, please describe a plan to address this risk.]

2\) Class Specificity:
If your test is intended for the detection of total antibody with no differentiation between different immunoglobulins, then this study does not apply. [In this case, please indicate that this study is not applicable.]

[If your test is intended for the detection of total antibody with no differentiation between different immunoglobulins, then this study does not apply. Please indicate not applicable.

If your test is intended to differentiate between different immunoglobulins, describe the approach used to evaluate class specificity.]

[If class specificity testing is needed for your test, please describe the study, or studies, performed to demonstrate that the assay accurately detects each antibody class (e.g., IgG and IgM). This should include a description of the studies performed to evaluate the potential for human IgM to cross react and therefore produce false positive results for IgG, and the reverse, and the potential for IgM to compete with IgG and produce false negative results. Please indicate the number of samples, and the number of replicates per sample, tested. FDA believes that evaluating at least 5 samples positive for both antibody classes (IgM positive while also IgG positive), in duplicate, may be acceptable.]

Approaches to evaluate class specificity depend on the assay format. If you have well-characterized the anti-IgG and anti-IgM reagents, used in your test class specificity testing may not be needed. In this case, please describe how the reagents were characterized and such characterization supports class specificity. One recommended approach includes treating the specimen with dithiothreitol (DTT) where the final IgG result will remain unaffected and the final IgM signal will decrease or be negative. A positive control should also be included that confirms DTT activity.

[Please provide the protocol and results, including line data, from any class specificity testing.]

FDA believes that 100% agreement with expected result would establish antibody class specificity.

If a DTT Treatment approach is followed, below is an example table for IgM and IgG:

| Sample ID | Replicates | Result NO DTT Treatment (IgM/IgG) | Result DTT Treatment (IgM/IgG) | Expected result with DTT treatment (IgM/IgG) | Result Agreement |
|-----------|------------|-----------------------------------|--------------------------------|----------------------------------------------|-------------------|
| 1 | 1 | +/+ | -/+ | -/+ | yes |
|   | 2 | +/+ | -/+ | -/+ | yes |
| 2 | 1 | +/+ | -/+ | -/+ | yes |
|   | 2 | +/+ | -/+ | -/+ | yes |
| 3 | 1 | +/+ | -/+ | -/+ | yes |
|   | 2 | +/+ | -/+ | -/+ | yes |
| 4 | 1 | +/+ | -/+ | -/+ | yes |
|   | 2 | +/+ | -/+ | -/+ | yes |
| 5 | 1 | +/+ | -/+ | -/+ | yes |
|   | 2 | +/+ | -/+ | -/+ | yes |
||

3\) Clinical Agreement Study:
[Please describe the clinical study used to evaluate the clinical performance of the test. Please note that the exact requirements for the clinical evaluation depend on access to COVID-19 disease clinical specimens at the time of the studies and the nature of the emergency.]

Initial clinical agreement trials typically evaluate all matrices that the sponsor intends to claim in their EUA submission.

The comparator method used to establish clinical truth for the patient at this time is a PCR based assay. Results from the comparator PCR method are obtained using specimens that have been validated for use with the comparator method. Consider collecting nasal swab samples from a patient for PCR and then follow with a fingerstick or blood draw from the same patient. [Please identify the PCR comparator that was used. If the PCR comparator is not an EUA-authorized test, please provide Limit of Detection (LoD) and cross-reactivity validation data. If it is an EUA-authorized test, then no validation is needed.]

Ideally, performance characteristics are established in a clinical study with prospective samples. If a prospective study is not feasible, an acceptable alternative would be to test retrospectively collected SARS-CoV-2 antibody positive specimens from patients that have been previously confirmed infected by SARS-CoV-2 RT PCR, accompanied by basic information such as the population from which the sample was drawn and the comparator method, specimen collection date, date of onset of symptoms (if present/known), and comparator method to confirm patients as SARS-CoV-2 infected or not infected (see above).

Clinical agreement data should be provided using at least 30 antibody positive samples for each immunoglobulin claimed and 75 antibody negative samples from patients tested for SARS-CoV-2 and confirmed as negative and the data should demonstrate a minimum overall 90.0% positive percent agreement and overall 95.0% negative percent agreement, and for tests that report specifically IgM and IgG results, a minimum positive percent agreement for IgM of 70% and a minimum positive percent agreement for IgG of 90%. Point estimates not lower than 93% for combined NPA, not lower than 90% for combined PPA, and for tests that specifically report IgG or IgG and IgM, PPA for IgG not lower than 87%, and PPA for IgM not lower than 67% may be acceptable if a larger number of samples are evaluated and the lower bounds of the 95% confidence intervals are higher than would be demonstrated in a clinical agreement study with 30 antibody positive and 75 antibody negative samples.

If a claim for fingerstick is desired, we believe evaluating a minimum of 30 positive and 30 negative fingerstick whole blood samples may be acceptable to demonstrate clinical performance in fingerstick samples.

[Please specify how the samples were generated, collected, and sourced. Please also specify if the samples were fully prospective, mix of prospective, retrospective and/or contrived. Please specify inclusion/exclusion criteria, collection and testing sites, number of samples collected and tested, and number of operators performing the testing, as available.]

[Please clearly describe the data analysis methods used and provide the results from the study, including line data. We suggest calculating positive and negative percent agreement between the candidate device and the comparator method results separately for each claimed matrix, using 2 x 2 tables as follows:

| |  | Comparator method/Clinical truth ||
|:-:|:-----------:|:--------------------------------:|:----------:|
| | | Positive | Negative |
| Your Device| Positive | A | B |
| | Negative | C | D |
||

Percent Positive Agreement = A/(A + C) or
True Positives/(True Positives + False Negatives)

Negative Percent Agreement = D/(B + D) or
True Negatives/(True Negatives + False positives)

If you claim that your test can differentiate between IgG and IgM, PPA and NPA for IgG and IgM separately would be calculated separately.]

4\) Matrix Equivalency
[Please describe the protocol and results from any matrix equivalency studies performed to support the performance of the assay in claimed sample matrices (serum, EDTA plasma, venipuncture whole blood, different anticoagulants, etc.) that were not evaluated in the initial clinical agreement study.]

Matrix equivalency studies are performed to evaluate specimen matrices for which clinical agreement isn't initially assessed. In these studies, the matrix in which the clinical study(ies) are conducted is the comparator matrix/specimen type and each matrix set (whole blood, plasma, serum) comes from the same donor (i.e., paired samples).

Typically, negative, low positive, and moderate positive samples are evaluated. We believe five samples, run in duplicate for each concentration for a total of 30 results per matrix (assuming 3 concentrations were evaluated) may be acceptable. To allow for comparison, negative samples for each claimed specimen type/matrix are spiked with the same amount of analyte (SARS-CoV-2 IgG and IgM). We believe confirming samples are antibody seronegative with the candidate assay before spiking with SARS-CoV-2 IgG and IgM antibodies is important.

For these types of studies, typically, each sample is assayed with the candidate device, and the results obtained for the comparator matrix are compared to the results obtained for each additional matrix under evaluation for each subject. Positive percent agreement and negative percent agreement for each matrix with respect to the comparator matrix are calculated. We believe that at least 95% agreement across all matrices/subject may be acceptable to demonstrate that performance between the matrices can be considered equivalent.

#### I. UNMET NEED ADDRESSED BY THE PRODUCT
This section will be completed by FDA.

#### J. APPROVED/CLEARED ALTERNATIVE PRODUCTS
Currently no methods for the qualitative detection of SARS-CoV-2 IgM or IgG antibodies have been approved or cleared by FDA.

#### K. RISKS AND BENEFITS:
This section will be completed by FDA.

#### L. FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:
[Include proposed Fact Sheets for Patients and Healthcare Providers] - see examples for authorized EUA tests on our website. During review, FDA will make available Fact Sheet templates.

#### M. INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:
[In lieu of a package insert or labeling, please include your Laboratory SOP/protocol.]

#### N. RECORD KEEPING AND REPORTING INFORMATION TO FDA:
The laboratory will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report on adverse events, and this website is referenced in the Fact Sheet for Health Care providers. The laboratory will maintain will information on the performance of the test, and report to FDA any suspected change in performance of which they become aware. The laboratory will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.


# 9,407  2020-05-11_FDA Guidance - COVID IVD Test Developers v4.md
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title: FDA Guidance - COVID IVD Test Developers v4
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summary_short: The FDA Guidance for COVID IVD Test Developers v4 updates the May 4, 2020 policy by emphasizing the expanded availability of downloadable EUA templates for different COVID-19 test types and clarifying expectations for labs, states, and commercial manufacturers operating under enforcement discretion during the public health emergency. It maintains the core “validate + notify + submit EUA within a defined window” framework (including listing/removal on FDA’s notification pages) while continuing tighter controls and labeling expectations for serology tests and broader validation guidance for molecular, antigen, and serological assays. The guidance helps developers navigate a more standardized EUA process by pairing policy flexibilities with clearer submission tools and oversight triggers.


CONTENT

***INTERNAL TITLE:*** Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)
Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff

**Document issued on the web on May 11, 2020.**

**This document supersedes "Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency: Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff" issued May 4, 2020.**

U.S. Department of Health and Human Services  
Food and Drug Administration  
Center for Devices and Radiological Health

## Preface
### Public Comment
This guidance is being issued to address the Coronavirus Disease 2019 (COVID-19) public health emergency. This guidance is being implemented without prior public comment because the Food and Drug Administration (FDA or Agency) has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency's good guidance practices.

Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov. All comments should be identified with the docket number FDA-2020-D-0987 and complete title of the guidance in the request.

### Additional Copies
Additional copies are available from the FDA webpage titled "COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders," available at https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders, and the FDA webpage titled "Search for FDA Guidance Documents," available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. You may also send an e-mail request to CDRH-Guidance@fda.hhs.gov to receive an additional copy of the guidance. Please include the document number 20010-R3 and complete title of the guidance in the request.

### Questions
For questions about this document, contact CDRH-EUA-Templates@fda.hhs.gov.

## Table of Contents
|  |  |  |
|---------|-------|------|
| I. | Introduction | 4 |
| II. | Background | 5 |
| III. | Scope | 6 |
| IV. | Policy | 6 |
| A. | Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing Using Their Validated Diagnostic Tests Prior to EUA Submission | 8 |
| 1. | Validation | 8 |
| 2. | FDA Notification | 9 |
| 4. | EUA Request | 9 |
| 5. | Clinical Testing | 10 |
| B. | State Authorization of Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High-Complexity Testing | 11 |
| C. | Commercial Manufacturer Development and Distribution of Diagnostic Tests Prior to EUA Submission | 12 |
| 1. | Validation | 12 |
| 2. | FDA Notification | 12 |
| 4. | EUA Request | 13 |
| 5. | Clinical Testing | 14 |
| D. | Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Prior to or Without an EUA | 14 |
| 1. | Validation | 15 |
| 2. | FDA Notification | 16 |
| 4. | EUA Request | 17 |
| V. | Validation Study Recommendations Based on the Technological Principles of Tests | 17 |
| A. | Molecular Diagnostic Tests | 18 |
| (1) | Limit of Detection | 18 |
| (2) | Clinical Evaluation | 18 |
| (3) | Inclusivity | 19 |
| (4) | Cross-reactivity | 19 |
| B. | Antigen Detection Tests | 19 |
| C. | Serological Tests | 20 |
| VI. | Availability of EUA Templates | 20 |
||

## I. Introduction
FDA plays a critical role in protecting the United States from threats such as emerging infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support response efforts to this pandemic.

FDA is issuing this guidance to provide a policy to help accelerate the availability of novel coronavirus (COVID-19) tests developed by laboratories and commercial manufacturers for the duration of the public health emergency. Rapid detection of COVID-19 cases in the United States requires wide availability of testing to control the emergence of this rapidly spreading, severe illness. This guidance describes a policy for laboratories and commercial manufacturers to help accelerate the use of tests they develop in order to achieve more rapid and widespread testing capacity in the United States.

This policy is intended to remain in effect only for the duration of the public health emergency related to COVID-19 declared by the Secretary of Health and Human Services (HHS) on January 31, 2020, effective January 27, 2020, including any renewals made by the HHS Secretary in accordance with section 319(a)(2) of the Public Health Service Act (PHS Act).

Given this public health emergency, and as discussed in the Notice in the Federal Register of March 25, 2020, titled "Process for Making Available Guidance Documents Related to Coronavirus Disease 2019," available at https://www.govinfo.gov/content/pkg/FR-2020-03-25/pdf/2020-06222.pdf, this guidance is being implemented without prior public comment because FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency's good guidance practices.

In general, FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.

## II. Background
There is currently a pandemic of respiratory disease caused by a novel coronavirus. The virus has been named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) and the disease it causes has been named "Coronavirus Disease 2019" (COVID-19). On January 31, 2020, HHS issued a declaration of a public health emergency related to COVID-19 and mobilized the Operating Divisions of HHS. In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19.

SARS-CoV-2 has demonstrated the capability to spread rapidly, leading to significant impacts on healthcare systems and causing societal disruption. The potential public health threat posed by COVID-19 is high, both globally and to the United States. To respond effectively to the COVID-19 outbreak, rapid detection of cases and contacts, appropriate clinical management and infection control, and implementation of community mitigation efforts are critical. FDA believes the policies set forth in this guidance will help address these urgent public health concerns by helping to expand the number and variety of tests, as well as available testing capabilities in reference and commercial laboratories and healthcare settings, while helping ensure these tests are accurate and reliable.

The Centers for Disease Control and Prevention (CDC) laboratories have supported the COVID-19 response, including development of a diagnostic assay that was issued an Emergency Use Authorization (EUA) on February 4, 2020. Since authorizing CDC's EUA, FDA has been actively working with other SARS-CoV-2 diagnostic test developers to help accelerate development programs and respond to requests for in vitro diagnostic EUAs. However, the severity and scope of the current COVID-19 situation around the globe necessitates greater testing capacity for the virus than is currently available.

The EUA authorities allow FDA to help strengthen the nation's public health protections against chemical, biological, radiological, and nuclear (CBRN) threats by facilitating the availability and use of medical countermeasures initiatives (MCMs) needed during certain public health emergencies. Under section 564 of the FD&C Act, the FDA Commissioner may authorize the use of unapproved medical products, or unapproved uses of approved medical products, in certain emergency circumstances, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use, to diagnose, treat, or prevent serious or life-threatening disease or conditions caused by CBRN threat agents when certain criteria are met.

## III. Scope
The policies described in this guidance for accelerating availability of testing for COVID-19 apply to certain laboratories and commercial manufacturers developing SARS-CoV-2 tests during the public health emergency, as described below.

## IV. Policy
This guidance describes policies intended to help rapidly expand testing capacity by facilitating the development and use of SARS-CoV-2 tests during the public health emergency.

This guidance describes two policies for accelerating the development of certain laboratory-developed diagnostic tests for COVID-19 – one leading to an EUA submission to FDA, and the other not leading to an EUA submission when the test is developed under the authorities of the State in which the laboratory resides and the State takes responsibility for COVID-19 testing by laboratories in its State. The policy leading to an EUA remains unchanged from the initial publication of this guidance on February 29, 2020, though some process updates and clarifications have been made as discussed further below. The policy for State oversight remains unchanged from the second publication of this guidance on March 16, 2020.

In addition, this guidance describes a policy for commercial manufacturers to more rapidly distribute their SARS-CoV-2 diagnostic tests to laboratories for specimen testing after validation, while an EUA is being prepared for submission to FDA. This policy remains unchanged from the second publication of this guidance on March 16, 2020, though some process updates and clarification have been made as discussed further below.

This guidance also describes a policy regarding SARS-CoV-2 serological testing, which was modified in the May 4, 2020 publication of this guidance as it pertains to commercial manufacturers but not laboratories. At the time of prior issuance on March 16, 2020, FDA provided flexibility for serology tests to be marketed with notification to FDA and certain labeling information, but without submission of an EUA. FDA's policy was based on the considerations that serology tests are not meant to diagnose active SARS-CoV-2 infection and that early availability and use of these tests could help answer critical questions about the prevalence of COVID-19 infections in different communities, whether the presence of antibodies conveys immunity, and, if so, for how long. That policy succeeded in encouraging development of serology tests.

In addition to this policy, FDA has authorized several serology tests under individual EUAs and has issued an umbrella EUA providing a streamlined approach for EUA authorization of commercial serology tests that are evaluated by the National Institutes of Health's National Cancer Institute (NIH/NCI). Also since the March 16, 2020 publication of this guidance, FDA has become aware that a concerning number of commercial serology tests are being promoted inappropriately, including for diagnostic use, or are performing poorly based on an independent evaluation by the NIH, indicating that greater FDA oversight of commercial serology tests is important to protect the public health.

As outlined in the May 4, 2020 update, FDA does not intend to object as described below where commercial manufacturers develop and distribute their serology tests after validation, for a limited period of time, while an EUA is being prepared for submission to FDA. Appendices with templates for such submissions have been added to facilitate and streamline the EUA process.

The policy for serological tests developed and used by laboratories that are certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing has not changed from the March 16, 2020 guidance, though FDA continues to encourage such laboratories to submit EUAs for their laboratory developed tests.

In the context of a public health emergency involving pandemic infectious disease, it is critically important that tests are validated because false results not only can negatively impact the individual patient but also can have broad public health impact. In this guidance, FDA provides recommendations regarding validation of COVID-19 tests based on the available information. FDA encourages test developers to discuss any alternative technological approaches to validating their test with FDA.

The latest update addresses availability, through download from our website, of a series of templates that developers may choose to use to facilitate the preparation, submission, and authorization of an EUA for various types of COVID-19 tests.

### A. Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High Complexity Testing Using Their Validated Diagnostic Tests Prior to EUA Submission
The policy described in this subsection applies to laboratories certified under CLIA that meet the CLIA regulatory requirements to perform high-complexity testing and that seek to develop and perform diagnostic tests to detect the SARS-CoV-2 virus and pursue an EUA from FDA for those tests. This policy does not apply to home collection of specimens to be sent for testing at a laboratory certified under CLIA for high-complexity testing.

FDA anticipates that clinical laboratories may need to design and manufacture the individual test kit components (e.g., primers, probes, etc.), or to purchase research use only (RUO) components from third party manufacturers, for the development of their assays.

In light of the increasing numbers of COVID-19 cases throughout the country and the urgent need to expand the nation's capacity for COVID-19 testing during the public health emergency, FDA does not intend to object to the use of these SARS-CoV-2 tests for specimen testing for a reasonable period of time, where the test has been validated and while the laboratory is preparing their EUA request, and where the laboratory gives notification of validation to FDA, as described below. FDA believes that 15 business days is a reasonable period of time to prepare an EUA submission for a test that has already been validated.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is critically important that tests are validated because false results can negatively impact not only the individual patient but also can have broad public health impact. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages laboratories to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

#### 2. FDA Notification
Following completion of assay validation, laboratories should notify FDA (e.g., email to CDRH-EUA-Templates@FDA.HHS.GOV) that their assay has been validated. This notification should include the name of the laboratory, name of the laboratory director, laboratory address, and contact person in this email. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the laboratory name to FDA's website listing. As noted above, FDA recommends that laboratories submit a completed EUA request within 15 business days of the notification to FDA that the assay has been successfully validated. If an EUA request is not submitted within this timeframe, FDA intends to remove the laboratory from its website listing of laboratories that have notified FDA and may take additional actions as appropriate.

It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Reporting of Results
In order to provide transparency, FDA recommends that test reports include a general statement that the test has been validated but FDA's independent review of this validation is pending.

Laboratories should immediately notify appropriate Federal, State, and local public health agencies of all positive results.

#### 4. EUA Request
FDA has made available, through download from our website, a template that laboratories may choose to use to facilitate the preparation, submission, and authorization of an EUA for a molecular diagnostic test. Laboratories that intend to use alternative approaches should consider seeking FDA's feedback or recommendation to help them through the pre-EUA and EUA process. FDA encourages laboratories to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

Soon after receiving the EUA request, FDA intends to perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the laboratory to address the problem (e.g., through labeling or bench testing). If any problems are significant and cannot be addressed in a timely manner, FDA would expect the laboratory to stop testing and issue corrected test reports indicating prior results may not be accurate. In such circumstances, FDA intends to remove the laboratory from the website listing of notifications.

Issued EUAs are posted on FDA's website.

When a laboratory makes a modification to an EUA authorized test for use of a new specimen type, FDA does not intend to object to the use of such a modified test without notification to FDA or a new or amended EUA where the new specimen type has been previously authorized for another test of the same technology and where the EUA authorized test is validated for the new specimen type. Modifications to an EUA authorized test for use of a new specimen type that has not been previously authorized for another test of the same technology must be authorized under a new or amended EUA prior to clinical use.

For all other types of modifications, FDA does not intend to object to the use of a test, without notification to FDA or a new or amended EUA, where the test is a modification of an EUA-authorized test and the modified test is validated using a bridging study to the EUA-authorized test. One way to bridge to a new component is to establish equivalent performance between parallel testing of the same specimens with the new and original components. We recommend testing 3-fold serial dilutions of SARS-CoV-2 viral materials (e.g., whole genomic viral RNA or inactivated virus, etc.) in a pooled respiratory sample matrix in triplicate until you achieve a hit rate of <100%. If the resultant Limit of Detection (LoD) is the same as the LoD for the unmodified authorized test (i.e., ≤3xLOD), then FDA believes the two tests can be considered to have equivalent performance.

When validating through a bridging study and not pursuing an EUA amendment for the modification, FDA would like to see the laboratory's validation data informally through an email to CDRH-EUA-Templates@FDA.HHS.GOV. If FDA's review of the bridged validation data indicates that it could be applicable to modifications of other tests with an EUA, or to other laboratories modifying the same authorized test, and the laboratory agrees to FDA sharing that information on our website for use by other laboratories, FDA intends to update our FAQs so other laboratories can refer to the validation for their testing, without conducting their own bridging study for the same modification. This informal sharing of data would not be considered to be a notification, as discussed above, or an EUA request.

#### 5. Clinical Testing
While awaiting an FDA determination on the EUA request, FDA recommends that clinical laboratories obtain confirmation of the first five positive and the first five negative clinical specimens using an EUA-authorized assay. This testing may be performed within the same laboratory using an EUA-authorized assay or may involve sending these ten specimens to another laboratory for confirmation. If any of these results cannot be confirmed, the laboratory should notify FDA at CDRH-EUA-Templates@FDA.HHS.GOV, and take other appropriate actions such as terminating testing patient specimens, and issuing corrected test reports indicating prior test results may not be accurate.

### B. State Authorization of Laboratories Certified under CLIA that Meet the CLIA Regulatory Requirements to Perform High Complexity Testing
On March 12, 2020, FDA issued enforcement discretion and stated that it was not objecting to the Wadsworth Center authorizing certain laboratories in the State of New York to begin patient testing under certain circumstances to increase availability of COVID-19 testing in response to a request from the Wadsworth Center of the New York State Department of Health (Wadsworth). Wadsworth had informed FDA that it would be willing to have clinical laboratories that currently hold a New York State Department of Health clinical laboratory permit to notify Wadsworth that they have validated a test for COVID-19, and to submit validation studies to Wadsworth. Wadsworth likewise said it would notify the laboratory if it identified any concerns, and request that the laboratory terminate testing patient specimens and issue corrected test reports indicating prior test results might not be accurate.

On March 13, 2020, the President issued a "Memorandum on Expanding State-Approved Diagnostic Tests" (Memorandum), which refers to the flexibility that FDA allowed New York State and states as follows:

"Should additional States request flexibility to authorize laboratories within the State to develop and perform tests used to detect COVID-19, the Secretary shall take appropriate action, consistent with law, to facilitate the request."

In accordance with the Memorandum, FDA describes below its policy regarding States and territories that authorize laboratories within their State or territory to develop their own COVID-19 tests and perform specimen testing, where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA.

A State or territory choosing to authorize laboratories within that State or territory to develop and perform a test for COVID-19 would do so under authority of its own State law, and under a process that it establishes. FDA does not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA, and where instead the State or territory takes responsibility for COVID-19 testing by laboratories in its State during the COVID-19 outbreak.

FDA requests that the State or territory notify us if they choose to use this flexibility to expedite COVID-19 testing. FDA will not be reviewing the process adopted by the State or territory, which we understand may be different than the process adopted by New York State. FDA expects that such states as part of their oversight process will require laboratories developing SARS-CoV-2 tests to validate those tests prior to use. FDA encourages laboratories that develop and perform a test for COVID-19 under this policy to notify FDA that they have started clinical testing by sending an email to that effect to CDRH-EUA-Templates@FDA.HHS.GOV. It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

### C. Commercial Manufacturer Development and Distribution of Diagnostic Tests Prior to EUA Submission
The policy described in this subsection applies to commercial manufacturers that seek to develop and distribute diagnostic test kits to detect the SARS-CoV-2 virus to clinical laboratories or to healthcare workers for point-of-care testing. Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to laboratories certified to perform high complexity testing, including testing at the point-of-care when the site is covered by the laboratory's CLIA certificate for high-complexity testing.

This policy does not apply to at-home testing, including at-home specimen collection.

In light of the increasing numbers of COVID-19 cases throughout the country and the urgent need to expand the nation's capacity for COVID-19 testing during the public health emergency, FDA does not intend to object to a commercial manufacturer's development and distribution of SARS-CoV-2 test kits for specimen testing for a reasonable period of time, where the test has been validated and while the manufacturer is preparing its EUA request, where the manufacturer gives notification of validation to FDA as described below, and where the manufacturer provides instructions for use of the test and posts data about the test's performance characteristics on the manufacturer's website. Transparency can help mitigate potential adverse impacts from a poorly designed test by facilitating better informed decisions by potential purchasers and users.

FDA believes that 15 business days is a reasonable period of time to prepare an EUA submission for a test that has already been validated. Soon after receiving the EUA request, FDA will perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the manufacturer to address the problem (e.g., through labeling or bench testing). If the problem is significant and cannot be addressed in a timely manner, and the manufacturer has already distributed the device, FDA would expect the manufacturer to suspend distribution and conduct a recall of the test.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is critically important that tests are validated because false results can negatively impact not only the individual patient but also can have broad public health impact. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages manufacturers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

#### 2. FDA Notification
Following completion of assay validation, manufacturers should notify FDA (e.g., e-mail to CDRH-EUA-Templates@FDA.HHS.GOV) that their assay has been validated and they intend to begin distribution. This notification should include the name of the manufacturer, address, contact person, a website link, and a copy of the instructions for use including a summary of assay performance. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the name of the manufacturer and test to FDA's website listing.

In circumstances where manufacturers use distributor(s) for their product, the manufacturers should identify the names of all distributors in their notification. Distributors and laboratories using these tests should not provide separate notification. As noted above, FDA recommends that manufacturers submit a completed EUA request within 15 business days of the notification to FDA that the assay has been successfully validated. If an EUA request is not submitted within this timeframe, FDA intends to remove the manufacturer/test from its website listing of notified tests and may take additional actions as appropriate.

It would be helpful to FDA if manufacturers provide information on testing capacity, as well as the number of laboratories in the U.S. with the required platforms installed. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Reporting of Results
In order to provide transparency, FDA recommends that instructions for use and test reports include a general statement that the test has been validated but FDA's independent review of this validation is pending.

#### 4. EUA Request
FDA has made available, through download from our website, templates that test kit manufacturers may choose to use to facilitate the preparation, submission, and authorization of EUAs for molecular and antigen diagnostics. Manufacturers can use alternative approaches. Manufacturers who intend to use alternative approaches should consider seeking FDA's feedback or recommendations to help them through the pre-EUA and EUA process. FDA encourages manufacturers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

Soon after receiving the EUA request, FDA intends to perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the manufacturer to address the problem (e.g., through labeling or bench testing). If any problems are significant and cannot be addressed in a timely manner, FDA would expect the manufacturer to suspend distribution and conduct a recall of the test, which should include a notification concerning corrected test reports indicating prior test results may not be accurate. In such circumstances, FDA intends to remove the manufacturer/test from the website listing of notifications.

Issued EUAs are posted on FDA's website.

A manufacturer may request certain modifications to its EUA-authorized test as an amendment to the EUA as specified in the EUA's Conditions of Authorization. Where validation data supporting the modification have been submitted in the amendment, FDA does not intend to object to implementation of the modification while FDA conducts its review, except for modifications to add specimen types that have not been previously authorized with another test of the same technology.

#### 5. Clinical Testing
While awaiting FDA determination on the EUA request, FDA recommends that manufacturers make publicly available on their website the instructions for use, including a summary of assay performance.

### D. Commercial Manufacturer Development and Distribution and Laboratory Development and Use of Serology Tests Prior to or Without an EUA
The policy described in this subsection applies to developers of serology tests that identify antibodies (e.g., IgG, IgM) to SARS-CoV-2 from clinical specimens. Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to laboratories certified to perform high complexity testing, and at the point-of-care when covered by the laboratory's CLIA certificate for high-complexity testing. This policy does not apply to at-home testing, including at-home specimen collection, due to additional considerations that require FDA review.

FDA does not intend to object to a commercial manufacturer's development and distribution of serology tests to identify antibodies to SARS-CoV-2 for a reasonable period of time, where the test has been validated and while the manufacturer is preparing its EUA request, where the manufacturer gives notification of validation to FDA as described in subsection D.2 below, and where the manufacturer includes information in the instructions for use as described in subsection D.3 below. FDA provided early market access through its March 16, 2020, updated guidance, but that access was premised on the understanding that tests should be validated before being marketed to fall under the enforcement discretion policy. Given that any test on the market under the March 16 enforcement discretion policy or this policy should already be validated by the manufacturer before being marketed, FDA believes that 10 business days (from the date of notification or the date of publication of this guidance, whichever is later) is a reasonable period of time to prepare an EUA submission for a test whose performance characteristics have already been validated.

If FDA becomes aware of questions or concerns about a test after notification, such as poor performance or misleading statements about the test, FDA will communicate those concerns to the manufacturer and provide the manufacturer an opportunity to address the questions or concerns. If the concerns cannot be or have not been addressed in a timely manner, and the manufacturer has already distributed the test, FDA would expect the manufacturer to suspend distribution of the test. FDA also intends to remove the test from the website listing of notifications and may take additional actions as appropriate.

While laboratories are encouraged to submit EUA requests for serology tests, FDA does not intend to object to the development and use of serology tests to identify antibodies to SARS-CoV-2 by laboratories that are certified under CLIA to perform high-complexity testing, where the test has been validated, notification is provided to FDA, and information is included in the test reports as described in subsection D.3 below. At this time, we believe it is most beneficial to focus our EUA review and authorization efforts on tests from commercial manufacturers, which have the potential to be distributed more broadly, rather than laboratory-developed serology tests that are not for diagnostic purposes, are being performed at one laboratory that is CLIA-certified to perform high-complexity testing, and that are validated in-house. However, if FDA becomes aware of questions or concerns about a laboratory-developed serology test, such as poor performance or misleading statements about the test, FDA will communicate those concerns to the laboratory and provide the laboratory an opportunity to address the questions or concerns. If the concerns cannot be or have not been addressed in a timely manner, FDA intends to remove the laboratory from the website listing of notifications and may take additional actions as appropriate.

#### 1. Validation
All clinical tests should be validated prior to use. In the context of a public health emergency, it is critically important that tests are validated because false results can negatively impact not only the individual patient but also can have broad public health impact. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity in section V below. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV and additionally encourages developers to refer to the templates provided as examples in the Appendices to this guidance for serology test manufacturers and laboratories.

#### 2. FDA Notification
Following completion of assay validation, developers should notify FDA by email to CDRH-EUA-Templates@FDA.HHS.GOV that their assay has been validated and they intend to begin distribution or testing.

   a. For tests developed and used by laboratories certified under CLIA that meet the CLIA regulatory requirements to perform high-complexity testing, this notification should include the name of the laboratory, name of the laboratory director, laboratory address, and contact person in this email. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the laboratory name to FDA's website listing.

   It would be helpful to FDA if laboratories provide information on testing capacity. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

   b. For tests developed and distributed by commercial manufacturers, this notification should include the name of the manufacturer, address, contact person, and a copy of the instructions for use that includes a summary of assay performance. FDA will acknowledge receipt of this notification via auto-reply, and generally will add the name of the manufacturer and test to FDA's website listing. As noted above, FDA recommends that manufacturers submit a completed EUA request within 10 business days of the notification to FDA that the assay has been successfully validated, or the date of publication of this guidance, whichever is later. If an EUA request is not submitted within this timeframe, FDA intends to remove the manufacturer/test from its website listing of notified tests and may take additional actions as appropriate.

   In circumstances where manufacturers use distributor(s) for their test, the manufacturer should identify the names of all distributors in their notification. Distributors should not provide separate notification.

   It would be helpful to FDA if manufacturers provide information on test production capacity, the number of laboratories in the U.S. with the required platforms installed. This information will help the Agency and Department monitor the landscape as we work to ensure adequate testing capacity across the country.

#### 3. Labeling and Reporting of Results
In order to provide important information about the intended use of the test and its limitations, FDA recommends that instructions for use and patient test reports include information that helps users and patients understand the test results, such as the following:

- This test has not been reviewed by the FDA.
- Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct testing for SARS-CoV-2 is necessary.
- Results from antibody testing should not be used to diagnose or exclude acute SARS-CoV-2 infection.
- Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

#### 4. EUA Request
FDA has made available through download from our website templates that commercial manufacturers and laboratories may choose to use to facilitate the preparation, submission, and authorization of an EUA for a serology test. Developers can use alternative approaches. Developers who intend to use alternative approaches should consider seeking FDA's feedback or recommendations to help them through the EUA process. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

FDA may leverage data from testing at the National Institutes of Health's National Cancer Institute (NIH/NCI), or at another federal government laboratory designated by FDA, to inform decisions on EUA requests and other actions. FDA has issued an EUA for certain serology tests evaluated in the NIH/NCI independent validation study, or by another government agency designated by FDA, that are confirmed by FDA to meet certain specific performance and other criteria, and added to the EUA.

FDA will communicate any questions or concerns regarding a pre-EUA or EUA submission to the developer. FDA will also work collaboratively to address any potential concerns or safety considerations raised in the pre-EUA submission or EUA request and will contact the developer regarding a final determination on the EUA request.

Issued EUAs are posted on FDA's website.

If FDA is not able to issue an EUA, FDA intends to notify the manufacturer. Where the manufacturer has distributed tests, FDA also would expect the manufacturer to suspend distribution of the test, which should include a notification indicating that prior test results may not be accurate. FDA intends to remove the manufacturer/test from the website listing of notifications. FDA may also take other action as may be appropriate in the circumstances.

## V. Validation Study Recommendations Based on the Technological Principles of Tests
In this section, FDA provides recommendations for developers regarding testing that should be performed to demonstrate that a SARS-CoV-2 test is validated based upon the underlying technological principles of the test. Depending on the characteristics of your test, additional validation studies may be recommended. FDA encourages test developers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-templates@FDA.HHS.GOV.

### A. Molecular Diagnostic Tests
FDA defines SARS-CoV-2 molecular diagnostic tests as tests that detect SARS-CoV-2 nucleic acids from human specimens. FDA recommends that the following validation studies be conducted for molecular SARS-CoV-2 diagnostic tests:

#### (1) Limit of Detection
FDA recommends that developers document the limit of detection (LoD) of their SARS-CoV-2 assay. FDA generally does not have concerns with spiking RNA or inactivated virus into artificial or real clinical matrix (e.g., Bronchoalveolar lavage [BAL] fluid, sputum, etc.) for LoD determination.

FDA recommends that developers test a dilution series of three replicates per concentration with inactivated virus on actual patient specimen, and then confirm the final concentration with 20 replicates. For this guidance, FDA defines LoD as the lowest concentration at which 19/20 replicates are positive. If multiple clinical matrices are intended for clinical testing, FDA recommends that developers submit in their EUA requests the results from the most challenging clinical matrix to FDA. For example, if testing respiratory specimens (e.g., sputum, BAL, nasopharyngeal (NP) swabs, etc.), laboratories should include only results from sputum in their EUA request.

#### (2) Clinical Evaluation
The availability of positive samples has increased as the pandemic has progressed. As such, FDA now recommends that developers use positive clinical samples for clinical validation. Moreover, due to the increased availability of clinical samples, FDA recommends that developers confirm performance of their assay by testing a minimum of 30 positive specimens and 30 negative specimens as determined by an authorized assay. If you do not have access to clinical samples as determined by an authorized assay, contrived clinical specimens may be considered. Contrived reactive specimens can be created by spiking RNA or inactivated virus into leftover clinical specimens, of which the majority can be leftover upper respiratory specimens such as NP swabs, or lower respiratory tract specimens such as sputum, etc. If contrived samples are used, FDA recommends that twenty of the contrived clinical specimens be spiked at a concentration of 1x-2x LoD, with the remainder of specimens spanning the assay testing range. For this guidance, FDA defines the acceptance criteria for the performance as 95% agreement at 1x-2x LoD, and 100% agreement at all other concentrations and for negative specimens.

#### (3) Inclusivity
Developers should document the results of an in silico analysis indicating the percent identity matches against publicly available SARS-CoV-2 sequences that can be detected by the proposed molecular assay. FDA anticipates that 100% of published SARS-CoV-2 sequences will be detectable with the selected primers and probes.

#### (4) Cross-reactivity
FDA recommends cross-reactivity wet testing on common respiratory flora and other viral pathogens at concentrations of 10^6 CFU/ml or higher for bacteria and 10^5 pfu/ml or higher for viruses, except for SARS-Coronavirus and MERS-Coronavirus, which can be accomplished by in silico analysis. As an alternative, FDA believes an in silico analysis of the assay primer and probes compared to common respiratory flora and other viral pathogens can be performed. For this guidance, FDA defines in silico cross-reactivity as greater than 80% homology between one of the primers/probes and any sequence present in the targeted microorganism. In addition, FDA recommends that developers follow recognized laboratory procedures in the context of the sample types intended for testing for any additional cross-reactivity testing.

Additional information for the validation of molecular diagnostics is included in the manufacturer and developers EUA templates available for download on our website.

### B. Antigen Detection Tests
FDA defines SARS-CoV-2 antigen tests as those that detect proteins that are part of the SARS-CoV-2 virus directly from clinical specimens. FDA recommends that the following validation studies be conducted for a SARS-CoV-2 antigen test:

- Limit of Detection/Analytical Sensitivity
- Cross-reactivity/Analytical Specificity
- Microbial Interference
- Clinical Agreement Study

The clinical agreement study is intended to establish the performance characteristics (e.g., sensitivity/PPA, specificity/NPA) of the test. FDA believes that clinical agreement should be established on human specimens, preferably leftover specimens from patients with or without SARS-CoV-2 infection.

FDA has made available through download from our website, a template that antigen test developers may choose to use to facilitate the preparation, submission, and authorization of an EUA for an antigen test. See more information in Section VI. For antigen tests, the template includes further recommendations concerning the above validation studies and make additional recommendations about other information that should be provided to FDA as part of the pre-EUA/EUA submission process. Developers can use alternative approaches. FDA encourages developers to discuss any alternative approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

### C. Serological Tests
FDA defines SARS-CoV-2 serological tests as tests that identify antibodies (e.g., IgG, IgM) to SARS-CoV-2 from clinical specimens. FDA recommends that the following validation studies be conducted for a SARS-CoV-2 serological assay:

- Cross-reactivity/Analytical Specificity
- Class Specificity
- Clinical Agreement Study

The clinical agreement study is intended to establish the performance characteristics (e.g., sensitivity/PPA, specificity/NPA) of the test. FDA recommends that clinical accuracy should be established on human specimens from patients with microbiologically confirmed COVID-19 infection.

FDA has made available through download from our website templates that commercial manufacturers and laboratories may choose to use to facilitate the preparation, submission, and authorization of an EUA for a serology test. See more information in Section VI. For serological tests, these templates include further recommendations concerning the above validation studies and make additional recommendations about other information that should be provided to FDA as part of the pre-EUA/EUA submission process. Developers can use alternative approaches. FDA encourages developers to discuss any alternative approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

## VI. Availability of EUA Templates
FDA has made available through download from our website a series of templates that developers may choose to use to facilitate the preparation, submission, and authorization of an EUA for various types of COVID-19 tests. The templates reflect FDA's current thinking on the data and information that developers should submit to facilitate the EUA process. The templates provide information and recommendations, and we plan to update them as appropriate as we learn more about the COVID-19 disease and gain experience with the EUA process for the various types of COVID-19 tests.

Developers can use alternative approaches. Developers who intend to use alternative approaches should consider seeking FDA's feedback or recommendations to help them through the EUA process. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through CDRH-EUA-Templates@FDA.HHS.GOV.

Members of the public can submit questions about the templates to CDRH-EUA-Templates@FDA.HHS.GOV, or they can submit comments regarding the templates to the public docket established for this guidance.


# 6,903  2020-05-29_FDA Template - Home Specimen Collection Molecular Diagnostic Template.md
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last updated: 2026-03-04 by BA
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title: FDA Template - Home Specimen Collection Molecular Diagnostic Template
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summary_short: The FDA Home Specimen Collection Molecular Diagnostic Template provides detailed recommendations for data, validation, and labeling needed to support pre-EUA/EUA submissions for prescription home collection kits used with authorized SARS-CoV-2 molecular assays. It specifies requirements for device description, manufacturing, shipping stability, usability, and clinical validation to ensure samples collected at home remain suitable for accurate laboratory testing. The template enables manufacturers and laboratories to standardize submissions and safely expand access to home-based COVID-19 specimen collection during the public health emergency.


CONTENT

***INTERNAL TITLE:*** Home Specimen Collection Molecular Diagnostic Template

This template (the “template”) provides the Food and Drug Administration’s (FDA) current recommendations concerning what data and information should be submitted to FDA in support of a pre-EUA/EUA submission for prescription use only home collection devices used by an individual to collect certain clinical specimen(s) that are then sent to a clinical laboratory for testing with a molecular diagnostic for SARS-CoV-2 that is authorized for use with the home collection kit. This template does not cover non-prescription home collection devices or over the counter (OTC) tests for COVID-19 testing. This template is intended to help manufacturers provide appropriate validation data and other information to FDA, but alternative approaches can be used. It reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should* means that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA Guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/media/97321/download).[2]

## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by the collection device developer (sponsor) as applicable to its specific device. Text in ***bold italic*** outlines FDA’s additional recommendations for the sponsors’ consideration when completing the suggested information in each section.

-   This template is intended for home collection kits for anterior nares swab or saliva specimens; if you are considering other types of respiratory specimens (e.g., sputum, throat/tongue swabs, or nasal aspirates) or non-respiratory specimens (e.g., stool, etc.), please contact FDA at CDRH-EUA-Templates ([CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov)) to discuss your validation strategy.

-   Authorization of a home collection kit must be accompanied by authorization of one or more molecular assays that has been validated with specimens collected and transported with the subject home collection kit. This template includes FDA’s current recommendations concerning the data and information that should be submitted to FDA in support of an EUA submission for a home collection kit. Please refer to the [Molecular Diagnostic Template for Manufacturers](https://www.fda.gov/media/135900/download) or the [Molecular Diagnostic Template for Laboratories](https://www.fda.gov/media/135658/download) for FDA’s current recommendations concerning what data and information should be submitted to FDA in support of an accompanying molecular diagnostic for SARS-CoV-2, which may be submitted in the same EUA request as the home collection kit or in an accompanying EUA request.

-   There are three options for how to authorize a molecular assay with a home collection kit:

    -   Within the same EUA at one time (i.e., when the same developer makes the home collection kit and molecular assay and seeks authorization at the same time for the assay and kit);

    -   In one or more EUAs (i.e., when the developer of the home collection kit is different from the developer(s) of the molecular assay(s)); or

    -   As an amendment to the EUA of a previously authorized assay to add home collection with the specific home collection kit.

-   A home collection kit authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   This is an EUA interactive review template for Pre-EUA/EUA submissions. We plan to update the template as appropriate as we learn more about the COVID-19 disease and gain experience with the EUA process for this home collection kit.

-   FDA recommends distributors of home collection specimen kits contact the Pipeline and Hazardous Materials Safety Administration (PHMSA) within the Department of Transportation (DOT) to confirm their packaging and shipping instructions will ensure users are in compliance with the hazardous materials regulations for shipping medical material. PHMSA can be contacted at [HMInfo@dot.gov](mailto:HMInfo@dot.gov).

## EXAMPLE TEMPLATE:
### A. PURPOSE FOR SUBMISSION

Emergency Use Authorization (EUA) request for distribution and/or use of the ***\[name of collection device\]*** for the \[***collection or collection and stabilization***\] of ***\[add all claimed specimen types, i.e., nasal swabs and/or saliva\]*** in ***\[add transport media or dry tube\]*** to transport viral SARS-CoV-2 RNA, from patients suspected of COVID-19 by a healthcare provider. The specimen collection device is for use in conjunction with molecular diagnostic testing performed at a clinical laboratory using an *in vitro* diagnostic (IVD) test for the detection of SARS-CoV-2 that is authorized for use with the home collected kit.

### B. APPLICANT

***\[Official name, address and contact information of applicant\]***

### D. PROPRIETARY AND ESTABLISHED NAMES

Proprietary Name - ***\[device name (home collection kit name)\]***

Established Name - ***\[device name (home collection kit name)\]***

### C. REGULATORY INFORMATION

***Approval/Clearance Status:***

The ***\[device name\]*** device is not cleared, approved, or subject to an approved investigational device exemption.

***Product Code:*** 
***QJR***
### D. PROPOSED INTENDED USE

##### *1) Intended Use:*

***The proposed IU will be finalized based on, among other things, the data and recommendations from Public Health authorities at the time of authorization – example text is provided below.***

***Example text for a home collection kit where the manufacturer does not hold the COVID-19 NAAT test EUA:***

The ***\[name of collection device\]***is intended for use by individuals to self-collect ***\[add all claimed specimen types, i.e., nasal swabs and/or saliva\]***at home, when determined by a healthcare provider to be appropriate based on \[***include mechanism via which the individual is determined to be appropriate for COVID-19 testing by a healthcare provider – to facilitate prescription use. For example (1) the results of an online COVID-19 questionnaire, or (2) telephone or online video appointment, etc. with a healthcare provider***\]. Specimens collected using the ***\[name of collection device\]*** are transported at ambient temperature for testing at a laboratory. SARS-CoV-2 RNA from the ***\[add all claimed specimen types, i.e., nasal swabs and/or saliva\]*** is maintained in the specimen packaging and is suitable for use in molecular diagnostic testing performed using an in vitro diagnostic (IVD) test for the detection of SARS-CoV-2 that has been issued an EUA for use with Home Collection Kits, that includes the ***\[name of collection device\]***.

Testing is limited to laboratories designated by ***\[name of manufacturer\]*** and certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high complexity tests. Testing is also limited to molecular diagnostic tests that are authorized for use with Home Collection Kits for collection of nasal swab specimens, including the ***\[name of collection device\]***.

The ***\[name of collection device\]***is only for use under the Food and Drug Administration’s Emergency Use Authorization.

***Example text for a home collection kit where the manufacturer also holds the COVID-19 NAAT test EUA (e.g., an already issued EUA is being revised to authorize home specimen collection as an option):***

The \[***name of the EUA test***\] is a real-time reverse transcription polymerase chain reaction (rRT-PCR) test for the qualitative detection of nucleic acid from SARS-CoV-2 in \[***name typical respiratory specimens collected, e.g., upper and lower respiratory specimens such as nasal, nasopharyngeal or oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate***\] collected from individuals suspected of COVID-19 by their healthcare provider.

This test is also for use with the \[***name of home collection device***\] to self-collect \[***name specimens, nasal swab or saliva***\] specimens at home by individuals when determined by a healthcare provider to be appropriate based on \[***include mechanism via which the individual is determined to be appropriate for COVID-19 testing by a healthcare provider – to facilitate prescription use. For example (1) the results of an online COVID-19 questionnaire, or (2) telephone or online video appointment, etc. with a healthcare provider***\].

Testing is limited to \[***specify laboratory/laboratories***\] certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high complexity tests.

Results are for the identification of SARS-CoV-2 RNA. The SARS-CoV-2 RNA is generally detectable in **\[*name specimen type, e.g. ***upper respiratory**\]** during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Laboratories within the United States and its territories are required to report all positive results to the appropriate public health authorities.

Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.

The ***\[test name\]*** is intended for use by **\[*include intended user, e.g., qualified and trained clinical laboratory personnel specifically instructed and trained in the techniques of real-time PCR and in vitro diagnostic procedures*\]**. The ***\[test name\]*** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

##### *2) Special Conditions for Use Statements:*

For Emergency Use Authorization (EUA) only.

For prescription use only.

For in vitro diagnostic use only.

For professional use only.

For use by people 18 years of age or older.

The ***\[name of collection device\]*** collection device is only authorized for use in conjunction with an in vitro diagnostic (IVD) test for the detection of SARS-CoV-2 that has been issued an EUA and is authorized for use with this collection device.

### E. DEVICE DESCRIPTION 

***Example text has been added below, please modify for your specific collection device. Please note that for new technologies FDA may request additional detailed information so we can adequately assess the risks and benefits associated with the device.***

##### 1.  *Device Description:*

***Describe the basic design of the collection device and the components included in the kit.***

The ***\[name of collection device\]*** collection device consists of a ***\[e.g., swabs, collection tube containing stabilizing liquid, gel pack, return shipping box/envelope, insulated pack, instructions\]***.

##### 2.  *Home Collection Kit Ordering and Processing:*

***Describe how individuals are selected as acceptable for receiving the home collection kit and who writes the prescription for the test. For example, do individuals fill out an online questionnaire that is reviewed by a physician before the home collection kit is shipped to the requesting individual? You should note if the screening follows CDC recommendations for testing prioritization. As a prescription use device, the home collection kit is not to be dispensed to the patient before the prescription for the test is written. Describe how the specimen is collected and then transferred into the collection device. Include details of all reagents/materials included in the kit and their function. Include how the components of the collection device stabilize the specimen and protect the virus/viral RNA for shipment. Describe the shipping conditions during transit \[for example; use of a drop box, sample waiting for pick up outside, etc.\]and how the transit/shipping time will be tracked. How does the home user know where to send their specimens? Are there specific shipping instructions? Please identify the company(ies) shipping specimens and if specimens will be placed in drop boxes or mail boxes for pickup. You should have an accessioning SOP for all laboratories to use when accepting \[name of collection device\] samples for testing, before entering them into the work flow.***

Individuals may request the \[***name of collection device***\] collection device \[***describe the mechanism via which individuals request the home collection kit and how they are determined appropriate for COVID-19 testing by a prescribing healthcare provider***\].

The *\[**name of collection device**\]* collects and stabilizes \[***virus/viral RNA\]*** from *\[**add all claimed specimen types, i.e., nasal swabs and/or saliva\]*** specimen***(s)***; it can also be used for the transportation and \[***short/long‐term room temperature storage***\] of a sample. The ***\[name of collection device**\]* is a non‐invasive alternative for collecting high quality and quantity \[***virus/viral RNA**\]* by/from individuals who are suspected of COVID-19 by their healthcare provider for use in molecular COVID-19 diagnostic assays that are authorized for use with the *\[**name of collection device**\]*.

The *\[**name of collection device**\]* consists of \[***e.g., a swab, a collection tube, stabilizing liquid optional sponges for assisted collection***\]. The individual using the *\[**name of collection device**\]* to collect *\[**add all claimed specimen types, i.e., nasal swabs and/or saliva\]*** specimen***(s)*** performs the following steps to collect the initial specimen.

After *\[**add all claimed specimen types, i.e., nasal swabs and/or saliva\]*** specimen***(s)*** is collected, the \[***swab is inserted, stabilizing liquid is mixed with the sample***\].

Upon contacting \[***e.g. clinical specimen, saliva cells, the stabilizing liquid lyses cellular and nuclear membranes to release and stabilize nucleic acids***\]. For device shipping, the individual must \[***describe steps and expected timeframe***\].

Specimens received at the clinical laboratory for testing with the \[***name of EUA test***\] undergo the following accessioning prior to acceptance for testing \[***describe the specimen log in, acceptance and rejection criteria, mechanism for handling rejected specimens, etc.***\]

Test results are communicated back to individuals that used the ***\[name of collection device***\] via ***\[describe the mechanism via which results are returned to patients that use the home collection device\].***

##### 3.  *Specimen Collection Control:*

***The accessioning process should include some type of control for adequate human specimen. This could include using an EUA authorized assay that includes some form of human sample control (e.g. RNaseP) to determine if sufficient sample was collected by the user. Alternatively, the laboratory could run a separate RT PCR in parallel for each sample type that targets a human housekeeping gene. A design feature of the collection device, such as changing color in the presence of human material, may also be an appropriate control. Sample collection visually observed by a healthcare provider through a telemedicine visit, and a method/procedure for the laboratory to confirm this, could also serve as this control.***

##### 4.  *Partnering Laboratories:*

***Fill out the table below to identify all laboratories that samples will be sent to and all tests that will be run with the samples at each laboratory.***

| Laboratory | EUA Assay | Lab Testing Capacity (per day or week) |
| --- | --- | --- |
| Lab Name Address Phone: CLIA #: | Assay Name Identify if Commercial Assay or LDT |  |
||

***We recommend requesting a letter from the developer of each test permitting FDA to discuss their submission with you.***

***Additionally, each test developer should submit an EUA or EUA amendment for authorization with \[collection device name\]. Please provide a right of reference to each test developer to allow the data validating your home collection device to be incorporated by reference in the test developer’s EUA request.***

### F. PRODUCT MANUFACTURING

The ***\[name of collection device\]*** has been validated using only the components referenced in this submission.

##### 1. *Overview of Manufacturing and Distribution:* 

The product will be manufactured at \[***manufacturer’s name and FDA registration number (if applicable******)\]*** by \[***manufacturer name***\] personnel consistent with practices for the production of **\[*types of devices*\]** based on \[***type of quality system\****\]**.** Material manufactured by \[***manufacturer’s name***\] may be bottled and kitted by \[***packager name***\] manufacturing facility.

The current manufacturing capabilities include the ability to manufacture approximately **\[*please insert the approximate number of units/products that can currently be manufactured per week at the manufacturing facility*\]** products per week; however, in the event of a surge in demand, this could be increased to **\[*please insert the approximate maximum number of units/products that could potentially be manufactured per week at the manufacturing facility if there was a surge in demand*\]** product per week within a **\[*please specify in weeks/months the expected timeframe required to increase product production if required*\]** timeframe.

The product will be distributed by **\[*please describe the distribution plan for the product and list all current distributors*\]**.

##### 2. *Components Included with the Home Collection Kit*

Components manufactured by \[***manufacturer’s name and FDA registration number (if applicable)***\] and supplied with the home collection kit include:

**List all components and reagents provided for your home collection kit, including a description, volumes, concentrations, quantities, buffer components, etc. If you plan to use non-traditional sources of swabs or media, please describe your qualification testing and validation procedures.  Collection media that contains hazardous or irritating materials (such as guanidinium salts) should not be used for home collection unless the collection device has specific safety features to reduce the risk of patient exposure (such as releasing preservative only when the container lid is closed). FDA will conduct a safety review of all collection media and containers.    **

**Kit components**

| Name | Description | Quantity | Material Supplier |
|------|-------------|----------|-------------------|
||

##### 3. *Collection Device Stability:* 

***Briefly describe stability test plan for \[name of collection device\]* *reagents and include any accelerated stability information if available. Please note that reagent stability studies do not need to be completed at the time of EUA issuance, however the study design should be agreed upon during interactive review and the stability studies started immediately following authorization, if not before. When designing your stability study, general recommendations are outlined below, for your consideration.***

-   For EUAs, you may follow the current FDA recognized CLSI Standard EP25 – Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline when evaluating the suitability of stability study designs. If you are planning to pursue a De Novo/510(k) for your device, we recommend discussing in more detail your stability design to facilitate potential use of the EUA data in your regular premarket submission.

-   We recommend testing a known positive diluted patient sample at 3-5x LoD rather than positive control material to establish reagent stability.

-   You should design your study to provide data for a timeframe that is about 10% longer than the one to be claimed – for example; a claim of 18 months should be supported by stability data out to 20 months and a claim of 7 days should include stability data out to 8 days.

-   FDA considers 15-30°C to represent room temperature conditions. Ideally you should evaluate stability at both 15°C and 30°C, however, for the purposes of the EUA evaluation at 30°C is acceptable as the worse-case scenario.

-   Shelf-Life Stability- Unopened kit:

    -   You should evaluate real-time kit stability studies with unopened kits stored at the claimed storage temperature for your test.

    -   Accelerated stability evaluations for unopened kits may be included in EUA submissions while the real-time studies are on-going. However, please note real-time stability data may be needed to meet the required statutory standard for pre-market approval/clearance and for EUA issuance.

-   Shipping Stability - Unopened kit: Study should evaluate the anticipated handling and shipping times and temperatures expected for unopened kits.

-   FDA analysis recommendations for real time stability studies are as follows:

    -   Baseline of the study (t=0 of stability study) should not exceed a month from bottling

    -   Clear baselines should be described (e.g., a month from bottling) for each stability claim under each study

    -   Claims should be determined based on regression analysis. Any %change (%shift) from time zero (baseline) should be calculated between the target claim and the zero-time as (Ttest-Tbaseline)/ Tbaseline\*100 with 95%CI using the regression equation obtained from plotting the mean values. When formulating your acceptance criteria for evaluating the shift from baseline you should consider the reproducibility of your device. However, generally, the shift at the target claim due to storage should not exceed 10-15%. The target stability is the next to last tested point that was within +/- 10% of time zero.

    -   Acceptance criterion may be different, depending on the test samples analyte concentration distribution in the intended use population and the risk, in other words, the impact of false results to public health.

### G. PERFORMANCE EVALUATION

***The following recommended validation studies should be performed during your device development:***

##### Home Collection Sample Stability Study Design

***If your kit will use foam or wrapped polyester nasal swabs transported in 0.9% saline, PBS or dry tubes you may reference stability studies conducted by Quantigen Biosciences, with support from The Gates Foundation and UnitedHealth Group and do not have to perform your own separate stability study for sample transport. Quantigen Biosciences has granted a right of reference to any sponsor wishing to pursue an EUA to leverage their COVID-19 swab stability data as part of that sponsor’s EUA request.***

***If you are shipping a dry swab you should also provide a rehydration SOP for laboratories to use and provide validation data for the rehydration protocol.***

The proposed study design is for validation of home sample collection for nasal swab samples in media (you should test all media you intend to use for shipping), or saliva. Testing should include 20 spiked samples at 2xLoD (low positives) and 10 spiked samples at 5-10x LoD (high positives). We also recommend testing 10 negative samples to monitor for false positives. Spiked samples for swab samples should be generated by spiking virus onto swabs and placing the swab in media, if appropriate. **Diluted clinical samples** can be used for spiking. Ideally, spiking material should be prepared with clinical matrix to most closely replicate a clinical specimen.

**Table1: Sample Panel**

| Sample        | Replicates | Titer     |
|---------------|------------|-----------|
| Low Positive  | 20         | 2xLoD     |
| High Positive | 10         | 5-10x LoD |
|  Negatives    | 10         | N/A       |
| **Total**     | **40**     |           |
||

The shipping study is designed to simulate the following situations in one study during home sample collection and shipping:

-   Storage of samples before the customer ships the sample

-   Sample sitting in mailbox or drop box waiting for pick-up

-   Shipping conditions after pick up, when the sample is shipped to testing lab

Total \# of samples: 40

**General Acceptance Criteria:  
**Low Positive Samples: ≥95% agreement with expected results. High Positive Samples: 100% agreement with expected results. Negative Samples: 100% agreement with expected results.

The table below describe each temperature profile to replicate worst case scenario shipping conditions (for spring/summer) for an 8 hour wait at the customer’s house before shipping and then a subsequent 48-hour shipping cycle. We also included a Winter Profile for testing if you plan to continue shipping your product past August 2020. If you plan to allow testing of samples that have been shipped by 3-5-day mail, please expand the shipping study times below. The sample panel in Table 1 should be cycled through the temperatures & times below and then tested with an assay that your lab will use that produces a Ct value. FDA expects that the samples not only remain positive but that the Ct value does not appreciably increase (more than 3 Ct).



**Table 2: Summer Profile \***

| **Temperature** | **Cycle Period** | **Cycle Period Hours** | **Total Time Hours** |
|-----------------|----------------|----------------------|-------------------|
| 40°C | 1 | 8 | 8 |
| 22°C | 2 | 4 | 12 |
| 40°C | 3 | 2 | 14 |
| 30°C | 4 | 36 | 50 |
| 40°C | 5 | 6 | 56 |
||

**Winter Profile\***

| **Temperature** | **Cycle Period** | **Cycle Period Hours** | **Total Time Hours** |
|-----------------------|-----------------|-----------------|-----------------|
| -10C | 1 | 8 | 8 |
| 18C | 2 | 4 | 12 |
| -10C | 3 | 2 | 14 |
| 10C | 4 | 36 | 50 |
| -10C | 5 | 6 | 56 |
||

\*Shipping conditions for cycle periods 2 through 5 are modeled after ISTA 7D 2007 shipping standard (48-hour domestic freight transport) where for cycle period 3 and 5 the temperature has been increased from 35°C to 40°C. The cycle period 1 (8 hours) has been included for the time delay between collection of the sample and shipment of the sample. The remaining time (48 hours) covers the domestic shipment within the continental U.S. Cycle periods are sequential with the "cycle period hours" required per cycle listed in the table. After each cycle period, the "total time hours" increments by the number of hours in the cycle period.

##### Clinical Validation of Saliva as a sample type (if the COVID-19 NAAT test EUA does not have saliva as an acceptable validated sample type):

***If you seek a claim for alternative respiratory specimens, such as saliva, oral fluid, buccal swabs, etc., you should test at least 30 paired, positive nasopharyngeal swabs and 30 of the same type of alternative respiratory specimen (e.g., all saliva). To minimize the occurrence of discordant results, the samples should be collected within short time of each other and both tested using your candidate EUA assay. FDA believes ≥95% positive agreement with similar Ct values for the paired specimen types is generally acceptable clinical performance. Please provide detailed information regarding the type of collection device and transport medium you validated for use with your assay.***

***If you plan to conduct this study, we strongly suggest you submit a short study design to FDA for review before commencing. ***

##### Flex studies:

For oral saliva - Sample Volume Tolerance: You should conduct a study to evaluate the effect of over or under filling the collection device.

##### Human Usability Study: for home-collection and mailing the sample to a CLIA-certified lab for testing:

-   Testing should include a minimum of 30 participants and takes place in an actual use environment or simulated environment.

-   The entire workflow should be performed by each individual participant using the kit, including kit registration, sample collection, packaging of the sample, and mailing to the laboratory with pre-prepared label.

-   The participants should be observed (either in person or by remote visual monitoring, such as a video conference) during sample collection and all difficulties should be noted.

-   After the entire process is completed the user should be given the questionnaire to indicate the ease of use of the kit and sample collection as well as understanding the consequences if steps are not performed correctly. The participant should be able to provide comments if needed.

-   The laboratory personnel should inspect the packaging and sample upon delivery and note all packaging errors and acceptability of the sample for testing.

-   The samples collected during the study should be tested for specimen adequacy using a human sample control assay. This could include using an EUA authorized assay that includes a human sample control (e.g. RNaseP) to determine if sufficient sample was collected by the user. Alternatively, the laboratory could run a separate RT PCR for each sample that targets a human housekeeping gene. A design feature of the collection device, such as changing color in the presence of human material, may also be an appropriate control.

-   Participants should include individuals representing varying education levels and ages. Participants with prior medical or laboratory training should be excluded. Participants who have prior experience with self-collection should be excluded.

-   The study should have pre-defined acceptance criteria and defined strategy to mitigate risk of errors identified in the study (e.g., modifying the instructions).

We encourage sponsors to submit their usability study protocols and questions for participants for FDA review prior to conducting the study.

##### User Labeling:

You should submit for review your packaging and directions for your specimen collection kit. FDA will review these documents for their ease of use and clarity of instructions. We recommend all directions be written at a 7^th^ grade reading level or below.

### H. UNMET NEED ADDRESSED BY THE PRODUCT 

**This section will be completed by FDA.**

### I. APPROVED/CLEARED ALTERNATIVE PRODUCTS

Currently no methods for specimen self-collection in conjunction with a laboratory-based molecular in vitro diagnostic EUA test for the detection of the SARS-CoV-2 have been approved/cleared by FDA.

### J. BENEFITS AND RISKS:

**This section will be completed by FDA.**

### K. FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:

**As set forth in the EUAs, Fact Sheets for Patients and Healthcare Providers generally are to be provided with the assays that will be used with the home collection kit *- see examples for authorized EUA tests on our website and templates will be made available.***

### L. INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:

**Include Instructions for Use, Box Labels, Vial Labels and any other proposed labeling for the test and/or home collection kit. You should also include copies of any questionnaires used to determine eligibility of the patient to receive the home collection kit.**

### M. RECORD KEEPING AND REPORTING INFORMATION TO FDA:

If authorized, conditions would likely be included in the EUA to require the following -

\[***Manufacturer name***\] will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report adverse events, and this website is referenced through the \[***Manufacturer name***\] Product Support website: \[***Include link to Website***\]. Each report of an adverse event will be processed according to \[***Manufacturer name******\]***’s Non-Conformance Reporting Requirements, and Medical Device Reports will be filed with the FDA as required. Through a process of inventory control, \[***Manufacturer name******\]*** will also maintain records of device usage/purchase. \[***Manufacturer name******\]*** will collect information on the performance of the test, and report to FDA any suspected occurrence of false positive or false negative results of which \[***Manufacturer name******\]*** becomes aware. \[***Manufacturer name******\]*** will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

[1] This template is part of the [Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) - Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised).

[2]  [https://www.fda.gov/media/97321/download](https://www.fda.gov/media/97321/download).


# 704  2020-07-21_FDA Letter - Serology IVD Umbrella Revocation.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-07-21_FDA Letter - Serology IVD Umbrella Revocation.md
file_date: 2020-07-21
title: FDA Letter - Serology IVD Umbrella Revocation
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: pdf
xfile_type: docx
gfile_url: https://docs.google.com/document/d/10alSr49q6Asxz7EN7eZ3QCqTF04Dic_o
xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fda-policy/2020-07-21_FDA%20Letter%20-%20Serology%20IVD%20Umbrella%20Revocation.docx
pdf_gdrive_url: https://drive.google.com/file/d/1oYZw2TXJUthcT1Nw7FARgjj17adCS06x
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2020-07-21_FDA%20Letter%20-%20Serology%20IVD%20Umbrella%20Revocation.pdf
conversion_input_file_type: pdf
conversion: claude
license: Public Domain
tokens: 704
words: 483
notes: 
summary_short: The FDA Serology IVD Umbrella Revocation letter announces the July 21, 2020 revocation of the April 28, 2020 umbrella EUA for certain SARS-CoV-2 antibody tests evaluated through NIH/NCI or other designated government validation. It explains that FDA shifted to issuing individual EUAs to allow test-specific indications, conditions of authorization, and more flexible amendments, even though no tests had been added to the umbrella EUA’s authorized list. This change tightened oversight and enabled more tailored regulatory control over serology test performance and labeling.


CONTENT

July 21, 2020

To Manufacturers and Other Stakeholders:

This letter is to notify you of the revocation of the Emergency Use Authorization (EUA) issued April 28, 2020, for emergency use of certain in vitro diagnostic SARS-CoV-2 Antibody Tests[^1] intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection, by detecting antibodies (IgG, or IgG and IgM, or total) to SARS-CoV-2 in human plasma and/or serum.

The authorization of a device for emergency use under section 564 of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 360bbb-3) may, pursuant to section 564(g)(2) of the Act, be revised or revoked when the criteria under section 564(b)(1) of the Act no longer exist, the criteria under section 564(c) of the Act for issuance of such authorization are no longer met, or other circumstances make such revision or revocation appropriate to protect the public health or safety.

FDA has determined that circumstances make revocation of this EUA appropriate to protect the public health or safety. Any SARS-CoV-2 Antibody Tests added to the list of authorized devices in Appendix A of the April 28, 2020, letter of authorization would have been authorized for: (1) human plasma and/or serum samples only, (2) use only at laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform moderate or high complexity tests, and (3) the detection of IgG only, IgG and IgM, or total antibodies (i.e., not for the detection and differentiation of IgA from other immunoglobulins). To date, no device has been listed in Appendix A.

Based on information and experience since issuance of the umbrella EUA, FDA has determined that circumstances support revocation of the umbrella EUA so that FDA may issue individual EUAs. Individual EUAs will allow for broader indications and scopes of authorization, individualized conditions of authorization to address any issue unique to a specific test, and more streamlined EUA amendments, such as additional uses that would not fall under this umbrella EUA. Accordingly, FDA has decided to revoke this EUA. Instead, FDA will issue individual EUAs for SARS-CoV-2 Antibody Tests that meet the requisite EUA statutory criteria.

FDA has determined that circumstances make revocation of this EUA appropriate to protect the public health or safety for purposes of section 564(g)(2)(C) of the Act.

Accordingly, pursuant to section 564(g)(2) of the Act, FDA revokes the EUA issued on April 28, 2020.

Notice of this revocation will be published in the Federal Register, pursuant to section 564(h)(1) of the Act.

Sincerely,

__________________________
RADM Denise M. Hinton
Chief Scientist
Food and Drug Administration



^1^ The SARS-CoV-2 Antibody Tests eligible for authorization under this EUA were Lateral Flow or Enzyme-linked immunosorbent assay (ELISA) tests that had been evaluated in an independent validation study performed at the National Institutes of Health's (NIH) National Cancer Institute (NCI), or by another government agency designated by FDA.


# 20,960  2020-07-28_FDA Template - Molecular Diagnostic Template for Commercial Manufacturers.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-07-28_FDA Template - Molecular Diagnostic Template for Commercial Manufacturers.md
file_date: 2020-07-28
title: FDA Template - Molecular Diagnostic Template for Commercial Manufacturers
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: docx
xfile_type: docx
gfile_url: https://docs.google.com/document/d/1FWhHbpMOCezPXxhqFQ4lcSdcWr9ymoPK
xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fda-policy/2020-07-28_FDA%20Template%20-%20Molecular%20Diagnostic%20Template%20for%20Commercial%20Manufacturers.docx
pdf_gdrive_url: https://drive.google.com/file/d/1tyB60wMUVIcWN_lubM6rveH69LIqiKsd
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2020-07-28_FDA%20Template%20-%20Molecular%20Diagnostic%20Template%20for%20Commercial%20Manufacturers.pdf
conversion_input_file_type: docx
conversion: pandoc
license: Public Domain
tokens: 20960
words: 15074
notes: 
summary_short: The FDA Molecular Diagnostic Template for Commercial Manufacturers is a detailed regulatory framework outlining recommended data, validation studies, and documentation for pre-EUA and EUA submissions of SARS-CoV-2 molecular diagnostic tests. It standardizes how manufacturers present analytical, clinical, manufacturing, and pooling performance information to FDA during the COVID-19 public health emergency.


CONTENT

***INTERNAL TITLE:*** Molecular Diagnostic Template for Commercial Manufacturers

This template (the “template”) provides FDA’s current recommendations concerning what data and information should be submitted to FDA in support of a pre-EUA/EUA submission for a molecular diagnostic for SARS-CoV-2. As outlined in Section V.A. of the FDA guidance document [*Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised), [2] FDA recommends that the following validation studies be conducted for a SARS-CoV-2 molecular diagnostic assay: Limit of Detection, Clinical Evaluation, Inclusivity, and Cross-reactivity. This template is intended to help manufacturers provide these validation data and other information to FDA, but alternative approaches can be used. It reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should* means that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA Guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/media/97321/download).[3]

## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by the test manufacturer (sponsor) as applicable to their specific test. Text in **bold** outlines the Food and Drug Administration’s (FDA) additional recommendations for the sponsors’ consideration when completing the suggested information in each section.

-   This template is intended for testing with respiratory specimens; if you are considering non-respiratory specimens (e.g., blood, stool, etc.), please contact FDA at CDRH-EUA-Templates (CDRH-EUA-Templates@fda.hhs.gov) to discuss your validation strategy.

-   A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   This is an EUA interactive review template for Pre-EUA/EUA submissions. We plan to update the template as appropriate as we learn more about the COVID-19 disease and gain experience with the EUA process for this test.

## EXAMPLE TEMPLATE:
### A. PURPOSE FOR SUBMISSION

Emergency Use Authorization (EUA) request for distribution and/or use of the ***\[test name\]*** to ***\[indicate labs, if applicable\]*** for the *in vitro* qualitative detection of RNA from the SARS-CoV-2 in ***\[add all claimed specimen types, e.g., nasopharyngeal/ oropharyngeal swabs, sputa, BAL, etc.\]*** ***\[select appropriate testing population, e.g.,*** ***from patients suspected of COVID-19 by a healthcare provider or for screening of individuals without symptoms or other reasons to suspect COVID-19.\]******.*** Additional testing and confirmation procedures should be performed in consultation with public health and/or other authorities to whom reporting is required. Test results should be reported in accordance with local, state, and federal regulations.

***If you plan to include a sample pooling protocol in your instructions for use please include a brief description of the pooling strategy in your EUA request.***

***If you plan to request authorization to test specimens collected with a home specimen collection kit, please refer to the*** [Home Specimen Collection Molecular Diagnostic Template](https://www.fda.gov/media/138412/download) ***and include any relevant information in this request.***

### B. MEASURAND

Specific nucleic acid sequences from the genome of the SARS-CoV-2 **\[*please specify the targeted gene(s) of the pathogen*\]**.

### C. APPLICANT

***\[Official name, address and contact information of applicant\]***

### D. PROPRIETARY AND ESTABLISHED NAMES

Proprietary Name - ***\[test name\]***

Established Name - ***\[test name\]***

### E. REGULATORY INFORMATION

***Approval/Clearance Status:***

The ***\[test name\]*** test is not cleared, CLIA waived, approved, or subject to an approved investigational device exemption.

***Product Code:***

QJR

### F. PROPOSED INTENDED USE

#### 1) Intended Use:

***The proposed IU will be finalized based on the performance data and recommendations from Public Health authorities at the time of authorization – example text is provided below for a qualitative molecular test that detects organism RNA but may be adapted according to the specific emergency situation addressed by the device.***

\[***Test name***\] is a \[***specify test technology such as, real-time RT-PCR test***\] intended for the \[***presumptive***\] qualitative detection of RNA from the SARS-CoV-2 in \[***describe all the specimen types, e.g. ***nasopharyngeal, nasal, and oropharyngeal swab specimens and lower respiratory tract, BAL, sputum\] ***\[If your test is intended for testing multiple respiratory pathogens, please list the specific analytes detected by your test.\] \[describe intended use population, e.g., from individuals suspected of COVID-19 by their healthcare provider or for screening of individuals without symptoms or other reasons to suspect COVID19 infection.\].*** Testing is limited to \[***laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high complexity tests, or by similarly qualified non-U.S. laboratories***\]. ***\[Describe the sample pooling approach and maximum number of specimens which can be pooled, as applicable.\]***

Results are for the identification of SARS-CoV-2 RNA. The SARS-CoV-2 RNA is generally detectable in **\[*name specimen type, e.g. upper respiratory*\]** during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Laboratories within the United States and its territories are required to report all test results to the appropriate public health authorities.

The ***\[test name\]*** is intended for use by **\[*include intended user, e.g., qualified and trained clinical laboratory personnel specifically instructed and trained in the techniques of real-time PCR and in vitro diagnostic procedures*\]**. The ***\[test name\]*** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

***\[Depending on the performance data submitted and patient population included in the clinical evaluation, additional limitations may be recommended and/or your intended use may be modified to include the following, as applicable:***

-   ***Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.***

-   ***Negative results from pooled samples should be treated as presumptive and, if inconsistent with clinical signs and symptoms or necessary for patient management, pooled samples should be tested individually. Negative results do not preclude SARS-CoV-2 infection and must not be used as the sole basis for patient management decisions. Negative results must be considered in the context of a patient’s recent exposures, history, presence of clinical signs and symptoms consistent with COVID-19.***

-   ***Use of the \[test name\] in a general, asymptomatic screening population is intended to be used as part of an infection control plan, that may include additional preventative measures, such as a predefined serial testing plan or directed testing of high-risk individuals. Negative results should be considered presumptive and do not preclude current or future infection obtained through community transmission or other exposures. Negative results must be considered in the context of an individual’s recent exposures, history, presence of clinical signs and symptoms consistent with COVID-19.\]***

If your test is intended for use at point of care settings the following statement should be included: ***Testing is limited to laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet the requirements to perform high, moderate, or waived complexity tests. The \[test name\] is authorized for use at the Point of Care (POC), i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation.***

#### 2) Special Conditions for Use Statements:

For Emergency Use Authorization (EUA) only

For prescription use only

For in vitro diagnostic use only

#### 3) Special Instrument Requirements:

The ***\[test name\]*** test is to be used with the \[***list all RT-PCR Instruments, software requirements, automated extraction instruments***\].

### G. DEVICE DESCRIPTION AND TEST PRINCIPLE

***Example text has been added under each of the sub-headings below for a fluorescence based rRT-PCR test for detection of organism RNA. If a different test principle is used by the test for the detection of a specific analyte please modify the description accordingly to capture the salient points in each of the sub-headings below. Please note that for new investigative technologies FDA may request additional detailed information so we can adequately assess the risks and benefits associated with the device.***

#### Product Overview/Test Principle:

***Describe the technology of the test and how this technology works to identify the measurand, the instruments employed/required to perform the test from sample collection to result (include all claimed extraction and PCR detection instruments), and the specimen types for which you claim to have specific performance characteristics as described below**. **If applicable, list all primer and probe sets and briefly describe what they detect. Please include the nucleic acid sequences for all primers and probes used in the test. Please indicate if the test uses biotin-Streptavidin/avidin chemistry in any of the steps for coupling reagents. Please note that an alignment with available reference genomes for different strains of the target pathogen is requested as part of the inclusivity evaluation (Section J).***

The ***\[test name\]*** is a real-time reverse transcription polymerase chain reaction (rRT -PCR) test. The SARS-CoV-2 primer and probe set(s) is designed to detect RNA from the SARS-CoV-2 in ***\[list all the specimens\]*** from patients suspected of COVID-19 by their healthcare provider.

#### Description of Test Steps: 

***List and describe in detail all the steps of the test sequentially from specimen collection to detection.***

Nucleic acids are isolated and purified from ***\[specimens\]*** using ***\[please describe the method(s) of extraction (please specify the*** ***specimen input volume for extraction and/or test, the nucleic acid elution volume and whether isolation/purification is manual and/or automated)\]******.*** The purified nucleic acid is reverse transcribed using ***\[enzyme mix/kits – please specify the input volume of purified nucleic acid added to the rRT-PCR reaction mix\]*** into cDNA which is then subsequently amplified in ***\[please describe the instrument(s) and enzyme mix\]***. In the process, the probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5’ nuclease activity of Taq polymerase degrades the probe, causing the reporter dye to separate from the quencher dye, generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle by ***\[please describe the detection instrument(s)\]***.

#### Control Material(s) to be Used with* \[*test name*\]*:

***List all control materials (provided with the test kit and/or required but not provided with the test kit and describe what they are, how they are expected to work, where in the testing process they are used, and the frequency of use. If a control is commercially available, provide supplier’s name and catalog number or other identifier; if your device relies on external controls that are manufactured by a third party please note that these controls should also be validated within your analytical and clinical studies described below in Section J.***

Controls that will be provided with the test kit include:

1.  A “no template” (negative) control is needed to ***\[describe need\]*** and is used ***\[describe use – please also specify frequency of use\]***

2.  A positive template control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the concentration of the positive control relative to the LoD of your test (note that ideally the positive control concentration should be such that it is close to the LoD of your test) and also specify frequency of use\]***

3.  An extraction control ***\[describe control\]*** is needed to ***\[describe need\]*** and is used ***\[describe use – please also specify frequency of use\].*** **Please note that if the no template control and positive control, are taken through the entire sample processing procedure, including the extraction, then a separate extraction control is not required**.

4.  An internal control ***\[describe control\]*** is needed to ***\[describe need\]*** and is used ***\[describe use\]***.

Controls that are required but not provided with the test kit include ***\[describe control – provide recommended sources of the control materials – either a separate control kit for purchase that you the applicant develops or a control material that can be purchased from a third party\].*** This/these control(s) is/are needed to ***\[describe need\]*** and is used ***\[describe use – please also specify frequency of use\]***.

***Please note that any control recommended to be used with your device (provided with the kit or not) should be validated in the context of your analytical and clinical study (i.e., you will need to run these controls as part of your studies). In instances where control material is not readily available through 3^rd^ party vendors (which is often the case at the beginning of an outbreak) FDA may request that you include suitable control material with your device. Please note that external control materials are considered particularly important when GMP requirements are waived and reagent stability studies are limited.***

### H. INTERPRETATION OF RESULTS

All test controls should be examined prior to interpretation of patient results. If the controls are not valid, the patient results cannot be interpreted. ***Please describe if a Ct cutoff is used as part of your testing algorithm and/or if the end user is required to review fluorescent curves for weakly positive samples before final interpretation. Although not typical for molecular-based tests, if the test result involves the use of an algorithm/calculation, for example a ratio value, when determining the final patient test result, please include a detailed description and any additional calibration materials that may be required.***

#### \[Test name\] Controls – Positive, Negative and Internal

***Describe in detail the expected results generated, including acceptance criteria, for all the controls described in detail in Section G above. Describe the measured values (if applicable) for valid and invalid controls and outline the recommended actions the laboratory should take in the event of an invalid control result.***

#### Examination and Interpretation of Patient Specimen Results:

***Describe when clinical specimen test results should be assessed and outline the criteria for test validity**. **Example text**:* Assessment of clinical specimen test results should be performed after the positive and negative controls have been examined and determined to be valid and acceptable. If the controls are not valid, the patient results cannot be interpreted.

***Clearly indicate how to interpret numeric test values (if applicable) as positive or negative for presence of the*** SARS-CoV-2***. Indicate if the end user is required to review fluorescent curves for weakly positive samples before final interpretation and how to identify indeterminate/inconclusive results (if they exist) results and how the user should resolve them, e.g. if repeat testing may be required.***

***When applicable, provide a table clearly describing the possible combinations of test result values for each primer/probe set, and how they should be combined into a final interpretation of the result for your test. If the test produces result that will be used as part of a CDC recommended testing algorithm, please indicate what follow-up testing/process should be conducted, if applicable.***

### I. PRODUCT MANUFACTURING

#### Overview of Manufacturing and Distribution: 

The product will be manufactured at \[***manufacturer’s name and FDA registration number (if applicable)***\] by \[***manufacturer name***\] personnel consistent with practices for the production of **\[*types of devices*\]** based on \[***type of quality system\****\]**.** Material manufactured by \[***manufacturer’s name***\] may be bottled and kitted by \[***packager name***\] manufacturing facility.

The current manufacturing capabilities include the ability to manufacture approximately **\[*please insert the approximate number of units/products that can currently be manufactured per week at the manufacturing facility*\]** products per week, however in the event of a surge in demand this could be increased to **\[*please insert the approximate maximum number of units/products that could potentially be manufactured per week at the manufacturing facility if there was a surge in demand*\]** product per week within a **\[*please specify in weeks/months the expected timeframe required to increase product production if required*\]** timeframe.

The product will be distributed by **\[*please describe the distribution plan for the product and list all current distributors*\]**.

**\*Under the Emergency Use Authorization (EUA) any of the 21 CFR Part 820 Quality System Regulation (QSR) requirements can be waived for the duration of the EUA but FDA recommends that developers follow comparable practices as much as possible if such requirements are waived. Among other things, FDA may consider previous compliance history when determining whether or not to waive certain QSR requirements for a specific product. Please note adverse events, as per 21 CFR Part 803, have to be reported for authorized devices (see Section P).**

#### Components Included with the Test

Components manufactured by \[***manufacturer’s name and FDA registration number (if applicable)***\] and supplied with the test include:

**List all components and reagents provided for your test, including a description of the primers and probes, volumes, concentrations, quantities, buffer components, etc.**

#### Components Required But Not Included with the Test

Components required but not included with the test:

***List all components and reagents not included with the test that must be supplied by the user to perform the test, with specific supplier names and catalog numbers or other identifiers for obtaining these components and reagents. Please include here all specific consumables that were validated for use with your device, that are not interchangeable with other products and that are needed to guarantee device performance as established in the EUA validation studies listed in Section J below.***

#### Software Validation

***If you are introducing a system onto the market which has not been previously reviewed by FDA, we recommend providing evidence that the software has been validated to ensure that:***

-   ***The inputs and outputs of the software are appropriate to fulfill the system and assay requirements;***

-   ***All expected inputs produce the expected outputs for all functions critical for system operation; and***

-   ***The system will be provided to the customer free of defects or defects will be known and mitigated.***

***If this evidence is not available prior to authorization, they may be incorporated into the conditions of authorization. If changes which impact assay performance or safety and effectiveness of the system are needed to address validation failures post-authorization, then these may be required to be submitted as an EUA amendment in a condition of authorization. If no changes are needed or changes which do not impact assay performance or safety and effectiveness of the system are implemented, then the condition of authorization may require that validation data be kept on file.***

***We recommend you:***

-   ***Perform electromagnetic compatibility (EMC) testing to International Electrotechnical Commission (IEC) 60601-1-2 Edition 4.0:2014;***

-   ***Evaluate cybersecurity of your system to ensure user and patient safety in the intended use environment;***

-   ***Complete validation of all systems and software to ensure that all functions of the system perform as labeled. For more information on system validation please see the following FDA guidance documents and resources:***

    -   ***[Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices](https://www.fda.gov/media/73065/download);***

    -   ***[General Principles of Software Validation; Final Guidance for Industry and FDA Staff](https://www.fda.gov/media/73141/download);***

    -   ***[Off-The-Shelf Software Use in Medical Devices](https://www.fda.gov/media/71794/download); and***

    -   ***[21 CFR 820.30 Subpart C](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=820.30) – Design Controls of the Quality System Regulation.***

#### Testing Capabilities 

***Briefly describe current sample throughput capacity, total time required to perform the test (from clinical specimen collection, specimen transport to result), and number of tests that can be performed per instrument run and per day.***

#### Reagent Stability: 

***Briefly describe stability test plan for reagents and include accelerated stability information, if available. Please note that reagent stability studies do not need to be completed at the time of EUA issuance, however the study design should be agreed upon during interactive review and the stability studies started immediately following authorization, if not before. You should consider the following recommendations when designing your stability study:***

-   ***For EUAs you may follow the current FDA recognized CLSI Standard EP25 – Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline when evaluating the suitability of stability study designs. If you are planning to pursue a De Novo/510(k) for your device we recommend discussing in more detail your stability design to facilitate potential use of the EUA data in your regular premarket submission.***

-   ***We recommend testing a known positive diluted patient sample at 3-5x LoD rather than positive control material to establish reagent stability.***

-   ***If you are claiming multiple clinical specimen types in which similar LoDs are determined, you should use the most challenging clinical matrix for this study.***

-   ***We typically recommend your stability study design includes the evaluation of at least 5 replicates. You should also evaluate, if available, 3 different lots of reagents.***

-   ***You should design your study to provide data for a timeframe that is about 10% longer than the one to be claimed – for example; a claim of 18 months should be supported by stability data out to 20 months and a claim of 7 days should include stability data out to 8 days.***

-   ***FDA considers 15-30°C to represent room temperature conditions. Ideally you should evaluate stability at both 15°C and 30°C, however, for the purposes of the EUA evaluation at 30°C is acceptable as the worse-case scenario.***

-   ***Shelf-Life Stability- Unopened kit:***

    -   ***You should evaluate real-time kit stability studies with unopened kits stored at the claimed storage temperature for your test.***

    -   ***Accelerated stability evaluations for unopened kits is acceptable for EUA submissions while the real-time studies are on-going. However, please note real-time stability data is required to support regular pre-market submissions and for the final claim of an EUA.***

-   ***Shipping Stability - Unopened kit: Study should evaluate the anticipated handling and shipping times and temperatures expected for unopened kits.***

-   ***In-use/Opened Kit Stability: Depending on your device your stability study design should also support in-use stability of the kit reagents once the kit has been opened, e.g., storage at 2-8 ^o^C for 7 days. This includes on board stability once reagents have been placed on the instrument (if applicable).***

-   ***Inverted stability (if applicable): Study should support inverted stability for of kits.***

-   ***Freeze-thaw Stability: If you recommend aliquoting the reagents to meet the end-users needs following the initial thaw this recommendation should be supported by a freeze-thaw stability study, including the specific number of allowed freeze-thaw cycles.***

-   ***FDA analysis recommendations for real time stability studies are as follows:***

    -   ***Baseline of the study (t=0 of stability study) should not exceed a month from bottling***

    -   ***Clear baselines should be described (e.g., a month from bottling) for each stability claim under each study***

    -   ***Claims should be determined based on regression analysis. Any %change (%shift) from time zero (baseline) should be calculated between the target claim and the zero-time as (Ttest-Tbaseline)/ Tbaseline\*100 with 95%CI using the regression equation obtained from plotting the mean values. When formulating your acceptance criteria for evaluating the shift from baseline you should consider the reproducibility of your device. However, generally, that the shift at the target claim due to storage cannot exceed 10-15%. The target stability is the next to last tested point that was within +/- 10% of time zero.***

    -   ***Acceptance criterion may be different, depending on the test samples analyte concentration distribution in the intended use population and the risk, in other words, the impact of false results to public health.***

#### Sample Stability:

***Please provide sample stability information, including the study design and results if the sample is shipped to a testing site from a location other than healthcare settings, e.g. samples collected at home.***

### J. PERFORMANCE EVALUATION

***The following validation studies should be performed during your assay development:***

#### Limit of Detection (LoD) - Analytical Sensitivity:

***You should determine the LoD of the test utilizing all components of the test system from sample preparation to detection.* *Testing quantified inactivated virus (e.g., heat treated or irradiated virus) spiked into real clinical matrix (e.g., BAL fluid, sputum, nasopharyngeal swab, etc.) for LoD determination is recommended since the inactivated virus most closely reflects live virus in a clinical sample.*** ***If you are unable to acquire inactivated virus, FDA believes that viral genomic RNA is the next best material to use to generated contrived samples for testing.*** ***As positive natural clinical specimens are increasingly becoming available, a quantified known positive clinical specimen as determined by an EUA authorized test can also be used to create dilutions in ******clinical matrix for LoD determination. Respiratory swab matrix should derive from swab specimens collected from SARS-CoV-2 negative individuals. FDA recommends that preliminary LoD be determined by testing a 2-3 fold dilution series of three replicates per concentration. The lowest concentration that gives positive results 100% of the time is defined as the preliminary LoD. The final LoD concentration should be confirmed by testing 20 individual extraction replicates at the preliminary LoD. FDA defines LoD as the lowest concentration at which 19/20 replicates are positive. If multiple clinical matrices are intended for clinical testing, you should submit to FDA the results from one representative matrix of each claimed clinical matrix type. For example:***

***- If testing common upper respiratory tract specimens (e.g., nasopharyngeal (NP) swabs, oropharyngeal (OP), swabs, nasal swabs, anterior nasal swabs, mid-turbinate nasal swabs, nasal aspirates, and nasal washes etc.), please submit results from the most challenging upper respiratory matrix. FDA considers nasopharyngeal (NP) swabs to be the most challenging upper respiratory matrix.***

***- If claiming common lower respiratory tract specimens (e.g., tracheal aspirates, sputum, etc.), please submit results from the most challenging lower respiratory matrix. FDA considers sputum to be the most challenging lower respiratory matrix.***

***- If claiming both, upper and lower respiratory matrixes, submitting results from sputum samples may suffice to support both upper and lower respiratory matrices.***

***- If claiming alternative respiratory specimens, such as saliva, oral fluid, buccal swab, etc., please submit results from testing each of the claimed uncommon respiratory specimen type.***

***- If needed, FDA recommends that you follow the most current version of the CLSI standard, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures (CLSI EP17).***

**\[*Please describe your LoD study, the specific material used (e.g., live or in-activated viral stocks, viral RNA), the specific clinical matrix used, and the LoD (with appropriate units) for your assay*\]**

#### Inclusivity (analytical sensitivity): 

***Laboratories should document the results of an inclusivity study that demonstrates the strains of SAR-CoV-2 that can be detected by the proposed molecular assay. It is acceptable to conduct an in silico analysis of published SARS-CoV-2 sequences using the assay’s primers and probes. FDA anticipates that 100% of published SAR-CoV-2 sequences will be detectable with the selected primers and probes.***

***\[Please describe your Inclusivity study and confirm that there was 100% detection of all SARS-CoV-2 strains.\]* *If sequences with less than 100% homology with any of the primers and probes in your test are identified, please provide a risk assessment on how such mismatches may impact the performance of your test.***

#### Cross-reactivity (Analytical Specificity): 

***Cross-reactivity studies are performed to** **demonstrate that the test does not react with related pathogens, high prevalence disease agents and normal or pathogenic flora that are reasonably likely to be encountered in a clinical specimen. For respiratory specimen claims excluding saliva and oral fluid, the recommended list of organisms to be analyzed in silico and by wet testing is provided in the table below. For non-respiratory matrices or saliva and oral fluid, an appropriate list of organisms should be tested, please see previous FDA decision summaries for recommended organisms or contact FDA for recommended organisms. For wet testing, concentrations of 10^6^ CFU/ml or higher for bacteria and 10^5^ pfu/ml or higher for viruses is recommended. In silico analyses alone may be acceptable for organisms that are difficult to obtain. FDA defines in silico cross-reactivity as greater than 80% homology between one of the primers/probes and any sequence present in the targeted microorganism. ***

**Recommended List of Organisms to be Analyzed *in silico*  
and by Wet Testing**

| **Other high priority pathogens from the same genetic family** | **High priority organisms likely present in a respiratory specimen** |
|----------------------------------|--------------------------------------|
| **Human coronavirus 229E** | **Adenovirus (e.g. C1 Ad. 71)** |
| **Human coronavirus OC43** | **Human Metapneumovirus (hMPV)** |
| **Human coronavirus HKU1** | **Parainfluenza virus 1-4** |
| **Human coronavirus NL63** | **Influenza A & B** |
| **SARS-coronavirus** | **Enterovirus (e.g. EV68)** |
| **MERS-coronavirus** | **Respiratory syncytial virus** |
|  | **Rhinovirus** |
|  | ***Chlamydia pneumoniae*** |
|  | ***Haemophilus influenzae*** |
|  | ***Legionella pneumophila*** |
|  | ***Mycobacterium tuberculosis*** |
|  | ***Streptococcus pneumoniae*** |
|  | ***Streptococcus pyogenes*** |
|  | ***Bordetella pertussis*** |
|  | ***Mycoplasma pneumoniae*** |
|  | ***Pneumocystis jirovecii* (PJP)** |
|  | **Pooled human nasal wash - *to represent diverse microbial flora in the human respiratory tract*** |
|  | ***Candida albicans*** |
|  | ***Pseudomonas aeruginosa*** |
|  | ***Staphylococcus epidermis*** |
|  | ***Streptococcus salivarius*** |
||

*Microbial Interference Studies:* ***If in silico analysis reveals ≥ 80% homology between the cross-reactivity microorganisms and your test primers/ probe(s), we recommend that you either perform (1) a microbial interference study with SARS-CoV-2 and the microorganisms that your test primers/ probe(s) have homology to, or (2) as an alternative to the microbial interference study, you may provide justification as to why (e.g., amount of primer(s)/ probe(s) included in your master mix) the performance of your test would not be impacted by the presence of a causative agent of a clinically significant co-infection, or (3) explain why the in silico results are clinically irrelevant (e.g., low prevalence of MERS-CoV, etc.). Competitive microbial interference testing should be conducted for multiplex panels. The study should assess the effects of clinically relevant co-infections by testing selected microorganisms commonly found in the claimed specimen matrix in the presence of SARS-CoV-2 at low concentration. The interference should be evaluated by testing with a minimum of 3 sample replicates spiked at a low (≤3x LoD) SARS-CoV-2 concentration and a high interferent level (preferably microorganisms), to represent the worst-case scenario. The interferent microorganisms can be tested individually or as a pool (of four or five) in the presence of low concentration of SARS-CoV-2. Each microorganism of a pool should be tested individually, if that pool shows interference. If you plan to claim both upper and lower respiratory clinical specimens, the study should be performed in the most challenging specimen matrix, i.e., sputum. If interference is observed at the level tested, an additional titration study should be performed to determine the highest microorganism interferent level your test can achieve the stated performance.***

*Endogenous Interference Substances Studies*: ***The extent of testing for endogenous interference substances depends on the matrix that is claimed for the device as well as on the technology of the device, e.g., if a nucleic acid extraction procedure is performed prior to testing or not. If your test uses extraction methods not previous reviewed by FDA as part of premarket submission or the test does not use an extraction procedure, we recommend testing of potential interferents. Please contact FDA to discuss the appropriate study designs.***

#### Clinical Evaluation 

#### a) Claims for testing respiratory specimens from patients suspected of COVID-19 by their healthcare provider:

***FDA recommends using natural clinical specimens in the clinical evaluation. Please refer to the following table for additional information regarding clinical study design:***

***Note: Clinical study recommendations listed in the table below do not apply to claims for screening individuals without symptoms or other reasons to suspect COVID-19 and to saliva or other alternative respiratory specimen type claims.***

| Minimum Number of Positive Specimens | A minimum of 30 individual natural (prospective or retrospective or leftover samples) positive clinical specimens should be collected from patients suspected of SARS-CoV-2 infection by a healthcare provider in COVID-19 disease endemic region(s). Samples can be a mixture of specimen types, if you are seeking an upper respiratory claim (e.g., nasopharyngeal (NP) swab, oropharyngeal (OP) swab, nasal swab (NS)). If you are seeking a sputum claim, and any other respiratory specimen claim except alternative respiratory specimen types (e.g., saliva), we recommend a combination of 15 NP and 15 sputum samples. Specimens collected from different anatomical sites from the same patient may be used to support claims for multiple specimen types. The use of frozen samples is acceptable. Specimens representing a wide range of viral load including low positive samples should be tested. The use of samples previously tested positive by another EUA RT-PCR assay may be acceptable without additional comparator testing. You should indicate the source of the samples, provide results for each tested sample, indicate specimen type, and initial test date. |
| --- | --- |
| Minimum Number of Negative Specimens | A minimum of 30 individual negative samples acquired from the following sources are acceptable; (1) prospective samples from the individuals suspected of COVID-19 by their healthcare provider, (2) archived/retrospective respiratory samples collected from patients with signs and symptoms of respiratory infection, and (3) other subjects that are expected to be negative for SARS-CoV-2, such as specimens collected prior to COVID-19 pandemic in the US. |
| Recommended Comparator Method for percent agreement performance calculations | Positive percent agreement should be calculated in comparison to an EUA RT-PCR test. We recommend using only a high sensitivity EUA RT-PCR assay which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction). If available, FDA recommends selecting a comparator assay that has established high sensitivity with an internationally recognized standard or FDA SARS-CoV-2 Reference Panel. Please contact CDRH-EUA-Templates@fda.hhs.gov to discuss options to establish the sensitivity of your comparator method. Please see the following website for the most recent list of FDA authorized 2019-nCoV tests: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations . Negative result agreement may be calculated in comparison to an EUA RT-PCR test (prospectively collected samples) or as agreement with expected results if samples were collected from individuals known to be negative for SARS-CoV2 (e.g. collected before December 2019). The comparator assay may have the same, or different, targets as your assay. False results can be investigated using an additional EUA RT-PCR assay, and/or Sanger sequencing. The results of the discordant analysis can be footnoted in your final performance table but cannot be used to change the final performance calculations. |
| Acceptance Criteria | FDA believes a minimum of 95% positive and negative agreement is acceptable clinical performance. |
| Natural Clinical Specimens IRB/Informed Consent Note | Prospective collection of clinical specimens to support the EUA request should be done in accordance with regulations for human subject protection, including IRB approval and informed consent. Use of leftover de-identified samples may follow the policy outlined in the FDA Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable ( https://www.fda.gov/media/122648/download ). |
| Testing Approach Note 1 | All clinical specimens tested in your study should be evaluated in accordance with your proposed diagnostic algorithm (i.e., tested using the procedure in the instructions for use), including retesting when appropriate. The limited volume of natural specimens may preclude retesting. In instances where retesting is indicated but not performed, for the purposes of performance evaluation, initial results will be analyzed for performance and equivocal/indeterminate/inconclusive results should count against your final performance. |
| Testing Approach Note 2 | Specimens should be tested in a blinded fashion, e.g., positive and negative samples should be presented to the end user in a blinded fashion. The end user should also be blinded to the results of any comparator method testing. |
||

#### b) Testing alternative specimens (i.e., other than respiratory specimens) from patients suspected of COVID-19 by their healthcare provider:

***If you seek a claim for alternative specimens, such as saliva, oral fluid, buccal swabs, etc., you should test two paired specimens from at least 30 positive and 30 negative patients. Consecutively collected specimens are preferred. Specimens representing a wide range of viral load including low positive samples should be tested. One specimen from each patient should be collected by a healthcare worker using a nasopharyngeal (NP) swab and tested with an assay authorized for use with NP specimens. FDA recommends selecting a comparator assay that has established high sensitivity with an internationally recognized standard or FDA SARS-CoV-2 Reference Panel. Please contact <CDRH-EUA-Templates@fda.hhs.gov> to discuss options to establish the sensitivity of your comparator method. The other specimen from each patient should be the alternative specimen and should be tested with your candidate EUA assay, provided it is authorized for testing of NP specimens, or using a previously authorized test with an NP swab claim. To minimize the occurrence of discordant results due to biological variability, both samples should be collected within a short time period. FDA believes ≥95% positive percent agreement with similar Ct values for the paired specimen types is acceptable performance.***

***Please provide detailed information regarding the type of collection device and transport media you propose to validate for use with your assay. Please note that some transport media may not be compatible with assays that do not use a nucleic acid extraction step. In addition, some transport medium may not be acceptable for use for at-home collection due to the presence of hazardous chemicals. For additional information that may be needed to support at-home sample collection and transport, please review the [Home Specimen Collection Molecular Diagnostic Template](https://www.fda.gov/media/138412/download) or contact FDA at <CDRH-EUA-Templates@fda.hhs.gov>.***

#### c) Screening individuals without symptoms or other reasons to suspect COVID-19 with a previously unauthorized test 

***The recommendations below reflect FDA’s current thinking. The study design and recommendations may change as additional information becomes available regarding asymptomatic infections, including but not limited to viral titer dynamics and transmission rates in this population.***

***If you seek claims for screening individuals without symptoms or other reasons to suspect COVID-19, FDA recommends that you conduct a clinical study in the intended population. In the clinical study, you should compare results from for your assay and a comparator assay for each patient enrolled. Please consider the following when designing your clinical validation study:***

-   ***The number of enrolled patients should be sufficient to ensure at least 20 positive samples are prospectively collected in the intended use population and be sufficient to demonstrate the following minimum performance:***

***PPA ≥95% (Lower Bound of the two-sided 95% confidence interval &gt;76%)***

***NPA ≥98% (Lower Bound of the two-sided 95% confidence interval &gt;95%)***

***The total number of samples needed will depend on the prevalence of SARS-CoV-2 in the intended use population.***

-   ***Samples for the candidate test should be collected according to the instruction for use.***

-   ***Samples for comparator method testing should be healthcare provider collected NP swabs. If an NP swab cannot be collected, a nasal swab may be used, however, both anterior nares should be sampled with the same swab. Sampling for the candidate test and comparator method should occur within a short timeframe to avoid biological variability in viral load.***

-   ***If available, FDA recommends selecting a comparator assay that has established high sensitivity with an internationally recognized standard or the FDA SARS-CoV-2 Reference Panel. Please contact <CDRH-EUA-Templates@fda.hhs.gov> to discuss options to establish the sensitivity of your test.***

-   ***In general, we recommend that you collect samples at a minimum of three geographically diverse sites, especially if you are planning to use the same data to support a subsequent De novo/510k submission. If this is not possible, FDA will consider samples collected at one or two sites in the context of an EUA.***

-   ***It may be possible to use archived samples that were collected from asymptomatic patients. We recommend you contact FDA to discuss such an approach prior to initiating your study.***

#### d) Adding population screening of individuals without symptoms or other reasons to suspect COVID-19 to an authorized test.

***Alternative approaches may be acceptable for tests that have been previously authorized with clinical data for symptomatic patients. For example:***

-   ***If your assay is highly sensitive as determined by testing with the FDA SARS-CoV-2 Reference Panel or a recognized international standard, a post-authorization study may be appropriate. We recommend testing a minimum of 20 consecutively collected asymptomatic positive specimens and at least 100 consecutively collected negative specimens based on the results of the candidate test. All specimens should then be tested with another EUA authorized molecular assay. Using estimates of the predictive values and the percentage of positive results, this study can be used to establish the sensitivity (PPA) and specificity (NPA) of your test in a general, asymptomatic population, as this is an important performance metric for tests intended for screening of large populations without symptoms or other reasons to suspect COVID-19. The FDA expectation is that PPA should be &gt;95% (lower bound of the two-sided 95% confidence interval &gt;76%) and NPA should be ≥98% (with a lower bound of the two-sided 95% confidence interval &gt;95%). If you do not have access to either the FDA SARS-CoV-2 Reference Panel or a recognized international standard then please contact <CDRH-EUA-templates@fda.hhs.gov> to discuss options.***

-   ***If you can demonstrate that performance of your assay in both populations is likely similar (i.e., the percent of positive individuals with Ct values representing low viral loads are similar in individuals suspected and not suspected of COVID-19 by their healthcare provider) you may include both populations in your evaluation. We encourage the use of historic data (i.e., existing or published data) for this evaluation.***

***FDA is open to considering additional alternative study designs to demonstrate that the performance of your assay is appropriate for screening individuals without symptoms or other reasons to suspect COVID-19. We recommend contacting FDA to discuss alternative study designs prior to beginning such a study.***

#### e) Specimen Pooling

-   ***The recommendations below reflect FDA’s current thinking. The study design and other recommendations may change as additional information becomes available. At this time, the need for testing remains greater than available resources. Combining multiple patient samples to create one pooled sample for testing could enable broader access to testing.***

-   ***To establish performance of your test with pooling, FDA recommends conducting a clinical validation study in the intended use population that includes testing each sample individually and using your proposed pooling strategy.***

-   ***Currently FDA recommends two approaches to patient specimen pooling: 1) pooling aliquots of transport media which each contain a single patient sample (sample/media pooling) or 2) adding swabs from multiple patients into a single volume of transport media (swab pooling). As more data become available and new approaches are identified, our recommendations may evolve.***

***Monitoring:***

-   ***Commercial test kit manufacturers should provide instructions for laboratories to incorporate ongoing monitoring of the pooling strategy by addressing the following in their Instructions for Use:***

    -   ***Before implementation of pooling, evaluate existing test data in the testing population from the previous 7-10 days to estimate the initial positivity rate.***

    -   ***When implementing a pooling strategy, continue to test a random sampling of patient samples without pooling to:***

        -   ***evaluate the positivity rate and percent of weak positive samples in the testing population and***

        -   ***identify differences in positivity rate between those tested individually and those tested through pooling.***

    -   ***Calculate the percent of positive results after implementation of pooling using a moving average (such as a rolling average updated daily using data from the previous 7-10 days) to determine whether there is a change in the positivity rates between individual testing and pooled testing. Reevaluate testing strategy if the moving average of the positivity rate for pooled samples starts trending in a positive or negative direction.***

    -   ***Finally, when resource availability is sufficient to meet testing demand, FDA recommends considering whether the risks of reduced test sensitivity with pooling continue to outweigh the benefits of resource conservation.***

***e.1) Sample/Media Pooling***

***A simple, or Dorfman, approach involves testing an “n-sample pool,” where n is the number of transport media samples included in the pool. A negative result implies that all samples in the pool are negative. A positive result indicates that at least one sample in the pool is positive. When an n-sample pool is positive, each sample within the pool must be individually tested to determine which is/are positive. When used effectively, n-sample pooling can generally enable testing of more individuals despite limited testing resources.***

-   ***When pooling transport media, rather than swabs, one individual sample is defined as a single specimen swab collected from a subject and placed in a specific volume of transport media. In this type of pooling, an aliquot of each individual sample is combined into non-overlapping pools of n samples and each n-sample pool is tested. Therefore, the volume of samples initially collected from an individual must be sufficient for both the pooled testing and individual follow-up testing, if needed.***

-   ***N-sample pooling should be considered in the context of the positivity rate of a test in the test population, analytical sensitivity of the test, and the percent of weak positive subjects in the tested population. Pooling of n samples reduces the analytical sensitivity of the test (increase in the LoD) because samples are diluted. The impact of decreased analytical sensitivity depends on the percent of subject specimens with viral genetic material concentrations close to the LoD (weak positives) in the tested population. Therefore, analytical sensitivity of the test with n-sample pools should be evaluated.***

-   ***FDA believes an n=5 is a reasonable starting point for validation of pooling for a high-sensitivity test in populations with a positivity rate of approximately 5% to 6%. In populations with lower prevalence, larger sample pools may be feasible. In populations with higher prevalence, smaller sample pools may be needed. FDA recommends that developers begin by validating their tests for pooling using an n=5. Tests validated and authorized for n=5 can then be used with any n≤5 depending on testing needs and taking into consideration local prevalence. In cases where a developer wants to validate an n&gt;5, or is considering alternate pooling schemes, FDA recommends that developers reach out to FDA at <CDRH-EUA-Templates@fda.hhs.gov> or submit a pre-EUA to discuss their approach and validation plan.***

-   ***The table below presents calculated n-sample pool sizes with the maximal efficiency (a maximum increase in the number of tested patients because of n-sample pooling strategy) for different positivity rates P. This n with maximal efficiency (n~maxefficiency~) should be a starting pool size for validation of pooling with positivity rate P. If the accuracy of the test with regard to missed positive patients because of n~maxefficiency~ samples pooling is not acceptable, n &lt; n~maxefficiency~ should be considered and accuracy of pooling with this n should be evaluated.***

| P, percent of positive subjects in the tested population | n~maxefficiency~ (n corresponding to the maximal efficiency) | Efficiency of n-sample pooling (a maximum increase in the number of tested patients when Dorfman n-pooling strategy used) |
| --- | --- | --- |
| 1% | 11 | 5.11 |
| 2% | 8 | 3.65 |
| 3% | 6 | 3.00 |
| 4% | 6 | 2.60 |
| 5% | 5 | 2.35 |
| 6% | 5 | 2.15 |
| 7% | 4 | 1.99 |
| 8% | 4 | 1.87 |
| 9% | 4 | 1.77 |
| 10% | 4 | 1.68 |
| 11% | 4 | 1.61 |
| 12% | 4 | 1.54 |
| 13% | 3 | 1.48 |
| 14% | 3 | 1.43 |
| 15% | 3 | 1.39 |
| 16% | 3 | 1.35 |
| 17% | 3 | 1.31 |
| 18% | 3 | 1.28 |
| 19% | 3 | 1.25 |
| 20% | 3 | 1.22 |
| 21% | 3 | 1.19 |
| 22% | 3 | 1.16 |
| 23% | 3 | 1.14 |
| 24% | 3 | 1.12 |
| 25% | 3 | 1.10 |
||

***Because a single positive sample in a pool requires individual retesting of each sample in the pool, the efficiency of any pooling strategy depends on the positivity rate. The efficiency (F) of n-sample pooling for positivity rate (P) can be calculated with the following formula F=1/(1+1/n-(1-P)^n^). The efficiency (F) indicates how many more patients can be tested with n-sample pools compared to individual testing. For example, a 3-sample pooling strategy increases the number of tested patients by 1.48 times for positivity rate P of 13% (F=1.48) and by 1.22 times for positivity rate P of 20% (F=1.22). At F=1.48, 1,000 tests can cover testing of 1,480 patients. Likewise, at F=1.22, 1,000 tests can cover testing of 1,220 patients.***

-   ***A test validated for a specific n-sample pooling strategy is also considered to be validated for any number of pooled samples below n. For example, a test validated for a 5-sample pooling strategy can be performed for any n≤5.***

-   ***Different specimen types should not be pooled together.***

-   ***FDA recommends that your instructions for use specify a sample volume great enough to allow for individual and pooled testing so that, during clinical use, any samples in a positive pool can be re-tested without the need for a second sample collection.***

-   ***Due to the reduction in analytical sensitivity, a pooling strategy should include risk mitigations such as additional language in the report noting that pooling was used during testing.***

***Validation:***

-   ***Test developers should characterize the reduction in assay analytical sensitivity (i.e., shift in Ct value for RT-PCR assays) with respect to the number (n) of samples to be pooled to ensure the selected n-sample pooling strategy will maintain appropriate sensitivity. This maximum number of samples acceptable to pool should be determined and validated using the recommendations below for each specimen type you intend to pool.***

-   ***We strongly recommend that you develop and validate a system for deconvoluting pooled test data which is intended to accurately identify individual patient samples composing each pooled sample. If you plan to use a software solution intended to deconvolute pooled SARS-CoV-2 diagnostic test data then we recommend providing validation data establishing that the software can achieve its intended use. For example, we recommend providing evidence that the software has been validated to ensure that:***

    -   ***The inputs and outputs of the software are appropriate for the intended use of the assay;***

    -   ***All expected inputs produce the expected outputs for all functions critical for system operation; and***

    -   ***The system will be provided to the customer free of defects or defects will be known and mitigated.***

**A) Sample pooling: adding a pooling strategy to a previously authorized (EUA) test**

***When requesting to add an n-sample pooling strategy to the authorized uses and the authorized Instructions for Use for your own previously authorized assay, you should submit an EUA amendment request with the appropriate validation data as described below. To add a pooling strategy to a previously authorized test, you generally do not need to establish performance with a separate comparator assay.***

***You should conduct a clinical study with at least 20 individual positive samples, comparing the performance of the EUA-authorized assay when testing single specimens according to the authorized Instructions for Use to the performance of the assay when testing n-sample pools. We strongly encourage you to work with your customers to gather existing data (e.g., 100 Ct values from individually tested positive patient samples) and evaluate the percentage of samples with Ct values close to your assay LoD (i.e., weak positives). A theoretical Ct shift of Log~2~(n) can be estimated for most RT-PCR tests (e.g., for n=5, a Ct shift of 2.3 would be expected). Therefore, if a large percentage of positive patient samples are close to your assay LoD, you may want to consider a smaller n, which will reduce the observed Ct shift and maintain higher sensitivity.***

***Please consider the following when designing your clinical validation study with 20 individually tested positive samples:***

-   ***If archived individual samples are available and have enough volume for testing with n-sample pools, we recommend that you use at least 20 archived positive samples. If these samples are not available with sufficient volume, we recommend that you enroll enough patients to collect at least 20 positive samples and an appropriate number of individual negative samples from the intended use population. For example, for a 5-sample pooling strategy, a total of 80 unique comparator method negative samples are recommended in order to make up 20 5-sample pools with the 20 positive samples (20 positives + 4x20 negatives). Additionally, 100 comparator method negative samples are recommended to make up 20 5-sample negative pools (5x20 negatives) as described below. If there is sufficient volume, the same negative patient samples can be used to create positive and negative pooled samples.***

-   ***We recommend that at least 25% of the validation samples be within 2-3 Ct of the cut off, and no more than within 2-4 Ct.***

-   ***Samples should be collected according to the instructions for use, keeping in mind that additional sample volume will be needed to test using an n-sample pooling strategy (n-sample pooling will need 1+1/n times the volume needed for individual testing).***

-   ***All samples should be individually tested by your assay, either previously for archived specimens or prospectively, and have recorded Ct values if using an RT-PCR test.***

-   ***To characterize the performance of your assay when testing pooled samples, those samples with positive results when tested individually should each be pooled with n-1 (e.g., where n=5, n-1=4) randomly selected negative samples. The resulting 20 pools, each consisting of 1 positive sample and n-1 negative samples, should be tested by your assay.***

-   ***To confirm that negative samples remain negative in n-sample pools, we recommend testing 20 pools each consisting of n (e.g., n=5) negative samples. If there is sufficient volume, the same negative patient samples can be used to create positive and negative pooled samples.***

***Analysis of data***

-   ***You should report estimates of positive and negative percent agreement comparing the performance of your test for pooled samples to the expected result. With regard to positive percent agreement (PPA), using a study design with 20 positives, you should calculate the percent of pools (1 positive and n-1 negative) with positive results. It is anticipated that all samples that were identified individually as positive by your test should still be positive when tested in pools with n-1 negative samples (PPA=100%); lower levels of PPA in the range of 85-90% may be acceptable depending on pooling efficiency and other factors. The n that allows a test to meet 85% or higher PPA should be validated for each test.***

-   ***Additionally, for RT-PCR tests, you should provide an analysis of Ct values for each target detected by your test. We recommend presenting the Ct values for the n-sample pools on the Y-axis and Ct values for the individually tested samples on the X-axis. The clinical validation study should demonstrate that individual positive samples with viral loads close to the assay’s LoD (i.e., weak positives) are accurately detected by your test in a pool with (n-1) negative samples.***

-   ***We recommend that you provide an appropriate type of regression analysis with slope and intercept along with 95% confidence interval. Using regression analysis, we recommend that you evaluate the shift in Ct values for the positive patient samples diluted with negative patient samples.***

**B) Sample pooling: new test (not previously authorized)**

***When requesting to include an n-sample pooling strategy for a new test, you should submit an EUA request with the appropriate validation data for individual testing in your proposed intended use population and for pooled testing, as described below. This should involve using a high-sensitivity comparator assay to characterize performance of your candidate test.***

***You should conduct a clinical study with at least 30 individual positive samples, as identified by the comparator assay, comparing the performance of the candidate assay both when testing single specimens and when testing n-sample pools to the performance of the comparator assay.***

***Please consider the following when designing your clinical validation study:***

-   ***The number of enrolled patient specimens should be sufficient to ensure at least 30 comparator method positive samples and an appropriate number of comparator method negative samples are collected from the intended use population. The number of comparator method negative samples depends on the pooling strategy. For instance, for a 5-sample pooling strategy, a total of 120 unique comparator method negative samples are recommended in order to make up 30 5-sample pools with the 30 positive samples (30 positives + 4x30 negatives). Additionally, 150 comparator method negative samples should make up 30 5-sample negative pools (5x30 negatives) as described below. If there is sufficient volume, the same negative patient samples can be used to create positive and negative pooled samples.***

-   ***Samples for comparator method testing should be healthcare provider collected NP swabs. If an NP swab cannot be collected, a nasal swab can be used however both anterior nares should be sampled with the same swab. Sampling for the candidate test and comparator method should occur within a short timeframe, such as during the same visit, to avoid biological variability in viral load.***

-   ***If available, FDA recommends selecting a comparator assay that has established high sensitivity with an internationally recognized standard or the FDA SARS-CoV-2 Reference Panel. Please contact <CDRH-EUA-Templates@fda.hhs.gov> to discuss options to establish sensitivity.***

-   ***Samples for the candidate test should be collected according to the instructions for use. Depending on the sample volume required for your test, a single specimen collected from each study participant may be sufficient for individual and pooled sample testing.***

-   ***In general, we recommend that you collect samples at a minimum of three geographically diverse sites, especially if you are planning to use the same data to support a subsequent De novo/510k submission. If this is not possible, FDA recommends samples collected at one or two sites in the context of an EUA.***

-   ***It may be possible to use archived positive samples that were collected from the intended use population. We recommend you contact FDA to discuss such an approach prior to initiating your study. If archived samples are available, we recommend that at least 25% of the validation samples should be within 2-3 Ct of the cut off, and no more than within 2-4 Ct.***

-   ***All samples should be individually tested by the comparator assay and individually tested by the candidate assay to characterize the performance of your assay when testing individual samples.***

-   ***To characterize the performance of your assay when testing n-sample pools, those samples with positive results by the comparator method should each be pooled with n-1 (e.g., where n=5, n-1=4) randomly selected comparator method negative samples. The resulting 30 pools, each consisting of 1 comparator method positive sample and n-1 comparator method negative samples, should be tested by your candidate assay.***

-   ***To confirm that samples with comparator method negative results remain negative in n-sample pools, we recommend testing 30 pools each consisting of n (e.g., n=5) comparator method negative samples.***

***Analysis of data***

-   ***You should report estimates of positive and negative percent agreement comparing individual results from your test and the comparator test, as well as performance of pooled samples to the expected results (i.e., a pool which includes a comparator method positive sample is expected to remain positive when pooled). With regard to positive percent agreement (PPA), using a study design with 30 positives, you should calculate the percent of pools (1 positive and n-1 negative) with positive results. It is anticipated that all samples that were identified individually as positive should still be positive when tested in pools with n-1 negative samples (PPA=100%); lower levels of PPA in the range of 85-90% may be acceptable depending on pooling efficiency and other factors. The n that allows a test to meet 85% or higher PPA should be validated for each test.***

-   ***Additionally, for RT-PCR tests, you should provide an analysis of Ct values of each target detected by your test. We recommend presenting the Ct values for the n-sample pools on the Y-axis and Ct values for the individually tested samples on the X-axis. The clinical validation study should demonstrate that individual positive samples with viral load close to the assay’s LoD (i.e., weak positives) are accurately detected by your test in a pool with (n-1) negative samples.***

-   ***We recommend that you provide an appropriate type of regression analysis with slope and intercept along with 95% confidence interval. Using regression analysis, we recommend that you evaluate the shift in Ct values for the positive patient samples diluted with negative patient samples.***

**C) Example of validation and data presentation.**

The information below is included as an example of how data can be presented to FDA in a pre-EUA or EUA request. It is for illustrative purposes only and is not reflective of data from any specific test nor the only way to present such information. This example is based on a 5-sample pooling strategy using an extraction method requiring a 500 uL sample.

1.  ***Used the candidate assay to individually test 500 uL aliquots of 30 comparator positive samples and 150 comparator negative samples.***

***Example of table for presenting calculation of PPA and NPA of the candidate test results for samples tested individually vs the comparator test results:***

| ***Samples Tested Individually*** | ***Comparator Method Result*** |  |
|------------------------|------------------------|------------------------|
| ***Candidate Test Result*** | ***Positive*** | ***Negative*** |
| ***Positive*** |  |  |
| ***Negative*** |  |  |
||

1.  ***Created expected positive 5-sample pools by combining 100 uL of one (1) individual positive patient sample with 100 uL aliquots from each of four (4) unique comparator method negative patient samples. This was done for all positive patient samples thereby creating 30 5-sample pools (i.e., a total of 30 positives combined with a total of 120 negatives).***

2.  ***Created expected negative 5-sample pools by combining 100 uL of five (5) individual negative patient samples using a total of 150 unique negative samples. When there was sufficient volume, the same negative patient samples were used to create positive and negative pooled samples.***

3.  ***Tested all 5-sample pools by following the instructions for use of the candidate test. All previous results were unknown to the user (i.e., an individual other than the user performing the testing prepared the samples such that testing was performed “blinded”).***

4.  ***Calculated the percent agreement of the pooled samples with respect to the expected results (i.e., if a positive patient sample was included in the 5-sample pools, the expected result was positive).***

***Example of table for presenting calculation of PPA and NPA of the candidate test results for samples tested in 5-sample pools vs expected results (where expected results are based on the individual testing):***

| ***Samples Tested in 5-sample pool*** | ***Expected Result*** |                |
|------------------------|------------------------|------------------------|
| ***Pooled Test Result***              | ***Positive***        | ***Negative*** |
| ***Positive***                        |                       |                |
| ***Negative***                        |                       |                |
||

1.  ***If the candidate assay is an RT-PCR test and cycle threshold values (Ct value) are available, we recommend that you provide a data plot (example below) of the positive sample Ct values of an individual tested positive (i.e., the Ct value of the individual positive sample used to create the positive pooled sample) and the positive pooled sample. We recommend that you include a diagonal line with a slope of 1 and a y-intercept of 0. We recommend that you provide an appropriate type of regression analysis with slope and intercept along with 95% confidence interval. Using the regression analysis, we recommend that you evaluate the shift in Ct values for the positive patient samples diluted with negative patient samples.***

_Scatter plot example showing individual positive sample Ct values (x-axis) vs. pooled positive sample Ct values (y-axis) with a diagonal reference line (slope=1, y-intercept=0) and regression analysis._

1.  ***Agreement should also be presented in a stratified manner so that performance over the range of Ct values can be evaluated. For example, if the cut-off for the candidate test is Ct = 40 then the following table should be provided:***

| Samples Tested in a 5-sample Pool | Expected Result Individual Samples with 37 < Ct < 40 |  |
| --- | --- | --- |
| Pooled Test Result | Positive | Negative |
| Positive |  |  |
| Negative |  |  |
|  | Expected Result Individual Samples with 34 < Ct < 37 |  |
| Positive |  |  |
| Negative |  |  |
|  | Expected Result Individual Samples with Ct < 34 |  |
| Positive |  |  |
| Negative |  |  |
|  | Expected Result All Individual Samples |  |
| Positive |  |  |
| Negative |  |  |
||

#### e.2) Swab Pooling

***Swab pooling is an approach which conserves transport media and has the potential to maintain sensitivity of the test; however, deconvolving which swab was positive cannot be done without collecting another specimen. This approach also results in a high concentration of swab specimen in transport media, therefore inhibition may be observed. The effects of inhibition due to high concentrations of swab specimens (e.g., mucin) and high concentrations of virus when there are multiple positive swabs in the swab pool should be investigated. We recommend performing swab pooling validation using the two studies described below using the highest number of swabs that is both desired and deemed feasible. If the data does not meet the acceptance criteria noted below we recommend evaluating a lower number of swabs until the recommended acceptance criteria are met. Laboratories can proceed testing with any number of pooled swabs up to the highest number of pooled swabs that was successfully validated.***

***In your instructions for use, you should provide a detailed procedure describing a method to combine swabs into a single volume of transport media. The procedure should include recommendations to maximize the amount of specimen resuspended into the transport media from the swab and help ensure that the user performs sample and swab handling in a manner consistent with current infection control procedures, which should also reduce the chance of carryover between sample pools.***

***The maximum number of swabs that can be pooled for maximum efficiency can be calculated the same way as the maximum number of samples as discussed above for Dorfman pooling.***

***To establish performance of your test with swab pooling, FDA recommends conducting a clinical validation study in the intended use population that includes testing each sample individually and using your proposed pooling strategy. Examples of clinical validation studies for adding pooling to a previously authorized (EUA) tests or to include pooling in an EUA request for a new test are included in the sample/media pooling section above. These studies can be adjusted to validate a swab pooling strategy.***

***For n-swab pooling strategies, the two studies below should also be conducted:***

1.  ***We recommend establishing performance related to test interference from multiple swab specimens in a single volume of transport media. N-swab samples containing the maximum number of swabs you intend to validate in the minimum volume of transport media you intend to validate should be tested with an analyte concentration of 2-3X LoD. The swabs should contain clinical matrix negative for SARS-CoV-2. The acceptable range of transport media volume should be noted in your instructions for use and interference performance should be validated by testing in the minimum recommended volume. We recommend testing replicates of three n-swab pooling samples at the same analyte concentration both with and without clinical matrix. Each n-swab pooling sample should contain maximum number of swabs you recommend pooling in your instructions for use.***

***For example, if you recommend pooling three swabs (n = 3) then we recommend acquiring a total of nine confirmed negative swabs from individual subjects and adding three unique swabs to three unique tubes of transport media thereby making three n-swab pooling samples. Each n-swab pooling sample should be spiked with either positive patient sample (in transport media), live virus, or inactivated virus at a concentration of 2-3X the LoD of your assay. We recommend testing a total of at least 20 replicates which can be composed of equal numbers of aliquots taken from each n-swab pooling sample (i.e., 7 replicates from each sample in this example). Ideally, negative n- swab sample matrix should be tested prior to spiking to ensure that the matrix is negative. Acceptance criteria should be at least 95% agreement with the expected results and an invalid rate of &lt; 5%. We recommend providing the Ct value line data (if applicable) for analysis.***

1.  ***We recommend evaluating the effect of high viral concentrations on assay performance. It appears that patients with SARS-CoV-2 infection can exhibit unusually high viral loads. This, combined with the possibility of pooling multiple positive swabs into a single volume of transport media, could result in unexpectedly high viral titer in the pooled sample. We recommend evaluating existing data on viral loads in infected subjects and, in combination with your existing LoD data, propose a maximum expected viral titer per swab. Using this number, estimate the expected viral titer in transport media with at least three positive swabs. For instance, if you expect a maximum of 100,000X LoD per swab we recommend spiking a single negative n-swab sample with 300,000X LoD target analyte and testing with 10 replicates. It is anticipated that all replicates are either positive or have an invalid rate of ≤5%.***

#### Studies to Support Point of Care Indication

***If your device is intended for near patient or Point of Care (POC) testing, please provide data to demonstrate that non-laboratory personnel can perform the test accurately in the intended use environment*** ***(i.e. a non-laboratorian healthcare provider accuracy study).*** ***Please also provide data to demonstrate the robustness of your device for near patient testing (e.g., as applicable, studies to demonstrate the impact of adding different volumes of sample, different volumes of reagents, incorrect order of sample or reagent application, etc.). For assays intended for use with a test system that was previously CLIA waived by the FDA, testing is generally only needed to establish the performance of the SARS-CoV-2 assay chemistry. In general, additional test data is not needed to demonstrate that the system is simple enough for use at the point-of-care, unless there is a feature of the SARS-CoV-2 assay that would make performing the test more complicated than assays previously cleared for use on the test system.***

##### Clinical Evaluation 

***The clinical study design should mimic how the test will be used in clinical practice.*** ***It is expected that a test with “POC” designation will be widely used in CLIA waived medical facilities (e.g., physician office, outpatient clinic, ER), but also in less traditional settings, such as tents, schools, etc. with health care worker oversight of testing. This clinical study design does not apply to testing sites where NO HCWs are present.***

1.  ***Sites and Test Users (Operators):***

***You should select one or two non-laboratory sites in the United States (U.S.) to assure that the operators are representative of operators in the U.S., e.g., doctor’s office, ER, outpatient clinic, drive-through testing facility, or another area in a medical facility outside the central laboratory where samples are collected and tested in real time. This would allow evaluation of the sample collection and handling, including addition into the sample port/well of the test, both of which may be significant sources of error. Four to six operators, representing healthcare professionals, but who are not laboratory trained (e.g., nurses, nursing assistants and doctors) should participate in the study. Testing should be performed using only Quick Reference Instructions (QRI); supplemental materials, such as a video or an app that can be easily accessed by the user, are encouraged but should not be used during the study (mimicking worst case scenario).***

1.  ***Comparator Method:***

***All patients tested during the clinical study with the POC device should also be tested by an FDA authorized SARS-CoV-2 molecular assay. The comparator method selected should be one of the more sensitive EUAs on the FDA website (supported by peer reviewed literature, comparative studies testing the FDA reference material, etc.) that uses a chemical lysis step followed by solid phase extraction of nucleic acid. Ideally the same comparator would be used for all samples. The comparator should be authorized for use with the specimen type and transport medium (if applicable) that is being tested. Typically, the standard of care specimen is collected first, so as not to compromise the medical care of the patient. After the standard of care specimen has been collected, swabs taken from the same area for the comparator and subject device (e.g., nasal swabs, OP swabs, etc.) should be randomized to ensure that bias is not introduced due to an unequal distribution of viral materials. Randomizing collection when two distinct anatomical sites are being assessed may not be needed (e.g., saliva compared to NP swabs).***

1.  ***Clinical Samples***

***A total of 30 prospectively collected positive (confirmed by an authorized test) and 30 negative natural clinical specimens should be tested (mock clinical samples are not acceptable). Testing should be conducted for at least 2 weeks. If an insufficient number of positive results is observed after such time (&lt;30), you may collect samples at another site to ship to the testing site or use banked specimens to supplement your positive specimens. Banked specimens should not be pre-selected based on Ct value and should be presented blinded (mixed with negatives) to the testing site. Ideally, the same comparator method should be used for banked and prospectively collected specimens.***

***A molecular POC test should demonstrate positive and negative agreement of ≥ 95%. However positive agreement of ≥ 80% may be considered with appropriate limitations added to the intended use that would mitigate the risk of false negative results.*** ***For example, negative results may be considered presumptive negative if the demonstrated PPA is lower than 95%.***

1.  ***Notification of public health authorities***

***When setting up the study, you should have a clear strategy for reporting test results to the CDC and/or local public health authorities both during the study and after authorization.***

##### Post Market Clinical Study

***If prospective clinical study results are not available at the time of the test authorization, manufacturers of new POC tests should conduct a post-market prospective clinical study to collect at least 30 positive and 30 negative natural clinical specimens to demonstrate the assay performance relative to an FDA-authorized comparator method. You should propose a post-market study design in your EUA submission for FDA review and feedback. Generally, a final study design will be agreed upon before authorization and will be a condition of authorization.***

##### Performance around LoD

***You should conduct testing with samples prepared in clinical matrix with SARS-CoV-2 viral load near the LoD of your assay. The testing should be performed by inexperienced users at the clinical sites. The test samples should consist of 10 low positives (&lt;2x LoD) and 10 negatives (matrix) per site. The blinded and randomized samples should be distributed among the operators; we recommend that each operator tests at least 3 low positive and 3 negative samples integrated into the site’s workflow with the clinical samples above.***

##### Flex Studies

***Flex studies assess the robustness of an assay performed with the device in its final design/format and should be performed in-house by staff who have been trained in the use of the test. The flex studies should evaluate the most common or likely sources of error based on the use locations and test procedure. Flex studies should be conducted by testing negative sample and a low positive (at 1.5x - 2x LoD) samples, under each condition being evaluated. In general, the flex studies should be conducted to the point of failure to determine the maximum deviation that will still generate accurate results. We recommend testing 3 replicates per condition per sample concentration. Line data for each condition evaluated should be provided. If erroneous results are observed during studies evaluating the robustness of the device, adequate mitigation(s) should be provided.***

***Each study should be performed using a pre-defined study protocol that includes the following:***

1.  ***The objective of the study***

2.  ***Detailed test procedure***

3.  ***Materials used***

***Examples of conditions that may be evaluated as potential user errors and anticipated environmental stresses (temperature and humidity extremes) are shown below:***

-   ***40°C and 95% RH (mimicking hot and humid climates) applicable to small portable devices that could be used outdoors (tents, mobile vans, etc.)***

-   ***Delay in sample testing***

-   ***Delay in operational steps***

-   ***Delay in reading results***

-   ***Sample volume variability***

-   ***Buffer volume variability***

-   ***Environmental stability of electronics (temperature and humidity, in combination)***

-   ***Vibrations***

-   ***Disturbance during analysis***

-   ***Placement on non-level surface***

-   ***If hand-held, positioning at 90° angle***

-   ***Sensitivity to power failures (e.g., surge protection, battery power failure)***

-   ***Error reporting and device failure handling instructions***

-   ***Electrical interference testing (e.g., validation of system functions in the presence of potential EM interference sources including cell phones, Bluetooth, Wi-Fi radios, medical equipment expected in the intended environment, etc.)***

***Please see Appendix A for more in-depth Flex Study designs. Alternative sources of information on Flex Studies that may be applicable to your device can be found on the FDA CDRH website containing CLIA Waiver by Application Decision Summaries (https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries).***

#### Multi-analyte Respiratory Panels Under EUA:

An emergency declaration by the HHS Secretary allowing for the issuance of EUAs is typically specific for a pathogen/ disease (i.e., there is a publicly declared health emergency involving a particular etiologic agent). Therefore, for tests, the EUA pathway is generally only an option for testing patients for that single agent in a given emergency. Given the overlap in signs and symptoms between SARS-CoV-2 and other respiratory viral infections, including influenza, FDA has authorized multi-analyte respiratory panels for the qualitative detection and differentiation of nucleic acid from multiple pathogens, including the SARS-CoV-2 virus. These panels are useful to efficiently detect and differentiate between multiple pathogens that are relevant to the event/disease outbreak that is the subject of the specific emergency declaration. They may also be useful in preserving critical testing resources during the public health emergency by reducing the number of tests, and therefore supplies, needed per patient.

When determining whether to issue an EUA for a multi-analyte respiratory panel FDA takes into consideration the use of the test (multi-analyte pathogen detection as an aid in differential diagnosis), clearance/approval status of IVDs for the other panel members, whether the proposed Intended Use fits within the HHS emergency declaration and how the panel test would fit into current public health authority patient testing algorithm recommendations. If you are requesting an EUA for a multi-analyte respiratory panel, analytical and clinical evaluations for each target analyte should be provided. We recommend you contact FDA at <CDRH-EUA-Templates@fda.hhs.gov> for specific feedback on this type of EUA request.

1.  ***Addition of SARS-CoV-2 to previously FDA-cleared Multi-Analyte Respiratory Panels***

***To add the SARS-CoV-2 target to respiratory panels previously cleared by the FDA where the SARS-CoV2 reagents are run in a separate well (or tube) and no modifications are required to the cleared portion of the assay, only studies for validation of the SARS-CoV-2 reagents described in this template are recommended.***

***To add the SARS-CoV-2 target to respiratory panels previously cleared by the FDA where the SARS-CoV-2 reagents are combined in the same well as the reagents for previously cleared analytes (in a multiplex reaction), the following studies should be conducted to validate the SARS-CoV-2 reagents and the modifications made to the cleared respiratory panel:***

-   ***Studies described in this template to validate the SARS-CoV-2 reagents***

-   ***LoD confirmation of the previously cleared analytes by conducting side by side testing of 3-5 replicates of serially diluted viruses with modified and original versions of the test to show that the LoD is unchanged due to modifications***

-   ***Testing 10 retrospective positive samples for each previously cleared analyte***

-   ***Competitive inhibition study with clinically relevant titers of each analyte in the panel (viruses 10^5^ PFU/mL, bacteria 10^6^ CFU/mL)***

1.  ***Multi-analyte Panels not Previously Cleared by the FDA***

***To support an EUA for a multi-analyte respiratory panel that was not previously cleared by FDA, analytical and clinical evaluations for each target analyte should be provided. The following analytical studies should be conducted and data provided to the FDA for review:***

-   ***Limit of Detection (Analytical Sensitivity)***

-   ***Cross-Reactivity / Microbial Interference ***

-   ***Inclusivity / Analytical Reactivity   ***

-   ***Collection Media Equivalency - each claimed additional sample collection media not used in your clinical study should be validated (if appropriate for study designs) ***

-   ***Co-infection (Competitive Interference) ***

-   ***Interfering Substances Study (Endogenous and Exogenous) ***

-   ***Clinical Specimen Stability ***

-   ***Reagent Stability testing protocol  ***

-   ***Carry over/Cross-Contamination (if a new instrument previously not reviewed by the FDA is used) ***

-   ***Reproducibility and Repeatability (if a new instrument previously not reviewed by the FDA is used) ***

    -   ***Fresh vs. Frozen If you intend submit data testing archived frozen specimens in support of your EUA, please conduct an analytical study to demonstrate that preservation of samples (e.g., by freezing at ≤-70°C) does not affect the accuracy of test results compared to freshly collected samples.***

***Clinical Performance***

***To evaluate the clinical performance of your multi-analyte test, a prospective clinical study should be conducted. Considering the public health needs in the current emergency, a clinical performance study in support of the EUA application may be conducted at one site testing archived positive and negative clinical samples with known specimen types. The pre-selection of archived positive samples should represent a range of viral load or Ct values including low positive samples near the assay cut-off.***

***Since your device has not been FDA-cleared for the respiratory pathogens included in your test, and it is likely that your test would be used in patients with respiratory symptoms in lieu of an FDA-cleared respiratory panel, FDA generally intends to include a condition of authorization that you conduct a post EUA prospective clinical study. The prospective clinical study should include a minimum of three sample collection sites and three testing sites, prospectively enrolling patients with general respiratory symptoms. You may consider conducting a prospective clinical study in Southern Hemisphere countries during their typical influenza/respiratory season to increase the likelihood of obtaining a sufficient number of positive samples (e.g., for influenza at least 50 positive Flu A and 30 positive Flu B samples) in a timely fashion.***

***The FDA performance expectation for SARS-CoV-2 is that PPA and NPA should be &gt;95% (with a lower bound of the two-sided 95% confidence interval &gt;85%); for Flu A/B, and other respiratory viruses,*** ***PPA should be &gt;90% (with a lower bound of the two-sided 95% confidence interval &gt;80%), and the NPA should be &gt;95% (with a lower bound of the two-sided 95% CI &gt;90%) in comparison to an EUA RT-PCR test. We recommend using only a high sensitivity EUA RT-PCR assay which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction).***

***We recommend that you submit a Pre-EUA with an outline of the studies that you plan to conduct to support the FDA-authorization or contact FDA at <CDRH-EUA-Templates@fda.hhs.gov> for specific feedback.***

**Claiming Multiple Instruments and/or Extraction Methods:**

***FDA recommends the following analytical and clinical validation for use of multiple instruments and/or extraction methods where the elution volumes from the extraction methods and PCR volumes on the different RT-PCR instruments are identical.***

-   ***Limit of Detection (LoD): These studies should be repeated for each clinical matrix claimed in the Intended Use. Pick one RT-PCR instrument and determine the tentative LoD (using 5 replicates in 10-fold dilution) followed by the confirmatory LoD (20 replicates spiked at tentative LoD) for each extraction method on the chosen instrument. Note: If you detect 20/20 replicates in your confirmatory LOD study you should test the next lower concentration, using a 3-fold dilution, until you achieve a hit rate of &lt;20/20.***

-   ***If the different extraction methods yield the same LoD (≤3xLOD) on the RT-PCR instrument chosen for initial testing, pick one extraction method for further LoD determination on the remaining RT-PCR instruments and follow the recommendations below.***

-   ***If the extraction methods do not yield the same LoD on the chosen RT-PCR instrument, please choose the extraction method with the worst LoD for further comparison of the LoD on all RT-PCR instruments.***

***For all other RT-PCR instruments you should use the following adaptive LoD study design:***

-   ***Please perform a refined tentative LoD study with 5 replicates at 0.5x, 1x, and 1.5 to 2x LoD. If you detect 4/5 replicates as positive at all the tested levels, you need to include the next higher concentration (i.e., 3x LoD). If you obtain 5/5 replicates at 0.5x LoD, you need to test the next lower concentration (i.e., 0.25x LoD). You will test in this manner until you find the lowest concentration that gives you 5/5 positive results for the tested RT-PCR instrument. This concentration should be used for a confirmatory LoD study for the given RT-PCR instrument using 20 replicates.***

***Final reported LoD: Please list all RT-PCR instruments with their respective LoDs if different LoDs are obtained. LoDs are considered comparable if they are between 1-3xLoD. These studies should be repeated for each clinical matrix claimed in the Intended Use.***

-   ***Interference Substances Studies (if applicable): FDA recommends evaluating interfering substances with the extraction method and RT-PCR instrument combination that has the worst overall LoD.***

-   ***Inclusivity Testing: FDA recommends evaluating inclusivity with the extraction method and RT-PCR instrument combination that has the worst overall LoD.***

-   ***Exclusivity Testing: FDA recommends evaluating exclusivity with any extraction/instrument combination.***

-   ***Clinical study: If an LoD study confirms equivalency for all RT-PCR instruments (between 2-3xLoD), then the clinical study may be conducted with any RT-PCR instrument. If one or more RT-PCR instruments have different LoDs, we recommend conducting the clinical study with the extraction method / RT-PCR instrument combination with the worst LoD.***

***Note, if there are differences in the extraction input volume, extraction elution volume and PCR input volume (extracted nucleic acid) then the LoD should be confirmed for each.***

**K. UNMET NEED ADDRESSED BY THE PRODUCT**

**This section will be completed by FDA.**

**L. APPROVED/CLEARED ALTERNATIVE PRODUCTS**

Currently no methods for the detection of the SARS-CoV-2 have been approved/ cleared by FDA.

**M. BENEFITS AND RISKS:**

**This section will be completed by FDA.**

**N. FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:**

**Include proposed Fact Sheets for Patients and Healthcare Providers *- see examples for authorized EUA tests on our website and templates will be made available.***

**O. INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:**

**Include Instructions for Use, Box Labels, Vial Labels and any other proposed labeling.**

**P. RECORD KEEPING AND REPORTING INFORMATION TO FDA:**

\[***Manufacturer name***\] will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report on adverse events, and this website is referenced in the Fact Sheet for Health Care providers as well as through the \[***Manufacturer name***\] Product Support website: \[***Include link to Website***\]. Each report of an adverse event will be processed according to \[***Manufacturer name******\]***’s Non-Conformance Reporting Requirements, and Medical Device Reports will be filed with the FDA as required. Through a process of inventory control, \[***Manufacturer name******\]*** will also maintain records of device usage/purchase. \[***Manufacturer name******\]*** will collect information on the performance of the test, and report to FDA any suspected occurrence of false positive or false negative results of which \[***Manufacturer name******\]*** becomes aware. \[***Manufacturer name******\]*** will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

### Appendix A: Flex Study Design Details. Perform as applicable for the device.

If incorrect results are observed under the test conditions, the sponsor should implement adequate mitigations to prevent reporting of erroneous results.

1.  **Reading Time:**

**Recommend evaluating test results at reading times four times below and three times above the recommended reading time. For example, for a test where the recommended read time is 20 minutes, reading time times would be performed to evaluate at least read times of 5, 10, 15, 20, 30, and 60 minutes.**

2.  **Specimen Volume:**

**Recommend evaluating test results at specimen volumes two times below and two times above the recommended specimen volume, and the maximum possible added. For example, for a test where the recommended specimen volume is 10 µL, specimen volume testing should be performed to evaluate at least specimen volumes of 5, 10, 20 µL and maximum volume. If incorrect results are observed at either 5 or 20 µL, additional testing at 7.5 and/or 15 uL may be needed. The diluent/buffer amount added should be that specified in the instructions for use.**

3.  **Sample Diluent Volume:**

**Recommend evaluating test results at diluent/buffer volumes at two times below and two times above the recommended diluent/buffer volume and the maximum volume. For example, for a test where the recommended buffer/diluent volume is 2 drops, sample diluent volume testing would be performed to evaluate at least sample diluent volumes of 1, 2, 3, 4 drops and whole bottle. The sample volume added should be that specified in the instructions for use.**

4.  **Sample Elution:**

**Recommend evaluating how mixing the swab in elution buffer (or other reagent) affects results. You should evaluate all extremes from not-mixing to vigorous shaking, generating bubbles as well as intermediate mixing, i.e. swirling 1 or 2 times, instead of the prescribed number from the instructions.**

5.  **Temperature and Humidity:**

**Recommend evaluating test results at temperature and humidity extremes that are likely to occur in the United States. For example, 40°C and 95% RH, mimicking hot and humid climate, and 5°C and 5% RH mimicking cold and dry climates.**

6.  **Light:**

**Recommend evaluating of test results in different lighting conditions that would be expected during use of the device, for visually read devices. For example, fluorescent, incandescent, and natural lighting mimicking the outside environment.**

7.  **Disturbance during analysis:**

**You should evaluate the effect on expected test results of moving the device while the test is running. This could include; dropping the test while it is being run, moving the test to another surface, unplugging the test, receiving a phone call while the mobile app is running, etc.**

8.  **Device Orientation:**

**Recommend evaluating unique device characteristics, as determined by a robust risk analysis. For example, if the device is intended to be run upright, evaluating test results if the device is used horizontally, or vice versa.**

[1] This template is part of the [Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) - Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised)

[2] <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>

[3] https://www.fda.gov/media/97321/download


# 9,546  2020-07-29_FDA Template - For Manufacturers of Molecular and Antigen Diagnostic COVID-19 Tests for Non-Laboratory Use.md
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last updated: 2026-03-04 by BA
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title: FDA Template - For Manufacturers of Molecular and Antigen Diagnostic COVID-19 Tests for Non-Laboratory Use
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summary_short: The FDA Template for Manufacturers of Molecular and Antigen Diagnostic COVID-19 Tests for Non-Laboratory Use outlines recommended data, validation studies, and submission structure for pre-EUA and EUA requests covering home and other non-laboratory testing settings. It emphasizes analytical performance, usability, flex studies, clinical evaluation in symptomatic and asymptomatic users, and result reporting to public health authorities. The template guides manufacturers in designing and documenting tests intended for lay users while addressing the higher risk of user error outside traditional laboratories.


CONTENT

***INTERNAL TITLE:*** Template for Manufacturers of Molecular and Antigen Diagnostic COVID-19 Tests for Non-Laboratory Use

This template (the “template”) provides FDA’s current recommendations concerning what data and information should be submitted to FDA in support of a pre-EUA/EUA submission for a molecular or antigen diagnostic test for SARS-CoV-2 for use in a non-laboratory setting. Such settings are likely to include a person’s home or certain non-traditional sites such as offices, sporting events, airports, schools etc. This template does not apply to home collection kits.

As outlined in Section V.A. and V.B. of the FDA guidance document [*Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised), [2] FDA recommends that the following validation studies be conducted for a SARS-CoV-2 molecular or antigen diagnostic assay: Limit of Detection, Clinical Evaluation, Inclusivity, Cross-reactivity, Usability and Flex Studies. This template is intended to help manufacturers provide these validation data and other information to FDA, but alternative approaches can be used. This template reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should* means that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA Guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/media/97321/download).[3]

## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by the test manufacturer (sponsor) as applicable to their specific test. Text in **bold** outlines the Food and Drug Administration’s (FDA) additional recommendations for the sponsors’ consideration when completing the suggested information in each section.

-   This template is intended for testing with respiratory specimens or saliva; if you are considering non-respiratory specimens (e.g., blood, stool, etc.), please contact FDA at CDRH-EUA-Templates (CDRH-EUA-Templates@fda.hhs.gov) to discuss your validation strategy.

-   This template applies to developers of molecular or antigen diagnostic tests, for use in non-laboratory settings (such as person’s home or certain non-traditional sites such as offices, sporting events, airports, schools etc.), intended to detect SARS-CoV-2 from individuals.

-   A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   This is an EUA interactive review template for Pre-EUA/EUA submissions. We plan to update the template as appropriate as we learn more about the COVID-19 disease and gain experience with the EUA process for these kinds of tests.

## EXAMPLE TEMPLATE:
### A. PURPOSE FOR SUBMISSION

Emergency Use Authorization (EUA) request for distribution and/or use of the ***\[test name\]*** to ***\[indicate non-laboratory testing sites\]*** for the *in vitro* qualitative detection of ***\[RNA or antigen\]*** from the SARS-CoV-2 in ***\[add all claimed specimen types, e.g., nasal swab or saliva\]***. This test is for ***\[prescription use at home and other non-laboratory sites and/or OTC use at home and other non-laboratory sites\]***. All test results will be reported to healthcare providers and relevant public health authorities in accordance with local, state, and federal requirements, using appropriate LOINC and SNOMED codes, as defined by the [Laboratory In Vitro Diagnostics (LIVD) Test Code Mapping for SARS-CoV-2 Tests](https://www.cdc.gov/csels/dls/sars-cov-2-livd-codes.html) provided by CDC. 

### B. MEASURAND

Specific nucleic acid sequences from the genome of the SARS-CoV-2 **\[*please specify the targeted gene(s) of the pathogen*\]**.

***OR***

Specific antigen(s) from the SARS-CoV-2 **\[*please specify the targeted antigen(s)*\]**.

### C. APPLICANT

***\[Official name, address and contact information of applicant\]***

### D. PROPRIETARY AND ESTABLISHED NAMES

Proprietary Name - ***\[test name\]***

Established Name - ***\[test name\]***

### E. REGULATORY INFORMATION

***Approval/Clearance Status:***

The ***\[test name\]*** test is not cleared, CLIA waived, approved, or subject to an approved investigational device exemption.

***Product Code:***

QJR-molecular diagnostic for SARS-CoV-2

**OR**

QKP-antigen diagnostic for SARS-CoV-2

### F. PROPOSED INTENDED USE

#### 1) Intended Use for Molecular Assays:

**The proposed Intended Use will be finalized based on the available information including data and recommendations from public health authorities at the time of authorization – example text is provided below for a home use qualitative molecular test that detects organism RNA in adults and children 2 years and older, but may be adapted according to the specific emergency situation addressed by the device*. ***

\[***Test name***\] is a \[***specify test technology such as, real-time RT-PCR test******, lateral flow immunoassay***\] intended to detect \[***RNA, \[protein name\] antigen***\] from the SARS-CoV-2 virus that causes COVID-19 in \[***describe all the specimen types, e.g.,* nasal swab, saliva**\] from ***\[individuals age 2 years and older\]*** or ***\[for prescription use only tests, describe the patient population requested, such as symptomatic individuals who are suspected of COVID-19 by a healthcare provider, or individuals with or without symptoms or other epidemiological reasons to suspect COVID-19 infection\]***.

Persons who test positive with the ***\[Test name\]*** should seek follow up care with their physician or healthcare provider as additional testing and public health reporting may be necessary. Positive results do not rule out bacterial infection or co-infection with other viruses. Persons who test negative and continue to experience COVID-19 like symptoms of fever, cough and/or shortness of breath may still have SARS-CoV-2 infection and should seek follow up care with their physician or healthcare provider.

All test results will be reported to healthcare providers and relevant public health authorities in accordance with local, state, and federal requirements, using appropriate LOINC and SNOMED codes, as defined by the [Laboratory In Vitro Diagnostics (LIVD) Test Code Mapping for SARS-CoV-2 Tests](https://www.cdc.gov/csels/dls/sars-cov-2-livd-codes.html) provided by CDC. 

The ***\[test name\]*** is intended for self-use ***\[and/or, as applicable for a lay user testing another person\]***  in a non-laboratory setting ***\[and, as applicable for healthcare provider testing of another person in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C 263a to perform moderate or high complexity tests and as applicable, Point of Care (POC) testing at patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation\].*** The ***\[test name\]*** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

#### 2) Special Conditions for Use Statements:

For Emergency Use Authorization (EUA) only

*\[**For prescription use only or For prescription use and over-the-counter use.**\]*

For in vitro diagnostic use only

#### 3) Special Instrument Requirements:

The ***\[test name\]*** test is to be used with the \[***list all instruments, smart phones, operating systems, camera and software requirements***\].

### G. DEVICE DESCRIPTION AND TEST PRINCIPLE

**We recommend providing a Device Description and Test Principle consistent with the recommendations in the Antigen Template for Manufacturers or Molecular Diagnostic Template for Manufacturers, as applicable. Please note that for new technologies, FDA is more likely to request additional detailed information so we can adequately assess the risks and benefits associated with the device.**

**Because of the greater potential for error in specimen collection at home, FDA recommends that the assay, which per the intended use allows specimens to be collected outside of a healthcare facility, have an internal control to indicate that adequate human sample was collected and placed into the test for analysis. If your assay does not have such a control you should address this risk using another mitigation, such as video observation of user by a trained professional or a design feature of the collection device.**

#### 1.  Product Overview/Test Principle:

**Describe the technology of the test and how this technology works to identify the measurand, the instruments employed/required to perform the test from sample collection to result (include all instruments, software, mobile app, etc.), and the specimen types for which you claim to have specific performance characteristics as described below**. **If applicable, list all primer and probe sets and briefly describe what they detect. Please include the nucleic acid sequences for all primers and probes used in the test. Please indicate if the test uses biotin-Streptavidin/avidin chemistry in any of the steps for coupling reagents.**

#### 2.  Description of Test Steps:

**List and describe in detail all the steps of the test sequentially from specimen collection to detection.** **Please note that FDA generally does not consider self-collection of nasopharyngeal, and oropharyngeal swabs by lay persons to be safe because such collection requires training to accurately collect the sample from the proper anatomical location. Moreover, incorrect technique can result in patient harm such as nose bleeds or esophageal spasms and choking. As such, we recommend that your test use either anterior nares (nasal) swabs, mid-turbinate swabs or saliva as sample types.**

#### 3.  Control Material(s) to be Used:

This section only applies to devices intended for high-volume use in non-laboratory settings. FDA believes that having control materials available for quality control and training is important in these non-laboratory settings and does not believe such materials will be necessary when these tests are intended only for use in an individual’s home or other non-laboratory low-volume settings.

**List all control materials (provided with the test kit and/or required but not provided with the test kit) and describe what they are, how they are expected to work, where in the testing process they are used, and the frequency of use. If a control is commercially available, provide supplier’s name and catalog number or other identifier.**

**Please note that any control recommended to be used with your device (provided with the kit or not) should be validated in the context of your analytical and clinical study (i.e., you should run these controls as part of your studies). In instances where control material is not readily available through 3^rd^ party vendors (which is often the case at the beginning of an outbreak), FDA may request that you include suitable control material with your device. Please note that external control materials are considered particularly important when GMP requirements are waived and reagent stability studies are limited.**

#### 4.  Quick Reference Instructions:

**You should develop a test procedure that will be easy to follow in the format of a Quick Reference Instructions (QRI). Because these tests are intended for use in non-laboratory settings and may be intended for parents to test children, we recommend you develop and test for usability and develop at least two sets of instructions: one for self-testing and one for a lay user testing another person (child and/or adult as appropriate per your IFU). User instructions should be oriented to users at no higher than a 7^th^ grade level. It is highly recommended that sponsors consider adding pictures and diagrams to facilitate performance of the test by a lay user and that the instructions be limited to 1-2 pages. Web or mobile application-based material such as videos may be particularly helpful**. **We recommend you perform Human Usability Studies on your device using the QRI before conducting your final clinical study as the final QRI should be evaluated in the clinical study. The QRI should be provided in both English and Spanish at a minimum.**

#### 5.  Test Result Reporting:

All test results will be reported to healthcare providers and relevant public health authorities in accordance with local, state, and federal requirements, using appropriate LOINC and SNOMED codes, as defined by the [Laboratory In Vitro Diagnostics (LIVD) Test Code Mapping for SARS-CoV-2 Tests](https://www.cdc.gov/csels/dls/sars-cov-2-livd-codes.html) provided by CDC. 

**You should describe how you will ensure all users of the test can report** **all test results to public health and/or other authorities to whom reporting is required, in accordance with local, state, and federal requirements. The approach adopted should facilitate reporting by all users and be easy to use and understand. There are several options to allow for reporting of test results including, but not limited to: *automatic reporting through mobile app, instructions directing users to a website where reporting is easily facilitated, etc.* FDA is open to alternative approaches to reporting that ensure appropriate reporting.**

**You should also describe how test reporting will capture the appropriate LOINC and SNOMED codes, in addition to location data, and other patient information that may be relevant or required.  **

#### 6.  Mobile Applications and Software

**Any smartphone application should be simple. Error messages should be readily understandable, and troubleshooting should be included in the device instruction. The display should promote understanding of results and what patients should do next, including how to care for themselves and when to seek follow up care.**

**Please list and describe any mobile applications, software or web applications used with the test. You should include the following information:**

**Verification & Validation:**

-   **To validate use of your App with a Smartphone, you should develop a set of minimum Smartphone specifications (e.g., memory, processor capability, minimum Operating System (OS) requirements, etc.). You should validate the software on models of Smartphones for each OS that meet those minimum hardware specifications.**

-   **You should summarize the verification and validation performed on your software/app.**

-   **Full functionality for the application should be demonstrated for the full range of platforms intended for use (e.g., if a web application, then demonstrating on popular modern browsers such as Chrome, FireFox, Microsoft Edge; if a mobile application, then demonstrating on popular modern smartphones and other mobile devices such as Android, and iOS based devices, etc.).**

-   **You should address the cybersecurity of your device and any private health information that may be contained on your device or in a mobile app or web application.**

-   **You should have a software update plan that covers mobile app updates, algorithm updates and web application updates that may impact the performance of the device**

-   **The application should automatically report all test results when appropriate in accordance with local, state, and federal requirements.**

### H. INTERPRETATION OF RESULTS

**Results that are displayed to the user should be simple and easy to interpret (e.g., positive, negative, and invalid).**

**Please describe the testing algorithm/calculation that is used by the device to return the simple qualitative result, for example a ratio value, fluorescence reading, cycle threshold and cut-off, etc. Please also provide any text for users that will accompany test results.**

**Please clearly indicate how invalid results will be displayed to the user and how the user will resolve invalid results, e.g. if repeat testing may be required, call hotline for replacement, etc.**

**You should also describe how results will be reported in accordance with local, state, and federal requirements. Please note whether identified information will be sent to local public health authorities and/or if de-identified information will be sent to CDC. If the test produces results that will be used as part of a CDC recommended testing algorithm, please indicate what follow-up testing/process should be conducted, if applicable.**

**Additional information about negative results should also be provided that instruct the user to seek follow up care from a healthcare physician if their symptoms persist or if they are concerned about their health.**

### I. PRODUCT MANUFACTURING

#### 1.  *Overview of Manufacturing and Distribution:*

The product will be manufactured at \[***manufacturer’s name and FDA registration number (if applicable)***\] by \[***manufacturer name***\] personnel consistent with practices for the production of **\[*types of devices*\]** based on \[***type of quality system\****\]**.** Material manufactured by \[***manufacturer’s name***\] may be bottled and kitted by \[***packager name***\] manufacturing facility.

The current manufacturing capabilities include the ability to manufacture approximately **\[*please insert the approximate number of units/products that can currently be manufactured per week at the manufacturing facility*\]** products per week, however in the event of a surge in demand this could be increased to **\[*please insert the approximate maximum number of units/products that could potentially be manufactured per week at the manufacturing facility if there was a surge in demand*\]** product per week within a **\[*please specify in weeks/months the expected timeframe required to increase product production if required*\]** timeframe.

The product will be distributed by **\[*please describe the distribution plan for the product and list all current distributors*\]**.

**\*Under the Emergency Use Authorization (EUA) any of the 21 CFR Part 820 Quality System Regulation (QSR) requirements can be waived for the duration of the EUA but FDA recommends that developers follow comparable practices as much as possible if such requirements are waived. Among other things, FDA may consider previous compliance history when determining whether or not to waive certain QSR requirements for a specific product. Please note adverse events, as per 21 CFR Part 803, have to be reported for authorized devices (see Section P).**

#### 2.  *Components Included with the Test*

Components manufactured by \[***manufacturer’s name and FDA registration number (if applicable)***\] and supplied with the test include:

**List all components and reagents for your test, including a description of the primers and probes, volumes, concentrations, quantities, buffer components, etc.**

**If you plan to use non-traditional sources of swabs or media, please describe your qualification testing and validation procedures.  Collection media and other test components that contains hazardous or irritating materials (such as guanidinium salts) should not be used for home (or other non-laboratory) testing unless the collection device has specific safety features to reduce the risk of patient exposure. FDA will conduct a safety review of all test components.    **

#### 3.  *Testing Capabilities*

**Briefly describe current sample throughput capacity, total time required to perform the test (from clinical specimen collection, to result), and, if applicable, number of tests that can be performed per instrument run and per day.**

#### 4.  EMC (electrical and mechanical safety) Testing:

**We recommend that EMC testing be conducted on any device that uses a battery or power source. Please provide FDA with any standards that were followed for EMC testing.**

#### 5.  Reagent Stability:

**Briefly describe stability test plan for reagents and include accelerated stability information, if available. Based on FDA’s experience thus far, FDA believes that reagent stability studies generally would not need to be completed at the time of EUA issuance, however, the study design generally will be agreed upon during interactive review and the stability studies started immediately following authorization, if not before. You should consider the following recommendations when designing your stability study:**

-   **You could follow the current FDA recognized CLSI Standard EP25 – Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline when evaluating the suitability of stability study designs. If you are planning to pursue a De Novo/510(k) for your device we recommend discussing in more detail your stability design to facilitate potential use of the EUA data in your premarket submission.**

-   **We recommend testing a known positive diluted patient sample at 3-5x LoD rather than positive control material to establish reagent stability. Use of DNA material is unlikely to be appropriate.**

-   **If you are claiming multiple clinical specimen types in which similar LoDs are determined, you should use the most challenging clinical matrix for this study.**

-   **We typically recommend your stability study design includes the evaluation of at least 5 replicates. You should also evaluate, if available, 3 different lots of reagents.**

-   **You should design your study to provide data for a timeframe that is about 10% longer than the one to be claimed – for example, a claim of 18 months should be supported by stability data out to 20 months and a claim of 7 days should include stability data out to 8 days.**

-   **FDA considers 15-30°C to represent room temperature conditions. Ideally you should evaluate stability at both 15°C and 30°C, however, for the purposes of the EUA evaluation 30°C is acceptable as the worse-case scenario.**

-   **Shelf-Life Stability - Unopened kit:**

    -   **You should evaluate real-time kit stability studies with unopened kits stored at the claimed storage temperature for your test.**

    -   **Accelerated stability evaluations for unopened kits is acceptable for EUA submissions while the real-time studies are on-going. However, please note real-time stability data is generally needed to support regular pre-market submissions.**

-   **Shipping Stability - Unopened kit: You should evaluate the anticipated handling and shipping times and temperatures expected for unopened kits.**

-   **In-use/Opened Kit Stability: Depending on your device, your stability study design should also support in-use stability of the kit reagents once the kit has been opened, e.g., storage at 2-8 ^o^C for 7 days.**

-   **Inverted stability (if applicable): Study should support stability for kits if stored inverted or in the wrong orientation.**

-   **FDA recommendations for analysis of real time stability studies are as follows:**

    -   **Baseline of the study (t=0 of stability study) should not exceed a month from bottling**

    -   **Clear baselines should be described (e.g., a month from bottling) for each stability claim under each study**

    -   **Claims should be determined based on regression analysis. Any %change (%shift) from time zero (baseline) should be calculated between the target claim and the zero-time as (Ttest-Tbaseline)/ Tbaseline\*100 with 95%CI using the regression equation obtained from plotting the mean values. When formulating your acceptance criteria for evaluating the shift from baseline you should consider the reproducibility of your device. However, generally, the shift at the target claim due to storage should not exceed 10-15%. The target stability is the next to last tested point that was within +/- 10% of time zero.**

    -   **Acceptance criterion may be different, depending on the intended use population and the risk of false results to public health.**

### J. PERFORMANCE EVALUATION

**We recommend including the studies listed below (as applicable) in your EUA request. Please note that, particularly for new technologies, FDA may request additional studies so we can adequately assess the risks and benefits associated with the device:**

#### 1.  Limit of Detection (LoD) - Analytical Sensitivity

**Please provide information consistent with the recommendations in the Antigen Template for Manufacturers or Molecular Diagnostic Template for Manufacturers.**

#### 2.  Inclusivity (analytical sensitivity)

**Please provide information consistent with the recommendations in the Antigen Template for Manufacturers or Molecular Diagnostic Template for Manufacturers.**

#### 3.  Cross-reactivity (Analytical Specificity)

**Please provide information consistent with the recommendations in the Antigen Template for Manufacturers or Molecular Diagnostic Template for Manufacturers. For all tests intended for use in a non-laboratory setting (e.g., a complete home test), FDA recommends wet testing of Cross-reactivity and Microbial Interference in addition to in silico analysis.**

a.  Cross-reactivity (organisms tested in the absence of SARS-CoV-2)

b.  Microbial Interference Studies (organisms tested in the presence of SARS-CoV-2)

c.  Endogenous Interference Substances Studies (including common household items such as cleaners, lotions, soap etc.)

#### 4.  High-dose Hook Effect Study for antigen tests

**Please provide information consistent with the recommendations in the Antigen Template for Manufacturers.**

#### 5.  Biotin interference, if applicable

**Please provide information consistent with the recommendations in the Antigen Template for Manufacturers.**

#### 6.  Flex Studies

**Flex studies assess the robustness of an assay performed with the device in its final design/format and should be performed in-house by staff who have been trained in the use of the test. The flex studies should evaluate the most common or likely sources of error based on the use locations and test procedure. Flex studies should be conducted by testing a negative sample and a low positive sample (at 1.5x - 2x LoD) for each condition being evaluated. In general, the flex studies should be conducted to the point of failure to determine the maximum deviation that will allow for generating accurate results. We recommend 3 replicates per condition per sample concentration. Data for each condition evaluated (i.e., line data) should be provided. If erroneous results are observed during studies evaluating the robustness of the device, adequate mitigation(s) should be provided. Each study should be performed using a pre-defined study protocol that includes the following:**

i.  **The objective of the study**

ii.  **Detailed test procedure**

iii.  **Materials used**

**An example of some conditions that may be evaluated as potential user errors and anticipated environmental stresses (temperature and humidity extremes) are shown below:**

iv.  **40°C and 95% RH (mimicking hot and humid climates)**

v.  **Delay in sample testing**

vi.  **Delay in operational steps**

vii.  **Delay in reading results**

viii.  **Sample volume variability (if applicable)**

ix.  **Buffer volume variability (if applicable)**

x.  **Mixing/swab expression variability (if applicable)**

xi.  **Disturbance during analysis**

xii.  **Placement on non-level surface**

xiii. **Impact of different light sources (if applicable)**

xiv. **If hand-held, positioning at 90° angle (simulating placing device in pocket or lifting to see result display screen)**

**Please see Appendix A for more in depth study designs for Flex Studies. Alternative sources of information that may be applicable to your device can be found on the FDA CDRH website containing CLIA Waiver by Application Decision Summaries (https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries).**

#### 7.  Human Usability Study

-   **Testing should include a minimum of 100 participants for non-prescription (OTC) tests and 30 participants for prescription only tests, and take place in an actual use environment or simulated environment. For OTC tests for use at non-laboratory sites, we recommend you split the usability study into two sections: 50 participants testing themselves and 50 participants testing another person (child or adult, depending on your intended use population). For prescription only tests for use on children, you should have 15 of the 30 usability participants be parents or legal guardians performing the test on their children.**

-   **The entire workflow should be performed by each individual participant using the kit, including kit registration, sample collection, testing, and results interpretation (if possible: we recommend users see a mock result to interpret).**

-   **You should collect data for your assay on any controls that are run during the test to assess sample adequacy. The data from this Usability Study should support that patients can effectively collect an adequate sample and run the assay without introducing contaminants or inhibitors.**

-   **The participants should be observed (either in person or by remote visual monitoring, such as a video conference) during sample collection and all difficulties should be noted.**

-   **After the entire process is completed the user should be given the questionnaire to indicate the ease of use of sample collection, test procedure and results interpretation as well as understanding the consequences if steps are not performed correctly. The participant should be able to provide comments if needed.**

-   **Participants should represent varying education levels and ages. A portion of your users should be Spanish speaking, and should be provided with instructions written in Spanish. A portion of your users should collect samples from themselves, while a subset should collect samples from others, including children. Participants with prior medical or laboratory training should be excluded. Participants who have prior experience with self-collection or self-testing (including glucose testing) should also be excluded.**

-   **The study should have pre-defined acceptance criteria and defined strategy to mitigate risk of errors identified in the study (e.g. modifying the instructions).**

**We encourage sponsors to submit their usability study protocols and questions for participants for FDA review prior to conducting the study. It may be possible to combine the Human Usability with the Clinical Evaluation; however, this study design does involve more risk as problems with the instructions for use could lead to a failed clinical study. FDA strongly recommends you discuss this option with FDA before design and execution.**

#### 8.  Clinical Evaluation:

**FDA recommends using natural clinical specimens for the clinical evaluation. You should conduct a clinical study to evaluate your device’s performance in symptomatic and asymptomatic individuals. This study design evaluates performance in asymptomatic individuals as well as symptomatic individuals. Since there is no mechanism to limit OTC testing to symptomatic individuals, FDA recommends this study design for all developers requesting an OTC claim. This study design is also recommended for developers requesting prescription use, unless the test is intended to be limited to symptomatic individuals.**

##### 1.  Testing Sites

-   **The sponsor should attempt to set up a minimum of 2 testing sites to encourage diverse enrollment or recruit for an at home clinical study through the internet. Conducting the study at home will generally be acceptable, but the following issues may arise and should be considered:**

    -   **Comparator samples should be collected at home using an FDA authorized home collection kit and SARS-COV-2 molecular assay.**

    -   **Recruitment by internet, especially if using monetary incentives, can drastically bias the population who enrolls in the study. We recommend that you consult FDA before starting a recruitment involving a monetary incentive.**

    -   **Possible injury during sample collection (applies to mid-turbinate swabs).**

    -   **Observed usability study recommended prior to at home clinical study to evaluate clarity and demonstrate robustness in using the instructions for use, etc.**

-   **Testing sites should be set up such that when a user is performing the test, they are unable to see/hear other patients performing the test (can be in separate rooms or areas partitioned with curtains)**

-   **The following testing situations are possible, all of which should have an observer present:**

    -   **Parent or legal guardian collects a sample from their child (e.g., age 3-13) and parent performs the test. The age of children that are tested by their parent or legal guardian should be consistent with the device’s intended use.**

    -   **Older child (e.g., age 14-17) self-collects sample and child performs the test (parent or legal guardian should not be present to intervene). The age range of children that self-collect should be consistent with the device’s intended use.**

    -   **Adults (age 18 and older) self-collect the sample and perform the test themselves.**

    -   **Adult (adult 1) collects a sample from another adult (adult 2) and adult 1 performs the test.**

##### 2. Patient Enrollment

-   **Study population should include individuals across all ages 2y-65+y**

    -   **&lt;14 years of age (target ~20%)**

    -   **14-24 years of age (target ~10-15%)**

    -   **24-64 years of age (24-64y target ~30-35%)**

    -   **≥65 years of age (target ~35%)**

-   **Parents or legal guardians must consent for children as required by law**

-   **Enrollment population should represent different socioeconomic and educational backgrounds**

-   **Study should include symptomatic and asymptomatic individuals**

-   **High risk individuals should not be excluded from the study**

-   **You should exclude participants who regularly use home use diagnostic tests, such as glucose meters.**

##### 3. Reference Sample/Comparator method

-   **FDA recommends the comparator be either a health care provider-collected NP swab sample (collected from each patient in the study within a reasonable time frame from when the test sample was obtained/tested same visit preferred) or a home-collected nasal or mid-turbinate swab. If you will conduct the study remotely, in a way where patients do not have in person visits with health care professionals, the comparator should be an FDA authorized home collected nasal or mid-turbinate swab. If you have difficulty in sourcing NP swabs, finding patients who consent to the NP swab procedure or finding clinical sites willing to collect NP swabs, please contact FDA about potential alternative swab types, such as mid-turbinate, oropharyngeal and nasal and the additional considerations for these comparator samples.**

-   **All comparator samples should be tested with a comparator method. The comparator method selected should be one of the more sensitive EUAs on the FDA website (supported by peer reviewed literature, comparative studies in lab, etc.) that uses both a chemical lysis step and solid phase extraction method. Ideally the same comparator would be used for all samples.**

##### 4. Discrepant analysis

-   **A plan for discrepant testing should be developed and should be implemented if a large number of discordant results are obtained in the clinical study.**

-   **Like with the original comparator method, discordant samples should be tested with a second EUA from FDA’s website that has also demonstrated high sensitivity, and which uses both a chemical lysis step and solid phase extraction method.**

-   **Discrepant analysis should not be used to alter the performance data but may be added to the performance table as a footnote.**

-   **If necessary, to help with discrepant resolution, positive samples can also be serially diluted and tested in parallel with the test device and a comparator method to demonstrate reduced or improved analytical sensitivity.**

##### 5. Study Size

**All Comers Testing**

-   **Patients should be enrolled in an “all comers” style, including both symptomatic and asymptomatic patients. Study testing should be continued until 30 positives are obtained. The overall study size should not be less than 150 individuals.**

-   **You should aim to have at least 10 positives from asymptomatic individuals.**

-   **If you would like to enrich your study to obtain positives more rapidly, you can enrich your population by including patients who have already tested positive by another assay. Please contact FDA for feedback on potential alternatives for enriching prospective positive patients in a clinical study.**

##### 6. Performance

-   For non-prescription (OTC) tests intended for use in non-laboratory settings, FDA recommends that tests have a PPA and NPA as follows:  **Positive Percent Agreement (PPA) ≥90% for asymptomatic and symptomatic**

-   **Negative Percent Agreement (NPA) ≥99% (LB &gt;95%)**

#### 9. Additional Studies

**FDA Reference Material Testing**

-   **All assays for use in non-laboratory settings should demonstrate high analytical sensitivity as determined by testing with the FDA SARS-CoV-2 Reference Panel or a recognized International Standard. If you do not have access to either the FDA SARS-CoV-2 Reference Panel or a recognized international standard then please contact <CDRH-EUA-templates@fda.hhs.gov> to discuss options.**

#### 10. Alternative Clinical Study Approaches:

#### A)  Adding Asymptomatic Testing Post-Authorization

**If your assay is already authorized for non-laboratory use without an asymptomatic claim, you may request the addition of asymptomatic testing through a post-authorization study. For a post-authorization study we generally recommend testing a minimum of 20 consecutively collected asymptomatic positive specimens and at least 100 consecutively collected negative specimens based on the results of the candidate test. All specimens should then be tested with another EUA authorized molecular assay. Using estimates of the predictive values and the percentage of positive results, this study can be used to establish the sensitivity (PPA) and specificity (NPA) of your test in an asymptomatic population, as this is an important performance metric for tests intended for asymptomatic screening of large populations. The FDA generally expects that PPA should be &gt;95% and NPA should be ≥98% (with a lower bound of the two-sided 95% confidence interval &gt;95%). **

#### B)  Symptomatic Patient Testing (prescription use only)

**If you wish to limit your assay to symptomatic individuals you may do this by offering your test by prescription only. Since there is no mechanism to limit OTC testing to symptomatic individuals, FDA recommends developers requesting an OTC claim consider the clinical study and performance recommendations for asymptomatic testing, as described above.**

**For a Prescription Non-Laboratory Test for symptomatic patients, you should follow the study design above with the recommended changes to Study Size and Performance below.**

**Study Size For Prescription Non-Laboratory Use Only**

-   Testing in symptomatic individuals should be continued until 30 positives and 30 negatives are obtained. (a population size of 150, in a prospective study, would be expected to yield 30 positive results if prevalence is 20%).

**Lower PPA and NPA may be acceptable for prescription non-laboratory use assays for symptomatic patients because the inclusion of symptoms as a requirement for testing increases the pre-test probability of a positive result (higher prevalence) and therefore increases the Positive Predictive Value of the test. FDA believes that a Positive Predictive Value of a test with below 90% PPA would be insufficient without this mitigation (confirming symptoms).**

**Performance For Symptomatic Use Only**

**For symptomatic use only tests, FDA recommends that the test have a PPA and NPA as follows:**

-   Positive Percent Agreement (PPA) ≥80% for symptomatic

-   Negative Percent Agreement (NPA) ≥99% (LB &gt;95%)

### K. UNMET NEED ADDRESSED BY THE PRODUCT

**This section will be completed by FDA.**

### L. APPROVED/CLEARED ALTERNATIVE PRODUCTS

Currently no methods for the detection of the SARS-CoV-2 have been approved/cleared by FDA.

### M. BENEFITS AND RISKS:

**This section will be completed by FDA.**

### N. FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:

**Include proposed Fact Sheets for Patients and Healthcare Providers *- see examples from authorized EUA tests on our website. Templates will be made available at sponsor’s request.***

### O. INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:

**Include Instructions for Use, Box Labels, Vial Labels and any other proposed labeling.**

### P. RECORD KEEPING AND REPORTING INFORMATION TO FDA:

**As allowed by Section 564(e) of the FD&C Act, FDA may require certain conditions as part of an emergency use authorization. FDA will generally include the following record keeping and reporting information requirements in the EUA which FDA believes are necessary to protect the public health.**

\[***Manufacturer name***\] will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report on adverse events, and this website is referenced in the Fact Sheet for Health Care providers as well as through the \[***Manufacturer name***\] Product Support website: \[***Include link to Website***\]. Each report of an adverse event will be processed according to \[***Manufacturer name******\]***’s Non-Conformance Reporting Requirements, and Medical Device Reports will be filed with the FDA as required. Through a process of inventory control, \[***Manufacturer name******\]*** will also maintain records of device usage/purchase. \[***Manufacturer name******\]*** will collect information on the performance of the test, and report to FDA any suspected occurrence of false positive or false negative results of which \[***Manufacturer name******\]*** becomes aware. \[***Manufacturer name******\]*** will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

### Appendix A: Recommended Flex Study Design Details, as appropriate for the device:

1.  **Reading Time:**

**You should evaluate test results at reading times four times below and three times above the recommended reading time. For example, for a test where the recommended read time is 20 minutes, reading time times would be performed to evaluate at least read times of 5, 10, 15, 20, 30, and 60 minutes. If incorrect results are observed, the sponsor should propose adequate mitigations for how the incorrect timing can be addressed.**

2.  **Specimen Volume:**

**You should evaluate test results at specimen volumes two times below and two times above the recommended specimen volume, and the maximum possible added. For example, for a test where the recommended specimen volume is 10 μL, specimen volume testing would be performed to evaluate at least specimen volumes of 5, 10, 20 μL and 100uL (whole volume). If incorrect results are observed at either 5 or 20 uL, additional testing at 7.5 and/or 15 uL may be needed. The diluent/buffer amount added should be that specified in the instructions for use**

3.  **Sample Diluent Volume:**

**You should evaluate test results at diluent/buffer volumes at two times below and two times above the recommended diluent/buffer volume and the maximum volume. For example, for a test where the recommended buffer/diluent volume is 2 drops, sample diluent volume testing would be performed to evaluate at least sample diluent volumes of 1, 2, 3, 4 drops and whole bottle. The sample volume added should be that specified in the instructions for use.**

4.  **Sample Elution:**

**You should evaluate how mixing the swab in elution buffer (or other reagent) affects results. You should evaluate all extremes from not-mixing to vigorous shaking, generating bubbles as well as intermediate mixing, i.e. Swirling 1 or 2 times, instead of the prescribed number from the instructions.**

5.  **Temperature and Humidity:**

**You should evaluate test results at temperature and humidity extremes that are likely to occur in the United States. For example, 40°C and 95% RH, mimicking hot and humid climate, and 5°C and 5% RH mimicking cold and dry climates.**

6.  **Light:**

**You should evaluate test results in different lighting conditions that would be expected during use of the device, for visually read devices. For example, fluorescent, Incandescent, and natural lighting mimicking the outside environment.**

7.  **Disturbance during analysis:**

**You should evaluate the effect of moving the device while the test is running on expected test results. This could include; dropping the test while it is run, moving the test to another surface, unplugging the test, receiving a phone call while the mobile app is running, etc.**

8.  **Device Orientation:**

**You should evaluate unique device characteristics, as determined by a robust risk analysis. For example, if the device is intended to be run upright, evaluating test results if the device is used horizontally, or vice versa.**

[1] This template is part of the [Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) - Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised)

[2] <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>

[3] https://www.fda.gov/media/97321/download


# 2,787  2020-08-04_FDA Policy IVD - Sensitivity and Specificity Study Outline ABBREVIATED STUDY.md
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last updated: 2026-03-04 by BA
file_name: 2020-08-04_FDA Policy IVD - Sensitivity and Specificity Study Outline ABBREVIATED STUDY.md
file_date: 2020-08-04
title: FDA Policy IVD - Sensitivity and Specificity Study Outline ABBREVIATED STUDY
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summary_short: The FDA Sensitivity and Specificity Study Outline (Abbreviated/Minimum Requirement) specifies a standardized protocol for evaluating SARS-CoV-2 diagnostic device performance using the FDA SARS-CoV-2 Reference Panel, including matrix suitability checks, LoD range-finding and confirmation (up to 20 replicates), and Ct-based reporting. It guides manufacturers on preparing dilution series, running blinded controls (T2–T5), and summarizing results (including a mean Ct vs log10 concentration plot) so FDA can compare new devices against previously authorized tests.


CONTENT

***INTERNAL TITLE:*** FDA Sensitivity and Specificity Study Outline – ABBREVIATED STUDY/ MINIMUM REQUIREMENT

## Purpose:

To provide the procedure to be used to evaluate **COVID-19** device sensitivity and specificity. Besides establishing an LoD for the device using the **COVID-19** strain supplied for this study, the study will enable FDA to compare sensitivity and specificity of new and previously authorized devices.

## Materials Provided:

-   FDA Verification Panel (FDA SARS-CoV-2 Reference Panel)– contains one heat-inactivated **COVID-19** strain and one heat-inactivated **MERS-CoV** in cell culture media obtained through collaboration with Center for Biologics Evaluation and Research (CBER). Panel contents:

    -   T1 – concentrated stock 1 (USA-WA1/2020: NR-52281, concentration ~**1.8x10^8^** RNA NAAT detectable units/ mL)

    -   T2 – control 1 (blinded testing)

    -   T3 – control 2 (blinded testing)

    -   T4 – control 3 (blinded testing)

    -   T5– control 4 (blinded testing)

*Note*: The controls in the validation panel were prepared to generate specific RNA NAAT detectable units/mL. These units may not be equivalent to units provided in copies/mL.

*Note 2*: Please store the stock at -80°C until use. Prior to use, please thaw the stock at room temperature, prepare dilutions, and test the samples the same day.

*Note 3*: Both vials of T1 are Sars-CoV-2. One vial of T1 is provided for the LoD determination study and another one for the LoD corroboration study. MERS-CoV is part of the unknowns.

**Do not store diluted reference material over-night, or freeze-thaw the stock since it will produce a decrease in performance due to degradation.**

## Materials Not Provided:

-   Negative matrix of choice

*Note*: If several specimen types are claimed, please choose NP clinical matrix. If NP is not a specimen type claimed by your device, please contact the FDA.

*Note 2*: For devices authorized for use with dry swab specimens only, please adjust the protocol for your assay as follows:

-dilution series could be done using NP swabs collected from individuals negative for COVID-19 diluted in saline or other diluent appropriate for analytical testing for your particular device

-prepare each dilution so there is sufficient volume to perform replicates as per FDA’s protocol below

-test each dilution following the number of replicates requested by the FDA’s protocol below 

For devices authorized for use with dry swab specimens only, prepare mock swabs by pipetting 50 μL of each diluted virus stock onto a swab, let the swab dry for a minimum of 20 minutes, and test the swab following the Instructions for Use for the device.

Please provide a detail description of the workflow of your dry swab assay (including input volumes at each step).

-   Device to be evaluated may contain the following:

    -   Real-time RT-PCR Primer and Probe Set

    -   Real-time RT-PCR Control Set

    -   Mastermix

    -   Extraction method authorized (or to be authorized) with the new device

-   Instrument(s) to be authorized with the device

*Note*: If you determine that one or more instrument(s) has/have a different LoD please select the extraction/ instrument combination with the worst LoD (anything that is within 1 to 2x of the established LoD in a side-by-side comparison is considered comparable).

## Study Outline for Negatives:

To ensure that your matrix of choice will not interfere with the results produced by the reference material, you should first demonstrate that unspiked matrices generate valid *negative results* for all virus-specific primer and probe (i.e., are positive for your internal control and negative for SARS-CoV-2 targets). To this end, unspiked clinical matrix should be extracted 10-20 times. Each extracted nucleic acid matrix should be tested once by your assay before using the matrix for spiking as explained below.

## Study Outline for Sensitivity using T1:

### 1.  Preparation of spiked NP samples for extraction:

-   To start, please prepare a 1:10 dilution of the provided material T1.

For example:

-   Pipette 0.9 mL of NP matrix (swab eluted in VTM) into 1 vial labeled T1.1.

-   From the FDA Verification Panel stored at -80°C, remove T1 and thaw it at room temperature (RT), vortex and briefly centrifuge.

-   Transfer 0.1 mL of T1 to one of the vials -labeled T1.1- containing the 0.9 mL of clinical matrix. Total volume should now be 1 mL and the concentration in the order of ~1.8x10^7^ RNA NAAT detectable units/ mL.

-   Place lid on vial and vortex to mix.

-   Centrifuge briefly to prevent aerosol upon opening the tube.

### 2.  Range-finding:

-   **For the NP clinical matrix** spiked with T1 as described in 1:

-   Prepare a 10-fold dilution series in matrix – 7 dilutions total for each (1.8x10^6^ down to 1.8x10^0^) in addition to T1.1 prepared in step 1. Change tips between dilutions.

We suggest pipetting 4.5 mL of normal matrix into 7 additional vials labeled T1.2-T1.8. Transfer 0.5 mL of the T1.1 to the T1.2 vial, place lid on vial and vortex to mix. Centrifuge briefly to prevent aerosol upon opening the tube.

Proceed with 1:10 dilutions until T1.8 is generated.

-   Extract T1.2-T1.8 three times each by the method authorized (or to be authorized) with the new device.

-   Test each of the extracted T1.2-T1.8 replicates with your assay.

### 3.  Sensitivity Confirmation: All the LoD corroboration study should BE COMPLETED ON A SINGLE DAY. Storage of diluted material is not recommended as degradation of material may occur.

-   For each dilution series of virus T1 in clinical matrix, identify the lowest concentration for which all three replicates generate positive results. This is the target dilution for confirmation for each virus.

    -   The initial dilution window to be further tested includes the target dilution(s) identified in the previous step.

    -   Using the same extraction method used in the range finding study that has been authorized (or to be authorized) with the device:

    -   For the targeted dilution for confirmation, if the confirmation is performed the same day of the range finding, 17 additional replicates should be tested from extraction to amplification/detection. Please add any triplicates from the range finding to the 17 replicates of the confirmatory study as applicable. If confirmation is performed on a following day, 20 replicates should be tested from extraction to amplification/detection for the targeted dilution to limit variability in Ct values.

    -   Test each individually extracted nucleic acid sample once by your assay.

A.  If you obtained 19/20 or 20/20 positive results, this dilution will be considered your LoD.

B.  If you obtained 20/20 positive results, you may choose to further define the LoD of your assay by testing one 3-fold dilution below the identified target(s). Dilutions should continue further down until at least 1of the 20 samples generate one negative result.

C.  If you obtained less than 19/20 positive results, you must still define the LoD of your assay by testing one 3-fold dilution above the identified target(s). Dilutions should continue further up until only 1of the 20 samples generate a negative result.

For both B and C:

-   Using the extraction method authorized (or to be authorized) with the device (also used in range-finding):

    -   For any of the two dilutions bracketing the targeted level for confirmation, 20 replicates should be tested from extraction to amplification/detection.

    <!-- -->

    -   Test each individually extracted nucleic acid sample once by your assay.

### 4.  Graphical Summary:

-   Please provide a plot of Mean Ct (with error bars) versus log~10~ (RNA NAAT detectable units/ mL).

## Study Outline for Blinded Controls using T2-T5:

-   Prepare a 1:10 dilution and a 1:100 dilution of provided material T2 to T5 in NP matrix as shown in Figure 1 and test the dilutions in red.

Figure 1. Panel Dilution Scheme

_Diagram showing the panel dilution scheme: serial dilution of SARS-CoV-2 reference material into multiple tubes at decreasing concentrations for limit of detection determination and confirmation._

For a 10 mL final volume:

-   Pipette 9 mL of normal human matrix into eight vials; designate two vials for each blinded control T2 (T2 and T2.1), T3 (T3 and T3.1), T4 (T4 and T4.1), and T5 (T5 and T5.1).

-   From the FDA Verification Panels stored at -80°C, remove T2-T5 and thaw them at RT, vortex and briefly centrifuge.

-   Transfer 1 mL of each of T2-T5 to its designated vial containing clinical matrix. Total volume should now be 10 mL in each vial.

-   Place lid on vial and vortex to mix.

-   Centrifuge briefly to prevent aerosol upon opening the tube.

-   Use these final T3 and T4 (all 1:10 dilutions) dilution for testing.

-   For T2, T3, T4 and T5 (all 1:10 dilutions), transfer 1 mL of T2 into the vial labeled T2.1., 1 mL of T3 into the vial labeled T3.1,1 mL of T4 into the vial labeled T4.1, and 1 mL of T5 into the vial labeled T5.1 to generate the 1:100 dilution. Use these final T2.1, T3.1, T4.1 and T5.1 (all 1:100) dilutions for testing.

-   Place lid on vial and vortex to mix.

-   Centrifuge briefly this vial to prevent aerosol upon opening the tube.

-   For each spiked matrix with T2.1 (1:100), T3 (1:10), T3.1(1:100), T4 (1:10), T4.1 (1:100) and T5.1 (1:100):

    -   Extract each control five times using the extraction method authorized (or to be authorized) with the new device. You will have half of the preparation unused in this case,

    -   Test the diluted specimens with your assay.

-   For each Ct value obtained for the blinded controls (30 values in total), please provide an estimated value of RNA NAT detectable units/ mL by comparing the Ct values of the controls to the corresponding 10-fold dilution with known concentrations in units/ mL used to construct the graph above.

*Note*: Please do not include the dilution factor in your estimation; provide the NAAT detectable units as measured in the sample tested.

*Note 2*: Please run all the unknowns on the same day.

*Note 3:* Please provide individual Ct values, average Ct values, error of the mean Ct values, and number of positive hits over total replicates in each step of the study.

*Summary of the vials provided:*

| Tube # | Volume (mL) | Number of tubes | Dilution to be tested |
| --- | --- | --- | --- |
| 1 | 0.6 | 2 | Serial dilution: one vial is for LoD determination and another one for LoD confirmation |
| 2 | 1.5 | 1 | 1:100 |
| 3 | 1.5 | 1 | 1:10 and 1:100 |
| 4 | 1.5 | 1 | 1:10 and 1:100 |
| 5 | 1.5 | 1 | 1:100 |
||

For a more robust study, please use the protocol entitled: **FDA Sensitivity and Specificity Study Outline – FULL STUDY**, which details a more extensive LoD corroboration study and additional blinded sample testing.

*Note: The material cannot be used for other purposes than the ones specified in this protocol.*

For additional questions, please contact Mayra Garcia, Ph.D., M.B.A., at (240) 402-7213 or at <Mayra.Garcia@fda.hhs.gov>


# 2,684  2020-08-04_FDA Policy IVD - Sensitivity and Specificity Study Outline FULL STUDY.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-08-04_FDA Policy IVD - Sensitivity and Specificity Study Outline FULL STUDY.md
file_date: 2020-08-04
title: FDA Policy IVD - Sensitivity and Specificity Study Outline FULL STUDY
category: regulatory
subcategory: fda-policy
tags: 
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pdf_gdrive_url: https://drive.google.com/file/d/15aOYfuHk4JV44odELrt66CvA_carCuPm
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2020-08-04_FDA%20Policy%20IVD%20-%20Sensitivity%20and%20Specificity%20Study%20Outline%20FULL%20STUDY.pdf
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summary_short: The FDA Sensitivity and Specificity Study Outline (Full Study) is a step-by-step protocol for evaluating SARS-CoV-2 test performance using the FDA Verification Panel, including LoD determination/corroboration, dilution schemes, replicate testing, and blinded controls (T2–T5). It standardizes how developers generate and report Ct-based sensitivity/specificity results—plus a required Ct vs. log10 concentration plot—so FDA can compare new and previously authorized COVID-19 assays under consistent conditions.


CONTENT

***INTERNAL TITLE:*** FDA Sensitivity and Specificity Study Outline – FULL STUDY

## Purpose:

To provide the procedure to be used to evaluate **COVID-19** device sensitivity and specificity. Besides establishing an LoD for the device using the **COVID-19** strain supplied for this study, the study will enable FDA to compare sensitivity and specificity of new and previously authorized devices.

## Materials Provided:

-   FDA Verification Panel (FDA SARS-CoV-2 Reference Panel)– contains one heat-inactivated **COVID-19** strain and one heat-inactivated **MERS-CoV** in cell culture media obtained through collaboration with Center for Biologics Evaluation and Research (CBER). Panel contents:

    -   T1 – concentrated stock 1 (USA-WA1/2020: NR-52281, concentration ~**1.8x10^8^** RNA NAAT detectable units/ mL)

    -   T2 – control 1 (blinded testing)

    -   T3 – control 2 (blinded testing)

    -   T4 – control 3 (blinded testing)

    -   T5– control 4 (blinded testing)

*Note*: The controls in the validation panel were prepared to generate specific RNA NAAT detectable units/mL. These units may not be equivalent to units provided in copies/mL.

*Note 2*: Please store the stock at -80°C until use. Prior to use, please thaw the stock at room temperature, prepare dilutions, and test the samples the same day.

*Note 3*: Both vials of T1 are Sars-CoV-2. One vial of T1 is provided for the LoD determination study and another one for the LoD corroboration study. MERS-CoV is part of the unknowns.

**Do not store diluted reference material over-night, or freeze-thaw the stock since it will produce a decrease in performance due to degradation.**

## Materials Not Provided:

-   Negative clinical matrix of choice

*Note*: If several specimen types are claimed, please choose NP clinical matrix. If NP is not a specimen type claimed by your device, please contact the FDA.

*Note 2*: For devices authorized for use with dry swab specimens only, please adjust the protocol for your assay as follows:

-dilution series could be done using NP swabs collected from individuals negative for COVID-19 diluted in saline or other diluent appropriate for analytical testing for your particular device

-prepare each dilution so there is sufficient volume to perform replicates as per FDA’s protocol below

-test each dilution following the number of replicates requested by the FDA’s protocol below 

For devices authorized for use with dry swab specimens only, prepare mock swabs by pipetting 50 μL of each diluted virus stock onto a swab, let the swab dry for a minimum of 20 minutes, and test the swab following the Instructions for Use for the device.

Please provide a detail description of the workflow of your dry swab assay (including input volumes at each step).

-   Device to be evaluated may contain the following:

    -   Real-time RT-PCR Primer and Probe Set

    -   Real-time RT-PCR Control Set

    -   Mastermix

    -   Extraction method authorized (or to be authorized) with the new device

-   Instrument(s) to be authorized with the device

*Note*: If you determine that one or more instrument(s) has/have a different LoD please select the extraction/ instrument combination with the worst LoD (anything that is within 1 to 2x of the established LoD in a side-by-side comparison is considered comparable).

## Study Outline for Negatives:

To ensure that your matrix of choice will not interfere with the results produced by the reference material, you should first demonstrate that unspiked matrices generate valid *negative results* for all virus-specific primer and probe (i.e., are positive for your internal control and negative for SARS-CoV-2 targets). To this end, unspiked clinical matrix should be extracted 20 times. Each extracted nucleic acid matrix should be tested once by your assay before using the matrix for spiking as explained below.

## Study Outline for Sensitivity using T1:

### 1.  Preparation of spiked NP samples for extraction:

-   To start, please prepare a 1:10 dilution of the provided material T1.

For example:

-   Pipette 0.9 mL of NP matrix (swab eluted in VTM) into 1 vial labeled T1.1.

-   From the FDA Verification Panel stored at -80°C, remove T1 and thaw it at room temperature (RT), vortex and briefly centrifuge.

-   Transfer 0.1 mL of T1 to one of the vials -labeled T1.1- containing the 0.9 mL of clinical matrix. Total volume should now be 1 mL and the concentration in the order of ~1.8x10^7^ RNA NAAT detectable units/ mL.

-   Place lid on vial and vortex to mix.

-   Centrifuge briefly to prevent aerosol upon opening the tube.

### 2.  Range-finding:

-   **For the NP clinical matrix** spiked with T1 as described in 1:

-   Prepare a 10-fold dilution series in matrix – 7 dilutions total for each (1.8x10^6^ down to 1.8x10^0^) in addition to T1.1 prepared in step 1. Change tips between dilutions.

We suggest pipetting 4.5 mL of normal matrix into 7 additional vials labeled T1.2-T1.8. Transfer 0.5 mL of the T1.1 to the T1.2 vial, place lid on vial and vortex to mix. Centrifuge briefly to prevent aerosol upon opening the tube. Proceed with 1:10 dilutions until T1.8 is generated.

-   Extract T1.2-T1.8 three times each by the method authorized (or to be authorized) with the new device.

-   Test each of the extracted T1.2-T1.8 replicates with your assay.

### 3.  Sensitivity Confirmation:

-   For each dilution series of virus T1 in clinical matrix, identify the lowest concentration for which all three replicates generate positive results. This is the target dilution for confirmation for each virus.

-   For the next testing step (confirmatory testing) you should test the target dilution(s) identified in the previous step plus one 3-fold dilution above and below the identified target dilution. Additional dilutions need to be made as applicable until at least 1of the 20 samples generate a negative result. If in the confirmatory testing none of the levels reaches at least 95% positivity, you will need to go further up in the dilution scheme until you can show at least 95% with 20 replicates (19/20 positive results).

-   Using the same extraction method used in the range finding study that has been authorized (or to be authorized) with the device:

    -   For the targeted dilutions for confirmation, if the confirmation is performed the same day of the range finding, 17 additional replicates should be tested from extraction to amplification/detection. Please add any triplicates from the range finding to the 17 replicates of the confirmatory study as applicable. If confirmation is performed on a following day, 20 replicates should be tested from extraction to amplification/detection for the targeted dilution to limit variability in Ct values.

    -   For the two dilutions bracketing the targeted level for confirmation, 20 replicates should be tested from extraction to amplification/detection.

-   Test each individually extracted nucleic acid sample once by your assay.

### 4.  Graphical Summary:

-   Please provide a plot of Mean Ct (with error bars) versus log~10~ (RNA NAAT detectable units/ mL).

**Study Outline for Blinded Controls using T2-T5**:

-   Prepare a 1:10 dilution and a 1:100 dilution of provided material T2 to T5 in NP matrix as shown in Figure 1 and test the dilutions in red.

Figure 1. Panel Dilution Scheme

_Diagram showing the panel dilution scheme: serial dilution of SARS-CoV-2 reference material into multiple tubes at decreasing concentrations for limit of detection determination and confirmation._

For 10mL final volume:

-   Pipette 9 mL of normal human matrix into eight vials; designate two vials for each blinded control T2 (T2 and T2.1), T3 (T3 and T3.1), T4 (T4 and T4.1), and T5 (T5 and T5.1).

-   From the FDA Verification Panels stored at -80°C, remove T2-T5 and thaw them at RT, vortex and briefly centrifuge.

-   Transfer 1 mL of each of T2-T5 to its designated vial containing clinical matrix. Total volume should now be 10 mL in each vial.

-   Place lid on vial and vortex to mix.

-   Centrifuge briefly to prevent aerosol upon opening the tube.

-   Use these final T3 and T4 (all 1:10 dilutions) dilution for testing.

-   For T2, T3, T4 and T5 (all 1:10 dilutions), transfer 1 mL of T2 into the vial labeled T2.1., 1 mL of T3 into the vial labeled T3.1, 1 mL of T4 into the vial labeled T4.1, and 1 mL of T5 into the vial labeled T5.1 to generate the 1:100 dilution. Use these final T2.1, T3.1, T4.1 and T5.1 (all 1:100) dilutions for testing.

-   Place lid on vial and vortex to mix.

-   Centrifuge briefly this vial to prevent aerosol upon opening the tube.

-   For each spiked matrix with T2.1 (1:100), T3 (1:10), T3.1(1:100), T4 (1:10), T4.1 (1:100) and T5.1 (1:100):

    -   Extract each control at least five times using the extraction method authorized (or to be authorized) with the new device. You will have half of the preparation unused in this case,

    -   Test the diluted specimens with your assay.

-   For each Ct value obtained for the blinded controls (30 values in total), please provide an estimated value of RNA NAT detectable units/ mL by comparing the Ct values of the controls to the corresponding 10-fold dilution with known concentrations in units/ mL used to construct the graph above.

*Note*: Please do not include the dilution factor in your estimation; provide the NAAT detectable units as measured in the sample tested.

*Note* 2: For a more robust study, please extract and test 10 times T2.1, T3, T3.1, T4, T4.1, and T5.1. This will result in 60 blinded testing values in total. In this case, you will use all the volume prepared above.

*Note 3*: Please run all the unknowns on the same day.

*Note 4:* Please provide individual Ct values, average Ct values, error of the mean Ct values, and number of positive hits over total replicates in each step of the study.

*Summary of the vials provided:*

| Tube # | Volume (mL) | Number of tubes | Dilution to be tested |
| --- | --- | --- | --- |
| 1 | 0.6 | 2 | Serial dilution: one vial is for LoD determination and another one for LoD confirmation |
| 2 | 1.5 | 1 | 1:100 |
| 3 | 1.5 | 1 | 1:10 and 1:100 |
| 4 | 1.5 | 1 | 1:10 and 1:100 |
| 5 | 1.5 | 1 | 1:100 |
||

*Note: The material cannot be used for other purposes than the ones specified in this protocol.*

For additional questions, please contact Mayra Garcia, Ph.D., M.B.A., at (240) 402-7213 or at [Mayra.Garcia@fda.hhs.gov](mailto:Mayra.Garcia@fda.hhs.gov)


# 3,275  2020-08-24_FDA Policy IVD - Pooled Sample Testing and Screening Testing for COVID-19.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2020-08-24_FDA Policy IVD - Pooled Sample Testing and Screening Testing for COVID-19.md
file_date: 2020-08-24
title: FDA Policy IVD - Pooled Sample Testing and Screening Testing for COVID-19
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: docx
xfile_type: docx
gfile_url: https://docs.google.com/document/d/1zUrK-zdaEbo4pRihH60blFNzvDfmcW5QJfYOBCaVKHk
xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fda-policy/2020-08-24_FDA%20Policy%20IVD%20-%20Pooled%20Sample%20Testing%20and%20Screening%20Testing%20for%20COVID-19.docx
pdf_gdrive_url: https://drive.google.com/file/d/1vW6FNrru6W_OWgL8Nr_wubXYmFmU9HwR
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2020-08-24_FDA%20Policy%20IVD%20-%20Pooled%20Sample%20Testing%20and%20Screening%20Testing%20for%20COVID-19.pdf
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notes: 
summary_short: The FDA “Pooled Sample Testing and Screening Testing for COVID-19” policy summarizes federal recommendations and linked resources for validating and using SARS-CoV-2 IVDs in pooled-sample workflows and in screening of asymptomatic individuals. It defines pooled testing approaches (sample/media vs. swab pooling), highlights key validation expectations (including ≥85% PPA vs. individual testing) and reporting/CLIA considerations to mitigate dilution-driven false negatives. It also distinguishes screening from surveillance testing and provides practical guidance for providers on when highly sensitive tests, serial testing, and confirmatory testing may be appropriate.


CONTENT

[08-24 New FDA Webpage on Pooled Sample Testing and Screening Testing](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/pooled-sample-testing-and-screening-testing-covid-19?utm_campaign=2020-08-21%20Pooled%20Sample%20Testing%20and%20Screening%20Testing&utm_medium=email&utm_source=Eloqua)

The U.S. Food and Drug Administration (FDA) has taken steps to encourage the development of tests for screening asymptomatic individuals and for testing pooled samples. Today, the FDA posted a new webpage that provides an overview of available resources related to SARS-CoV-2 screening testing and testing using pooled samples.

***INTERNAL TITLE:*** Pooled Sample Testing and Screening Testing for COVID-19

The FDA has taken steps to encourage the development of tests for screening asymptomatic individuals and for testing pooled samples, as summarized in the June 16, 2020, FDA Statement [Facilitating Diagnostic Test Availability for Asymptomatic Testing and Sample Pooling](https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-facilitating-diagnostic-test-availability-asymptomatic-testing-and). The FDA has continued to work with developers to facilitate testing of pooled samples, including providing more detailed recommendations in the July 6, 2020, and July 28, 2020, updates to the EUA templates.

This page provides an overview of available resources related to SARS-CoV-2 screening testing and testing using pooled samples.

### On this page:

-   [Overview](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/pooled-sample-testing-and-screening-testing-covid-19?utm_campaign=2020-08-21%20Pooled%20Sample%20Testing%20and%20Screening%20Testing&utm_medium=email&utm_source=Eloqua#overview)

-   [Pooled Sample Testing](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/pooled-sample-testing-and-screening-testing-covid-19?utm_campaign=2020-08-21%20Pooled%20Sample%20Testing%20and%20Screening%20Testing&utm_medium=email&utm_source=Eloqua#pooled)

-   [Screening of Asymptomatic Individuals](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/pooled-sample-testing-and-screening-testing-covid-19?utm_campaign=2020-08-21%20Pooled%20Sample%20Testing%20and%20Screening%20Testing&utm_medium=email&utm_source=Eloqua#screening)

-   [Surveillance Testing](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/pooled-sample-testing-and-screening-testing-covid-19?utm_campaign=2020-08-21%20Pooled%20Sample%20Testing%20and%20Screening%20Testing&utm_medium=email&utm_source=Eloqua#surveillance)

-   [Questions](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/pooled-sample-testing-and-screening-testing-covid-19?utm_campaign=2020-08-21%20Pooled%20Sample%20Testing%20and%20Screening%20Testing&utm_medium=email&utm_source=Eloqua#questions)

## Overview

The FDA encourages developers to consider validating their tests for the screening of asymptomatic individuals and for testing pooled samples.

### *Resources*

The FDA has provided these resources about testing using pooled samples and testing for asymptomatic screening:

-   [Emergency Use Authorization (EUA) Templates](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates): Include validation recommendations for tests, including for screening of asymptomatic individuals and pooled sample testing.

-   [FAQs on Testing for SARS-CoV-2](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/faqs-testing-sars-cov-2): Includes Frequently Asked Questions, including about screening of asymptomatic individuals and pooled sample testing, and discusses the differences between surveillance, screening, and diagnostic testing.

## Pooled Sample Testing

The FDA is aware that there is a great interest in performing testing using pooled samples. Pooling samples involves mixing several samples together in a "batch" or pooled sample, then testing the pooled sample with a diagnostic test. This approach increases the number of individuals that can be tested using the same amount of resources. For example, four samples may be tested together, using only the resources needed for a single test. However, because samples are diluted, which could result in less viral genetic material available to detect, there is a **greater likelihood of false negative results**, particularly if not properly validated. This method of pooling samples works well when there is a low prevalence of cases, meaning more negative results are expected than positive results.

### *Validation*

The FDA believes that sample pooling can be authorized for use in certain SARS-CoV-2 tests with appropriate mitigations and validation. The FDA has provided validation recommendations for tests intended for use with pooled samples in the [EUA Templates](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates).

Test developers seeking authorization for their test for use with pooled samples should validate their test for such use, considering the validation recommendations outlined in the EUA templates, and submit an EUA request to the FDA.

As discussed in the templates, there are currently two approaches to patient specimen pooling:

-   Sample/media pooling: Pooling aliquots of transport media each containing a single patient sample or

-   Swab pooling: Adding swabs from multiple patients into a single volume of transport media.

The templates include validation recommendations for both types of pooling approaches.

Generally, the FDA recommends validating the test with either pooling approach in a way that preserves the sensitivity of the test as much as possible. That is, it is preferable to use an approach where all specimens identified as positive when tested individually are also identified as positive when tested using the pooled testing approach. However, a decrease in performance is likely with pooling strategies, due to dilution of the primary clinical sample.

As discussed in the templates, since sample pooling will greatly increase the number of individuals that can be tested using existing resources, a small reduction in sensitivity may be acceptable depending on the pooling efficiency and other mitigations in place.

Therefore, the FDA generally recommends that, after pooling, test performance includes ≥85% percent positive agreement (PPA) when compared with the same test performed on individual samples. Additional limitations, such as considering negative results from pooled samples to be presumptive negatives, may be recommended based on the patient population included in the sponsor's clinical evaluation and the performance data submitted in the EUA request.

As discussed in the templates, a plan for ongoing monitoring of the positivity rate and of the performance of a test with a pooling strategy should be included in the test's procedures. As data become available and new approaches are identified, our recommendations in these templates may evolve.

### *Testing Considerations*

A [Clinical Laboratory Improvement Amendments](https://www.cdc.gov/clia/index.html) (CLIA) certified laboratory **using a test authorized for pooling** must follow the manufacturer's authorized Instructions for Use (IFU). Additionally, the Letter of Authorization issuing the EUA includes certain Conditions of Authorization, some of which apply to the authorized laboratories performing the test.

Generally, laboratories should report diagnostic or screening negative test results to the individuals in the pool according to the instructions for use or the EUA Summary of the FDA-authorized SARS-CoV-2 test that the laboratory used, including providing the associated Fact Sheet.

The test report given to the individuals in the pool should include any information specified in an EUA, such as indicating that the testing procedure involved specimen pooling and explaining the limitations of that type of testing.

As discussed in the CDC guidance, [Interim Guidance for Use of Pooling Procedures in SARS-CoV-2 Diagnostic, Screening, and Surveillance Testing](https://www.cdc.gov/coronavirus/2019-ncov/lab/pooling-procedures.html)

-   The CLIA-certified laboratory **must also report** those diagnostic or screening negative test results to appropriate federal, state, and local public health agencies in accordance with applicable federal, state, and local laws.

-   The CLIA-certified laboratory **should not report** positive or indeterminate results of a pooled test to either the individuals in the pool, or the local, state, tribal, or territory health department. All individual specimens that were in a pooled test with a positive or indeterminate result should be retested separately, and the subsequent individual diagnostic or screening results must be reported to the local, state, tribal, or territory health department as well as to the individuals tested.

## Screening of Asymptomatic Individuals

The FDA regulates screening tests as *in vitro* diagnostics (IVDs). Screening for COVID-19 systematically looks for individual infections in a group even if there is no reason to suspect those individuals are infected. Screening involves testing asymptomatic individuals who do not have known exposures with the intent of making individual decisions based on the test results. Screening tests are intended to identify infected individuals before they develop symptoms or to identify infected individuals who may not develop symptoms, so that measures can be taken to prevent further spread.

Examples of screening include testing, regardless of exposure or signs and symptoms, such as:

-   An employer testing all employees returning to the workplace

-   A school testing all students and faculty returning to the school.

In both examples, the intent of screening would be to use the results to determine who may return and what protective measures to take on an individual basis.

Laboratories may be interested in using pooling techniques when performing testing for screening of [asymptomatic](https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html#:~:text=An%20asymptomatic%20case%20is%20an,to%20disease%20transmission%20include%3A) individuals, since this involves testing a large volume of patient samples. Additionally, pooling is most effective when there is a low prevalence of cases, which may be more likely in an asymptomatic population, particularly if the population is at low risk for contracting COVID-19.

### *Validation*

Screening using a highly sensitive test, especially given the asymptomatic testing population, leads to the most accurate results when rapid turnaround times are available. The FDA has provided validation recommendations designed to establish high sensitivity for tests intended for screening in the [EUA Templates](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates). We encourage developers who want to offer a less sensitive test for screening to discuss validation approaches with us.

Developers seeking authorization for their test for screening asymptomatic individuals should validate their test for such use, considering the validation recommendations outlined in the EUA templates, and submit an EUA request to the FDA.

### *Testing Considerations for Providers*

Most currently authorized SARS-CoV-2 diagnostic tests are authorized for use on individuals suspected of COVID-19 by their healthcare provider. The FDA recognizes that the CDC has issued guidance related to screening—and that organizations may want to conduct screening—of asymptomatic individuals as part of a strategy to assure the safety of their employees, patients, students, and others. An asymptomatic individual may be suspected of COVID-19 by their healthcare provider for many reasons, including known exposure or working in a high-risk environment. Such use is within the authorized indications for use of tests for individuals suspected of COVID-19.

For healthcare providers who are ordering an authorized SARS-CoV-2 diagnostic test to be used off-label (outside the authorization) to screen asymptomatic individuals not suspected of having COVID-19, we recommend they consider the information below.

Although the current available literature suggests that symptomatic individuals with COVID-19 and asymptomatic individuals without known exposure may have similar levels of viral genetic material, there is limited data on the distribution of viral loads in individuals with and without symptoms across demographics, different settings, and specimen types. Therefore, when screening asymptomatic individuals, healthcare providers should consider using a highly sensitive test, especially if rapid turnaround times are available. If highly sensitive tests are not feasible, or if turnaround times are prolonged, health care providers may consider use of less sensitive point of care tests, even if they are not specifically authorized for this indication (commonly referred to as "off label"). For congregate care settings, like nursing homes or similar settings, repeated use of rapid point of care testing may be superior for overall infection control compared to less frequent, highly sensitive tests with prolonged turnaround times.

If less sensitive tests, such as some rapid point-of-care tests, are used, healthcare providers should be aware of the performance of the tests and may want to consider different testing approaches, such as serial testing.

As discussed in the [EUA Templates](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates), use of tests in a general, asymptomatic screening population is generally intended to be used as part of an infection control plan, that may include additional preventative measures, such as a predefined serial testing plan or directed testing of high-risk individuals. "Negative" results should be considered as "presumptive negative" and healthcare providers should consider them in the context of clinical observations, patient history, and epidemiological information. Thus, if there is a significant new outbreak in a congregate care facility, or high clinical suspicion of an infection in an individual resident, a negative point of care test should be confirmed with a highly sensitive molecular test (refer to CDC guidelines). It is not necessary to perform confirmatory high sensitivity molecular tests on individuals with negative antigen test or other point-of-care test results if they are obtained during routine screening or surveillance.

## Surveillance Testing

The FDA generally does not regulate surveillance testing. Surveillance testing is primarily used to gain information about infection at a community or population level, rather than an individual level. Surveillance testing can involve testing a certain percentage of a specific population to monitor for increasing or decreasing prevalence or to determine the effect of community interventions such as social distancing.

Surveillance for SARS-CoV-2 includes ongoing systematic activities, including collection, analysis, and interpretation of health-related data that are essential to planning, implementing, and evaluating public health practice. Surveillance testing is generally used to monitor for a community- or population-level occurrence, such as an infectious disease outbreak, or to characterize the occurrence once detected, such as looking at the incidence and prevalence of the occurrence.

-   *Example:* a testing plan developed by a state public health department to randomly select and sample 1 percent of all individuals in a city on a rolling basis to determine local infection rates and trends

Please refer to the Centers for Medicare & Medicaid Services (CMS) and the Centers for Disease Control and Prevention (CDC) for information on conducting surveillance testing and reporting results.

## Questions?

Contact the FDA at CDRH-EUA-Templates@fda.hhs.gov with specific proposals or questions about asymptomatic testing or pooled sample testing.


# 13,046  2020-10-26_FDA Template - Antigen Template for Test Developers.md
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last updated: 2026-03-04 by BA
file_name: 2020-10-26_FDA Template - Antigen Template for Test Developers.md
file_date: 2020-10-26
title: FDA Template - Antigen Template for Test Developers
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summary_short: The FDA “Antigen Template for Test Developers” is an interactive EUA review template that specifies the data, validation studies, and labeling information recommended for SARS-CoV-2 antigen test submissions. It details analytical, clinical, stability, manufacturing, software, and point-of-care performance expectations to support intended use claims, including screening and asymptomatic testing. It is used by test developers to structure pre-EUA/EUA submissions and align study design with FDA review expectations during the COVID-19 public health emergency.


CONTENT

***INTERNAL TITLE:*** Antigen Template for Test Developers

This template (the “template”) provides the Food and Drug Administration’s (FDA) current recommendations concerning what data and information should be submitted to FDA in support of a pre- Emergency Use Authorization (EUA)/EUA submission for a SARS-CoV-2 antigen test. As outlined in Section V.B. of the FDA guidance document: [*Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised),[2] FDA recommends that the following validation studies be conducted for a SARS-CoV-2 antigen assay: Limit of Detection/Analytical Sensitivity, Cross-reactivity/Analytical Specificity, Microbial Interference, and a Clinical Agreement Study. This template is intended to help test developers provide these validation data and other information to FDA, but alternative approaches can be used. It reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should* mean that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities).[3]

## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by the test developer (sponsor) as applicable to their specific test. Text in **bold** outlines the FDA’s additional recommendations for the sponsors’ consideration when completing the suggested information in each section.

-   A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   This is an EUA interactive review template for Pre-EUA/EUA submissions. We plan to update the template as appropriate as we learn more about the COVID-19 disease and gain experience with the EUA process for this test.

## EXAMPLE TEMPLATE:
### A.  PURPOSE FOR SUBMISSION

Emergency Use Authorization (EUA) request for distribution and/or use of the ***\[test name\]*** to ***\[indicate labs, if applicable\]*** for the *in vitro* qualitative detection of antigen from the SARS-CoV-2 in ***\[add all claimed specimen types, e.g., nasopharyngeal/ oropharyngeal swabs, sputa, BAL, and serum, etc.\]*** from patients who are suspected of COVID-19 by a healthcare provider ***\[within the first \[insert number\] days of symptom onset, or for screening of individuals without symptoms or other reasons to suspect COVID-19 infection, if applicable\].*** Additional testing and confirmation procedures should be performed in consultation with public health and/or other authorities to whom reporting is required. Test results should be reported in accordance with local, state, and federal regulations. 

***If you plan to request authorization to test specimens collected with a home specimen collection kit, please refer to the*** [Home Specimen Collection Molecular Diagnostic Template](https://www.fda.gov/media/138412/download)[4] ***and include any relevant information in this request.***

### B.  MEASURAND

Specific antigen(s) from the SARS-CoV-2 **\[*please specify the targeted antigen(s)*\]**.

### C.  APPLICANT

***\[Official name, address and contact information of applicant\]***

### D.  PROPRIETARY AND ESTABLISHED NAMES

Proprietary Name - ***\[test name\]***

Established Name - ***\[test name\]***

### E.  REGULATORY INFORMATION

**Approval/Clearance Status:**

The ***\[test name\]*** test is not cleared, CLIA waived, approved, or subject to an approved investigational device exemption.

**Product Code:** QKP

### F.  PROPOSED INTENDED USE

#### 1.  Intended Use:

Example text is provided below for a qualitative antigen test, but could be adapted according to the specific emergency situation addressed by the device, proposed intended use population, testing sites, or performance characteristics. Please note that if you seek authorization for testing at point of care (POC) sites or for asymptomatic screening, you should provide data from your clinical validation studies to support such use.

***\[Test name\]*** is a ***\[specify test technology, such as lateral flow immunoassay***\] intended for the qualitative detection of ***\[protein name\]*** antigen from SARS-CoV-2 in ***\[describe all the specimen types\] \[with specific brand of transport media, as applicable\]*** from individuals who are suspected of COVID-19 by their healthcare provider \[***within the first \[insert number\] days of symptom onset*** ***or for screening of individuals without symptoms or other reasons to suspect COVID-19 infection, if applicable******\]***. Testing is limited to laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet the requirements to perform ***\[moderate complexity, high complexity, or waived tests. This test is authorized for use at the Point of Care (POC), i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation.\].***

Results are for the identification of SARS-CoV-2 ***\[protein name\]*** antigen. Antigen is generally detectable in ***\[specimen type\]*** during the acute phase of infection. Positive results indicate the presence of viral antigens, but clinical correlation with patient history and other diagnostic information is necessary to determine infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Laboratories within the United States and its territories are required to report all positive results to the appropriate public health authorities.

Negative results should be treated as presumptive, and do not rule out SARS-CoV-2 infection and should not be used as the sole basis for treatment or patient management decisions, including infection control decisions. Negative results should be considered in the context of a patient’s recent exposures, history, and the presence of clinical signs and symptoms consistent with COVID-19, and confirmed with a molecular assay, if necessary, for patient management.

The ***\[test name\]*** is intended for use by ***\[include intended user, e.g., trained clinical laboratory personnel specifically instructed and trained in vitro diagnostic procedures\].*** The ***\[test name\]*** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

#### 2.  Special Conditions for Use Statements:

For prescription use only

For in vitro diagnostic use only

For Emergency Use Authorization only

#### 3.  Special Instrument Requirements:

The ***\[test name\]*** test is to be used with the ***\[list all instruments, software requirements, other applicable instrumentation, etc.\].***

### G.  DEVICE DESCRIPTION AND TEST PRINCIPLE

***Example text has been added under each of the sub-headings. If a different test principle is used by the test for the detection of a specific analyte, please modify the description accordingly to capture the salient points in each of the sub-headings below. For new investigative technologies FDA may request additional detailed information so we can adequately assess the risks and benefits associated with the device.***

#### 1.  Product Overview/Test Principle:
\[Describe the technology of the test and how this technology works to identify the measurand, the instruments employed/required to perform the test from sample collection to result, and the specimen types for which you claim to have specific performance characteristics, as described below. Please indicate if the test uses biotin-Streptavidin/avidin chemistry in any of the steps for coupling reagents. Please specifically state if your device is intended to be used with viral transport media and if so, provide the specific brands of transport media with which you have validated your device.\]

The ***\[test name\]*** is a ***\[description of technology (e.g., lateral flow, etc.)\]*** test. The ***\[test name\]*** is designed to detect antigen from the SARS-CoV-2 in ***\[list all the specimens\]*** from patients who are suspected of COVID-19 by their healthcare provider ***\[within the first \[number of days\] of symptom onset or for screening of individuals without symptoms or other reasons to suspect COVID-19 infection, if applicable\]***. The ***\[test name\]*** is validated for use from direct specimens testing without transport media and/or specimens with ***\[specific brand\]*** transport media.

#### 2.  Description of Test Steps:
\[List and describe in detail all of the steps of the test sequentially, from specimen collection to assay report.\] 

1.  ***\[Step one\]***

2.  ***\[Step two\]***

3.  ***Etc.…\]***

#### 3.  Control Material(s) to be Used with \[test name\]:
List all controls materials (provided with the test kit and/or required but not provided with the test kit) and describe what they are, how they are expected to work, where in the testing process they are used, and the frequency of use. If a control is commercially available, provide supplier’s name and catalog number or other identifier; if your device relies on external controls that are manufactured by a third party, please note that these controls should also be validated within your analytical and clinical studies, described below in Section J.

Controls that will be provided with the test kit include:

a.  An external positive control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the concentration of the positive control relative to the Limit of Detection (LoD) of your test (note that ideally the positive control concentration should be such that it is close to the LoD of your test) and specify frequency of use\]***

b.  An external negative control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the composition of the negative control and specify frequency of use\]***

c.  A ***\[other (e.g., sample adequacy, internal, etc.)\]*** control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the composition of the control and specify frequency of use\]***

Controls that are required but not provided with the test kit include ***\[describe control – provide recommended sources of the control materials – either a separate control kit for purchase that you, the applicant, develops, or a control material that can be purchased from a third party\].*** This/these control(s) is/are needed to ***\[describe need\]*** and is/are used ***\[describe use – please also specify frequency of use\]***.

**Please note that any control recommended to be used with your device (provided with the kit or not) should be validated in the context of your analytical and clinical study (i.e., your studies should include use of these controls). In instances where control material is not readily available through 3^rd^ party vendors, FDA recommends that you include suitable control material with your device. Please note that external control materials are considered particularly important when good manufacturing practice (GMP) requirements are waived and reagent stability studies are limited.**

### H.  INTERPRETATION OF RESULTS

All test controls should be examined prior to interpretation of patient results. If the controls are not valid, the patient results cannot be interpreted. ***\[If the test result involves the use of an algorithm/calculation when determining the final patient test result, please include a detailed description and any additional calibration materials that may be required.\]***

#### 1.  \[Test name\] Controls – Positive, Negative, and Others:
\[Describe in detail the expected results generated, including the acceptance criteria, for all the controls described in detail in Section G above. Describe the measured values (if applicable) for valid and invalid controls and outline the recommended actions the laboratory should take in the event of an invalid control result.\]

#### 2.  Examination and Interpretation of Patient Specimen Results:
\[Describe when clinical specimen test results should be assessed and outline the criteria for test validity.\]

Example text: Assessment of ***\[test name\]*** results should be performed after the positive and negative controls have been examined and determined to be valid and acceptable. If the controls are not valid, the patient results cannot be interpreted.

***\[Clearly indicate how to interpret numeric test values (if applicable) as detected or not detected for presence of COVID-19 antigen. If applicable, indicate how to identify indeterminate/inconclusive/equivocal results. When applicable, we recommend providing a table clearly describing the possible combinations of test result values for each detected antigen, if applicable, and controls. Describe how they should be combined into a final interpretation of the result for your test. If the test produces an equivocal or indeterminate result, please indicate what follow-up testing/process should be conducted.\]***

### I.  PRODUCT MANUFACTURING

The ***\[test name\]*** has been validated using only the components referenced in this submission and will not be changed without prior concurrence from the FDA.

#### 1.  Overview of Manufacturing and Distribution:

The product will be manufactured at ***\[test developer’s name and FDA registration number\]*** by ***\[test developer name\]*** personnel consistent with practices for the production of ***\[types of devices\]*** based on ***\[type of quality system\].*** Material manufactured by ***\[test developer’s name\]*** may be bottled and kitted by ***\[packager name\]*** manufacturing facility.

The current manufacturing capabilities include the ability to manufacture approximately ***\[please insert the approximate number of units/products that can currently be manufactured per week at the manufacturing facility\]*** products per week, however in the event of a surge in demand this could be increased to ***\[please insert the approximate maximum number of units/products that could potentially be manufactured per week at the manufacturing facility if there was a surge in demand\]*** products per week within a ***\[please specify in weeks/months the expected timeframe to increase product production, if conditions warrant\]*** timeframe.

The product will be distributed by ***\[please describe the distribution plan for the product and list all current distributors\]**.*

#### 2.  Components Included with the Test:

Components manufactured by ***\[test developer’s name and FDA registration number\]*** and supplied with the test include:

***\[List all components and reagents provided for your test, including a description of the reagents (including antibodies), volumes, concentrations, quantities, buffer components, etc.\]***

#### 3.  Components Required But Not Included with the Test:

\[List all components and reagents not included with the test that must be supplied by the user to perform the test, with specific supplier names and catalog numbers or other identifiers for obtaining these components and reagents. Please include here all specific consumables that were validated for use with your device, that are not interchangeable with other products, and that are needed to guarantee device performance as established in the EUA validation studies listed in Section J below.\]

#### 4.  Software Validation:

If you are introducing a system onto the market that has not been previously reviewed by FDA, we recommend providing evidence that the software has been validated to ensure that:

-   **The inputs and outputs of the software are appropriate to fulfill the system and assay requirements;**

-   **All expected inputs produce the expected outputs for all functions critical for system operation; and**

-   **The system will be provided to the customer free of defects, or defects will be known and mitigated.**

**If this evidence is not available prior to authorization and the software and hardware have been designed and developed in a manner consistent with current GMPs (for additional information on the Quality System Regulation/Medical Device Good Manufacturing Practices, see <https://www.fda.gov/medical-devices/postmarket-requirements-devices/quality-system-qs-regulationmedical-device-good-manufacturing-practices>**[5]**), additional software validation documentation may be incorporated into the conditions of authorization. If changes which impact assay performance or safety and effectiveness of the system are needed to address validation failures post-authorization, an EUA supplement may be required under the conditions of authorization.**

**If not available prior to authorization, FDA recommends the following evaluations be performed as soon as possible post-authorization and documentation kept on file and may be incorporated as a condition of authorization:**

-   **Perform electromagnetic compatibility (EMC) testing to International Electrotechnical Commission (IEC) 60601-1-2 Edition 4.0:2014;**

-   **Evaluate cybersecurity of your system to ensure user and patient safety in the intended use environment;**

-   **Complete validation of all systems and software to ensure that all functions of the system perform as labeled. For more information on system validation please see the following FDA guidance documents and resources:**

    a.  **[Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissions-software-contained-medical-devices);**[6]

    b.  **[General Principles of Software Validation](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-principles-software-validation);**[7]

    c.  **[Device Software Functions Including Medical Applications](https://www.fda.gov/medical-devices/digital-health/device-software-functions-including-mobile-medical-applications);**[8]

    d.  **[Cybersecurity](https://www.fda.gov/medical-devices/digital-health/cybersecurity);**[9]

    e.  **[Off-The-Shelf Software Use in Medical Devices](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices#:~:text=Off%2Dthe%2Dshelf%20(OTS,to%20run%20device%2Dspecific%20functions.);**[10] **and**

    f.  **[21 CFR 820.30](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=820.30).**

**Below are some examples of tables which could be populated with information sufficient to fulfill the three bullets above. Text in the tables is provided as an example only. In the example, the tables are completed with system-appropriate information and a thorough functional description of the system software and instrumentation needed to fulfill the intended use of the test.**

**System specifications and validation example**

| Critical specifications: Description of the specification | Evidence that the design of the system can fulfill the specification. This column should consist of system-level validation data. |
| --- | --- |
| Optical system of each instrument sent to a user has sufficient dynamic range to appropriately differentiate between positive and negative test results |  |
| Software displays appropriate result during test run |  |
| If reader stores test result, software accurately stores and retrieves test results |  |
| System has a defined lifetime where the user can expect the system to maintain performance as stated in the label |  |
| Etc… |  |
||



  **Hazard analysis example**

| ID | Hazard | Adverse Effect | Severity | Potential causes of hazard | Risk mitigation measure | Risk of experiencing the hazard after mitigation |
|--------|---------|----------|---------|--------------|--------------|----------|
| 1 | Invalid result | Delay in returning test result | Low | User inserts cartridge incorrectly | Labeling noting correct orientation | Low |
| 2 | False result | Wrong result returned to user | High | Incorrect alignment of test strip and optics; test strip inserted in the wrong orientation | Mechanical design of reader input slot | Moderate |
| 3 | False negative result | Wrong result returned to user | High | User reads test strip too early; incubation time not sufficient | Labeling noting correct incubation time | Moderate |
| 4 | False result | Wrong result returned to user | High | Incorrect alignment of test strip and optics; control line misinterpreted | Software interprets data from optical system identifying a valid/invalid control | Moderate |
| 5 | False result | Wrong result returned to user | High | Control reaction intensity is misinterpreted | Software interprets data from optical system identifying a valid/invalid control | Moderate |
| 6 | False result | Wrong result returned to user | High | Analyte reaction intensity is misinterpreted | Software interprets data from optical system identifying a valid/invalid control | Moderate |
||

#### 5.   Testing Capabilities:

*\[Briefly describe current sample throughput capacity, total time to perform the test (from clinical specimen collection, specimen transport, to result), and number of tests that can be performed per instrument run and per day.\]*

#### 6.  Reagent Stability:

*\[Briefly describe stability test plan for \[test name\] reagents and include any accelerated stability information, if available. Please note that reagent stability studies do not need to be completed at the time of EUA issuance, however the study design should be agreed upon during interactive review and the stability studies started immediately following authorization, if not before.\] *

**General recommendations for reagent stability study design:**

-   For EUAs, you may follow the current FDA recognized “CLSI Standard EP25 – Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline” when evaluating the suitability of stability study designs. If you are planning to pursue clearance or approval for your device, we recommend discussing in more detail your stability design to facilitate potential use of the EUA data in your regular premarket submission.

-   Please note that use of only the positive controls is not recommended for reagent stability evaluation because controls are usually formulated at a moderate positive level. For all the stability evaluations, in addition to your external positive and negative controls and the no-template control, you should include for the EUA evaluation at least one sample, which should be prepared by spiking negative clinical matrix at an analyte concentration of 3-5xLoD.

-   If you are claiming multiple clinical specimen types in which similar LoDs are determined, you should use the most challenging clinical matrix for this study.

-   Please note we typically recommend your stability study design include the evaluation of at least 5 replicates. You should also evaluate, if available, 3 different lots of reagents.

-   You should design your study to provide data for a timeframe that is about 10% longer than the one to be claimed. For example; a claim of 18 months should be supported by stability data out to 20 months and a claim of 7 days should include stability data out to 8 days.

-   FDA considers 15-30°C to represent room temperature conditions. Ideally, you should evaluate stability at both 15°C and 30°C; however, for the purposes of the EUA evaluation, we believe 30°C is acceptable as it represents the worse-case scenario.

-   Unopened kit Shelf-Life Stability:

    1.  You should evaluate real-time kit stability studies with unopened kits stored at the claimed storage temperature for your test.

    2.  Accelerated stability evaluations for unopened kits can be included for EUA submissions while the real-time studies are on-going.

-   Unopened kit Shipping Stability: Study should evaluate the anticipated handling and shipping times and temperatures expected for unopened kits.

-   In-use/Opened Kit Stability: Depending on your device, your stability study design should also support in-use stability of the kit reagents once the kit has been opened, e.g., storage at 2-8°C for 7 days. This includes on board stability once reagents have been placed on the instrument (if applicable).

-   Inverted stability (if applicable): Study should support inverted stability for kits.

-   Freeze-thaw Stability: If you recommend aliquoting the reagents to meet the end-users needs following the initial thaw, this recommendation should be supported by a freeze-thaw stability study, including the specific number of allowed freeze-thaw cycles.

-   FDA analysis recommendations for real time stability studies are as follows:

    -   Baseline of the study (t=0 of stability study) should not exceed a month from bottling;

    -   Clear baselines should be described (e.g., a month from bottling) for each stability claim under each study;

    -   Claims should be determined based on regression analysis. Any %change (%shift) from time zero (baseline) should be calculated between the target claim and the zero-time as (Ttest-Tbaseline)/ Tbaseline\*100 with 95% confidence interval (CI) using the regression equation obtained from plotting the mean values. When formulating your acceptance criteria for evaluating the shift from baseline, you should consider the reproducibility of your device. However, generally, the shift at the target claim due to storage cannot exceed 10-15%. The target stability is the next to last tested point that was within +/- 10% of time zero; and

    -   Acceptance criterion may be different, depending on the test samples analyte concentration distribution in the intended use population and the risk of false results to public health.

### J.  PERFORMANCE EVALUATION

***The following validation studies should be performed during your assay development:***

1.  **Limit of Detection (LoD) - Analytical Sensitivity: You should determine the LoD of the device utilizing the entire test system from sample preparation to detection. It is recommended to spike inactivated virus (e.g., irradiated virus) into real clinical matrix (e.g., nasal or nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid, sputum, etc.) for LoD determination. The use of recombinant antigen is not recommended for the LoD determination. It is recommended that test developers test a 2-3 fold dilution series of 3-5 replicates per concentration, and then confirm the final concentration with 20 replicates. FDA defines LoD as the lowest concentration at which 19 of 20 replicates are positive. If multiple matrices are intended for clinical testing, test developers should submit the results from one representative of each claimed clinical matrix to FDA. For example, if testing respiratory specimens (e.g., sputum, BAL, NP swabs, etc.), please submit results from one upper respiratory matrix and one lower respiratory matrix. The most challenging matrix of the claimed matrices should be tested. FDA considers NP swabs with and without your claimed viral transport media (VTM) to be the most challenging upper respiratory matrix and sputum to be the most challenging lower respiratory matrix, as applicable. If claiming other specimen types (saliva, blood, etc.), we recommend that you establish your LoD in each matrix, with and without transport media, as applicable. If needed, we recommend that you follow the most current version of the CLSI standard, “Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures (CLSI EP17).”**

***\[Please describe your LoD study, the specific viral material used to assess the LoD (e.g., irradiated virus),*** ***and the LoD (with appropriate units) for your assay. Please provide the line data for the LoD study as part of your submission.\]***

LoD studies determine the lowest detectable concentration of SARS-CoV-2 at which approximately 95% of all (true positive) replicates test positive. The LoD was determined by limiting dilution studies using characterized ***\[please described samples used in the study, e.g. viral stocks\]***.

***\[List/describe the following in this section:***

-   ***Titers and strains of the SARS-CoV-2 stocks used for the LoD study and how the organism stocks were prepared and how the titers were determined.***

-   ***The dilution factor and number of serial dilutions of the characterized SARS-CoV-2 that were tested to determine the LoD.\]***

Serial dilutions of the characterized SARS-CoV-2 were then tested in ***\[number of replicates\]*** replicates. The lowest concentration at which all ***\[number of replicates\]*** replicates were positive was treated as the tentative LoD for each test. The LoD of each test was then confirmed by testing ***\[number of replicates (at least 20 recommended)\]*** with concentrations at the tentative limit of detection. The final LoD of each test was determined to be the lowest concentration resulting in positive detection of ***\[number of positive replicates (at least 19 out of 20 replicates)\]. \[Include analysis of LoD results, indicating the final LoD for each test.\]***

2.  **Cross-reactivity (Analytical Specificity): Cross-reactivity studies are performed to demonstrate that the test does not react with related pathogens, high prevalence disease agents, and normal or pathogenic flora that are reasonably likely to be encountered in the clinical specimen. We recommend that the organisms in the table below are wet-tested in negative clinical matrix; please contact FDA if you are unable to obtain specific organisms to discuss potential options and labeling mitigations. If multiple matrices are claimed, the most challenging should be used for cross-reactivity testing. For wet testing, concentrations of 10^6^ CFU/ml or higher for bacteria and 10^5^ pfu/ml or higher for viruses is recommended.**

**Recommended List of Organisms for Respiratory Specimens**

| **Other high priority pathogens from the same genetic family** | **High priority organisms likely in the circulating area** |
|------------------------------------|------------------------------------|
| **Human coronavirus 229E (Wet-testing)** | **Adenovirus (e.g. C1 Ad. 71) (Wet-testing)** |
| **Human coronavirus OC43 (Wet-testing)** | **Human Metapneumovirus (hMPV) (Wet-testing)** |
| **Human coronavirus NL63 (Wet-testing)** | **Parainfluenza virus 1-4 (Wet-testing)** |
| **MERS-coronavirus (Wet-testing)** | **Influenza A & B (Wet-testing)** |
| **SARS-coronavirus (Wet-testing)** | **Enterovirus (Wet-testing)** |
| **Human coronavirus HKU1 (In-silico (protein blast))** | **Respiratory syncytial virus (Wet-testing)** |
|  | **Rhinovirus (Wet-testing)** |
|  | ***Haemophilus influenzae* (Wet-testing)** |
|  | ***Streptococcus pneumoniae* (Wet-testing)** |
|  | ***Streptococcus pyogenes* (Wet-testing)** |
|  | ***Candida albicans* (Wet-testing)** |
|  | **Pooled human nasal wash – *representative of normal respiratory microbial flora* (Wet-testing)** |
|  | ***Bordetella pertussis* (Wet-testing)** |
|  | ***Mycoplasma pneumoniae* (Wet-testing)** |
|  | ***Chlamydia pneumoniae* (Wet-testing)** |
|  | ***Legionella pneumophila* (Wet-testing)** |
|  | ***Staphylococcus aureus* (Wet-testing)** |
|  | ***Staphylococcus epidermidis* (Wet-testing)** |
|  | ***Mycobacterium tuberculosis* (In-silico (protein blast))** |
|  | ***Pneumocystis jirovecii* (PJP) (In-silico (protein blast))** |
||

**Recommended List of Organisms for Blood Specimens**

| **Other high priority pathogens from the same genetic family** | **High priority organisms likely in the circulating area** |
|------------------------------------|------------------------------------|
| **Human coronavirus 229E (Wet-testing)** | **Cytomegalovirus (CMV) (Wet-testing)** |
| **Human coronavirus OC43 (Wet-testing)** | **Epstein-Barr Virus (EBV) (Wet-testing)** |
| **Human coronavirus NL63 (Wet-testing)** | **Varicella Zoster Virus (VZV) (Wet-testing)** |
| **MERS-coronavirus (Wet-testing)** | **Parvovirus B19 (Wet-testing)** |
| **SARS-coronavirus (Wet-testing)** | **Human Immunodeficiency Virus – 1 (HIV-1) (Wet-testing)** |
| **Human coronavirus HKU1 (In-silico (protein blast))** | **Human Immunodeficiency Virus – 2 (HIV-2) (Wet-testing)** |
|  | **Hepatitis C Virus (HCV) (Wet-testing)** |
|  | **Hepatitis B Virus (HBV) (Wet-testing)** |
|  | **Herpes Simplex Virus-1 (HSV-1) (Wet-testing)** |
|  | **Herpes Simplex Virus-2 (HSV-2) (Wet-testing)** |
|  | ***Escherichia coli* (Wet-testing)** |
|  | ***Streptococcus pneumoniae* (Wet-testing)** |
|  | ***Streptococcus pyogenes* (Wet-testing)** |
|  | ***Staphylococcus aureus* (Wet-testing)** |
|  | ***Staphylococcus epidermidis* (Wet-testing)** |
||

3.  ***Microbial Interference Studies: If cross-reactivity is not observed between your assay and any of the microorganisms listed above, you should conduct a microbial interference study. A microbial interference study demonstrates that false negatives will not occur when SARS-CoV-2 is present in a specimen with other microorganisms. You should prepare contrived specimens in your most challenging claimed matrix with SARS-CoV-2 and common organisms found in that matrix. You should provide a list of common pathogens or commensal organisms for your most challenging matrix as part of your submission.***

***If applicable, microbial interference should be evaluated using samples spiked at a low (3x LoD) SARS-CoV-2 concentration and a high interferent level (preferably microorganisms), to represent the worst-case scenario, with a minimum of 3 replicates. The interferent microorganisms can be tested individually or as a pool (of 4-5); each microorganism should be tested individually if that pool shows interference. If you plan to claim both upper and lower respiratory matrices, the study should be performed in the most challenging respiratory matrix (i.e., sputum). If interference is observed at the level tested, an additional titration study should be performed to determine the highest microorganism interferent level your test can tolerate.***

4.  ***Endogenous Interference Substances Studies***: ***The extent of testing for endogenous interference substances depends on the matrix that is claimed for the device, as well as on the technology of the device. For respiratory specimens, please test the following substances listed in the table below with inactivated virus at 3xLoD.***

| **Substance**                     | **Concentration** |
|-----------------------------------|-------------------|
| Whole Blood                       | 4%                |
| Mucin                             | 0.5%              |
| Chloraseptic (Menthol/Benzocaine) | 1.5 mg/mL         |
| Naso GEL (NeilMed)                | 5% v/v            |
| CVS Nasal Drops (Phenylephrine)   | 15% v/v           |
| Afrin (Oxymetazoline)             | 15% v/v           |
| CVS Nasal Spray (Cromolyn)        | 15% v/v           |
| Zicam                             | 5% v/v            |
| Homeopathic (Alkalol)             | 1:10 dilution     |
| Sore Throat Phenol Spray          | 15% v/v           |
| Tobramycin                        | 4 μg/mL           |
| Mupirocin                         | 10 mg/mL          |
| Fluticasone Propionate            | 5% v/v            |
| Tamiflu (Oseltamivir Phosphate)   | 5 mg/mL           |
||

5.  ***High-dose Hook Effect*: *A high-dose hook effect refers to the false negative result which can be seen when very high levels of target are present in a tested sample. We recommend you conduct studies to evaluate if a hook effect occurs by testing increasing antigen concentrations and, if applicable, indicate the concentration which begins to affect assay performance.***

6.  ***Specimen Stability: Testing should be conducted to demonstrate specimen stability throughout the real-world conditions in which they are collected and tested, according to your instructions for use. When the test is intended to be performed on the specimen immediately or shortly after obtaining the specimen, specimen stability testing could be relatively short (i.e., 2 hours at room temperature) and conducted with contrived specimens at 3xLoD using inactivated virus. If you intend to test retrospective clinical specimens that have been frozen, you should also conduct fresh versus frozen studies to support use of these specimens.***

7.  ***Clinical Evaluation: Use of natural clinical specimens is needed for the clinical evaluation. You should not use contrived clinical specimens as FDA believes they are inadequate to support the clinical performance of a test of this type. You should confirm the performance of your assay by testing a minimum of 30 positive specimens and 30 negative specimens in a randomized blinded fashion. We recommend only using an EUA test with high sensitivity and reverse transcription polymerase chain reaction (RT-PCR), which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction) as the comparator method. The comparator method should be one of the more sensitive RT-PCR assays authorized by FDA. We encourage you to review the results from the FDA SARS-CoV-2 Reference Panel available [here](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data) when selecting your comparator method; we strongly recommend you contact us to discuss your choice of comparator assay.***

***Specimens may be prospectively or retrospectively collected. For prospective specimen collection, patients should be sequentially enrolled and tested blindly. Please contact us to discuss any proposed enrichment strategies. We believe it may be appropriate to use retrospective clinical specimens, but they should be randomized with negative specimens and tested blindly. Retrospective specimens should be reflective of the natural distribution of SARS-CoV-2 viral loads, and approximately 10-20% of the clinical specimens should be low positives (i.e., RT-PCR Ct counts &gt;30), as has been observed in other sequentially enrolled clinical studies. Please note that FDA has observed erroneous results in association with clinical specimens stored in transport media. Therefore, if you validate your assay using 30 positive and 30 negative retrospective specimens in transport media, you should also present the results from at least five positive clinical specimens that are prospectively collected and processed directly without transport media. The remainder of the 30 positive clinical specimens tested directly could potentially be provided post-authorization and incorporated as a condition of authorization. When collecting specimens, the standard of care specimen should be collected first. Swabs taken from the same anatomical area for the comparator and subject device (e.g., nasal swabs, oropharyngeal (OP) swabs, etc.) should be randomized to ensure that bias is not introduced due to an unequal distribution of viral materials. When two distinct anatomical sites are being assessed, FDA does not believe it is necessary to randomize specimen collection order (e.g., saliva compared to NP swabs).***

***If you intend to seek a claim for saliva, oral fluid, blood, or other specimen types, you should test at least 30 positive specimens with paired polymerase chain reaction (PCR) results from an NP swab.***

***\[When you describe your clinical study please indicate/include:***

1.  ***Clinical study protocol, including collection and testing sites, number of samples collected, and number of operators used to run your assay***

2.  ***Enrollment criteria (inclusion/exclusion criteria)***

3.  ***The name of the comparator assay***

4.  ***How the samples were collected or sourced***

5.  ***Please describe the total number of samples tested. If the study was not a prospective study, please also list the numbers of prospective, and/or retrospective tested by each category.***

6.  ***The sample matrix(ces) tested***

7.  ***The technique and collection device(s), including transport media, used to obtain clinical samples. All clinical specimens tested in your study should be evaluated in accordance with your proposed diagnostic algorithm, including retesting when appropriate.***

8.  ***The conditions used to collect and store specimens***

***Please provide the study data in an Excel file as part of the EUA submission for each specimen. The study data should include the following:***

-   ***Specimen type for the antigen test***

-   ***Specimen collection date and time for the antigen test***

-   ***Specimen testing date and time for the antigen test***

-   ***VTM type, as applicable, for the antigen test and PCR***

-   ***Antigen test result with the analyzer or reader value***

-   ***Specimen type for RT-PCR***

-   ***Specimen collection date and time for RT-PCR test***

-   ***Specimen testing date and time for RT-PCR test***

-   ***Name of RT-PCR used as the comparator***

-   ***RT-PCR test results (+/-)***

-   ***RT-PCR test value results (Ct values)***

-   ***Number of days post-onset of patient symptoms***

-   ***Patient age and gender, if available***

***For clinical specimens collected to support the EUA request, you must adhere to all applicable rules of human subject protection, including IRB approval consistent with 21 CFR part 50 and 21 CFR 56.103(a). Use of leftover de-identified samples may follow the policy outlined in the FDA Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable (<https://www.fda.gov/media/122648/download>).***

**Tests should demonstrate a minimum sensitivity of ≥ 80% for all sample types submitted.**

***Strategies for serial testing with less sensitive tests, such as 70% sensitivity, could increase overall sensitivity and be considered cumulatively rather than based on one-time testing. If you are proposing serial testing as a mitigation for a less sensitive assay, you should provide supportive evidence documenting clinical performance ≥ 80% sensitivity with serial testing. You should provide detailed instructions for conducting serial testing in your package insert, including a recommended testing interval, that is supported by your clinical data. You should also discuss how you will ensure compliance with serial testing post-authorization, such as multi-test packs, software applications, or other mitigations. Additional post-authorization studies may be necessary to assess the success of your proposed mitigations.***

8.  ***Studies to support a POC claim, as applicable: \[If the device is intended for near patient or POC testing, please provide data to demonstrate that non-laboratory personnel can perform the test accurately in the intended use environment (i.e. a non-laboratorian healthcare provider accuracy study). Please also provide data to demonstrate robust use of your device for POC patient testing (e.g., as applicable, studies to demonstrate the impact of adding different volumes of sample, different volumes of reagents, incorrect order of sample or reagent application, etc.).\] ***

    1.  ***POC Clinical Evaluation: A POC clinical evaluation should include 5-6 minimally trained operators at 1-2 non-laboratory (e.g., CLIA waived) sites in the United States. Each operator should test at least three positive and three negative specimens using only the test instructions and/or quick reference guide. As part of the EUA application, provide the detailed individual replicate result data and protocols for each of your studies, including:***

        -   ***The objective of the study***

        -   ***Detailed test procedure***

        -   ***Materials used***

        -   ***A list of samples tested***

        -   ***Results (presented in tabular format), including invalid results***

        -   ***Conclusions***

        -   ***Mitigation*** ***measures, if required (e.g., labeling changes, changes to test design, etc.)***

***You should also conduct testing with samples prepared with SARS-CoV-2 viral load near the LoD of your assay in clinical matrix. The testing should be conducted by minimally trained operators, and should consist of 10 low positives (&lt;2xLoD) and 10 negative specimens per site. All contrived specimens should be blinded and randomized and each operator should test at least three low positive and three negative specimens. These specimens are intended to supplement, not replace, the clinical specimens in your study.***

***All testing should be conducted in a blinded fashion in which patients with an unknown SARS-CoV-2 status are presented to minimally trained operators. We recommend only using a high sensitivity EUA RT-PCR test that uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction) as the comparator method.*** ***The comparator method should be one of the more sensitive RT-PCR assays authorized by FDA. We encourage you to review the results from the FDA SARS-CoV-2 Reference Panel available [here](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data) when selecting your comparator method; please contact us to discuss your choice of comparator assay. Ideally, patients should be prospectively enrolled and tested sequentially and blindly. It may be acceptable to use retrospective clinical specimens (e.g., leftover specimens in VTM), provided they are randomized with negative specimens and tested blindly. Retrospective specimens should be reflective of the natural distribution of SARS-CoV-2 viral loads, and approximately 10-20% of the clinical specimens should be low positives (i.e., RT-PCR Ct counts &gt;30) as has been observed in other sequentially enrolled clinical studies. Please note that FDA has observed erroneous results in association with clinical specimens stored in transport media. Therefore, if you validate your assay using retrospective specimens in transport media, you should also present the results from at least five positive clinical specimens that are prospectively collected and processed directly without transport media. The remainder of the 30 positive clinical specimens tested directly can be provided post-authorization and incorporated as a condition of authorization.***

***When collecting specimens for the investigational device and the comparator method, the standard of care specimen should be collected first, so as not to compromise the medical care of the patient. After the standard of care specimen has been collected, swabs taken from the same area for the comparator and subject device (e.g., nasal swabs, OP swabs, etc.) should have their order of collection randomized to ensure that bias is not introduced due to an unequal distribution of viral materials. Randomizing order of collection when two distinct anatomical sites are being assessed may not be needed (e.g., saliva compared to NP swabs).***

***Your study data should be presented in an Excel file and include the same data elements outlined in item 7 above.***

2.  ***POC Flex Studies: You should also conduct a thorough hazard analysis considering the main known sources of errors. Based upon your hazard analysis, you should conduct flex studies to evaluate the impact of errors, or out-of-specifications conditions, on the assay performance. Each sample should be prepared at 2xLoD in negative clinical matrix and should be evaluated in three replicates for each condition under evaluation. Flex studies can be conducted with trained operators at an internal testing site. Each study should be performed using a pre-defined study protocol that includes the following:***

    -   ***The objective of the study***

    -   ***Detailed test procedure***

    -   ***Materials used***

***Potential stress conditions include:***

-   ***40°C and 95% room humidity (RH) (mimicking hot and humid climates)***

-   ***Delay in sample testing or reading time***

-   ***Delay and/or disturbance in operational steps***

-   ***Sample volume variability***

-   ***Buffer volume variability***

-   ***Other, as appropriate***

***Please see Appendix A for more in-depth flex study designs. Alternative sources of information on flex studies that may be appropriate for your device can be found on the FDA CDRH website containing [CLIA Waiver by Application Decision Summaries](https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries).***[11]

9.  ***Studies to support asymptomatic claim, as applicable: If you seek authorization for screening individuals without symptoms or other reasons to suspect COVID-19, FDA recommends that you conduct a clinical study in the intended population. In the clinical study, you should compare results from your assay and a comparator assay for each patient enrolled. In addition to the clinical study recommendations listed above, you should enroll at least 20 positive asymptomatic individuals to collect unique specimens. It may also be acceptable to present the results from 10 positive specimens from asymptomatic individuals to support EUA authorization, provided data from symptomatic individuals are also submitted and analysis of cycle threshold (Ct) values demonstrates reasonably similar distribution of viral loads. The remainder of the 20 positive clinical specimens collected from unique asymptomatic individuals can be provided post-authorization and incorporated as a condition of authorization. Ideally, the specimens should be sequentially collected in a blinded fashion, and therefore, the total sample size of your study will depend on the prevalence of SARS-CoV-2 in your study population. You can also consider use of an enrichment strategy, in which individuals with a known COVID-19 infection status are invited to participate in your clinical validation study. If using an enrichment strategy, you should carefully consider how you will randomize and blind operators to the participant’s infection status and minimize potential bias. As discussed previously, FDA anticipates that any data from an enriched study design will also represent the full range of viral loads, with both low and high positives specimens included in the study data. It may also be possible to use archived specimens. Please contact FDA to discuss any alternative study designs.***

10.  ***Studies to support multi-analyte respiratory panels under EUA: To support an EUA for a multi-analyte respiratory panel, analytical and clinical evaluations for each target analyte should be provided. The validation needed to support an EUA may vary if the test platform was previously cleared by FDA, as noted below. The following analytical studies should be conducted, and data provided to the FDA for review:***

-   ***Limit of Detection (Analytical Sensitivity)***

-   ***Cross-Reactivity / Microbial Interference***

-   ***Inclusivity / Analytical Reactivity, when different strains become available***

-   ***Co-infection (Competitive Interference)***

-   ***Interfering Substances Study (Endogenous and Exogenous)***

-   ***Clinical Specimen Stability***

-   ***Reagent Stability testing protocol***

-   ***Carry over/Cross-Contamination\****

-   ***Reproducibility and Repeatability\****

- ***Fresh vs. Frozen - If you intend to submit data collected from testing archived frozen specimens in support of your EUA, please conduct an analytical study to demonstrate that preservation of samples (e.g., by freezing at ≤-70°C) does not affect the accuracy of test results compared to freshly collected samples.***

***\* Recommended for new instruments not previously reviewed by the FDA. If the instrument was previously reviewed by FDA, please identify the submission number.***

***For multiplex devices that include Influenza A and/or Influenza B, you should establish the LoD on at least two strains of Influenza A and Influenza B. We recommend using the H12009 and H3N2 for Influenza A and the Yamagata and Victoria lineages for Influenza B.***

***Clinical Performance: To evaluate the clinical performance of your multi-analyte test, a prospective clinical study should be conducted. Considering the public health needs in the current emergency, a clinical performance study in support of the EUA submission may be conducted at one site testing positive and negative clinical samples with known specimen types. Retrospective clinical specimens can be used, however, your positive samples should include results from an EUA RT-PCR device for COVID-19, or an FDA cleared RT-PCR device in which 10-20% of the specimens are low positive samples (Ct value &gt; 30).***

***If your device has not been previously FDA-cleared for influenza or other respiratory pathogens, FDA generally intends to include a condition of authorization that you will conduct a post EUA prospective clinical study. The prospective clinical study should include a minimum of three sample collection sites and three testing sites, prospectively enrolling patients with general respiratory symptoms. You may consider conducting a prospective clinical study in the Southern Hemisphere during their typical influenza/respiratory season to increase the likelihood of obtaining a sufficient number of positive samples (e.g., for influenza at least 50 positive Flu A and 30 positive Flu B samples) in a timely fashion.***

***If your device has been previously FDA-cleared for influenza or other respiratory pathogens, you should confirm that the LoD for the previously cleared pathogens is unchanged due to the modification by conducting side-by-side testing of 3-5 replicates of serially diluted viruses with the original and modified versions of your device. You should also test at least 10 retrospective positive clinical specimens of each previously cleared analyte. You should perform a competitive inhibition study with clinically relevant titers of each analyte in the panel (viruses 10^5^ PFU/mL, bacteria 10^6^ CFU/mL).***

***All multiplex devices that include Influenza A and B should also verify the analytical reactivity of the device against the Centers for Disease Control and Prevention (CDC) human influenza panel to ensure adequate performance against currently circulating strains of influenza. Information on how to request this panel can be found at CDC’s “[Request for CDC Influenza Virus Panel” website](https://www.cdc.gov/flu/dxfluviruspanel/index.htm).***[12]

### K.  UNMET NEED ADDRESSED BY THE PRODUCT

**This section will be completed by FDA.**

### L.  APPROVED/CLEARED ALTERNATIVE PRODUCTS

Currently no methods for the detection of the SARS-CoV-2 have been approved/ cleared by FDA.

### M.  BENEFITS AND RISKS:

**This section will be completed by FDA.**

### N.  FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:

***\[You should include proposed Fact Sheets for Patients and Healthcare Providers\]* S*ee examples for authorized EUA tests on our website. During review, FDA will make available Fact Sheet templates.***

### O.  INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:

***\[You should include Instructions for Use, Box Labels, Vial Labels, and any other proposed labeling.\]***

### P. RECORD KEEPING AND REPORTING INFORMATION TO FDA:

***\[Test Developer name\]*** will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report on adverse events, and this website is referenced in the Fact Sheet for Health Care providers as well as through the ***\[Test Developer name\]*** Product Support website: ***\[Include link to Test Developer’s Website\].*** Each report of an adverse event will be processed according to ***\[Test Developer name\]***’s Non-Conformance Reporting Requirements, and Medical Device Reports will be filed with the FDA as required. Through a process of inventory control, ***\[Test Developer name\]*** will also maintain records of device usage/purchase. ***\[Test Developer name\]*** will collect information on the performance of the test, and report to FDA any suspected occurrence of false positive or false negative results of which ***\[Test Developer name\]*** becomes aware. ***\[Test Developer name\]*** will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

### Appendix A: Sample Flex Study Design Details.

1.  **Delay in Reading Time: We recommend evaluating test results at reading times four times below and three times above the recommended reading time. For example, for a test where the recommended read time is 20 minutes, reading time times would be performed to evaluate at least read times of 5, 10, 15, 20, 30, and 60 minutes.**

2.  **Specimen Volume Variability: We recommend evaluating test results at specimen volumes two times below and two times above the recommended specimen volume, and the maximum possible added. For example, for a test where the recommended specimen volume is 10 µL, specimen volume testing should be performed to evaluate at least specimen volumes of 5, 10, 20 µL, and maximum volume. If incorrect results are observed at either 5 or 20 µL, additional testing at 7.5 and/or 15 uL may be needed. The diluent/buffer amount added should be that specified in the instructions for use.**

3.  **Buffer Volume Variability: We recommend evaluating test results at diluent/buffer volumes at two times below and two times above the recommended diluent/buffer volume and the maximum volume. For example, for a test where the recommended buffer/diluent volume is 2 drops, sample diluent volume testing would be performed to evaluate at least sample diluent volumes of 1, 2, 3, 4 drops, and whole bottle. The sample volume added should be that specified in the instructions for use.**

4.  **Temperature and Humidity: We recommend evaluating test results at temperature and humidity extremes that are likely to occur in the United States. For example, 40°C and 95% RH, mimicking hot and humid climates, and 5°C and 5% RH, mimicking cold and dry climates.**

5.  **Disturbance during analysis: We recommend evaluating the effect on expected test results of moving the device while the test is running, such as dropping/moving the test, unplugging the test, receiving a phone call while the mobile app is running, etc.**

[1] This template is part of the “[Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised),” available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[2] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[3] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities>.

[4] All templates can be accessed at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.

[5] Available at <https://www.fda.gov/medical-devices/postmarket-requirements-devices/quality-system-qs-regulationmedical-device-good-manufacturing-practices>.

[6] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissions-software-contained-medical-devices>.

[7] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-principles-software-validation>.

[8] Available at <https://www.fda.gov/medical-devices/digital-health-center-excellence/device-software-functions-including-mobile-medical-applications>.

[9] Available at <https://www.fda.gov/medical-devices/digital-health/cybersecurity>.

[10] Available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices#:~:text=Off%2Dthe%2Dshelf%20(OTS,to%20run%20device%2Dspecific%20functions](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices#:~:text=Off%2Dthe%2Dshelf%20(OTS,to%20run%20device%2Dspecific%20functions.).

[11] Available at <https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries>*.*

[12] Available at <https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries> *(last accessed on September 22, 20209). Note this website is not controlled by FDA.*


# 967  2021-03-13_FDA Fact Sheet - Screening for COVID-19 Deciding Which Test to Use When Establishing Testing Programs.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-03-13_FDA Fact Sheet - Screening for COVID-19 Deciding Which Test to Use When Establishing Testing Programs.md
file_date: 2021-03-13
title: FDA Fact Sheet - Screening for COVID-19 Deciding Which Test to Use When Establishing Testing Programs
category: regulatory
subcategory: fda-policy
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pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-03-13_FDA%20Fact%20Sheet%20-%20Screening%20for%20COVID-19%20Deciding%20Which%20Test%20to%20Use%20When%20Establishing%20Testing%20Programs.pdf
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notes: 
summary_short: The FDA fact sheet “Screening for COVID-19: Deciding Which Test to Use When Establishing Testing Programs” explains how screening of asymptomatic individuals differs from diagnostic testing and why tests have specific authorized use claims. It provides practical guidance for schools, workplaces, and communities on selecting tests, including considerations around sensitivity, turnaround time, pooling, serial testing, and interpreting presumptive negative results. It is useful for designing screening programs that align test performance with public health goals and mitigation strategies.


CONTENT

***INTERNAL TITLE:*** FDA FACT SHEET

## Screening for COVID-19: Deciding Which Test to Use When Establishing Testing Programs

### How is screening different from diagnostic testing?
- **Diagnostic testing:** Diagnostic testing identifies current infection at the individual level and is performed when a person has signs or symptoms of infection, or when a person is asymptomatic but has recent known or suspected exposure. Most tests the FDA has authorized are for diagnosing SARS-CoV-2 in people suspected of COVID-19 by their health care provider, whether or not they are symptomatic. Some diagnostic tests are authorized for use only in symptomatic individuals.
- **Screening testing:** Screening testing looks for individual infections in a group even if there is no reason to suspect those individuals are infected. Screening involves testing asymptomatic individuals who do not have known or suspected exposure to COVID-19 in order to make individual decisions based on the test results. The FDA has authorized some tests for screening.

### Why are there different claims for how a test is used?
Test developers decide the use they will seek to have authorized by the FDA. The FDA cannot compel developers to create tests, and the FDA does not decide the type of test, the use, or the price of tests that developers request to be authorized.

Test developers gather evidence to support their test's use and submit this evidence to the FDA. When the FDA issues an emergency use authorization (EUA) for a test, it means that the FDA reviewed scientific and clinical evidence to determine that the test may be effective when used as authorized, such as to diagnose individuals with SARS-CoV-2.

If the data provided for FDA review demonstrate that the test may be effective for testing certain individuals (e.g., individuals suspected of COVID-19) but is not effective for testing others (e.g., all individuals), the FDA generally includes an explicit limitation in the labeling regarding those other individuals. So, for tests authorized for use on a specific population (e.g., individuals suspected of COVID-19), the lack of a limitation in the labeling regarding use on other populations generally means that evidence to support a broader use (e.g., testing all individuals) was not provided to the FDA for review.

This should be considered by health care providers who choose to order authorized tests for individuals who fall outside the test authorization.

### How does one set up a screening program?
Schools, workplaces, communities, and others looking to establish testing programs to screen asymptomatic individuals without known or suspected exposure are using various options, including:

1. Using a test authorized for screening.
2. Health care providers on behalf of the program ordering an authorized diagnostic test for screening.
   - When using a test that is not specifically authorized for screening, it is particularly important to understand what you know and don't know about the test's performance and combine it with other strategies, taking the following into consideration:
     - Consider using a highly sensitive authorized test, especially if rapid turnaround times are available. If highly sensitive authorized tests are not feasible, or if turnaround times are prolonged, consider using a less sensitive authorized point-of-care test, such as an antigen test.
     - Consider using a pooling strategy to conserve testing supplies. Several tests have been authorized for pooling.
     - Consider frequent serial testing, such as the repeated use of rapid point-of-care or at-home tests for self-testing at a predetermined testing interval.
     - Negative results should be considered as "presumptive negative," and health care providers should consider them in the context of clinical observations, patient history, and epidemiological information. If there is a concern that an individual with a negative antigen, other point-of-care or at-home test result may have COVID-19 (e.g., because of a new outbreak in a congregate setting), consider retesting the individual with a highly sensitive authorized molecular test.

Regardless of the test selected, it's important to monitor for updates from the FDA or the test developer for new information regarding the performance of the selected test with emerging mutations of the virus in your community. It is important to note that testing, even serial testing, is of limited value if it is not combined with appropriate mitigations for individuals who test positive (such as quarantine), good contact tracing, and effective behavioral protocols (such as mask wearing, hand washing and social distancing), even for individuals who test negative.

---

*The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, and products that give off electronic radiation, and for regulating tobacco products.*


# 1,998  2021-03-16_FDA Template - Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing.md
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file_date: 2021-03-16
title: FDA Template - Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing
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summary_short: The FDA “Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing” outlines recommended data and labeling elements to support EUA requests for screening claims that rely on serial testing rather than pre-authorization asymptomatic studies. It specifies expected serial testing intervals (typically twice over 2–3 days, 24–36 hours apart), clinical performance expectations (including PPA thresholds and confidence intervals for POC/at-home tests), and how these recommendations supplement the primary molecular/antigen EUA templates. It also describes likely post-authorization study conditions to establish asymptomatic performance and how results could affect continued authorization.


CONTENT

***INTERNAL TITLE:*** Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing

This template provides the Food and Drug Administration’s (FDA) current recommendations concerning what data and information should be submitted to FDA in support of a pre-Emergency Use Authorization (EUA) submission/EUA request for a molecular or antigen diagnostic test for SARS-CoV-2 used for screening with serial testing.

As outlined in Sections V.A. and V.B. of the FDA guidance document: [*Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised),[2] FDA recommends certain validation studies be conducted for a SARS-CoV-2 molecular or antigen diagnostic assay. The [EUA Templates](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates)[3] are intended to help test developers provide validation data and other information to FDA, but alternative approaches can be used. Current templates for molecular and antigen diagnostic tests include recommendations that the developer provide validation data on asymptomatic individuals prior to authorization of a screening claim, including when using a serial testing approach. This template is intended to provide supplemental recommendations for developers of molecular and antigen tests seeking claims for screening with serial testing without studying asymptomatic individuals prior to authorization, including for point-of-care (POC) and at-home tests.

It reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should* means that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/media/97321/download).[4]

## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by test developers (sponsor) as applicable to their specific test. Text in **bold** outlines the FDA’s additional recommendations for the sponsors’ consideration when completing the suggested information in each section.

-   This template should be used by developers of molecular or antigen diagnostic tests, for use in serial testing programs as well as tests for serial at-home[5] use by individuals separate from a testing program, including to support authorization for over-the-counter use, intended to detect SARS-CoV-2 from individuals with or without symptoms or other epidemiological reasons to suspect COVID-19 infection.

-   The information in this template does not reflect complete validation data or information that FDA recommends be included in a pre-EUA submission/EUA request; it supplements the recommendations in the Molecular Diagnostic Template for Commercial Manufacturers, Antigen Template for Test Developers, and Template for Manufacturers of Molecular and Antigen Diagnostic COVID-19 Tests for Non-Laboratory Use, all available for download from FDA’s website.[6] Test developers should use one of these referenced templates as their primary template and incorporate information from this supplemental template as applicable.

-   A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   This is an EUA interactive review template for Pre-EUA submissions/EUA requests. We plan to update the template as appropriate as we learn more about the COVID-19 disease and gain experience with the EUA process for these kinds of tests.


## EXAMPLE TEMPLATE:

**\[Note: This is intended to provide information to supplement completion of the EUA template most appropriate for your test type. This is not a complete template.\]**

**The supplemental information included in this template is for test developers of molecular or antigen tests interested in offering their test for screening (i.e., testing individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection) with serial testing prior to conducting the asymptomatic validation studies recommended in the corresponding EUA template(s). We note that these recommendations will generally not be applicable to developers with tests for which data has already demonstrated poor performance (e.g., less than 80% PPA) for testing asymptomatic individuals.**

### A. PROPOSED INTENDED USE

**FDA recommends including the following in the requested intended use:**

**\[…*****individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection, when tested twice over two (or three) days with at least 24 hours (and no more than 36 hours) between tests.\]***

**Alternative testing intervals, such as testing every 3 days or testing twice a week (such as Monday/Thursday or Tuesday/Friday), may be considered for molecular or antigen tests intended for use as part of a testing program.**

**A weekly testing interval may be considered for higher sensitivity molecular tests.**

### B. CLINICAL PERFORMANCE EVALUATION

**FDA recommends following the recommendations for clinical performance evaluation in the appropriate EUA template, except we are including information below for test developers seeking a screening claim (i.e., testing of individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection) with serial testing who have conducted the clinical evaluation with symptomatic patients suspected of COVID-19 infection by their healthcare providers. For a screening claim with serial testing, FDA would generally expect labeling to indicate that testing be done twice over two (or three) days with at least 24 hours (and no more than 36 hours) between tests. Alternative testing intervals may be considered for molecular or antigen tests intended for use as part of a testing program, as discussed above.**

**In such circumstances, the developer should generally follow the clinical performance evaluation recommendations in the corresponding molecular or antigen template for validation with symptomatic individuals or individuals otherwise suspected of COVID-19 infection by their healthcare providers.  Additionally, for POC and at-home tests, including OTC tests, FDA would consider authorizing tests with a positive percent agreement (PPA) of at least 80% with 70% at the lower bound of the two-sided 95% confidence interval.**

**As discussed in the Antigen Template for Test Developers, strategies for serial testing with less sensitive tests (i.e., PPA &lt;80%) may be able to be support authorization; however, clinical evaluation in an asymptomatic population would generally be expected prior to authorization of a screening claim, including for OTC use, for such tests.**

**When FDA authorizes a test for screening with serial testing, but the clinical validation does not include any or the recommended total number of asymptomatic individuals, FDA generally intends to include a condition of authorization in the letter of authorization that the developer conduct a study to establish performance with asymptomatic individuals within a pre-specified timeframe. A study protocol for the post-authorization study, generally including at least 20 positive asymptomatic individuals, should be agreed upon with FDA prior to study initiation. If the post-authorization study is not completed within the agreed upon timeframe or does not demonstrate adequate performance in asymptomatic individuals, FDA would consider taking additional actions as appropriate under section 564 of the FD&C Act, including revoking or revising the authorization to remove any intended use(s) that is not adequately supported.**

### C. INSTRUCTIONS FOR USE/PROPOSED LABELING/PACKAGE INSERT:

**Proposed labeling should clearly identify the population in which the test’s performance has been validated, and clearly identify any populations included in the intended use for which the test’s performance has not yet been established and will be established during the above referenced post-authorization study.**

[1] This template is part of the “[Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised)”, available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[2] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[3] All EUA templates can be found at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.

[4] Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities.

[5] At-home tests are tests labeled for self-testing in any environment outside a clinical laboratory setting, professional healthcare facility, or point-of-care patient care setting operating under a Clinical Laboratory Improvement Amendments (CLIA) certificate. This includes but is not limited to homes, outdoor environments, office environments, schools, vehicles, emergency shelters, and independent living retirement homes.  If the test is intended to be used in a clinical laboratory setting, professional healthcare facility, or patient care setting operating under a CLIA certificate and also outside those facilities, it meets this definition.

[6] All EUA templates can be found at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.


# 955  2021-03-16_FDA Website - FDA takes steps to streamline path for COVID-19 screening tools.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-03-16_FDA Website - FDA takes steps to streamline path for COVID-19 screening tools.md
file_date: 2021-03-16
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web_url: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-steps-streamline-path-covid-19-screening-tools-provides
summary_short: The FDA takes steps to streamline the path for COVID-19 screening tools announces a March 16, 2021 policy to accelerate EUAs for tests used in serial screening of asymptomatic individuals. It outlines a new supplemental EUA template allowing certain molecular, antigen, and at-home tests to be authorized for screening and OTC use based on strong symptomatic performance combined with serial testing. The update also provides guidance to schools, workplaces, and communities on selecting appropriate tests for screening programs.


CONTENT

Coronavirus (COVID-19) Update: FDA takes steps to streamline path for COVID-19 screening tools, provides information to help groups establishing testing programs

The following is attributed to Jeff Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health, and Tim Stenzel, M.D., Ph.D., director of the Office of In Vitro Diagnostics in the Center for Devices and Radiological Health

For Immediate Release:
March 16, 2021
Statement From:
Jeff Shuren, M.D., J.D.
Director - CDRH Offices: Office of the Center Director

Testing remains an important cornerstone of our nation’s fight against COVID-19. This includes schools, workplaces, communities and other locations using testing to screen asymptomatic individuals who may still spread the virus. Screening involves testing asymptomatic individuals who do not have known or suspected exposure to COVID-19 in order to make individual decisions, such as whether an individual should participate in an activity, based on the test results.  

Today, we are providing information for test developers about a streamlined path to emergency use authorization for these important screening tools as well as information to help these groups as they set up testing programs. Our actions complement those taken by the Centers for Disease Control and Prevention (CDC) and are not intended to replace CDC’s testing or other public health guidance.

First, the FDA issued a [new supplemental template](https://www.fda.gov/media/146695/download) for test developers seeking emergency use authorization (EUA) of certain tests for screening with serial testing. Serial testing involves testing the same individual multiple times within a few days, and can increase chances of detecting asymptomatic infection that might not always show up with a single test. CDC recommends serial testing at least once per week, along with other mitigation measures, such as masking and social distancing, to reduce disease transmission. This template applies to developers of molecular and antigen tests, for use in serial testing programs, as well as at-home tests for use in a serial manner outside of a testing program, intended to detect SARS-CoV-2 from individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection. This includes tests conducted in any location, including in a laboratory, at the point-of-care (POC), or even places such as a person’s home or certain non-traditional sites such as offices, sporting venues, airports, schools, etc.

We believe this effort will pave the way for further expanding the availability of tests authorized for screening asymptomatic individuals, help bolster existing and new testing programs and increase consumer access to testing.

As part of this new template for test developers, the agency provided recommendations aimed to streamline the authorization of screening tests with serial testing. The recommendations apply to test developers who seek an EUA from the FDA for certain screening tests prior to conducting certain performance evaluations with asymptomatic individuals. For example, in certain circumstances, a POC test or an at-home test could be authorized for over-the-counter (OTC) use without the need for validating its use in asymptomatic individuals prior to authorization. The FDA believes that evidence of a test’s strong performance in symptomatic patients combined with serial testing can mitigate the risk of false results when testing asymptomatic individuals. 

Additionally, today the FDA issued a fact sheet that outlines considerations for selecting a test for use in a screening testing program. The fact sheet will help schools, workplaces, communities and other locations as they are selecting a test for screening and help them understand the difference between tests used for diagnosis of suspected COVID-19 compared to those used for screening asymptomatic individuals.

This information we’re providing will be helpful to groups as they set up testing programs. We believe these combined efforts will further expand the availability of tests authorized for screening asymptomatic individuals, including OTC use, help bolster existing and new testing programs and increase consumer access to testing.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation and for regulating tobacco products.

Related Information
[Emergency Use Authorization Supplemental Template](https://www.fda.gov/media/146695/download)
[Fact Sheet](https://www.fda.gov/about-fda/page-not-found)
[FAQs on Testing for SARS-CoV-2](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/faqs-testing-sars-cov-2)


# 2,458  2021-04-20_FDA Fact Sheet - Sample Updated Fact Sheet for Health Care Providers.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-04-20_FDA Fact Sheet - Sample Updated Fact Sheet for Health Care Providers.md
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notes: 
summary_short: The FDA “Sample Updated Fact Sheet for Health Care Providers” is a fill-in template that EUA test sponsors use to communicate authorized use, specimen types, and key interpretation guidance for a COVID-19 diagnostic test. It provides standardized language on what positive and negative results mean (including limitations for asymptomatic and pooled testing), biosafety and specimen handling considerations, EUA status, and reporting requirements. It helps ensure consistent, compliant provider-facing instructions and risk/benefit disclosures across EUA-authorized tests.


CONTENT

***INTERNAL TITLE:*** FACT SHEET FOR HEALTHCARE PROVIDERS
**COMPANY/LAB NAME**  
**Month DD, YYYY**  
**DEVICE/TEST NAME**  

**Coronavirus Disease 2019 (COVID-19)**

This Fact Sheet informs you of the significant known and potential risks and benefits of the emergency use of the DEVICE/TEST NAME.

The DEVICE/TEST NAME is authorized for use with specific respiratory (and/or salvia) specimens collected from individuals consistent with the Emergency Use Authorization (EUA).

All patients whose specimens are tested with this assay will receive the Fact Sheet for Patients: COMPANY/LAB NAME - DEVICE/TEST NAME.

This test is to be performed only using specific respiratory (and/or salvia) specimens collected from individuals consistent with the Emergency Use Authorization (EUA).

## What are the symptoms of COVID-19?
Many patients with COVID-19 have developed fever and/or symptoms of acute respiratory illness (e.g., cough, dyspnea), although some individuals experience only mild symptoms or no symptoms at all. The current information available to characterize the spectrum of clinical illness associated with COVID-19 suggests that, when present, symptoms include cough, shortness of breath or dyspnea, fever, chills, myalgias, headache, sore throat, new loss of taste or smell, nausea or vomiting or diarrhea. Signs and symptoms may appear any time from 2 to 14 days after exposure to the virus, and the median time to symptom onset is approximately 5 days. For further information on the symptoms of COVID-19 please see the link provided in "Where can I go for updates and more information?" section.

Public health officials have identified cases of COVID-19 infection throughout the world, including the United States. Please check the CDC COVID-19 webpage (see link provided in "Where can I go for updates and more information?" section at the end of this document) or your local jurisdictions website for the most up to date information.

## What do I need to know about COVID-19 testing?
Current information on COVID-19 for healthcare providers is available at CDC's webpage, Information for Healthcare Professionals (see links provided in "Where can I go for updates and more information?" section).

- The DEVICE/TEST NAME can be used to test LIST ALL SPECIMEN TYPES CLAIMED.
- The DEVICE/TEST NAME should be ordered for the detection of COVID-19 in individuals who INDICATION STATEMENT.
- THIS IS EXAMPLE BULLET FOR TESTS THAT ARE AUTHORIZED WITH HOME COLLECTION KITS: The DEVICE/TEST NAME can be used to test individual nasal swab specimens that are self-collected at home or in a healthcare setting by individuals using an authorized home-collection kit when determined to be appropriate by a healthcare provider.
- INCLUDE YOUR SAMPLE POOLING INDICATION HERE: The DEVICE/TEST NAME can also be used to test up to [INCLUDE INDICATION BASED ON THE EXHIBIT YOU ARE CLAIMING].
- The DEVICE/TEST NAME is authorized for use in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet requirements to perform [high / high or moderate / high, moderate or waived] complexity tests.

Specimens should be collected with appropriate infection control precautions. Current guidance is available at the CDC's website (see links provided in "Where can I go for updates and more information?" section).

When collecting and handling specimens from individuals suspected of being infected with COVID-19, appropriate personal protective equipment should be used as outlined in the CDC Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19). For additional information, refer to CDC Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under Investigation (PUIs) for Coronavirus Disease 2019 (COVID-19) (see links provided in "Where can I go for updates and more information?" section).

## What does it mean if the specimen tests positive for the virus that causes COVID-19?
A positive test result for COVID-19 indicates that RNA from SARS-CoV-2 was detected, and therefore the patient is infected with the virus and presumed to be contagious. Laboratory test results should always be considered in the context of clinical observations and epidemiological data (such as local prevalence rates and current outbreak/epicenter locations) in making a final diagnosis and patient management decisions. Patient management should be made by a healthcare provider and follow current CDC guidelines.

The DEVICE/TEST NAME has been designed to minimize the likelihood of false positive test results. However, it is still possible that this test can give a false positive result, even when used in locations where the prevalence is below 5%. In the event of a false positive result, risks to patients could include the following: a recommendation for isolation of the patient, monitoring of household or other close contacts for symptoms, patient isolation that might limit contact with family or friends and may increase contact with other potentially COVID-19 patients, limits in the ability to work, delayed diagnosis and treatment for the true infection causing the symptoms, unnecessary prescription of a treatment or therapy, or other unintended adverse effects.

Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result.

All laboratories using this test must follow the standard testing and reporting guidelines according to their appropriate public health authorities.

## What does it mean if the specimen tests negative for the virus that causes COVID-19?
A negative test result for this test means that SARS-CoV-2 RNA was not present in the specimen above the limit of detection. However, a negative result does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions. It is possible to test a person too early or too late during COVID-19 infection to make an accurate diagnosis via DEVICE/TEST NAME.

In addition, asymptomatic people infected with COVID-19 may not shed enough virus to reach the limit of detection of the test, giving a false negative result. In the absence of symptoms, it is difficult to determine if asymptomatic people have been tested too late or too early. Therefore, negative results in asymptomatic individuals may include individuals who were tested too early and may become positive later, individuals who were tested too late and may have serological evidence of infection, or individuals who were never infected.

Specimens with low viral loads may not be detected in sample pools due to the decreased sensitivity or increased interference of pooled testing. Your interpretation of negative results should take into account clinical and epidemiological risk factors.

When diagnostic testing is negative, the possibility of a false negative result should be considered in the context of a patient's recent exposures and the presence of clinical signs and symptoms consistent with COVID-19. The possibility of a false negative result should especially be considered if the patient's recent exposures or clinical presentation indicate that COVID-19 is likely, and diagnostic tests for other causes of illness (e.g., other respiratory illness) are negative.

If COVID-19 is suspected based on exposure history together with other clinical findings, re-testing using a new sample with a sensitive method or without pooling should be considered by healthcare providers in consultation with public health authorities. Additional testing may be helpful to ensure testing was not conducted too early.

Risks to a patient of a false negative test result include: delayed or lack of supportive treatment, lack of monitoring of infected individuals and their household or other close contacts for symptoms resulting in increased risk of spread of COVID-19 within the community, or other unintended adverse events.

The performance of this test was established based on the evaluation of a limited number of clinical specimens. The clinical performance has not been established in all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.

## What is an EUA?
The United States FDA has made this test available under an emergency access mechanism called an Emergency Use Authorization (EUA). The EUA is supported by the Secretary of Health and Human Service's (HHS's) declaration that circumstances exist to justify the emergency use of in vitro diagnostics (IVDs) for the detection and/or diagnosis of the virus that causes COVID-19.

An IVD made available under an EUA has not undergone the same type of review as an FDA-approved or cleared IVD. FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, available alternatives, and based on the totality of scientific evidence available, it is reasonable to believe that this IVD may be effective in diagnosing COVID-19.

The EUA for this test is in effect for the duration of the COVID-19 declaration justifying emergency use of IVDs, unless terminated or revoked (after which the test may no longer be used).

## What are the approved available alternatives?
Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here: https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases. A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available. FDA has issued EUAs for other tests that can be found at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.

## Where can I go for updates and more information?
### CDC webpages:
- General: https://www.cdc.gov/COVID19
- Symptoms: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html
- Healthcare Professionals: https://www.cdc.gov/coronavirus/2019-nCoV/guidance-hcp.html
- Information for Laboratories: https://www.cdc.gov/coronavirus/2019-nCoV/guidance-laboratories.html
- Laboratory Biosafety: https://www.cdc.gov/coronavirus/2019-nCoV/lab-biosafety-guidelines.html
- Isolation Precautions in Healthcare Settings: https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html
- Specimen Collection: https://www.cdc.gov/coronavirus/2019-nCoV/guidelines-clinical-specimens.html
- Infection Control: https://www.cdc.gov/coronavirus/2019-ncov/infection-control/index.html

### FDA webpages:
- General: www.fda.gov/novelcoronavirus
- EUAs: (includes links to patient fact sheet and manufacturer's instructions) https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas

### COMPANY/LAB NAME:
COMPANY/LAB NAME  
ADDRESS LINE 1  
ADDRESS LINE 2  

**Customer Support:**  
+1 800 XXX-XXXX  
customersupportemail@company.com

**Technical Support:**  
+1 800 XXX-XXXX  
techsupportemail@company.com

---

*Report Adverse events, including problems with test performance or results, to MedWatch by submitting the online FDA Form 3500 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home) or by calling 1-800-FDA-1088*


# 1,652  2021-04-20_FDA Fact Sheet - Sample Updated Fact Sheet for Patients.md
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tokens: 1652
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notes: 
summary_short: The FDA “Sample Updated Fact Sheet for Patients” is a standardized, fill-in template that EUA test sponsors provide to individuals whose samples were tested for COVID-19 with an authorized device. It explains what the test is, why someone may be tested (including serial and pooled testing), and what positive or negative results mean, including the risks of false positives/negatives and recommended follow-up actions. It supports clear patient-facing communication of EUA status, benefits/limitations, and where to find additional public health guidance.


CONTENT

***INTERNAL TITLE:*** FACT SHEET FOR PATIENTS
**COMPANY/LAB NAME**  
**Month, DD, YYYY**  
**DEVICE/TEST NAME**  

**Coronavirus Disease 2019 (COVID-19)**

You are being given this Fact Sheet because your sample(s) was tested for the Coronavirus Disease 2019 (COVID-19) using the DEVICE/TEST NAME.

This Fact Sheet contains information to help you understand the risks and benefits of using this test for the diagnosis of COVID-19. After reading this Fact Sheet, if you have questions or would like to discuss the information provided, please talk to your healthcare provider.

For the most up to date information on COVID-19 please visit the CDC Coronavirus Disease 2019 (COVID-19) webpage: https://www.cdc.gov/COVID19

## What is COVID-19?
COVID-19 is caused by the SARS-CoV-2 virus which is a new virus in humans causing a contagious respiratory illness. COVID-19 can present with a mild to severe illness, although some people infected with COVID-19 may have no symptoms at all. Older adults and people of any age who have underlying medical conditions have a higher risk of severe illness from COVID-19. Serious outcomes of COVID-19 include hospitalization and death. The SARS-CoV-2 virus can be spread to others not just while one is sick, but even before a person shows signs or symptoms of being sick (e.g., fever, coughing, difficulty breathing, etc.). A full list of symptoms of COVID-19 can be found at the following link: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.

## What is the DEVICE/TEST NAME?
The test is designed to detect the virus that causes COVID-19 in respiratory specimens, for example nasal or oral swabs – depending on device.

## Why was my sample tested?
You were tested because your healthcare provider believes you may have been exposed to the virus that causes COVID-19 based on your signs and symptoms (e.g., fever, cough, difficulty breathing), and/or because:
- You are being tested at regular intervals (serial testing) even though you do not have symptoms or risk factors for COVID-19; or
- You live in or have recently traveled to a place where transmission of COVID-19 is known to occur, and/or
- You have been in close contact with an individual suspected of or confirmed to have COVID-19.
- You and your healthcare provider believe there is another reason to investigate your COVID-19 infection status.

Testing of the samples will help find out if you may have COVID-19.

Laboratories may use pooling when testing your specimen, which means they combine your sample with other individuals samples prior to testing and test them as a "pool". The laboratory may return a result for the entire pool together or may return individual results.

## What are the known and potential risks and benefits of the test?
Potential risks include:
- Possible discomfort or other complications that can happen during sample collection.
- Possible incorrect test result (see below for more information).

Potential benefits include:
- The results, along with other information, can help your healthcare provider make informed recommendations about your care.
- The results of this test may help limit the spread of COVID-19 to your family and those you come in contact with.

## What does it mean if I have a positive test result?
If you have a positive test result, it is very likely that you have COVID-19. Therefore, it is also likely that you may be placed in isolation to avoid spreading the virus to others. You should follow CDC guidance to reduce the potential transmission of disease.

If you were tested as part of a pool that returned a positive or invalid test result, you may have COVID-19 and should consider yourself to have a positive test result unless or until you receive a negative test result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, you should isolate until receiving a negative result when re-tested individually and should not be grouped with other individuals who have received a positive or presumptive positive result.

There is a smaller possibility that this test can give a positive result that is wrong (a false positive result) particularly when used in a population without many cases of COVID-19 infection. Your healthcare provider will work with you to determine how best to care for you based on the test results along with medical history, and your symptoms

## What does it mean if I have a negative test result?
A negative test result means that the virus that causes COVID-19 was not found in your sample.

However, it is possible for this test to give a negative result that is incorrect (false negative) in some people with COVID-19. You might test negative if the sample was collected early during your infection. You could also be exposed to COVID-19 after your sample was collected and then have become infected.

In particular, people infected with COVID-19 but who have no symptoms may not shed enough virus to trigger a positive test. This means that you could possibly still have COVID-19 even though the test result is negative. If your test is negative, your healthcare provider will consider the test result together with all other aspects of your medical history (such as symptoms, possible exposures, and geographical location of places you have recently traveled) in deciding how to care for you.

If your test result indicates your specimen was pooled and you have a negative test result there a small chance that your result is incorrect. You should talk with your healthcare provider if you are concerned.

If you have no symptoms but have been tested because your doctor thought you may have been exposed to COVID-19, you should continue to monitor your health and let your healthcare provider know if you develop any symptoms of COVID-19. If you develop symptoms you may need another test to determine if you have contracted the virus causing COVID-19.

If you develop symptoms or your symptoms get worse you should seek medical care. If you have the following symptoms you should seek immediate medical care at the closest emergency room:
- Trouble breathing
- Persistent pain or pressure in the chest
- New confusion
- Inability to wake up or stay awake
- Bluish lips or face

It is important that you work with your healthcare provider to help you understand the next steps you should take.

## Is this test FDA-approved or cleared?
No. This test is not yet approved or cleared by the United States FDA. FDA may issue an Emergency Use Authorization (EUA) when certain criteria are met, which includes that there are no adequate, approved, available alternatives. The EUA for this test is supported by the Secretary of Health and Human Service's (HHS's) declaration that circumstances exist to justify the emergency use of in vitro diagnostics for the detection and/or diagnosis of the virus that causes COVID-19. This EUA will remain in effect (meaning this test can be used) for the duration of the COVID-19 declaration justifying emergency of IVDs, unless it is terminated or revoked by FDA (after which the test may no longer be used).

## What are the approved alternatives?
Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here: https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases. A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available. FDA has issued EUAs for other tests that can be found at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization

---

Where can I go for updates and more information? The most up-to-date information on COVID-19 is available at the CDC General webpage: https://www.cdc.gov/COVID19. In addition, please also contact your healthcare provider with any questions/concerns.


# 10,719  2021-04-20_FDA Letter - Amendment Letter.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-04-20_FDA Letter - Amendment Letter.md
file_date: 2021-04-20
title: FDA Letter - Amendment Letter
category: regulatory
subcategory: fda-policy
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pdf_gdrive_url: https://drive.google.com/file/d/1j5PHj5Ukp0M4RfIlJL03CkOGzitr2_gY
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-04-20_FDA%20Letter%20-%20Amendment%20Letter.pdf
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notes: 
summary_short: The FDA “Amendment Letter” (April 20, 2021) authorizes certain EUA RT-PCR molecular tests to add screening indications using pooled anterior nasal specimens when deployed in serial testing programs (typically at least weekly), with appendices specifying pooling type (swab vs. media) and maximum pool sizes (e.g., up to 3, 5, or 10). It defines eligibility criteria for which EUAs can be amended, the required validation/notification package for inclusion on FDA’s Exhibit 1 list, and detailed conditions for developers and CLIA high-complexity laboratories (including follow-up for positive/invalid pools, reporting language, and positivity-rate monitoring). It also prescribes required updates to provider and patient fact sheets to address presumptive positives from pools and the limitations of negative results in asymptomatic and pooled testing.


CONTENT

April 20, 2021

To: Developers of Molecular-Based Diagnostic Tests Authorized for Emergency Use for Coronavirus Disease 2019 (COVID-19) as of Today’s Date

Re: Amending Certain EUAs for RT-PCR Molecular-Based Diagnostic Tests to Authorize the Detection of Nucleic Acid from SARS-CoV-2 from Pooled Anterior Nasal Respiratory Specimens for Screening When Used as Part of a Serial Testing Program

On February 4, 2020, pursuant to Section 564(b)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 360bbb-3(c)), the Secretary of the Department of Health and Human Services (HHS) determined that there is a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad, and that involves the virus that causes COVID-19. Pursuant to Section 564 of the Act, and on the basis of such determination, the Secretary of HHS then declared that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the virus that causes COVID-19 subject to the terms of any authorization issued under Section 564(a) of the Act.¹

On April 20, 2021, pursuant to Section 564 of the Act, in response to public health needs to expand the nation’s testing capacity,² FDA is issuing this letter to authorize additional indications for EUAs that are within the Scope of this Amendment (Section II). For such indications, use is limited to laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meet requirements to perform high complexity tests, except that tests authorized for use in specific named or designated high complexity laboratories can only be used in such laboratories.

As set forth throughout, this authorization amends certain EUAs to authorize the tests for additional indications for use. There are multiple indications for use in the appendices but they all contain these essential elements: tests with EUAs that are amended by this letter are authorized for use with pooled anterior nasal specimens for screening (i.e., testing individuals without symptoms or other epidemiological reasons to suspect COVID-19) when used as part of a serial testing program. This means that tests with EUAs that are amended by this authorization may be used with pooled anterior nasal respiratory specimens from individuals without known or suspected COVID-19 when such individuals are tested as part of a testing program that includes testing at regular intervals, at least once per week, such as those implemented by schools, workplaces and community groups. The indications in each appendix (A-H) differ in the number of specimens that can be pooled (i.e., up to 3, up to 5, or up to 10) and the type of pooling that can be done (i.e., media or swab pooling). Tests with EUAs that are amended by this authorization will be added to Exhibit 1, annotated with the authorized indication(s) for each test, which will be maintained on FDA’s webpage.³ FDA’s determination that the indications added by this amendment meet the criteria for issuance under section 564(c) of Act is based on the available scientific evidence, including recent studies involving antigen tests used in a serial manner, knowledge of recently authorized antigen and molecular tests, as well as our experience with SARS-CoV-2 tests over the past year.

Having concluded, based on the available scientific evidence, that the criteria for issuance of this authorization under Section 564(c) of the Act are met, I am authorizing the emergency use of the tests identified in the Scope of this Amendment (Section II) and subject to the Conditions of Authorization (Section IV), for use in laboratories certified under the CLIA, 42 U.S.C. § 263a, that meet the requirements to perform high complexity tests to detect SARS-CoV-2 in anterior nasal respiratory specimens from individuals, except that tests authorized for use in specific named or designated high complexity laboratories can only be used in such laboratories.⁴

## I. Criteria for Issuance of Authorization
I have concluded that the emergency use of the authorized tests meets the criteria for issuance of an authorization under Section 564(c) of the Act, because I have concluded that:

1. The SARS-CoV-2 can cause a serious or life-threatening disease or condition, including severe respiratory illness, to humans infected by this virus;

2. Based on the totality of scientific evidence available to FDA, it is reasonable to believe that the authorized tests may be effective in diagnosing COVID-19 for the indications set forth in the appendices, and that the known and potential benefits of the authorized tests when used for such use, outweigh the known and potential risks of the authorized tests; and

3. There are no adequate, approved, and available alternatives to the emergency use of the authorized tests.⁵

## II. Scope of this Amendment
I have concluded, pursuant to Section 564(d)(1) of the Act, that the scope of this amendment is limited to authorized tests identified below for the additional indications for use⁶ given in the applicable appendix(es) for use in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meet requirements to perform high complexity tests, except that tests authorized for use in specific named or designated high complexity laboratories can only be used in such laboratories.

### Authorized Tests
The emergency use authorization (EUA) of a molecular diagnostic SARS-CoV-2 test is amended consistent with this letter where:

1. The test is an RT-PCR test authorized under an EUA specific to that test as of today’s date for the qualitative detection of SARS-CoV-2 in respiratory specimens collected by anterior nasal swabs, with a PPA ≥ 95% based on validation with positive patient specimens as stated in the test’s authorized labeling;

2. The test as authorized is designed to detect two or more viral targets on the SARS-CoV-2 genome;

3. The test as authorized includes a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction);

4. The test is authorized for detecting only SARS-CoV-2;

5. Prior to notification pursuant to Condition of Authorization C of this letter, either validation data has not been submitted to FDA for testing pooled specimens, or such validation data has been submitted to FDA and FDA authorized the test for testing pooled specimens⁷; and

6. Prior to notification pursuant to Condition of Authorization C of this letter, either validation data has not been submitted to FDA for testing specimens from asymptomatic individuals, or such validation data has been submitted to FDA and FDA authorized the test for screening (i.e., testing individuals without symptoms or other reasons to suspect COVID-19).⁸

As set forth in Condition of Authorization A of this letter, and notwithstanding other statements and conditions concerning authorized labeling in the EUAs being amended, developers must make the following changes to the test’s authorized labeling before distributing or using the test for any indication added by this authorization:

- Update your Instructions for Use and/or laboratory procedure to add the following language: 
  - The following indication is authorized under the Pooling and Serial Testing Amendment [include link to this letter] for use in [laboratories certified under CLIA to perform high complexity tests] OR [for tests authorized for use in specific named or designated high complexity laboratories, insert the language included under “Authorized Laboratories” in your EUA]: [insert indication from applicable appendix]
  - This indication is authorized with the following validated protocol: [insert the relevant validated protocol for testing with pooled specimens that meets Condition of Authorization D]; and
- Update your Fact Sheet for Health Care Providers and Fact Sheet for Patients with the relevant additional information set forth in Appendix I.

This labeling will be added to FDA’s webpage and posted with the EUA being amended after it is submitted to FDA per the process outlined below.

A test may not be distributed or used for any additional indications authorized by this letter until the pooling protocol for that indication is validated in accordance with the applicable appendix and the required notification is submitted and confirmed to be complete by FDA in accordance with Condition of Authorization C of this letter.

Tests limited for use at specific named or designated laboratories that are not authorized to be distributed per the EUA being amended continue to be authorized for use only in those laboratories and not for distribution even if the EUAs are amended as set forth in this authorization.

### Addition to Exhibit 1
An EUA that meets the above will be added to Exhibit 1 after FDA confirms that the required documentation set forth below has been submitted to FDA. At that time, FDA will notify the developer of the inclusion of its test(s) in Exhibit 1 by replying to the email. Please note that being added to Exhibit 1 does not necessarily mean that FDA has reviewed the underlying validation data submitted or confirmed that the test is appropriately validated. Instead, being added to Exhibit 1 only means that the developer has submitted complete documentation. FDA may revise or revoke an EUA under certain circumstances, such as when there are concerns with the test’s performance.

As set forth in Condition of Authorization C of this letter, developers must notify FDA by sending a message to FDA with the subject line “Addition to Exhibit 1 of the Pooling and Serial Testing Amendment” to CDRH-EUA-Templates@fda.hhs.gov with the information below before the test can be distributed (if authorized to be distributed per the EUA being amended) and used for the additional indication(s):

- Developer (company) name
- Contact individual’s name, address, phone number, email address
- Test name
- EUA# and link to the EUA being amended
- The specific new indication(s), referenced by noting the applicable appendix
- The required validation data as set forth in the applicable appendices
- Revised (redline and final) labeling as set forth above and required by Condition of Authorization A
- The following information on testing capacity:
  1. The number of individual tests that can be run with normal operation in a 24-hour period;
  2. The number of patient samples that can be tested in a 24-hour period if all samples are pooled at the maximum ratio permitted by the additional indication(s) added by this amendment; and
  3. For distributed test kits, the number of laboratories in the United States with the required platforms installed.
- Statement certifying that the six criteria above are met, no changes have been made to the authorized test other than to add the indication(s) for use set forth in the applicable appendix, no changes have been made to the authorized labeling other than those required by this amendment, and that all information submitted is truthful and accurate, for example:
  - I certify that, in my capacity as [the position held in company] of [company name], I believe to the best of my knowledge that all six criteria described in this amendment have been met, no changes have been made to the authorized test other than to add the indication(s) for use set forth in the applicable appendix(ces), no changes have been made to the authorized labeling other than those required by this amendment, and that all data and information I am submitting are truthful and accurate and no material fact has been omitted.

Authorized tests are qualitative tests for the detection of nucleic acid from SARS-CoV-2 in anterior nasal respiratory specimens from individuals without symptoms or other reasons to suspect COVID-19, when tested with pooled testing at least once per week as part of a serial testing program, as set forth in the applicable appendix.

Negative results from pooled testing should not be treated as definitive. If a patient’s clinical signs and symptoms are inconsistent with a negative result or results are necessary for patient management, then the patient should be considered for individual testing. Specimens included in pools with a positive or invalid result must be reported as presumptive positive or tested individually prior to reporting a result. Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result. Specimens with low viral loads may not be detected with pooled testing due to decreased sensitivity or increased interference from pooled testing.

For serial testing programs, additional confirmatory testing for negative results may be necessary, if there is a high likelihood of COVID-19, such as an individual with a close contact with COVID-19 or with suspected exposure to COVID-19 or in communities with high prevalence of infection. Additional confirmatory testing for positive results may also be necessary, if there is a low likelihood of COVID-19, such as in individuals without known exposure to COVID-19 or residing in communities with low prevalence of infection.

The above described tests, with the authorized labeling provided as set forth in the Scope of this Amendment (Section II) and subject to the Conditions of Authorization (Section IV) of this letter, are authorized to be distributed (if previously authorized to be distributed per the underlying EUA) and used in accordance with the Scope of this Amendment (Section II) and the Conditions of Authorization (Section IV), despite the fact that such tests do not meet certain requirements otherwise required by applicable federal law.

I have concluded, pursuant to Section 564(d)(2) of the Act, that it is reasonable to believe that the known and potential benefits of the authorized tests, when used consistent with the Scope of this Amendment (Section II), outweigh the known and potential risks of such authorized tests.

I have concluded, pursuant to Section 564(d)(3) of the Act, based on the totality of scientific evidence available to FDA, that it is reasonable to believe that the authorized tests may be effective in diagnosing COVID-19 as set forth in Section I of this letter, when used consistent with the Scope of this Amendment (Section II), pursuant to Section 564(c)(2)(A) of the Act.

FDA has reviewed the scientific information available to FDA, including the information supporting the conclusions described in Section I above, and concludes that the authorized tests (as described in the Scope of this Amendment (Section II)) meet the criteria set forth in Section 564(c) of the Act concerning safety and potential effectiveness.

The emergency use of the authorized tests under this amendment must be consistent with, and may not exceed the terms of this letter, including the Scope of this Amendment (Section II) and the Conditions of Authorization (Section IV). Subject to the terms of this amendment and under the circumstances set forth in the Secretary of HHS’s determination under Section 564(b)(1)(C) described above and the Secretary of HHS’s corresponding declaration under Section 564(b)(1), the authorized tests are authorized for the additional indications set forth in the applicable appendix.

## III. Waiver of Certain Requirements
This amendment does not change the waiver of any requirements included in the EUAs being amended.

## IV. Conditions of Authorization
Pursuant to Section 564(e) of the Act, I am establishing the conditions below, which are specific to the indications added by this amendment for which developers intend to distribute or use their test. The conditions in the EUAs being amended continue to apply to all authorized indications for use, including any indications added by this amendment for which developers intend to distribute or use their test.

### Developer (You)
A. You must update your labeling in accordance with Section II of this letter.

B. You must provide any authorized distributor(s) with a copy of this amendment and its authorized accompanying materials (e.g., Fact Sheets).

C. In order for your test to be distributed (if authorized to be distributed per the underlying EUA) and used for any of the indications authorized by this letter, you must first validate your test in accordance with the requirements in the applicable appendix and notify FDA by submitting the information set forth in Section II to FDA at [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) using the subject line “Addition to Exhibit 1 of the Pooling and Serial Testing Amendment”.

D. You must have a pooling protocol that includes instructions for follow-up for positive and invalid pools, including follow-up instructions to be provided to the organizer of the testing program. For media pooling, the instructions for follow up for positive and invalid pools must include deconvoluting to retest individual samples. For swab pooling, the instructions for follow up for positive and invalid pools must include reporting as “presumed positive” unless or until the individual is re-tested individually and must include instructions to collect a new specimen to be tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, the instructions must indicate that such individuals should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result.

E. You must immediately cease distribution and use of your test for an indication added by this amendment upon written notification by FDA that the test has not been validated for that indication in accordance with the applicable requirements, and must notify authorized laboratories to which your test has been distributed that they must immediately cease use of your test for that indication. You must also relabel any tests that have been distributed for that indication to no longer include such indication.

F. If, prior to the date of this letter, your test was not authorized for screening (i.e., testing individuals without symptoms or other reasons to suspect COVID-19), you must further evaluate the clinical performance of your test to support the serial testing claim in an FDA agreed upon post authorization clinical evaluation study within 6 months of submitting the notification pursuant to Condition C of this letter (unless otherwise agreed to with DMD/OHT7-OIR/OPEQ/CDRH). Results from this study must be submitted to FDA at [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov). After FDA concurs with the data, you must update your authorized labeling to reflect the additional testing. Such labeling updates must be made only after concurrence by DMD/OHT7-OIR/OPEQ/CDRH. If FDA does not concur with the results from the study, then you must cease distributing or using the test for screening and relabel such tests that have already been distributed to reflect this change.

### Authorized Laboratories
G. Authorized laboratories that use a test that has been amended by this letter must notify the relevant public health authorities of their intent to run the authorized test for the new indication(s) set forth in this amendment prior to initiating testing.

H. Authorized laboratories testing pooled specimens with your test must include with test result reports for specific individuals whose specimen(s) were the subject of pooling, a notice that pooling was used during testing and that “Individual specimens with low viral loads may not be detected due to the decreased sensitivity or increased interference when tested with pooled testing.”

I. Authorized laboratories must follow your pooling protocol that includes instructions for follow up for positive and invalid pools, including follow-up instructions to be provided to the organizer of the testing program. For media pooling, the instructions for follow up for positive and invalid pools must include deconvoluting to retest individual samples. For swab pooling, the instructions for follow up for positive and invalid pools must include reporting as “presumed positive” unless or until the individual is re-tested individually and must include instructions to collect a new specimen to be tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, the instructions must indicate that such individuals should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result.

J. Authorized laboratories testing pooled specimens with your test must include with test result reports for specific individuals whose specimen(s) were the subject of pooling, a notice that their test result is “presumed positive” unless or until they are re-tested individually if the pool in which they were included returns a positive or invalid result. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, the report must include instructions to collect a new specimen to be tested individually and must indicate that such individuals should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result.

K. Authorized laboratories testing specimens using pooled testing with your test must monitor the positivity rate of the specimens tested using pooled testing by calculating the percent positive results using a moving average (such as a rolling average updated daily using data from the previous 7-10 days).

L. Authorized laboratories must keep records of specimen pooling test result data, daily testing totals including number of pooled test results, number of individuals tested and daily running average of percent positive results. For the first 12 months from the date of their creation, such records must be made available to FDA upon request within 48 business hours for inspection. After 12 months from the date of their creation, upon FDA request, such records must be made available for inspection within a reasonable time.

Sincerely,

RADM Denise M. Hinton  
Chief Scientist  
Food and Drug Administration

Enclosures

## Appendix A
### Swab pooling up to n=3
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication without needing additional validation and may be distributed (if previously authorized for distribution per the EUA being amended) and used for this indication after a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing up to 3 individual human anterior nasal swabs placed in a single vial containing transport media after being collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week as part of a serial testing program.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

## Appendix B
### Swab pooling up to n=5
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication and may be distributed (if previously authorized for distribution per the EUA being amended) and used for this indication after validation is completed as set forth in this Appendix and a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing up to 5 individual human anterior nasal swabs placed in a single vial containing transport media after being collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19, when tested as part of a serial testing program including testing at least once per week.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

Validation for this indication includes both validation protocols outlined below, “Validation of Expected Limit of Detection (LoD)” and “Validation of High Viral Concentrations”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. **Validation of Expected Limit of Detection (LoD)**

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your IFU or procedure for testing 5-swab pools.

   To generate a 5-swab pool positive for SARS-CoV-2, prepare a single positive swab by spiking a known amount of inactivated virus or quantified positive patient sample onto the swab prior to immersion in the volume of transport media you intend to include in your IFU or procedure for 5-swab pooling. The remaining four swabs added to transport media should only contain negative patient clinical matrix. The final concentration of the transport media must be approximately 3x the LoD of your previously authorized assay. To ensure this concentration is achieved, factor in how much volume the swab absorbs, and the SARS-CoV-2 concentration needed on the single positive swab to achieve a final concentration of approximately 3x the LoD in the transport media. This is the concentration you should use to prepare the positive swabs for your validation study.

   Test at least 20 independent extraction replicates of individual swabs in the same volume of buffer used in the LoD study as described in your authorized test’s IFU or procedure, using the testing protocol in your authorized test’s IFU or procedure. Test 20 paired 5-swab pools in parallel, each containing a single positive swab and 4 individual negative swabs in the volume of transport media you intend to include in your IFU or procedure for testing 5-swab pools, using the testing protocol you intend to include in your IFU or procedure for testing 5-swab pools.

   Your validation must demonstrate that:

   - ≥95% of pooled replicates are detected as positive using the swab pooling protocol;
   - The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

2. **Validation of High Viral Concentrations**

   Prepare three swabs simulating high viral concentrations by spiking 10^6 copies/mL of inactivated virus or quantified positive patient sample. Test 10 replicates of viral transport material containing the three spiked positive swabs and 2 individual negative swabs in the volume of transport media you intend to include in your IFU or procedure for testing 5-swab pools, using the testing protocol you intend to include in your IFU or procedure for testing 5-swab pools.

   Your validation must demonstrate that:

   - All 10 replicates are detected as positive; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix C
### Swab pooling up to n=10
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication and may be distributed (if previously authorized for distribution per the underlying EUA) and used for this indication after validation is completed as set forth in this Appendix and a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing up to 10 individual human anterior nasal swabs placed in a single vial containing transport media after being collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19, when tested as part of a serial testing program including testing at least once per week.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

Validation for this indication includes both validation protocols outlined below, “Validation of Expected Limit of Detection (LoD)” and “Validation of High Viral Concentrations”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. **Validation of Expected Limit of Detection (LoD)**

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your IFU or procedure for testing 10-swab pools.

   To generate a 10-swab pool positive for SARS-CoV-2, prepare a single positive swab by spiking a known amount of inactivated virus or quantified positive patient sample onto the swab prior to immersion in the volume of transport media you intend to include in your IFU or procedure for 10-swab pooling. The remaining four swabs added to transport media should only contain negative patient clinical matrix. The final concentration of the transport media must be approximately 3x the LoD of your previously authorized assay. To ensure this concentration is achieved, factor in how much volume the swab absorbs, and the SARS-CoV-2 concentration needed on the single positive swab to achieve a final concentration of approximately 3x the LoD in the transport media. This is the concentration you should use to prepare the positive swabs for your validation study.

   Test at least 20 independent extraction replicates of individual swabs in the same volume of buffer used in the LoD study as described in your authorized test’s IFU or procedure, using the testing protocol in your authorized test’s IFU or procedure. Test 20 paired 10-swab pools in parallel, each containing a single positive swab and 9 individual negative swabs in the volume of transport media you intend to include in your IFU or procedure for testing 10-swab pools, using the testing procedure you intend to include in your IFU or procedure for testing 10-swab pools.


   Your validation must demonstrate that:
- ≥95% of pooled replicates are detected as positive using the swab pooling protocol;
- The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
- The invalid rate in the swab pooling protocol does not exceed 5%.


2. **Validation of High Viral Concentrations**

   Prepare three swabs simulating high viral concentrations by spiking 10^6 copies/mL of inactivated virus or quantified positive patient sample. Test 10 replicates of viral transport material containing the three spiked positive swabs and 7 individual negative swabs in the volume of transport media you intend to include in your IFU or procedure for testing 10-swab pools, using the testing protocol you intend to include in your IFU or procedure for testing 10-swab pools.

   Your validation must demonstrate that:

   - All 10 replicates are detected as positive; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix D
### Media pooling up to n=3
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication without needing additional validation and may be distributed (if previously authorized for distribution per the underlying EUA) and used for this indication after a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing aliquots of transport media from up to 3 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials containing transport media when tested as part of a serial testing program including testing at least once per week.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

## Appendix E
### Media pooling up to n=5 – validation option 1
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication and may be distributed (if previously authorized for distribution per the underlying EUA) and used for this indication after validation is completed as set forth in this Appendix and a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing aliquots of transport media from up to 5 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials containing transport media, when tested as part of a serial testing program including testing at least once per week.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

Validation for this indication includes the validation protocol outlined below, “Validation of Expected Limit of Detection (LoD)”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. **Validation of Expected Limit of Detection (LoD)**

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your IFU or procedure for testing 5-sample pools.

   Prepare positive samples for your validation study at 5x the LoD of your previously authorized assay.

   Test at least 20 independent extraction replicates of individual samples using the testing protocol in your authorized test’s IFU or procedure. Test 20 paired 5-sample pools in parallel, each containing aliquots from a single positive sample and 4 individual negative samples, using the volumes and testing protocol you intend to include in your IFU or procedure for testing 5-sample pools.

   Your validation must demonstrate that:

   - ≥95% of pooled replicates are detected as positive using the sample pooling protocol;
   - The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix F
### Media pooling up to n=10 – validation option 1
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication and may be distributed (if previously authorized for distribution per the underlying EUA) and used for this indication after validation is completed as set forth in this Appendix and a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing aliquots of transport media from up to 10 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials containing transport media, when tested as part of a serial testing program including testing at least once per week.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

Validation for this indication includes the validation protocol outlined below, “Validation of Expected Limit of Detection (LoD)”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. **Validation of Expected Limit of Detection (LoD)**

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your IFU or procedure for testing 10-sample pools.

   Prepare positive samples for your validation study at 10x the LoD of your previously authorized assay.

   Test at least 20 independent extraction replicates of individual samples using the testing protocol in your authorized test’s IFU or procedure. Test 20 paired 10-sample pools in parallel, each containing aliquots from a single positive sample and 9 individual negative samples, using the volumes and testing protocol you intend to include in your IFU or procedure for testing 10-sample pools.

   Your validation must demonstrate that:

   - ≥95% of pooled replicates are detected as positive using the sample pooling protocol;
   - The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix G
### Media pooling up to n=5 – validation option 2
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication and may be distributed (if previously authorized for distribution per the underlying EUA) and used for this indication after validation is completed as set forth in this Appendix and a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing aliquots of transport media from up to 5 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials containing transport media, when tested as part of a serial testing program including testing at least once per week.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

Validation for this indication includes the validation protocol outlined below, “Validation of the Effect on the Percent Agreement”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. **Validation of the Effect on the Percent Agreement**

   Test at least 20 individual positive clinical specimens using the testing protocol in your authorized test’s IFU or procedure. Test 20 paired 5-sample pools in parallel, each containing aliquots from a single positive specimen and 4 randomly selected individual negative clinical specimens (collection of negative anterior nasal specimens from healthy individuals is acceptable), using the testing protocol you intend to include in your IFU or procedure for testing 5-sample pools. 

   20 unique positive specimens and 80 unique negative specimens are needed to comprise twenty 5-sample pools. At least 20% of positive clinical specimens used for this validation study should be low positives, where, for 5-sample pooling, a low positive is within 2.32 Ct of the mean Ct at LoD for your previously authorized test.

   Archived individual clinical anterior nasal specimens are acceptable for this validation study, if available, given they contain enough volume for both individual and 5-sample pool testing. If archived specimens are used, the original diagnostic results are acceptable in lieu of repeating the individual specimen testing, if the original diagnostic results were acquired according to your previously authorized test’s IFU or procedure for individual testing.

   If you cannot acquire at least 20% low positive samples as natural clinical specimens, you may dilute positive clinical specimens into pooled negative anterior nasal clinical matrix prepared as described here. Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your IFU or procedure for testing 5-sample pools.

   Your validation must demonstrate that:

   - ≥85% agreement between pooled testing and individual testing; and
   - The invalid rate in the pooling protocol does not exceed 5%.

## Appendix H
### Media pooling up to n=10 – validation option 2
Subject to the terms of this EUA, a test that is within the Scope of this Amendment (Section II) is authorized for the following additional indication and may be distributed (if previously authorized for distribution per the underlying EUA) and used for this indication after validation is completed as set forth in this Appendix and a notification has been submitted to FDA and confirmed by FDA to be complete in accordance with Condition of Authorization C of this letter:

Qualitative detection of RNA from SARS-CoV-2 in pooled samples containing aliquots of transport media from up to 10 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials containing transport media, when tested as part of a serial testing program including testing at least once per week.

This indication is authorized for use in laboratories certified under CLIA to perform high complexity tests, except that tests authorized for use in specific named or designated laboratories can only be used in such high complexity laboratories.

Tests will be added to Exhibit 1 after FDA determines it has received a complete notification.

Validation for this indication includes the validation protocol outlined below, “Validation of the Effect on the Percent Agreement”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. **Validation of the Effect on the Percent Agreement**

   Test at least 20 individual positive clinical specimens using the testing protocol in your authorized test’s IFU or procedure. Test 20 paired 10-sample pools in parallel, each containing aliquots from a single positive specimen and 9 randomly selected individual negative clinical specimens (collection of negative anterior nasal specimens from healthy individuals is acceptable), using the testing protocol you intend to include in your IFU or procedure for testing 10-sample pools.

   20 unique positive specimens and 180 unique negative specimens are needed to comprise twenty 10-sample pools. At least 20% of positive clinical specimens used for this validation study should be low positives, where, for 10-sample pooling, a low positive is within 3.32 Ct of the mean Ct at LoD for your previously authorized test.

   Archived individual clinical anterior nasal specimens are acceptable for this validation study, if available, given they contain enough volume for both individual and 10-sample pool testing. If archived specimens are used, the original diagnostic results are acceptable in lieu of repeating the individual specimen testing, if the original diagnostic results were acquired according to your previously authorized test’s IFU or procedure for individual testing.

   If you cannot acquire at least 20% low positive samples as natural clinical specimens, you may dilute positive clinical specimens into pooled negative anterior nasal clinical matrix prepared as described here. Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your IFU or procedure for testing 10-sample pools.

   Your validation must demonstrate that:

   - ≥85% agreement between pooled testing and individual testing; and
   - The invalid rate in the pooling protocol does not exceed 5%.

## Appendix I
### Required Changes to Authorized Labeling – Fact Sheets
Per Condition of Authorization A and as set forth in the Scope of this Amendment (Section II), your labeling must be updated in the following ways:

A) Fact Sheet for Healthcare Providers (a sample updated Fact Sheet for Healthcare Providers is included in Appendix J):

1) Include the additional authorized indication(s) from the applicable appendix in all places where the Fact Sheet includes the indications.

2) In the section titled “What does it mean if the specimen tests positive for the virus that causes COVID-19?” add the following paragraph immediately following the first paragraph:

   _Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result._

3) In the section titled “What does it mean if the specimen tests negative for the virus that causes COVID-19?” add the following three paragraphs immediately following the first paragraph:

   _In addition, asymptomatic people infected with COVID-19 may not shed enough virus to reach the limit of detection of the test, giving a false negative result. In the absence of symptoms, it is difficult to determine if asymptomatic people have been tested too late or too early. Therefore, negative results in asymptomatic individuals may include individuals who were tested too early and may become positive later, individuals who were tested too late and may have serological evidence of infection, or individuals who were never infected._

   _Specimens with low viral loads may not be detected in sample pools due to the decreased sensitivity or increased interference of pooled testing. Your interpretation of negative results should take into account clinical and epidemiological risk factors._

   _If COVID-19 is suspected based on exposure history together with other clinical findings, re-testing using a new sample with a sensitive method or without pooling should be considered by healthcare providers in consultation with public health authorities. Additional testing may be helpful to ensure testing was not conducted too early._

B) Fact Sheet for Patients (a sample updated Fact Sheet for Healthcare Providers is included in Appendix K):

1. In the section titled “Why was my sample tested?” add the following to the beginning of the section:

   *You are being tested at regular intervals (serial testing) even though you do not have symptoms or risk factors for COVID-19; or*

   And add the following to the end of the section:

   *Laboratories may use pooling when testing your specimen, which means they combine your sample with other individuals samples prior to testing and test them as a “pool”. The laboratory may return a result for the entire pool together or may return individual results.*

2. In the section titled “What does it mean if I have a positive test result?” add the following to the beginning of the section:

   *If you were tested as part of a pool that returned a positive or invalid test result, you may have COVID-19 and should consider yourself to have a positive test result unless and until you receive a negative test result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, you should isolate until receiving a negative result when re-tested individually and should not be grouped with other individuals who have received a positive or presumptive positive result.*

3. In the section titled “What does it mean if I have a negative test result?” add the following after the second paragraph of the section:

   *In particular, people infected with COVID-19 but who have no symptoms may not shed enough virus to trigger a positive test.*

   *If your test result indicates your specimen was pooled and you have a negative test result there a small chance that your result is incorrect. You should talk with your healthcare provider if you are concerned.*

   And add the following paragraph and text box to the end of the section:

   *If you have no symptoms but have been tested because your doctor thought you may have been exposed to COVID-19, you should continue to monitor your health and let your healthcare provider know if you develop any symptoms of COVID-19. If you develop symptoms you may need another test to determine if you have contracted the virus causing COVID-19.*

**If you develop symptoms or your symptoms get worse you should seek medical care. If you have the following symptoms you should seek immediate medical care at the closest emergency room:**
   - Trouble breathing
   - Persistent pain or pressure in the chest
   - New confusion
   - Inability to wake up or stay awake
   - Bluish lips or face

## Appendix J
### Sample Updated Fact Sheet for Health Care Providers

## Appendix K
### Sample Updated Fact Sheet for Patients

¹ U.S. Department of Health and Human Services, *Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3*. 85 FR 7316 (February 7, 2020)  
² Based on the production and testing capacity estimates provided by test developers and the anticipated demand by schools, workplaces and other groups setting up testing programs, the need for testing remains greater than available resources. If such testing programs are scaled up using individual tests, it would likely overwhelm the supply chain for many of the consumables used for diagnostic testing. Pooled testing strategies are intended to address public health needs by mitigating potential shortages.  
³ CDRH IVD EUA webpage [FDA EUA](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas).  
⁴ For ease of reference, this letter uses the phrase “authorized tests” to refer to molecular-based tests authorized by this amendment to detect nucleic acid from SARS-CoV-2 with pooled anterior nasal respiratory specimens for screening when used as part of a serial testing program.  
⁵ No other criteria of issuance have been prescribed by regulation under Section 564(e)(4) of the Act.  
⁶ The additional indications for use authorized by this amendment are limited to anterior nasal swab specimens and do not include any additional indications for other specimen types, such as saliva.  
⁷ In other words, this amendment does not amend EUAs for tests for which validation data for pooling was submitted, reviewed, and not authorized for pooling.  
⁸ In other words, this amendment does not amend EUAs for tests for which validation data from asymptomatic individuals was submitted, reviewed, and not authorized for screening.


# 404  2021-04-20_FDA Website - Pooling and Serial Testing Amendment.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-04-20_FDA Website - Pooling and Serial Testing Amendment.md
file_date: 2021-04-20
title: FDA Website - Pooling and Serial Testing Amendment
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: website
xfile_type: NA
gfile_url: NA
xfile_github_download_url: NA
pdf_gdrive_url: NA
pdf_github_url: NA
conversion_input_file_type: docx
conversion: manual cut and paste
license: Public Domain
tokens: 404
words: 298
notes: date converted 2024-03-27
web_url: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2#amendment
summary_short: The Pooling and Serial Testing Amendment explains FDA’s April 20, 2021 amendment that allowed certain authorized molecular SARS-CoV-2 tests to use pooled anterior nasal specimens from asymptomatic individuals within serial testing programs after developers submit a complete notification and validation documentation. It specifies CLIA high-complexity laboratory limitations and describes how authorized pooling parameters vary by appendix (pool sizes up to 3, 5, or 10 and media vs. swab pooling). It also clarifies that FDA adding a test to the exhibit/list reflects receipt of required documentation and does not necessarily indicate FDA review of the underlying validation data.


CONTENT

On April 20, 2021, the FDA issued an amendment allowing certain authorized molecular diagnostic SARS-CoV-2 tests to be distributed and used to pool anterior nasal respiratory specimens from asymptomatic individuals as part of a serial testing program after developers submit a complete notification, including meeting required validation data, as set forth in the letter. Use of tests for these indications is limited to laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high complexity tests, except that tests authorized for use in specific named or designated high complexity laboratories can only be used in such laboratories.

This means that tests with EUAs that are amended by this authorization may be used with pooled anterior nasal specimens from individuals without known or suspected COVID-19 when such individuals are tested as part of a testing program that includes testing at regular intervals, at least once per week. The indications in each appendix (A-H) differ in the number of specimens that can be pooled (up to 3, up to 5, or up to 10) and the type of pooling that can be done (media pooling or swab pooling).

Prior to a test being distributed or used for any new indication, the developer must submit a notification to the FDA with the information required by the amendment, including self-certifying that the applicable validation has been completed. Tests will be added to Exhibit 1 once FDA confirms that the required documentation has been submitted. Please note that being added to Exhibit 1 does not necessarily mean that the FDA has reviewed the underlying validation data submitted or confirmed that the test is appropriately validated.

[Amendment Letter](https://www.fda.gov/media/147737/download?attachment)
[Appendix J - Sample Updated Fact Sheet for Health Care Providers](https://www.fda.gov/media/147735/download?attachment)
[Appendix K - Sample Updated Fact Sheet for Patients](https://www.fda.gov/media/147736/download?attachment)


# 2,666  2021-09-23_FDA Letter - Viral Mutation Revision Letter.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-09-23_FDA Letter - Viral Mutation Revision Letter.md
file_date: 2021-09-23
title: FDA Letter - Viral Mutation Revision Letter
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: pdf
xfile_type: NA
gfile_url: NA
xfile_github_download_url: NA
pdf_gdrive_url: https://drive.google.com/file/d/1gZNI6dqEWCLUV53lH6YIuPVIjQ9K8hxZ
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-09-23_FDA%20Letter%20-%20Viral%20Mutation%20Revision%20Letter.pdf
conversion_input_file_type: pdf
conversion: megaparse-v
license: Public Domain
tokens: 2666
words: 1664
notes: 
summary_short: The FDA “Viral Mutation Revision Letter” (September 23, 2021) adds new EUA Conditions of Authorization for certain molecular, antigen, and serology COVID-19 IVDs to address potential performance impacts from emerging SARS-CoV-2 variants. It requires developers to update authorized labeling within a defined timeframe to include variant-related limitations, conduct ongoing evaluations of mutation impacts (including multi-analyte targets), and rapidly notify FDA and implement additional risk-mitigation labeling if concerns arise. It is used to standardize post-authorization surveillance and communication about variant-driven performance changes across EUA-authorized tests.


CONTENT

September 23, 2021

To: Developers of Certain Molecular, Antigen and Serology In Vitro Diagnostics (IVDs) Authorized for Emergency Use for Coronavirus Disease 2019 (COVID-19) as of Today’s Date

Re: Establishing additional Conditions of Authorization for the EUAs of Certain Molecular, Antigen and Serology IVDs related to viral mutations.

On February 4, 2020, pursuant to Section 564(b)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 360bbb-3(b)(1)(C)), the Secretary of the Department of Health and Human Services (HHS) determined that there is a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad, and that involves the virus that causes COVID-19. Pursuant to Section 564 of the Act, and on the basis of such determination, the Secretary of HHS then declared that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the virus that causes COVID-19 subject to the terms of any authorization issued under Section 564(a) of the Act.^1^ FDA subsequently authorized the emergency use of numerous in vitro diagnostics (IVDs) for detection and/or diagnosis SARS-CoV-2, the virus that causes COVID-19.^2^

Pursuant to Section 564 of the Act, and in response to the continued emergence of new genetic viral variants of SARS-CoV-2,^3^ FDA is issuing this letter to establish additional Conditions of Authorization on EUAs that are within the Scope of this Revision (Section I).

As set forth throughout, this letter revises the EUAs that are within the scope of this letter to require the additional Conditions of Authorization included in Section III of this letter. These conditions generally concern labeling updates and performance evaluations related to SARS-CoV-2 viral mutations for authorized tests that are within the scope of this revision.^4^ FDA’s determination that the Conditions of Authorization established by this revision are necessary or appropriate to protect the public health is based on the available scientific evidence and FDA’s continuing efforts to monitor the performance of authorized molecular, antigen, and serology IVDs with respect to emerging SARS-CoV-2 mutations.

Having concluded that establishing these additional conditions on the EUAs that are within the scope of this letter (section I) is appropriate to protect the public health or safety, I am hereby revising all such EUAs pursuant to Section 564(g)(2)(C) to establish the additional conditions set forth in this letter as permitted by Section 564(e) of the Act. This action is based on the available scientific evidence,^5^ including widespread detection of variants of the SARS-CoV-2 virus.

## I. Scope of this Revision
Except as provided in the next paragraph, this letter revises the EUAs of the following SARS-CoV-2 IVD devices that have been issued as of today’s date by establishing the additional conditions of authorization set forth in Section IV of this letter on such authorizations:

- [Molecular IVD devices](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas/molecular-diagnostic-tests-sars-cov-2).

- [Antigen IVD devices](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas/antigen-diagnostic-tests-sars-cov-2).

- [Serology IVD devices](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-serology-and-other-adaptive-immune-response-tests-sars-cov-2).

This revision does not apply to EUAs for authorized IL-6 assays, EUAs for standalone specimen collection devices, or EUAs for standalone home collection kits. Nor does this revision apply to EUAs that include substantially equivalent viral mutation conditions of authorization.

All updated labeling will be added to FDA’s webpage and posted with the EUA after it is submitted to FDA as required by Condition of Authorization (1) of this letter.

## II. Waiver of Certain Requirements
This revision does not change the waiver of any requirements included in the EUAs being amended.

## III. Conditions of Authorization
Pursuant to Section 564(e) of the Act, I am establishing the additional conditions below with respect to SARS-CoV-2 viral mutations.

**Developer (You)**
1. You must update your authorized labeling as set forth in Appendix A and B of this letter within 3 months of today’s date by submitting the updated labeling to FDA as a supplement to your EUA, unless otherwise agreed to by the Division of Microbiology (DMD)/Office of Health Technology 7 (OHT7)-Office of In Vitro Diagnostics and Radiological Health (OIR)/Office of Product Evaluation and Quality (OPEQ)/Center for Devices and Radiological Health (CDRH).^9^

2. You must evaluate the impact of SARS-CoV-2 viral mutations on your product’s performance. For multi-analyte tests, you must evaluate the impact of SARS-CoV-2 viral mutations and all other target analytes. Such evaluations must occur on an ongoing basis and must include any additional data analysis that is requested by FDA in response to any performance concerns you or FDA identify during routine evaluation. Additionally, if requested by FDA, you must submit records of these evaluations for FDA review within 48 hours of the request. If your evaluation identifies viral mutations that affect the stated expected performance of your device, you must notify FDA immediately (via email: CDRH-EUA-Reporting@fda.hhs.gov).

3. If requested by FDA, you must update your labeling within 7 calendar days to include any additional labeling risk mitigations identified by FDA regarding the impact of viral mutations on test performance. Such updates will be made in consultation with, and require concurrence of, DMD/OHT7-OIR/OPEQ/CDRH.

Sincerely,

/S/

RADM Denise M. Hinton  
Chief Scientist  
Food and Drug Administration

Enclosure

## Appendix A
**Required Changes to Authorized Labeling – IFU/Laboratory SOP and/or EUA Summary**

As required by Condition of Authorization (1), you must update your authorized labeling (e.g., IFU, Laboratory SOPs and/or EUA Summary) to include the limitation below:

*The performance of this test was established based on the evaluation of a limited number of clinical specimens. Clinical performance has not been established with all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.*

## Appendix B
**Required Changes to Authorized Labeling – Fact Sheet for Healthcare Providers**

As required by Condition of Authorization (1), you must update the Fact Sheet for Healthcare Providers as follows:

1. For molecular and antigen IVDs at the end of the section titled “What does it mean if the specimen tests negative for the virus that causes COVID-19?” add the following paragraph:

   *The performance of this test was established based on the evaluation of a limited number of clinical specimens. The clinical performance has not been established in all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.*

2. For serology IVDs at the end of the section titled “What does it mean if the specimen tests negative for antibodies against virus that causes COVID-19?” add the following paragraph:

   *The performance of this test was established based on the evaluation of a limited number of clinical specimens. The clinical performance has not been established in all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.*
^1^: U.S. Department of Health and Human Services, *Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3, 85 FR 7316 (February 7, 2020)*

^2^: In Vitro Diagnostics EUAs: [FDA Website](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas), includes links to tables of currently authorized IVD EUAs for SARS-CoV-2.

^3^: Like all viruses, the SARS-CoV-2 genome has changed over the course of the COVID-19 pandemic through mutation, with new genetic viral variants of the virus documented in the United States and globally. Sometimes new mutations emerge and disappear, and other times they persist and the resulting new viral variants grow in prevalence. CDRH has been monitoring SARS-CoV-2 genetic viral mutations because of their potential to affect authorized SARS-CoV-2 IVDs. CDRH’s monitoring of SARS-CoV-2 genetic viral mutations resulted in FDA releasing a January 8, 2021 [safety alert](https://www.fda.gov/news-events/press-announcements/fda-issues-alert-regarding-sars-cov-2-viral-mutation-health-care-providers-and-clinical-laboratory) to healthcare providers and clinical laboratory staff about the potential impact of viral mutations on the performance of authorized molecular SARS-CoV-2 IVDs. This was subsequently followed by an FDA [guidance document](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-evaluating-impact-viral-mutations-covid-19-tests), issued in February 2021 - *“Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests: Guidance for Test Developers and Food and Drug Administration Staff, February 2021,”* outlining the FDA’s concerns about the impact of viral mutations and recommendations for evaluating molecular, antigen and serology IVDs accordingly. In addition, a webpage was developed to provide information regarding the impact of viral mutations on SARS-CoV-2 tests, including the recommendations for clinical laboratory staff and health care providers from the safety alert, and information about certain tests for which the FDA has identified potential impacts on performance due to SARS-CoV-2 genetic mutations. This website was first posted in March 2021 and updated in June 2021: [SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests | FDA](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-viral-mutations-impact-covid-19-tests).
^4^: Authorized labeling potentially impacted by the additional conditions established by this letter include some combination of the following documents: Instructions for Use (IFU), laboratory Standard Operating procedures (SOPs), EUA Summary and/or Fact Sheet for Healthcare Providers. Note that the EUA Summary is generated by FDA who will update the document after it receives the supplement request to update the test’s other labeling consistent with this revision.

^5^: *SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests | FDA*: [FDA Website](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-viral-mutations-impact-covid-19-tests).

^9^: FDA will update the Healthcare Provider Fact Sheet for the “Umbrella EUA for Molecular Diagnostic Tests for SARS-CoV-2 Developed and Performed By Laboratories Certified Under CLIA To Perform High Complexity Tests.” Test developers that use this Fact Sheet for their tests should begin using the updated version no later than 3 months from today’s date.

^10^: The Fact Sheet for Patients/Individuals/Recipients does not include language specific to viral mutations and therefore does not need to be updated as part of this revision.


# 435  2021-09-23_FDA Website - Revision Concerning Viral Mutations.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-09-23_FDA Website - Revision Concerning Viral Mutations.md
file_date: 2021-09-23
title: FDA Website - Revision Concerning Viral Mutations
category: regulatory
subcategory: fda-policy
tags: 
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license: Public Domain
tokens: 435
words: 284
notes: date converted 2024-03-27
web_url: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2#Revision
summary_short: The Revision Concerning Viral Mutations summarizes FDA’s September 23, 2021 update to certain molecular, antigen, and serology COVID-19 test EUAs adding new Conditions of Authorization to address emerging SARS-CoV-2 variants. It requires EUA holders to monitor viral mutations for potential performance impacts, communicate identified risks to FDA and end users, and update and submit revised labeling within three months. The change was intended to reduce false negatives linked to decreased sensitivity or non-reactivity from new mutations, with specific exclusions for some EUA categories.


CONTENT

On September 23, 2021, the FDA revised the EUAs of certain molecular, antigen, and serology tests to establish additional Conditions of Authorization in response to the continued emergence of new variants of SARS-CoV-2. The revision requires test developers to update their authorized labeling and evaluate the impact of SARS-CoV-2 viral mutations on their test's performance as outlined in the letter. This revision is effective as of September 23, 2021 for all EUAs that are within the scope of the revision. This revision does not apply to EUAs for authorized IL-6 assays or standalone specimen collection devices and does not apply to EUAs that include substantially equivalent viral mutation conditions of authorization.

The FDA has determined that establishing additional conditions is necessary to mitigate the potential risk of false negative results due to either decreased sensitivity or non-reactivity associated with SARS-CoV-2 viral mutations. As set forth in the September 23, 2021 letter, developers of authorized tests that are within the scope of the revision are now required to routinely monitor emerging viral mutations and their potential impact on the performance of the authorized SARS-CoV-2 test(s).  If potential impacts are identified, the EUA holder must communicate with the FDA and end users about the potential risk that presence of the mutations may have on test performance. The EUA holder must also update their authorized labeling consistent with the revision letter and submit the labeling to the FDA within 3 months of September 23, 2021. By taking these steps, the FDA and the test developer can quickly act in response to the potential risks identified and, when applicable, share the findings on [SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-viral-mutations-impact-covid-19-tests?utm_medium=email&utm_source=govdelivery). 

[Viral Mutation Revision Letter - September 23, 2021](https://www.fda.gov/media/152406/download?attachment)


# 31,076  2021-10-06_FDA Template - For Developers of Molecular Diagnostic Tests.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-10-06_FDA Template - For Developers of Molecular Diagnostic Tests.md
file_date: 2021-10-06
title: FDA Template - For Developers of Molecular Diagnostic Tests
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: docx
xfile_type: docx
gfile_url: https://docs.google.com/document/d/1APPBLs59clpaOt2qBMzYbHVXvFpqkJas
xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fda-policy/2021-10-06_FDA%20Template%20-%20For%20Developers%20of%20Molecular%20Diagnostic%20Tests.docx
pdf_gdrive_url: https://drive.google.com/file/d/1xQ8iaicJm2rzOVlw351yDv5gKlFahDqc
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-10-06_FDA%20Template%20-%20For%20Developers%20of%20Molecular%20Diagnostic%20Tests.pdf
conversion_input_file_type: docx
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license: Public Domain
tokens: 31076
words: 20940
notes: 
summary_short: The FDA “Template for Developers of Molecular Diagnostic Tests” is a detailed pre-EUA/EUA submission template outlining recommended validation, clinical study design, and labeling content for SARS-CoV-2 molecular diagnostics. It covers core analytical studies (LoD, inclusivity/variant monitoring, cross-reactivity, interference, stability), clinical performance expectations for symptomatic and asymptomatic screening populations, and requirements for pooled testing, including validation approaches and ongoing pooling monitoring/re-assessment. It is used by developers to structure submissions and align evidence packages with FDA review criteria, including manufacturing, software, reporting, and post-authorization obligations.


CONTENT

***INTERNAL TITLE:*** Template for Developers of Molecular Diagnostic Tests

This template provides the Food and Drug Administration’s (FDA) current recommendations concerning what data and information should be submitted to FDA in support of a pre-Emergency Use Authorization (EUA)/EUA request for a SARS-CoV-2 molecular diagnostic test. FDA generally recommends that the following validation studies be conducted for SARS-CoV-2 molecular diagnostic tests: limit of detection (LOD), inclusivity, cross-reactivity, sample stability, and clinical evaluation.

As described in the FDA guidance document [*Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised), [2] FDA is providing recommendations in this and other EUA templates regarding testing that should be performed to ensure appropriate analytical and clinical validity, including descriptions of appropriate comparators, for different types of tests. The EUA templates[3] are intended to help test developers provide recommended validation data and other information to FDA, but alternative approaches can be used. This template reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should,* means that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/media/97321/download).[4]

Test developers interested in pursuing an EUA may submit a pre-EUA to begin discussions with the FDA or may submit an EUA request to <Covid19DX@fda.hhs.gov>.

FDA recommends that all developers of molecular SARS-CoV-2 tests include the [Molecular EUA Template Cover Sheet](https://www.fda.gov/media/152768/download)[5] when submitting their EUA request to <Covid19DX@fda.hhs.gov> to help streamline the routing, triage, and review of EUA requests.

## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by the test developer as applicable to their specific test. Text in **bold** outlines the FDA’s additional recommendations for the developers’ consideration when completing the suggested information in each section.

-   Not all portions of this template may be relevant for all developers/tests. FDA recommends developers complete all portions that are relevant to facilitate a streamlined review.

-   This template addresses tests intended for use with respiratory samples and saliva; if you are considering other sample types, please contact FDA at CDRH-EUA-Templates (<Covid19DX@fda.hhs.gov>) to discuss your validation strategy.

-   A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   We may update the template as appropriate as we learn more about COVID-19 and gain experience with the EUA process for these kinds of tests.

-   A developer that has provided data to the FDA may grant a right of reference to other developers, either broadly or to individual developers, to leverage that data. A right of reference provides a developer the ability to rely upon, and otherwise use, existing information in one regulatory submission for the purpose of supporting a different regulatory submission. In these cases, if the data is applicable to the new developer's test, the new developer may not have to repeat that validation for its submission to the FDA or FDA may recommend only a bridging study. Any developer seeking to leverage data regarding another developer’s EUA-authorized assay must obtain a right of reference from that developer. [6]

## EXAMPLE TEMPLATE:
### A. PURPOSE FOR SUBMISSION

Emergency Use Authorization (EUA) request for distribution and/or use of the ***\[test name\]*** for the *in vitro* qualitative detection of RNA from the SARS-CoV-2 in ***\[add all claimed sample types, e.g., nasopharyngeal/ oropharyngeal swabs, sputa, bronchoalveolar lavage (BAL), etc.\]*** ***\[select appropriate testing population, e.g.,*** ***from patients suspected of COVID-19 by a healthcare provider or for screening of individuals without symptoms or other reasons to suspect COVID-19.\]******.*** Test results should be reported in accordance with local, state, and federal regulations.

***\[If you plan to include a sample pooling protocol in your instructions for use, please include a brief description of the pooling strategy.\]***

***\[If you plan to request authorization for screening with serial testing, please refer to the*** *[Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing](https://www.fda.gov/media/146695/download) **and include any relevant information.****\]***

***\[If you plan to request authorization to test samples collected with a home specimen collection kit, please refer to the** [Home Specimen Collection Molecular Diagnostic Template](https://www.fda.gov/media/138412/download) **and include any relevant information.****\]***

### B. MEASURAND

Specific nucleic acid sequences from the genome of the SARS-CoV-2 ***\[please specify the targeted gene(s) of the pathogen\]***.

### C. APPLICANT

***\[Official name, address, and contact information (including phone number and email address) of applicant and primary correspondent.\]***

### D. PROPRIETARY AND ESTABLISHED NAMES

Proprietary Name - ***\[test name\]***

Established Name - ***\[test name\]***

### E. REGULATORY INFORMATION

***Approval/Clearance Status:***

The ***\[test name\]*** test is not cleared, CLIA waived, approved, or subject to an approved investigational device exemption.

***\[If the test has been previously reviewed in an EUA request or pre-EUA submission, please provide the submission number.\]***

Panel Code: MI for Microbiology tests

Review Group: Division of Microbiology Devices/VIR1

***Product Code:***

QJR (for SARS-CoV-2 only tests)

**OR**

QLP (for multi-analyte tests that include SARS-CoV-2)

### F. PROPOSED INTENDED USE

#### 1) Intended Use (IU):

**The proposed IU will be finalized based on, among other things, the data provided and recommendations from Public Health authorities at the time of authorization – example text is provided below for a qualitative molecular test that detects organism RNA but may be adapted according to the specific emergency situation addressed by the device, proposed intended use population, testing sites, or performance characteristics.**

The ***\[test name\]*** is a ***\[specify test technology such as, real-time RT-PCR test\]*** intended for the ***\[presumptive\]*** qualitative detection of RNA from SARS-CoV-2 in ***\[describe all the sample types that were evaluated, e.g., nasopharyngeal, nasal, and oropharyngeal swab samples and lower respiratory tract, BAL, sputum\]*** ***\[If your test is intended for testing multiple respiratory pathogens, please list the specific analytes detected by your test.\] \[describe intended use population, e.g., from individuals suspected of COVID-19 by their healthcare provider or for screening of individuals without symptoms or other reasons to suspect COVID19 infection.\].*** Testing is limited to ***\[laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet the requirements to \[insert testing complexity, e.g., moderate complexity, high complexity, or waived tests. This test is authorized for use at the Point of Care (POC), i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation.\].***

***\[Describe the sample pooling approach, as appropriate\].*** This test is also for the qualitative detection of nucleic acid from SARS-CoV-2 in pooled samples containing up to ***\[maximum number\]*** individual ***\[type of sample and collection method\],*** where each specimen is collected using ***\[type of sample and collection method\]***. Negative results from pooled testing should not be treated as definitive. If a patient’s clinical signs and symptoms are inconsistent with a negative result or if results are necessary for patient management, then the patient should be considered for individual testing. Specimens included in pools with a positive or invalid result must be tested individually prior to reporting a result. Specimens with low viral loads may not be detected in sample pools due to the decreased sensitivity of pooled testing. For specific patients whose specimen(s) were the subject of pooling, a notice that pooling was used during testing must be included when reporting the result to the clinician or healthcare provider.

Results are for the identification of SARS-CoV-2 RNA. The SARS-CoV-2 RNA is generally detectable in ***\[name sample type, e.g., upper respiratory\]*** during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Laboratories within the United States and its territories are required to report all test results to the appropriate public health authorities.

The ***\[test name\]*** is intended for use by ***\[include intended user, e.g., qualified, and trained clinical laboratory personnel specifically instructed and trained in the techniques of RT-PCR and in vitro diagnostic procedures\]***.

The ***\[test name\]*** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

**Depending on the performance and the populations studied in the clinical evaluation, additional limitations may be recommended.**

#### 2) Special Conditions for Use Statements:

For prescription use only

For *in vitro* diagnostic use

For Emergency Use Authorization only

#### 3) Special Instruments

The ***\[test name\]*** test is to be used with the ***\[list all RT-PCR instruments, software, and automated extraction instruments, other applicable instrumentation, etc.\]***.

**If your test system includes an instrument, the instrumentation manual should be submitted as part of the EUA request. If your test system includes an instrument that was not previously cleared, approved, or authorized by FDA, please see additional discussion in the Product Manufacturing section and note that additional labeling information may be discussed during the EUA review.**

### G. DEVICE DESCRIPTION AND TEST PRINCIPLE

**Please provide a device description. The example provided below applies to fluorescence based real-time reverse-transcriptase-polymerase chain reaction (RT-PCR) tests for detection of organism RNA. Please modify the example text as appropriate for tests that use a different test principle. For new technologies, FDA may request additional information so we can adequately assess the known and potential risks and benefits associated with the device*.***

#### 1) Product Overview/Test Principle:

***\[Describe the technology of the test and how this technology works to identify the measurand (i.e., the test principle), the instruments/reader employed/required to perform the test from sample collection to result (include all claimed extraction and PCR detection instruments), and the sample types for which the performance of the test has been established**. **If applicable, list all primer and probe sets, briefly describe what they detect, and include the nucleic acid sequences. Please indicate if the test uses biotin-Streptavidin/avidin chemistry in any of the steps for coupling reagents.\]***

The ***\[test name\]*** is a real-time reverse transcription polymerase chain reaction (RT-PCR) test. The SARS-CoV-2 primer and probe set(s) is designed to detect RNA from the SARS-CoV-2 in ***\[list all the sample types\]*** from patients suspected of COVID-19 by their healthcare provider.

#### 2) Description of Test Steps: 

***\[List and describe in detail all the steps of the test sequentially from sample collection to assay report.\]***

1.  ***\[Step one\]***

2.  ***\[Step two\]***

3.  ***Etc.…\]***

Nucleic acids are isolated and purified from ***\[samples\]*** using ***\[please describe the method(s) of extraction (please specify the*** ***sample input volume for extraction and/or test, the nucleic acid elution volume and whether isolation/purification is manual and/or automated)\]******.*** The purified nucleic acid is reverse transcribed using ***\[enzyme mix/kits – please specify the input volume of purified nucleic acid added to the RT-PCR reaction mix\]*** into cDNA which is then subsequently amplified in ***\[please describe the instrument(s) and enzyme mix\]***. In the process, the probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5’ nuclease activity of Taq polymerase degrades the probe, causing the reporter dye to separate from the quencher dye, generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle by ***\[please describe the detection instrument(s)\]***.

#### 3) Control Material(s):

***\[List all control materials (provided with the test kit and/or required but not provided with the test kit, e.g., sold as a separate kit) and describe what they are, how they are expected to work, where in the testing process they are used, and the frequency of use. If a control is commercially available, provide supplier’s name and catalog number or other identifier; if your device relies on external controls that are manufactured by a third party please note that these controls should also be validated within your analytical and clinical studies described below in Section J.\]***

Controls that will be provided with the test kit include:

a.  An external positive template control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the concentration of the positive control relative to the LoD of your test (note that ideally the positive control concentration should be such that it is close to the LoD of your test) and specify frequency of use.\]***

b.  An external negative control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the composition of the negative control and specify frequency of use.\]***

c.  An extraction control ***\[describe control\]*** is needed to ***\[describe need\]*** and is used ***\[describe use – please also specify frequency of use\].*** **Please note that if the positive control is taken through the entire sample processing procedure, including the extraction, then a separate extraction control is not required**.

d.  A ***\[other (e.g., sample adequacy, internal, etc.)\]*** control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the composition of the control and specify frequency of use\]***

Controls that are required but not provided with the test kit include ***\[describe control – provide recommended sources of the control materials – either a separate control kit for purchase that you the applicant develops or a control material that can be purchased from a third party\].*** This/these control(s) is/are needed to ***\[describe need\]*** and is used ***\[describe use – please also specify frequency of use\]***.

**Please note that any control used with your device (provided with the kit or not) should be validated in the context of your analytical and clinical studies (i.e., your studies should include use of these controls). In instances where control material is not readily available through 3^rd^ party vendors, FDA recommends that you include suitable control material with your device. External control materials are considered particularly important when good manufacturing practice (GMP) requirements are waived, and reagent stability studies are limited.**

#### 4) Test Result Reporting:

All test results are to be reported to healthcare providers and relevant public health authorities in accordance with local, state, and federal requirements, using appropriate LOINC and SNOMED codes, as defined by the [*Laboratory In Vitro Diagnostics (LIVD) Test Code Mapping for SARS-CoV-2 Tests*](https://www.cdc.gov/csels/dls/sars-cov-2-livd-codes.html)[7] provided by the Centers for Disease Control and Prevention (CDC).  Core diagnostic data elements[8] are to be collected for all tests, which have been defined by the Department of Health and Human Services (HHS), along with technical specifications for implementation for lab-based[9] and non-lab-based[10] tests.

### H. INTERPRETATION OF RESULTS

All test controls should be examined prior to interpretation of patient results. If the controls are not valid, the patient results cannot be interpreted. ***\[Appropriate control interpretation criteria should appear in your product labeling.*** ***Please describe if a Ct (cycle threshold) cutoff is used as part of your testing algorithm and/or if the end user is required to review curves before final result interpretation. Although not typical for molecular-based tests, if the test result involves the use of an algorithm/calculation, for example a ratio value, when determining the final patient test result, please include a detailed description and any additional calibration materials that may be required.\]***

#### 1)  *\[Test name\] Controls – Positive, Negative, and Others:*

\[Describe in detail the expected results generated, including acceptance criteria, for all the controls described in Section G above. Describe the measured values (if applicable) for valid and invalid controls and outline the recommended actions the laboratory should take in the event of an invalid control result.\]

#### 2)  *Examination and Interpretation of Patient Sample Results:*

\[Describe when clinical sample test results should be assessed and outline the criteria for test validity.\]  

**Example text:** Assessment of \[test name\] results should be performed after the positive and negative controls have been examined and determined to be valid and acceptable. If the controls are not valid, the patient results cannot be interpreted.

***\[Clearly indicate how to interpret numeric test values (if applicable) as positive or negative for presence of SARS-CoV-2. Indicate if the end user is required to review curves before final result interpretation and, if applicable, how to identify indeterminate/inconclusive/equivocal results. When applicable, we recommend providing a table clearly describing the possible combinations of test result values for each primer/probe set. Describe how they should be combined into a final interpretation of the result for your test. If the test produces an equivocal or indeterminate result, please indicate what follow-up testing/process should be conducted, if applicable.\]***

### I. PRODUCT MANUFACTURING

The \[test name\] has been validated using only the components referenced in this request and will not be changed after authorization without prior concurrence from the FDA.

#### 1) Overview of Manufacturing and Distribution: 

The product will be manufactured at ***\[test developer’s name and FDA registration number (if applicable)\]*** by ***\[test developer’s name\]*** personnel consistent with practices for the production of ***\[types of devices\]*** based on ***\[type of quality system (e.g., 21 CFR 820 or ISO13485)\]*.** Material manufactured by ***\[test developer’s name\]*** may be bottled and kitted by ***\[packager name\]*** manufacturing facility.

The current manufacturing capabilities include the ability to manufacture approximately ***\[please insert the approximate number of tests/kits that can currently be manufactured per week at the manufacturing facility\]*** products per week for distribution in the United States, however, in the event of a surge in demand this could be increased to ***\[please insert the approximate maximum number of tests/kits that could potentially be manufactured per week at the manufacturing facility if there was a surge in demand\]*** product per week within a ***\[please specify in weeks/months the expected timeframe required to increase product production if conditions warrant\]*** timeframe.

**Under an EUA, certain sections of the 21 CFR Part 820 Quality System Regulation (QSR) requirements may be waived for an authorized produced during the duration of the EUA, but FDA recommends that test developers follow comparable practices as much as possible, even if such requirements are waived. Please see recent letters of authorization for examples of which QSR requirements have been required.**

***\[Please specify any instruments or other components of your test which are labeled as research use only (RUO) or are otherwise not labeled with the statement “For In Vitro Diagnostic Use” or a symbol found in a standard to the same effect.\]***

**For distributed tests (i.e., tests intended to be performed in more than one laboratory location), that use an RUO instrument, please provide the following information, as applicable:**

***FOR AN RUO INSTRUMENT WHERE THE EUA REQUESTER IS NOT THE MANUFACTURER OF THE INSTRUMENT:***

**Please include in the instructions for use found in your test’s labeling, appropriate procedures, including acceptance criteria, that laboratory customers should follow to qualify the performance of the RUO instrument prior to use with your test.**

**These procedures could include wet testing of quantitated test material with your test, or confirmation that key specifications of the instruments that are applicable to your test are within an acceptable range. The quantitated virus material could either be positive control material included with your kit or commercially available positive virus control material. If commercially available material is not labeled with the statement “For *In Vitro* Diagnostic Use” or a symbol found in a standard to the same effect, then you should qualify lots of this material in-house and have a mechanism to notify laboratory customers which lots are appropriate to use for qualification (i.e., posting on a website). For the qualification protocol, you should include a recommendation to test multiple dilutions of virus material with your test, with, at minimum, 3 replicates per dilution. There should be at least one dilution near the LoD (i.e., within 3x LoD) of your test. The protocol should outline the acceptance criteria for each dilution tested.**

***\[Please also provide the following** **labeling documentation with your request:***

1.  ***A "For Emergency Use Authorization only" label that users can affix to the instrument after it has been qualified. This can be provided as an Appendix in the assay instructions for use.***

2.  ***Please ensure that your test’s labeling either reproduces the parts of the instrument operating manual that are relevant to run your test or references the relevant sections of the manual.\]***

***FOR AN RUO INSTRUMENT WHERE THE EUA REQUESTER IS THE MANUFACTURER OF THE INSTRUMENT:***

***\[Please either provide the qualification protocol as described above or the following information to demonstrate your instrument meets the minimum quality system requirements for authorization:***

1.  ***The ISO 13485 certificate for the site where your instrument is manufactured.***

2.  ***A document mapping out the parts of your quality system that fulfill each of the following 21 CFR part 820 requirements:***

-   ***Subpart H (Acceptance Activities, 21 CFR 820.80 and 21 CFR 820.86),***

-   ***Subpart I (Nonconforming Product, 21 CFR 820.90), and***

-   ***Subpart O (Statistical Techniques, 21CFR 820.250).***

***Please provide the following labeling documentation with your request:***

1.  ***A “For Emergency Use Authorization only” label that the users can affix to the instrument after it has been qualified. This can be provided as an Appendix in the assay instructions for use.***

2.  ***The instrument operating manual. Please note that the manual should not include any unapproved, uncleared, or unauthorized uses.***

3.  ***An instrument manual addendum that will be distributed along with your EUA test kit. The addendum may have the following format:\]***

***Instrument Operation Manual Addendum:***

For emergency use authorization only with the ***\[test name\]***.

The ***\[test name\]*** is authorized for use under the US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) with the ***\[name of instruments\]*** for the ***\[presumptive\]*** qualitative detection of RNA from SARS-CoV-2 ***\[intended use of test\].*** Refer to the ***\[test name\]*** instructions for use for additional information ***\[provide hyperlink\].***

This instrument operation manual addendum applies to the instruments listed in Table below that are authorized for use with the ***\[test name\].***

**Table: Instruments Authorized for Emergency Use Only with the *\[test name\] ***

| **Catalog Number** | **Product Name** |
|--------------------|------------------|
|                    |                  |
|                    |                  |
|                    |                  |
|                    |                  |
||

Warnings:

-   This product has not been FDA cleared or approved; the product has been authorized by FDA as part of ***\[test name\]*** under an EUA for emergency use only by authorized laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C § 263a.

-   This product has been authorized only for the detection of nucleic acid from SARS-CoV-2, not for any other viruses or pathogens.

-   The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of *in vitro* diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated, or authorization is revoked sooner.

#### 2) Components & Other Materials/Information Included with the Test:

Components manufactured by ***\[test developer’s name and FDA registration number (if applicable)\]*** and supplied with the test include:

***\[List all components and other materials/information included with your test, including a description of the primers and probes, volumes, concentrations, quantities, buffer components, etc.\]***

**Table: Example: Kit Components & Other Materials/Information**

| Kit Components & Other Materials/Information | Main Reagents Composition/ Matrix | Concentration/ Quantity/Volume | Manufacturer |
| --- | --- | --- | --- |
| Test Cassette with test strip |  |  |  |
| Negative control |  |  |  |
| Positive control |  |  |  |
| Calibrators |  |  |  |
| Sample buffer (bottle) |  |  |  |
| Transfer pipette |  |  |  |
| Instructions for Use leaflet |  |  |  |
| Packing materials |  |  |  |
| Others, as applicable |  |  |  |
||

#### 3) Components and Other Materials/Information Required but Not Included with the Test:

***\[List all components and other materials/information (e.g., instruments, reagents) not included with the test that must be supplied by the user to perform the test, with specific supplier names and catalog numbers or other identifiers for obtaining the components. Please include here all specific consumables that were validated for use with your device, that are not interchangeable with other products and that are needed to guarantee device performance as established in the EUA validation studies listed in Section J below.\]***

#### 4) Software Validation:

**If you are introducing a system onto the market that has not been previously reviewed by FDA, we recommend providing evidence that the software has been validated to ensure that:**

-   **The inputs and outputs of the software are appropriate to fulfill the system and assay requirements;**

-   **All expected inputs produce the expected outputs for all functions critical for system operation; and**

-   **The system will be provided to the customer free of defects, or defects will be known and mitigated.**

**If this evidence is not available prior to authorization and the software and hardware have been designed and developed in a manner consistent with current GMPs (for additional information, please see the discussion of “*Quality System Regulation/Medical Device Good Manufacturing Practices*,” on the FDA website**[11]**), additional software validation documentation may be incorporated into the conditions of authorization. If changes which impact assay performance or safety and effectiveness of the system are needed to address validation failures post-authorization, an EUA supplement may be required under the conditions of authorization.**

**Below are examples of tables for providing system specific information and your evidence that specifications have been met (e.g., hazard analysis). Text in the tables is provided as an example only. *\[Please provide thorough functional descriptions of system software and instrumentation specifications needed to support the intended use of the test and provide evidence that specifications have been fulfilled.\]***

** System specifications and validation example**

| Critical specifications: Description of the specification | Evidence that the design of the system can fulfill the specification. This column should consist of system-level validation data. |
| --- | --- |
| Optical system of each instrument sent to a user has sufficient dynamic range to appropriately differentiate between positive and negative test results |  |
| Software displays appropriate result during test run |  |
| If reader stores test result, software accurately stores and retrieves test results |  |
| System has a defined lifetime where the user can expect the system to maintain performance as stated in the label |  |
| Etc. |  |
||



**Hazard analysis examples**

_Diagram showing a sample hazard analysis workflow: identifying hazards, assessing severity and probability, determining risk mitigation measures, and evaluating residual risk._

| **ID** | **Hazard** | **Adverse Effect** | **Severity** | **Potential causes of hazard** | **Risk mitigation measure** | **Risk of experiencing the hazard after mitigation** |
|-------|---------|----------|--------|--------------|-------------|-------------|
| 1 | Invalid result | Delay in returning test result | Low | User inserts cartridge incorrectly | Labeling noting correct orientation | Low |
| 2 | False result | Wrong result returned to user | High | Incorrect alignment of test strip and optics; test strip inserted in the wrong orientation | Mechanical design of reader input slot | Moderate |
| 3 | False negative result | Wrong result returned to user | High | User reads test strip too early; incubation time not sufficient | Labeling noting correct incubation time | Moderate |
| 4 | False result | Wrong result returned to user | High | Incorrect alignment of test strip and optics; control line misinterpreted | Software interprets data from optical system identifying a valid/invalid control | Moderate |
| 5 | False result | Wrong result returned to user | High | Control reaction intensity is misinterpreted | Software interprets data from optical system identifying a valid/invalid control | Moderate |
| 6 | False result | Wrong result returned to user | High | Analyte reaction intensity is misinterpreted | Software interprets data from optical system identifying a valid/invalid control | Moderate |
||

**If applicable to your test, FDA recommends the following evaluations be performed and documentation kept on file. If not completed by the time of authorization, these evaluations may be required in a condition of authorization.**

-   **You should evaluate the cybersecurity of your system to ensure user and patient safety in the intended use environment;**[12]

-   **You should complete validation of all systems and software to ensure that all functions of the system perform as labeled. For more information on system validation please see the following FDA guidance documents and resources:**

    -   ***[Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissions-software-contained-medical-devices);***[13]

    -   ***[General Principles of Software Validation](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-principles-software-validation);***[14]

    -   ***[Device Software Functions Including Mobile Medical Applications](https://www.fda.gov/medical-devices/digital-health/device-software-functions-including-mobile-medical-applications);***[15]

    -   **[*Off-The-Shelf Software Use in Medical Devices*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices#:~:text=Off%2Dthe%2Dshelf%20(OTS,to%20run%20device%2Dspecific%20functions.);**[16] **and**

    -   **[21 CFR 820.30](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=820.30).**

#### 5) Basic Safety and Essential Performance:

***\[If you are introducing a system onto the market which has not been previously reviewed by the FDA, please describe how you addressed basic safety hazards such as electrical hazards (e.g., electrical shock to the operator and/or patient), fire hazards, and mechanical hazards.\]* We recommend that you consult the general requirements for basic safety, as indicated in International Electrotechnical Commission (IEC) 60601-1 (Medical electrical equipment – Part 1: General requirements for basic safety and essential performance). IEC 60601-1 is a standard that specifies the general requirements for basic safety and essential performance. IEC 60601-1 defines basic safety as freedom from unacceptable risk directly caused by physical hazards when medical electrical equipment is used under normal condition and single fault condition.**

#### 6) Electromagnetic Compatibility (EMC) Testing (if applicable)

**We recommend that EMC testing be conducted on any assay that uses a battery or power source. *\[Please provide FDA with any standards that were followed for EMC testing.\]* We recommend that you perform EMC testing according to the International Electrotechnical Commission (IEC) 60601-1-2 Edition 4.0:2014. *\[If you perform EMC testing to a different standard or use alternate methodologies to evaluate EMC, please provide a test plan, test report, acceptance criteria, and risk analysis to support your approach.\]***

#### 7) Manufacturing and Testing Capabilities 

***\[Briefly describe current sample throughput testing capacity, the total time required to perform the test (from clinical sample collection to result), and the number of tests that can be performed per day (8-hour shift), excluding controls and calibrators, as applicable. Please provide the number of kits you can manufacture per day/week for distribution in the United States.\]***

#### 8) Distribution Plan

The product will be distributed by ***\[please describe the distribution plan for the product and list all current US distributors*\]**.

#### 9) Reagent Stability 

***\[Briefly describe the stability test plan for \[test name\] reagents and include any accelerated stability information, if available.\]* Reagent stability studies generally do not need to be completed at the time of EUA issuance; however, the study design should be agreed upon during interactive review and the stability studies started immediately following authorization, if not before. You should consider the following recommendations when designing your stability study:**

-   **For EUAs you may follow the current FDA recognized “Clinical Laboratory Standards Institute (CLSI) Standard EP25 – *Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline*” when evaluating the suitability of stability study designs. If you are planning to pursue a clearance or approval for your device, we recommend discussing with FDA in more detail your stability design to facilitate potential use of the EUA data in your regular premarket submission.**

-   **For all the stability evaluations, you should include your external positive and negative controls and at least one sample, which should be prepared by spiking negative clinical matrix at an analyte concentration of 3-5x LoD of inactivated SARS-CoV-2, not recombinant protein. Please note that use of the positive controls alone is not recommended for reagent stability evaluation because controls are usually formulated at a moderate positive level.**

-   **If you are using multiple clinical sample types in which similar LoDs are determined, you should use the most challenging clinical matrix for this study.**

-   **You should evaluate at least 5 replicates and, if available, 3 different lots of reagents.**

-   **You should design your study to provide data for a timeframe that is about 10% longer than the one to be authorized. For example, 18 months should be supported by stability data out to 20 months and 7 days should include stability data out to 8 days.**

-   **FDA considers 15-30°C to represent room temperature conditions. Ideally you should evaluate stability at both 15°C and 30°C; however, for the purposes of the EUA evaluation, 30°C is generally appropriate as the worst-case scenario.**

-   **Unopened Kit Shelf-Life Stability:**

    -   **You should evaluate real-time kit stability studies with unopened kits stored at the claimed storage temperature for your test.**

    -   **Accelerated stability evaluations for unopened kits can be included for EUA requests to support shelf-life claims up to six months while the real-time studies are on-going. However, please note real-time stability data is generally needed to support regular pre-market submissions.**

-   **Unopened Kit Shipping Stability: You should evaluate the anticipated handling and shipping times and temperatures expected for unopened kits under different temperature conditions (e.g., summer, winter). The recommended summer profile is storage at 40℃ for 8 hours and then 22℃ for 4 hours and the recommended winter profile is -10℃ for 8 hours and then 18℃ for 4 hours.**

-   **In-use/Opened Kit Stability: Depending on your device, your stability study design should also support in-use stability of the kit reagents once the kit has been opened, e.g., storage at 2-8°C for 7 days. This includes on board stability once reagents have been placed on the instrument (if applicable).**

-   **Inverted stability (if applicable): Study should support stability for kits if stored inverted or in the wrong orientation.**

-   **Freeze-thaw Stability: If you recommend aliquoting the reagents to meet the end-users needs following the initial thaw this recommendation should be supported by a freeze-thaw stability study, including the specific number of allowed freeze-thaw cycles.**

-   **FDA recommendations for analysis of real time stability studies are as follows:**

    -   **Baseline of the study (t=0 of stability study) should not exceed one month from production;**

    -   **Clear baselines should be described (e.g., one month from production) for each stability claim under each study;**

    -   **Claims should be determined based on regression analysis. Any %change (%shift) from time zero (baseline) should be calculated between the target claim and the zero-time as (Ttest-Tbaseline)/ Tbaseline\*100 with 95% confidence interval (CI) using the regression equation obtained from plotting the mean values. When formulating your acceptance criteria for evaluating the shift from baseline you should consider the reproducibility of your device. Generally, the shift at the target claim due to storage cannot exceed 10-15%. The target stability is the next to last tested point that was within +/- 10% of time zero; and**

    -   **Acceptance criteria may differ depending on the reproducibility of your device, the distribution of analyte concentration expected in samples from the intended use population, and the risk of false results to public health.**

### J. PERFORMANCE EVALUATION

**The following validation studies should be performed to support your EUA request. Please note that, particularly for new technologies, FDA may request additional studies so we can adequately assess the known and potential risks and benefits associated with the candidate test. *\[For each validation study, you should provide a study protocol that includes a detailed, step-by-step description of how samples were prepared and how testing was conducted. You should also include complete study line data in an Excel-compatible format for all validation studies. Such line data should include the following information in individual columns:***

-   ***coded identifiers for all samples and replicates;***

-   ***the clinical matrix tested;***

-   ***the SARS-CoV-2 concentration (applicable to studies using contrived samples);***

-   ***raw signal output (i.e., cycle threshold (Ct) values) and final results for each distinguishable target for both the candidate test and the comparator test (as applicable); and***

-   ***for both the candidate test and the comparator test, a final result for each sample/replicate based on the result interpretation algorithm of the test.\]***

#### 1) Limit of Detection (LoD) - Analytical Sensitivity:

**You should determine the LoD of the candidate test utilizing the entire test system from sample preparation and extraction to detection. We recommend spiking quantified inactivated virus (e.g., heat treated, chemically modified, or irradiated virus) into real clinical matrix (e.g., nasal or nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid, sputum, etc.).** **As positive natural clinical samples are generally available, a quantified known positive clinical sample as determined by an EUA**- **authorized test can be used to create dilutions in clinical matrix for LoD determination. Synthetic RNA is not an appropriate test material for the LoD studies. Respiratory samples collected from SARS-CoV-2 negative individuals can be used as clinical matrix. Collection media without clinical matrix or collection kits that were not used to collect a clinical sample are generally not considered real clinical matrix.**

**FDA recommends that preliminary LoD be determined by testing a 2-3-fold dilution series of 3 replicates per concentration, and then confirmed with 20 replicates of the concentration determined to be the preliminary LoD. For purposes of this document, the preliminary LoD is the lowest concentration that gives positive results 100% of the time and the final LoD is the lowest concentration at which at least 19 of 20 replicates are positive. The preliminary LoD studies should include at least one concentration that does not yield 100% positive results. If multiple clinical matrices are intended for clinical testing, you should include the results from one representative matrix of each indicated clinical matrix to FDA. The most challenging matrix of the claimed matrices should be tested. For example:**

-   **If the candidate test is indicated for testing common upper respiratory tract samples (e.g., nasopharyngeal (NP) swabs, oropharyngeal (OP), swabs, nasal swabs, anterior nasal swabs, mid-turbinate nasal swabs, nasal aspirates, and nasal washes etc.), please submit results from NP swabs as FDA considers this to be the most challenging upper respiratory matrix.**

-   **If the candidate test is indicated for testing common lower respiratory tract samples (e.g., tracheal aspirates, sputum, etc.), please submit results from sputum as FDA considers this to be the most challenging lower respiratory matrix.**

-   **If the candidate test is indicated for testing both, upper and lower respiratory matrixes, submitting results from sputum samples may suffice to support both upper and lower respiratory matrices.**

-   **If the candidate test is indicated for testing alternative samples, such as saliva, oral fluid, buccal swab, etc., please submit results from testing each of the claimed uncommon sample types.**

-   **If relevant, FDA recommends that you follow the most current version of the CLSI EP17 “*Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures*.”**

***\[Please provide your complete LoD study protocol that includes a step-by-step description of how samples were prepared and tested with your device, the specific viral material used to assess the LoD (e.g., irradiated virus),** **and the LoD (with appropriate units) for your assay. Please provide the line data for the LoD study in an Excel-compatible format. If the assay includes use of an analyzer or application to generate test results, please include the analyzer value for each test replicate.\]***

LoD studies determine the lowest detectable concentration of SARS-CoV-2 at which approximately 95% of all (true positive) replicates test positive. The LoD was determined by limiting dilution studies using characterized ***\[please describe samples used in the study, e.g., viral stocks\]***.

***\[List/describe the following in this section:***

-   ***Titers and strains of the SARS-CoV-2 stocks used for the LoD study and how the organism stocks were prepared and how the titers were determined.***

-   ***The dilution factor and number of serial dilutions of the characterized SARS-CoV-2 that were tested to determine the LoD.***

-   ***The starting concentration, dilution factor used to reach target concentration, the volume of negative matrix with inactivated SARS-CoV-2 spiked onto each swab in your LoD study, and the type of dilutant used (e.g., Phosphate Buffered Saline (PBS), saline, etc.) to prepare each replicate in your LoD study. Please note that it is generally not appropriate to prepare samples with your assay reagents (e.g., extraction buffer) nor is it generally appropriate to dilute clinical matrix in VTM if the test is not indicated for use with VTM.\]***

Serial dilutions of the characterized SARS-CoV-2 made in clinical matrix obtained from individuals who tested negative for SARS-CoV-2 were then tested in ***\[number of replicates\]*** replicates. The lowest concentration at which all ***\[number of replicates\]*** replicates were positive was treated as the tentative LoD for each test. The LoD of each test was then confirmed by testing ***\[number of replicates (at least 20 recommended)\]*** with concentrations at the tentative limit of detection. The final LoD of each test was determined to be the lowest concentration resulting in positive detection of ***\[number of positive replicates (at least 19 out of 20 replicates)\]. \[Include analysis of LoD results, indicating the final LoD for each test.\]***

**Note: The LoD range finding study should include at least one concentration that achieves 95% detectability of replicates and at least one concentration that achieves less than 95% detectability. Replicates should be interpreted per the result interpretation of your test.**

#### 2) Inclusivity (analytical reactivity): 

**Mutations in the SARS-CoV-2 genome have been identified as the virus has spread. A mutation is an individual genetic change in a SARS-CoV-2 virus sequence when compared with a reference sequence such as Wuhan-Hu1 or USA-WA1/2020. A new virus variant of SARS-CoV-2 has one or more mutations that differentiate it from the wild type or predominant virus variants already circulating in the general population. Variants of SARS-CoV-2 are identified by genomic sequences that contain mutation(s) in the RNA genome, which could result in amino acid substitutions, insertions, and/or deletions in viral proteins. Different variants can result in different phenotypes (e.g., a difference in antigenicity, transmissibility, or virulence). Viral mutations and viral variants could result in altered immunogenicity relative to the originally isolated virus, which could impact the performance of in vitro tests.**

**Test developers should monitor new and emerging viral mutations and variants that could impact molecular test performance on an ongoing basis. This includes assessing the prevalence of viral mutations in sequence databases (e.g., the GISAID**[17] **database), as mutations observed in these databases at a significant frequency may signify that the mutation is present in an increasing proportion of infected individuals in the U.S. FDA currently considers a significant frequency to be greater than 5% (when considering at least 2000 sequences over a recent period of time, such as the past week, month, or quarter). Monitoring should also include identifying if there are multiple credible reports indicating that a given viral variant (which may have one or more mutations) has the potential to increase virulence, increase transmission, or otherwise increase the public health risk. FDA recommends monitoring on at least a monthly basis in light of the rate of occurrence of mutations and variants and the importance of assessing their impact.**

**For any viral mutations and variants that are identified as prevalent and/or clinically significant as described above, you should assess whether the resulting predicted amino acid change(s) in the viral proteins are critical to your test design. This may be accomplished via *in silico* analysis of published SARS-CoV-2 sequences compared to the assay’s primers and probes. If the mutations are found to be critical to your test design, such mutations and variants should be evaluated using clinical (or contrived, as available and as appropriate) samples to assess the impact of the mutation or variant on your test’s performance. The aggregate impact of the mutations should not reduce the clinical performance of the test by 5% or more or decrease the clinical performance point estimates for the test below the clinical performance recommendations described in Section J(10). Please see the FDA guidance document “[*Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests*](https://www.fda.gov/media/146171/download)” for additional discussion regarding monitoring the impact of genetic variants on molecular diagnostic tests.**[18]** **

**FDA also has ongoing monitoring efforts and may identify a viral mutation or variant as clinically significant for which testing with clinical (or contrived, as available and as appropriate) samples would be recommended to assess the impact of the mutation or variant on the performance of your test.**

**We recommend providing a summary of the strategy used to choose targeted amplification regions and the specific primer and probe regions, as applicable. Developers should document the methodology and results of an *in silico* inclusivity analysis that establishes the extent to which variation in the SARS-CoV-2 genome may impact sensitivity of test performance.**

***\[Please provide your plan for monitoring for new and emerging SARS-CoV-2 viral mutations and variants on an ongoing basis and for assessing the impact of mutations and variants that have been identified as prevalent and/or clinically significant on the performance of your assay over time.\] ***

***\[For mutations and variants that have been identified as prevalent and/or clinically significant as part of ongoing monitoring at the time of your EUA request, please provide information on the potential impact of the mutation(s) and variants on your test’s performance or explain how the risk associated with the unknown performance of your device in samples from individuals with the variant(s) can be adequately mitigated.\]***

#### 3) Cross-reactivity (Analytical Specificity):
**Cross-reactivity studies are performed to demonstrate that the test does not react with related pathogens, high prevalence disease agents, and normal or pathogenic flora that are reasonably likely to be encountered in a clinical sample. It is appropriate to conduct an in silico analysis of published genome sequences using the assay’s primers and probes. If in silico analyses of the target primers and probes reveal ≥ 80% homology between the cross-reactivity microorganism(s) and your test primers/ probe(s), we recommend that you conduct wet testing with that organism(s). We recommend using concentrations of 10^6^ CFU/ml or higher for bacteria and 10^5^ pfu/ml or higher for viruses. In silico analyses alone may be appropriate for organisms that are difficult to obtain. We recommend assessing potential cross-reactivity of the organisms listed in the table below, as applicable to the claimed sample type. If you are claiming an alternative matrix not listed below, please contact FDA to discuss the list of microorganisms recommended for testing.** 

***\[Please provide your complete cross-reactivity protocol, including a step-by-step description of how samples were prepared (e.g., starting concentration, dilution factor used to reach target concentration, volume of organism suspension, volume of clinical matrix, etc.) and tested with your device, the specific materials used to assess cross-reactivity and where these materials were obtained. Please include the Certificates of Analysis for each microorganism that is tested, or equivalent information (e.g., the culture protocol, lot number, manufacturing date, viral strain, a description of viral inactivation, pre-inactivation titer, and pre-inactivation sterility for viral isolates, etc.). For bacterial isolates, information may also include the isolate source, method for identification, number of passages, microbiological features, or other information. Please provide the line data for the cross-reactivity study as part of your request, in an Excel-compatible format. If the assay includes use of an analyzer or application to generate test results, please include the analyzer value with each test replicate.\]* **

**Recommended List of Organisms to be Analyzed *in silico*  
and by Wet Testing for All Respiratory Samples**

| **High priority pathogens from the same genetic family** | **High priority organisms likely present in respiratory samples** |
|---------------------------|---------------------------------------------|
| **Human coronavirus 229E** | **Adenovirus (e.g., C1 Ad. 71)** |
| **Human coronavirus OC43** | **Human Metapneumovirus (hMPV)** |
| **Human coronavirus HKU1** | **Parainfluenza virus 1-4** |
| **Human coronavirus NL63** | **Influenza A & B** |
| **SARS-CoV-1** | **Enterovirus (e.g., EV68)** |
| **MERS-coronavirus** | **Respiratory syncytial virus** |
|  | **Rhinovirus** |
|  | ***Chlamydia pneumoniae*** |
|  | ***Haemophilus influenzae*** |
|  | ***Legionella pneumophila*** |
|  | ***Mycobacterium tuberculosis\**** |
|  | ***Streptococcus pneumoniae*** |
|  | ***Streptococcus pyogenes*** |
|  | ***Bordetella pertussis*** |
|  | ***Mycoplasma pneumoniae*** |
|  | ***Pneumocystis jirovecii* (PJP)\*** |
|  | **Pooled human nasal wash - *to represent diverse microbial flora in the human respiratory tract*** |
|  | ***Candida albicans*** |
|  | ***Pseudomonas aeruginosa*** |
|  | ***Staphylococcus epidermis*** |
|  | ***Streptococcus salivarius*** |
||

*\*M. tuberculosis* and *P. jirovecii* are applicable to lower respiratory matrices only (e.g., BAL, sputum, etc.).

**High Priority Organisms Likely Present in Saliva Samples Recommended List of Organisms to be Analyzed *in silico* and by Wet Testing for Saliva Samples\*\***

| **High priority pathogens from the same genetic family** | **High priority organisms likely in the circulating area** |
|---------------------------|---------------------------------------------|
| **Human coronavirus 229E** | **Adenovirus (e.g., C1 Ad. 71)** |
| **Human coronavirus OC43** | **Human Metapneumovirus (hMPV)** |
| **Human coronavirus HKU1** | **Parainfluenza virus 1-4** |
| **Human coronavirus NL63** | **Influenza A & B** |
| **SARS-coronavirus** | **Rhinovirus** |
| **MERS-coronavirus** | **Respiratory syncytial virus** |
|  | **Herpes simplex virus type 1 (HSV-1)** |
|  | **Epstein-Barr virus (EBV)** |
|  | **Cytomegalovirus (CMV)** |
|  | ***Moraxella catarrhalis*** |
|  | ***Porphyromonas gingivalis*** |
|  | ***Bacteroides oralis*** |
|  | ***Nocardia sp.*** |
|  | ***Streptococcus mutans*** |
|  | ***Streptococcus mitis or other Strep viridans*** |
|  | ***Eikenella sp.*** |
|  | ***Neisseria sp.*** |
|  | ***Candida albicans*** |
|  | ***Pseudomonas aeruginosa*** |
|  | ***Staphylococcus epidermis*** |
|  | ***Streptococcus salivarius*** |
|  | ***Lactobacillus sp.*** |
||

*\*\*These organisms should be analyzed/tested in addition to the ones included in the immediately preceding table.*

#### 4) Microbial Interference Studies:

**If *in silico* analysis reveals ≥ 80% homology between the cross-reactivity microorganisms and your test primers/ probe(s) set(s), we recommend that you either perform (1) a microbial interference study with SARS-CoV-2 and the microorganisms that your test primers/ probe(s) have homology to, or, as an alternative to the microbial interference study, (2) you may provide justification as to why (e.g., amount of primer(s)/ probe(s) included in your master mix) the performance of your test would not be impacted by the presence of a causative agent of a clinically significant co-infection, or (3) explain why the *in silico* results are clinically irrelevant (e.g., low prevalence of MERS-CoV, etc.).**

**Competitive microbial interference testing should be conducted for multiplex panels. The study should assess the effects of clinically relevant co-infections by testing selected microorganisms commonly found in the claimed sample matrix in the presence of SARS-CoV-2 at low concentration. The interference should be evaluated by testing with a minimum of 3 sample replicates spiked at a low (≤3x LoD) SARS-CoV-2 concentration and a high interferent level (preferably microorganisms), to represent the worst-case scenario. The interferent microorganisms can be tested individually or as a pool (of four or five) in the presence of low concentration of SARS-CoV-2. Each microorganism of a pool should be tested individually if that pool shows interference. If you plan to claim both upper and lower respiratory clinical samples, the study should be performed in the most challenging sample matrix, i.e., sputum. If interference is observed at the level tested, an additional titration study should be performed to determine the highest microorganism interferent level your test can achieve the stated performance.**

***\[Please provide your complete microbial interference study protocol, including a step-by-step description of how samples were prepared (e.g., starting concentration, dilution factor used to reach target concentration, and volume of organism suspension for both inactivated SARS-CoV-2 and microbial interferent, volume of clinical matrix, etc.) and tested with your device, the specific materials used to assess microbial interference and where these materials were obtained. Please provide the line data for the microbial interference study in an Excel-compatible format. If the assay includes use of an analyzer or application to generate test results, please include the analyzer value with each test replicate.\]***

#### 5) Endogenous/Exogenous Interference Substances Studies: 

**The extent of testing for studies of interference substances depends on the matrix that is indicated for the candidate test as well as on the technology of the candidate test. If the candidate test uses extraction methods not previously reviewed by FDA as part of premarket submission or the candidate test does not use an extraction procedure (as for example, many point-of-care tests), we recommend testing for potential interferents. The following Table includes suggested potential interferents that might be appropriate to test for a test indicated for upper respiratory samples and/or oral fluid or saliva.** **We recommend testing the following substances listed in the table below, as applicable based on the indicated matrices, with and without inactivated virus at 2-3x LoD in three replicates for each substance. Please contact FDA if you have questions about appropriate study designs.**

**List of Potential Interfering Substances Recommended for Testing When the Candidate Test is Indicated for Respiratory Samples**

| Potential Interfering Substances | Concentration |
| --- | --- |
| Afrin Original nasal spray | 15% v/v |
| Sore throat and cough lozenges such as Cepacol Lozenges (benzocaine/menthol) | 3 mg/mL |
| Chloroseptic Sore Throat spray | 5% v/v |
| Mouth Wash (Saliva) | 5% v/v |
| Cough syrup (e.g., Robitussin) | 5% |
| Mucin: bovine submaxillary gland, type I-S | 2.5 mg/ml |
| Nicotine or Tobacco | 0.03 mg/ml |
| Toothpaste (Saliva) | 0.5% v/v |
||

***\[If a concentration is not listed in the table above, please determine an appropriate concentration and provide the scientific justification supporting your proposed concentration as part of your EUA request.\]***

#### 6) Sample Stability:

**Testing should be conducted to demonstrate sample stability throughout the real-world conditions in which they are collected and tested, according to your instructions for use. When the test is intended to be performed on the sample immediately or shortly after obtaining the sample, sample stability testing could be relatively short (i.e., 2 hours at room temperature) and conducted with contrived samples at 3x LoD using inactivated virus spiked into negative clinical matrix. If you intend to test retrospective clinical samples that have been frozen, you should also conduct fresh versus frozen studies to support use of these samples.**

| LoD Target Level | Number of Samples |
| --- | --- |
| 3-5 times LoD | 10 |
| 1-2 times LoD | 30 |
| Negative | 10 |
| Total | 50 |
||

***\[Please provide a complete sample stability protocol, including a detailed, step-by-step description of how you prepared and tested each replicate, and provide all study data in an Excel-compatible format, with analyzer values, if applicable. The protocol should also include sample stability information, including the study design and results if the sample is shipped to a testing site from another location (e.g., samples collected at home or physician’s office).\]***

#### 7.  *Clinical Evaluation for Patients Suspected of COVID-19:*

**FDA recommends conducting prospective, blinded, randomized clinical agreement trials with at least 30 positive samples and 30 negative natural clinical samples (prospective, retrospective, or leftover) from patients suspected of COVID-19 by their healthcare provider. The number of negative samples may vary according to the disease prevalence at the time of your study. Evaluations with contrived clinical samples are inadequate to support the clinical performance of molecular diagnostic tests at this time.**

**If you seek authorization for multiple sample types, each sample type should be evaluated. This may be done by collecting samples from different anatomical sites from the same patient. To minimize the occurrence of discordant results due to biological variability, both samples should be collected within a short time period (e.g., within the same healthcare visit). Types of upper and lower respiratory samples are noted by the CDC at the following website: <https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html>.**[19] **Please note that specimens with and without VTM are considered two distinct types of specimens. If you are seeking indications for testing with sputum and any other respiratory sample, we recommend testing either 30 sputum samples or a combination of upper respiratory samples and sputum samples, such as 15 NP and 15 sputum samples, or 15 combined upper respiratory samples and 15 sputum samples.**

**You may use frozen samples if you demonstrate analytically that preservation of samples (e.g., by freezing at ≤-70°C) does not affect the accuracy of test results compared to freshly collected samples.**

**You may use samples that previously tested positive by another authorized RT-PCR assay without additional comparator testing. *\[Please provide the type and source of the samples, results, and numerical output signals such as Ct values or numerical output for each tested sample, and the initial test date.\]***

**Approximately 25% of the positive samples should have a low viral load (i.e., low positives) as measured by the comparator test (i.e., Ct values should be within 3 Ct of the mean Ct at the LoD of the comparator test). When conducting a prospective study, if fewer than 25% of positive samples are low positives per the comparator assay, the prospective samples may be supplemented with additional low positive samples (i.e., archived samples, samples collected from convalescent patients, etc.).**

**Samples from each individual should be evaluated with the candidate test and an authorized RT-PCR test which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction) and reports a Ct value. The comparator test may have the same, or different, targets as the candidate test; however, different primer and probe regions are recommended. The comparator test should be one of the more sensitive RT-PCR assays authorized by FDA. We encourage you to review the results from the FDA SARS-CoV-2 Reference Panel**[20] **and contact us to discuss your choice of comparator test. Evaluations with the comparator test should be conducted per the authorized instructions for use. If any modifications are made to the authorized comparator test, additional bridging studies may be necessary. Please contact FDA if you are considering using a modified configuration of an authorized RT-PCR assay.**

**When collecting samples, the standard of care sample (i.e., the sample used for clinical and not investigational purposes) should always be collected first, including when the comparator test is also the standard of care. If the comparator test is not the standard of care, swabs taken from the same anatomical area for the comparator test and candidate test (e.g., anterior nasal swabs, oropharyngeal (OP) swabs, etc.) should be randomized to ensure that bias is not introduced due to an unequal distribution of viral materials. When two distinct anatomical sites are being assessed, it is not necessary to randomize sample collection order (e.g., saliva compared to NP swabs).**

**You may consider use of an enrichment strategy in which individuals with a known COVID-19 infection status are invited to participate in your clinical evaluation study. If using an enrichment strategy, you should carefully consider how you will randomize and blind operators to the participant’s infection status and minimize potential bias. Data from an enriched study design should represent the full range of viral loads, with both low and high positives samples. Please contact FDA to discuss any alternative study designs or enrichment strategies.**

**All clinical samples tested in your study should be evaluated in accordance with the candidate test’s proposed diagnostic algorithm (i.e., tested using the procedure in the instructions for use), including retesting when appropriate. The limited volume of natural samples may preclude retesting. In instances where retesting is indicated but not performed, for the purposes of performance evaluation, initial results should be analyzed for performance and equivocal/indeterminate/inconclusive results should count against your final performance. Samples should be tested in a blinded fashion, e.g., positive, and negative samples should be presented to the end user in a blinded fashion. The end user should also be blinded to the results of any comparator method testing.**

**FDA recommends establishing a discordant analysis plan prior to your clinical study. Discordant samples should be tested with a second EUA authorized RT-PCR test that has also demonstrated high sensitivity, and which uses a chemical lysis step followed by solid phase extraction of nucleic acids (e.g., silica bead extraction). Results from a Discrepant analysis should not be included in the calculation of negative percent agreement (NPA) and positive percent agreement (PPA) but may be added to the performance table as a footnote.**

**Studies involving clinical samples (human specimens) conducted in support of an EUA request are subject to applicable requirements for Institutional Review Board (IRB) review and approval and informed consent (see 21 CFR parts 50, 56, and 812). FDA’s policy regarding informed consent requirements for certain studies using leftover, de-identified samples is outlined in the FDA guidance “[*Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-informed-consent-vitro-diagnostic-device-studies-using-leftover-human-specimens-are-not).”**[21] 

**Candidate tests should demonstrate a minimum of 95% positive and negative agreement for all sample types requested. In addition, for studies where multiple sample types from the same patient are evaluated by the candidate test, there should be no significant evidence of a trend in Ct values that is indicative of the potential for false negative results.**

***\[Please describe the clinical study used to evaluate the clinical performance of the test.\]  
***

***\[Please specify how the samples were generated, collected, and sourced. Please also specify if the samples were fully prospective or a mix of prospective and retrospective. Please specify inclusion/exclusion criteria, collection and testing sites, number of samples collected and tested, and number of operators performing the testing.\]***

##### a. Clinical Evaluation for Screening Individuals Without Symptoms or Other Reasons to Suspect COVID-19: 

**The recommendations below reflect FDA’s current thinking. The study design and recommendations may change as additional information becomes available regarding asymptomatic infections, including but not limited to viral titer dynamics and transmission rates in this population.**

**If you seek claims for screening individuals without symptoms or other reasons to suspect COVID-19, FDA recommends that you conduct a prospective clinical study in asymptomatic individuals free of any symptoms of SARS-CoV-2 infection for at least two weeks prior to enrollment and testing, if not known to be previously positive. Asymptomatic individuals who are suspected of COVID-19 (i.e., via exposure) should be excluded. As part of your clinical study protocol and data, you should document how you screened and confirmed that all enrolled individuals were asymptomatic and consistent with your proposed intended use.**

**You should follow the clinical study recommendations listed above (i.e., 30 symptomatic positive and negative samples), except that the number of enrolled patients should be sufficient to ensure at least 20 positive samples (as per a highly sensitive comparator test) are consecutively collected. A minimum of 100 consecutive SARS-CoV-2 negative samples (as per the comparator test), should be collected. The total number of samples needed will depend on the prevalence of SARS-CoV-2 in the intended use population. If less than 20 SARS-CoV-2 positive samples, as determined by the highly sensitive comparator test, are obtained from the prospective study, or prevalence in the test population is very low, you may consider enrichment strategies. For example, you may conduct an additional prospective study in an asymptomatic screening population that is under quarantine due to possible exposure, to increase the chances of obtaining more SARS-CoV-2 positive samples. Please consult FDA prior to implementing enrichment approaches in your clinical study design.**

**In the clinical study, you should compare results from your candidate test and a highly sensitive comparator test for each patient enrolled. Please refer to recommendations above regarding selection of a comparator test. Samples for the candidate test should be collected according to the instruction for use. Samples for testing with the comparator test should be healthcare provider collected NP swabs. If an NP swab cannot be collected, a MT swab may be used. Sampling for the candidate test and comparator test should occur within a short timeframe to avoid biological variability in viral load.**

**In the context of an EUA request, FDA considers samples collected at one or two sites to be appropriate. However, if you are planning to use the same data to support a subsequent De Novo/510(k) submission, we recommend that you collect samples at a minimum of three geographically and demographically diverse sites.**

**It may be possible to use archived samples that were collected from asymptomatic patients. We recommend you contact FDA to discuss such an approach prior to initiating your study.**

**The data should be sufficient to demonstrate the following minimum performance:**

-   **PPA ≥95% (Lower Bound of the two-sided 95% confidence interval &gt;76%)**

-   **NPA ≥98% (Lower Bound of the two-sided 95% confidence interval &gt;95%)**

##### b. Adding Population Screening of Individuals Without Symptoms or Other Reasons to Suspect COVID-19 to an Authorized Test:

**Alternative approaches may be appropriate for candidate tests that have been previously authorized for use with common upper respiratory samples (i.e., NP, MT, nasal swabs, etc.) from symptomatic patients. For example, if your assay is highly sensitive as determined by testing with the FDA SARS-CoV-2 Reference Panel or a recognized international standard, FDA will consider expanding your authorization to cover asymptomatic screening with a condition of authorization that you complete the study outlined above. Developers may also refer to the [*Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing*](https://www.fda.gov/media/146695/download)**[22]** for additional options when seeking a screening claim with serial testing when a clinical evaluation with symptomatic patients suspected of COVID-19 infection by their healthcare providers has been performed. FDA is open to considering additional alternative study designs to demonstrate that the performance of the candidate test is appropriate for screening individuals without symptoms or other reasons to suspect COVID-19. We recommend contacting FDA to discuss alternative study designs prior to beginning such a study.**

#### 8)  *Pooled Testing:*

**Combining multiple patient samples to create one pooled sample for testing could enable broader access to testing by increasing throughput, though it may also reduce the sensitivity of a test because samples are diluted. Therefore, FDA does not recommend sample pooling for tests with performance &lt;95% PPA** **when testing individual samples, based on validation with positive patient samples. Use of pooling should be considered in the context of the positivity rate of a test in the test population, the analytical sensitivity of the test, and the percent of weak positive subjects in the tested population. The impact of decreased analytical sensitivity depends on the percent of subject samples with viral genetic material concentrations close to the LoD (weak positives) in the tested population. Therefore, analytical sensitivity of the test with n-sample pools should be evaluated, where n is the number of samples included in the pool. When resource availability is sufficient to meet testing demand, FDA recommends considering whether the risks of reduced test sensitivity with pooling continue to outweigh the benefits of resource conservation.**

**When pooling, a negative result implies that all samples in the pool are negative. A positive result indicates that at least one sample in the pool is positive. When an n-sample pool is positive, each sample within the pool must be individually tested to determine which is/are positive. Due to the reduction in analytical sensitivity, the test report should state that pooling was used during testing.**

**A test validated for a specific n-sample pooling strategy is also considered to be validated for any number of pooled samples below n. For example, a test validated for a 5-sample pooling strategy can be performed for any n≤5 pools.**

**If you seek authorization for testing of pooled specimens, your instructions for use should include instructions for laboratories to select and implement an initial validated sample pool size and to perform ongoing monitoring of the selected and implemented pool size.**

1.  **Pooling Implementation – Determine the appropriate pool size based on percent positivity rate in the testing population and pooled testing efficiency. For swab pooling, this should include a detailed procedure describing a method to combine swabs into a single volume of transport media. The procedure should include recommendations to maximize the amount of sample resuspended into the transport media from the swab and help ensure that the user performs sample and swab handling in a manner consistent with current infection control procedures, which should also reduce the chance of carryover between sample pools.**

2.  **Pooling Monitoring – Monitor the positivity rate from pooled samples.**

3.  **Pooling Re-assessment – Reassess the impact of pooled testing on test performance.**

**These activities are described in more detail in Appendix B.**

**FDA is providing recommendations for two approaches to patient sample pooling: 1) pooling aliquots of transport media which each contain a single patient sample (media pooling) or 2) adding swabs from multiple patients into a single volume of transport media (swab pooling).**

##### a.  *Media Pooling:*

**When pooling transport media, one individual sample is defined as a single sample swab collected from a subject and placed in a specific volume of transport media. In this type of pooling, an aliquot of each individual sample is combined into non-overlapping pools of n samples and each n-sample pool is tested. Therefore, the instructions for use should specify a sample volume great enough to allow for individual and pooled testing so that, during clinical use, any samples in a positive pool can be re-tested without the need for a second sample collection.**

**FDA believes an n=5 is a reasonable starting point for validation of pooling for a high-sensitivity test in populations with a positivity rate of approximately 5% to 6%. In populations with a lower positivity rate, larger sample pools may be feasible. In populations with higher prevalence, smaller sample pools may be needed. FDA recommends that developers begin by validating their tests for pooling using an n=5. Tests validated and authorized for n=5 can then be used with any n≤5 pools, depending on testing needs and taking into consideration local positivity rate.**

**We strongly recommend that test developers develop and validate a system for deconvoluting pooled test data which is intended to accurately identify individual patient samples composing each pooled sample. If a test developer plans to use a software solution intended to deconvolute pooled SARS-CoV-2 diagnostic test data, then we recommend providing validation data establishing that the software can achieve its intended use. For example, we recommend including evidence that the software has been validated to ensure that:**

-   **The inputs and outputs of the software are appropriate for the intended use of the candidate test;**

-   **All expected inputs produce the expected outputs for all functions critical for system operation; and**

-   **The system will be provided to the customer free of defects or defects will be known and mitigated.**

**Please see section I(4) for more information on appropriate software validation approaches.**

i.  ***Media pooling: adding a pooling strategy to a previously EUA-authorized test:***

**To add an n-sample pooling strategy to an authorized assay, *you* should submit a supplemental EUA request with the appropriate validation data, as described in Appendix A. If the authorized assay has a PPA ≥ 95% when testing individual samples, based on validation with positive patient samples, the authorized assay may be used as the comparator test for the pooling validation study.**

ii.  ***Media pooling: new test (not previously authorized)***

**To include an n-sample pooling strategy for a candidate test that has not been previously authorized, you should submit an EUA request with the appropriate validation data for individual testing in the proposed intended use population (see section J(5)) as well as appropriate validation data for sample pooling, as described in Appendix A.**

##### b.  *Swab Pooling:*

**Swab pooling is an approach which conserves transport media and has the potential to maintain sensitivity of the test; however, deconvoluting which swab was positive cannot be done without collecting another sample. This approach also results in a high concentration of swab samples in transport media and thus inhibition may be observed. The effects of inhibition due to high concentrations of swab samples (e.g., mucin) and high concentrations of virus when there are multiple positive swabs in the swab pool should be investigated.**

**The validation recommendations for swab pooling are the same for tests that have and have not been previously authorized for individual sample testing. We recommend performing the two swab pooling validation studies using the highest number of swabs that is both desired and deemed feasible. If the data do not meet the acceptance criteria noted below, we recommend evaluating a lower number of swabs until the recommended acceptance criteria are met. Laboratories can proceed with testing with any number of pooled swabs up to the highest number of pooled swabs that was successfully validated.**

**If the candidate test has not been previously authorized for individual sample testing, test developers should submit an EUA request that also includes the appropriate validation for individual sample testing in the proposed intended use population. Refer to section J(5) of this template for recommendations regarding recommended clinical evaluation of individual sample testing.**

***Swab pooling validation:***

***\[For n-swab pooling strategies, the two studies below should be conducted, and the results included in your EUA request\]*:**

1.  **You should establish performance related to test interference from multiple swab samples in a single volume of transport media. N-swab samples containing the maximum number of swabs you intend to validate in the minimum volume of transport media you intend to validate should be tested with an analyte concentration of 2-3X LoD for the individual swab. The swabs should contain clinical matrix negative for SARS-CoV-2. The acceptable range of transport media volume and the maximum number of swabs should be noted in your instructions for use. We recommend testing replicates of three n-swab pooling samples at the same analyte concentration both with and without SARS-CoV-2.**

**For example, if the instructions for use for the candidate test recommends pooling three swabs (n = 3), then we recommend acquiring a total of nine confirmed negative swabs from individual subjects and adding three unique swabs to three unique tubes of transport media, thereby making three n-swab pooling samples. Each n-swab pooling sample should be spiked with either a positive patient sample (in transport media), live virus, or inactivated virus at a concentration of 2-3X the LoD of the candidate test. We recommend testing a total of at least 20 replicates, which can be composed of equal numbers of aliquots taken from each n-swab pooling sample (i.e., 7 replicates from each sample in this example). Ideally, negative n-swab sample matrix should be tested prior to spiking to ensure that the matrix is negative. Acceptance criteria should be at least 95% agreement with the expected results and an invalid rate of &lt; 5%. *\[Please include the Ct value line data (if applicable) in your EUA request.\]***

1.  **You should evaluate the effect of high viral concentrations on candidate test performance. It appears that patients with SARS-CoV-2 infection can exhibit unusually high viral loads. This, combined with the possibility of pooling multiple positive swabs into a single volume of transport media, could result in unexpectedly high viral titer in the pooled sample. We recommend evaluating existing data on viral loads in infected subjects and, in combination with your existing LoD data, propose a maximum expected viral titer per swab. Using this number, estimate the expected viral titer in transport media with at least three positive swabs. For instance, if you expect a maximum of 100,000X LoD per swab, we recommend spiking a single negative n-swab sample with 300,000X LoD target analyte and testing with 10 replicates. It is anticipated that all replicates are either positive or have an invalid rate of ≤5%.**

#### 9) Studies to Support Point of Care (POC) Use, as applicable:

***\[If the device is intended for POC testing, please provide a detailed study description and data to demonstrate that non-laboratory healthcare providers can perform the test accurately in the intended use environment\].* Your studies to support a POC claim should include the following: (1) a POC clinical evaluation including use of appropriate sites and test users, (2) supplemental POC samples, and (3) POC flex studies. For more details, please see each section below**

##### a. Clinical Evaluation 

**The clinical study design should reflect how the test will be used in clinical practice. It is expected that a test with “POC” designation will be widely used in CLIA waived medical facilities (e.g., physician office, outpatient clinic, emergency room (ER)), but also in less traditional settings (e.g., tents, schools, etc., with health care provider oversight of testing) where health care providers are present.**

###### i. Sites and Test Users (Operators):

**You should select one or two non-laboratory sites in the United States (U.S.) to assure that the operators are representative of intended operators in the U.S., e.g., doctor’s office, ER, outpatient clinic, drive-through testing facility, or another area in a medical facility outside the central laboratory where samples are collected and tested in real time. This would allow evaluation of the sample collection and handling, including addition into the sample port/well of the test, both of which may be significant sources of error. Four to six operators, representing intended healthcare provider operators, but who are not laboratory trained (e.g., nurses, nursing assistants and doctors) should participate in the study. Testing should be performed using only Quick Reference Instructions (QRI) - supplemental materials, such as a video or a mobile application that can be easily accessed by the user, are encouraged to be included with the proposed candidate test but should not be used during this study to mimic the worst-case scenario.**

***\[Please provide the detailed individual replicate result data in an Excel-compatible formant and protocols for each of your studies, including:***

-   ***The objective of the study;***

-   ***Detailed test procedure;***

-   ***Materials used;***

-   ***A list of samples tested;***

-   ***Results (presented in tabular format), including invalid results;***

-   ***Conclusions;***

-   ***Any appropriate mitigation** **measures (e.g., labeling changes, changes to test design, etc.); and***

-   ***Operator background (e.g., education, training, experience, etc.)***

***As part of your EUA request, please include a table in which your study results are stratified by operator.\]***

###### ii. Comparator Method:

**A description of an appropriate clinical comparator test is included in section J7 above.**

###### iii. Clinical Samples

**A total of 30 prospectively collected positive (confirmed by an EUA-authorized test) and 30 negative natural clinical samples should be tested (mock clinical samples are not appropriate). Testing should be conducted for at least 2 weeks. If an insufficient number of positive results is observed after such time (&lt;30), you may collect samples at another site to ship to the testing site or use banked samples to supplement your positive samples. Banked samples should not be pre-selected based on Ct value and should be presented blinded (mixed with negatives) to the testing site. Ideally, the same comparator test should be used for banked and prospectively collected samples.**

###### iv.  *Clinical Performance*

**A molecular POC candidate test should demonstrate positive and negative agreement of ≥ 95%. However positive agreement of ≥ 80% may be considered with appropriate limitations added to the intended use that would mitigate the risk of false negative results. For example, negative results may be considered presumptive negative if the demonstrated PPA is lower than 95%.**

##### b. Performance around LoD

You should also conduct testing with samples prepared with SARS-CoV-2 viral load near the LoD of your assay in clinical matrix. The testing should be conducted by minimally trained operators and should consist of 10 low positives (&lt;2 times LoD) and 10 negative samples per site. All contrived samples should be blinded and randomized and each operator should test at least three low positive and three negative samples integrated into the site’s workflow with the clinical samples above. These samples are intended to supplement, not replace, the clinical samples in your study. 

***\[Please include a table in an Excel-compatible format in which your study results are stratified by operator.\]***

##### c. POC Flex Studies

**You should also conduct a thorough hazard analysis considering the main known sources of errors. Based upon your hazard analysis, you should conduct flex studies to evaluate the impact of errors, or out-of-specifications conditions, on the candidate test performance. Each sample should be prepared at 2xLoD in negative clinical matrix and should be evaluated in three replicates for each condition under evaluation. Flex studies can be conducted with trained operators at an internal testing site. Each study should be performed using a pre-defined study protocol that includes the following:**

-   **The objective of the study;**

-   **Detailed test procedure; and**

-   **Materials used.**

**Potential stress conditions include:**

-   **40°C and 95% room humidity (RH) (mimicking hot and humid climates);**

-   **Delay in sample testing or reading time;**

-   **Delay and/or disturbance in operational steps;**

-   **Sample volume variability;**

-   **Buffer volume variability;**

-   **Read time variability; and**

-   **Other, as appropriate.**

***\[Please provide a detailed, step-by-step description of how you prepared and tested each replicate and provide all study data in an Excel compatible format, with analyzer values, if applicable.*** ***Data for each sample evaluated (i.e., line data) should be provided. If erroneous results are observed during studies evaluating the robustness of the device, adequate mitigation(s) should be provided.\]***

**Please see the Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Home Use**[23] **for more in-depth flex study designs. Alternative sources of information on flex studies that may be appropriate for the candidate test can be found on the FDA CDRH website containing *[CLIA Waiver by Application Decision Summaries](https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries).***[24]

#### 10) Studies to Support Authorization of Multi-analyte Respiratory Panels:

**If you are requesting an EUA for a multi-analyte respiratory panel, analytical and clinical evaluations for each target analyte should be included. We recommend considering the study designs and data summaries noted in the published EUA Summaries and Instructions For Use of authorized multi-analyte tests.**

**If you are planning to use the Right of Reference to the CDC Influenza SARS-CoV-2 (Flu SC2) performance data, please see the web page <https://www.cdc.gov/coronavirus/2019-ncov/lab/multiplex-faq.html>**[25] **for more information.**

##### a. Addition of SARS-CoV-2 to Previously FDA-cleared Multi-Analyte Respiratory Panels:

**To add the SARS-CoV-2 target to respiratory panels previously cleared by the FDA where the SARS-CoV-2 reagents are run in a separate well (or tube) and no modifications are required to the cleared portion of the panel, only studies for validation of the SARS-CoV-2 reagents previously described in this template are recommended.**

**To add the SARS-CoV-2 target to respiratory panels previously cleared by the FDA where the SARS-CoV-2 reagents are combined in the same well as the reagents for previously cleared analytes (in a multiplex reaction), the following studies should be conducted to validate the SARS-CoV-2 reagents and the modifications made to the cleared respiratory panel:**

-   **Studies previously described in this template to validate the SARS-CoV-2 reagents**

-   **LoD confirmation of the previously cleared analytes by conducting side by side testing of 3-5 replicates of serially diluted viruses with modified and original versions of the test to show that the LoD is unchanged due to modifications**

-   **Testing 10 retrospective positive samples for each previously cleared analyte**

-   **Competitive inhibition study with clinically relevant titers of each analyte in the panel (viruses 10^5^ PFU/mL, bacteria 10^6^ CFU/mL)**

##### b. Multi-analyte Panels not Previously Cleared by the FDA: 

**To support an EUA for a multi-analyte respiratory panel candidate test that was not previously cleared by FDA, analytical and clinical evaluations for each target analyte should be provided.**

###### A. Analytical Performance:

**The following analytical studies should be conducted by wet testing and data provided to the FDA for review:**

-   **Limit of Detection (Analytical Sensitivity)**

-   **Cross-Reactivity / Microbial Interference **

-   **Inclusivity / Analytical Reactivity   **

-   **Collection Media Equivalency – each claimed additional sample collection media not used in your clinical study should be validated (if appropriate for study designs) **

-   **Competitive microbial interference (for organisms for which the test is not indicated for use)**

-   **Competitive inhibition (for analytes for which the test is indicated for use)**

-   **Interfering Substances Study (Endogenous and Exogenous) **

-   **Clinical Sample Stability **

-   **Reagent Stability testing protocol  **

-   **Carry over/Cross-Contamination (if a new instrument not previously cleared/approved by the FDA is used with the candidate test) **

-   **Reproducibility and Repeatability (if a new instrument not previously cleared/approved by the FDA is used with the candidate test) **

-   **Fresh vs. Frozen Samples. If you intend submit data testing archived frozen samples in support of your EUA request, please conduct an analytical study to demonstrate that preservation of samples (e.g., by freezing at ≤-70°C) does not affect the accuracy of test results compared to freshly collected samples.**

##### c. Clinical Performance:

**To evaluate the clinical performance of your multi-analyte candidate test, a prospective clinical study should be conducted. Considering the public health needs in the current emergency, a clinical performance study in support of the EUA request may be conducted at one site testing archived positive and negative clinical samples with known sample types. The pre-selection of archived positive samples should represent a range of viral load or Ct values including low positive samples near the candidate test cut-off.**

**For the non-SARS-CoV-2 analytes, such as Influenza A, Influenza B, and Respiratory Syncytial Virus (RSV), etc., a minimum of 50 positive Influenza A, 30 positive Influenza B, and 30 positive RSV archived samples should be included in the clinical study.**

**Since your candidate test has not been FDA-cleared for the respiratory pathogens for which it is indicated, and it is likely that the candidate test would be used in patients with respiratory symptoms in lieu of an FDA-cleared respiratory panel, FDA generally intends to include a condition of authorization that you conduct a post EUA prospective clinical study. The prospective clinical study should include a minimum of three sample collection sites and three testing sites, prospectively enrolling patients with general respiratory symptoms. Until the post-EUA prospective clinical study is completed, and the study results are reviewed by the FDA, FDA recommends including a warning/limiting statement in the instructions for use for your test indicating that results (positive and negative) for the non-SARS-CoV-2 analytes should be confirmed with an FDA-cleared nucleic acid amplification test (NAAT) if clinically indicated.**

**For multiplex candidate devices that detect and differentiate SARS-CoV-2, Influenza A/B, and RSV viral nucleic acids, a minimum of 50 positive SARS-CoV-2, 50 positive Influenza A, 30 positive Influenza B, and 30 positive RSV prospectively collected and tested samples should be included in the prospective clinical study enrolling prospective samples (an all-comers study) post-authorization.**

**The clinical performance of the candidate test for the non-SARS-CoV-2 analytes (e.g., Influenza A/B and RSV, etc.) should be determined by comparison to an FDA-cleared molecular test used as a comparator test. Using an FDA-cleared molecular test with prospective clinical study data from the past 5 years as the comparator test for assessing clinical performance of your device is recommended.**

**Since most FDA-cleared comparator test options have been validated and cleared for use with NP swab and/or nasal swab samples only, if you intend to assess clinical performance of your device testing other typical upper respiratory tract sample types (e.g., nasal mid-turbinate swab, nasopharyngeal wash/aspirate, nasal wash/aspirate, and oropharyngeal swabs, etc.), and the FDA-cleared molecular test you intend to use as the comparator test has not been cleared for use with the other typical** **upper respiratory tract sample types you wish to claim, you should conduct a paired-sample study in which one of the paired samples of an FDA-cleared sample type (e.g., NPS or NS) is tested with the FDA-cleared comparator test and the other paired sample of a typical upper respiratory tract sample type you intend to claim (e.g., nasal mid-turbinate swab or nasopharyngeal wash, etc.) is tested with your candidate device. Alternatively, as a less burdensome approach, you could validate the FDA-cleared comparator test for use with the desired sample type by performing an analytical LoD comparison study between the desired typical upper respiratory tract sample type and an FDA-cleared upper respiratory tract sample type using the comparator test prior to initiating the clinical evaluations.**

**If you intend to assess clinical performance of your device testing an atypical sample type (e.g., saliva, buccal swabs, etc.), and the FDA-cleared molecular test you intend to use as the comparator test has not been cleared for use with the atypical sample type you wish to claim, you should conduct a paired-sample study in which one of the paired samples of an FDA-cleared sample type (e.g., NPS or NS) is tested with the FDA-cleared comparator test and the other paired sample of an atypical sample type you intend to claim (e.g., saliva, oral fluid, and buccal swabs, etc.) is tested with your candidate device. The alternative approach described above for the typical upper respiratory tract sample types is not appropriate, and therefore, not appropriate, for the atypical sample types.**

**The performance expectation and recommended comparator method for SARS-CoV-2 are noted in Section J(5). For Flu A/B, and other respiratory viruses,** **PPA should be &gt;90% (with a lower bound of the two-sided 95% confidence interval &gt;80%), and the NPA should be &gt;95% (with a lower bound of the two-sided 95% CI &gt;90%) in comparison to an FDA-cleared molecular test.**

**We recommend that you submit a Pre-EUA with an outline of the studies that you plan to conduct to support the FDA-authorization or contact FDA at <CDRH-EUA-Templates@fda.hhs.gov> for specific feedback.**

##### d. Claiming Multiple Typical Upper Respiratory Tract Sample Types for use with Multi-analyte Panels not Previously Cleared by the FDA: 

We recommend that you conduct an LoD study using the most challenging typical upper respiratory tract sample type you wish to claim with your candidate device (e.g., NP swab and nasal swab, etc.). In addition, you should attempt to include all typical upper respiratory tract sample types that you intend to claim for use with the candidate test in the pre-authorization clinical performance evaluation study. If you are unable to include all desired typical upper respiratory tract sample types in the pre-authorization clinical performance evaluation study, after demonstrating due diligence on your part to enroll such samples, you may claim the following typical upper respiratory tract sample types if you have validated your device analytically and clinically with NP swabs, nasal swabs, and/or MT swabs: NP swabs, anterior nasal swabs, MT swabs, NP washes/aspirates, nasal washes/aspirates, and oropharyngeal swabs, as long as all your claimed typical upper respiratory tract sample types are incorporated into the post-authorization prospective clinical study. For any typical upper respiratory tract sample type(s) that was/were not evaluated in the pre-authorization clinical study, we recommend including a limiting statement in your test’s labeling indicating that the performance of your test testing such typical upper respiratory tract sample type(s) has not been evaluated. Once the post-authorization prospective clinical study is completed and the clinical performance of your test testing such typical upper respiratory tract sample type(s) is deemed appropriate by the FDA, you may remove this limiting statement from your test’s labeling. 

Atypical sample types (e.g., saliva, oral fluid, and buccal swabs, etc.) and lower respiratory tract sample types (e.g., BAL and sputum, etc.) should be validated with LoD studies performed in each of the claimed sample matrices. Additionally, both the pre-authorization and post-authorization clinical evaluation studies should include these sample types in the study design.

#### 11) Claiming Multiple Instruments and/or Extraction Methods:

**FDA recommends the following analytical and clinical validation to validate use of a new test with multiple thermocyclers and extraction methods.**

-   ***Limit of Detection (LoD):***

**These studies should be repeated for each clinical matrix for which the candidate test is indicated for use. Pick one RT-PCR instrument and determine the tentative LoD (using 5 replicates in 10-fold dilution) followed by the confirmatory LoD (20 replicates spiked at tentative LoD) for each extraction method on the chosen instrument. Note: If you detect 20/20 replicates in your confirmatory LOD study you should test the next lower concentration, using a 3-fold dilution, until you achieve a hit rate of &lt;20/20.**

-   **If the different extraction methods yield a similar LoD (≤3 times LOD) on the RT-PCR instrument chosen for initial testing, pick one extraction method for further LoD determination on the remaining RT-PCR instruments and follow the recommendations below.**

-   **If the extraction methods do not yield a similar LoD on the chosen RT-PCR instrument, please choose the extraction method with the worst LoD for further comparison of the LoD on all RT-PCR instruments.**

**For all other RT-PCR instruments you should use the following adaptive LoD study design:**

-   **Please perform a refined tentative LoD study with 5 replicates at 0.5, 1, and 1.5 to 2 times LoD. If you detect 4/5 replicates as positive at all the tested levels, you need to include the next higher concentration (i.e., 3 times LoD). If you obtain 5/5 replicates at 0.5 times LoD, you need to test the next lower concentration (i.e., 0.25 times LoD). You should test in this manner until you find the lowest concentration that gives you 5/5 positive results for the tested RT-PCR instrument. This concentration should be used for a confirmatory LoD study for that RT-PCR instrument using 20 replicates.**

**Final reported LoD: *\[Please include in your EUA request a list of all RT-PCR instruments with their respective LoDs, if different LoDs are obtained.\]* LoDs are considered comparable if they are between 1-3 times LoD. These studies should be repeated for each clinical matrix for which the candidate test is indicated.**

**Note, if there are differences in the extraction input volume, extraction elution volume, and PCR input volume (extracted nucleic acid) then the LoD should be confirmed for each.**

-   ***Interference Substances Studies (if applicable):***

**FDA recommends evaluating interfering substances with the extraction method and RT-PCR instrument combination that has the least sensitive LoD.**

-   ***Inclusivity Testing:***

**FDA recommends evaluating inclusivity with the extraction method and RT-PCR instrument combination that has the least sensitive overall LoD.**

-   ***Exclusivity Testing:***

**FDA recommends evaluating exclusivity with all extraction/instrument combinations.**

-   ***Clinical study:***

**If an LoD study confirms equivalency for all RT-PCR instruments (between 2-3 times LoD), then the clinical study may be conducted with any RT-PCR instrument. If one or more RT-PCR instruments have different LoDs, we recommend conducting the clinical study with the extraction method / RT-PCR instrument combination with the worst LoD.**

### K. UNMET NEED ADDRESSED BY THE PRODUCT 

**This section will be completed by FDA.**

### L. APPROVED/CLEARED ALTERNATIVE PRODUCTS

**There is no adequate, approved, and available alternative to the emergency use of the product.**

### M. BENEFITS AND RISKS:

**This section will be completed by FDA.**

### N. FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:

**During review, FDA will make available Fact Sheet templates. See examples for authorized tests on our website.**[26]

### O. INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:

***\[You should include Instructions for Use, Box Labels, Vial Labels, and any other proposed labeling.\]***

### P. RECORD KEEPING AND REPORTING INFORMATION TO FDA:

**As allowed by Section 564(e) of the FD&C Act, FDA may require certain conditions as part of an EUA. FDA generally includes the following record keeping and reporting information requirements in the EUA.**

***\[Test Developer name\]*** will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report on adverse events, and this website[27] is referenced in the Fact Sheet for Health Care providers as well as through the ***\[Test Developer name\]*** Product Support website: ***\[Include link to Test Developer’s Website\]***. Each report of an adverse event will be processed according to ***\[Test Developer name\]***’s Non-Conformance Reporting Requirements, and Medical Device Reports will be filed with the FDA as required. Through a process of inventory control, ***\[Test Developer name\]*** will also maintain records of device usage/purchase. ***\[Test Developer name\]*** will collect information on the performance of the test, and report to FDA any suspected occurrence of false positive or false negative results of which ***\[Test Developer name\]*** becomes aware. ***\[Test Developer name\]*** will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

### Appendix A: Media Pooling Validation

***Preliminary Clinical Sample Pooling Validation Study***

**The test developer should conduct a preliminary clinical sample pooling validation study with individual positive clinical samples, comparing the performance of the candidate test when testing n-sample pools to the performance of a comparator test when assaying individual samples. We recommend using only a high sensitivity EUA-authorized RT-PCR assay which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction) as the comparator test. If available, FDA recommends selecting a comparator test that has established high sensitivity with an internationally recognized standard or FDA SARS-CoV-2 Reference Panel.** [28] **This study design is written assuming the study uses a separate comparator test. As discussed earlier, if requesting to add pooling to a previously authorized test, a separate comparator may not be needed, and this study design can be modified accordingly.**

**We recommend that the test developer evaluate in this preliminary clinical sample pooling validation study a minimum of 20 positive clinical samples (can be archived samples), as determined by the comparator test, with sufficient volume. The 20 samples should include 25% weak positive samples, as determined by the comparator test (i.e., (Ct values in a SARS-CoV-2 positive samples should be within 1-3 Ct of the mean Ct at the LoD of the comparator test). If weak positive samples, as determined by the comparator test, represent less than 25% of the total number of positive samples, the test developer should preferably supplement the validation sample set with additional natural weak positive samples to make up to 25% of the total enrolled positive samples. However, diluting individual natural positive samples with individual or pooled natural negative samples to reach the 25% goal is also appropriate. If archived samples are acquired, the test developer should consider using the most recently archived samples to minimize the potential risk of sample degradation due to prolonged storage.**

**All positive samples in the preliminary clinical sample pooling validation study should be individually tested by the candidate test and the comparator test. To characterize the performance of the candidate test when testing pooled samples, each individual positive sample (as determined by the comparator test) should be pooled with n-1 (e.g., where n=5, n-1=4) negative samples, as determined by the candidate test. The resulting sample pools, each consisting of 1 positive sample and n-1 negative samples, should be tested by the candidate test.**

**In order to construct the 20 n-sample pools for testing in this preliminary validation study, the test developer should use an appropriate number of individual negative samples (as determined by the candidate test) from the intended use population. While the (n-1) negative samples in a given n-sample positive pool should all be different negative samples collected from unique individuals, the same negative samples may be used in building different n-sample positive pools.**

**Based on this recommended study design, the preliminary clinical sample pooling validation study should generate the following three types of results for each enrolled positive sample: Candidate test individual sample testing result (Candidate~individual~), Candidate test pooled sample testing result (Candidate~pool~), and Comparator individual sample testing result (Comparator~individual~).**

**PPA between testing individual samples using the candidate test and testing individual samples using the comparator test (PPA, Candidate~individual~ vs. Comparator~individual~) should be estimated initially. If PPA (Candidate~individual~ vs. Comparator~individual~) is &lt;95%, the candidate test should not be used to test pooled samples. If PPA (Candidate~individual~ vs. Comparator~individual~) is ≥95%, PPA between testing pooled samples using the candidate test and testing individual samples using the comparator test (PPA, Candidate~pool~ vs. Comparator~individual~) should then be calculated as the percent of positive pools by the candidate test among 20 individual positive samples by the comparator test. When calculating PPA for the preliminary clinical sample pooling validation study, all non-negative results testing pooled samples should be counted as in agreement with positive individually tested results.**

**If PPA (Candidate~pool~ vs. Comparator~individual~) is ≥80%, the n-sample pool is preliminarily validated. If PPA (Candidate~pool~ vs. Comparator~individual~) is &lt;80%, the test developer should repeat the preliminary validation study with smaller pool sizes to compensate for excessive loss in test sensitivity due to pooling at the larger sample size tested, until the PPA (Candidate~pool~ vs. Comparator~individual~) for a smaller pool size is ≥80%. If there is sufficient volume, the same positive samples utilized in the evaluation of a larger pool size can be used in the validation of a smaller pool size. If ≥80% PPA (Candidate~pool~ vs. Comparator~individual~) cannot be achieved for any pool sizes evaluated, the candidate test should not be used to test pooled samples.**

**To confirm that negative samples remain negative in n-sample pools, the test developer should also test in the preliminary clinical sample pooling validation study a sufficient number of individual negative samples, as determined by the candidate test, to generate at least 20 pools, each consisting of n negative samples for testing using the candidate test. For example, 100 negative samples are recommended to make up 20 5-sample negative pools (5x20 negatives). If there is sufficient volume, the same negative samples can be used to create positive and negative pooled samples.**

***Clinical Sample Pooling Validation Study with Samples from Three Geographically Diverse US Sites:***

**For tests intended to be performed at multiple laboratory sites (i.e., distributed tests), or at a single laboratory site receiving samples from geographically diverse sites, the below validation should be conducted to evaluate pooled testing in populations that may have different distributions of viral loads and different positivity rates.**

A.  ***Option A (appropriate for all tests):***

**The test developer should conduct an additional clinical sample pooling validation study with individual positive clinical samples at three geographically diverse sites in the US, assessing the PPA (Candidate~pool~ vs. Candidate~individual~) between testing n-sample pools (n is the preliminarily validated pool size) and assaying single samples using the candidate test. Each of the three sites should initiate n-sample pooling and enroll a minimum of 15 consecutive positive samples with sufficient volume for a minimum of 45 consecutive positive samples in total.**

**The validation study at each site should start from the starting time T0 and should consist of individual sample testing in parallel with the pooled testing. However, since all non-negative sample pools require testing of all individual samples included in the pool as a part of the n-sample pooling and deconvoluting workflow, the validation study essentially adds testing individual samples from the negative n-sample pools.**

**The validation study at each site may conclude at time T1, when a minimum of 15 consecutive positive individual results are obtained, including both positive individual results generated from individual testing of samples from the non-negative sample pools following the n-sample pooling and deconvoluting workflow, and positive individual results obtained from individual testing of samples from the negative sample pools for the time period from T0 to T1 \[T0, T1\].**

**Defining the number of positive individual sample results among negative sample pools as K, PPA between testing n-sample pools (n is the preliminarily validated pool size) and individual samples using the candidate test at each site should be calculated as PPA (Candidate~pool~ vs. Candidate~individual~) = 100% x (15-K)/15. It is critical that all consecutive positive samples from time period \[T0, T1\] are included in the PPA calculations. When calculating PPA for this sample pooling validation study, all non-negative results testing pooled samples should be counted as in agreement with positive individually tested results. Test developers should present PPA (Candidate~pool~ vs. Candidate~individual~) for each of three geographically diverse sites in the US separately.**

***Acceptance Criteria for Option A of the Clinical Sample Pooling Validation Study at Three Geographically Diverse US Sites:***

-   **If PPA (Candidate~pool~ vs. Candidate~individual~) for each site is ≥85%, the validation data supports n-sample pooling.**

-   **If PPA (Candidate~pool~ vs. Candidate~individual~) is ≥85% at 2 out of 3 sites, at the site where PPA (Candidate~pool~ vs. Candidate~individual~) is &lt;85%, additional data with at least 15 additional consecutive positive samples should be generated and an estimate of the PPA (Candidate~pool~ vs. Candidate~individual~) for the combined data of at least 30 consecutive positive samples should be calculated with an overall PPA target of ≥85%.**

-   **If PPA (Candidate~pool~ vs. Candidate~individual~) is ≥85% at 0 or 1 out of 3 sites, or 1 site has PPA (Candidate~pool~ vs. Candidate~individual~) &lt;85% calculated with a combined data of at least 30 consecutive individual positive samples, the validation data does not support n-sample pooling and a new decreased n (e.g., n-1) should be considered and validated.**

    B.  ***Option B (appropriate for RT-PCR tests that can generate Ct values):***

**As an alternative and potentially less burdensome approach for assessing the PPA (Candidate~pool~ vs. Candidate~individual~) at three geographically diverse sites in the US using the candidate RT-PCR test that can generate Ct values, the test developer may acquire historical individual sample testing positive results from three geographically diverse sites in the US to perform in silico analysis of PPA (Candidate~pool~ vs. Candidate~individual~) for each site. We recommend acquiring at least 30 consecutive individually positive sample results by the candidate test (could be recently acquired historical data) from each of the three sites, for a minimum of 90 consecutive individually positive sample results in total.**

**In order to conduct in silico PPA (Candidate~pool~ vs. Candidate~individual~) analyses, for each candidate test target, the test developer should estimate the Ct shift that corresponds to n-sample pools (dilution of 1:n) using both the wet testing data generated from the preliminary clinical sample pooling validation study and additional wet testing of dilutions of a positive clinical sample in replicates using the candidate test at n x LoD, LoD and LoD/n, as described below:**

-   **Assess LoD by testing serial dilutions of a positive clinical sample in pooled negative clinical samples;**

-   **Test 5 replicates of this positive clinical sample at a concentration of n x LoD (designated as sample A);**

-   **Test 10 replicates of sample A combined with (n-1) individual negative clinical samples at the LoD concentration (designated as sample B);**

-   **Test 10 replicates of sample B combined with (n-1) individual negative clinical samples at the concentration of LoD/n (designated as sample C). Percent of positive results for sample C is designated as %D.**

**Recommendations regarding estimating the Ct shift corresponding to n-sample pools (dilution of 1:n) are provided below:**

-   **Construct and present a scatter plot of Ct ~pool~ (Y-axis) vs Ct ~individual~ (X-axis) using the data from wet testing the 20 positive clinical samples in the preliminary clinical sample pooling validation study, and the first replicate of sample A (Sample A Ct ~individual~) and first replicate of sample B (Sample A Ct ~pool~).**

-   **Divide the data points into 3 subintervals based on individual Ct values: ~7 points of high Ct values, ~7 points of medium Ct values, and ~7 points of low Ct values.**

-   **Calculate the difference between Ct ~pool~ (Y-axis) vs Ct ~individual~ (X-axis) for each data point and calculate the average of differences for each subinterval as Average ~Low\ Ct\ Values,~ Average ~Medium\ Ct\ Values~, Average ~High\ Ct\ Values~.**

-   **Analyze visually whether there is a tendency that the average of the differences for high individual Ct values is larger than the average of the differences for low individual Ct values.**

-   **If such tendency is observed, use Average ~High\ Ct\ Values~ as the estimate of Ct shift for the n-sample pools. If such tendency is not observed, take an average of the differences of all 21 samples, and use this average value as the estimate of Ct shift for the n-sample pools.**

**Using the estimated Ct shift for the n-sample pools (Ct Shift) and data from the wet testing of dilutions of a positive clinical sample in replicates at n x LoD, LoD, and LoD/n, the following rules for in silico PPA (Candidate~pool~ vs. Candidate~individual~) analyses for each candidate test target can be established:**

| **Interval of individual Ct values** | **Percent of Detected in n-Sample Pools** |
|------------------------------------|------------------------------------|
| ***\[Cutoff Ct, Cutoff Ct – Ct Shift\]*** | ***0% detected*** |
| ***\[Cutoff Ct – Ct Shift, Ct at the LoD\],*** | ***(D+0)/2 % detected*** |
| ***\[Ct at the LoD, Ct at the LoD - Ct Shift\]*** | ***(95+D)/2 % detected*** |
| ***\[Ct less than Ct at the LoD - Ct Shift\]*** | ***100% detected*** |
||

**Test developers should calculate and present PPA (Candidate ~pool~ vs. Candidate ~individual~) in silico for each of the three geographically diverse sites in the US separately.**

**To lessen the burden of individual laboratory customers intending to utilize the candidate test for testing pooled samples after FDA authorization, with regard to continued monitoring after sample pooling implementation, we strongly recommend that test developers perform preliminary clinical sample pooling validations and wet testing of dilutions of a positive clinical sample in replicates at n x LoD, LoD, and LoD/n for all pool sizes that are less than or equal to n (i.e., n = 5, 4, 3, and 2) to characterize the reduction in test analytical sensitivity (i.e., shift in Ct values and the percent of individual positive samples with low viral load that may be missed due to sample pooling) with respect to each of the pool sizes. The goal of the validation is to generate the following reference table to be included in the instructions for use:**

-   **A reference table containing rules for in silico PPA (Candidate~pool~ vs. Candidate~individual~) analyses for each candidate test target for all validated pool sizes, so that each laboratory that intends to utilize the assay for testing pooled samples may utilize these rules to perform in silico PPA analyses as part of a continued monitoring plan after sample pooling implementation. See Appendix B for more information regarding the pooling re-assessment.**

***Acceptance Criteria for Option B of the Clinical Sample Pooling Validation Study at Three Geographically Diverse US Sites:***

-   **If the PPA (Candidate~pool~ vs. Candidate~individual~) in silico for each site is ≥85%, the historical data supports n-sample pooling.**

-   **If PPA (Candidate~pool~ vs. Candidate~individual~) in silico is ≥85% at 2 out of 3 sites, at the site where PPA (Candidate~pool~ vs. Candidate~individual~) in silico is &lt;85%, additional recent historical individual testing data from at least 30 additional consecutive positive samples should be acquired and an estimate of the PPA (Candidate~pool~ vs. Candidate~individual~) in silico for the combined data of at least 60 consecutive positive samples should be calculated.**

-   **If PPA (Candidate~pool~ vs. Candidate~individual~) in silico is ≥85% at 0 or 1 out of 3 sites, or 1 site has PPA (Candidate~pool~ vs. Candidate~individual~) in silico &lt;85% calculated with a combined data of at least 60 consecutive individual positive samples, the in silico validation data does not support n-sample pooling and a new decreased n (e.g., n-1) should be considered and validated.**

**Appendix B: Pooling Implementation and Monitoring**

**The recommendations in this appendix use media pooling as the basis for examples. However, the concepts also apply to swab pooling.**

***Pooling Implementation (Laboratory Monitoring Part A):***

**Prior to implementation of pooled testing using a test authorized for such indication, a laboratory should determine the appropriate pool size based on percent positivity rate in the testing population and pooling testing efficiency. Test developers should include directions in their instructions for use to enable laboratories to complete this step, such as using historical data and the information included in Table 2, as described below.**

***A.1 If Historical Data for Individual Samples are Available***

**Positivity Rate of Individual Testing**

-   **Estimate positivity rate (P~individual~) in the laboratory based on individual sample testing, considering the previous 7-10 days. P~individual~ is the number of positive results divided by the total number of tested patients during these 7-10 days.**

**Selection of n for n-sample pooling**

-   **n should never be higher than the n validated by the test developer and included in the EUA-authorized instructions for use.**

-   **Use P~individual~ and Table 2 to choose an appropriate validated pool size. Table 2 presents the maximum efficiency for the validated pool sizes corresponding to different positivity rates. If the positivity rate (P~individual~) is in Table 2, choose n from Table 2 which corresponds to the maximum efficiency (F).**

-   **If P ~individual~ in your laboratory is not listed in Table 2, you should calculate the efficiency for the maximum n which was validated, using formula F=1/ (1+ 1/n-(1-P)^n^). For example, if P ~individual~ in your laboratory is 1% and the maximum n which was validated is 5, the efficiency F=4.02 for n=5. An F of 4.02 generally means that an average of 4,020 individual samples can be tested using only 1,000 tests. You can use the same formula to calculate the efficiency for smaller sample sizes with a particular P ~individual~ as well.**

-   **If P ~individual~ is greater than 25%, then pooling patient samples is not efficient and should not be implemented.**

***A.2 If Historical Individual Data for Individual Samples is Unavailable:***

**If historical data from the previous 7-10 days is unavailable, the maximum pool size validated in the EUA and any smaller pool sizes can still be implemented, as the EUA-authorized test has been validated for the maximum pool size sample pooling. However, note that without P ~individual~, the laboratory may choose a pooling size that does not maximize pooling efficiency.**

**Table 2: Efficiency of pooling based on the positivity of SARS-CoV-2 RNA in individual samples (as an example)**

| P~individual~, percent of positive subjects in the tested population | n~maxefficiency~ (n corresponding to the maximal efficiency) | F (Efficiency of n-sample pooling corresponding to n~maxefficiency~ (a maximum increase in the number of tested patients when Dorfman n- pooling strategy used)) |
| --- | --- | --- |
| 1% | 11 | 5.11 |
| 2% | 8 | 3.65 |
| 3% | 6 | 3.00 |
| 4% | 6 | 2.60 |
| 5% | 5 | 2.35 |
| 6% | 5 | 2.15 |
| 7% | 4 | 1.99 |
| 8% | 4 | 1.87 |
| 9% | 4 | 1.77 |
| 10% | 4 | 1.68 |
| 11% | 4 | 1.61 |
| 12% | 4 | 1.54 |
| 13% | 3 | 1.48 |
| 14% | 3 | 1.43 |
| 15% | 3 | 1.39 |
| 16% | 3 | 1.35 |
| 17% | 3 | 1.31 |
| 18% | 3 | 1.28 |
| 19% | 3 | 1.25 |
| 20% | 3 | 1.22 |
| 21% | 3 | 1.19 |
| 22% | 3 | 1.16 |
| 23% | 3 | 1.14 |
| 24% | 3 | 1.12 |
| 25% | 3 | 1.10 |
||

***Pooling Monitoring (Laboratory Monitoring Part B):***

**After implementation of pooled testing using a test authorized for such indication, a laboratory should perform ongoing monitoring of the positivity rate of pooled samples (i.e., P~individual~ is the historical positivity rate and P~pool~ = the positivity rate from pooled samples from a rolling 7-10 day\* period) to ensure pooled testing remains efficient. Test developers should include directions in their instructions for use to enable laboratories to complete this monitoring, as described below.**

**\* It is recommended that P~individual~ be calculated from the previous 7-10 days (i.e., prior to implementing pooled testing), while P~pool~ is calculated from data collected during a rolling 7-10 day time frame. However, when determining if 7-10 days is appropriate, take into consideration the laboratory testing volume and percent positivity, among other factors. Note that if the number of individual or pooled positive results collected during a given time frame is less than 10, P~individual~ and P~pool~ may not be representative of the percent positivity in the testing population and the laboratory may want to consider extending the time period to increase the chance of capturing positives.**

***B.1 Historical Data for Individual Samples is Available:***

**If historical data for individual samples is available, compare P ~pool~ to P ~individual~ periodically, where P~individual~ is the historical positivity rate. If P ~pool~ is less than 85% of P ~individual~ (P ~pool~ &lt; 0.85 × P ~individual~), it is recommended that:**

-   **The n-sample pooling should be re-assessed by conducting a re-assessment study as described in “Pooling Re-assessment (Laboratory Monitoring Part C)” below.**

-   **Alternatively, if the EUA-authorized test is a high sensitivity RT-PCR assay which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction), and has established high sensitivity with an internationally recognized standard or FDA SARS-CoV-2 Reference Panel,** [29] **the size of pools may be increased taking into consideration Table 2, and the new n should not be more than the test developer validated as the maximum n in the EUA.**

-   **If P ~pool~ is greater than 25%, pooling of patient samples is not efficient and should be discontinued until the percent positivity rate decreases.**

***B.2 Historical Data for Individual Samples is Unavailable:***

**If historical data for individual samples is not available, it is recommended that n-sample pooling be assessed as follows:**

-   **After implementing a n-sample pooling strategy, first calculate the positivity rate (P ~pool-initial~) based on n-sample pool size using the data from testing pooled samples from the first 7-10 days.**

    -   **If P ~pool-initial~ is greater than 25%, pooling of patient samples is not efficient and should be discontinued until the percent positivity rate decreases.**

    -   **If P ~pool-initial~ is less than or equal to 25%, pooling of patient samples can be continued.**

-   **Continue to monitor n-sample pooling strategy by calculating the positivity rate among patient samples during n-sample pooling (P ~pools-x~) for ongoing 7-10 day periods based on n-sample pool testing. (P ~pool-x~) should be updated daily using a moving average.**

**Compare P ~pool-initial~ to P ~pool-x~ periodically. If P ~pool-x~ is less than 90% of P ~pool-initial~ (P ~pool-x~ &lt; 0.90 × P ~pool-initial~), it is recommended that:**

-   **The n-sample pooling should be re-assessed by conducting a re-assessment study, as described in “Pooling Re-assessment (Laboratory Monitoring Part C)” below.**

-   **Alternatively, if the EUA-authorized test is a high sensitivity RT-PCR assay which uses a chemical lysis step followed by solid phase extraction of nucleic acid (e.g., silica bead extraction), and has established high sensitivity with an internationally recognized standard or FDA SARS-CoV-2 Reference Panel,** [30] **the size of pools may be increased taking into consideration Table 2, and the new n should not be more than the test developer validated as the maximum n in the EUA.**

-   **If P ~pool~ is greater than 25%, pooling of patient samples is not efficient and should be discontinued until the percent positivity rate decreases.**

***Pooling Re-assessment (Laboratory Monitoring Part C):***

**If, during monitoring of the positivity rate of pooled samples, a laboratory determines a drop in the positivity rate, as discussed above, the laboratory should conduct a re-assessment study. Test developers should include directions in their instructions for use to enable laboratories to complete this step, as described below.**

***Option 1: Re-assess pooling using individually tested samples:***

-   **Pause n-sample pooling and return to individual testing.**

-   **Patient samples should be tested individually until 10 consecutive positive samples have been collected. The total number of samples, tested individually, depends on the positivity rate.**

-   **Using these samples, 10 pools should be created and tested with 1 positive and (n-1) negative samples and the PPA between testing sample pools and individual samples should be calculated.**

-   **Alternatively, if the laboratory is using an EUA-authorized RT-PCR test that can generate Ct values, the laboratory may be able to assess PPA (PPA~pool~ vs. PPA~individual~) in silico based on the individually tested sample results without performing any testing of pooled samples. In order to perform this in silico PPA assessment, the instructions for use of this EUA-authorized test must include a reference table containing information regarding the in silico PPA (PPA~pool~ vs. PPA~individual~) analysis rules established by the test developer for each test target for all validated pool sizes. Refer to the “Clinical Sample Pooling Validation Study at Three Geographically Diverse US Sites” section in Appendix A for more information regarding this reference table.**

***Option 2: Re-assess pooling using individual testing and n-sample pooled testing:***

-   **The re-assessment study should start from starting time T0 and should consist of individual sample testing in parallel with the pooled testing. However, since all non-negative sample pools should include individual testing of all individual samples included in the pool as a part of the n-sample pooling and deconvoluting workflow, the re-assessment study essentially consists of testing individual samples from the negative n-sample pools.**

-   **The re-assessment study may stop and assess at time T1 when a minimum of 10 consecutive positive individual results are obtained, including both positive individual results generated from individual testing of samples from the non-negative sample pools following the n-sample pooling and deconvoluting workflow, and positive individual results obtained from individual testing of samples from the negative sample pools for the time period from T0 to T1 \[T0, T1\].**

-   **Defining the number of positive individual sample results among negative pools as K, PPA between testing n-sample pools and individual samples using the EUA-authorized test should be calculated as PPA (PPA~pool~ vs. PPA~individual~) = 100% x (10-K)/10. It is critical that all consecutive positive samples from time period \[T0, T1\] are included in the PPA calculations. With regard to calculating the PPA, all non-negative results testing pooled samples should be counted as in agreement with positive individually tested results.**

***Re-assessment Acceptance Criteria for Option 1 and Option 2:***

-   **If the PPA (PPA~pool~ vs. PPA~individual~) is ≥ 90% (9 out of 10 or 10 out of 10), then implementation of testing using n-sample pooling is appropriate.**

-   **If the PPA between pooled-testing results and individual-testing results is less than 90%:**

-   **If PPA ≤70% (7 out of 10), reduce the pool size (consider a new n as n-1).**

-   **If PPA is 80% (8 out of 10), collect an additional 10 consecutive individually positive samples. Then, calculate the PPA from the combined data of 20 samples, between pooled testing results and individual testing results. If the PPA is ≥ 85%, then implementation of testing using n-sample pooling is appropriate. Or, to compensate for lost sensitivity, reduce the pool size (consider a new n as n-1) and continue with the re-assessment testing until PPA of pooled compared to individual testing is ≥ 90%.**

-   **If PPA of at least 85% cannot be reached for any pool size evaluated in the re-assessment, cease pooling patient samples.**

**If n-sample pooling is acceptable based on re-assessment, re-establish P ~individual~ in your laboratory by estimating the positivity rate from individual testing in the population from which the 10 (or 20) consecutive individual positive samples were collected. If the total number of samples (N\*) that needed to be tested to obtain the 10 (or 20) consecutive positive samples is stopped at the 10^th^ (or 20^th^) positive sample, then the positivity rate of 10/N\* (or 20/N\*) is overestimated. The positivity rate should be corrected by the following corresponding multiplier:**

-   **Positivity rate for 10 samples is (10/N\*) × (10/11).**

-   **Positivity rate for 20 samples is (20/N\*) × (20/21).**

**This updated new positivity rate should be used as P ~individual~ in the future laboratory monitoring (see “Pooling Monitoring (Laboratory Monitoring Part B)” above.**

[1] This template is part of the “[Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised),” available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[2] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[3] All EUA templates can be found at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.

[4] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities>.

[5] Available at <https://www.fda.gov/media/152768/download>.

[6] The CDC has granted a right of reference to the performance data contained in the CDC's EUA request for the [CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel (CDC)](https://www.fda.gov/media/134919/download) (FDA submission number EUA200001) to any entity seeking authorization for a COVID-19 diagnostic device. The CDC has also granted a right of reference to the performance data contained in the CDC's EUA request for their [Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay](https://www.fda.gov/media/139744/download) (FDA submission number EUA201781) to any entity seeking authorization for a multi-analyte respiratory panel that includes SARS-CoV-2. CDC has published the primer and probe sequences for the Influenza SARS-CoV-2 Multiplex Assay on [the CDC website](https://www.cdc.gov/coronavirus/2019-ncov/lab/multiplex-primer-probes.html).

[7] Available at <https://www.cdc.gov/csels/dls/sars-cov-2-livd-codes.html> *(last accessed on July 7, 2021). Note this website is not controlled by FDA.*

[8] Available at [https://www.hhs.gov/coronavirus/testing/covid-19-diagnostic-data-reporting/index.html](https://www.hhs.gov/coronavirus/testing/covid-19-diagnostic-data-reporting/index.html%20%20) *(last accessed on July 24, 2021). Note this website is not controlled by FDA.*

[9] Available at [https://www.hhs.gov/sites/default/files/hhs-guidance-implementation.pdf](https://www.hhs.gov/sites/default/files/hhs-guidance-implementation.pdf%20) *(last accessed on July 24, 2021). Note this website is not controlled by FDA.*

[10] Available at [https://www.hhs.gov/sites/default/files/non-lab-based-covid19-test-reporting.pdf](https://www.hhs.gov/sites/default/files/non-lab-based-covid19-test-reporting.pdf%20) *(last accessed on July 24, 2021). Note this website is not controlled by FDA.*

[11] Available at <https://www.fda.gov/medical-devices/postmarket-requirements-devices/quality-system-qs-regulationmedical-device-good-manufacturing-practices>.

[12] Further information regarding cybersecurity is available at <https://www.fda.gov/medical-devices/digital-health/cybersecurity>.

[13] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissions-software-contained-medical-devices>.

[14] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-principles-software-validation>.

[15] Available at <https://www.fda.gov/medical-devices/digital-health-center-excellence/device-software-functions-including-mobile-medical-applications>.

[16] Available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices#:~:text=Off%2Dthe%2Dshelf%20(OTS,to%20run%20device%2Dspecific%20functions](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices#:~:text=Off%2Dthe%2Dshelf%20(OTS,to%20run%20device%2Dspecific%20functions.).

[17] GISAID is a global science initiative and primary source that provides open-access to genomic data of influenza viruses and the novel coronavirus responsible for COVID-19 (See <https://www.gisaid.org/> *(last accessed on July 26, 2021). Note this website is not controlled by FDA.*)

[18] <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-evaluating-impact-viral-mutations-covid-19-tests>

[19] *Last accessed on July 9, 2021. Note this website is not controlled by FDA.*

[20] Available at https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data.

[21] <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-informed-consent-vitro-diagnostic-device-studies-using-leftover-human-specimens-are-not>.

[22] Available at <https://www.fda.gov/media/146695/download>.

[23] All templates can be accessed at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.

[24] Available at <https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries>*.*

[25] *Last accessed on July 6, 2021. Note this website is not controlled by FDA.*

[26] A list of EUA-authorized tests and their accompanying fact sheets are available at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas>.

[27] Report Adverse events, including problems with test performance or results, to MedWatch by submitting the online FDA Form 3500 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home) or by calling 1-800-FDA-1088

[28]

[29] Please see the following website for the most recent list of FDA authorized SARS-CoV-2 molecular tests: <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2>.

Please see the following website for the results of the FDA SARS-CoV-2 reference panel testing: <https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data>.

[30] Please see the following website for the most recent list of FDA authorized SARS-CoV-2 molecular tests: <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2>.

Please see the following website for the results of the FDA SARS-CoV-2 reference panel testing: <https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data>.


# 2,420  2021-10-25_FDA Template - Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing.md
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last updated: 2026-03-04 by BA
file_name: 2021-10-25_FDA Template - Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing.md
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summary_short: The FDA “Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing” provides recommendations for supporting EUA screening claims that rely on repeat testing rather than pre-authorization asymptomatic studies. It specifies expected serial testing intervals, minimum clinical performance thresholds in symptomatic populations, post-authorization study obligations for asymptomatic performance, and labeling requirements for serial, POC, and at-home use. It is used alongside primary molecular or antigen EUA templates to structure submissions and labeling for serial screening programs.


CONTENT

***INTERNAL TITLE:*** Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing

This template provides the Food and Drug Administration’s (FDA) current recommendations concerning what data and information should be submitted to FDA in support of a pre-Emergency Use Authorization (EUA) submission/EUA request for a molecular or antigen diagnostic test for SARS-CoV-2 used for screening with serial testing. FDA generally recommends certain validation studies be conducted for a SARS-CoV-2 molecular or antigen diagnostic assays. These recommendations are captured in EUA templates specific to each test type. Test developers should utilize the appropriate template when determining required testing to support each type of test.

As described in the FDA guidance document: [*Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised),[2] FDA is providing recommendations in this and other EUA templates regarding testing that should be performed to ensure appropriate analytical and clinical validity, including descriptions of appropriate comparators, for different types of tests and indications.

The [EUA Templates](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates)[3] are intended to help test developers provide recommended validation data and other information to FDA, but alternative approaches can be used. Current templates for molecular and antigen diagnostic tests include recommendations that the developer provide validation data on asymptomatic individuals prior to authorization of a screening claim, including when using a serial testing approach. This template is intended to provide supplemental recommendations for developers of molecular and antigen tests seeking claims for screening with serial testing without studying asymptomatic individuals prior to authorization, including for point of care (POC) and at-home tests. This template reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should,* means that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/media/97321/download).[4]

Test developers interested in pursuing an EUA may submit a pre-EUA to begin discussions with the FDA or may submit an EUA request [to covid19dx@fda.hhs.gov](mailto:to%20covid19dx@fda.hhs.gov).

FDA recommends that all developers of molecular SARS-CoV-2 tests include the [Molecular EUA Template Cover Sheet](https://www.fda.gov/media/152768/download)[5] when submitting their EUA request to <covid19dx@fda.hhs.gov> to help streamline the routing, triage, and review of EUA requests.


## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by the test developer as applicable to their specific test. Text in **bold** outlines the FDA’s additional recommendations for the developers’ consideration when completing the suggested information in each section.

-   This template should be used by developers of molecular or antigen diagnostic tests for use in serial testing programs. This template also applies to tests for serial at-home[6] use by individuals separate from a testing program, including to support authorization for over-the-counter (OTC) use, intended to detect SARS-CoV-2 from individuals with or without symptoms or other epidemiological reasons to suspect COVID-19 infection. **This template is not applicable to tests for which data has already demonstrated poor performance (e.g., less than 80% PPA) for testing asymptomatic individuals.**

-   **This is not a complete template.** The information in this template does not reflect complete validation data or information that FDA recommends be included in a pre-EUA submission/EUA request; it supplements the recommendations in the Template for Molecular Diagnostic Test Developers, Template for Antigen Test Developers, and Template for Test Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Home Use, all available for download from FDA’s website.[7] Test developers should use the referenced template most appropriate for their test type as their primary template and incorporate information from this supplemental template as applicable.

-   A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   We plan to update the template as appropriate as we learn more about COVID-19 and gain experience with the EUA process for these kinds of tests.


## EXAMPLE TEMPLATE:
### A. PROPOSED INTENDED USE

**FDA recommends including the following in the requested intended use:**

***\[…******individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection, when tested twice over three days with at least 24 hours and no more than 48 hours between tests.\]***

**Alternative testing intervals, such as testing twice a week (e.g., Monday/Thursday or Tuesday/Friday), may be considered for molecular or antigen tests intended for use as part of a testing program.**

**A weekly testing interval may be considered for higher sensitivity molecular tests.**

**When requesting an intended use that includes both serial testing and single-use testing for different patient populations, FDA recommends including a requested intended use in the following format, with the details adjusted based on your test and validation:**

***\[The \[test name\] is a lateral flow assay intended for the qualitative detection of nucleocapsid protein antigen from SARS-CoV-2.***

***This test is authorized for non-prescription home use with self-collected direct anterior nasal (nares) swab samples from individuals aged 14 years or older with symptoms of COVID-19 within the first 10 days of symptom onset. This test is also authorized for non-prescription home use with adult-collected nasal swab samples from individuals aged 2 years or older with symptoms of COVID-19 within the first 10 days of symptom onset.***

***This test is also authorized for non-prescription home use with self-collected anterior nasal (nares) swab samples from individuals aged 14 years or older, or adult collected anterior nasal swab samples from individuals aged 2 years or older, with or without symptoms or other epidemiological reasons to suspect COVID-19 when tested twice over three days with at least 24 hours (and no more than 48 hours) between tests.\]***

### B. CLINICAL PERFORMANCE EVALUATION

**FDA recommends following the recommendations for clinical performance evaluation in the appropriate EUA template to demonstrate a positive percent agreement (PPA) of at least 80% with 70% at the lower bound of the two-sided 95% confidence interval, in symptomatic patients suspected of COVID-19 infection by their healthcare providers.**

**When FDA authorizes a test for screening with serial testing, but the clinical validation does not include at least 20 asymptomatic individuals, FDA intends to include a condition of authorization that the developer conduct a study to establish performance with asymptomatic individuals within a pre-specified timeframe. A study protocol for the study, generally including at least 20 positive asymptomatic individuals, should be agreed upon with FDA prior to study initiation. If the post-authorization study is not completed within the agreed upon timeframe or does not demonstrate adequate performance in asymptomatic individuals, FDA will consider taking additional actions as appropriate under section 564 of the FD&C Act, including revoking or revising the authorization to remove any intended use(s) not adequately supported.**

### C. INSTRUCTIONS FOR USE/PROPOSED LABELING/PACKAGE INSERT:

**Proposed labeling should indicate that testing be done twice over three days with at least 24 hours and no more than 48 hours between tests. Alternative testing intervals may be considered for molecular or antigen tests intended for use as part of a testing program.**

**Proposed labeling should clearly identify the population in which the test’s performance has been validated. The labeling should also clearly identify any populations included in the intended use for which the test’s performance has not yet been established but will be established during the post-authorization study.**

**The test package should contain adequate testing materials to support your intended use. Therefore, tests intended for serial testing should be packaged to enable serial testing, such as providing at least two tests in a package or, when also intended for single-use testing for symptomatic individuals, include language in the labeling, including on the outer box, such as “If you do not have symptoms of COVID-19, you will need at least two tests per person. You may need to purchase additional tests to perform serial (repeat) testing.”**

**FDA recommends including the following limitations in your Instructions for Use, especially when requesting an intended use that includes both serial testing and single-use testing for different patient populations:**

-   **Testing for asymptomatic individuals should be performed at least twice over three days, with at least twenty-four hours and no more than 48 hours between tests. You may need to purchase additional tests to perform this serial (repeat) testing.**

-   **There is a higher chance of false negative results with home use tests than with laboratory-based molecular tests. This means that there is a higher chance this test will give you a negative result when you have COVID-19.**

-   **Serial testing (i.e., testing every day or every other day) is more likely to detect COVID-19, especially when you do not have any symptoms.**

[1] This template is part of the “[Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised)”, available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[2] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[3] All EUA templates can be found at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.

[4] Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities.

[5] Available at <https://www.fda.gov/media/152768/download>.

[6] At-home tests are tests labeled for self-testing in any environment outside a clinical laboratory setting, professional healthcare facility, or point of care patient care setting operating under a Clinical Laboratory Improvement Amendments (CLIA) certificate. This includes but is not limited to homes, outdoor environments, office environments, schools, vehicles, emergency shelters, and independent living retirement homes.  If the test is intended to be used in a clinical laboratory setting, professional healthcare facility, or patient care setting operating under a CLIA certificate and also outside those facilities, it meets this definition.

[7] All EUA templates can be found at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.


# 10,768  2021-11-09_FDA Template - For Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Home Use.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-09_FDA Template - For Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Home Use.md
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summary_short: The FDA “Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Home Use” outlines recommended validation and labeling for SARS-CoV-2 tests intended for self-testing at home and other non-laboratory settings, including OTC and prescription pathways. It specifies expected analytical and clinical performance evidence plus home-use specific studies such as usability, user comprehension, flex/robustness testing, and software/mobile-app validation and reporting workflows. It is used by test developers to structure pre-EUA/EUA submissions and create clear, low-reading-level instructions, packaging, and mitigations appropriate for lay users.


CONTENT

***INTERNAL TITLE:*** Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Home Use

This template provides the Food and Drug Administration’s (FDA) current recommendations concerning what data and information should be submitted to FDA in support of a pre-Emergency Use Authorization (EUA) submission/EUA request for a SARS-CoV-2 molecular or antigen diagnostic test for home use. Home use tests may also be used in additional non-laboratory settings, such as offices, sporting events, airports, schools, etc., where an individual performs the test themselves, including reading and receiving the results themselves.[2] This template does not apply to home collection kits.[3] FDA generally recommends that the following validation studies be conducted for a SARS-CoV-2 molecular or antigen diagnostic assay: limit of detection (LOD), clinical evaluation, inclusivity, cross-reactivity, usability, and flex.

As described in the FDA guidance document [*Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised), [4] FDA is providing recommendations in this and other EUA templates regarding testing that should be performed to ensure appropriate analytical and clinical validity, including descriptions of appropriate comparators, for different types of tests.

The EUA templates[5] are intended to help test developers provide appropriate validation data and other information to FDA, but alternative approaches can be used. This template reflects FDA’s current thinking on the topic, and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should,* means that something is suggested or recommended, but not required. For more information about EUAs in general, please see the FDA Guidance document: [*Emergency Use Authorization of Medical Products and Related Authorities*](https://www.fda.gov/media/97321/download).[6]

Test developers interested in pursuing an EUA may submit a pre-EUA to begin discussions with the FDA or may submit an EUA request [to covid19dx@fda.hhs.gov](mailto:to%20covid19dx@fda.hhs.gov).

FDA recommends that all developers of molecular SARS-CoV-2 tests include the [Molecular Diagnostic EUA Templates Cover Sheet](https://www.fda.gov/media/152768/download)[7] when submitting their EUA request to <CDRH-EUA-Templates@fda.hhs.gov> to help streamline the routing, triage, and review of EUA requests.

## GENERAL INFORMATION ABOUT THIS TEMPLATE

-   Text highlighted in yellow ***\[Text\]*** should be completed by test developers as applicable to their specific test. Text in **bold** outlines the FDA’s additional recommendations for the developers’ consideration when completing the suggested information in each section.

-   Not all portions of this template may be relevant for all developers/tests. FDA recommends developers complete all portions that are relevant to facilitate a streamlined review.

-   This template addresses tests intended for use with respiratory samples or saliva; if you are considering non-respiratory samples (e.g., blood, stool, etc.), please contact FDA at CDRH-EUA-Templates (<covid19dx@fda.hhs.gov>) to discuss your validation strategy.

-   This template is for developers of molecular or antigen diagnostic tests for home use, including non-laboratory settings outside of the home (such as offices, sporting events, airports, schools etc.), that are intended to detect SARS-CoV-2 from individuals.

-   A test authorized under an EUA is only authorized for emergency use while the EUA is in effect.

-   We may update the template as appropriate as we learn more about COVID-19 and gain experience with the EUA process for these tests.

-   A developer that has provided data to the FDA may grant a right of reference to other developers, either broadly or to individual developers, to leverage that data. A right of reference provides a developer the ability to rely upon, and otherwise use, existing information in one regulatory submission for the purpose of supporting a different regulatory submission. In these cases, if the data is applicable to the new developer’s test, the new developer may not have to repeat that validation for its submission to the FDA or FDA may recommend a bridging study. Any developer seeking to leverage data regarding another developer’s EUA-authorized assay must obtain a right of reference from that developer.

## EXAMPLE TEMPLATE:
### A. PURPOSE FOR SUBMISSION

Emergency Use Authorization (EUA) request for distribution and/or use of the ***\[test name\]*** for the *in vitro* qualitative detection of ***\[ribonucleic acid (RNA) or antigen\]*** from SARS-CoV-2 in ***\[add all sample types, e.g., nasal swab or saliva\]***. This test is for ***\[prescription and/or over-the-counter (OTC) use\]*** at home and other non-laboratory sites. 

### B. MEASURAND

Specific nucleic acid sequences from the genome of SARS-CoV-2 **\[*please specify the targeted gene(s) of the pathogen*\]**.

***OR***

Specific antigen(s) from SARS-CoV-2 **\[*please specify the targeted antigen(s)*\]**.

### C. APPLICANT

***\[Official name, address, and contact information (including phone number and email address) of applicant and primary correspondent.\]***

### D. PROPRIETARY AND ESTABLISHED NAMES

Proprietary Name - ***\[test name\]***

Established Name - ***\[test name\]***

### E. REGULATORY INFORMATION

***Approval/Clearance Status:***

The ***\[test name\]*** test is not cleared, CLIA waived, approved, or subject to an approved investigational device exemption.

***\[If the test has been previously reviewed in an EUA request or pre-EUA submission, please provide the submission number.\]***

***Product Code:***

QJR-molecular diagnostic for SARS-CoV-2

**OR**

QKP-coronavirus antigen detection test system

### F. PROPOSED INTENDED USE

#### *1) Intended Use (IU):*

**The proposed intended use will be finalized based on, among other things, the data provided and recommendations from public health authorities at the time of authorization. Example text is provided below for a home use qualitative molecular or antigen test that detects organism RNA or antigen in adults and children 2 years and older, but may be adapted according to the specific emergency situation addressed by the device*. ***

The ***\[test name\]*** is a ***\[specify test technology such as, real-time reverse-transcriptase-polymerase chain reaction (RT-PCR) test, lateral flow immunoassay, etc.\]*** intended to detect ***\[RNA, \[protein name\] antigen\]*** from the SARS-CoV-2 virus that causes COVID-19 in ***\[describe all the sample types, e.g., anterior nasal swab, saliva\]*** from ***\[individuals age 2 years and older; describe the testing population requested, such as symptomatic individuals who are suspected of COVID-19 by a healthcare provider, or individuals with or without symptoms or other epidemiological reasons to suspect COVID-19 infection\]***.

Persons who test positive with the **\[test name\]** should seek follow up care with their physician or healthcare provider as additional testing and public health reporting may be necessary. Positive results do not rule out bacterial infection or co-infection with other viruses. Persons who test negative and continue to experience COVID-19 like symptoms of fever, cough and/or shortness of breath may still have SARS-CoV-2 infection and should seek follow up care with their physician or healthcare provider.

Laboratories within the United States and its territories are required to report all results to the appropriate public health authorities.

The ***\[test name\]*** is intended for home use ***\[and/or, as applicable for a lay user testing another person\],***  including self-testing in a non-laboratory setting ***\[and, as applicable, for healthcare provider testing of another person in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, that meet the requirements to perform moderate complexity, high complexity, or waived tests and, as applicable, Point of Care (POC), i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation\].***

The ***\[test name\]*** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

#### *2) Special Conditions for Use Statements:*

For prescription use only **(as applicable)**

For *in vitro* diagnostic use

For Emergency Use Authorization only

#### *3) Special Instruments:*

The ***\[test name\]*** test is to be used with the *\[**list all instruments, software, cameras, smart phones, operating systems, other applicable instrumentation, etc.**\]*.

**If your test system includes an instrument, the instrumentation manual should be submitted as part of the EUA request. If your test system includes an instrument that was not previously cleared, approved, or authorized by FDA, please see additional discussion in the Product Manufacturing section and note that additional labeling information may be discussed during the EUA review.**

### G. DEVICE DESCRIPTION AND TEST PRINCIPLE

***\[Provide a Device Description and Test Principle consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate*.*\]* For new technologies, FDA may request additional information so we can adequately assess the known and potential risks and benefits associated with the device.**

**Because of the greater potential for error in testing of samples collected at home, FDA recommends that the test include an internal control to indicate that adequate human sample was collected and placed into the test for analysis. If your assay does not have such a control, you should address this risk using another mitigation, such as video observation of user by a trained healthcare professional or a design feature of the collection device.**

**FDA recommends that your test use either anterior nares (nasal) swabs, mid-turbinate swabs (collected using the appropriate swab type), or saliva as sample types. Generally, FDA does not consider self-collection of nasopharyngeal (NP) and oropharyngeal swabs by lay persons to be safe because such collection requires training to accurately collect the sample from the proper anatomical location. Moreover, incorrect technique can result in patient harm such as nose bleeds or esophageal spasms and choking.**

#### 1.  *Product Overview/Test Principle:*

***\[Describe the technology of the test and how this technology works to identify the measurand (i.e., the test principle), the instruments/reader employed/required to perform the test from sample collection to result (include all instruments, software, mobile applications, etc.), and the sample types for which you claim to have specific performance characteristics, as described below. If applicable, list all primer and probe sets and briefly describe what they detect. Please include the nucleic acid sequences for all primers and probes used in the test. Please indicate if the test uses biotin-Streptavidin/avidin chemistry in any of the steps for coupling reagents.\]***

#### 2.  *Description of Test Steps:*

***\[List and describe in detail all the steps of the test sequentially from sample collection to assay report.\]***

1.  ***\[Step one\]***

2.  ***\[Step two\]***

3.  ***\[Etc.…\]***

#### 3. *Control Material(s):*

***\[For any controls that you intend to be used with your test, please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.\]***

#### 4.  *Quick Reference Instructions:*

**You should develop a test procedure that will be easy to follow in the format of a Quick Reference Instructions (QRI). User instructions should be oriented to users at no higher than a 7^th^ grade level. It is highly recommended that developers consider adding pictures and diagrams to facilitate performance of the test by a lay user and that the instructions be limited to 1-2 pages. Web or mobile application-based material such as videos may be particularly helpful**. **We recommend you perform Human Usability Studies on your device using the QRI before conducting your final clinical study as the final QRI should be evaluated in the clinical study.**

**The QRI may eliminate the need for a separate Patient Fact Sheet if the QRI contains all necessary elements of a Patient Fact Sheet.**

#### 5.  *Test Result Reporting:*

All test results are to be reported to healthcare providers and relevant public health authorities in accordance with local, state, and federal requirements, using appropriate LOINC and SNOMED codes, as defined by the [*Laboratory In Vitro Diagnostics (LIVD) Test Code Mapping for SARS-CoV-2 Tests*](https://www.cdc.gov/csels/dls/sars-cov-2-livd-codes.html)[8] provided by CDC.  Core diagnostic data elements[9] are to be collected for all tests, which have been defined by the Department of Health and Human Services (HHS), along with technical specifications for implementation for lab-based[10] and non-lab-based[11] tests.

***\[You should describe how you will ensure all users of the test can report** **all test results to public health and/or other authorities to whom reporting is required, in accordance with local, state, and federal requirements. Please note whether identified information will be sent to local public health authorities and/or if de-identified information will be sent to CDC. If the test produces results that will be used as part of a CDC recommended testing algorithm, please indicate what follow-up testing/process should be conducted, if applicable. Please also describe how test reporting will capture the appropriate LOINC and SNOMED codes, in addition to location data, and other patient information that may be relevant or required.\]*** **The approach adopted should facilitate reporting by all users and be easy to use and understand. There are several options to allow for reporting of test results, including automatic reporting through a mobile application, instructions directing users to a website where reporting is easily facilitated, etc. FDA is open to alternative approaches that ensure appropriate reporting.**

**Note that in some cases, developers may add a reporting mechanism post-authorization to ensure that all test results are reported in accordance with local, state, and federal requirements.**

#### 6.  *Mobile Applications and Software*

**Any smartphone application should be simple. Error messages should be readily understandable, and troubleshooting should be included in the device instruction. The display should promote understanding of results and what individuals should do next, including how to care for themselves and when to seek follow up care. The application should automatically report all test results when appropriate in accordance with local, state, and federal requirements. If your application is intended to interpret test results or otherwise function as part of the test system, it should be included in your analytical and clinical validation studies.**

***\[Please list and describe any mobile applications, software, or web applications used with the test and provide the following information:***

-   ***A summary of the verification and validation performed on your software/application. To validate use of your application with a smartphone, you should develop a set of minimum smartphone specifications (e.g., memory, processor capability, minimum operating system (OS) requirements, etc.). You should validate the software on smartphones with each OS that meets those minimum hardware specifications. Full functionality for the application should be demonstrated for the full range of platforms intended for use (e.g., if a web application, then demonstrating on popular modern browsers such as Chrome, Firefox, Microsoft Edge; if a mobile application, then demonstrating on popular modern smartphones and other mobile devices such as Android, and iOS-based devices, etc.).***

-   ***Address the cybersecurity of your device, including information that may be contained on your device or in a mobile application or web application. For communications between components (e.g., application to reader, application to cloud service provider), the security of the communications protocol should be described (including version number, configuration, cipher suite), tested, and assessed for risks, especially when the communication security could impact the integrity of the results. For cloud-based functionality, the security of the application programming interface (API), communications, and updates should also be described, tested, and assessed for risks.***

-   ***A software update plan that covers mobile application updates, algorithm updates, and web application updates that may impact the performance or safe reporting of the device.\]***

### H. INTERPRETATION OF RESULTS

**Results that are displayed to the user should be simple and easy to interpret (e.g., positive, negative, and invalid). Additional information about test results should also be provided that instructs the users to seek follow up care from a healthcare physician if their symptoms persist or if they are concerned about their health.**

***\[Please describe the testing algorithm/calculation that is used by the device to return the simple qualitative result, for example a ratio value, fluorescence reading, cycle threshold and cut-off, etc. Please also provide any text for users that will accompany test results. Please clearly indicate how invalid results will be displayed to the user and how the user will resolve invalid results, e.g., if repeat testing may be required, call hotline for replacement, etc.\]***

### I. PRODUCT MANUFACTURING

The ***\[test name\]*** has been validated using only the components referenced in this request and will not be changed after authorization without prior concurrence from the FDA.

#### 1.  *Overview of Manufacturing and Distribution:*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.*\]**

#### 2.  *Components and Other Materials/Information Included with the Test:*

Components manufactured by ***\[test developer’s name and FDA registration number (if applicable)\]*** and supplied with the test include:

***\[List all components and other materials/information included with your test, including a description of the primers and probes, volumes, concentrations, quantities, buffer components, etc.\]***

***\[Present a detailed assessment of the toxicology profile of the components of your assay, and propose assay labeling that informs users of the risks associated with use of your device, as well as any recommendations for personal protective equipment. Please specify the volumes and concentrations of each reagent included in your test kit.\]* FDA will conduct an independent risk assessment to determine if the proposed mitigations are appropriate.**

***\[If you plan to use non-traditional sources of swabs or media, please describe your qualification testing and validation procedures.\]    ***

**Example: Kit components**

| **Name** | **Description** | **Quantity** | **Material Supplier** | **Catalog Number** |
|----------------|-------------------|-----------|--------------|--------------|
|  |  |  |  |  |
||

#### 3.  *Software Validation:*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.*\]**

#### 4.  *Basic Safety and Essential Performance:*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.\]***

#### 5.  *Electromagnetic Compatibility (EMC) Testing*

***\[Please provide information consistent with the recommendations in the*** ***Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.\]***

#### 6.  *Manufacturing and Testing Capabilities:*

***\[Please provide the number of kits you can manufacture per day/week for distribution in the United States.\]***

#### 7.  *Distribution Plan:*

This product will be distributed by ***\[please describe the distribution plan for the product and list all current US distributors.\]***

#### 8.  *Reagent Stability*

***\[Briefly describe the stability test plan for reagents and include any accelerated stability information, if available.\]* Reagent stability studies generally do not need to be completed at the time of EUA issuance; however, the study design should be agreed upon during interactive review and the stability studies started immediately following authorization, if not before. You should consider the recommendations** **in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate, when designing your stability study.**

### J. PERFORMANCE EVALUATION

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate, with additional considerations and recommendations specific to Home Use Tests provided here.\]***

**The following validation studies should be performed to support your EUA request. Please note that, particularly for new technologies, FDA may request additional studies so we can adequately assess the risks and benefits associated with the candidate test. *\[For each validation study, you should provide a study protocol that includes a detailed, step-by-step description of how samples were prepared and how testing was conducted. You should also include the study data from each validation study in an Excel-compatible format.\]***

#### 1.  *Limit of Detection (LoD) - Analytical Sensitivity:*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.\]***

#### 2.  *Inclusivity (Analytical Sensitivity):*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.\]***

#### 3.  *Cross-reactivity (Analytical Specificity):*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers or Molecular Diagnostic Template for Test Developers, as appropriate.\]* Additionally, for home use tests, FDA recommends wet testing of Cross-reactivity and Microbial Interference in addition to in silico analysis.**

a.  **Cross-reactivity (organisms tested in the absence of SARS-CoV-2)**

b.  **Microbial Interference Studies (organisms tested in the presence of SARS-CoV-2)**

c.  **Endogenous Interference Substances Studies (including common household items such as cleaners, lotions, soap etc.)**

#### 4.  *Biotin interference for antigen tests:*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers.\]***

#### 5.  *High-dose Hook Effect Study for antigen tests:*

***\[Please provide information consistent with the recommendations in the Antigen Template for Test Developers.\]***

#### 6.  *Flex Studies:*

**Flex studies assess the robustness of an assay performed with the device in its final design/format and should be performed in-house by staff who have been trained in the use of the test. The flex studies should evaluate the most common or likely sources of error based on the use locations and test procedure. Flex studies should be conducted by testing a negative sample and a low positive sample (at 1.5 - 2 times LoD) for each condition being evaluated. In general, the flex studies should be conducted to the point of failure to determine the maximum deviation that will still generate accurate results. We recommend testing 3 replicates per condition per sample concentration. *\[You provide the line data from each flex study in an Excel-compatible format.\]* If erroneous results are observed during studies evaluating the robustness of the device, adequate mitigation(s) should be provided.**

**Each study should be performed using a pre-defined study protocol that includes the following:**

i.  **The objective of the study**

ii.  **Detailed test procedure**

iii.  **Materials used**

**Examples of some conditions that may be evaluated as potential user errors and anticipated environmental stresses (temperature and humidity extremes) are shown below:**

-   **40°C and 95% relative humidity (RH) (mimicking hot and humid climates)**

-   **Delay in sample testing**

-   **Delay in operational steps**

-   **Delay in reading results**

-   **Sample volume variability (if applicable)**

-   **Buffer volume variability (if applicable)**

-   **Environmental stability of electronics (temperature and humidity, in combination)**

-   **Vibrations**

-   **Mixing/swab expression variability (if applicable)**

-   **Disturbance during analysis**

-   **Placement on non-level surface**

-   **Impact of different light sources (if applicable)**

-   **Sensitivity to power failures (e.g., surge protection, battery power failure)**

-   **Error reporting and device failure handling instructions**

-   **Electrical interference testing (e.g., validation of system functions in the presence of potential EM interference sources including cell phones, Bluetooth, Wi-Fi radios, medical equipment expected in the intended environment, etc.)**

**Please see Appendix A for detailed Flex Study designs. CLIA Waiver by Application Decision Summaries**[12] **available on the FDA website may include additional alternative flex study designs potentially applicable to your test.**

**Please contact FDA to discuss the design of a flex study for a multiplexed test.**

#### 7.  *Usability Study:*

**FDA recommends a usability study be performed to evaluate the ability of users to perform the test when the test design or instructions for use are not similar to previously authorized home use COVID-19 tests. If you believe that your test design and instructions for use are similar to previously authorized home use COVID-19 tests, such that a usability study may not be needed, FDA recommends that you provide information to help FDA understand how the proposed test design and instructions for use are similar to currently authorized tests and why any differences do not reduce the usability of the test. FDA recommends that you include a comprehensive description of the similarities and differences between the new test and previously authorized tests.**

**FDA encourages developers to submit their usability study protocols, including questions for study participants, to FDA for feedback prior to conducting the study. This is especially important for multiplexed tests.**

**It may be possible to combine the usability study with the clinical evaluation study; however, this presents risk of a failed clinical study if there are problems with the instructions for use. FDA strongly recommends you discuss this option with FDA before design and execution.**

**FDA recommends evaluating the ability of users to perform the entire workflow in an actual use environment or simulated environment as follows:**

-   **The study should have pre-defined acceptance criteria and a defined strategy to mitigate risk of errors identified in the study (e.g., modifying the instructions).**

-   **For home use tests, we recommend evaluating a minimum of 30 participants split evenly into two sections: 15 participants testing themselves and 15 participants testing another person (child or adult, depending on your intended use population). FDA generally expects demonstrated usability for nasal swab** **samples for children ≥ 2 years of age when collected by an adult and for saliva samples for school aged children.**

-   **Participants with prior medical or laboratory training or prior experience with self-collection or self-testing (including infectious disease home tests) should be excluded.**

-   **The entire workflow should be performed by each individual participant using the kit, including kit registration, sample collection, testing, and results interpretation.**

-   **The participants should be observed (either in person or by remote visual monitoring, such as a video conference) during sample collection and all difficulties should be noted.**

-   **Enrollment population should represent different socioeconomic and educational backgrounds. You should collect data on any controls that are run during the test to assess sample adequacy. These data should support that individuals can effectively collect an adequate sample and run the test without introducing contaminants or inhibitors.**

-   **After the entire process is completed, participants should be given a questionnaire to assess the ease of use of sample collection, test procedure, and results interpretation as well as the user’s ability to understand the consequences if steps are not performed correctly. The participants should be able to provide comments.**

***\[Please provide FDA with the version of the instructions that was used in the usability study and resulting summary and line data from your usability study\]***

#### 8.  *User Comprehension of Test Results/Procedure:*

**FDA recommends performing a study to evaluate user comprehension of test results (i.e., interpreting positive, negative, and invalid results) and instructions for use when the test design or instructions for use are not similar to previously authorized home use COVID-19 tests. This is particularly important for tests intended to be run by lay users without involvement of a physician, as there are significant risks associated with misinterpretation and misuse of test results.**

**If you believe that your test design and instructions for use are similar to previously authorized tests home use COVID-19 tests, such that a user comprehension study may not be needed, FDA recommends that you provide information to help FDA understand how the proposed test design and instructions for use, including reading and interpreting results, are similar to currently authorized tests and why any differences do not reduce the user comprehension for the test. FDA recommends that you include a comprehensive description of the similarities and differences between the new test and previously authorized tests.**

***\[Please provide FDA with user comprehension study data to verify that users can accurately interpret the test results and carry out any follow up actions.\]***

#### 9.  *Clinical Evaluation:*

**FDA recommends conducting a prospective, randomized clinical evaluation in the intended use population in which fresh samples are collected, tested, and interpreted by lay-users and results are compared to paired samples evaluated with an authorized high sensitivity molecular test. Please contact FDA regarding recommendations for clinical evaluation designs of multiplexed tests.**

##### a.  Testing Sites

-   **The clinical evaluation should generally include a minimum of 2 testing sites in the United States to encourage diverse enrollment. This may include an at home clinical study or a study at a testing site with a simulated home environment.**

-   **Prior to conducting the at home clinical study, you should first complete an observed usability study to evaluate clarity and demonstrate robustness in using the instructions for use, unless you have provided information to FDA as to why a usability study may not be needed, as described in Section J(7) above.**

-   **Recruitment by internet, especially if using monetary incentives, can drastically bias the population who enrolls in the study. We recommend that you consult FDA before starting a recruitment involving a monetary incentive.**

-   **Sample types should be non-invasive and safe to prevent possible injury during sample collection. Mid-turbinate swabs may need additional safety features to be appropriate, specifically for pediatric populations.**

-   **If collected at home, comparator samples should be collected using an FDA authorized home collection kit, which in combination with a SARS-COV-2 molecular assay comprise the comparator test for the study.**

-   **Testing sites should be set up in a way that precludes a user from seeing or hearing other users performing the test (e.g., in separate rooms or areas partitioned with curtains).**

-   **The entire workflow should be performed by each individual participant using the kit, including kit registration, sample collection, testing, and results interpretation.**

##### b.  Patient Enrollment

-   **Parents or legal guardians must consent for children as required by law.**

-   **Enrollment population should represent different socioeconomic and educational backgrounds.**

-   **High risk individuals should not be excluded from the study.**

-   **If you are seeking an OTC or prescription authorization for a home test for use in all patient populations, including individuals with or without symptoms or other epidemiological reasons to suspect COVID-19, you should evaluate both symptomatic and asymptomatic individuals and include an adequate number of pediatric subjects from ages 2-13 years of age. We recommend testing at least 30 children between the ages of 2-13 years of age between your usability and clinical evaluations, to ensure that your proposed sample collection techniques can be conducted by parents or guardians in a home use setting. Study population should include individuals across all ages 2 years - 65+ years**

    -   **&lt;14 years of age, where the Parent or legal guardian collects a sample from their child (e.g., age 2-13) and performs the test**

    -   **14-24 years of age**

    -   **24-64 years of age**

    -   **≥65 years of age**

-   **If you believe that your test design and instructions for use are similar to previously authorized home use COVID-19 tests, such that inclusion of pediatric subjects may not be needed to confirm performance across different age ranges, FDA recommends that you provide information to help FDA understand how the proposed test design and instructions for use are similar to currently authorized tests and why any differences do not impact the performance of the test across different age ranges. FDA recommends that you include a comprehensive description of the similarities and differences between the new test and previously authorized tests.**

-   **If you are not able to enroll sufficient asymptomatic individuals in your clinical validation study, you may consider seeking an OTC or prescription home use authorization for use only in individuals with symptoms of COVID-19. For antigen tests, all recommended elements of the clinical study data should be provided, including the days since symptom onset for each symptomatic individual included in your clinical validation study. If your clinical validation study includes symptomatic individuals only (or insufficient numbers of asymptomatic individuals) and you are interested in seeking authorization for serial testing of asymptomatic individuals based on this data, please consult the “[Supplemental Template for Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing](https://www.fda.gov/media/146695/download)”.** [13]

##### c.  Reference Sample/Comparator method

-   **FDA recommends the comparator sample type be either a health care provider-collected NP or mid-turbinate swab sample (collected from each patient in the study within a reasonable time frame from when the test sample was obtained/tested, preferably during the same visit) or a home-collected nasal swab. If you conduct the study remotely without in-person visits with health care professionals, the comparator sample should be collected with an FDA authorized home collected nasal swab.**

-   **You should describe your randomization approach for swab collection, as applicable. If study participants are collecting the reference sample for comparator testing and the study sample, you should clearly describe the order in which swabs will be collected and describe how swab order was randomized to ensure that bias is not introduced due to an unequal distribution of viral materials. If healthcare providers are collecting the reference sample for comparator testing, you should ensure that study participants are not provided additional training by observing how healthcare providers collected a sample, particularly if collected from the same anatomical area as the study sample.**

-   **All comparator samples should be tested with a comparator test. The comparator test selected should be an authorized highly-sensitive RT-PCR test that uses both a chemical lysis step and solid phase extraction of nucleic acids (e.g., silica bead extraction). The comparator test should be one of the more sensitive RT-PCR assays authorized by FDA. We encourage you to review the results from the FDA SARS-CoV-2 Reference Panel**[14] **and contact us to discuss your choice of comparator test. The same comparator test should be used for all samples, if possible. Evaluations with the comparator test should be conducted per the authorized instructions for use. If any modifications are made to the authorized comparator test, additional bridging studies may be necessary. Please contact FDA if you are considering using a modified configuration of an authorized RT-PCR assay. *\[Please submit the instrumentation and detailed laboratory protocols, including the platform and extraction kit, for each RT-PCR assay used in your validation studies.\]***

##### d.  Discrepant analysis

-   **You can establish a discordant analysis plan prior to your clinical study, if preferred. Discordant samples should be tested with a second authorized RT-PCR test that has also demonstrated high sensitivity, and which uses both a chemical lysis step and solid phase extraction of nucleic acids (e.g., silica bead extraction). Results from a Discrepant analysis should not be included in the calculation of negative percent agreement (NPA) and positive percent agreement (PPA) but may be added to the performance table as a footnote.**

##### e.  Study Size

-   **Individuals should be consecutively enrolled (i.e., in an “all comers” style) until 30 positives and 30 negatives are obtained.**

-   **If your test is intended for use in asymptomatic individuals not suspected of COVID-19, you should enroll at least 10 positive individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection. Additional post-authorization studies in individuals with or without symptoms or other epidemiological reasons to suspect COVID-19 infection may be recommended. If you do not enroll at least 10 positive individuals without symptoms, you may consider the approach in the “[Supplemental Template for Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing](https://www.fda.gov/media/146695/download)”.** [15]

-   **If using an enrichment strategy to speed enrollment, you should carefully consider how you will randomize and blind study participants to their infection status or the infection status of the individual they are testing and describe how you will minimize potential bias when conducting self-testing. Blinding study participants to their infection status, particularly if positive, raises potential ethical issues and should be discussed with FDA and the study IRB. Data from an enriched study design should represent the full range of viral loads, with both low and high positives samples. Therefore, it is not appropriate to use a rapid antigen test to enrich for participants, as it will select for strong positive samples. We strongly recommend discussing your proposed enrichment strategy with FDA prior to conducting your clinical validation study.**

##### f.  Performance

**FDA believes that data should generally demonstrate the following:**

-   **NPA ≥98%**

-   **PPA**

    -   **For OTC single-use testing in all patient populations, including individuals with or without symptoms or other epidemiological reasons to suspect COVID-19: ≥ 80% PPA demonstrated in a clinical evaluation including both symptomatic and asymptomatic individuals;**

    -   **For OTC testing in all patient populations, including individuals with or without symptoms or other epidemiological reasons to suspect COVID-19, with additional mitigations such as serial screening, as discussed in the “Supplemental Template for Developers of Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing”**[16]**: ≥ 80% PPA with a lower bound (LB) of the two sided 95% confidence interval (CI) ≥70%, demonstrated in a clinical evaluation including symptomatic individuals only or both symptomatic and asymptomatic individuals;**

    -   **For prescription home use single-use testing in individuals suspected of COVID-19 by their healthcare provider: ≥ 80% PPA demonstrated in a clinical evaluation including symptomatic individuals only (note that, for antigen tests, the indication may be limited to symptomatic individuals within a certain number of days of symptom onset, depending on the data); or**

    -   **For OTC single-use testing in symptomatic individuals: ≥80% PPA demonstrated in a clinical evaluation including symptomatic individuals only (note that, for antigen tests, the indication may be limited to symptomatic individuals within a certain number of days of symptom onset, depending on the data).**

**The indications for use for tests with PPA &lt;95% should be limited to providing presumptive negative results.**

#### 10.  *Standard Material Testing*

**All molecular tests for home use should demonstrate high analytical sensitivity as determined by testing with a recognized international standard. If you do not have access to a recognized international standard, then please contact <CDRH-EUA-templates@fda.hhs.gov> to discuss options. If this is not completed prior to submission of an EUA request, it may be required as a Condition of Authorization.**

### K. UNMET NEED ADDRESSED BY THE PRODUCT

**This section will be completed by FDA.**

### L. APPROVED/CLEARED ALTERNATIVE PRODUCTS

**There is no adequate, approved, and available alternative to the emergency use of the product.**

### M. BENEFITS AND RISKS:

**This section will be completed by FDA.**

### N. FACT SHEET FOR HEALTHCARE PROVIDERS AND PATIENTS:

**During review, FDA will make available Fact Sheet templates. See examples for authorized tests on our website.** [17]

### O. INSTRUCTIONS FOR USE/ PROPOSED LABELING/PACKAGE INSERT:

**\[*You should include Instructions for Use, Box Labels, Vial Labels and any other proposed labeling.*\]**

***\[You should submit for review your packaging and directions for your specimen collection kit.\]*** **FDA will review these documents for their ease of use and clarity of instructions. We recommend all directions be written at a 7^th^ grade reading level or below.**

**The following limitations should be included in the Instructions for Use of a home use test, as applicable:**

-   **Testing for asymptomatic individuals should be performed at least twice over three days, with at least twenty-four hours and no more than 48 hours between tests. You may need to purchase additional tests to perform this serial (repeat) testing.**

-   **There is a higher chance of false negative results with home use tests than with laboratory-based molecular tests. This means that there is a higher chance this test will give you a negative result when you have COVID-19.**

-   **Serial testing (i.e., testing every day or every other day) is more likely to detect COVID-19, especially when you do not have any symptoms.**

**The following should be included on the outer box of a home use test, as applicable:**

-   **Expiration date (sticker): Based on component of kit with the earliest expiration date**

-   **For Emergency Use Authorization (EUA) only**

-   **For in vitro diagnostic use**

-   **Must be 18+ to use this kit**

-   **If you have symptoms of COVID-19, you can use a single test**

-   **If you do not have symptoms of COVID-19, you will need at least two tests per person**

-   **You may need to purchase additional tests to perform serial (repeat) testing**

-   **This test is more likely to give you a false negative result when you have COVID-19 than a lab-based molecular test**

-   **Storage temperature**

-   **Summary of box contents**

-   **Items necessary to use the kit: e.g., access to computer/smartphone, internet, email account**

-   **Summary of how the kit works**

-   **Warnings and related information from EUA letter of authorization**

### P. RECORD KEEPING AND REPORTING INFORMATION TO FDA:

**As allowed by Section 564(e) of the FD&C Act, FDA may require certain conditions as part of an EUA. FDA generally includes the following record keeping and reporting information requirements in the EUA.**

\[***Test Developer name***\] will track adverse events and report to FDA under 21 CFR Part 803. A website is available to report on adverse events, and this website is referenced in the Fact Sheet for Health Care providers as well as through the \[***Test Developer name***\] Product Support website: \[***Include link to Test developer’s Website***\]. Each report of an adverse event will be processed according to \[***Test Developer name******\]***’s Non-Conformance Reporting Requirements, and Medical Device Reports will be filed with the FDA as required. Through a process of inventory control, \[***Test Developer name******\]*** will also maintain records of device usage/purchase. \[***Test Developer name******\]*** will collect information on the performance of the test, and report to FDA any suspected occurrence of false positive or false negative results of which \[***Test Developer name******\]*** becomes aware. \[***Test Developer name******\]*** will maintain records associated with this EUA and ensure these records are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.


### Appendix A: Recommended Flex Study Design Details, as appropriate for the device:

If incorrect results are observed under the test conditions, the test developer should implement adequate mitigations to prevent reporting of erroneous results.

1.  **Reading Time:**

**You should evaluate test results at multiple reading times four-fold below and three-fold above the recommended reading time for the candidate test. For example, where the recommended read time is 20 minutes, you should evaluate read times of 5, 10, 15, 20, 30, and 60 minutes, at a minimum. If incorrect results are observed, the developer should propose adequate mitigations.**

2.  **Sample Volume:**

**You should evaluate candidate test results at sample volumes two times below and two times above the recommended sample volume, and the maximum possible added. For example, where the recommended sample volume is 10 μL, you should evaluate sample volumes of 5, 10, and 20 μL, as well as at the maximum sample volume. If incorrect results are observed at either 5 or 20 uL, additional testing at 7.5 and/or 15 uL may be needed. The amount of diluent/buffer added should be that specified in the instructions for use.**

3.  **Sample Diluent/Buffer Volume:**

**You should evaluate candidate test results at diluent/buffer volumes at two times below and two times above the recommended diluent/buffer volume specified in the instructions for use and the maximum volume. For example, where the recommended buffer/diluent volume is 2 drops, you should evaluate sample diluent volumes of 1, 2, 3, 4 drops and the whole bottle.**

4.  **Sample Elution:**

**You should evaluate how mixing the swab in elution buffer (or other reagent) affects candidate test results. You should evaluate all extremes from not-mixing to vigorous shaking, including generating bubbles and intermediate mixing (i.e. swirling 1 or 2 times).**

5.  **Temperature and Humidity:**

**You should evaluate candidate test results at temperature and humidity extremes that are likely to occur in the United States (i.e., 40°C and 95% RH to mimic a hot and humid climate and 5°C and 5% RH to mimic a cold and dry climate.)**

6.  **Light:**

**You should evaluate candidate test results in different lighting conditions that would be expected during use (i.e., fluorescent, incandescent, and natural lighting mimicking the outside environment.)**

7.  **Disturbance during analysis:**

**You should evaluate the effect on expected candidate results of moving the candidate test while the candidate test is running. This could include dropping the candidate test while it is being run, moving the candidate test to another surface, unplugging the candidate test, receiving a phone call while the mobile app is running, etc.**

8.  **Device Orientation:**

**You should evaluate unique device characteristics, as determined by a robust risk analysis. For example, if the candidate test is intended to be run upright, you should evaluate candidate test results if the candidate test is run horizontally, or vice versa.**

[1] This template is part of the [Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) - Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised).

[2] Operators of non-traditional testing sites should consult with the Centers for Medicare and Medicaid Services (CMS) to determine whether testing at their site would be considered “home use” or would be considered a laboratory under the Clinical Laboratory Improvement Amendments (CLIA). Please see <https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA> *(last accessed on July 6, 2021). Note this website is not controlled by FDA.*

[3] Please refer to the Home Specimen Collection Molecular Diagnostic Template available at <https://www.fda.gov/media/138412/download>.

[4] Available at <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised>.

[5] All EUA templates can be found at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#covid19ivdTemplates>.

[6] Available at <https://www.fda.gov/media/97321/download>.

[7] Available at <https://www.fda.gov/media/152768/download>.

[8] Available at <https://www.cdc.gov/csels/dls/sars-cov-2-livd-codes.html> *(last accessed on July 7, 2021). Note this website is not controlled by FDA.*

[9] Available at [https://www.hhs.gov/coronavirus/testing/covid-19-diagnostic-data-reporting/index.html](https://www.hhs.gov/coronavirus/testing/covid-19-diagnostic-data-reporting/index.html%20%20) *(last accessed on July 24, 2021). Note this website is not controlled by FDA.*

[10] Available at [https://www.hhs.gov/sites/default/files/hhs-guidance-implementation.pdf](https://www.hhs.gov/sites/default/files/hhs-guidance-implementation.pdf%20) *(last accessed on July 24, 2021). Note this website is not controlled by FDA.*

[11] Available at [https://www.hhs.gov/sites/default/files/non-lab-based-covid19-test-reporting.pdf](https://www.hhs.gov/sites/default/files/non-lab-based-covid19-test-reporting.pdf%20) *(last accessed on July 24, 2021). Note this website is not controlled by FDA.*

[12] Available at <https://www.fda.gov/about-fda/cdrh-transparency/clia-waiver-application-decision-summaries>.

[13] Available at <https://www.fda.gov/media/146695/download>.

[14] Available at https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data.

[15] Available at <https://www.fda.gov/media/146695/download>.

[16] Available at <https://www.fda.gov/media/146695/download>.

[17] A list of EUA-authorized tests and their accompanying fact sheets are available at <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas>.


# 2,806  2021-11-15_FDA Fact Sheet - Fact Sheet for Health Care Providers Template.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Fact Sheet - Fact Sheet for Health Care Providers Template.md
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summary_short: The FDA “Fact Sheet for Health Care Providers Template” (v1.0, Nov 15, 2021) is a standardized, fill-in document for EUA-authorized COVID-19 tests that explains authorized use (including serial testing in individuals with or without symptoms), specimen type, and key result interpretation and reporting expectations. It includes required language on false positives/negatives, considerations for asymptomatic testing, optional pooling and home-collection language, and a variant-performance limitation statement. It helps test sponsors and high-complexity laboratories produce consistent provider-facing labeling that aligns with EUA conditions and public health reporting needs.


CONTENT

***INTERNAL TITLE:*** FACT SHEET FOR HEALTHCARE PROVIDERS
**Coronavirus Disease 2019 (COVID-19)** 
**v1.0 (November 15, 2021)**
**LABORATORY NAME - TEST NAME     Month DD, YYYY**

This Fact Sheet informs you of the significant known and potential risks and benefits of the emergency use of the \[DEVICE/TEST NAME\].

**This test is to be performed only using anterior nasal respiratory specimens from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.**

The \[DEVICE/TEST NAME\] is authorized for use with anterior nasal respiratory specimens from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.

**All patients whose specimens are tested with this assay will receive the Fact Sheet for Patients: \[LABORATORY NAME\] - \[DEVICE/TEST NAME\].**

**What are the symptoms of COVID-19?**

Many patients with COVID-19 have developed fever and/or symptoms of acute respiratory illness (e.g., cough, dyspnea), although some individuals experience only mild symptoms or no symptoms at all. The current information available to characterize the spectrum of clinical illness associated with COVID-19 suggests that, when present, symptoms include cough, shortness of breath or dyspnea, fever, chills, myalgias, headache, sore throat, new loss of taste or smell, nausea or vomiting or diarrhea. Signs and symptoms may appear any time from 2 to 14 days after exposure to the virus, and the median time to symptom onset is approximately 5 days. For further information on the symptoms of COVID-19 please see the link provided in “*Where can I go for updates and more information?*” section.

Public health officials have identified cases of COVID-19 throughout the world, including the United States. Please check the CDC COVID-19 webpage (see link provided in “*Where can I go for updates and more information?*” section at the end of this document) or your local jurisdictions website for the most up to date information.

**What do I need to know about COVID-19 testing?**

Current information on COVID-19 for healthcare providers is available at CDC’s webpage, *Information for Healthcare Professionals* (see links provided in “*Where can I go for updates and more information?*” section).

-   The \[DEVICE/TEST NAME\] can be used to test anterior nasal respiratory specimens.

-   The \[DEVICE/TEST NAME\] should be ordered for the detection of SARS-CoV-2 in individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.

-   \[INCLUDE THE FOLLOWING BULLET IF YOUR TEST INCLUDES USE OF AN AUTHORIZED HOME COLLECTION KIT – MODIFY TO INCLUDE HOME COLLECTION INDICATION BASED ON THE APPENDIX YOU ARE CLAIMING: The \[DEVICE/TEST NAME\] can also be used to test anterior nasal respiratory specimens collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP or self-collected at home using the following authorized home collection kit(s) \[INCLUDE NAME OF AUTHORIZED KIT\]\].

-   \[INCLUDE THE FOLLOWING BULLET IF YOUR TEST ALLOWS SPECIMEN POOLING – BASED ON THE APPENDIX YOU ARE CLAIMING\]: The \[DEVICE/TEST NAME\] can also be used to test up to \[INCLUDE POOLING INDICATION BASED ON THE APPENDIX YOU ARE CLAIMING\].

-   The \[DEVICE/TEST NAME\] is only authorized for use at the \[NAME OF LABORATORY\] that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

Specimens should be collected with appropriate infection control precautions. Current guidance is available at the CDC’s website (see links provided in “*Where can I go for updates and more information?*” section).

When collecting and handling specimens from individuals suspected of being infected with the virus that causes COVID-19, appropriate personal protective equipment should be used as outlined in the CDC *Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19)*. For additional information, refer to CDC *Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under Investigation (PUIs) for Coronavirus Disease 2019 (COVID-19) (*see links provided in “*Where can I go for updates and more information?*” section).

**What does it mean if the specimen tests positive for the virus that causes COVID-19?**

A positive test result for COVID-19 indicates that RNA from SARS-CoV-2 was detected, and therefore the patient is infected with the virus and presumed to be contagious. Laboratory test results should always be considered in the context of clinical observations and epidemiological data (such as local prevalence rates and current outbreak/epicenter locations) in making a final diagnosis and patient management decisions. Patient management should be made by a healthcare provider and follow current CDC guidelines.

The \[DEVICE/TEST NAME\] has been designed to minimize the likelihood of false positive test results. However, it is still possible that this test can give a false positive result, even when used in locations where the prevalence is below 5%. In the event of a false positive result, risks to patients could include the following: a recommendation for isolation of the patient, monitoring of household or other close contacts for symptoms, patient isolation that might limit contact with family or friends and may increase contact with other potentially COVID-19 patients, limits in the ability to work, delayed diagnosis and treatment for the true infection causing the symptoms, unnecessary prescription of a treatment or therapy, or other unintended adverse effects.

\[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should **not** be cohorted with other individuals who have received a positive or presumptive positive result.\]

All laboratories using this test must follow the standard testing and reporting guidelines according to their appropriate public health authorities.

**What does it mean if the specimen tests negative for the virus that causes COVID-19?**

A negative test result for this test means that SARS-CoV-2 RNA was not present in the specimen above the limit of detection. However, a negative result does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions. It is possible to test a person too early or too late during SARS-CoV-2 infection to make an accurate diagnosis via \[DEVICE/TEST NAME\].

In addition, asymptomatic people infected with the virus that causes COVID-19 may not shed enough virus to reach the limit of detection of the test, giving a false negative result. In the absence of symptoms, it is difficult to determine if asymptomatic people have been tested too late or too early. Therefore, negative results in asymptomatic individuals may include individuals who were tested too early and may become positive later, individuals who were tested too late and may have serological evidence of infection, or individuals who were never infected.

\[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: Specimens with low viral loads may not be detected in sample pools due to the decreased sensitivity or increased interference of pooled testing. Your interpretation of negative results should take into account clinical and epidemiological risk factors.\]

When diagnostic testing is negative, the possibility of a false negative result should be considered in the context of a patient’s recent exposures and the presence of clinical signs and symptoms consistent with COVID-19. The possibility of a false negative result should especially be considered if the patient’s recent exposures or clinical presentation indicate that COVID-19 is likely, and diagnostic tests for other causes of illness (e.g., other respiratory illness) are negative.

If COVID-19 is suspected based on exposure history together with other clinical findings, re-testing using a new sample with a sensitive method \[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: or without pooling\] should be considered by healthcare providers in consultation with public health authorities. Additional testing may be helpful to ensure testing was not conducted too early.

Risks to a patient of a false negative test result include: delayed or lack of supportive treatment, lack of monitoring of infected individuals and their household or other close contacts for symptoms resulting in increased risk of spread of COVID-19 within the community, or other unintended adverse events.

The performance of this test was established based on the evaluation of a limited number of clinical specimens. The clinical performance has not been established in all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.

**What is an EUA?**

The United States FDA has made this test available under an emergency access mechanism called an Emergency Use Authorization (EUA). The EUA is supported by the Secretary of Health and Human Service’s (HHS’s) declaration that circumstances exist to justify the emergency use of in vitro diagnostics (IVDs) for the detection and/or diagnosis of the virus that causes COVID-19. An IVD made available under an EUA has not undergone the same type of review as an FDA-approved or cleared IVD. FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, available alternatives, and based on the totality of scientific evidence available, it is reasonable to believe that this IVD may be effective in diagnosing COVID-19.

This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing \[include link to this letter\] for use in \[the specific laboratory, that is certified under CLIA and meets requirements to perform high complexity tests, in which it was developed\] for \[insert indication(s) from applicable appendix(ces)\] using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing.

The EUA for this test is in effect for the duration of the COVID-19 declaration justifying emergency use of IVDs, unless terminated or revoked (after which the test may no longer be used).

**What are the approved available alternatives?**

Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here: <https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases>. A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available.  FDA has issued EUAs for other tests that can be found at:

<https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization>.

**Where can I go for updates and more information?**

**CDC webpages:**

**General:** <https://www.cdc.gov/coronavirus/2019-ncov/index.html>

**Symptoms:**

<https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html>

**Healthcare Professionals:**

[https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html](https://www.cdc.gov/coronavirus/2019-nCoV/guidance-hcp.html)

**Information for Laboratories:** <https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html>

**Laboratory Biosafety:** <https://www.cdc.gov/coronavirus/2019-nCoV/lab-biosafety-guidelines.html>

**Isolation Precautions in Healthcare Settings:**

[https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html](https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html%20)

**Specimen Collection:** <https://www.cdc.gov/coronavirus/2019-nCoV/guidelines-clinical-specimens.html>

**Infection Control:** <https://www.cdc.gov/coronavirus/2019-ncov/php/infection-control.html>

**FDA webpages:**

**General:** [www.fda.gov/novelcoronavirus](http://www.fda.gov/novelcoronavirus)

**EUAs:**(includes links to fact sheet for individuals and manufacturer’s instructions) <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas>

**LABORATORY NAME:**

ADDRESS LINE 1

ADDRESS LINE 2



**Customer Support:**

+1 800 XXX-XXXX

customersupportemail@company.com

**Technical Support:**

+1 800 XXX-XXXX

techsupportemail@company.com


# 2,447  2021-11-15_FDA Fact Sheet - Fact Sheet for Healthcare Providers.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Fact Sheet - Fact Sheet for Healthcare Providers.md
file_date: 2021-11-15
title: FDA Fact Sheet - Fact Sheet for Healthcare Providers
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subcategory: fda-policy
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summary_short: The FDA “Fact Sheet for Healthcare Providers – Molecular Laboratory Developed Test (LDT) COVID-19 Authorized Tests” (updated Nov 15, 2021) provides standardized provider-facing risk/benefit, intended-use, and result-interpretation language for EUA-authorized molecular LDTs used on respiratory specimens from individuals suspected of COVID-19. It explains what positive and negative results mean, highlights false positive/false negative risks and variant-related performance limitations, and reiterates CLIA high-complexity and public health reporting expectations. It supports consistent communication to clinicians across laboratories operating under the molecular LDT umbrella EUA.


CONTENT

***INTERNAL TITLE:*** FACT SHEET FOR HEALTHCARE PROVIDERS  
Molecular Laboratory Developed Test (LDT) COVID-19 Authorized Tests  
Updated: November 15, 2021  
Coronavirus Disease 2019 (COVID-19)

This Fact Sheet informs you of the significant known and potential risks and benefits of the emergency use of a Molecular Laboratory Developed Test (LDT) COVID-19 Authorized Test (Molecular LDT COVID-19 Authorized Test) that has been issued an Emergency Use Authorization (EUA) by FDA.

The Molecular LDT COVID-19 Authorized Test is authorized for use on respiratory specimens collected from individuals suspected of COVID-19 by their healthcare provider.

**All patients whose specimens are tested with an authorized test will receive the Fact Sheet for Patients: Molecular Laboratory Developed Test (LDT) COVID-19 Authorized Tests.**

**This test is to be performed only using respiratory specimens collected from individuals suspected of COVID-19 by their healthcare provider.**

### What are the symptoms of COVID-19? 
Many patients with COVID-19 have developed fever and/or symptoms of acute respiratory illness (e.g., cough, dyspnea), although some individuals experience only mild symptoms or no symptoms at all. The current information available to characterize the spectrum of clinical illness associated with COVID-19 suggests that, when present, symptoms include cough, shortness of breath or dyspnea, fever, chills, myalgias, headache, sore throat, new loss of taste or smell, nausea or vomiting or diarrhea. Signs and symptoms may appear any time from 2 to 14 days after exposure to the virus, and the median time to symptom onset is approximately 5 days. For further information on the symptoms of COVID-19 please see the link provided in "Where can I go for updates and more information?" section.

Public health officials have identified cases of COVID-19 throughout the world, including the United States. Please check the CDC COVID-19 webpage (see link provided in "Where can I go for updates and more information?" section at the end of this document) or your local jurisdictions website for the most up to date information.

### What do I need to know about COVID-19 testing? 
Current information on COVID-19 for healthcare providers is available at CDC’s webpage, *Information for Healthcare Professionals* (see links provided in "Where can I go for updates and more information?" section).

- The Molecular LDT COVID-19 Authorized Test can be used to test respiratory specimens validated in the laboratory that developed the test for COVID-19.
- The Molecular LDT COVID-19 Authorized Test should be ordered for the detection of nucleic acid from SARS-CoV-2 in individuals suspected of COVID-19 by their healthcare provider.
- The Molecular LDT COVID-19 Authorized Test is only authorized for use at the laboratory that developed the test for COVID-19 that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. 263a, to perform high complexity tests.

Specimens should be collected with appropriate infection control precautions. Current guidance for COVID-19 infection control precautions are available at the CDC’s website (see links provided in "Where can I go for updates and more information?" section).

When collecting and handling specimens from individuals suspected of being infected with the virus that causes COVID-19, appropriate personal protective equipment should be used as outlined in the CDC Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19). For additional information, refer to CDC Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under Investigation (PUIs) for Coronavirus Disease 2019 (COVID-19) (see links provided in "Where can I go for updates and more information?" section).

### What does it mean if the specimen tests positive for the virus that causes COVID-19? 
A positive test result for COVID-19 indicates that RNA from SARS-CoV-2 was detected, and therefore the patient is infected with the virus and presumed to be contagious. Laboratory test results should always be considered in the context of clinical observations and epidemiological data (such as local prevalence rates and current outbreak/epicenter locations) in making a final diagnosis and patient management decisions. Patient management should be made by a healthcare provider and follow current CDC guidelines.

The Molecular LDT COVID-19 Authorized Test has been designed to minimize the likelihood of false positive test results. However, it is still possible that this test can give a false positive result, even when used in locations where the prevalence is below 5%. In the event of a false positive result, risks to patients could include the following: a recommendation for isolation of the patient, monitoring of household or other close contacts for symptoms, patient isolation that might limit contact with family or friends and may increase contact with other potentially COVID-19 patients, limits in the ability to work, the delayed diagnosis and treatment for the true infection causing the symptoms, unnecessary prescription of a treatment or therapy, or other unintended adverse effects.

All laboratories using this test must follow the standard testing and reporting guidelines according to their appropriate public health authorities.

### What does it mean if the specimen tests negative for the virus that causes COVID-19?
A negative test result for this test means that SARS-CoV-2 RNA was not present in the specimen above the limit of detection. However, a negative result does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions. It is possible to test a person too early or too late during infection to make an accurate diagnosis via the Molecular LDT COVID-19 Authorized Test.

When diagnostic testing is negative, the possibility of a false negative result should be considered in the context of a patient’s recent exposures and the presence of clinical signs and symptoms consistent with COVID-19. The possibility of a false negative result should especially be considered if the patient’s recent exposures or clinical presentation indicate that COVID-19 is likely, and diagnostic tests for other causes of illness (e.g., other respiratory illness) are negative. If COVID-19 is still suspected based on exposure history together with other clinical findings, re-testing with an alternative method should be considered by healthcare providers in consultation with public health authorities. Additional testing may be helpful to ensure testing was not conducted too early.

Risks to a patient of a false negative test result include: delayed or lack of supportive treatment, lack of monitoring of infected individuals and their household or other close contacts for symptoms resulting in increased risk of spread of COVID-19 within the community, or other unintended adverse events.

The performance of this test was established based on the evaluation of a limited number of clinical specimens. The clinical performance has not been established in all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARSCoV-2 and their prevalence, which change over time.

### What is an EUA?
The United States FDA has made this test available under an emergency access mechanism called an Emergency Use Authorization (EUA). The EUA is supported by the Secretary of Health and Human Service’s (HHS’s) declaration that circumstances exist to justify the emergency use of in vitro diagnostics (IVDs) for the detection and/or diagnosis of the virus that causes COVID-19.

An IVD made available under an EUA has not undergone the same type of review as an FDA-approved or cleared IVD. FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, available alternatives, and based on the totality of scientific evidence available, it is reasonable to believe that this IVD may be effective in diagnosing COVID-19.

The EUA for this test is in effect for the duration of the COVID-19 declaration justifying emergency use of IVDs, unless terminated or revoked (after which the test may no longer be used).

### What are the approved available alternatives?
Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here: [https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases](https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases). A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available. FDA has issued EUAs for other tests that can be found at: [https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization).

### Where can I go for updates and more information?
#### CDC webpages:
**General:** [https://www.cdc.gov/coronavirus/2019-ncov/index.html](https://www.cdc.gov/coronavirus/2019-ncov/index.html)
**Symptoms:**
[https://www.cdc.gov/coronavirus/2019-ncov/symptoms-](https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html)
[testing/symptoms.html](https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html)
**Healthcare Professionals:** [https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html](https://www.cdc.gov/coronavirus/2019-nCoV/guidance-hcp.html)
**Information for Laboratories:** [https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html](https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html)
**Laboratory Biosafety:** [https://www.cdc.gov/coronavirus/2019-nCoV/lab-biosafety-guidelines.html](https://www.cdc.gov/coronavirus/2019-nCoV/lab-biosafety-guidelines.html)
**Isolation Precautions in Healthcare Settings:** [https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html](https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html)
**Specimen Collection:** [https://www.cdc.gov/coronavirus/2019-nCoV/guidelines-clinical-specimens.html](https://www.cdc.gov/coronavirus/2019-nCoV/guidelines-clinical-specimens.html)
**Infection Control:** [https://www.cdc.gov/coronavirus/2019-ncov/php/infection-control.html](https://www.cdc.gov/coronavirus/2019-ncov/php/infection-control.html)

#### FDA webpages:
**General:** [www.fda.gov/novelcoronavirus](http://www.fda.gov/novelcoronavirus)
**EUAs:**(includes links to fact sheet for individuals and manufacturer’s instructions) [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas)

#### LABORATORY CONTACT:
Contact information for the laboratory that developed the Molecular LDT COVID-19 Authorized Test must be provided to the Healthcare Provider in the test report or material/mechanism (e.g., email) that accompanies this Fact Sheet and the test results.


# 1,791  2021-11-15_FDA Fact Sheet - Fact Sheet for Patients Template.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Fact Sheet - Fact Sheet for Patients Template.md
file_date: 2021-11-15
title: FDA Fact Sheet - Fact Sheet for Patients Template
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: docx
xfile_type: docx
gfile_url: https://docs.google.com/document/d/1buxdsyDhN_T_c6FVW3PIPMM_duc8Nnv4
xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fda-policy/2021-11-15_FDA%20Fact%20Sheet%20-%20Fact%20Sheet%20for%20Patients%20Template.docx
pdf_gdrive_url: https://drive.google.com/file/d/1NIqDxLqy-csW9Upw2VhSpQtXYZ90LoM7
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-11-15_FDA%20Fact%20Sheet%20-%20Fact%20Sheet%20for%20Patients%20Template.pdf
conversion_input_file_type: docx
conversion: pandoc
license: Public Domain
tokens: 1791
words: 1327
notes: 
summary_short: The FDA “Fact Sheet for Patients Template” (v1.0, Nov 15, 2021) is a fill-in patient-facing document for EUA-authorized COVID-19 testing that explains what the test is, why someone may be tested (including serial testing), and how to interpret positive and negative results. It includes optional standardized language for pooled testing, follow-up and emergency-care guidance, and required EUA status and alternatives statements tied to the umbrella EUA for serial testing. It helps labs and test sponsors provide consistent, plain-language risk/benefit and next-step instructions to individuals receiving results.


CONTENT

***INTERNAL TITLE:*** FACT SHEET FOR PATIENTS
**Coronavirus Disease 2019 (COVID-19)**
**v1.0 (November 15, 2021)**
**LABORATORY NAME - TEST NAME     Month DD, YYYY**

You are being given this Fact Sheet because your sample(s) was tested for the Coronavirus Disease 2019 (COVID-19) using the \[DEVICE/TEST NAME\].

This Fact Sheet contains information to help you understand the risks and benefits of using this test for the diagnosis of COVID-19. After reading this Fact Sheet, if you have questions or would like to discuss the information provided, please talk to your healthcare provider.

**For the most up to date information on COVID-19 please visit the CDC Coronavirus Disease 2019 (COVID-19) webpage:**

[**https://www.cdc.gov/COVID19**](https://www.cdc.gov/nCoV)

**What is COVID-19?**

COVID-19 is caused by the SARS-CoV-2 virus which is a new virus in humans causing a contagious respiratory illness. COVID-19 can present with a mild to severe illness, although some people infected with COVID-19 may have no symptoms at all. Older adults and people of any age who have underlying medical conditions have a higher risk of severe illness from COVID-19. Serious outcomes of COVID-19 include hospitalization and death. The SARS-CoV-2 virus can be spread to others not just while one is sick, but even before a person shows signs or symptoms of being sick (e.g., fever, coughing, difficulty breathing, etc.). A full list of symptoms of COVID-19 can be found at the following link: <https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html>.

**What is the \[DEVICE/TEST NAME\]?**

The test is designed to detect the virus that causes COVID-19 in anterior nasal swabs.

**Why was my sample tested?**

You were tested because your healthcare provider believes you may have been exposed to the virus that causes COVID-19 based on your signs and symptoms (e.g., fever, cough, difficulty breathing), and/or because:

-   You are being tested at regular intervals (serial testing) even though you do not have symptoms or risk factors for COVID-19; or

-   You live in or have recently traveled to a place where transmission of COVID-19 is known to occur; or

-   You have been in close contact with an individual suspected of or confirmed to have COVID-19; or

-   You and your healthcare provider believe there is another reason to investigate your COVID-19 status.

Testing of the samples will help find out if you may have COVID-19.

\[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: Laboratories may use pooling when testing your specimen, which means they combine your sample with other individuals’ samples prior to testing and test them as a “pool”. The laboratory may return a result for the entire pool together or may return individual results.\]

**What are the known and potential risks and benefits of the test?**

Potential risks include:

-   Possible discomfort or other complications that can happen during sample collection.

-   Possible incorrect test result (see below for more information).

Potential benefits include:

-   The results, along with other information, can help your healthcare provider make informed recommendations about your care.

-   The results of this test may help limit the spread of COVID-19 to your family and those you come in contact with.

**What does it mean if I have a positive test result?**

If you have a positive test result, it is very likely that you have COVID-19. Therefore, it is also likely that you may be placed in isolation to avoid spreading the virus to others. You should follow CDC guidance to reduce the potential transmission of disease.

\[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: If you were tested as part of a pool that returned a positive or invalid test result, you may have COVID-19 and should consider yourself to have a positive test result unless or until you receive a negative test result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, you should isolate until receiving a negative result when re-tested individually and should not be grouped with other individuals who have received a positive or presumptive positive result.\]

There is a smaller possibility that this test can give a positive result that is wrong (a false positive result) particularly when used in a population without many cases of COVID-19 infection. Your healthcare provider will work with you to determine how best to care for you based on the test results along with medical history, and your symptoms

**What does it mean if I have a negative test result?**

A negative test result means that the virus that causes COVID-19 was not found in your sample.

However, it is possible for this test to give a negative result that is incorrect (false negative) in some people with COVID-19. You might test negative if the sample was collected early during your infection. You could also be exposed to COVID-19 after your sample was collected and then have become infected.

In particular, people infected with COVID-19 but who have no symptoms may not shed enough virus to trigger a positive test. This means that you could possibly still have COVID-19 even though the test result is negative. If your test is negative, your healthcare provider will consider the test result together with all other aspects of your medical history (such as symptoms, possible exposures, and geographical location of places you have recently traveled) in deciding how to care for you.

\[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: If your test result indicates your specimen was pooled and you have a negative test result there a small chance that your result is incorrect. You should talk with your healthcare provider if you are concerned.\]

If you have no symptoms but have been tested because your healthcare provider thought you may have been exposed to COVID-19, you should continue to monitor your health and let your healthcare provider know if you develop any symptoms of COVID-19. If you develop symptoms you may need another test to determine if you have contracted the virus causing COVID-19.

**If you develop symptoms or your symptoms get worse, you should seek medical care. If you have the following symptoms you should seek immediate medical care at the closest emergency room:**

\- Trouble breathing

\- Persistent pain or pressure in the chest

\- New confusion

\- Inability to wake up or stay awake

\- Bluish lips or face

It is important that you work with your healthcare provider to help you understand the next steps you should take.

**Is this test FDA-approved or cleared?**

No. This test is not yet approved or cleared by the United States FDA. FDA may issue an Emergency Use Authorization (EUA) when certain criteria are met, which includes that there are no adequate, approved, available alternatives. The EUA for this test is supported by the Secretary of Health and Human Service’s (HHS’s) declaration that circumstances exist to justify the emergency use of in vitro diagnostics for the detection and/or diagnosis of the virus that causes COVID-19. This EUA will remain in effect (meaning this test can be used) for the duration of the COVID-19 declaration justifying the emergency use of in vitro diagnostics, unless it is terminated or revoked by FDA (after which the test may no longer be used).

This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing \[include link to this letter\] for use in \[the specific laboratory, that is certified under CLIA and meets requirements to perform high complexity tests, in which it was developed\] for \[insert indication(s) from applicable appendix(ces)\] using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing.

**What are the approved alternatives?**

Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here:<https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases>. A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available.  FDA has issued EUAs for other tests that can be found at:

<https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization>


# 1,407  2021-11-15_FDA Fact Sheet - Fact Sheet for Patients.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Fact Sheet - Fact Sheet for Patients.md
file_date: 2021-11-15
title: FDA Fact Sheet - Fact Sheet for Patients
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: pdf
xfile_type: NA
gfile_url: NA
xfile_github_download_url: NA
pdf_gdrive_url: https://drive.google.com/file/d/15IYuV9oStHUdX__pWbgcong0pukyfFSz
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-11-15_FDA%20Fact%20Sheet%20-%20Fact%20Sheet%20for%20Patients.pdf
conversion_input_file_type: pdf
conversion: megaparse-v
license: Public Domain
tokens: 1407
words: 960
notes: 
summary_short: The FDA “Fact Sheet for Patients – Molecular Laboratory Developed Test (LDT) COVID-19 Authorized Tests” (updated Nov 15, 2021) explains, in plain language, what an EUA-authorized molecular LDT COVID-19 test is and why a patient may have been tested. It describes what positive and negative results mean, including the possibility of false results, and emphasizes follow-up with a healthcare provider for next steps. It also clarifies that the test is authorized under an EUA (not fully FDA approved/cleared) and points patients to CDC and FDA resources for current information.


CONTENT

***INTERNAL TITLE:*** FACT SHEET FOR PATIENTS  
Molecular Laboratory Developed Test (LDT) COVID-19 Authorized Tests  
Updated: November 15, 2021  
Coronavirus Disease 2019 (COVID-19)

You are being given this Fact Sheet because your sample(s) was tested for the Coronavirus Disease 2019 (COVID-19) using a Molecular Laboratory Developed Test (LDT) COVID-19 Authorized Test (Molecular LDT COVID-19 Authorized Test) that has been issued an Emergency Use Authorization (EUA) by FDA.

This Fact Sheet contains information to help you understand the risks and benefits of using this test for the diagnosis of COVID-19. After reading this Fact Sheet, if you have questions or would like to discuss the information provided, please talk to your healthcare provider.

**For the most up to date information on COVID-19 please visit the CDC Coronavirus Disease 2019 (COVID-19) webpage:**  
[https://www.cdc.gov/COVID19](https://www.cdc.gov/COVID19)

### What is COVID-19?
COVID-19 is caused by the SARS-CoV-2 virus which is a new virus in humans causing a contagious respiratory illness. COVID-19 can present with a mild to severe illness, although some people with COVID-19 may have no symptoms at all. Older adults and people of any age who have underlying medical conditions have a higher risk of severe illness from COVID-19. Serious outcomes of COVID-19 include hospitalization and death. The SARS-CoV-2 virus can be spread to others not just while one is sick, but even before a person shows signs or symptoms of being sick (e.g., fever, coughing, difficulty breathing, etc.). A full list of symptoms of COVID-19 can be found at the following link:  
[https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html](https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html).

### What is the Laboratory Developed Test?
The Molecular LDT COVID-19 Authorized Test is designed, for use in a single laboratory, to detect the virus that causes COVID-19 in respiratory specimens, for example nasal or oral swabs.

### Why was my sample tested?
You were tested because your healthcare provider believes you may have been exposed to the virus that causes COVID-19 based on your signs and symptoms (e.g., fever, cough, difficulty breathing), and/or because:
- You live in or have recently traveled to a place where transmission of COVID-19 is known to occur, and/or
- You have been in close contact with an individual suspected of or confirmed to have COVID-19.

Testing of the samples will help find out if you may have COVID-19.

### What are the known and potential risks and benefits of the test?
Potential risks include:
- Possible discomfort or other complications that can happen during sample collection.
- Possible incorrect test result (see below for more information).

Potential benefits include:
- The results, along with other information, can help your healthcare provider make informed recommendations about your care.
- The results of this test may help limit the spread of COVID-19 to your family and others in your community.

### What does it mean if I have a positive test result?
If you have a positive test result, it is very likely that you have COVID-19. Therefore, it is also likely that you may be placed in isolation to avoid spreading the virus to others. You should follow CDC guidance to reduce the potential transmission of disease. There is a smaller possibility that this test can give a positive result that is wrong (a false positive result) particularly when used in a population without many cases of COVID-19. Your healthcare provider will work with you to determine how best to care for you based on the test results along with medical history, and your symptoms.

### What does it mean if I have a negative test result?
A negative test result means that the virus that causes COVID-19 was not found in your sample.

However, it is possible for this test to give a negative result that is incorrect (false negative) in some people with COVID-19. You might test negative if the sample was collected early during your infection. You could also be exposed to COVID-19 after your sample was collected and then have become infected.

This means that you could possibly still have COVID-19 even though the test is negative. If your test is negative, your healthcare provider will consider the test result together with all other aspects of your medical history (such as symptoms, possible exposures, and geographical location of places you have recently traveled) in deciding how to care for you.

It is important that you work with your healthcare provider to help you understand the next steps you should take.

### Is this test FDA-approved or cleared?
No. This test is not yet approved or cleared by the United States FDA. FDA may issue an Emergency Use Authorization (EUA) when certain criteria are met, which includes that there are no adequate, approved, available alternatives. The EUA for this test is supported by the Secretary of Health and Human Service’s (HHS’s) declaration that circumstances exist to justify the emergency use of in vitro diagnostics for the detection and/or diagnosis of the virus that causes COVID-19. This EUA will remain in effect (meaning this test can be used) for the duration of the COVID-19 declaration justifying the emergency use of in vitro diagnostics, unless it is terminated or revoked by FDA (after which the test may no longer be used).

### What are the approved alternatives?
Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here:  
[https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases](https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases). A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available. FDA has issued EUAs for other tests that can be found at:  
[https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization).

**Where can I go for updates and more information?** The most up-to-date information on COVID-19 is available at the CDC General webpage: [https://www.cdc.gov/COVID19](https://www.cdc.gov/COVID19). In addition, please also contact your healthcare provider with any questions/concerns.


# 3,812  2021-11-15_FDA Fact Sheet - Test Summary Template.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Fact Sheet - Test Summary Template.md
file_date: 2021-11-15
title: FDA Fact Sheet - Test Summary Template
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: docx
xfile_type: docx
gfile_url: https://docs.google.com/document/d/1hCGpvQwuLnzFif5So2fCKvXc6HbzDlqf
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pdf_gdrive_url: https://drive.google.com/file/d/1YClkMKU4YVojP28wnwyDhl_7QIzaQylH
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-11-15_FDA%20Fact%20Sheet%20-%20Test%20Summary%20Template.pdf
conversion_input_file_type: docx
conversion: pandoc
license: Public Domain
tokens: 3812
words: 2611
notes: 
summary_short: The FDA “Test Summary Template” is an EUA-ready summary document for a laboratory-developed SARS-CoV-2 molecular test that standardizes how intended use, test principles, instruments/reagents, controls, result interpretation, and performance data are presented. It includes optional sections for pooling, home collection, and asymptomatic screening, plus required language on confirmatory testing considerations and variant-related performance limitations. It helps CLIA high-complexity laboratories package key validation and labeling elements in a consistent format aligned with the umbrella EUA for serial testing.


CONTENT

***[Laboratory Name - Test Name]***
Test Summary - ***[DATE]***

**EMERGENCY USE AUTHORIZATION (EUA) TEST SUMMARY FOR THE *\[LABORATORY NAME – TEST NAME\]***

For *In vitro* Diagnostic Use
Rx Only
For use under Emergency Use Authorization (EUA) only

**The *\[test name\]* will be performed at the *\[laboratory name\]* located at *\[laboratory address\]*, which is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform high complexity tests.**

### INTENDED USE

The ***\[test name\]*** is intended for the *in vitro* ***\[insert indication(s) from applicable appendix(ces)\]***. Testing is limited to ***\[laboratory name\]*** laboratory located at ***\[laboratory address\]***, which is certified under Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform high-complexity testing.

The ***\[test name\]*** is intended for use by qualified and trained clinical laboratory personnel specifically instructed and trained in the techniques of real-time PCR and in vitro diagnostic procedures. The ***\[test name\]*** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

Results are for the detection and identification of SARS-CoV-2 RNA. The SARS-CoV-2 nucleic acid is generally detectable in anterior nasal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.

Laboratories within the United States and its territories are required to report all results to the appropriate public health authorities.

\[INCLUDE THIS PARAGRAPH IF YOUR INDICATION INCLUDES POOLING:\] Negative results from pooled testing should not be treated as definitive. If a patient’s clinical signs and symptoms are inconsistent with a negative result or results are necessary for patient management, then the patient should be considered for individual testing. Specimens included in pools with a positive or invalid result must be reported as presumptive positive or tested individually prior to reporting a result. Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result. Specimens with low viral loads may not be detected with pooled testing due to decreased sensitivity or increased interference from pooled testing.

For serial testing programs, additional confirmatory testing for negative results may be necessary, if there is a high likelihood of COVID-19, such as an individual with a close contact with COVID-19 or with suspected exposure to COVID-19 or in communities with high prevalence of infection. Additional confirmatory testing for positive results may also be necessary, if there is a low likelihood of COVID-19, such as in individuals without known exposure to COVID-19 or residing in communities with low prevalence of infection.

#### 1.  *Special Conditions for Use Statements:*

For use under Emergency Use Authorization (EUA) only

For prescription use only

For *in vitro* diagnostic use only

\[INCLUDE THIS PARAGRAPH IF YOUR INDICATION INCLUDES HOME COLLECTION:\] Testing of specimens self-collected at home is limited to specimens collected with the ***\[name of authorized home collection kit with which your test is validated\]*** by ***\[the patient population authorized in the home collection kit EUA\]***.

This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing \[include link to this letter\] for use in \[the specific laboratory, that is certified under CLIA and meets requirements to perform high complexity tests, in which it was developed\] for \[insert indication(s) from applicable appendix(ces)\] using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing.

### DEVICE DESCRIPTION AND TEST PRINCIPLE

The \[***Test Name*\]** assay is a reverse transcription polymerase chain reaction (RT -PCR) test. The SARS-CoV-2 primer and probe set(s) is designed to detect RNA from the SARS-CoV-2 ***\[genes/regions\]*** in anterior nasal swab specimens that were collected from individuals, including individuals without symptoms or other reasons to suspect COVID-19.

***\[Describe the processes used to perform the test, including, as applicable, 1) nucleic acid extraction, 2) reverse transcription of target RNA to cDNA, 3) PCR amplification of target and internal control, and 4) simultaneous detection of PCR amplicons by fluorescent dye labeled probes. Include key parameters such as input volumes, reverse transcription (RT) time and temperature, PCR cycling parameters including dwell temperature and dwell times.\]***

### INSTRUMENTS USED WITH TEST

#### Instruments

The \[***test name***\], a real-time RT-PCR test, is to be used with the \[***list extraction kit(s)***\] and the \[***list RT-PCR Instrument(s)***\] and \[***RT-PCR Instrument Software***\].

#### Collection Kits (if applicable)

This assay can be used with the **\[*list EUA authorized Home Collection Kit(s)*\].**

#### Reagents

The primary reagents used in \[***test name***\] assay:

| Kits and Reagents | Manufacturer | Catalog # |
| --- | --- | --- |
||

### CONTROL MATERTIAL(s) TO BE USED WITH *\[test name\]:*

***\[List all control materials used with the test and describe what they are, how they are expected to work, where in the testing process they are used, and the frequency of use. If a control is commercially available, provide supplier’s name and catalog number or other identifier; if your device relies on external controls that are manufactured by a third party please note that these controls must also be validated within your analytical and clinical studies.\]***

Controls that are used with the test include:

1.  A “no template” (negative) control is needed to ***\[describe need\]*** and is used ***\[describe use – please also specify frequency of use\]***

2.  A positive template control is needed to ***\[describe need\]*** and is used ***\[describe use – please specify the concentration of the positive control relative to the LoD of your test (note that ideally the positive control concentration should be such that it is close to the LoD of your test) and also specify frequency of use\]***

3.  An extraction control ***\[describe control\]*** is needed to ***\[describe need\]*** and is used ***\[describe use – please also specify frequency of use\].*** **Please note that if the no template control and positive control, are taken through the entire sample processing procedure, including the extraction, then a separate extraction control is not required**.

4.  An internal control ***\[describe control\]*** is needed to ***\[describe need\]*** and is used ***\[describe use\]***.

### INTERPRETATION OF RESULTS

All test controls must be examined prior to interpretation of patient results. If the controls are not valid, the patient results cannot be interpreted. Appropriate control interpretation criteria and result interpretation criteria are described here. **You must describe if a Ct cutoff is used as part of your testing algorithm and/or if the end user is required to review curves before final result interpretation. Although not typical for molecular-based tests, if the test result involves the use of an algorithm/calculation, for example a ratio value, when determining the final patient test result, include a detailed description and any additional calibration materials that may be required.**

#### 1.  Examination and Interpretation of Control Results

***\[Describe in detail the expected results generated, including acceptance criteria, for all the controls used in test. Describe the measured values (if applicable) for valid and invalid controls and outline the actions to take in the event of an invalid control result.\]***

#### 2.  Examination and Interpretation of Patient Specimen Results:

Assessment of clinical specimen test results must be performed after the controls have been examined and determined to be valid and acceptable. If the controls are not valid, the patient results cannot be interpreted.

***\[Describe when clinical specimen test results should be assessed and outline the criteria for test validity**. **Clearly indicate how to interpret numeric test values (if applicable) as positive or negative for presence of SARS-CoV-2. Indicate if the end user is required to review curves before final result interpretation and, if applicable, how to identify indeterminate/inconclusive/equivocal results. When applicable, we recommend providing a table clearly describing the possible combinations of test result values for each primer/probe set. Describe how they should be combined into a final interpretation of the result for your test. If the test produces an equivocal or indeterminate result, please indicate what follow-up testing/process should be conducted, if applicable.\]***

***\[If your test is indicated for pooling, also include a pooling results interpretation table, indicating how to interpret each possible result, including when samples should be retested individually.\]***

### PERFORMANCE EVALUATION

#### 1. Limit of Detection (LoD) -Analytical Sensitivity:

The LoD for the ***\[test name\]*** was evaluated and verified using ***\[validation material, e.g., SARS-CoV-2 inactivated virus (e.g., heat treated or irradiated)\]*** per the validation required by Appendix A of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing. Nucleic acid was extracted from the swabs using ***\[specify nucleic acid extraction\]*** and the reverse transcription RT-PCR was performed using the ***\[specify RT-PCR Instrument and, if applicable, interpretive software version\]***. Preliminary and Confirmation LoD results are included in the tables below.

***\[insert table such as:\]* Table Example: Preliminary Determination of LoD**

| Virus Concentration | Target 1 Ct Value | Target 2 Ct Value | Internal Control Ct Value | # of Replicates |
| --- | --- | --- | --- | --- |
||

***\[insert table such as:\]* Table Example: LoD Confirmation**

| **Targets**           | **Target 1** | **Target 2** |
|-----------------------|--------------|--------------|
| Analyte Concentration |              |              |
| Positives/Total       |              |              |
| % Detected            |              |              |
| Mean Ct               |              |              |
| Mean SD               |              |              |
| CV                    |              |              |
||

The data confirmed the assay analytical sensitivity is ***\[specify LoD represented as genome copies or equivalents/mL\]***.

#### 2. Inclusivity (Analytical Reactivity):

An alignment was performed with the oligonucleotide primer and probe sequences of the ***\[test name\]*** with ***\[number of sequences\]*** publicly available SARS-CoV-2 sequences (including mutation variants of high prevalence, i.e., B.1.617.2 and sub-lineages at the time of issuance of this letter) from ***\[specify sequence data base, e.g., GISAID\]*** to demonstrate the predicted inclusivity of the assay.

***\[Insert summary of results of inclusivity analysis.\]***

#### 3.  Cross-reactivity (Analytical Specificity):

Analytical specificity of the primer/probe combination for ***\[test name\]*** was evaluated by conducting sequence alignment of the primer/probe sequences of the test with publicly available genome sequences for potential cross-reacting microorganisms. The following organisms were tested with ***\[test name\]*** primer probe set.

***\[insert table such as:\]* Table Example: Organisms Analyzed for Cross Reactivity**

| Organism | Strain | Target 1 | Target 2 |
| --- | --- | --- | --- |
||

#### 4. Clinical Evaluation:

Clinical evaluation of the ***\[test name\]*** was conducted with 30 individual natural positive and 30 negative anterior nasal swab clinical specimens collected from patients suspected of SARS-CoV-2 infection by a healthcare provider in COVID-19 disease endemic region(s). These specimens were ***\[prospective, retrospective, or leftover samples\]***. Nucleic acid was extracted from the swabs using ***\[specify nucleic acid extraction\]*** and the reverse transcription RT-PCR was performed using the ***\[specify RT-PCR Instrument and, if applicable, interpretive software version\]***.

Data is summarized in the Table below:

**Table: Summary Performance on individual anterior nasal swab specimens in comparison to an FDA-authorized method for specimens collected from individuals suspected of COVID-19 by a healthcare provider**

| [Test Name] | FDA EUA RT-PCR Assay | Total | % Performance Agreement | 95% CI |  |
| --- | --- | --- | --- | --- | --- |
| Detected | Not Detected |  |  |  |  |
| Detected | A | B | A+B | PPA= 100% x A/(A+C) |  |
| Not Detected | C | D | C+D | NPA= 100% x D/(B+D) |  |
| Total | A+C | B+D |  |  |  |
||

\[IF VALIDATION WAS ALSO COMPLETED WITH SPECIMENS COLLECTED FROM INDIVIDUALS WITHOUT SYMPTOMS OR OTHER REASONS TO SUSPECT COVID-19, ALSO INCLUDE THOSE RESULTS:\] Clinical evaluation of the ***\[test name\]*** was conducted with 20 positive and 100 negative specimens collected from individuals without symptoms or other reasons to suspect COVID-19 in COVID-19 disease endemic region(s). These specimens were ***\[prospective, retrospective, or leftover samples\]***. Nucleic acid was extracted from the swabs using ***\[specify nucleic acid extraction\]*** and the reverse transcription RT-PCR was performed using the ***\[specify RT-PCR Instrument and, if applicable, interpretive software version\]***.

Data is summarized in the Table below:

**Table: Summary Performance on individual anterior nasal swab specimens in comparison to an FDA-authorized method for specimens collected from individuals without symptoms or other reasons to suspect COVID-19**

| [Test Name] | FDA EUA RT-PCR Assay | Total | % Performance Agreement | 95% CI |  |
| --- | --- | --- | --- | --- | --- |
| Detected | Not Detected |  |  |  |  |
| Detected | A | B | A+B | PPA= 100% x A/(A+C) |  |
| Not Detected | C | D | C+D | NPA= 100% x D/(B+D) |  |
| Total | A+C | B+D |  |  |  |
||

#### 5. Additional Validation for *\[indication provided by appendix(ces) B -K, e.g., Media Pooling up to n=10 with validation option 2\]*:

***\[For each additional indication, include a section with the required validation and documentation from the applicable appendix.\]***

### LIMITATIONS

-   The performance of this test was established based on the evaluation of a limited number of clinical specimens collected between ***\[include collection window dates between MONTH, YEAR AND MONTH, YEAR, and the location(s) of clinical evaluation (Countr(ies)– identify if it was multiple sites in the country or limited locations – if known)\]***. The clinical performance of this test has not been established in all circulating variants but is anticipated to be reflective of the variants in circulation at the time and location(s) of the clinical evaluation. As such, performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2, and their prevalence, which change over time.

-   \[If evaluation of specimens collected from individuals without symptoms or other reasons to suspect COVID-19 have not yet been evaluated, include this statement:\] Clinical performance has been established in specimens collected from subjects suspected of COVID-19 by a healthcare provider. Performance of specimens collected from individuals without symptoms or other reasons to suspect COVID-19 has not been established. A study to determine the performance in individuals without symptoms or other reasons to suspect COVID-19 will be completed.

### WARNINGS:

-   This product has not been FDA cleared or approved, but has been authorized by FDA under an Emergency Use Authorization (EUA) for use by the laboratory that developed the test and which is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform high complexity tests.

-   This product has been authorized only for the detection of nucleic acid from SARS- CoV-2, not for any other viruses or pathogens; and

-   The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.


# 11,054  2021-11-15_FDA Guidance - COVID IVD Test Developers v5.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Guidance - COVID IVD Test Developers v5.md
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title: FDA Guidance - COVID IVD Test Developers v5
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summary_short: The FDA “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)” (v5, Nov 15, 2021) sets the overarching regulatory and enforcement framework for COVID-19 diagnostic and serology IVDs during the pandemic. It defines FDA’s EUA review priorities, expectations for validation, rules for offering tests during FDA review, state and laboratory policies, and how authorized tests may be modified. It guides developers and laboratories on which tests FDA will prioritize, how to maintain compliance, and when EUA authorization is expected before distribution.


CONTENT

***INTERNAL TITLE:*** Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*
Guidance for Developers and Food and Drug Administration Staff

Document issued on the web on November 15, 2021.

This document supersedes “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised): Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff” issued May 11, 2020.

U.S. Department of Health and Human Services  
Food and Drug Administration  
Center for Devices and Radiological Health

*This is the fifth edition of this guidance, which originally issued February 29, 2020 and was subsequently revised on March 16, May 4, and May 11, 2020.

## Preface
### Public Comment
This guidance is being issued to address the Coronavirus Disease 2019 (COVID-19) public health emergency. This guidance is being implemented without prior public comment because the Food and Drug Administration (FDA or Agency) has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices.

Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to [https://www.regulations.gov](https://www.regulations.gov). All comments should be identified with the docket number FDA-2020-D-0987 and complete title of the guidance in the request.

### Additional Copies
Additional copies are available from the FDA webpage titled “COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders,” available at [https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders](https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders), and the FDA webpage titled “Search for FDA Guidance Documents,” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents](https://www.fda.gov/regulatory-information/search-fda-guidance-documents). You may also send an e-mail request to CDRH-Guidance@fda.hhs.gov to receive an additional copy of the guidance. Please include the document number 20010-R4 and complete title of the guidance in the request.

### Questions
For questions about this document, contact CDRH-EUA-Templates@fda.hhs.gov.


## Table of Contents

I. Introduction ............................................................................................................................. 4  
II. Background ............................................................................................................................ 5  
III. Scope .................................................................................................................................... 6  
IV. Policy ..................................................................................................................................... 7  
  A. Prioritization of Review of EUA Requests for Tests ............................................................... 7  
  B. State Authorization of High-Complexity CLIA-Certified Laboratories ................................. 10  
  C. Distribution and Offering of SARS-CoV-2 Diagnostic and Serology Tests During FDA
  Review ...................................................................................................................................... 11  
    (1) Diagnostic and Serology Tests on Notification Lists for which an EUA Request was
    Submitted ................................................................................................................................. 12  
    (2) Laboratory Serology Tests on the Notification List and Certain LDTs for Which an
    EUA Request was Not Submitted ............................................................................................ 13  
    (3) Recommendations Regarding Test Reports and Other Information for Tests Offered
    During FDA Review of EUA Requests ....................................................................................... 14  
    (4) FDA Review of EUA Requests ............................................................................................. 14  
  D. Modifications to EUA-Authorized Diagnostic COVID-19 Tests ............................................ 15  
    (1) Certain Modifications Made After Issuance of this Updated Guidance .............................. 16  
    (2) Certain Modifications Made Before Issuance of this Updated Guidance ........................... 16  
V. Validation .............................................................................................................................. 17  
VI. Availability of EUA Templates .............................................................................................. 18  
Appendix A – FDA Review of EUA Requests for COVID-19 Tests Not Offered Prior to
November 15, 2021* ................................................................................................................. 19  
Appendix B – FDA Review of EUA Requests for COVID-19 Tests Offered Prior to November
15, 2021 and Policies for Distribution and Offering of Such Tests During FDA Review * ......... 20  

## I. Introduction
FDA plays a critical role in protecting the United States from threats such as emerging infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support response efforts to this pandemic.

FDA is issuing this guidance to provide FDA’s enforcement policies regarding certain novel coronavirus (COVID-19) tests for the duration of the public health emergency. Rapid detection of COVID-19 cases in the United States requires wide availability of testing to control this rapidly spreading, severe illness. This document supersedes “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised): Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff” issued May 11, 2020.

The policies in this guidance are intended to remain in effect only for the duration of the public health emergency related to COVID-19 declared by the Secretary of Health and Human Services (HHS) on January 31, 2020, effective January 27, 2020, including any renewals made by the HHS Secretary in accordance with section 319(a)(2) of the Public Health Service Act (PHS Act). FDA continues to assess the evolving situation and intends to update this guidance as appropriate.

Given this public health emergency, and as discussed in the Notice in the _Federal Register_ of March 25, 2020, titled “Process for Making Available Guidance Documents Related to Coronavirus Disease 2019,” _available at_ [https://www.govinfo.gov/content/pkg/FR-2020-03-25/pdf/2020-06222.pdf](https://www.govinfo.gov/content/pkg/FR-2020-03-25/pdf/2020-06222.pdf), this guidance is being implemented without prior public comment because FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices.

The contents of this document do not have the force and effect of law and are not meant to bind the public in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word _should_ in Agency guidance means that something is suggested or recommended, but not required.

## II. Background
There is currently a pandemic of respiratory disease caused by a novel coronavirus. The virus has been named “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) and the disease it causes has been named “Coronavirus Disease 2019” (COVID-19). On January 31, 2020, HHS issued a declaration of a public health emergency related to COVID-19 and mobilized the Operating Divisions of HHS.^1^ In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19.^2^

Under section 564 of the FD&C Act, the FDA Commissioner may authorize the use of unapproved medical products, or unapproved uses of approved medical products, in certain emergency circumstances, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use, to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by chemical, biological, radiological, and nuclear (CBRN) threat agents when certain criteria are met. The Emergency Use Authorization (EUA) authorities allow FDA to help strengthen the nation’s public health protections against CBRN threats by facilitating the availability and use of medical countermeasures needed during certain public health emergencies.

As of November 15, 2021, FDA has authorized more than 420 tests for COVID-19, including more than 300 diagnostic and 90 serology tests. In the context of a public health emergency involving pandemic infectious disease, it is critically important that tests are validated because false results not only can negatively impact the individual patient but also can have a broad public health impact. False positive results for diagnostic tests, for example, can lead to unnecessary quarantine, wasted contact tracing and testing resources, and delay in accurate diagnosis and appropriate treatment for the individual. False negative results can lead to lack of appropriate treatment for the individual and further spread of the disease.

Previous versions of this guidance described policies regarding the distribution and offering of certain tests for clinical use prior to or without an EUA. These policies were issued to help quickly increase availability of tests in the early stages of the pandemic. Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under the Clinical Laboratory Improvement Amendments (CLIA), section 353 of the Public Health Service Act (42 USC 263a), use of that test is limited to laboratories that are certified under CLIA, and meet the requirements to perform tests of high-complexity, and at the point-of-care (POC) when covered by such a laboratory’s CLIA certificate. Throughout this guidance, references to “high-complexity CLIA-certified laboratories” are referring to laboratories that are certified under CLIA and meet the requirements to perform tests of high-complexity. In addition, these policies did not apply to at-home tests or tests with home specimen collection. As such, these policies did not increase the availability of at-home tests, tests with home specimen collection, or other tests for use outside of a high-complexity CLIA-certified laboratory, including most POC tests.

We are now in a different stage of the COVID-19 pandemic than when the previous versions of this guidance were issued, and many more EUA-authorized COVID-19 tests are available than in May 2020. To facilitate the availability of tests for COVID-19 that FDA believes will be most beneficial at the current stage of the pandemic, FDA has revised this guidance to clarify the types of tests on which the Agency intends to focus its review to facilitate development and authorization of tests that will increase testing capacity, accessibility, and increased understanding of immune responses to SARS-CoV-2. In addition, FDA has revised the enforcement policies in this guidance to reflect that at this stage of the pandemic, the Agency generally expects COVID-19 tests to have been issued an EUA prior to the tests being distributed or offered.

## III. Scope
This guidance applies to diagnostic and serology tests for COVID-19.^3^ The policies and recommendations described in this guidance are intended to facilitate availability of tests for COVID-19 that FDA believes will be most beneficial at the current stage of the public health emergency.

FDA notes that the enforcement policies in this guidance do not address medical device reporting (MDR) under 21 CFR Part 803 for tests offered prior to authorization as described in the guidance. Developers offering such tests are expected to comply with applicable MDR requirements, including reporting of medical device events that reasonably suggest that their device may have caused or contributed to a death or serious injury, and malfunctions that would be likely to cause or contribute to a death or serious injury if they were to recur. Moreover, unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to laboratories certified under CLIA that meet the requirements to perform tests of high-complexity, including testing at the point-of-care when the site is covered by the laboratory’s CLIA certificate for high-complexity testing.

## IV. Policy
### A. Prioritization of Review of EUA Requests for Tests
The issuance of an EUA is discretionary. FDA's decision to review and process an EUA request, and ultimately issue an EUA if the relevant statutory criteria are met, is based on a determination, on a case-by-case basis, that such action is necessary to protect the public health in an emergency. It is an authorization that the government “may” issue when necessary to protect the public health in an emergency (see section 564(a)(1) of the FD&C Act (21 U.S.C. 360bbb-3(a)(1)), which states, in relevant part, “subject to the provisions of this section, the Secretary may authorize the introduction into interstate commerce…a drug, device, or biological product intended for use in an actual or potential emergency”). FDA’s January 2017 guidance, [Emergency Use Authorization of Medical Products and Related Authorities](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities),^4^ describes factors that FDA intends to use in its prioritization of EUA requests, such as the public health need for the product, the availability of the product, the availability and adequacy of the information concerning the likelihood that the product may be safe and effective in preventing, treating, or diagnosing the condition, and whether the product is included in government stakeholder stockpiles. Additionally, given the need to address urgent public health priorities, FDA may need to further prioritize among the EUA requests it receives for COVID-19 tests. At this stage in the pandemic, for SARS-CoV-2 diagnostic tests, FDA intends to encourage development and facilitate the authorization of tests that will significantly increase testing capacity and accessibility. For serology tests, FDA intends to focus on quantitative and neutralizing antibody tests that promote an increased understanding of immune responses to SARS-CoV-2.

Specifically, at this stage of the pandemic, FDA intends to focus its review on EUA requests for the following types of tests:

- **Diagnostic tests (molecular and antigen)** that can be used at the POC or completely at home from developers who have indicated the ability to scale up manufacturing capacity shortly after authorization (e.g., a manufacturing capacity of ≥500,000 tests per week within 3 months of authorization);^5^

- **Laboratory-based molecular diagnostic tests** that are: highly sensitive; high throughput;^7^ intended for pooling, home specimen collection, screening, or detection of multiple analytes; and from experienced developers^8^ who have indicated the ability to scale up manufacturing capacity shortly after authorization (e.g., a manufacturing capacity of ≥500,000 tests per week within 3 months of authorization);^9^

- **Home specimen collection kits** intended for use with laboratory-based molecular diagnostic tests, where the manufacturer has indicated the ability to scale up to a manufacturing capacity shortly after authorization (e.g., ≥500,000 kits per week within 3 months of authorization);^10^

- **Laboratory-based and POC serology tests** that are: high throughput, if laboratory-based; intended for the quantitative measurement of antibody titers; and from developers who have indicated the ability to scale up manufacturing capacity shortly after authorization (e.g., a manufacturing capacity of ≥500,000 tests per week within 3 months of authorization);^11^

- **Laboratory-based and POC serology tests** that are: intended for the quantitative detection of neutralizing antibodies; and from developers who have indicated the ability to scale up manufacturing capacity shortly after authorization (e.g., a manufacturing capacity of ≥500,000 tests per week within 3 months of authorization);^12^ and

- **Tests for which the EUA request is from (or supported by) a US government stakeholder**, such as tests funded by the Biomedical Advanced Research and Development Authority (BARDA) or the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx).

Further, for tests intended for use on instruments not used for previously authorized tests, FDA intends to prioritize those tests where the developer indicates sufficient instrument and kit production capacity.^14^ For tests intended for use with home collection kits, FDA intends to prioritize those tests where there is sufficient assay and collection kit production capacity.

In order to make effective use of FDA resources, FDA generally intends to focus its review on EUA requests for tests that are within these priorities.^15^ Appendix A includes a visual overview of these review priorities. FDA believes these priorities are appropriate to address the public health needs at the current stage of the public health emergency and may adjust these priorities as more tests are authorized or public health needs change. FDA encourages test developers to consider these priorities and focus on these areas of need as they develop and validate their tests.

For tests not authorized and not being offered at the time this updated guidance issues, FDA expects it will only review EUA requests for priority tests. FDA intends to notify test developers of such tests by email if FDA declines to review or otherwise decides not to authorize the test.^16^

For tests on one of the notification lists on FDA’s website at the time this guidance issues and laboratory developed tests (LDTs) being offered following the HHS August 2020 Web Statement entitled “Rescission of Guidances and Other Informal Issuances Concerning Premarket Review of Laboratory Developed Tests” (“August 2020 HHS Announcement”), FDA generally intends to review EUA requests as outlined in Section IV.C of this guidance.

### B. State Authorization of High-Complexity CLIA-Certified Laboratories
Previous versions of this guidance described a policy regarding States and territories that authorize laboratories within their State or territory to develop their own COVID-19 tests and perform specimen testing, where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA.

Under such policy, a State or territory choosing to authorize laboratories within that State or territory to develop and perform a test for COVID-19 would do so under authority of its own State law, and under a process that it established, and FDA did not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation was not submitted to FDA and the laboratory did not submit an EUA request to FDA, and where instead the State or territory took responsibility for COVID-19 testing by laboratories in its State during the COVID-19 outbreak. This policy applied only to tests designed, developed, and used within a single, high-complexity, CLIA-certified laboratory. The policy did not apply to at-home tests or tests with home specimen collection, or any testing outside of a high-complexity CLIA-certified laboratory.

In previous versions of this guidance, FDA requested that the State or territory notify us if it chose to use this flexibility to expedite COVID-19 testing. FDA indicated that it would not be reviewing the process adopted by the State or territory. FDA expected that such States and territories as part of their oversight process would require laboratories developing SARS-CoV-2 tests to validate those tests prior to use. FDA encouraged laboratories that developed and performed a test for COVID-19 that was authorized by a State or territory to notify FDA that they have started clinical testing by sending an email to [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV), and provide information on testing capacity.

At the current stage of the pandemic, FDA is revising this policy such that FDA no longer intends to apply the policy to any additional States or territories going forward. For the States and territories listed on the notification list on FDA’s website prior to the date of issuance of this updated guidance that are continuing to authorize laboratories within that State or territory to develop and perform a test for COVID-19, FDA does not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA, and where instead the State or territory takes responsibility. This policy applies only to tests designed, developed, and used within a single, high-complexity CLIA-certified laboratory. This policy does not apply to at-home tests or tests with home specimen collection, or any testing outside of a high-complexity CLIA-certified laboratory.

FDA notes that laboratories offering testing authorized by States or territories should be aware of requirements to report test results to appropriate federal, state, and local public health agencies in accordance with applicable federal, state, and local laws.

### C. Distribution and Offering of SARS-CoV-2 Diagnostic and Serology Tests During FDA Review
For the enforcement policies in the May 2020 editions of this guidance, where a developer notified FDA that it intended to distribute or offer its validated test as outlined in the guidance, FDA would generally add the developer/test to one of the notification lists on FDA’s website. As discussed in those policies, FDA generally did not intend to object to developers distributing and offering a test on the notification list as described in the policies.

FDA is revising the prior policies because we are at a different stage of the pandemic, and there are many more EUA-authorized COVID-19 tests available now. In addition, experience has shown that many of the COVID-19 tests offered prior to FDA review were determined to have poor performance, either upon FDA review of the EUA request or, for some serology tests, upon evaluation by the National Institutes of Health’s National Cancer Institute (NIH/NCI).

As outlined below, among other things, FDA no longer intends to add tests to the notification lists. Further, for tests already on the notification lists, FDA intends to remove tests for which FDA has either issued an EUA or has notified the test developer by email that FDA declines to review, declines to issue, or otherwise decides not to authorize the test for any reason.

#### (1) Diagnostic and Serology Tests on Notification Lists for which an EUA Request was Submitted
For SARS-CoV-2 diagnostic or serology tests on one of the notification lists and for which an EUA request was submitted prior to issuance of this updated guidance, FDA does not intend to object to continued distribution or offering of those tests for a period of time while FDA reviews the EUA requests for the tests where:

1. The developer submitted its EUA request after February 1, 2021; or
2. The developer submitted its EUA request prior to February 1, 2021 and the developer confirms to FDA (through an email to [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov)), within 45 calendar days from the date of issuance of this updated guidance, that:
   a. the developer wants FDA to continue reviewing its EUA request;
   b. the EUA request is for the current version of the test; and
   c. either the developer does not have additional data to add, or the developer submits updated information to FDA within that 45 calendar-day timeframe including, if not previously provided, validation with clinical specimens using an appropriate comparator. FDA believes that 45 calendar days is reasonable for this.

If FDA does not receive confirmation from a test developer that submitted its EUA request prior to February 1, 2021 confirming that the developer wants FDA to continue reviewing its EUA request, FDA intends to decline to review (or decline to further review where review has already begun) the EUA request.

For tests described in this section, FDA intends to notify test developers by email if FDA declines to review, declines to issue, or otherwise decides not to authorize the test for any reason, including lack of response or a determination that there is a lack of adequate data to support authorization. If so notified, FDA generally expects developers to cease distributing, marketing, and offering their tests within 15 calendar days. Moreover, if FDA identifies a significant problem or concern with a test, based either on the provided information or external reports, FDA generally would expect the developer to take appropriate steps to address such problems, which could include conducting a recall of the test and/or notification concerning corrected test reports indicating prior test results may not be accurate.

#### (2) Laboratory Serology Tests on the Notification List and Certain LDTs for Which an EUA Request Was Not Submitted
Certain serology tests developed by laboratories are being offered without FDA authorization after the developer notified FDA as described in the previous version of this guidance. In addition, FDA understands that some LDTs for SARS-CoV-2 are being offered without FDA authorization or submission of an EUA request following the August 2020 HHS Announcement. The policy below applies to serology tests developed by laboratories offered without submission of an EUA request after notifying FDA as described in the previous version of this guidance and LDTs being offered without submission of an EUA request following the August 2020 HHS Announcement. ^25^

For such tests, FDA does not intend to object to continued offering of the tests while FDA reviews the EUA requests where the developer submits the EUA request to FDA through an email to [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) within 60 calendar days from the date of issuance of this updated guidance. ^26^ ^27^ FDA believes this is sufficient time for a test developer to prepare and submit an EUA request, considering that the validation recommendations included in the EUA templates ^28^ have been publicly available and generally consistent since Spring 2020, and such tests should have already been validated prior to being offered. As for all test developers seeking an EUA, these laboratories may use the optional EUA templates, which generally recommend providing information on the indication of the test, a description of the test, the validated performance of the test, a description of how the test was validated, and validation data. FDA understands that developers of these tests may not have files that align with the templates or EUA process. As such, FDA is clarifying that, because the EUA templates are optional, instead of using the EUA templates, laboratories may submit an email to FDA with supporting information, such as a description of their test and intended use and attach existing validation test reports and excel data files that they already have on file in accordance with their internal procedures. Laboratories should submit this and any additional information they believe would support authorization. ^29^ If the test developer does not submit an EUA request within 60 calendar days from the date of issuance of this updated guidance, FDA generally expects developers to cease marketing and offering their tests within 60 calendar days from the date of issuance of the updated guidance. ^30^

For tests described in this section, FDA intends to notify test developers by email if FDA declines to issue or otherwise decides not to authorize a test for any reason, including a determination that there is a lack of adequate data to support authorization. If so notified, FDA generally expects developers to cease marketing and offering their test within 15 calendar days. Moreover, if FDA identifies a significant problem or concern with a test, based either on the provided information or external reports, FDA generally would expect the developer to take appropriate steps to address such problems, which could include a recall of the test and/or notification concerning corrected test reports indicating prior test results may not be accurate.

#### (3) Recommendations Regarding Test Reports and Other Information for Tests Offered During FDA Review of EUA Requests
FDA continues to recommend the following:

1. Test reports should prominently disclose that the test has not been reviewed by FDA. Until the test is authorized by FDA, any statements in the test reports and other labeling that expressly state or imply that the test has been authorized by FDA would be false. Similarly, any statements in the test reports and other labeling that state or imply that EUA issuance or FDA authorization are imminent or pending could be misleading.

2. Developers should make publicly available on their website the instructions for use for the test and data about the test’s performance characteristics, including a summary of assay performance.

3. Instructions for use and patient test reports for serology tests should include information that helps users and patients understand the test results, including the following:
   - Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct (i.e., diagnostic) testing for SARS-CoV-2 is necessary.
   - Results from antibody testing should not be used to diagnose or exclude acute SARS-CoV-2 infection.
   - Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

In addition, as noted in the May 2020 editions of this guidance and earlier in this updated guidance, unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to laboratories certified under CLIA that meet the requirements to perform tests of high-complexity, including testing at the POC when the site is covered by such a laboratory’s CLIA certificate.

#### (4) FDA Review of EUA Requests
For tests described in Sections IV.C.1 and IV.C.2 of this guidance, FDA generally intends not to authorize a test where the EUA request does not demonstrate that the test has been appropriately validated, including validation with clinical specimens using an appropriate comparator as described in Section V of this guidance. FDA’s recommendations for validation, including descriptions of appropriate comparators for different types of tests, can be found in the EUA templates ^31^ for different types of tests.

For tests described in Sections IV.C.1 and IV.C.2 of this guidance, FDA intends to consider the priorities outlined in Section IV.A, as well as other relevant considerations for these currently available tests (e.g., safety concerns), to inform the Agency’s review and prioritization of EUA requests for these tests. Appendix B includes a visual overview of the review policies for tests described in section IV.C.1 and IV.C.2.

### D. Modifications to EUA-Authorized Diagnostic COVID-19 Tests
A developer may request certain modifications to its EUA-authorized test that was authorized in an individual EUA, and such changes shall be implemented as specified in the EUA’s Conditions of Authorization, including having concurrence from FDA prior to modification. ^32^ FDA also has discussed various modification policies in previous editions of the guidance relating to authorized COVID-19 tests. As discussed further below, FDA is updating these policies.

The policies in this section do not apply to at-home testing, including at-home specimen collection.

In addition, as noted in the May 2020 editions of this guidance and earlier in this updated guidance, unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to laboratories certified under CLIA that meet the requirements to perform tests of high-complexity, including testing at the POC when the site is covered by such a laboratory’s CLIA certificate.

In order to provide transparency, when a developer is distributing or offering a test that is a modification of an EUA-authorized diagnostic test prior to or without authorization of the modified test, as discussed in this section, the recommendations in Section IV.C.3 of this updated guidance apply. FDA further recommends that the developer post data about the modified test’s performance characteristics on the developer’s website, and that the instructions for use or test protocol and the test reports accurately reflect the modification and prominently disclose that the test has been modified since authorization by FDA and that the modified test has not been reviewed by FDA.

If FDA identifies a significant problem or concern with a modified test, based either on the provided information or external reports, that cannot be addressed in a timely manner, FDA generally would expect the developer to cease distribution, marketing and offering the modified test. 

#### (1) Certain Modifications Made After Issuance of this Updated Guidance
When a commercial manufacturer is modifying its authorized COVID-19 molecular diagnostic test to make modifications that do not change the indication for use set forth in the EUA (e.g., including new/different extraction kits or instruments) and do not change the analyte specific reagents (e.g., PCR primers and/or probes),^33^ where the developer has submitted validation data supporting the modification to FDA in a supplemental EUA request, FDA does not intend to object to implementation of the modification to the diagnostic test while FDA conducts its review.

When a high-complexity CLIA-certified laboratory is modifying an authorized COVID-19 molecular diagnostic test, including one for which such laboratory is not the developer of the original, EUA-authorized test, and the modifications do not change the indication for use set forth in the EUA (e.g., including new/different extraction kits or instruments) and do not change the analyte specific reagents (e.g., PCR primers and/or probes),^34^ FDA does not intend to object to implementation of the modification to the diagnostic test without notification to FDA or a new or amended EUA where the laboratory has validated the modification and confirmed that the performance of the modified test is equivalent to the performance of the authorized test, and use of the test is limited to the high-complexity CLIA-certified laboratory in which the modification was made.^35^

FDA encourages the laboratory to collaborate with the developer of the authorized test so that validation data supporting the modifications can be submitted by the original developer to FDA in a supplemental EUA request. Supplemental EUA requests such as this, which have the potential to increase testing capacity by allowing more laboratories to use the test with additional components, are more likely to meet FDA’s review priorities, discussed in Section IV.A of this guidance.

#### (2) Certain Modifications Made Before Issuance of this Updated Guidance
Under the previous version of the guidance, when a commercial manufacturer made certain modifications to its EUA-authorized COVID-19 diagnostic test, and where validation data supporting the modification had been submitted in a supplemental EUA request, FDA stated that it did not intend to object to implementation of the modification while FDA conducted its review, except for modifications to add specimen types that have not been previously authorized with another test of the same technology. For such modifications made and implemented as discussed in the policies in the previous version of the guidance, FDA does not intend to object to such commercial manufacturers continuing to implement the modification while FDA conducts its review.

Under the previous version of the guidance, when a high-complexity CLIA-certified laboratory modified an EUA-authorized COVID-19 diagnostic test^36^ for use with a new specimen type, where the new specimen type has been previously authorized for another test of the same technology^37^ and where the lab had validated the test for the new specimen type, FDA stated that it did not intend to object to the use of such a modified test without notification to FDA or a new or amended EUA. For all other types of modifications made by a high-complexity CLIA-certified laboratory for an EUA-authorized COVID-19 diagnostic test, in the previous version of the guidance, FDA stated that it did not intend to object to the use of the test by high-complexity CLIA-certified laboratories, without notification to FDA or a new or amended EUA, where the test is a modification of an EUA-authorized diagnostic test and the modified test is validated using a bridging study to the EUA-authorized test.

For such modifications made and implemented by high-complexity CLIA-certified laboratories as discussed in the policies in the previous version of the guidance, FDA does not intend to object to such laboratories continuing to offer any of those modified tests.

In such cases, where the laboratory performing the modified test is not the developer of the original, EUA-authorized test, FDA encourages the laboratory to share its validation data with the developer of the original, EUA-authorized test so that the developer of the original, EUA-authorized test can use the validation data in support of a supplemental EUA request to add the modification. Supplemental EUA requests such as this, which have the potential to increase testing capacity by allowing more laboratories to use the test with additional components, are more likely to meet FDA’s review priorities, discussed in Section IV.A of this guidance.

## V. Validation
All clinical tests should be validated using clinical specimens and an appropriate comparator test prior to use.

In the context of a public health emergency, it is critically important that tests be validated prior to use because false results not only can negatively impact the individual patient but also can have a broad public health impact. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity, including descriptions of appropriate comparators for different types of tests, in the EUA templates available through download from our website.^38^ Depending on the characteristics of a developer’s test, additional validation studies may be recommended.

Developers can use alternative approaches. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV).

Additionally, FDA continues to expect certain serology tests to be independently evaluated by NIH/NCI,^39^ prior to authorization, when requested by the FDA. When performed, this additional testing can assist FDA in determining whether the EUA issuance criteria in section 564 of the FD&C Act have been met and whether FDA should authorize the test.

## VI. Availability of EUA Templates
FDA has made available through download from our website^40^ a series of templates that developers may choose to use to facilitate the preparation and submission of an EUA request for various types of COVID-19 tests. The templates reflect FDA’s current thinking on validation recommendations for SARS-CoV-2 tests and the data and information that developers should submit to facilitate the EUA process. The templates provide information and recommendations, and FDA plans to update them as appropriate as more is learned about COVID-19 and more experience is gained with the EUA process for the various types of COVID-19 tests.

Developers can use alternative approaches. Developers who intend to use alternative approaches should consider seeking FDA’s feedback or recommendations to help them through the EUA process. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV).

Members of the public can submit questions about the templates to [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV), or they can submit comments regarding the templates to the public docket established for this guidance.

## Appendix A – FDA Review of EUA Requests for COVID-19 Tests Not Offered Prior to November 15, 2021*
_Flowchart showing the FDA review pathway for EUA requests for molecular, antigen, and serology COVID-19 tests not offered prior to November 15, 2021, illustrating decision points and outcomes for each test type._

*The flowcharts above give a general overview of the policies in Section IV.A of this guidance. Readers should refer to that section for the policies themselves. The flowcharts do not address policies discussed in other sections of this guidance.

## Appendix B – FDA Review of EUA Requests for COVID-19 Tests Offered Prior to November 15, 2021 and Policies for Distribution and Offering of Such Tests During FDA Review*
_Flowchart showing the FDA review pathway and distribution policies for EUA requests for COVID-19 tests that were offered prior to November 15, 2021, during FDA review._

*The flowchart above gives a general overview of the policies in Section IV.C of this guidance. Readers should refer to that section for the policies themselves. The flowchart does not address policies discussed in other sections of this guidance.

---

^1^ Secretary of Health and Human Services, Determination that a Public Health Emergency Exists (originally issued on Jan. 31, 2020, and subsequently renewed), available at [link](https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx).
^2^ Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak (Mar. 13, 2020), available at [link](https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/). On February 24, 2021, there was a Presidential Declaration continuing the national emergency concerning the COVID-19 pandemic beyond March 1, 2021. See Continuation of the National Emergency Concerning the Coronavirus Disease 2019 (COVID-19) Pandemic (February 24, 2021), available at [link](https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic).
^3^ Throughout this guidance, the term “diagnostic test” is generally used to refer to molecular or antigen tests, both of which can be used to diagnose infection with the SARS-CoV-2 virus. Screening tests, which are used for testing individuals without symptoms or other reasons to suspect COVID-19, are a subset of diagnostic tests. Molecular tests detect the presence of viral RNA and antigen tests detect the presence of viral proteins that are part of the SARS-CoV-2 virus. The terms “serology” or “antibody” tests are generally used to refer to tests that detect antibodies to the SARS-CoV-2 virus. Because the antibodies are part of the body’s immune response to exposure and not the virus itself, such testing cannot be used for diagnosis of acute infection.
^4^ See [FDA Guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities).
^5^ Diagnostic tests, including those for screening, that can be manufactured in high volume and used at the POC or completely at home increase accessibility to tests and results from such tests are typically returned faster than other diagnostic tests. FDA believes that 500,000 tests per week is a reasonable and achievable manufacturing capacity for many manufacturers of POC or at-home tests.
^6^ For the purposes of this guidance, “laboratory-based tests” are tests intended for use in laboratories certified under CLIA that meet the requirements to perform tests of moderate or high complexity. Such tests do not include POC or at-home tests, which are addressed in the first bullet. As a practical matter, only laboratory-based tests are likely to be the type of highly-sensitive, high throughput tests we are seeking to prioritize here.
^7^ To illustrate, we would generally consider tests that support two 384 well thermocycler runs per 8 hours in combination with an automated extraction and liquid handling platform as “high throughput.”
^8^ For the purposes of this guidance, “experienced developers” refers to developers who have interacted with FDA through an EUA request or pre-EUA submission during the current public health emergency or have similar experience. FDA has interacted with over 1,000 test developers through the EUA and pre-EUA processes during the SARS-CoV-2 pandemic. The Agency has found that EUA requests from inexperienced developers are more resource-intensive to review. At this phase of the pandemic, and given our experience to date, we believe that for high or moderate complexity laboratory tests, FDA’s review resources are more impactful when working with experienced developers given the design and validation complexities associated with such tests. As a result, FDA intends to prioritize the review of EUA requests for such high and moderate complexity tests from experienced developers.
^9^ In order for diagnostic tests to significantly increase testing capacity, which has been identified as a US government testing priority, they should be high volume and high throughput and for use on broad patient populations (i.e., not only on symptomatic patients or patients suspected of COVID-19). FDA authorization of high and moderate complexity tests with manufacturing capacities lower than 500,000 tests per week will not sufficiently scale US testing capacity. Furthermore, based on surge manufacturing capacity data received in EUA requests to date, FDA believes that 500,000 tests per week is a reasonable and achievable manufacturing capacity for many manufacturers of high and moderate complexity tests. Similarly, highly manual, low throughput tests will not allow laboratories to scale testing volumes to those needed for large screening programs. With respect to laboratory-based diagnostic tests, FDA intends to prioritize molecular, and not antigen, diagnostic tests that have the other characteristics described since antigen tests are generally not as sensitive as molecular tests, and the primary benefits from antigen tests in this phase of the pandemic come from their ability to scale up for use at POC or completely at home. Reviewing laboratory-based antigen tests would take resources away from reviewing POC and at-home antigen tests. Therefore, FDA intends to focus its resources on the types of antigen tests more likely to provide greater benefit to the nation’s COVID-19 response.
^10^ Home specimen collection kits intended for use with high volume and high throughput laboratory-based tests will support and enable increased testing with such tests by increasing their accessibility.
^11^ Laboratory-based and POC serology tests that are high throughput, can be manufactured in high volume, and that are intended for the quantitative measurement of antibody titers promote an increased understanding of immune responses to SARS-CoV-2.
^12^ Laboratory-based and POC serology tests that can be manufactured in high volume and that are intended for the quantitative detection of neutralizing antibodies promote an increased understanding of immune responses to SARS-CoV-2.
^13^ Prioritization of EUA requests from (or supported by) government stakeholders is discussed in the Guidance for Industry and Other Stakeholders: Emergency Use Authorization of Medical Products and Related Authorities, available at [FDA Guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities).
^14^ FDA has received EUA requests for tests that require a new instrument to perform the test, but the instrument production capacity is such that the test developers would not be able to produce and distribute it in a timely manner enough instruments to perform all the tests they are planning to offer. The addition of an instrument greatly increases the complexity of an EUA review. In addition, laboratories, including POC sites, are unlikely to purchase new instruments that will only be able to run a single test and will potentially not be able to run any tests after the pandemic.
^15^ Developers of tests that are not within these priorities may consider modifications to their test prior to submitting an EUA request to FDA to better align with the current public health needs. Alternatively, they may consider pursuing marketing authorization through a traditional premarket review pathway. If developers of tests that are not within these priorities and are a new type of test where the developer believes the test can help address current public health needs, the developers and/or laboratories are welcome to provide FDA their rationale for the public health need for the individual test and the reasons why FDA review of an EUA request should be considered, by sending an email to CDRH-EUA-Templates@fda.hhs.gov.
^16^ FDA may decline to review or otherwise decide not to authorize a test based on any number of factors, including lack of adequate data to support emergency use authorization, as discussed in Guidance for Industry and Other Stakeholders: Emergency Use Authorization of Medical Products and Related Authorities, available at [FDA Guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities).
^25^ If developers of these serology tests and LDTs submitted an EUA request to FDA prior to issuance of this guidance, the policy discussed in Section IV.C.1 of this guidance applies.
^26^ This policy does not apply to at-home tests or tests with home specimen collection, or any testing outside of a laboratory certified under CLIA that meets the requirements to perform tests of high-complexity.
^27^ When submitting such an EUA request, developers should consider submitting information relating to the priorities outlined in Section IV.A as tests falling under those priorities reflect the public health needs at the current stage of the public health emergency and the tests for which FDA will be focusing its review.
^28^ Available at: [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas).
^29^ If sufficient information is not submitted to support authorization, FDA may reach out to laboratories to request additional information.
^30^ If developers are not able to prepare and submit an EUA request within 60 calendar days, but they believe it is of significant public health importance that they continue to offer their unauthorized test beyond that timeframe, the developer is welcome to provide FDA their rationale for the continued public health need for their individual test and the reasons why additional time is needed to prepare and submit an EUA request, by sending an email to [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov).
^31^ Available at: [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas).
^32^ We note that modifications to a test authorized under an umbrella EUA are handled differently given the nature of umbrella EUAs. As such, the policy set forth in this subsection regarding modifications does not apply to tests authorized under an umbrella EUA.
^33^ Other modifications, including new claimed specimen types, test settings (e.g., point-of-care, home testing), and new patient populations (e.g., asymptomatic individuals), among others, do not fall under this policy.
^34^ Other modifications, including new claimed specimen types, test settings (e.g., point-of-care, home testing), and new patient populations (e.g., asymptomatic individuals), among others, do not fall under this policy.
^35^ FDA generally considers equivalent performance to be where the LoD of the modified test (using the same validation material used in the LoD study described in the authorized test’s Instructions For Use (IFU)) is within 3x of the LoD established in the authorized test’s IFU or that the LoD of the modified test is within 3x of the LoD of the authorized test in a direct comparison LoD study.
^36^ This applies to modifications to any EUA-authorized diagnostic test, including a laboratory’s own test with an EUA or a purchased kit from a commercial manufacturer with an EUA.
^37^ For the purposes of this guidance, all nucleic acid amplification tests are considered to have the same technology.
^38^ See <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas>.
^39^ The FDA is working with the NIH, the Centers for Disease Control and Prevention (CDC), and BARDA to assess the performance of certain commercial manufacturers’ serology tests. As part of this project, the FDA, working with its partnering agencies, has designed a performance assessment protocol that offers a mechanism for an independent evaluation of certain lateral flow and certain enzyme-linked immunosorbent assay (ELISA) or similar technology-based SARS-CoV-2 antibody tests in a laboratory environment. Under this protocol, each test evaluated at the NIH/NCI will be evaluated with a well-characterized sample panel consisting of positive and negative plasma and/or serum samples. The approach represents a balanced attempt to provide a reasonable understanding of the potential performance of a significant number of the tests within a short time period. Performance results are considered during FDA’s review of an EUA request for the test.
^40^ See <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas>.


# 24,421  2021-11-15_FDA Letter - EUA Letter of Authorization.md
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last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Letter - EUA Letter of Authorization.md
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summary_short: The FDA “EUA Letter of Authorization” (November 15, 2021) is the legally operative document that authorizes certain laboratory-developed RT-PCR SARS-CoV-2 tests under an Umbrella EUA for Serial Testing. It defines who may use the test (a single CLIA high-complexity laboratory), exactly what indications are authorized (individual and pooled anterior nasal specimens used at least weekly, including asymptomatic screening), and the validation pathways required for each indication (Appendices A–K). The letter also establishes binding Conditions of Authorization, including labeling requirements, post-authorization studies, mutation monitoring, pooling controls, reporting obligations, and limits on modifications. Only tests that meet the nine eligibility criteria and are properly added to Exhibit 1 are considered authorized.


CONTENT

November 15, 2021

To:  
Laboratories That Have Developed Certain Molecular-Based Tests for SARS-CoV-2

Authorized Tests:  
Certain RT-PCR Molecular-Based Tests for Detection of Nucleic Acid from SARS-CoV-2 from Anterior Nasal Respiratory Specimens for Use as part of a Serial Testing Program

Authorized Laboratories:  
Testing is limited to the single laboratory that developed the authorized test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

On February 4, 2020, pursuant to Section 564(b)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 360bbb-3(b)(1)(C)), the Secretary of the Department of Health and Human Services (HHS) determined that there is a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad, and that involves the virus that causes COVID-19. Pursuant to Section 564 of the Act, and on the basis of such determination, the Secretary of HHS then declared that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the virus that causes COVID-19 subject to the terms of any authorization issued under Section 564(a) of the Act. ^1^

On November 15, 2021, pursuant to Section 564 of the Act, in response to public health needs to maintain the nation’s testing capacity and adapt to current testing uses, ^2^ FDA is issuing this letter to authorize certain tests that are within the Scope of this Authorization (Section II). Under this Emergency Use Authorization (EUA), authorized tests are authorized for use only in the single laboratory that developed the authorized test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, and meets requirements to perform high complexity tests.

As set forth throughout, this EUA authorizes certain tests that are within the Scope of this Authorization (Section II) for certain specified indications for use. ^3^ This letter authorizes tests (also referred to as products) for multiple indications for use as set forth in the appendices. These indications all contain these essential elements: use with individual or pooled anterior nasal specimens to test individuals, including individuals without symptoms or other epidemiological reasons to suspect COVID-19, when tested at least once per week. This means that tests authorized by this letter may be used with individual or pooled anterior nasal respiratory specimens from individuals with or without known or suspected exposure to COVID-19 when such individuals are tested at least once per week, such as testing at regular intervals as part of a testing program implemented by schools, workplaces, or community groups. The indications in each appendix (A-K) differ in the number of specimens that can be tested or pooled (i.e., 1, up to 3, up to 5, or up to 10), the type of pooling that can be done (i.e., media or swab pooling), and whether the test is authorized for use with home collected specimens. A test is authorized by this EUA if it has been validated in accordance with Appendix A. Appendix A includes the base validation requirements and indication but does not authorize testing of pooled specimens or testing with home collected specimens. Appendices B-K set forth the validation requirements for the pooling and home collection indications. FDA will add tests to Exhibit 1 once it confirms it has received a complete notification as set forth in Section II of this letter. Exhibit 1 will be annotated with the authorized indication(s) for each test and will be maintained on FDA’s webpage. ^4^

FDA’s determination that the tests authorized by this EUA meet the criteria for issuance under Section 564(c) of the Act is based on the available scientific evidence, including recent studies involving antigen tests used in a serial manner, knowledge of recently authorized antigen and molecular tests, our experience with SARS-CoV-2 tests since the start of the emergency, as well as the inclusion of additional risk mitigations, such as limiting the use to serial testing.

Having concluded, based on the available scientific evidence, that the criteria for issuance of this authorization under Section 564(c) of the Act are met, I am authorizing the emergency use of the authorized tests identified in the Scope of this Authorization (Section II) and subject to the Conditions of Authorization (Section IV), for use in the single laboratory that developed the authorized test and that is certified under the CLIA, 42 U.S.C. § 263a and meets the requirements to perform high complexity tests, to detect SARS-CoV-2 in anterior nasal respiratory specimens from individuals.

## I. Criteria for Issuance of Authorization
I have concluded that the emergency use of the authorized tests meets the criteria for issuance of an authorization under Section 564(c) of the Act, because I have concluded that:

1. The SARS-CoV-2 can cause a serious or life-threatening disease or condition, including severe respiratory illness, to humans infected by this virus;

2. Based on the totality of scientific evidence available to FDA, it is reasonable to believe that the authorized tests may be effective in diagnosing infection with SARS-CoV-2 by detecting the presence of SARS-CoV-2 viral material for the indications set forth in the appendices, and that the known and potential benefits of the authorized tests when used for such use, outweigh the known and potential risks of the authorized tests; and

3. There are no adequate, approved, and available alternatives to the emergency use of the authorized tests. ^5^

## II. Scope of this Authorization
I have concluded, pursuant to Section 564(d)(1) of the Act, that the scope of this authorization is limited to the tests described below for the indication in Appendix A and any additional indication(s) for use ^6^ given in the applicable appendix(ces) for which the test is validated consistent with, for use in the single laboratory that developed the authorized test and that is certified under CLIA, 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

### Authorized Tests
Tests that meet all of the following eligibility criteria are authorized consistent with this letter:

1. The test is an RT-PCR test that is *not* already authorized for emergency use as of today’s date for the qualitative detection of SARS-CoV-2 in respiratory specimens collected by anterior nasal swabs;
2. The test is validated in accordance with Appendix A (base validation);
3. The test is validated in accordance with the applicable Appendix B-K if indicated for more than the base indication set forth in Appendix A;
4. The test detects two or more viral targets on the SARS-CoV-2 genome;
5. The test includes a chemical lysis step followed by a nucleic acid isolation step (e.g., silica bead extraction);
6. The test detects only SARS-CoV-2;
7. The test is designed, manufactured, and used within a single CLIA certified laboratory that meets requirements to perform high complexity tests;
8. The test is for prescription (Rx) use only; and
9. The test uses a combination of control materials that control for specimen quality and test system performance. ^7^

Authorized tests are qualitative tests for the detection of nucleic acid from SARS-CoV-2 in anterior nasal respiratory specimens from individuals, including those without symptoms or other reasons to suspect COVID-19, when tested at least once per week, as set forth in Appendix A and any additional appendix(ces) that the test is validated consistent with.

The SARS-CoV-2 nucleic acid is generally detectable in anterior nasal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.

Negative results from pooled testing should not be treated as definitive. If a patient’s clinical signs and symptoms are inconsistent with a negative result or results are necessary for patient management, then the patient should be considered for individual testing. Specimens included in pools with a positive or invalid result must be reported as presumptive positive or tested individually prior to reporting a result. Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result. Specimens with low viral loads may not be detected with pooled testing due to decreased sensitivity or increased interference from pooled testing.

For serial testing programs, additional confirmatory testing for negative results may be necessary, if there is a high likelihood of COVID-19, such as an individual with a close contact with COVID-19 or with suspected exposure to COVID-19 or in communities with high prevalence of infection. Additional confirmatory testing for positive results may also be necessary if there is a low likelihood of COVID-19, such as in individuals without known exposure to COVID-19 or residing in communities with low prevalence of infection.

Authorized tests must be accompanied by labeling that is consistent with this letter. For this EUA, such labeling must include the test procedures, a Fact Sheet for Healthcare Providers, a Fact Sheet for Patients, and a Test Summary. Developers must include, at a minimum, the relevant information in the applicable appendix (see Appendices L–N) and the following statement: This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing [include link to this letter] for use in [the single laboratory (CLIA certified and meets the requirements to perform high complexity tests) in which it was developed] for [insert indication(s) from applicable appendix(ces)] using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing.

In addition, the Fact Sheets are required to be made available to healthcare providers and patients receiving test results.

Authorized tests, when labeled consistent with this letter and subject to the Conditions of Authorization (Section IV) of this letter, are authorized to be used in accordance with the Scope of this Authorization (Section II) and the Conditions of Authorization (Section IV) by the laboratory that developed the authorized test, despite the fact that they do not meet certain requirements otherwise required by applicable federal law.

### Addition to Exhibit 1
A test will be added to Exhibit 1 after FDA confirms that the required documentation set forth below has been submitted via email to FDA. At that time, FDA will notify the developer of the inclusion of its test(s) in Exhibit 1 by replying to the email. Please note that being added to Exhibit 1 does not necessarily mean that FDA has reviewed the underlying validation data submitted or has confirmed that the test is appropriately validated. Instead, being added to Exhibit 1 only means that the developer has submitted complete documentation. However, if FDA determines that a test listed on Exhibit 1 does not meet one or more of the nine eligibility criteria listed above, it will remove the test from Exhibit 1. Tests removed from Exhibit 1 will be included in a list maintained on FDA’s EUA webpage.

To be added to Exhibit 1, developers must notify FDA by sending an email to FDA with the subject line “Addition to Exhibit 1 of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing” to CDRH-EUA-Templates@fda.hhs.gov with the information below:

- Developer (laboratory) name
- Contact individual’s name, address, phone number, email address
- Test name
- The specific indication(s), referenced by noting the applicable appendix
- The required information, including validation data, as set forth in the applicable appendices
- Authorized labeling (i.e., Test Summary, test procedure(s), Fact Sheet for Healthcare Providers, and Fact Sheet for Patients) as set forth above and required by Condition of Authorization A
- The following information on testing capacity:
  - i. The number of individual tests that can be run with normal operation in a 24-hour period; and
  - ii. The number of individual samples that can be tested in a 24-hour period if all samples are pooled at the maximum ratio authorized pursuant to the applicable appendix of this letter.
- Statement certifying that the nine eligibility criteria listed above are met and that all information submitted is truthful and accurate, for example:
  - I certify that, in my capacity as [the position held in laboratory] of [laboratory name], I believe to the best of my knowledge that all nine eligibility criteria described in FDA’s November 15, 2021, letter have been met and that all data and information I am submitting are truthful and accurate and no material fact has been omitted.

Your Fact Sheets and Test Summary will be added to FDA’s webpage when your test is added to Exhibit 1.

### Conclusions
I have concluded, pursuant to Section 564(d)(2) of the Act, that it is reasonable to believe that the known and potential benefits of the authorized tests, when used consistent with the Scope of this Authorization (Section II), outweigh the known and potential risks of such authorized tests.

I have concluded, pursuant to Section 564(d)(3) of the Act, based on the totality of scientific evidence available to FDA, that it is reasonable to believe that the authorized tests may be effective in diagnosing infection with SARS-CoV-2 by detecting the presence of SARS-CoV-2 viral material as set forth in Section I of this letter, when used consistent with the Scope of this Authorization (Section II), pursuant to Section 564(c)(2)(A) of the Act.

FDA has reviewed the scientific information available to FDA, including the information supporting the conclusions described in Section I above, and concludes that the authorized tests (as described in the Scope of this Authorization of this letter (Section II)) meet the criteria set forth in Section 564(c) of the Act concerning safety and potential effectiveness.

The emergency use of the authorized tests under this EUA must be consistent with, and may not exceed the terms of this letter, including the Scope of this Authorization (Section II) and the Conditions of Authorization (Section IV). Subject to the terms of this EUA and under the circumstances set forth in the Secretary of HHS’s determination under Section 564(b)(1)(C) of the Act described above and the Secretary of HHS’s corresponding declaration under Section 564(b)(1) of the Act, the authorized tests are authorized for the indication(s) set forth in Appendix A and any additional appendix for which the test is validated consistent with.

## III. Waiver of Certain Requirements
I am waiving the following requirements for the authorized tests during the duration of this EUA:

- Current good manufacturing practice requirements, including the quality system requirements under 21 CFR Part 820 with respect to the design, manufacture, packaging,labeling, storage, and distribution of your product.

## IV. Conditions of Authorization
Pursuant to Section 564(e) of the Act, I am establishing the following conditions on this authorization:

### Authorized Laboratories (You)
A. Your product’s labeling must be consistent with the information set forth in this letter and must consist of, at a minimum, a Fact Sheet for Healthcare Providers, a Fact Sheet for Patients, a Test Summary, and test procedure(s). Your Fact Sheet for Healthcare Providers and Fact Sheet for Patients must include the relevant information set forth in Appendices L and M, respectively. Your Test Summary must include the relevant information set forth in Appendix N. Additionally, all of your authorized labeling must include the following statement: This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing [include link to this letter] for use in [the single laboratory (certified under the CLIA and meets requirements to perform high complexity tests) in which it was developed] for [insert indication(s) from applicable appendix(ces)] using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing. Your product’s labeling must not include any information that is inconsistent with this authorization.

B. You must evaluate the impact of SARS-CoV-2 viral mutations on your product’s performance. Such evaluations must occur on an ongoing basis and must include any additional data analysis that is requested by FDA in response to any performance concerns you or FDA identify during routine evaluation. Additionally, if requested by FDA, you must submit records of these evaluations for FDA review within 48 hours of the request. If your evaluation identifies viral mutations that affect the stated expected performance of your product, you must notify FDA immediately (via email: CDRH-EUA-Reporting@fda.hhs.gov).

C. If requested by FDA, you must update your labeling within 7 days to include any additional labeling risk mitigations identified by FDA, such as those related to the impact of viral mutations on test performance. Such updates will be made in consultation with, and require concurrence of, DMD/OHT7-OIR/OPEQ/CDRH.

D. Your authorized product must comply with the following labeling requirements under FDA regulations: the intended use statement (21 CFR 809.10(a)(2), (b)(2)); adequate directions for use (21 U.S.C. § 352(f)), (21 CFR 809.10(b)(5), (7), and (8)); appropriate limitations on the use of the device including information required under 21 CFR 809.10(a)(4); and any available information regarding performance of the product, including requirements under 21 CFR 809.10(b)(12).

E. You must make available on your website(s), if applicable, the Fact Sheet for Healthcare Providers and Fact Sheet for Patients.

F. You are authorized to make available additional information relating to the emergency use of your authorized product that is consistent with, and does not exceed, the terms of this letter of authorization.

G. You may make modifications to your authorized product and implement such changes if the test continues to be within the Scope of this Authorization (Section II), and the modifications do not change the indication for use set forth in the applicable appendix(ces) (e.g., including new/different extraction kits or instruments) and do not change the analyte specific reagents (e.g., PCR primers and/or probes).^8^ Prior to implementing modifications under this Condition of Authorization, you must first validate your modified test in accordance with the requirements in the applicable appendix(ces) and notify FDA by submitting any information set forth in Section II that has changed from your prior notification, including updated labeling to reflect the modification(s), to FDA at CDRH-EUA-Templates@fda.hhs.gov using the subject line “Modification to Test on Exhibit 1 of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing”. You must also resubmit the certifying statement required for inclusion in Exhibit 1 as set forth in Section II of this letter. Provided that the modification(s) do not affect whether your product is within the scope of this authorization, the updated labeling will be added to FDA’s website after FDA confirms that the required documentation set forth in Section II has been submitted to FDA. At that time, FDA will notify the developer of the inclusion of its updated labeling on FDA’s website by replying to the email. Please note that adding the updated labeling does not necessarily mean that FDA has reviewed the underlying validation data submitted or has confirmed that the modification(s) is appropriately validated. Instead, being added to FDA’s website only means that the developer has submitted complete documentation as set forth in Section II and consistent with this paragraph.

H. You must inform relevant public health authorities of this EUA, including the terms and conditions herein, and any updates made to your authorized product and authorized labeling.

I. You must notify the relevant public health authorities of your intent to run your product.

J. You must have a process in place for reporting test results to healthcare providers and relevant public health authorities, as appropriate.

K. You must include with test result reports all authorized Fact Sheets. Under exigent circumstances, other appropriate methods for disseminating these Fact Sheets may be used, which may include mass media.

L. You must use your product as outlined in the authorized labeling. Your test procedures must include the use of control materials that control for specimen quality and test system performance, as set forth in Section II of this letter. The test procedures must indicate the expected results for each control that are necessary for a test to be considered valid. Deviations from your authorized test procedures, including the instruments extraction methods, clinical specimen types, control materials, other ancillary reagents and materials required to use your product are not permitted. Any modifications to your authorized product, including the authorized labeling, must be made in accordance with Condition of Authorization G of this letter.

M. All laboratory personnel using your product must be appropriately trained in RT-PCR techniques and use appropriate laboratory and personal protective equipment when handling this product and use your product in accordance with the authorized labeling.

N. Upon request from FDA, you must evaluate the analytical limit of detection and assess traceability^9^ of your product with any FDA-recommended reference material(s). After submission to and concurrence with the data by FDA, you must update your labeling to reflect the additional testing. Such labeling updates will be made in consultation with, and require concurrence of, DMD/OHT7-OIR/OPEQ/CDRH. After concurrence, the updated labeling will be added to FDA’s website.

O. You must collect information on the performance of your product. You must report to DMD/OHT7-OIR/OPEQ/CDRH (via email: CDRH-EUA-Reporting@fda.hhs.gov) any suspected occurrence of false positive or false negative results and significant deviations from the established performance characteristics of your product of which you become aware.

P. You must have a process in place to track adverse events of your product in accordance with 21 CFR Part 803. Serious adverse events must be immediately reported to DMD/OHT7-OIR/OPEQ/CDRH (via email: CDRH-EUA-Reporting@fda.hhs.gov).

Q. You must ensure that any records associated with this EUA are maintained until otherwise notified by FDA. Such records will be made available to FDA for inspection upon request.

R. If your product is used with specimens collected using an authorized home specimen collection kit per Appendix J or K, you must follow any specimen accessioning protocols and other authorized labeling provided with the authorized home specimen collection kit.

S. If your product is used with specimens collected using an authorized home specimen collection kit per Appendix J or K of this letter, you must have a process in place for informing the manufacturer(s) of any authorized home collection kit used with your authorized product of any adverse events that you become aware of related to such kit(s).

T. If testing pooled specimens with your product, you must have and follow a pooling protocol that includes instructions for follow-up for positive and invalid pools, including follow-up instructions to be provided to the organizer of the testing program. For media pooling, the instructions for follow up for positive and invalid pools must include deconvoluting to retest individual samples. For swab pooling, the instructions for follow up for positive and invalid pools must include reporting as “presumed positive” unless or until the individual is re-tested individually and must include instructions to collect a new specimen to be tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, the instructions must indicate that such individuals should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result.

U. You must include with test result reports for specific individuals whose specimen(s) were the subject of pooling, a notice that pooling was used during testing and that “Individual specimens with low viral loads may not be detected due to the decreased sensitivity or increased interference when tested with pooled testing.”

V. If testing pooled specimens with your product, you must include with test result reports for specific individuals whose specimen(s) were the subject of pooling, a notice that their test result is “presumed positive” unless or until they are re-tested individually if the pool in which they were included returns a positive or invalid result. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, the report must include instructions to collect a new specimen to be tested individually and must indicate that such individuals should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result.

W. If testing specimens using pooled testing with your product, you must monitor the positivity rate of the specimens tested using pooled testing by calculating the percent positive results using a moving average (such as a rolling average updated daily using data from the previous 7-10 days).

X. You must keep records of specimen pooling test result data, daily testing totals including number of pooled test results, number of individuals tested and daily running average of percent positive results. For the first 12 months from the date of their creation, such records must be made available to FDA upon request within 48 business hours. After 12 months from the date of their creation, upon FDA request, such records must be made available for inspection within a reasonable time.

Y. You must evaluate the clinical performance of your product by completing the clinical evaluation study for asymptomatic individuals set forth in Appendix A. If this clinical evaluation is not included in the original notification submitted to FDA, then these results must be submitted to FDA at [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) using the subject line “Post-Authorization Screening Data for Test on Exhibit 1 of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing” within 6 months of submitting the notification required by Section II of this letter (unless otherwise agreed to with DMD/OHT7-OIR/OPEQ/CDRH). If FDA concurs with the data, you must update your authorized labeling to reflect the additional testing. Such labeling updates must be made only after concurrence by DMD/OHT7-OIR/OPEQ/CDRH. If FDA does not concur that the data submitted meets the validation requirements set forth in Appendix A, FDA may determine that your product is not authorized. As described in Section II, FDA will remove any product from Exhibit 1 that it determines is not authorized, e.g., if such product does not meet the validation requirements set forth in Appendix A.

### Conditions Related to Printed Materials, Advertising and Promotion
Z. All descriptive printed matter, advertising, and promotional materials relating to the use of your product shall be consistent with the authorized labeling, as well as the terms set forth in this EUA and meet the requirements set forth in section 502(a), (q)(1), and (r) of the Act, as applicable, and FDA implementing regulations.

AA. No descriptive printed matter, advertising, or promotional materials relating to the use of your product may represent or suggest that this product is safe or effective for the detection of SARS-CoV-2.

BB. All descriptive printed matter, advertising, and promotional materials relating to the use of your test shall clearly and conspicuously state that:

- This product has not been FDA cleared or approved, but has been authorized for emergency use by FDA under an EUA for use by the authorized laboratory;
- This product has been authorized only for the detection of nucleic acid from SARS-CoV-2, not for any other viruses or pathogens; and
- The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.

The emergency use of your product as described in this letter of authorization must comply with the conditions and all other terms of this authorization.

## V. Duration of Authorization
This EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 is terminated under Section 564(b)(2) of the Act or the EUA is revoked under Section 564(g) of the Act.

Sincerely,


____________________________
Jacqueline A. O’Shaughnessy, Ph.D.
Acting Chief Scientist
Food and Drug Administration

Enclosure

## Appendix A
### Base Validation for Testing Individual Specimens
As explained in Section II of this letter, all tests must be validated in accordance with this appendix in order to be authorized. After the test is validated, the developer must notify FDA by submitting the information set forth in Section II to FDA at [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) using the subject line “Addition to Exhibit 1 of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing”. Developers who wish to be authorized for additional indications (e.g., pooling) must also validate their test in accordance with the applicable Appendices B-K.

As noted in Appendices B-K, all tests must validate consistent with this appendix (including all protocols outlined below) in order to be authorized. If no other indication(s) is requested in the notification described in Section II, then the indication noted in this appendix will be the only indication for which the test is authorized under this EUA.

Subject to the terms of this EUA, a test that is otherwise within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in this appendix:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swab samples collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

Tests will be added to Exhibit 1 for this indication after FDA determines it has received a complete notification.

Validation specific to this indication, and needed prior to performing validation for any indications set forth in other appendices in this letter, includes the four validation protocols outlined below: (1) Limit of Detection (LoD); (2) Validation for Inclusivity (Analytical Reactivity); (3) Validation for Cross-Reactivity (Analytical Specificity); and (4) Clinical Evaluation.

As part of the notification to FDA, methodology and summary data must be submitted for each validation protocol. This includes line data with the Ct score for each sample tested in the clinical evaluation. If you are leveraging data from another developer’s EUA-authorized test, such as _in silico_ or cross-reactivity data, you must submit a right of reference from that developer as part of your notification or indicate that you intend to leverage the CDC’s general right of reference. ^10^

 1. *Limit of Detection (LoD)*
   You must determine the LoD of the test utilizing all components of the test system from sample preparation and extraction to detection. Testing quantified live or inactivated virus (i.e., heat treated, chemically modified, or irradiated virus) spiked into real clinical matrix (anterior nasal swab or nasopharyngeal swab samples) for LoD determination is acceptable since this most closely represents a clinical sample. Quantified known positive clinical specimen, as determined by an EUA authorized test, can be used to create dilutions in clinical matrix for LoD determination. Synthetic RNA is not an acceptable test material for the LoD studies. Anterior nasal swab or nasopharyngeal swab samples collected from SARS-CoV-2 negative individuals can be used as clinical matrix. You must determine a preliminary LoD by testing a 2-3 fold dilution series of three replicates per concentration. The lowest concentration that gives positive results 100% of the time is defined as the preliminary LoD. During the preliminary LoD determination at least one concentration that does not yield 100% positive results must be tested. The final LoD concentration must be confirmed by testing 20 individual extraction replicates at the preliminary LoD. For this letter, the LoD is the lowest concentration at which ≥19/20 replicates are positive.

   You must determine the LoD of your test for each type of media you intend to use with your test (e.g., saline, PBS, VTM, dry swab reconstituted with PBS).

   As part of the notification to FDA, you must provide documentation of the methodology and results of your LoD determination.

2. *Validation for Inclusivity (Analytical Reactivity)*
   Genetic variants of SARS-CoV-2 are emerging which may have the potential to impact test performance. This is discussed in the FDA guidance [Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-evaluating-impact-viral-mutations-covid-19-tests), which includes recommendations for evaluating the potential impact of emerging and future viral mutations of SARS-CoV-2 on COVID-19 tests. ^11^

   You must perform an _in silico_ inclusivity analysis by conducting sequence alignment of the primer/probe sequences of your test with publicly available SARS-CoV-2 genomes, such as those in the GISAID database.

   As part of the notification to FDA, you must provide documentation of the specific primer and probe sequences for your test and the methodology and results of your _in silico_ inclusivity analysis. Include a discussion of your _in silico_ analysis results for the particular SARS-CoV-2 variants that are circulating with high prevalence (i.e., B.1.617.2 and sub-lineages at the time of issuance of this letter). ^12^

   Repeat the _in silico_ inclusivity analysis on a regular basis (at least monthly) prior to and after authorization.

   Your _in silico_ inclusivity analysis (initial and recurring) must demonstrate, for at least one of the viral targets in your test, 100% homology to at least 95% of sequences (when analyzing at least 2000 sequences within the last 30 days prior to your submission) representing circulating SARS-CoV-2 variants.

3. *Validation for Cross-reactivity (Analytical Specificity)*

   You must assess the potential cross-reactivity of your test with the organisms listed in the table below to demonstrate that the test does not react with related pathogens, high prevalence disease agents and normal or pathogenic flora that are reasonably likely to be encountered in a clinical specimen. Specifically, conduct sequence alignment of the primer/probe sequences of your test with publicly available genome sequences for the organisms listed in the table below to determine the extent to which cross-reactivity may impact test performance.

   Your validation must demonstrate <80% homology between potential cross-reacting microorganism(s) and your test primers/ probe(s).

   As part of the notification to FDA, you must provide documentation of the methodology and results of your cross-reactivity validation.

| High priority pathogens from the same genetic family | High priority organisms likely present in respiratory specimens    |
|-----------------------------------------------------|------------------------------------------------------------------|
| Human coronavirus 229E                               | Adenovirus (e.g., C1 Ad. 71)                                     |
| Human coronavirus OC43                               | Human Metapneumovirus (hMPV)                                     |
| Human coronavirus HKU1                               | Parainfluenza virus 1-4                                          |
| Human coronavirus NL63                               | Influenza A & B                                                  |
| SARS-CoV-1                                           | Enterovirus (e.g., EV68)                                         |
||


| High priority pathogens from the same genetic family | High priority organisms likely present in respiratory specimens |
|-----------------------------------------------------|---------------------------------------------------------------|
| MERS-coronavirus                                    | Respiratory syncytial virus                                   |
|                                                     | Rhinovirus                                                    |
|                                                     | _Chlamydia pneumoniae_                                        |
|                                                     | _Haemophilus influenzae_                                      |
|                                                     | _Legionella pneumophila_                                      |
|                                                     | _Streptococcus pneumoniae_                                    |
|                                                     | _Streptococcus pyogenes_                                      |
|                                                     | _Bordetella pertussis_                                        |
|                                                     | _Mycoplasma pneumoniae_                                       |
|                                                     | _Candida albicans_                                            |
|                                                     | _Pseudomonas aeruginosa_                                      |
|                                                     | _Staphylococcus epidermis_                                    |
|                                                     | _Streptococcus salivarius_                                    |
||

4. *Clinical Evaluation*
   You must perform a clinical evaluation to determine the clinical sensitivity and specificity of your test using natural clinical specimens. Test a minimum of 30 positive and 30 negative specimens collected from a total of 60 patients suspected of SARS-CoV-2 infection by a healthcare provider in COVID-19 disease endemic region(s).

   You must also test an additional 20 positive and 100 negative specimens collected from individuals without symptoms or other reasons to suspect COVID-19 in COVID-19 disease endemic region(s). As explained in Condition of Authorization Y of this letter, this information must be submitted to FDA as part of your initial notification or within 6 months of your notification date.

   Acceptable Specimens:^13^

   Positive specimens must be individual natural (prospective or retrospective or leftover samples) positive clinical specimens collected in COVID-19 disease endemic region(s).

   20-25% of the positive specimens must be “low positive” by the comparator method, meaning the specimen is no more than 3 Ct below the mean Ct of the target with the highest Ct (if there are multiple targets) at the LoD of the comparator test. If collecting specimens prospectively and fewer than 20% of comparator positive specimens representing low positives as per the comparator assay are obtained, supplement the prospective specimens with additional low positive specimens such as archived samples or samples collected from convalescent patients.

   The use of frozen samples is acceptable if an analytical study is performed and demonstrates that preservation of samples (e.g., by freezing at ≤-70°C) does not change the sensitivity of your test by more than 3 Ct at LoD when compared to freshly prepared samples.

   Samples previously tested positive by another highly sensitive EUA RT-PCR assay (defined below) may be used without additional comparator testing.

   Negative specimens must be individual negative samples acquired from the following acceptable sources: (1) prospective samples from individuals suspected of COVID-19 by their healthcare provider, (2) archived/retrospective respiratory samples collected from patients with signs and symptoms of respiratory infection, and (3) other subjects that are expected to be negative for SARS-CoV-2, such as specimens collected prior to COVID-19 pandemic in the U.S.

   Comparator Method:

   As your comparator method, you must use a highly sensitive EUA (or cleared) RT-PCR assay that uses a chemical lysis step followed by a nucleic acid isolation step (e.g., silica bead extraction), and generates Ct values. An EUA RT-PCR assay is considered highly sensitive when the test’s authorized labeling, posted on FDA’s website, indicates a PPA ≥ 95% based on validation with positive patient specimens. The EUA authorized comparator assay must be used according to authorized labeling (e.g., using only claimed matrices, etc.).

   The comparator assay may have the same, or different, targets as your assay.

   Validation:

   Test clinical specimens in accordance with your proposed diagnostic algorithm (i.e., tested using your proposed test procedure), including retesting when appropriate. The limited volume of natural specimens may preclude retesting. In instances where retesting is indicated per your proposed test procedure but not performed, calculate your test’s performance using the initial results, where equivocal/indeterminate/inconclusive results will count against your final performance.

   Test specimens in a blinded fashion (e.g., present positive and negative samples to the end user in a blinded fashion), including blinding the end user to the results of any comparator method testing.

   Investigate potential false results using an additional highly sensitive EUA RT-PCR assay and/or Sanger sequencing. The results of the discordant analysis can be footnoted in your final performance table but cannot be used to change the final performance calculations.

   Test Performance:

   Calculate positive percent agreement (PPA) by comparing the results for each specimen tested with your test compared to the comparator assay.

   Calculate negative percent agreement (NPA) by comparing the results for each specimen tested with your test compared to the comparator assay (for prospectively collected samples) or as agreement with expected results if samples were collected from individuals known to be negative for SARS-CoV2 (e.g., collected before December 2019).

   Calculate positive and negative percent agreement separately for the two datasets (i.e., specimens collected from patients suspected of SARS-CoV-2 infection by a healthcare provider and specimens collected from individuals without symptoms or other reasons to suspect COVID-19), as well as combined.

   Your validation must demonstrate a minimum of 95% positive and negative percent agreement.

   Documentation:

   Provide documentation of the methodology and results, including line data and Ct scores, of your clinical evaluation. Results from specimens collected from patients suspected of SARS-CoV-2 infection by a healthcare provider must be provided as part of your notification to FDA required by Section II of this letter. Results from specimens collected from individuals without symptoms or other reasons to suspect COVID-19 may be provided either in your notification to FDA or post-authorization as set forth in Condition of Authorization Y of this letter.

## Appendix B
### Swab pooling up to n=3
Subject to the terms of this EUA, a test that is within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing up to 3 individual human anterior nasal swabs placed in a single vial after being collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

## Appendix C
### Swab pooling up to n=5
Subject to the terms of this EUA, a test that is otherwise within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in this appendix and Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing up to 5 individual human anterior nasal swabs placed in a single vial after being collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Validation specific to this indication must include both validation protocols outlined below, “Validation of Expected Limit of Detection (LoD)” and “Validation of High Viral Concentrations”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. *Validation of Expected Limit of Detection (LoD)*

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your procedure for testing 5-swab pools.

   To generate a 5-swab pool positive for SARS-CoV-2, prepare a single positive swab by spiking a known amount of inactivated virus or quantified positive patient sample onto the swab prior to immersion in the volume of media you intend to include in your procedure for 5-swab pooling. Add an additional four swabs containing only negative patient clinical matrix. The final viral analyte concentration in the media must be approximately 3x the LoD determined when performing the validation as set forth in Appendix A for testing an individual specimen. To ensure this concentration is achieved, factor in how much volume the swab absorbs, and the SARS-CoV-2 concentration needed on the single positive swab to achieve a final concentration of approximately 3x the LoD in the media. This is the concentration you should use to prepare the positive swabs for your validation study.

   Test at least 20 independent extraction replicates of individual swabs in the same volume of buffer used in the LoD study as set forth in Appendix A for validation of individual specimen testing, using the testing protocol in your test’s procedure for testing an individual specimen, validated as set forth in Appendix A. Test 20 paired 5-swab pools in parallel, each containing a single positive swab and 4 individual negative swabs in the volume of media you intend to include in your procedure for testing 5-swab pools, using the testing protocol you intend to include in your procedure for testing 5-swab pools.

   Your validation must demonstrate that:

   - ≥95% of pooled replicates are detected as positive using the swab pooling protocol;
   - The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

2. *Validation of High Viral Concentrations*

   Prepare three swabs simulating high viral concentrations by spiking 10^6 copies/mL of inactivated virus or quantified positive patient sample. Test 10 replicates of media containing the three spiked positive swabs and 2 individual negative swabs in the volume of media you intend to include in your procedure for testing 5-swab pools, using the testing protocol you intend to include in your procedure for testing 5-swab pools.

   Your validation must demonstrate that:

   - All 10 replicates are detected as positive; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix D
### Swab pooling up to n=10
Subject to the terms of this EUA, a test that is otherwise within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in this appendix and Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing up to 10 individual human anterior nasal swabs placed in a single vial after being collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Validation specific to this indication must include both validation protocols outlined below, “Validation of Expected Limit of Detection (LoD)” and “Validation of High Viral Concentrations”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. *Validation of Expected Limit of Detection (LoD)*

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your procedure for testing 10-swab pools.

   To generate a 10-swab pool positive for SARS-CoV-2, prepare a single positive swab by spiking a known amount of inactivated virus or quantified positive patient sample onto the swab prior to immersion in the volume of media you intend to include in your procedure for 10-swab pooling. Add an additional nine swabs containing only negative patient clinical matrix. The final viral analyte concentration in the media must be approximately 3x the LoD determined when performing the validation as set forth in Appendix A for testing an individual specimen. To ensure this concentration is achieved, factor in how much volume the swab absorbs, and the SARS-CoV-2 concentration needed on the single positive swab to achieve a final concentration of approximately 3x the LoD in the media. This is the concentration you should use to prepare the positive swabs for your validation study.

   Test at least 20 independent extraction replicates of individual swabs in the same volume of buffer used in the LoD study as set forth in Appendix A for validation of individual specimen testing, using the testing protocol in your test’s procedure for testing an individual specimen, validated as set forth in Appendix A. Test 20 paired 10-swab pools in parallel, each containing a single positive swab and 9 individual negative swabs in the volume of media you intend to include in your procedure for testing 10-swab pools, using the testing protocol you intend to include in your procedure for testing 10-swab pools.

   Your validation must demonstrate that:

   - ≥95% of pooled replicates are detected as positive using the swab pooling protocol;
   - The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

2. *Validation of High Viral Concentrations*

   Prepare three swabs simulating high viral concentrations by spiking 10^6 copies/mL of inactivated virus or quantified positive patient sample. Test 10 replicates of media containing the three spiked positive swabs and 7 individual negative swabs in the volume of media you intend to include in your procedure for testing 10-swab pools, using the testing protocol you intend to include in your procedure for testing 10-swab pools.

   Your validation must demonstrate that:

   - All 10 replicates are detected as positive; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix E
### Media pooling up to n=3
Subject to the terms of this EUA, a test that is within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing aliquots of media from up to 3 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

## Appendix F
### Media pooling up to n=5 – validation option 1
Subject to the terms of this EUA, a test that is otherwise within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in this appendix and Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing aliquots of media from up to 5 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Validation specific to this indication must include the validation protocol outlined below, *“Validation of Expected Limit of Detection (LoD)”*. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. *Validation of Expected Limit of Detection (LoD)*

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your procedure for testing 5-sample pools.

   Prepare positive samples for your validation study at 5x the LoD determined when performing the validation as set forth in Appendix A for testing an individual specimen.

   Test at least 20 independent extraction replicates of individual samples using the testing protocol in your test’s procedure for testing an individual specimen, validated as set forth in Appendix A. Test 20 paired 5-sample pools in parallel, each containing aliquots from a single positive sample and 4 individual negative samples, using the volumes and testing protocol you intend to include in your procedure for testing 5-sample pools.

   Your validation must demonstrate that:

   - ≥95% of pooled replicates are detected as positive using the sample pooling protocol;
   - The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix G
### Media pooling up to n=10 – validation option 1
Subject to the terms of this EUA, a test that is otherwise within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in this appendix and Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing aliquots of media from up to 10 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Validation specific to this indication must include the validation protocol outlined below, **“Validation of Expected Limit of Detection (LoD)”**. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. *Validation of Expected Limit of Detection (LoD)*

   Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your procedure for testing 10-sample pools.

   Prepare positive samples for your validation study at 10x the LoD determined when performing the validation as set forth in Appendix A for testing an individual specimen.

   Test at least 20 independent extraction replicates of individual samples using the testing protocol in your test’s procedure for testing an individual specimen, validated as set forth in Appendix A. Test 20 paired 10-sample pools in parallel, each containing aliquots from a single positive sample and 9 individual negative samples, using the volumes and testing protocol you intend to include in your procedure for testing 10-sample pools.

   Your validation must demonstrate that:

   - ≥95% of pooled replicates are detected as positive using the sample pooling protocol;
   - The Ct score difference between the pooled and single swab protocols does not exceed 1.7 Ct; and
   - The invalid rate in the swab pooling protocol does not exceed 5%.

## Appendix H
### Media pooling up to n=5 – validation option 2
Subject to the terms of this EUA, a test that is otherwise within the Scope of this Authorization (Section II) is authorized for the following additional indication and may be used for this indication after validation is completed as set forth in this appendix and Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing aliquots of media from up to 5 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Validation specific to this indication must include the validation protocol outlined below, “Validation of the Effect on the Percent Agreement”. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. *Validation of the Effect on the Percent Agreement*

   Test at least 20 individual positive clinical specimens using the testing protocol in your test’s procedure for testing an individual specimen, validated as set forth in Appendix A. Test 20 paired 5-sample pools in parallel, each containing aliquots from a single positive specimen and 4 randomly selected individual negative clinical specimens (collection of negative anterior nasal specimens from healthy individuals is acceptable), using the testing protocol you intend to include in your procedure for testing 5-sample pools.

   20 unique positive specimens and 80 unique negative specimens are needed to comprise twenty 5-sample pools. At least 20% of positive clinical specimens used for this validation study must be low positives, where, for 5-sample pooling, a low positive is within 2.32 Ct of the mean Ct at the LoD determined when performing the validation as set forth in Appendix A for testing an individual specimen.

   Archived individual clinical anterior nasal specimens are acceptable for this validation study, if available, given they contain enough volume for both individual and 5-sample pool testing. If archived specimens are used, the original diagnostic results are acceptable in lieu of repeating the individual specimen testing, if the original diagnostic results were acquired according to your test’s procedure for testing an individual specimen, validated as set forth in Appendix A.

   If you cannot acquire at least 20% low positive samples as natural clinical specimens, you may dilute positive clinical specimens into pooled negative anterior nasal clinical matrix prepared as described here. Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your procedure for testing 5-sample pools.

   Your validation must demonstrate that:

   - ≥85% agreement between pooled testing and individual testing; and
   - The invalid rate in the pooling protocol does not exceed 5%.

## Appendix I
### Media pooling up to n=10 – validation option 2
Subject to the terms of this EUA, a test that is otherwise within the Scope of this Authorization (Section II) is authorized for the following additional indication and may be used for this indication after validation is completed as set forth in this appendix and Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swabs or pooled samples containing aliquots of media from up to 10 individual human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP from individuals, including individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials, when tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Validation specific to this indication must include the validation protocol outlined below, **“Validation of the Effect on the Percent Agreement”**. As part of the notification to FDA, summary data must be submitted, including the percent of positive pools detected, the Ct score difference, and the line data including the Ct score for each pool and individual sample tested.

1. *Validation of the Effect on the Percent Agreement*

   Test at least 20 individual positive clinical specimens using the testing protocol in your test’s procedure for testing an individual specimen, validated as set forth in Appendix A. Test 20 paired 10-sample pools in parallel, each containing aliquots from a single positive specimen and 9 randomly selected individual negative clinical specimens (collection of negative anterior nasal specimens from healthy individuals is acceptable), using the testing protocol you intend to include in your procedure for testing 10-sample pools.

   20 unique positive specimens and 180 unique negative specimens are needed to comprise twenty 10-sample pools. At least 20% of positive clinical specimens used for this validation study must be low positives, where, for 10-sample pooling, a low positive is within 3.32 Ct of the mean Ct at the LoD determined when performing the validation as set forth in Appendix A for testing an individual specimen.

   Archived individual clinical anterior nasal specimens are acceptable for this validation study, if available, given they contain enough volume for both individual and 10-sample pool testing. If archived specimens are used, the original diagnostic results are acceptable in lieu of repeating the individual specimen testing, if the original diagnostic results were acquired according to your test’s procedure for testing an individual specimen, validated as set forth in Appendix A.

   If you cannot acquire at least 20% low positive samples as natural clinical specimens, you may dilute positive clinical specimens into pooled negative anterior nasal clinical matrix prepared as described here. Use either diluted positive clinical samples quantified in copies/mL using a standard curve, or inactivated virus of a known quantity represented as copies/mL. Prepare samples using negative anterior nasal clinical matrix (collection from healthy individuals is acceptable) using sample volumes you intend to include in your procedure for testing 10-sample pools.

   Your validation must demonstrate that:

   - ≥85% agreement between pooled testing and individual testing; and
   - The invalid rate in the pooling protocol does not exceed 5%.

## Appendix J
### Individual Home Specimen Collection
Subject to the terms of this EUA, a test that is within the Scope of this Authorization (Section II) is authorized for the following indication and may be used for this indication after validation is completed as set forth in this appendix and Appendix A:

Qualitative detection of RNA from SARS-CoV-2 in individual human anterior nasal swab samples collected by a healthcare provider (HCP), self-collected under the supervision of an HCP, or self-collected at home using the following authorized home collection kit(s): [insert authorized home collection kit with which your test was validated], when used consistent with the home collection kit’s authorization for individuals tested at least once per week.

This test is authorized for use in the single laboratory that developed the test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

A list of authorized home collection kits can be found on FDA’s website, available here: [FDA Authorized Home Collection Kits](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2#individual-molecular).

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Developers who seek this indication must confirm that the transport media used in the authorized home collection kit is the same transport media used for the validation set forth in Appendix A, or, for specimens collected in dry tubes, that the media used for reconstitution of specimens collected with the authorized home collection kit is the same media used for reconstitution of specimens for the validation set forth in Appendix A. If the validation set forth in Appendix A was completed using a different media than used with the authorized home collection kit, an additional LoD determination, as set forth in Appendix A, must be completed for specimens collected with the authorized home collection kit, with results demonstrated that the LoD is within 3x of the LoD determined with the original validation.

Moreover, developers must clearly include in their test’s authorized labeling that the authorized home collection kit must be used consistent with the home collection kit’s authorization.

## Appendix K
### Pooled Home Specimen Collection
Subject to the terms of this EUA, a test that is within the Scope of this Authorization (Section II) and validated for at least one of the indications set forth in Appendices B-I, is also authorized for use with anterior nasal swab specimens collected using an authorized home collection kit after validation is completed as set forth in this appendix and Appendix A.

The indication of such a test, as set forth in the applicable Appendix B-I, shall include the following clause after “self-collected under the supervision of an HCP”, replacing “from individuals, including individuals without symptoms or other reasons to suspect COVID-19 and placed in individual vials, when tested at least once per week.”:

“or self-collected at home using the following authorized home collection kit(s): [insert authorized home collection kit with which your test was validated] when used consistent with the home collection kit’s authorization for individuals tested at least once per week.”

Such that the portion of the indication discussing specimen collection shall read:
“… human anterior nasal swab specimens that were collected by a healthcare provider (HCP) or self-collected under the supervision of an HCP or self-collected at home using the following authorized home collection kit(s): [insert authorized home collection kit with which your test was validated] when used consistent with the home collection kit’s authorization for individuals tested at least once per week.”

A list of authorized home collection kits can be found on FDA’s website, available here: [FDA Authorized Kits](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2#individual-molecular).

This indication will be added to Exhibit 1 for the relevant test after FDA determines it has received a complete notification.

Developers who seek this indication must confirm that the transport media used in the authorized home collection kit is the same transport media used for the validation set forth in Appendix A, or, for specimens collected in dry tubes, that the media used for reconstitution of specimens collected with the authorized home collection kit is the same media used for reconstitution of specimens for the validation set forth in Appendix A. If the validation set forth in Appendix A was completed using a different media than used with the authorized home collection kit, an additional LoD determination, as set forth in Appendix A, must be completed for specimens collected with the authorized home collection kit, with results demonstrated that the LoD is within 3x of the LoD determined with the original validation.

Moreover, developers must clearly include in their test’s authorized labeling that the authorized home collection kit must be used consistent with the home collection kit’s authorization.

## Appendix L
### Fact Sheet for Healthcare Providers
As set forth in Section II of this letter and required by Condition of Authorization A of this letter, your test’s labeling must include a Fact Sheet for Healthcare Providers that includes the relevant information in this appendix. FDA has provided a template for a Fact Sheet for Healthcare Providers on the FDA website with this letter to facilitate the creation of your test specific fact sheet.

You must include the following in your Fact Sheet for Healthcare Providers:

Fact Sheet for Healthcare Providers  
[DATE]  
[LABORATORY NAME]  
[DEVICE/TEST NAME]

This Fact Sheet informs you of the significant known and potential risks and benefits of the emergency use of the [DEVICE/TEST NAME].

The [DEVICE/TEST NAME] is authorized for use with anterior nasal respiratory specimens from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.

**All patients whose specimens are tested with this assay will receive the Fact Sheet for Patients: [LABORATORY NAME] - [DEVICE/TEST NAME].**

#### What are the symptoms of COVID-19?
Many patients with COVID-19 have developed fever and/or symptoms of acute respiratory illness (e.g., cough, dyspnea), although some individuals experience only mild symptoms or no symptoms at all. The current information available to characterize the spectrum of clinical illness associated with COVID-19 suggests that, when present, symptoms include cough, shortness of breath or dyspnea, fever, chills, myalgias, headache, sore throat, new loss of taste or smell, nausea or vomiting or diarrhea. Signs and symptoms may appear any time from 2 to 14 days after exposure to the virus, and the median time to symptom onset is approximately 5 days. For further information on the symptoms of COVID-19 please see the link provided in “Where can I go for updates and more information?” section.

Public health officials have identified cases of COVID-19 throughout the world, including the United States. Please check the CDC COVID-19 webpage (see link provided in “Where can I go for updates and more information?” section at the end of this document) or your local jurisdictions website for the most up to date information.

#### What do I need to know about COVID-19 testing?
Current information on COVID-19 for healthcare providers is available at CDC’s webpage, *Information for Healthcare Professionals* (see links provided in “Where can I go for updates and more information?” section).

**This test is to be performed only using anterior nasal respiratory specimens from individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.**

- The [DEVICE/TEST NAME] can be used to test anterior nasal respiratory specimens.
- The [DEVICE/TEST NAME] should be ordered for the detection of SARS-CoV-2 in individuals, including individuals without symptoms or other reasons to suspect COVID-19, when tested at least once per week.
- **[INCLUDE THE FOLLOWING BULLET IF YOUR TEST INCLUDES USE OF AN AUTHORIZED HOME COLLECTION KIT – MODIFY TO INCLUDE HOME COLLECTION INDICATION BASED ON THE APPENDIX YOU ARE CLAIMING: The [DEVICE/TEST NAME] can also be used to test anterior nasal respiratory specimens collected by a healthcare provider (HCP) or self-collected at home using the following authorized home collection kit(s) [INCLUDE NAME OF AUTHORIZED KIT].]**
- **[INCLUDE THE FOLLOWING BULLET IF YOUR TEST ALLOWS SPECIMEN POOLING – BASED ON THE APPENDIX YOU ARE CLAIMING: The [DEVICE/TEST NAME] can also be used to test up to [INCLUDE POOLING INDICATION BASED ON THE APPENDIX YOU ARE CLAIMING].]**
- The [DEVICE/TEST NAME] is only authorized for use at the [NAME OF LABORATORY] that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests.

Specimens should be collected with appropriate infection control precautions. Current guidance is available at the CDC’s website (see links provided in “Where can I go for updates and more information?” section).

When collecting and handling specimens from individuals suspected of being infected with the virus that causes COVID-19, appropriate personal protective equipment should be used as outlined in the CDC *Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19)*. For additional information, refer to CDC *Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under Investigation (PUIs) for Coronavirus Disease 2019 (COVID-19)* (see links provided in “Where can I go for updates and more information?” section).

#### What does it mean if the specimen tests positive for the virus that causes COVID-19?
A positive test result for COVID-19 indicates that RNA from SARS-CoV-2 was detected, and therefore the patient is infected with the virus and presumed to be contagious. Laboratory test results should always be considered in the context of clinical observations and epidemiological data (such as local prevalence rates and current outbreak/epicenter locations) in making a final diagnosis and patient management decisions. Patient management should be made by a healthcare provider and follow current CDC guidelines.

The **[DEVICE/TEST NAME]** has been designed to minimize the likelihood of false positive test results. However, it is still possible that this test can give a false positive result, even when used in locations where the prevalence is below 5%. In the event of a false positive result, risks to patients could include the following: a recommendation for isolation of the patient, monitoring of household or other close contacts for symptoms, patient isolation that might limit contact with family or friends and may increase contact with other potentially COVID-19 patients, limits in the ability to work, delayed diagnosis and treatment for the true infection causing the symptoms, unnecessary prescription of a treatment or therapy, or other unintended adverse effects.

**[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result.]**

All laboratories using this test must follow the standard testing and reporting guidelines according to their appropriate public health authorities.

#### What does it mean if the specimen tests negative for the virus that causes COVID-19?
A negative test result for this test means that SARS-CoV-2 RNA was not present in the specimen above the limit of detection. However, a negative result does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions. It is possible to test a person too early or too late during SARS-CoV-2 infection to make an accurate diagnosis via **[DEVICE/TEST NAME]**.

In addition, asymptomatic people infected with the virus that causes COVID-19 may not shed enough virus to reach the limit of detection of the test, giving a false negative result. In the absence of symptoms, it is difficult to determine if asymptomatic people have been tested too late or too early. Therefore, negative results in asymptomatic individuals may include individuals who were tested too early and may become positive later, individuals who were tested too late and may have serological evidence of infection, or individuals who were never infected.

**[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: Specimens with low viral loads may not be detected in sample pools due to the decreased sensitivity or increased interference of pooled testing. Your interpretation of negative results should take into account clinical and epidemiological risk factors.]**

When diagnostic testing is negative, the possibility of a false negative result should be considered in the context of a patient’s recent exposures and the presence of clinical signs and symptoms consistent with COVID-19. The possibility of a false negative result should especially be considered if the patient’s recent exposures or clinical presentation indicate that COVID-19 is likely, and diagnostic tests for other causes of illness (e.g., other respiratory illness) are negative.

If COVID-19 is suspected based on exposure history together with other clinical findings, re-testing using a new sample with a sensitive method **[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: or without pooling]** should be considered by healthcare providers in consultation with public health authorities. Additional testing may be helpful to ensure testing was not conducted too early.

Risks to a patient of a false negative test result include: delayed or lack of supportive treatment, lack of monitoring of infected individuals and their household or other close contacts for symptoms resulting in increased risk of spread of COVID-19 within the community, or other unintended adverse events.

The performance of this test was established based on the evaluation of a limited number of clinical specimens. The clinical performance has not been established in all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. 

Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.

#### What is an EUA?
The United States FDA has made this test available under an emergency access mechanism called an Emergency Use Authorization (EUA). The EUA is supported by the Secretary of Health and Human Service’s (HHS’s) declaration that circumstances exist to justify the emergency use of in vitro diagnostics (IVDs) for the detection and/or diagnosis of the virus that causes COVID-19. An IVD made available under an EUA has not undergone the same type of review as an FDA-approved or cleared IVD. FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, available alternatives, and based on the totality of scientific evidence available, it is reasonable to believe that this IVD may be effective in diagnosing COVID-19.

This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing \[include link to this letter\] for use in \[the specific laboratory, that is certified under CLIA and meets requirements to perform high complexity tests, in which it was developed\] for \[insert indication(s) from applicable appendix(ces)\] using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing.

The EUA for this test is in effect for the duration of the COVID-19 declaration justifying emergency use of IVDs, unless terminated or revoked (after which the test may no longer be used).

#### What are the approved available alternatives?
Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here: [https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases](https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases). A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available. FDA has issued EUAs for other tests that can be found at:

[https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization).

#### Where can I go for updates and more information?
**CDC webpages:**

**General:** [https://www.cdc.gov/coronavirus/2019-ncov/index.html](https://www.cdc.gov/coronavirus/2019-ncov/index.html)
**Symptoms:** [https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html](https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html)
**Healthcare Professionals:** [https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html](https://www.cdc.gov/coronavirus/2019-nCoV/guidance-hcp.html)
**Information for Laboratories:** [https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html](https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html)
**Laboratory Biosafety:** [https://www.cdc.gov/coronavirus/2019-nCoV/lab-biosafety-guidelines.html](https://www.cdc.gov/coronavirus/2019-nCoV/lab-biosafety-guidelines.html)
**Isolation Precautions in Healthcare Settings:** [https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.ht](https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html) [ml](https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html)
**Specimen Collection:** [https://www.cdc.gov/coronavirus/2019-nCoV/guidelines-clinical-specimens.html](https://www.cdc.gov/coronavirus/2019-nCoV/guidelines-clinical-specimens.html)
**Infection Control:** [https://www.cdc.gov/coronavirus/2019-ncov/php/infection-control.html](https://www.cdc.gov/coronavirus/2019-ncov/php/infection-control.html)

**FDA webpages:**
**General:** [www.fda.gov/novelcoronavirus](http://www.fda.gov/novelcoronavirus)
**EUAs:**(includes links to fact sheet for individuals and manufacturer’s instructions) <https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas>

**LABORATORY NAME:**
ADDRESS LINE 1
ADDRESS LINE 2

**Customer Support:**
+1 800 XXX-XXXX
customersupportemail@company.com

**Technical Support:**
+1 800 XXX-XXXX
techsupportemail@company.com

**Report Adverse events,** including problems with test performance or results, to MedWatch by submitting the online FDA Form 3500 ([https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home](https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home)) or by calling **1-800-FDA-1088**

## Appendix M
### Fact Sheet for Patients
As set forth in Section II of this letter and required by Condition of Authorization A of this letter, your test’s labeling must include a Fact Sheet for Patients that includes the relevant information in this appendix. FDA has provided a template for a Fact Sheet for Patients on the FDA website with this letter to facilitate the creation of your test-specific fact sheet.

You must include the following in your Fact Sheet for Patients:

Fact Sheet for Patients  
[DATE]  
[LABORATORY NAME]  
[DEVICE/TEST NAME]  

You are being given this Fact Sheet because your sample(s) was tested for the Coronavirus Disease 2019 (COVID-19) using the [DEVICE/TEST NAME].

This Fact Sheet contains information to help you understand the risks and benefits of using this test for the diagnosis of COVID-19. After reading this Fact Sheet, if you have questions or would like to discuss the information provided, please talk to your healthcare provider.

For the most up to date information on COVID-19 please visit the CDC Coronavirus Disease 2019 (COVID-19) webpage:  
[https://www.cdc.gov/COVID19](https://www.cdc.gov/COVID19)


#### What is COVID-19?
COVID-19 is caused by the SARS-CoV-2 virus which is a new virus in humans causing a contagious respiratory illness. COVID-19 can present with a mild to severe illness, although some people infected with COVID-19 may have no symptoms at all. Older adults and people of any age who have underlying medical conditions have a higher risk of severe illness from COVID-19. Serious outcomes of COVID-19 include hospitalization and death. The SARS-CoV-2 virus can be spread to others not just while one is sick, but even before a person shows signs or symptoms of being sick (e.g., fever, coughing, difficulty breathing, etc.). A full list of symptoms of COVID-19 can be found at the following link:  
[https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html](https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html).

#### What is the [DEVICE/TEST NAME]?
The test is designed to detect the virus that causes COVID-19 in anterior nasal swabs.

#### Why was my sample tested?
You were tested because your healthcare provider believes you may have been exposed to the virus that causes COVID-19 based on your signs and symptoms (e.g., fever, cough, difficulty breathing), and/or because:

- You are being tested at regular intervals (serial testing) even though you do not have symptoms or risk factors for COVID-19; or
- You live in or have recently traveled to a place where transmission of COVID-19 is known to occur; or
- You have been in close contact with an individual suspected of or confirmed to have COVID-19; or
- You and your healthcare provider believe there is another reason to investigate your COVID-19 status.

Testing of the samples will help find out if you may have COVID-19.

[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: Laboratories may use pooling when testing your specimen, which means they combine your sample with other individuals' samples prior to testing and test them as a "pool". The laboratory may return a result for the entire pool together or may return individual results.]

#### What are the known and potential risks and benefits of the test?
Potential risks include:

- Possible discomfort or other complications that can happen during sample collection.
- Possible incorrect test result (see below for more information).

Potential benefits include:

- The results, along with other information, can help your healthcare provider make informed recommendations about your care.
- The results of this test may help limit the spread of COVID-19 to your family and those you come in contact with.

#### What does it mean if I have a positive test result?
If you have a positive test result, it is very likely that you have COVID-19. Therefore, it is also likely that you may be placed in isolation to avoid spreading the virus to others. You should follow CDC guidance to reduce the potential transmission of disease.

[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: If you were tested as part of a pool that returned a positive or invalid test result, you may have COVID-19 and should consider yourself to have a positive test result unless or until you receive a negative test result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, you should isolate until receiving a negative result when re-tested individually and should not be grouped with other individuals who have received a positive or presumptive positive result.]

There is a smaller possibility that this test can give a positive result that is wrong (a false positive result) particularly when used in a population without many cases of COVID-19 infection. Your healthcare provider will work with you to determine how best to care for you based on the test results along with medical history, and your symptoms.

#### What does it mean if I have a negative test result?
A negative test result means that the virus that causes COVID-19 was not found in your sample.

However, it is possible for this test to give a negative result that is incorrect (false negative) in some people with COVID-19. You might test negative if the sample was collected early during your infection. You could also be exposed to COVID-19 after your sample was collected and then have become infected.

In particular, people infected with COVID-19 but who have no symptoms may not shed enough virus to trigger a positive test. This means that you could possibly still have COVID-19 even though the test result is negative. If your test is negative, your healthcare provider will consider the test result together with all other aspects of your medical history (such as symptoms, possible exposures, and geographical location of places you have recently traveled) in deciding how to care for you.

[INCLUDE THIS TEXT IF YOUR INDICATION INCLUDES POOLING: If your test result indicates your specimen was pooled and you have a negative test result there is a small chance that your result is incorrect. You should talk with your healthcare provider if you are concerned.]

If you have no symptoms but have been tested because your healthcare provider thought you may have been exposed to COVID-19, you should continue to monitor your health and let your healthcare provider know if you develop any symptoms of COVID-19. If you develop symptoms you may need another test to determine if you have contracted the virus causing COVID-19.

If you develop symptoms or your symptoms get worse you should seek medical care. If you have the following symptoms you should seek immediate medical care at the closest emergency room:

- Trouble breathing
- Persistent pain or pressure in the chest
- New confusion
- Inability to wake up or stay awake
- Bluish lips or face

It is important that you work with your healthcare provider to help you understand the next steps you should take.

#### Is this test FDA-approved or cleared?
No. This test is not yet approved or cleared by the United States FDA. FDA may issue an Emergency Use Authorization (EUA) when certain criteria are met, which includes that there are no adequate, approved, available alternatives. The EUA for this test is supported by the Secretary of Health and Human Service’s (HHS’s) declaration that circumstances exist to justify the emergency use of in vitro diagnostics for the detection and/or diagnosis of the virus that causes COVID-19. This EUA will remain in effect (meaning this test can be used) for the duration of the COVID-19 declaration justifying the emergency use of in vitro diagnostics, unless it is terminated or revoked by FDA (after which the test may no longer be used).

This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing [include link to this letter] for use in [the specific laboratory, that is certified under CLIA and meets requirements to perform high complexity tests, in which it was developed] for [insert indication(s) from applicable appendix(ces)] using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing.

#### What are the approved alternatives?
Any tests that have received full marketing status (e.g., cleared, approved), as opposed to an EUA, by FDA can be found by searching the medical device databases here:  
[https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases](https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/medical-device-databases). A cleared or approved test should be used instead of a test made available under an EUA, when appropriate and available. FDA has issued EUAs for other tests that can be found at:  
[https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization)

#### Where can I go for updates and more information?
The most up-to-date information on COVID-19 is available at the CDC General webpage:  
[https://www.cdc.gov/COVID19](https://www.cdc.gov/COVID19). In addition, please also contact your healthcare provider with any questions/concerns.

## Appendix N
### Authorized Test Summary
As set forth in Section II of this letter and required by Condition of Authorization A, your test’s labeling must include a Test Summary that includes the relevant information in this appendix. FDA has provided a template for a Test Summary on the FDA website with this letter to facilitate the creation of your test specific summary.

You must include the following information in your Test Summary, replacing text highlighted in yellow **[Text]** with information applicable to your specific test:

### TEST SUMMARY
For **In vitro** Diagnostic Use  
Rx Only  
For use under Emergency Use Authorization (EUA) only

The **[test name]** will be performed at the **[laboratory name]** located at **[laboratory address]**, which is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform high complexity tests.

#### INTENDED USE
The **[test name]** is intended for the **in vitro [insert indication(s) from applicable appendix(ces)]**. Testing is limited to **[laboratory name]** laboratory located at **[laboratory address]**, which is certified under Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform high-complexity testing.

The **[test name]** is intended for use by qualified and trained clinical laboratory personnel specifically instructed and trained in the techniques of real-time PCR and in vitro diagnostic procedures. The **[test name]** is only for use under the Food and Drug Administration’s Emergency Use Authorization.

Results are for the detection and identification of SARS-CoV-2 RNA. The SARS-CoV-2 nucleic acid is generally detectable in anterior nasal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.

Laboratories within the United States and its territories are required to report all results to the appropriate public health authorities.

**[INCLUDE THIS PARAGRAPH IF YOUR INDICATION INCLUDES POOLING:]** Negative results from pooled testing should not be treated as definitive. If a patient’s clinical signs and symptoms are inconsistent with a negative result or results are necessary for patient management, then the patient should be considered for individual testing. Specimens included in pools with a positive or invalid result must be reported as presumptive positive or tested individually prior to reporting a result. Individuals included in a pool that returns a positive or invalid result should be treated as a presumptive positive unless or until they receive a negative result when re-tested individually. However, as most individuals in a positive pool will likely receive a negative result when re-tested individually, they should isolate until receiving a negative result when re-tested individually and should not be cohorted with other individuals who have received a positive or presumptive positive result. Specimens with low viral loads may not be detected with pooled testing due to decreased sensitivity or increased interference from pooled testing.

For serial testing programs, additional confirmatory testing for negative results may be necessary, if there is a high likelihood of COVID-19, such as an individual with a close contact with COVID-19 or with suspected exposure to COVID-19 or in communities with high prevalence of infection. Additional confirmatory testing for positive results may also be necessary, if there is a low likelihood of COVID-19, such as in individuals without known exposure to COVID-19 or testing in communities with low prevalence of infection.

1) **Special Conditions for Use Statements:**

- For use under Emergency Use Authorization (EUA) only
- For prescription use only
- For **in vitro** diagnostic use only

**[INCLUDE THIS PARAGRAPH IF YOUR INDICATION INCLUDES HOME COLLECTION:]** Testing of specimens self-collected at home is limited to specimens collected with the **[name of authorized home collection kit with which your test is validated]** by **[the patient population authorized in the home collection kit EUA]**.

This test is authorized under the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing **[include link to this letter]** for use in **[the specific laboratory, that is certified under CLIA and meets requirements to perform high complexity tests, in which it was developed]** for **[insert indication(s) from applicable appendix(ces)]** using the test procedures validated in accordance with the requirements of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing.

#### DEVICE DESCRIPTION AND TEST PRINCIPLE
The **[Test Name]** assay is a reverse transcription polymerase chain reaction (RT-PCR) test. The SARS-CoV-2 primer and probe set(s) is designed to detect RNA from the SARS-CoV-2 **[genes/regions]** in anterior nasal swab specimens that were collected from individuals, including individuals without symptoms or other reasons to suspect COVID-19.

*[Describe the processes used to perform the test, including, as applicable, 1) nucleic acid extraction, 2) reverse transcription of target RNA to cDNA, 3) PCR amplification of target and internal control, and 4) simultaneous detection of PCR amplicons by fluorescent dye labeled probes. Include key parameters such as input volumes, reverse transcription (RT) time and temperature, PCR cycling parameters including dwell temperature and dwell times.]*

#### INSTRUMENTS USED WITH TEST
Instruments
The **[test name]**, a real-time RT-PCR test, is to be used with the **[list extraction kit(s)]** and the **[list RT-PCR Instrument(s)]** and **[RT-PCR Instrument Software]**.

Collection Kits (if applicable)
This assay can be used with the **[list EUA authorized Home Collection Kit(s)]**.

Reagents
The primary reagents used in **[test name]** assay:

| Kits and Reagents | Manufacturer | Catalog # |
|-------------------|--------------|-----------|
|                   |              |           |
|                   |              |           |
||

### CONTROL MATERIAL(s) TO BE USED WITH [test name]
*[List all control materials used with the test and describe what they are, how they are expected to work, where in the testing process they are used, and the frequency of use. If a control is commercially available, provide supplier’s name and catalog number or other identifier; if your device relies on external controls that are manufactured by a third party please note that these controls must also be validated within your analytical and clinical studies.]*

Controls that are used with the test include:

a) A “no template” (negative) control is needed to *[describe need]* and is used *[describe use – please also specify frequency of use]*

b) A positive template control is needed to *[describe need]* and is used *[describe use – please specify the concentration of the positive control relative to the LoD of your test (note that ideally the positive control concentration should be such that it is close to the LoD of your test) and also specify frequency of use]*

c) An extraction control *[describe control]* is needed to *[describe need]* and is used *[describe use – please also specify frequency of use]*. Please note that if the no template control and positive control, are taken through the entire sample processing procedure, including the extraction, then a separate extraction control is not required.

d) An internal control *[describe control]* is needed to *[describe need]* and is used *[describe use]*.

### INTERPRETATION OF RESULTS
All test controls must be examined prior to interpretation of patient results. If the controls are not valid, the patient results cannot be interpreted. Appropriate control interpretation criteria and result interpretation criteria are described here. You must describe if a Ct cutoff is used as part of your testing algorithm and/or if the end user is required to review curves before final result interpretation. Although not typical for molecular-based tests, if the test result involves the use of an algorithm/calculation, for example a ratio value, when determining the final patient test result, include a detailed description and any additional calibration materials that may be required.

1. **Examination and Interpretation of Control Results**

   *[Describe in detail the expected results generated, including acceptance criteria, for all the controls used in test. Describe the measured values (if applicable) for valid and invalid controls and outline the actions to take in the event of an invalid control result.]*

2. **Examination and Interpretation of Patient Specimen Results**

   Assessment of clinical specimen test results must be performed after the controls have been examined and determined to be valid and acceptable. If the controls are not valid, the patient results cannot be interpreted.

   *[Describe when clinical specimen test results should be assessed and outline the criteria for test validity. Clearly indicate how to interpret numeric test values (if applicable) as positive or negative for presence of SARS-CoV-2. Indicate if the end user is required to review curves before final result interpretation and, if applicable, how to identify indeterminate/inconclusive/equivocal results. When applicable, we recommend providing a table clearly describing the possible combinations of test result values for each primer/probe set. Describe how they should be combined into a final interpretation of the result for your test. If the test produces an equivocal or indeterminate result, please indicate what follow-up testing/process should be conducted, if applicable.]*

   *[If your test is indicated for pooling, also include a pooling results interpretation table, indicating how to interpret each possible result, including when samples should be retested individually.]*

### PERFORMANCE EVALUATION
1) **Limit of Detection (LoD) - Analytical Sensitivity:**

   The LoD for *[test name]* was evaluated and verified using *[validation material, e.g., SARS-CoV-2 inactivated virus (e.g., heat treated or irradiated)]* per the validation required by Appendix A of the Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing. Nucleic acid was extracted from the swabs using *[specify nucleic acid extraction]* and the reverse transcription RT-PCR was performed using the *[specify RT-PCR Instrument and, if applicable, interpretive software version]*. Preliminary and Confirmation LoD results are included in the tables below.

   | Virus Concentration | Target 1 Ct Value | Target 2 Ct Value | Internal Control Ct Value | # of Replicates |
   |---------------------|-------------------|-------------------|---------------------------|-----------------|
   |                     |                   |                   |                           |                 |
   ||

   | Targets             | Target 1 | Target 2 |
   |---------------------|----------|----------|
   | Analyte Concentration |          |          |
   | Positives/Total       |          |          |
   | % Detected            |          |          |
   | Mean Ct               |          |          |
   | Mean SD               |          |          |
   | CV                    |          |          |
   ||

   The data confirmed the assay analytical sensitivity is *[specify LoD represented as genome copies or equivalents/mL]*.

2) **Inclusivity (Analytical Reactivity):**

   An alignment was performed with the oligonucleotide primer and probe sequences of the *[test name]* with *[number of sequences]* publicly available SARS-CoV-2 sequences (including mutation variants of high prevalence, i.e., B.1.617.2 and sub-lineages at the time of issuance of this letter) from *[specify sequence data base, e.g., GISAID]* to demonstrate the predicted inclusivity of the assay.

   *[Insert summary of results of inclusivity analysis.]*

3) **Cross-reactivity (Analytical Specificity):**

   Analytical specificity of the primer/probe combination for *[test name]* was evaluated by conducting sequence alignment of the primer/probe sequences of the test with publicly available genome sequences for potential cross-reacting microorganisms. The following organisms were tested with *[test name]* primer probe set.

   | Organism | Strain | Target 1 | Target 2 |
   |----------|--------|----------|----------|
   |          |        |          |          |
||

4) **Clinical Evaluation:**

   Clinical evaluation of the *[test name]* was conducted with 30 individual natural positive and 30 negative anterior nasal swab clinical specimens collected from patients suspected of SARS-CoV-2 infection by a healthcare provider in COVID-19 disease endemic region(s). These specimens were *[prospective, retrospective, or leftover samples]*. Nucleic acid was extracted from the swabs using *[specify nucleic acid extraction]* and the reverse transcription RT-PCR was performed using the *[specify RT-PCR Instrument and, if applicable, interpretive software version]*.

   Data is summarized in the Table below:

**Table: Summary Performance on individual anterior nasal swab specimens in comparison to an FDA-authorized method for specimens collected from individuals suspected of COVID-19 by a healthcare provider**

| [Test Name] | FDA EUA RT-PCR Assay | Total | % Performance Agreement | 95% CI |
|-------------|----------------------|-------|-------------------------|--------|
|             | Detected             | Not Detected |       |                         |        |
| Detected    | A                    | B            | A+B   | PPA= 100% x A/(A+C)    |        |
| Not Detected| C                    | D            | C+D   | NPA= 100% x D/(B+D)    |        |
| Total       | A+C                  | B+D          |       |                         |        |
||

[IF VALIDATION WAS ALSO COMPLETED WITH SPECIMENS COLLECTED FROM INDIVIDUALS WITHOUT SYMPTOMS OR OTHER REASONS TO SUSPECT COVID-19, ALSO INCLUDE THOSE RESULTS:] Clinical evaluation of the [test name] was conducted with 20 positive and 100 negative specimens collected from individuals without symptoms or other reasons to suspect COVID-19 in COVID-19 disease endemic region(s). These specimens were [prospective, retrospective, or leftover samples]. Nucleic acid was extracted from the swabs using [specify nucleic acid extraction] and the reverse transcription RT-PCR was performed using the [specify RT-PCR Instrument and, if applicable, interpretive software version].

Data is summarized in the Table below:

**Table: Summary Performance on individual anterior nasal swab specimens in comparison to an FDA-authorized method for specimens collected from individuals without symptoms or other reasons to suspect COVID-19**

| [Test Name] | FDA EUA RT-PCR Assay | Total | % Performance Agreement | 95% CI |
|-------------|----------------------|-------|-------------------------|--------|
|             | Detected             | Not Detected |       |                         |        |
| Detected    | A                    | B            | A+B   | PPA= 100% x A/(A+C)    |        |
| Not Detected| C                    | D            | C+D   | NPA= 100% x D/(B+D)    |        |
| Total       | A+C                  | B+D          |       |                         |        |
||

5) **Additional Validation for [indication provided by appendix(ces) B -K, e.g., Media Pooling up to n=10 with validation option 2]**

[For each additional indication, include a section with the required validation and documentation from the applicable appendix.]

### LIMITATIONS
- The performance of this test was established based on the evaluation of a limited number of clinical specimens collected between [include collection window dates between MONTH, YEAR AND MONTH, YEAR and the location(s) of clinical evaluation (Country(ies)– identify if it was multiple sites in the country or limited locations – if known)]. The clinical performance of this test has not been established in all circulating variants but is anticipated to be reflective of the variants in circulation at the time and location(s) of the clinical evaluation. As such, performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2, and their prevalence, which change over time.

- [IF EVALUATION OF SPECIMENS COLLECTED FROM INDIVIDUALS WITHOUT SYMPTOMS OR OTHER REASONS TO SUSPECT COVID-19 HAVE NOT YET BEEN EVALUATED, INCLUDE THIS STATEMENT:] Clinical performance has been established in specimens collected from subjects suspected of COVID-19 by a healthcare provider. Performance of specimens collected from individuals without symptoms or other reasons to suspect COVID-19 has not been established. A study to determine the performance in individuals without symptoms or other reasons to suspect COVID-19 will be completed.

### WARNINGS:
- This product has not been FDA cleared or approved, but has been authorized by FDA under an Emergency Use Authorization (EUA) for use by the laboratory that developed the test and which is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform high complexity tests.

- This product has been authorized only for the detection of nucleic acid from SARS-CoV-2, not for any other viruses or pathogens; and

- The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.

---

^1^ U.S. Department of Health and Human Services, *Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3*. 85 FR 7316 (February 7, 2020)
^2^ Many laboratories have been providing SARS-CoV-2 testing with tests that are not FDA authorized for emergency use, including as discussed in FDA policies in place earlier in the public health emergency. This authorization is intended to provide an efficient mechanism by which some of these tests can become authorized.
^3^ For ease of reference, this letter uses the phrase “authorized tests” to refer to molecular-based tests that are developed and used by the single laboratory, that is certified under CLIA and meets requirements to perform high complexity tests, that developed the test and that are within the Scope of Authorization (Section II).
^4^ CDRH IVD EUA webpage [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas)
^5^ No other criteria of issuance have been prescribed by regulation under Section 564(c)(4) of the Act.
^6^ The indications for use for tests authorized by this EUA are limited to anterior nasal swab specimens in dry tubes or tubes containing viral transport media (VTM), saline, or phosphate-buffered saline (PBS) and do not include any indications for other specimen types, such as saliva. The indications for use for tests authorized by this EUA also do not include specimens in tubes containing inactivating transport media (ITM), such as those containing guanidine thiocyanate or similar chemicals.
^8^ Other modifications, including new claimed specimen types or test settings (e.g., point-of-care, home testing), or any other modifications that change the indication for use, are not authorized under this EUA and must be authorized under an individual EUA prior to use.
^9^ Traceability refers to tracing analytical sensitivity/reactivity back to an FDA-recommended reference material.
^10^ The Centers for Disease Control and Prevention (CDC) has granted a right of reference to the performance data contained in the CDC’s EUA request for the [CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel (CDC)](https://www.cdc.gov/coronavirus/2019-ncov/lab/testing.html) (FDA submission number EUA200001) to any entity seeking authorization for a COVID-19 diagnostic device. The CDC has also granted a right of reference to the performance data contained in the CDC’s EUA request for their [Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay](https://www.cdc.gov/coronavirus/2019-ncov/lab/testing.html) (FDA submission number EUA201781) to any entity seeking authorization for a multi-analyte respiratory panel that includes SARS-CoV-2. CDC has published the primer and probe sequences for the Influenza SARS-CoV-2 Multiplex Assay on the [CDC website](https://www.cdc.gov/coronavirus/2019-ncov/lab/testing.html).
^11^ Available at: [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-evaluating-impact-viral-mutations-covid-19-tests](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-evaluating-impact-viral-mutations-covid-19-tests).
^12^ For additional information on the estimated proportions of SARS-CoV-2 lineages, see: [https://covid.cdc.gov/covid-data-tracker/#variant-proportions](https://covid.cdc.gov/covid-data-tracker/#variant-proportions).


# 3,586  2021-11-15_FDA Letter - Laboratories Who Have Developed a Molecular-Based Test.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Letter - Laboratories Who Have Developed a Molecular-Based Test.md
file_date: 2021-11-15
title: FDA Letter - Laboratories Who Have Developed a Molecular-Based Test
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: pdf
xfile_type: NA
gfile_url: NA
xfile_github_download_url: NA
pdf_gdrive_url: https://drive.google.com/file/d/1NzCFlg7IGG9P2x4JmM0y0GmxeRQ9V_ZP
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2021-11-15_FDA%20Letter%20-%20Laboratories%20Who%20Have%20Developed%20a%20Molecular-Based%20Test.pdf
conversion_input_file_type: pdf
conversion: megaparse-v
license: Public Domain
tokens: 3586
words: 2599
notes: 
summary_short: The FDA “Laboratories Who Have Developed a Molecular-Based Test” letter (Nov 15, 2021) reissues and narrows an EUA for certain molecular laboratory-developed tests listed in Appendix A, authorizing them only for qualitative SARS-CoV-2 detection in respiratory specimens from individuals suspected of COVID-19 by a healthcare provider. It explains that no additional tests will be added under this EUA and updates conditions and fact sheets to reflect the current phase of the pandemic and FDA’s shift toward separate serial screening/pooling pathways. It also sets enforceable conditions for authorized single-lab use (CLIA high complexity), reporting, labeling, adverse event tracking, and ongoing evaluation of viral mutation impacts.


CONTENT

November 15, 2021

To:  
Laboratories with tests listed in Appendix A.

Authorized Tests:  
Tests listed in Appendix A.^1^

Indication:  
Qualitative detection of nucleic acid from SARS-CoV-2 in respiratory specimens collected from individuals suspected of COVID-19^2^ by their healthcare provider. Use of the test is limited to the authorized laboratory.

Authorized Laboratories:  
Testing is limited to the single laboratory that developed the authorized test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform tests of high complexity. The authorized laboratory for each authorized test is listed in Appendix A.

On February 4, 2020, pursuant to Section 564(b)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act), the Secretary of the Department of Health and Human Services (HHS) determined that there is a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad, and that involves the virus that causes COVID-19. Pursuant to Section 564 of the Act, and on the basis of such determination, the Secretary of HHS then declared that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the virus that causes COVID-19 subject to the terms of any authorization issued under Section 564(a) of the Act.^3^

On March 31, 2020, in response to this evolving public health emergency and continued concerns about the availability of sufficient in vitro diagnostic tests, FDA issued this EUA for certain molecular-based laboratory developed tests (LDTs) for use by the single developing laboratory (as described in the Scope of Authorization (Section II)) under Section 564 of the Act (21 U.S.C. § 360bbb-3). Under this EUA, authorized tests are authorized for use only in the single laboratory that developed the authorized test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets the requirements to perform tests of high complexity.

FDA has continued to periodically review the circumstances and the appropriateness of authorizing the emergency use of tests under this EUA as required by Section 564(g)(1) of the Act since it was issued on March 31, 2020. Based on this review and all available information, FDA has concluded that the criteria for issuance under Section 564(c) of the Act are met with respect to the authorized tests and has also determined that it is no longer appropriate to include any additional authorized tests under this EUA. As described below, FDA’s decision to reissue this EUA pursuant to Section 564(c) of the Act is based in part on the changing circumstances of this pandemic. This includes a significant shift towards tests that can be used with pooled specimens that are collected as part of a serial testing program for screening. Such tests are outside the scope of this EUA. Given this, FDA is reissuing this EUA such that only tests that are listed in Appendix A are authorized for use as described in Section II of this letter when used consistent with the Conditions of Authorization (Section IV). FDA has updated the Conditions of Authorization and also updated the fact sheets to reflect the most up-to-date information as part of this reissuance.

FDA may authorize additional tests, as appropriate, either in individual EUAs or under a new umbrella EUA. At this stage of the pandemic, FDA intends to focus its review on the types of tests needed to meet the current public health needs, including tests intended for use as part of serial screening testing programs. Serial screening testing programs are expected to be a cornerstone of the current phase of the country’s pandemic response as many schools, workplaces, communities, and other entities are setting up testing programs to rapidly screen for COVID-19, and FDA is providing streamlined approaches for authorization of tests intended for use in these programs. FDA will review individual EUA requests for tests based on a number of factors and may issue an EUA when the statutory criteria for issuance are met.

Having concluded that the criteria for issuance under Section 564(c) of the Act are met with respect to the tests listed in Appendix A of this letter, I am authorizing the emergency use of the tests listed in Appendix A as described in the Scope of Authorization (Section II) and pursuant to the Conditions of Authorization (Section IV) to detect SARS-CoV-2 in respiratory specimens from individuals suspected of COVID-19 by their healthcare provider for use in the single laboratory that developed the authorized test and that is certified under the CLIA, 42 U.S.C. § 263a, and meets the requirements to perform tests of high complexity.

## I. Criteria for Issuance of Authorization
I have concluded that the emergency use of the authorized tests listed in Appendix A of this reissued letter of authorization meet the criteria for issuance of an authorization under Section 564(c) of the Act, because I have concluded that:

1. The SARS-CoV-2 can cause a serious or life-threatening disease or condition, including severe respiratory illness, to humans infected by this virus;

2. Based on the totality of scientific evidence available to FDA, it is reasonable to believe that the authorized tests may be effective in diagnosing COVID-19, and that the known and potential benefits of the authorized tests when used for diagnosing COVID-19, outweigh the known and potential risks of the authorized tests; and

3. There is no adequate, approved, and available alternative to the emergency use of the authorized tests.^4^

## II. Scope of Authorization
I have concluded, pursuant to Section 564(d)(1) of the Act, that the scope of this authorization is limited to the authorized tests listed in Appendix A for the indication above.

Authorized Tests

Tests listed in Appendix A, when labeled consistent with the authorized test procedures and as described in the authorized test’s EUA summary (available at [FDA EUA Summary](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2)), are authorized to be used by the single laboratory that developed the authorized test, despite the fact that they do not meet certain requirements otherwise required by applicable federal law.

Authorized tests must be accompanied by the following product information pertaining to their emergency use, which is required to be made available to healthcare providers and patients:

- Fact Sheet for Healthcare Providers: Molecular LDT COVID-19 Authorized Test
- Fact Sheet for Patients: Molecular LDT COVID-19 Authorized Test

These facts sheets, the authorized test procedures, and the authorized test’s EUA summary are collectively referred to below as the “authorized labeling” for each authorized test.

I have concluded, pursuant to Section 564(d)(2) of the Act, that it is reasonable to believe that the known and potential benefits of the authorized tests outweigh the known and potential risks of such authorized tests.

I have concluded, pursuant to Section 564(d)(3) of the Act, based on the totality of scientific evidence available to FDA, that it is reasonable to believe that the authorized tests listed in Appendix A may be effective for the indication above, when used consistently with the Scope of Authorization of this letter (Section II), pursuant to Section 564(c)(2)(A) of the Act.

FDA has reviewed the scientific information available to FDA, including the information supporting the conclusions described in Section I above, and concludes that the authorized tests (as described in the Scope of Authorization of this letter (Section II)) meet the criteria set forth in Section 564(c) of the Act concerning safety and potential effectiveness.

The emergency use of the authorized tests under this EUA must be consistent with, and may not exceed the terms of this letter, including the Scope of Authorization (Section II) and the Conditions of Authorization (Section IV).

Conditions of Authorization (Section IV). Subject to the terms of this EUA and under the circumstances set forth in the Secretary of HHS's determination under Section 564(b)(1)(C) of the Act described above and the Secretary of HHS’s corresponding declaration under Section 564(b)(1) of the Act, the tests are authorized for the indication above.

This EUA will cease to be effective when the HHS declaration that circumstances exist to justify the EUA is terminated under Section 564(b)(2) of the Act or when the EUA is revoked under Section 564(g) of the Act.

## III. Waiver of Certain Requirements
I am waiving the following requirements for the product during the duration of this EUA:

- Current good manufacturing practice requirements, including the quality system requirements under 21 CFR Part 820 with respect to the design, manufacture, packaging, labeling, storage, and distribution of your product.

## IV. Conditions of Authorization
Pursuant to Section 564(e) of the Act, I am establishing the following conditions on this authorization:

### Authorized Laboratories (You)
A. Your authorized product must comply with the following labeling requirements under FDA regulations: the intended use statement (21 CFR 809.10(a)(2), (b)(2)); adequate directions for use (21 U.S.C. 352(f)), (21 CFR 809.10(b)(5), (7), and (8)); appropriate limitations on the use of the device including information required under 21 CFR 809.10(a)(4); and any available information regarding performance of the product, including requirements under 21 CFR 809.10(b)(12).

B. You must inform relevant public health authorities of this EUA, including the terms and conditions herein, and any updates made to your authorized product or authorized labeling.

C. You must notify the relevant public health authorities of your intent to run your authorized product.

D. You must have a process in place for reporting test results to healthcare providers and relevant public health authorities, as appropriate.

E. You must include with test results, all authorized Fact Sheets. Under exigent circumstances, other appropriate methods for disseminating these Fact Sheets may be used, which may include mass media.

F. You must make available on your website(s), if applicable, the Fact Sheet for Healthcare Providers and the Fact Sheet for Patients.

G. You are authorized to make available additional information relating to the emergency use of your authorized product that is consistent with, and does not exceed, the terms of this letter of authorization.

H. You must use your authorized product as outlined in the authorized test procedures. Deviations from the authorized test procedures, including the authorized instruments, authorized extraction methods, authorized clinical specimen types, authorized control materials, authorized other ancillary reagents and/or authorized materials required to use your product are not permitted.

I. You must collect information on the performance of your authorized product. You must report to DMD/OHT7-OIR/OPEQ/CDRH (via email: [CDRH-EUA-Reporting@fda.hhs.gov](mailto:CDRH-EUA-Reporting@fda.hhs.gov)) any suspected occurrence of false positive or false negative results and significant deviations from the established performance characteristics of your authorized product of which you become aware.

J. You may request changes to the authorized labeling. Any request for changes to the authorized labeling must be submitted to the Division of Microbiology (DMD)/Office of Health Technology 7 (OHT7)-Office of In Vitro Diagnostics and Radiological Health (OIR)/Office of Product Evaluation and Quality (OPEQ)/Center for Devices and Radiological Health (CDRH) and require appropriate authorization from FDA prior to implementation.

K. You must evaluate the analytical limit of detection and assess traceability of your authorized product with any FDA-recommended reference material(s), if requested by FDA. After submission to FDA and DMD/OHT7-OIR/CDRH’s review and concurrence with the data, FDA will update the EUA summary to reflect the additional testing. Such updates will be made in consultation with, and require concurrence of, DMD/OHT7-OIR/OPEQ/CDRH.

L. You must track adverse events, including any occurrence of false results with your authorized product and report any such events to FDA pursuant to 21 CFR Part 803.

M. All laboratory personnel using your authorized product must be appropriately trained in molecular techniques and use appropriate laboratory and personal protective equipment when handling this product, and use your authorized product in accordance with the authorized test procedure.

N. You must ensure that any records associated with this EUA are maintained until otherwise notified by FDA. Such records will be made available to FDA for inspection upon request.

O. You must evaluate the impact of SARS-CoV-2 viral mutations on your product’s performance. Such evaluations must occur on an ongoing basis and must include any additional data analysis that is requested by FDA in response to any performance concerns you or FDA identify during routine evaluation. Additionally, if requested by FDA, you must submit records of these evaluations for FDA review within 48 hours of the request. If your evaluation identifies viral mutations that affect the stated expected performance of your product, you must notify FDA immediately via email to [CDRH-EUA-Reporting@fda.hhs.gov](mailto:CDRH-EUA-Reporting@fda.hhs.gov).

P. If requested by FDA, you must update your labeling within 7 calendar days to include any additional labeling risk mitigations identified by FDA regarding the impact of viral mutations on test performance. Such updates will be made in consultation with, and require concurrence of, DMD/OHT7-OIR/OPEQ/CDRH.

### Conditions Related to Printed Materials, Advertising and Promotion
Q. All descriptive printed matter, advertising, and promotional materials, relating to the use of your authorized product shall be consistent with the authorized labeling, as well as the terms set forth in this EUA, and meet the requirements set forth in section 502(q)(1) and (r) of the Act, as applicable, and FDA implementing regulations.

R. No descriptive printed matter, advertising, or promotional materials relating to the use of your authorized product may represent or suggest that such test is safe or effective when used for detection SARS-CoV-2.

S. All descriptive printed matter, advertising, and promotional material relating to the use of your authorized product shall clearly and conspicuously state that:

- This product has not been FDA cleared or approved by FDA, but has been authorized by FDA under an EUA for use by authorized laboratories;

- This product has been authorized only for the detection of nucleic acid from SARS-CoV-2, not for any other viruses or pathogens; and

- The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or the authorization is revoked sooner.

The emergency use of your product as described in this letter of authorization must comply with the conditions and all other terms of this authorization.

## V. Duration of Authorization
This EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 is terminated under Section 564(b)(2) of the Act or the EUA is revoked under Section 564(g) of the Act.

Sincerely,


Jacqueline A. O’Shaughnessy, Ph.D.  
Acting Chief Scientist  
Food and Drug Administration

Enclosure

---

^1^ For ease of reference, this letter will refer to the tests listed in Appendix A as the “authorized tests.” Appendix A is included on the FDA website at: [FDA EUA](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2)
^2^ On February 11, 2020, the virus tentatively named 2019-nCoV was formally designated as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Also on February 11, 2020, the disease caused by SARS-CoV-2 was formally designated as Coronavirus Disease 2019 (COVID-19). This document uses the updated names.
^3^ U.S. Department of Health and Human Services, _Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act_, 21 U.S.C. § 360bbb-3, 85 FR 716 (February 7, 2020).
^4^ No other criteria of issuance have been prescribed by regulation under Section 564(c)(4) of the Act.
^5^ Traceability refers to tracing analytical sensitivity/reactivity back to an FDA-recommended reference material. FDA may request, for example, that you perform this study in the event that we receive reports of adverse events concerning your authorized test.


# 507  2021-11-15_FDA Website - Umbrella EUA.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2021-11-15_FDA Website - Umbrella EUA.md
file_date: 2021-11-15
title: FDA Website - Umbrella EUA
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: website
xfile_type: NA
gfile_url: NA
xfile_github_download_url: NA
pdf_gdrive_url: NA
pdf_github_url: NA
conversion_input_file_type: docx
conversion: manual cut and paste
license: Public Domain
tokens: 507
words: 352
notes: date converted 2024-03-27
web_url: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2#umbrella-eua
summary_short: The Umbrella EUA describes FDA’s November 15, 2021 authorization for certain laboratory-developed RT-PCR SARS-CoV-2 tests using anterior nasal specimens for serial testing programs, including optional pooled testing and screening of asymptomatic individuals at least weekly. It specifies eligibility criteria, pooling parameters that vary by appendix (pool sizes up to 10, media vs. swab pooling, and possible home collection), and limits use to the single CLIA-certified high-complexity laboratory that developed the test. It also explains the notification/self-certification process for being added to Exhibit 1 and notes that listing does not necessarily mean FDA reviewed the underlying validation data.


CONTENT

On November 15, 2021, the FDA issued an umbrella EUA for certain RT-PCR molecular-based tests, developed by laboratories, for detection of nucleic acid from SARS-CoV-2 from anterior nasal respiratory specimens for use as part of a serial testing program, that meet certain criteria for eligibility specified in the EUA. Under this EUA, authorized tests can be used with individual or pooled anterior nasal specimens for testing individuals, including individuals without symptoms or other epidemiological reasons to suspect COVID-19, when tested at least once per week. This means that tests authorized by this EUA may be used with individual or pooled anterior nasal respiratory specimens from individuals with or without known or suspected exposure to COVID-19 when such individuals are tested at least once per week, such as testing at regular intervals as part of a testing program implemented by schools, workplaces, or community groups. The indications in each appendix (A-K) differ in the number of specimens that can be pooled (1, up to 3, up to 5, or up to 10), the type of pooling that can be done (media pooling or swab pooling), and whether the test can be used with home collected specimens.

Use of tests authorized by this EUA is limited to use in the single laboratory that developed the authorized test and that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, and meets requirements to perform high complexity tests. 

Tests will be added to Exhibit 1 of this EUA following submission of a complete notification to the FDA with the information required by the EUA, including self-certifying that the applicable validation has been completed, and confirmation by the FDA that the required documentation has been submitted. Being added to Exhibit 1 does not necessarily mean that the FDA has reviewed the underlying validation data submitted or confirmed that the test is appropriately validated.

[EUA Letter of Authorization - Umbrella EUA for SARS-CoV-2 Molecular Diagnostic Tests for Serial Testing](https://www.fda.gov/media/154111/download?attachment)
[Appendix L - Fact Sheet for Health Care Providers (Template)](https://www.fda.gov/media/154112/download?attachment)
[Appendix M - Fact Sheet for Patients (Template)](https://www.fda.gov/media/154114/download?attachment)
[Appendix N - Test Summary (Template)](https://www.fda.gov/media/154113/download?attachment)


# 8,418  2022-09-27_FDA Guidance - COVID IVD Test Developers v6.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2022-09-27_FDA Guidance - COVID IVD Test Developers v6.md
file_date: 2022-09-27
title: FDA Guidance - COVID IVD Test Developers v6
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: pdf
xfile_type: NA
gfile_url: NA
xfile_github_download_url: NA
pdf_gdrive_url: https://drive.google.com/file/d/1E0cRvVwMURRjdzvBD_95HOaD5hLkPLAM
pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2022-09-27_FDA%20Guidance%20-%20COVID%20IVD%20Test%20Developers%20v6.pdf
conversion_input_file_type: pdf
conversion: megaparse-v
license: Public Domain
tokens: 8418
words: 5857
notes: 
summary_short: The FDA “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)” (v6, Sept 27, 2022) updates FDA’s review priorities and enforcement policies for COVID-19 diagnostic and serology IVDs, superseding the November 15, 2021 version. It narrows EUA review to a smaller set of tests and supplemental requests from experienced developers that address unmet needs (e.g., variants or innovative technologies), while encouraging most developers to pursue traditional premarket pathways. It also clarifies ongoing policies for tests previously offered during FDA review, state-authorized single-lab testing, permitted modifications to authorized molecular tests, and baseline expectations for validation and reporting.


CONTENT

***INTERNAL TITLE:*** Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)*
Guidance for Developers and Food and Drug Administration Staff

Document issued on the web on September 27, 2022.

This document supersedes “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised): Guidance for Developers and Food and Drug Administration Staff” issued November 15, 2021.

_U.S. Department of Health and Human Services_  
_Food and Drug Administration_  
_Center for Devices and Radiological Health_

*This is the sixth edition of this guidance, which originally issued February 29, 2020, and was subsequently revised on March 16, May 4, May 11, 2020, and November 15, 2021.*


## Preface
### Public Comment
This guidance is being issued to address the Coronavirus Disease 2019 (COVID-19) public health emergency. This guidance is being implemented without prior public comment because the Food and Drug Administration (FDA or Agency) has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices.

Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to [https://www.regulations.gov](https://www.regulations.gov). All comments should be identified with the docket number FDA-2020-D-0987 and complete title of the guidance in the request.

### Additional Copies
Additional copies are available from the FDA webpage titled “COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders,” available at [https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders](https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders), and the FDA webpage titled “Search for FDA Guidance Documents,” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents](https://www.fda.gov/regulatory-information/search-fda-guidance-documents). You may also send an e-mail request to [CDRH-Guidance@fda.hhs.gov](mailto:CDRH-Guidance@fda.hhs.gov) to receive an additional copy of the guidance. Please include the document number 20010-R5 and complete title of the guidance in the request.

### Questions
For questions about this document, contact [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov).


## Table of Contents
I. Introduction .......................................................................................................................... 4  
II. Background .......................................................................................................................... 5  
III. Scope ................................................................................................................................. 6  
IV. Policy ................................................................................................................................. 7  
   A. Review of EUA Requests for COVID-19 Tests ................................................................. 7  
   B. State Authorization of High-Complexity CLIA-Certified Laboratories ............................ 8  
   C. Distribution and Offering of SARS-CoV-2 Diagnostic and Serology Tests During FDA Review ................................................................................................................................. 10  
   (1) FDA Review of EUA Requests ........................................................................................ 10  
   (2) Recommendations Regarding Test Reports and Other Information for Tests Offered During FDA Review of EUA Requests .......................................................................... 11  
   D. Modifications to EUA-Authorized Diagnostic COVID-19 Tests ....................................... 11  
   (1) Modifications Made After Issuance of this Updated Guidance .................................... 12  
   (2) Certain Modifications Made Before Issuance of this Updated Guidance .................... 12  
V. Validation .......................................................................................................................... 14  
VI. Availability of EUA Templates and Inquiries Regarding Validation ............................ 15  

## I. Introduction
FDA plays a critical role in protecting the United States from threats such as emerging infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support response efforts to this pandemic.

FDA is issuing this guidance to provide FDA’s review priorities and enforcement policies regarding novel coronavirus (COVID-19) tests for the duration of the public health emergency. Rapid detection of COVID-19 cases in the United States requires wide availability of testing to control the spread of this highly contagious infection. This document supersedes “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised): Guidance for Developers and Food and Drug Administration Staff” issued November 15, 2021.

The policies in this guidance are intended to remain in effect only for the duration of the public health emergency related to COVID-19 declared by the Secretary of Health and Human Services (HHS) on January 31, 2020, effective January 27, 2020, including any renewals made by the HHS Secretary in accordance with section 319(a)(2) of the Public Health Service Act (PHS Act). FDA continues to assess the evolving situation and intends to update this guidance as appropriate.

Given this public health emergency, and as discussed in the Notice in the _Federal Register_ of March 25, 2020, titled “Process for Making Available Guidance Documents Related to Coronavirus Disease 2019,” available at [https://www.govinfo.gov/content/pkg/FR-2020-03-25/pdf/2020-06222.pdf](https://www.govinfo.gov/content/pkg/FR-2020-03-25/pdf/2020-06222.pdf), this guidance is being implemented without prior public comment because FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word _should_ in Agency guidance means that something is suggested or recommended, but not required.

## II. Background
There is currently a pandemic of respiratory disease caused by a novel coronavirus. The virus has been named “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) and the disease it causes has been named “Coronavirus Disease 2019” (COVID-19). On January 31, 2020, HHS issued a declaration of a public health emergency related to COVID-19 and mobilized the Operating Divisions of HHS. [^1] In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19. [^2]

Under section 564 of the FD&C Act, the FDA Commissioner may authorize the use of unapproved medical products, or unapproved uses of approved medical products, in certain emergency circumstances, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use, to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by chemical, biological, radiological, and nuclear (CBRN) agents when certain criteria are met. The Emergency Use Authorization (EUA) authorities allow FDA to help strengthen the nation’s public health protections against CBRN threats by facilitating the availability and use of medical countermeasures needed during certain public health emergencies.

As of August 15, 2022, FDA has issued EUAs for more than 439 tests for COVID-19, including more than 354 diagnostic and 85 serology or other immune response tests. Further, two molecular diagnostic COVID-19 tests have been granted marketing authorization through the traditional device premarket review pathways. In the context of a public health emergency involving pandemic infectious disease, it is critically important that tests are validated because false results not only can negatively impact the individual patient but also can have a broad public health impact. False positive results for diagnostic tests, for example, can lead to unnecessary quarantine and potential further spread when presumed positive individuals are quarantined together, wasted contact tracing and testing resources, and delay in accurate diagnosis and appropriate treatment for the individual. False negative results can lead to lack of appropriate treatment for the individual and further spread of the disease.

Previous versions of this guidance described policies regarding the distribution and offering of certain tests for clinical use prior to or without an EUA. These policies were issued to help quickly increase availability of tests in the early stages of the pandemic. Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under the Clinical Laboratory Improvement Amendments (CLIA), section 353 of the Public Health Service Act (42 USC 263a), use of that test is limited to laboratories that are certified under CLIA, and meet the requirements to perform tests of high complexity, and at the point-of-care (POC) when covered by such a laboratory’s CLIA certificate. Throughout this guidance, references to “high-complexity CLIA-certified laboratories” are referring to laboratories that are certified under CLIA and meet the requirements to perform tests of high complexity. These policies did not apply to at-home tests or tests with home specimen collection.

FDA has updated these policies when appropriate in response to the changing landscape of this pandemic. The previous update on November 15, 2021, explained FDA’s intent to review EUA requests for certain types of tests that FDA believed would be most beneficial at that stage of the pandemic. In addition, in the November 15, 2021, version, FDA revised the previous enforcement policies to reflect that, at that stage of the pandemic, the Agency generally expected COVID-19 tests to have been issued an EUA prior to the tests being distributed or offered.

FDA has continued to closely monitor the COVID-19 testing landscape and believes it is again appropriate to update its policies to reflect the current needs of the pandemic. As explained throughout this updated guidance, FDA intends to review the EUA requests for a smaller subset of tests based on the review priorities described in section IV.A. Traditional marketing pathways remain available to all developers and FDA encourages developers of tests that fall outside the scope of the priorities outlined in this updated guidance to pursue those routes. In sum, FDA has revised this guidance to update the types of COVID-19 tests for which the Agency intends to review EUA requests, to discuss the use of the traditional premarket review pathways for other types of COVID-19 tests for which the Agency does not intend to review EUA requests, and to make minor updates to the enforcement policies.

## III. Scope
This guidance applies to diagnostic and serology tests for COVID-19. [^3] The policies and recommendations described in this guidance are intended to facilitate availability of tests for COVID-19 that FDA believes will be most beneficial at the current stage of the public health emergency.

FDA notes that the enforcement policies in this guidance do not address medical device reporting (MDR) under 21 CFR Part 803 for tests offered prior to authorization as described in the guidance. Developers offering such tests are expected to comply with applicable MDR requirements, including reporting of medical device events that reasonably suggest that their device may have caused or contributed to a death or serious injury, and malfunctions that would be likely to cause or contribute to a death or serious injury if they were to recur. Moreover, unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to high-complexity CLIA-certified laboratories, including testing at the point-of-care when the site is covered by the laboratory’s CLIA certificate for high complexity testing.

## IV. Policy
### A. Review of EUA Requests for COVID-19 Tests
The issuance of an EUA is discretionary. FDA’s decision to review and process an EUA request, and ultimately issue an EUA if the relevant statutory criteria are met, is based on a determination, on a case-by-case basis, that such action is necessary to protect the public health in an emergency. It is an authorization that the government “may” issue when necessary to protect the public health in an emergency (see section 564(a)(1) of the FD&C Act (21 U.S.C. 360bbb-3(a)(1)), which states, in relevant part, “subject to the provisions of this section, the Secretary may authorize the introduction into interstate commerce…a drug, device, or biological product intended for use in an actual or potential emergency”). FDA’s January 2017 guidance, *Emergency Use Authorization of Medical Products and Related Authorities*, describes factors that FDA intends to use in its prioritization of EUA requests, such as the public health need for the product, the availability of the product, the availability and adequacy of the information concerning the likelihood that the product may be safe and effective in preventing, treating, or diagnosing the condition, and whether the product is included in government stakeholder stockpiles.

Given the need to address urgent public health priorities, FDA has and continues to prioritize reviewing the EUA requests it receives for COVID-19 tests.

At this stage of the pandemic, FDA intends to prioritize its review of EUA requests and supplemental EUA requests from experienced developers for diagnostic tests that are likely to have a significant public health benefit (e.g., employ innovative technology) or are likely to fulfill an unmet need (e.g., diagnosing infection with a new variant or subvariant).

FDA generally intends to focus its review on EUA requests and supplemental EUA requests for tests that are within these priorities. In addition to the above priorities, FDA also intends to focus its review on EUA requests that are from or supported by a U.S. government stakeholder, such as tests funded by the Biomedical Advanced Research and Development Authority (BARDA) or the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx). FDA intends to notify test developers of its intent by email if FDA declines to review or otherwise decides not to authorize a test/modification in an EUA request or supplemental EUA request.

In general, FDA believes these priorities are appropriate to address the public health needs at the current stage of the public health emergency based on the available information and may adjust these priorities as public health needs change. Specifically, there is generally sufficient availability of authorized high-throughput laboratory-based diagnostic tests intended for use with pooled samples and authorized home-use antigen tests that are available for over-the-counter (OTC) or prescription use.

FDA believes that the number of EUA requests that fall within FDA’s current review priorities described in this guidance are likely limited and generally encourages developers to submit COVID-19 tests through traditional premarket review pathways. If you are unsure whether your test may be prioritized for review, we encourage you to reach out to CDRH-EUA-Templates@fda.hhs.gov; however, at this stage, FDA strongly encourages developers of new tests and existing tests for which modifications are sought to pursue traditional pre-market pathways.

### B. State Authorization of High-Complexity CLIA-Certified Laboratories
Versions of this guidance prior to November 15, 2021, described a policy regarding States and territories that authorize laboratories within their State or territory to develop their own COVID-19 tests and perform specimen testing, where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA.

Under such policy, a State or territory choosing to authorize laboratories within that State or territory to develop and perform a test for COVID-19 would do so under authority of its own State law, and under a process that it established, and FDA did not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation was not submitted to FDA and the laboratory did not submit an EUA request to FDA, and where instead the State or territory took responsibility for COVID-19 testing by laboratories in its State during the COVID-19 outbreak. This policy applied only to tests designed, developed, and used within a single, high-complexity, CLIA-certified laboratory. The policy did not apply to at-home tests or tests with home specimen collection, or any testing outside of a high-complexity CLIA-certified laboratory.

In versions of this guidance prior to November 15, 2021, FDA requested that the State or territory notify us if it chose to use this flexibility to expedite COVID-19 testing. FDA indicated that it would not be reviewing the process adopted by the State or territory. FDA expected that such States and territories as part of their oversight process would require laboratories developing SARS-CoV-2 tests to validate those tests prior to use. FDA encouraged laboratories that developed and performed a test for COVID-19 that was authorized by a State or territory to notify FDA that they have started clinical testing by sending an email to that effect to CDRH-EUA-Templates@fda.hhs.gov, and provide information on testing capacity.

In the November 15, 2021, version of this guidance, FDA revised this policy such that FDA no longer intended to apply the policy to additional States or territories going forward. The FDA is maintaining the policy in Section IV.B. of the November 15, 2021, policy, without further revision. For the States and territories listed on the notification list on FDA’s website prior to November 15, 2021, that are continuing to authorize laboratories within their State or territory to develop and perform a test for COVID-19, FDA does not intend to object to the use of such tests for specimen testing where notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA and the State or territory takes responsibility. This policy applies only to tests designed, developed, and used within a single, high-complexity CLIA-certified laboratory. This policy does not apply to at-home tests or tests with home specimen collection, or any testing outside of a high-complexity CLIA-certified laboratory.

FDA notes that laboratories should be aware of requirements to report test results to appropriate federal, state, and local public health agencies in accordance with applicable federal, state, and local laws.[^12]

### C. Distribution and Offering of SARS-CoV-2 Diagnostic and Serology Tests During FDA Review
Previous versions of this guidance document described enforcement policies where FDA generally did not intend to object to developers distributing and offering certain tests prior to FDA authorization, as described in the policies. Those policies were updated in the November 15, 2021, version of the guidance, and FDA is generally continuing those updated policies and clarifying them, as discussed below.

#### (1) FDA Review of EUA Requests
For the following tests, FDA does not intend to object to the continued distribution or offering of the test while FDA reviews the EUA request for the test:

- Tests on one of the [notification lists](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/notifications-and-emergency-use-authorizations-faqs-testing-sars-cov-2)[^13] on FDA’s website at the time of issuance of this updated guidance; and,
- Laboratory developed tests (LDTs)[^14] offered following the HHS August 2020 Web Statement entitled, “Rescission of Guidances and Other Informal Issuances Concerning Premarket Review of Laboratory Developed Tests” (“August 2020 HHS Announcement”) and prior to November 15, 2021, where an EUA request was submitted to FDA as described in Section IV.C.2 of the November 15, 2021 version of this guidance document.[^15]

For tests described in this section, FDA intends to notify test developers by email if FDA declines to review, declines to issue, or otherwise decides not to authorize the test for any reason, including lack of response or a determination that there is a lack of adequate data to support authorization. If so notified, FDA generally expects developers to cease distributing, marketing, and offering their tests within 15 calendar days. Moreover, if FDA identifies a significant problem or concern with a test, based either on the provided information or external reports, FDA generally would expect the developer to take appropriate steps to address such problems, which could include conducting a recall of the test and/or notification concerning corrected test reports indicating prior test results may not be accurate.

#### (2) Recommendations Regarding Test Reports and Other Information for Tests Offered During FDA Review of EUA Requests
FDA continues to recommend the following:

1. Test reports should prominently disclose that the test has not been reviewed by FDA. Until the test is authorized by FDA, any statements in the test reports and other labeling that expressly state or imply that the test has been authorized by FDA would be false. Similarly, any statements in the test reports and other labeling that state or imply that EUA issuance or FDA authorization are imminent or pending could be misleading.

2. Developers should make publicly available on their website the instructions for use of the test and data about the test’s performance characteristics, including a summary of assay performance.

3. Instructions for use and patient test reports for serology tests should include information that helps users and patients understand the test results, including the following:
   - Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct (i.e., diagnostic) testing for SARS-CoV-2 is necessary.
   - Results from antibody testing should not be used to diagnose or exclude acute SARS-CoV-2 infection.
   - Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

In addition, as noted in previous versions of this guidance and earlier in this updated guidance, unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to high-complexity CLIA-certified laboratories, including testing at the POC when the site is covered by such a laboratory’s CLIA certificate.

### D. Modifications to EUA-Authorized Diagnostic COVID-19 Tests
Throughout the course of the pandemic FDA has issued various policies with respect to modifications and as discussed further below, FDA is updating these policies. The policies in this section do not apply to at-home tests or tests with at-home specimen collection.

In order to provide transparency, when a developer is distributing or offering a test that is a modification of an EUA-authorized diagnostic test prior to or without authorization of the modified test, as discussed in this section, the recommendations in Section IV.C.2 of this updated guidance apply. FDA further recommends that the developer post data about the modified test’s performance characteristics on the developer’s website, and that the instructions for use or test protocol and the test reports accurately reflect the modification and prominently disclose that the test has been modified since authorization by FDA and that the modified test has not been reviewed by FDA.

If FDA identifies a significant problem or concern with a modified test, based either on the provided information or external reports, that cannot be addressed in a timely manner, FDA generally would expect the developer to cease distribution, marketing and offering the modified test and address such problem, which could include conducting a recall of the modified test and/or notification concerning corrected test reports indicating prior test results may not be accurate.

#### (1) Modifications Made After Issuance of this Updated Guidance
In addition to the priorities above, FDA intends to review supplemental EUA requests that fulfill a condition of an EUA. For other supplemental requests, such as those that are beyond the priorities outlined above, FDA encourages developers to consider including the modification in a submission through a traditional premarket review pathway. In general, FDA expects such modified tests to be authorized under an EUA or pursuant to a traditional premarket review pathway before being distributed or offered.

When a high-complexity CLIA-certified laboratory is modifying an authorized COVID-19 molecular diagnostic test, including one for which such laboratory is not the developer of the original, EUA-authorized test, and the modifications do not change the indication for use set forth in the EUA (e.g., including new/different extraction kits or instruments that would not be expected to change the indication for use) and do not change the analyte specific reagents (e.g., the modifications do not change the PCR primers and/or probes),[^16] FDA does not intend to object to implementation of the modification to the diagnostic test without notification to FDA or a new or amended EUA where the laboratory has validated the modification and confirmed that the performance of the modified test is equivalent to the performance of the authorized test, and use of the test is limited to the high-complexity CLIA-certified laboratory in which the modification was made.[^17]

In such cases, where the laboratory modifying and performing the test is not the developer of the original, EUA-authorized test, FDA encourages the laboratory to collaborate with the developer of the authorized test so that validation data supporting the modifications can be submitted by the original developer to FDA in a supplemental EUA request or incorporated into a future submission through the traditional premarket review pathways.

#### (2) Certain Modifications Made Before Issuance of this Updated Guidance
Under previous versions of this guidance, when a commercial manufacturer made certain modifications to its EUA-authorized COVID-19 diagnostic test, and where validation data supporting the modification had been submitted in a supplemental EUA request, FDA stated that it did not intend to object to implementation of the modification while FDA conducted its review, except for modifications to add specimen types that have not been previously authorized with another test of the same technology. For such modifications made and implemented as discussed in the policies in the previous version of the guidance, FDA does not intend to object to such commercial manufacturers continuing to implement the modification while FDA conducts its review.

Under the previous version of the guidance, when a high-complexity CLIA-certified laboratory modified an EUA-authorized COVID-19 diagnostic test[^18] prior to November 15, 2021, for use with a new specimen type, where the new specimen type has been previously authorized for another test of the same technology[^19] and where the laboratory had validated the test for the new specimen type, FDA stated that it did not intend to object to the use of such a modified test without notification to FDA or a new or amended EUA. For all other types of modifications made by the high-complexity CLIA-certified laboratory prior to November 15, 2021, for an EUA-authorized COVID-19 diagnostic test, in the previous version of the guidance, FDA stated that it did not intend to object to the use of the test by high-complexity CLIA-certified laboratories, without notification to FDA or a new or amended EUA, where the modified test is validated using a bridging study to the EUA-authorized test.

For high-complexity CLIA-certified laboratories that modified an authorized COVID-19 molecular diagnostic test after November 15, 2021, but before issuance of this updated guidance, including one for which such laboratory is not the developer of the original, EUA-authorized test, and the modifications do not change the indication for use set forth in the EUA (e.g., including new/different extraction kits or instruments that would not be expected to change the indication for use) and do not change the analyte specific reagents (e.g., the modifications do not change the PCR primers and/or probes),[^20] FDA stated that it did not intend to object to implementation of the modification to the diagnostic test without notification to FDA or a new or amended EUA where the laboratory has validated the modification and confirmed that the performance of the modified test is equivalent to the performance of the authorized test, and use of the test is limited to the high-complexity CLIA-certified laboratory in which the modification was made.[^21]

For such modifications made and implemented by high-complexity CLIA-certified laboratories as discussed in the policies in the previous versions of the guidance, FDA does not intend to object to such laboratories continuing to offer any of those modified tests.

In such cases, where the laboratory performing the modified test is not the developer of the original, EUA-authorized test, FDA encourages the laboratory to share its validation data with the developer of the original, EUA-authorized test so that the developer of the original, EUA-authorized test can use the validation data in support of a supplemental EUA request to add the modification or can incorporate it into a future submission through the traditional premarket review pathways.

## V. Validation
All clinical tests should be validated using clinical specimens and an appropriate comparator test prior to use.

In the context of a public health emergency, it is critically important that tests be validated prior to use because false results not only can negatively impact the individual patient but also can have a broad public health impact. However, FDA also generally accepts a lower level of evidence of validation for an EUA than for traditional premarket review pathways. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity to the level of evidence expected for an EUA, including descriptions of appropriate comparators for different types of tests, in the EUA templates available through download from our website.[^22] Depending on the characteristics of a developer’s test, additional validation studies may be recommended.

Because the level of evidence required for authorization under traditional premarket review pathways is higher than that required for an EUA, the recommendations in the EUA templates may not be sufficient for developers seeking marketing authorization of their tests through traditional premarket review pathways. FDA can provide recommendations specific to a test developer’s situation through inquiries to [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) or through pre-submission interactions.[^23]

Developers can use alternative approaches. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV).

Additionally, FDA continues to expect certain serology tests to be independently evaluated by NIH/NCI,[^24] prior to authorization, when requested by the FDA. When performed, this additional testing can assist FDA in determining whether the EUA issuance criteria in section 564 of the FD&C Act have been met and whether FDA should authorize the test. This independent evaluation may also be used to assist FDA in determining whether the criteria for marketing authorization have been met for tests submitted through traditional premarket review pathways.

## VI. Availability of EUA Templates and Inquiries Regarding Validation
FDA has made available through download from our website[^25] a series of templates that developers may choose to use to facilitate the preparation and submission of an EUA request for various types of COVID-19 tests. The templates reflect FDA’s current thinking on validation recommendations for SARS-CoV-2 tests and the data and information that developers should submit to facilitate the EUA process. The templates provide information and recommendations, and FDA plans to update them as appropriate as more is learned about COVID-19 and more experience is gained with the EUA process for the various types of COVID-19 tests. Developers may use alternative approaches. Developers who are considering alternative approaches should consider seeking FDA’s feedback.

FDA can provide validation recommendations specific to a test developer’s situation both for those seeking EUA and for those seeking marketing authorization through traditional review pathways. Developers can send simple inquiries to [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) or submit a pre-EUA or pre-submission for more complex inquiries.[^26] For tests seeking marketing authorization through traditional premarket review pathways, FDA may recommend validation studies or supportive evidence in addition to the recommendations in the EUA templates.

Members of the public can submit questions about the templates to [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV), or they can submit comments regarding the templates to the public docket established for this guidance.

---

[^1]: Secretary of Health and Human Services, Determination that a Public Health Emergency Exists (originally issued on Jan. 31, 2020, and subsequently renewed), available at [https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx](https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx).
[^2]: Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak (Mar. 13, 2020), available at [https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/](https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/). On February 24, 2021, there was a Presidential Declaration continuing the national emergency concerning the COVID-19 pandemic beyond March 1, 2021. See Continuation of the National Emergency Concerning the Coronavirus Disease 2019 (COVID-19) Pandemic (February 24, 2021), available at [https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic](https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic).
[^3]: Throughout this guidance, the term “diagnostic test” is generally used to refer to molecular or antigen tests, both of which can be used to diagnose infection with the SARS-CoV-2 virus. Diagnostic tests may be designed for use in various settings, such as in a CLIA-certified laboratory, at the point of care at a site covered by a laboratory’s CLIA certificate, or at home. Screening tests, which are used for testing individuals without symptoms or other reasons to suspect COVID-19, are a subset of diagnostic tests. Molecular tests detect the presence of viral RNA and antigen tests detect the presence of viral proteins that are part of the SARS-CoV-2 virus. There may also be diagnostic tests that incorporate different technologies, such as breath tests, that have a reasonable expectation of technical and clinical success. While the principles in this guidance are generally still applicable to such tests, there are fewer available, so different approaches may be appropriate. Therefore, FDA recommends that developers of such tests
[^12]: Under section 18115 of the CARES Act (Public Law 116-136), laboratories, including those in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance or Certificate of Accreditation, must report the results of COVID-19 tests to HHS or its designee, in such form and manner as the Secretary may prescribe, during the declared public health emergency. For additional information on the laboratory data reporting guidance and FAQs from HHS, please see: [HHS Guidance](https://www.hhs.gov/coronavirus/testing/covid-19-diagnostic-data-reporting/index.html).
[^13]: [FDA Notification Lists](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/notifications-and-emergency-use-authorizations-faqs-testing-sars-cov-2)
[^14]: LDTs are typically considered tests that are designed, manufactured, and used within a single laboratory that is certified under CLIA and meets the requirements to perform tests of high complexity.
[^15]: This does not apply to EUA requests for which FDA has already notified the test developer by email that FDA declines to review, declines to issue, or otherwise decides not to authorize the test for any reason, including lack of response or a determination that there is a lack of adequate data to support authorization. Developers of such tests were generally expected to cease distributing, marketing, and offering their tests within 15 calendar days of receiving such an email.
[^16]: Other modifications, including new specimen types, test settings (e.g., point-of-care, home testing), and new patient populations (e.g., asymptomatic individuals), among others, do not fall under this policy.
[^17]: FDA generally considers equivalent performance to be where the LoD of the modified test (using the same validation material used in the LoD study described in the authorized test’s Instructions For Use (IFU)) is within 3x of the LoD established in the authorized test’s IFU or that the LoD of the modified test is within 3x of the LoD of the authorized test in a direct comparison LoD study.
[^18]: This applies to modifications to any EUA-authorized diagnostic test, including a laboratory’s own test with an EUA or a purchased kit from a commercial manufacturer with an EUA, but does not apply to modifications of authorized home collection kits.
[^19]: For the purposes of this guidance, all nucleic acid amplification tests are considered to have the same technology.
[^20]: Other modifications, including new specimen types, test settings (e.g., point-of-care, home testing), and new patient populations (e.g., asymptomatic individuals), among others, do not fall under this policy.
[^21]: FDA generally considers equivalent performance to be where the LoD of the modified test (using the same validation material used in the LoD study described in the authorized test’s Instructions For Use (IFU)) is within 3x of the LoD established in the authorized test’s IFU or that the LoD of the modified test is within 3x of the LoD of the authorized test in a direct comparison LoD study.
[^22]: See [FDA EUA Guidance](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas).
[^23]: See FDA Guidance document “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program,” available at: [FDA Guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program).
[^24]: The FDA is working with the NIH, the Centers for Disease Control and Prevention (CDC), and BARDA to assess the performance of certain commercial manufacturers’ serology tests. As part of this project, the FDA, working with partnering agencies, has designed a performance assessment protocol that offers a mechanism for an independent evaluation of certain lateral flow and certain enzyme-linked immunosorbent assay (ELISA) or similar technology-based SARS-CoV-2 antibody tests in a laboratory environment. Under this protocol, each test evaluated at the NIH/NCI will be evaluated with a well-characterized sample panel consisting of positive and negative plasma and/or serum samples. The approach represents a balanced attempt to provide a reasonable understanding of the potential performance of a significant number of the tests within a short time period. Performance results are considered during FDA’s review of an EUA request for the test.
[^25]: See [FDA EUA Guidance](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas).
[^26]: See FDA Guidance document “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program,” available at: [FDA Guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program).


# 9,097  2022-11-01_FDA Letter - Repeat Testing Revision Letter.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2022-11-01_FDA Letter - Repeat Testing Revision Letter.md
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summary_short: The FDA “Repeat Testing Revision Letter” (November 1, 2022) revises all EUA-authorized SARS-CoV-2 antigen tests to require updated serial testing frequencies based on new clinical evidence. It mandates labeling changes specifying at least two tests over three days for symptomatic individuals and at least three tests over five days for asymptomatic individuals, while removing prior post-authorization study requirements. It standardizes consumer, healthcare provider, and digital app instructions to emphasize that negative antigen results are presumptive and that repeat testing is essential for accuracy.


CONTENT

November 1, 2022

To:  
Developers of Antigen In Vitro Diagnostics (IVDs) Authorized for Emergency Use for Coronavirus Disease 2019 (COVID-19) as of Today’s Date

Re:  
Revisions Related to Serial (Repeat) Testing for the EUAs of Antigen IVDs

On February 4, 2020, pursuant to Section 564(b)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 360bbb-3(b)(1)(C)), the Secretary of the Department of Health and Human Services (HHS) determined that there is a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad, and that involves the virus that causes COVID-19. Pursuant to Section 564 of the Act, and on the basis of such determination, the Secretary of HHS then declared that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the virus that causes COVID-19 subject to the terms of any authorization issued under Section 564(a) of the Act. [^1] FDA subsequently authorized the emergency use of numerous in vitro diagnostics (IVDs) for detection and/or diagnosis of SARS-CoV-2, the virus that causes COVID-19. [^2]

Pursuant to Section 564 of the Act, and in response to new data regarding performance of antigen tests from a study assessing at-home COVID-19 antigen test performance (“the antigen study”), [^3] FDA is revising the authorized uses [^4] and requiring updates to product labeling of all tests that are within the scope of this letter. This revision also establishes one additional Condition of Authorization, and eliminates one Condition of Authorization, on EUAs that are within the scope of this revision (Section I).

The additional condition of authorization established by this revision concerns updates to the authorized labeling [^5] to reflect the revised authorized use for tests that are within the scope of this revision. FDA’s determination that the Condition of Authorization established by this revision is necessary or appropriate to protect the public health is based on the available scientific evidence and FDA’s continuing efforts to evaluate the performance of authorized antigen IVDs with respect to the use of serial testing. The eliminated condition of authorization concerns the collection of additional data to evaluate the performance of authorized antigen IVDs with respect to the use of serial testing. FDA’s determination that the Condition of Authorization eliminated by this revision is no longer necessary or appropriate to protect the public health in light of the antigen study.

Having concluded that the revisions to the EUAs of tests that are within the scope of this letter (section I) are appropriate to protect the public health or safety, I am hereby revising all such EUAs pursuant to Section 564(g)(2)(C), including to revise the authorized use and to establish the additional condition set forth in this letter as permitted by Section 564(e) of the Act. This action is based on the available scientific evidence [^6] on the impact of serial testing on the performance of SARS-CoV-2 antigen tests.

## I. Scope of this Revision
This letter revises all current EUAs for antigen SARS-CoV-2 IVD devices [^7] as of today’s date by:

1. Revising the authorized use to be for serial testing at least twice over three days for individuals with symptoms of COVID-19 and, for tests previously authorized for testing individuals without symptoms, revising the authorized use to be for serial testing at least three times over five days for individuals without symptoms of COVID-19, as set forth in Appendix A of this letter.
2. Establishing a new condition of authorization, as set forth in Section III of this letter, on such authorizations, and
3. Eliminating a condition of authorization, as set forth in Section III of this letter, on such authorizations.

This revision does not apply to EUAs for non-antigen based authorized assays (e.g., molecular, serology), EUAs for authorized IL-6 assays, EUAs for standalone specimen collection devices, or EUAs for standalone home collection kits.

All updated labeling will be added to FDA’s webpage and posted with the EUA after it is submitted to FDA as required by Condition of Authorization (1) of this letter.

## II. Waiver of Certain Requirements
This revision does not change the waiver of any requirements included in the EUAs being revised.

## III. Revisions to Conditions of Authorization
A. Pursuant to Section 564(e) of the Act, I am establishing the additional condition below with respect to repeat testing on all authorized tests within this letter’s scope.

**Developer (You)**
1. You must update your authorized labeling to reflect the revised authorized use in Appendix A and as set forth in Appendix B of this letter by submitting your proposed updated labeling to FDA as a supplement to your EUA within 10 business days of today’s date, unless otherwise agreed to by the Division of Microbiology (DMD)/Office of Health Technology 7 (OHT7)-Office of In Vitro Diagnostics/Office of Product Evaluation and Quality (OPEQ)/Center for Devices and Radiological Health (CDRH). Following FDA’s concurrence with the supplement, you must update your electronic labeling and electronic/mobile applications (apps) within 20 business days. You must update your paper labeling within 30 business days of FDA’s concurrence and all tests distributed subsequently must be accompanied by the updated paper labeling.

B. Pursuant to section 564(g)(2)(C) of the Act, and in consideration of the establishment of Condition of Authorization (1) above, I am eliminating the following condition (or similar condition) from EUAs within the scope (section I above):

**Developer (You)**
You must evaluate the clinical performance of your product to support the serial screening claim in an FDA agreed upon post authorization clinical evaluation study within 4 months of the date of this letter (unless otherwise agreed to with DMD/OHT7/OPEQ/CDRH). After submission to and concurrence with the data by FDA, you must update the authorized labeling to reflect the additional testing. Such labeling updates will be made in consultation with, and require concurrence of, DMD/OHT7/OPEQ/CDRH.

Sincerely,

____________________

Namandjé N. Bumpus, Ph.D.  
Chief Scientist  
Food and Drug Administration  

Enclosure

## Appendix A  
### Revised Authorized Uses
The authorized uses for tests that are within the scope (Section I) of this letter are revised as follows:

1. Where a test was previously authorized for testing of symptomatic individuals (e.g., within the first [number specific to each test] days of symptom onset), the test is now authorized for use at least twice over three days with at least 48 hours between tests.

2. Where a test was previously authorized for testing of asymptomatic individuals (e.g., individuals without symptoms or other epidemiological reasons to suspect COVID-19), the test is now authorized for use at least three times over five days with at least 48 hours between tests.

## Appendix B  
### Required Changes to Authorized Labeling
As required by Condition of Authorization (1), you must update your authorized labeling to include the labeling elements, sections, and statements below:

#### 1. Intended Use:[^8]

   In addition to name, technology, analyte specific information and other validated claims, the Intended Use must include the updated frequency of testing for symptomatic and asymptomatic individuals (as applicable).

   - For tests referenced in Appendix A, #1, this means including language that the test is for serial testing for use at least twice over three days with at least 48 hours between tests;
   - For tests referenced in Appendix A, #2, this means including language that the test is for serial testing for use at least three times over five days with at least 48 hours between tests and removing language regarding testing at least twice over two or three days with at least 24 and no more than 36 hours between tests.

   In addition, the Intended Use must include the following statements:

   - “negative results are presumptive”
   - “The [Test Name] is only for in vitro diagnostic use under the Food and Drug Administration’s Emergency Use Authorization. This product has not been FDA cleared or approved.”

#### 2. Outer Box and Subassembly Labeling (as applicable):

   - Expiration date (sticker): Based on component of kit with the earliest expiration date
   - Summary of box contents
   - Items necessary to use the test but not provided in the test kit: [e.g., access to computer/smartphone, internet, email account]
   - Storage temperature
   - Summary of how the kit works

   Statements that must be present on the outer box:

   - For Emergency Use Authorization (EUA) only
   - For in vitro diagnostic use
   - In the USA, this product has not been FDA cleared or approved, but has been authorized by FDA under an EUA.
   - This product has been authorized only for the detection of proteins from SARS-CoV-2 [for multi-analyte tests please insert the additional on-panel analytes, e.g., influenza A/B], not for any other viruses or pathogens.
   - The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.
   - Determining a negative result requires multiple tests. You may need to purchase additional tests to perform serial (repeat) testing. This test is more likely to give you a false negative result when you have COVID-19 than a lab-based molecular test.

#### 3. Instructions for Use
##### a. Lay User Labeling (applicable only to tests authorized for home use)
**i.Test Interpretation**

Repeat testing is needed to improve test accuracy. Please follow the table below when interpreting test results for COVID-19.

| Status on First Day of Testing | First Result Day 1 | Second Result Day 3 | Third Result Day 5 | Interpretation |
|-------------------------------|-------------------|-------------------|------------------|----------------|
| With Symptoms | Positive | N/A | N/A | Positive for COVID-19 |
| With Symptoms | Negative | Positive | N/A | Positive for COVID-19 |
| With Symptoms | Negative | Negative | N/A | Negative for COVID-19 |
| Without Symptoms | Positive | N/A | N/A | Positive for COVID-19 |
| Without Symptoms | Negative | Positive | N/A | Positive for COVID-19 |
| Without Symptoms | Negative | Negative | Positive | Positive for COVID-19 |
| Without Symptoms | Negative | Negative | Negative | Negative for COVID-19 |
||

Results should be considered in the context of an individual’s recent exposures, history, and the presence of clinical signs and symptoms consistent with COVID-19.

***COVID-19 Positive (+)***
If the Control (C) line and the Test (T) line are visible, the test is positive. Any faint visible \[*color*\] test (T) line with the control line (C) should be read as positive.
**You do not need to perform repeat testing if you have a positive result at any time.**

A positive test result means that the virus that causes COVID-19 was detected in your sample and it is very likely you have COVID-19 and are contagious. Please contact your doctor/primary care physician or your local health authority immediately and adhere to the local guidelines regarding self-isolation. There is a very small chance that this test can give a positive result that is incorrect (a false positive).

***COVID-19 Negative (-)***
If the Control (C) line is visible, but the Test (T) line is not visible, the test is negative.
**To increase the chance that the negative result for COVID-19 is accurate, you should:**
- **Test again in 48 hours if you have symptoms on the first day of testing.**
- **Test 2 more times at least 48 hours apart if you do not have symptoms on the first day of testing.**

A negative test result indicates that the virus that causes COVID-19 was not detected in yoursample. Anegativeresultispresumptive, meaning itisnotcertain thatyou do nothave COVID-19. You may still have COVID-19 and you may still be contagious. There is a higherchanceoffalsenegativeresultswith antigen testscompared to laboratory-based tests such as PCR. If you test negative and continue to experience COVID-19-like symptoms, (e.g., fever, cough, and/or shortness of breath) you should seek follow up care with your health care provider.

***Invalid***
If the control (C) line is not visible, the test is invalid. Re-test with a new swab and new test device.

**ii. How to Use This Test**
The Lay User labeling must include a specific section “How to Use this Test” with the following information:
- Serial testing should be performed in all individuals with negative results; individuals with symptoms of COVID-19 and initial negative results should be tested again after 48 hours. Individuals without symptoms of COVID-19, and with initial negative results, should be tested again after 48 hours and, if the 2nd test is also negative, a 3rd time after an additional 48 hours. You may need to purchase additional tests to perform this serial (repeat) testing.
- If you test negative but continue to have symptoms of COVID-19, and both your first and second tests are negative, you may not have COVID-19, however you should follow-up with your healthcare provider.
- If your test is positive, then proteins from the virus that causes COVID-19 have been found in your sample and you likely have COVID-19.

**iii. Warnings, Precautions, and Safety Information**
The Lay User labeling must include the following warnings, precautions and/or safety information:
- Read all instructions carefully before performing the test. Failure to follow the instructions may result in inaccurate test results.
- In the USA, this product has not been FDA cleared or approved, but has been authorized by FDA under an Emergency Use Authorization. This product has been authorized only for the detection of proteins from SARS-CoV-2, not for any other viruses or pathogens. The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.
- Serial testing should be performed in individuals with negative results at least twice over three days (with 48 hours between tests) for symptomatic individuals and three times over five days (with at least 48 hours between tests) for asymptomatic individuals. You may need to purchase additional tests to perform this serial (repeat) testing.
- An anterior nasal swab sample can be self-collected by an individual age \[*X*\] years and older. Children age 2 to \[*X*\] years should be tested by an adult.
- Do not use on anyone under 2 years of age.
- Wear a safety mask or other face-covering when collecting a specimen from a child or another individual.
- Do not use if any of the test kit contents or packaging is damaged.
- Test components are single-use. Do not re-use.
- Do not use kit past its expiration date.
- Do not touch the swab tip.
- Once opened, the test card should be used within \[*X*\] minutes.
- Do not read test results before \[*X*\] minutes or after \[*Y*\] minutes. Results read before \[*X*\] minutes or after \[*Y*\] minutes may lead to a false positive, false negative, or invalid result.
- If applicable: Keep testing kit and kit components away from children and pets before and after use. Avoid contact with your \[e.g., *skin, eyes, nose, or mouth*\]. Do not ingest any kit components. The reagent solution contains harmful chemicals (see table below). If the solution contacts your \[e.g., *e.g., skin, eyes, nose, or mouth\]*, flush with large amounts of water.
**If irritation persists, seek medical advice:** [**https://www.poisonhelp.org**](https://www.poisonhelp.org/) **or1-800-222-1222**. *\[Note: Please do not use the following website in your labeling:https://www.poison.org/contact-us](https://www.poison.org/contact-us). Also, please populate the following table as appropriate for your device and per FDA toxicological assessment of your device:*\]

   | Chemical Name | GHS Code for each Ingredient | Concentrations |
   |--------------|----------------------------|----------------|
   | e.g., Microcide III | H315, skin irritation | 0.2% |
||
   |
- For more information on EUAs please visit: [https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization)
- For the most up to date information on COVID-19, please visit: [www.cdc.gov/COVID19](https://www.cdc.gov/COVID19)

**iv. Limitations**
- There is a higher chance of false negative results with antigen tests than with laboratory-based molecular tests due to the sensitivity of the test technology. This means that there is a higher chance this test will give a false negative result in an individual with COVID-19 as compared to a molecular test, especially in samples with low viral load.
- The performance of this test was established based on the evaluation of a limited number of clinical specimens collected between [month, year and month, year]. The clinical performance has not been established for all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.
- All COVID-19 antigen test negative results are presumptive and confirmation with a molecular assay may be necessary. If you continue to have symptoms of COVID-19, and both your first and second tests are negative, you may not have COVID-19, however you should follow-up with a healthcare provider.
- If the test is positive, then proteins from the virus that causes COVID-19 have been found in the sample and you likely have COVID-19.
- This test is read visually and has not been validated for use by those with impaired vision or color-impaired vision.
- Incorrect test results may occur if a specimen is incorrectly collected or handled.

**v. Frequently Asked Questions (FAQ):**
The following FAQ section should be added to the Lay User IFU (and, if applicable, the QRI) for those Lay User IFUs that also contain the information typically found in a Patient Fact Sheet for OTC tests:

WHAT ARE THE KNOWN AND POTENTIAL RISKS AND BENEFITS OF THE TEST?
Potential risks include:

- Possible discomfort during sample collection.
- Possible incorrect test result (see Warnings and Result Interpretation sections for more information).

Potential benefits include:

- The results, along with other information, can help you and your healthcare provider make informed recommendations about your care.
- The results of this test may help limit the potential spread of COVID-19 to your family and others in your community.

For more information on EUAs go here: [https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization)

**WHAT IS THE DIFFERENCE BETWEEN AN ANTIGEN AND MOLECULAR TEST?**
There are different kinds of tests for the SARS-CoV-2 virus that causes COVID-19. Molecular tests detect genetic material from the virus. Antigen tests, such as the [Test Name], detect proteins from the virus. Due to the lower sensitivity of antigen tests, there is a higher chance this test will give you a false negative result when you have COVID-19 than a molecular test would.

**HOW ACCURATE IS THIS TEST?**
Clinical studies have shown that antigen tests more accurately determine whether you are infected with the virus that causes COVID-19 when taken multiple times across several days. Repeat testing improves test accuracy. This serial testing approach is recommended to minimize the risk of incorrect results. For more information on the performance of the test and how the performance may apply to you, please refer to the performance data in the Healthcare Provider Instructions for Use (IFU), available at [insert developer’s website’s address].

**WHAT IF I HAVE A POSITIVE TEST RESULT?**
A positive result means that it is very likely you have COVID-19 because proteins from the virus that causes COVID-19 were found in your sample. You should self-isolate from others and contact a healthcare provider for medical advice about your positive result.

**WHAT IF I HAVE A NEGATIVE TEST RESULT?**
A negative test result indicates that antigens from the virus that causes COVID-19 were not detected in your sample. However, if you have symptoms of COVID-19, and your first test is negative, you should test again in 48 hours since antigen tests are not as sensitive as molecular tests. If you do not have symptoms and received a negative result, you should test at least two more times with 48 hours in between tests for a total of three tests. If you have a negative result, it does not rule out SARS-CoV-2 infection; you may still be infected and you may still infect others. It is important that you work with your healthcare provider to help you understand the next steps you should take.

**WHAT DOES AN INVALID TEST RESULT MEAN?**
An invalid result means the test was not able to tell if you have COVID-19 or not. If the test is invalid, a new swab should be used to collect a new nasal specimen and you should test again with a new test.

**IMPORTANT**
Do not use this test as the only guide to manage your illness. Consult your healthcare provider if your symptoms persist or become more severe.

Individuals should provide all results obtained with this product to their healthcare provider.

##### b. HCP Labeling
**i. Test Interpretation**
Repeat testing is needed to improve test accuracy. Please follow the table below when interpreting test results.

| Status on first day of Testing | First Result Day 1 | Second Result Day 3 | Third Result Day 5 | Interpretation              |
|-------------------------------|--------------------|---------------------|-------------------|-----------------------------|
| With Symptoms                 | Positive           | N/A                 | N/A               | Positive for COVID-19       |
| With Symptoms                 | Negative           | Positive            | N/A               | Positive for COVID-19       |
| With Symptoms                 | Negative           | Negative            | N/A               | Negative for COVID-19       |
| Without Symptoms              | Positive           | N/A                 | N/A               | Positive for COVID-19       |
| Without Symptoms              | Negative           | Positive            | N/A               | Positive for COVID-19       |
| Without Symptoms              | Negative           | Negative            | Positive          | Positive for COVID-19       |
| Without Symptoms              | Negative           | Negative            | Negative          | Negative for COVID-19       |
||

Results should be considered in the context of an individual’s recent exposures, history, and the presence of clinical signs and symptoms consistent with COVID-19.

**COVID-19 Positive (+)**
If the Control (C) line and the Test (T) line are visible, the test is positive. Any faint visible [color] test (T) line with the control line (C) should be read as positive.

**Repeat testing does not need to be performed if patients have a positive result at any time.**
A positive test result means that the virus that causes COVID-19 was detected in the sample, and it is very likely the individual has COVID-19 and is contagious. Please contact the patient’s doctor/primary care physician (if applicable) and the local health authority immediately and instruct your patient to adhere to the local guidelines regarding self-care.

Isolation. There is a very small chance that this test can give a positive result that is incorrect (a false positive).

Positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Individuals who test positive with the [Test Name] should self-isolate and seek follow up care with their physician or healthcare provider as additional confirmatory testing with a molecular test for positive results may also be necessary, if there is a low likelihood of COVID-19, such as in individuals without known exposures to COVID-19 or residing in communities with low prevalence of infection.

**COVID-19 Negative (-)**
If the Control (C) line is visible, but the Test (T) line is not visible, the test is negative.

**To increase the chance that the negative result for COVID-19 is accurate, you should:**
- **Test again in 48 hours if the individual has symptoms on the first day of testing.**
- **Test 2 more times at least 48 hours apart if the individual does not have symptoms on the first day of testing.**

A negative test result indicates that the virus that causes COVID-19 was not detected in the sample. A negative result does not rule out COVID-19. There is a higher chance of false negative results with antigen tests compared to laboratory-based tests such as PCR tests. If the test is negative but COVID-19-like symptoms, e.g., fever, cough, and/or shortness of breath continue, follow up testing for SARS-CoV-2 with a molecular test or testing for other respiratory disease should be considered. If applicable, seek follow up care with the primary health care provider.

All negative results should be treated as presumptive and confirmation with a molecular assay may be necessary if there is a high likelihood of SARS-CoV-2 infection, such as in an individual with a close contact with COVID-19 or with suspected exposure to COVID-19 or in communities with high prevalence of infection. Negative results do not rule out SARS-CoV-2 infection and should not be used as the sole basis for treatment or patient management decisions, including infection control decisions.

***Invalid***
If the control (C) line is not visible, the test is invalid. Re-test with a new swab and new test device.

**ii. Warnings, Precautions, and Safety Information**
The following Warnings, Precautions, and Safety Information should be included in the full HCP IFU; in addition, the warning statements of the first three bullet points below should also be included in the Quick Reference Guide (QRI) of all tests authorized for point-of-care (PoC) use.

- Read all instructions carefully before performing the test. Failure to follow the instructions may result in inaccurate test results.
- In the USA, this product has not been FDA cleared or approved, but has been authorized by FDA under an Emergency Use Authorization. This product has been authorized only for the detection of proteins from SARS-CoV-2\[*for multi-analyte tests please insert the additional on-panel analytes, e.g., influenza A/B*\], not for any other viruses or pathogens. The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.
- **Serial testing should be performed in individuals with negative results at least twice over three days (with 48 hours between tests) for symptomatic individuals and three times over five days (with at least 48 hours between tests) for asymptomatic individuals. You may need to purchase additional tests to perform this serial (repeat) testing**.
- An anterior nasal swab sample can be self-collected by an individual age \[*X*\] years and older. Children age 2 to \[*X*\] years should be tested by an adult.
- Do not use on anyone under 2 years of age.
- Wear a safety mask or other face-covering when collecting a specimen from a child or another individual.
- Do not use if any of the test kit contents or packaging is damaged.
- Test components are single-use. Do not re-use.
- Do not use kit past its expiration date.
- Do not touch the swab tip.
- Once opened, the test card should be used within \[*X*\] minutes.
- **Do not read test results before \[*X*\] minutes or after \[*Y*\] minutes. Results read before \[*X*\] minutes or after \[*Y*\] minutes may lead to a false positive, false negative, or invalid result.**
- **Keep testing kit and kit components away from children and pets before and after use. Avoid contact with your \[*e.g., skin, eyes, nose, or mouth\]*. Do not ingest any kit components. The reagent solution contains harmful chemicals (see table below). If the solution contacts your \[e.g., *skin, eyes, nose, or mouth\]*, flush with large amounts of water. If irritation persists, seek medical advice:** [**https://www.poisonhelp.org**](https://www.poisonhelp.org/) **or 1-800-222-1222**.
*\[Note: Please do not use the following website in your labeling:<https://www.poison.org/contact-us>. Also, please populate the following table as appropriate for your device and per FDA toxicological assessment of your device:*\]
   | Chemical Name | GHS Code for each Ingredient | Concentrations |
   |--------------|----------------------------|----------------|
   | e.g., Microcide III | H315, skin irritation | 0.2% |
   ||
- For more information on EUAs please visit: [https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization)
- For the most up to date information on COVID-19, please visit: [www.cdc.gov/COVID19](http://www.cdc.gov/COVID19)

**iii. Limitations**
- The performance of this test was established based on the evaluation of a limited number of clinical specimens collected between \[*month, year and month, year*\]. The clinical performance has not been established for all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.
- There is a higher chance of false negative results with antigen tests than with laboratory-based molecular tests due to the sensitivity of the test technology. This means that there is a higher chance this test will give a false negative result in an individual with COVID-19 as compared to a molecular test, especially in samples with low viral load.
- All COVID-19 antigen test negative results are presumptive and confirmation with a molecular assay may be necessary.
- If the patient continues to have symptoms of COVID-19, and both the patient’s first and second tests are negative, the patient may not have COVID-19, however additional follow-up may be needed.
- If the test is positive, then proteins from the virus that causes COVID-19 have been found in the sample and the individual likely has COVID-19.
- This test is read visually and has not been validated for use by those with impaired vision or color-impaired vision.
- Incorrect test results may occur if a specimen is incorrectly collected or handled.
- This test detects both viable (live) and nonviable SARS-CoV-2. Test performance
depends on the amount of virus (antigens) in the sample and may or may not correlate with viral culture results performed on the same sample.

**iv. Performance Section of HCP labeling**
A prospective clinical study was conducted between January 2021 and May 2022 as a component of the Rapid Acceleration of Diagnostics (RADx) initiative from the National Institutes of Health (NIH). A total of 7,361 individuals were enrolled via a decentralized clinical study design, with a broad geographical representation of the United States. Per inclusion criteria, all individuals were asymptomatic upon enrollment in the study and at least 14 days prior to it and did not have a SARS-CoV-2 infection in the three months prior to enrollment. Participants were assigned to one of three EUA authorized SARS-CoV-2 OTC rapid antigen tests to conduct serial testing (every 48 hours) for 15 days. If an antigen test was positive, the serial-antigen testing result is considered positive.

At each rapid antigen testing time point, study subjects also collected a nasal swab for comparator testing using a home collection kit (using a 15-minute normalization window between swabs). SARS-CoV-2 infection status was determined by a composite comparator method on the day of the first antigen test, using at least two highly sensitive EUA RT-PCRs. If results of the first two molecular test were discordant a third highly sensitive EUA RT-PCR test was performed, and the final test result was based upon the majority rule.

Study participants reported symptom status throughout the study using the MyDataHelps app. Two-day serial antigen testing is defined as performing two antigen tests 36 - 48 hours apart. Three-day serial antigen testing is defined as performing three antigen tests over five days with at least 48 hours between each test.

Out of the 7,361 participants enrolled in the study, 5,609 were eligible for analysis. Among eligible participants, 154 tested positive for SARS-CoV-2 infection based on RT-PCR, of which 97 (62%) were asymptomatic on the first day of their infection, whereas 57 (39%) reported symptoms on the first day of infection. Pre-symptomatic subjects were included in the positive percent agreement (PPA) of asymptomatic individuals, if they were asymptomatic on the first day of antigen testing, regardless of whether they developed symptoms at any time after the first day of testing.

Performance of the antigen test with serial testing in individuals is described in Table YYY.

**Table YYY:** Data establishing PPA of COVID-19 antigen serial testing compared to the molecular comparator single day testing throughout the course of infection with serial testing. Data is from all antigen tests in study combined.

| DAYS AFTER FIRST PCR POSITIVE TEST RESULT | ASYMPTOMATIC ON FIRST DAY OF TESTING | | | SYMPTOMATIC ON FIRST DAY OF TESTING | | |
|------------------------------------------|---------------------------------------|---------------------------------------|---------------------------------------|---------------------------------------|---------------------------------------|---------------------------------------|
| | Ag Positive / PCR Positive (Antigen Test Performance % PPA) | | | | | |
| | 1 Test | 2 Tests | 3 Tests | 1 Test | 2 Tests | 3 Tests |
| 0 | 9/97 (9.3%) | 35/89 (39.3%) | 44/78 (56.4%) | 34/57 (59.6%) | 47/51 (92.2%) | 44/47 (93.6%) |
| 2 | 17/34 (50.0%) | 23/34 (67.6%) | 25/32 (78.1%) | 58/62 (93.5%) | 59/60 (98.3%) | 43/43 (100%) |
| 4 | 16/21 (76.2%) | 15/20 (75.0%) | 13/15 (86.7%) | 55/58 (94.8%) | 53/54 (98.1%) | 39/40 (97.5%) |
| 6 | 20/28 (71.4%) | 21/27 (77.8%) | 16/18 (88.9%) | 27/34 (79.4%) | 26/33 (78.8%) | 22/27 (81.5%) |
| 8 | 13/23 (56.5%) | 13/22 (59.1%) | 4/11 (36.4%) | 12/17 (70.6%) | 12/17 (70.6%) | 7/11 (63.6%) |
| 10 | 5/9 (55.6%) | 5/8 (62.5%) | - | 4/9 (44.4%) | 3/7 (42.9%) | - |
||

1 Test = one (1) test performed on the noted days after first PCR positive test result. Day 0 is the first day of documented infection with SARS-CoV-2.
2 Tests = two (2) tests performed an average of 48 hours apart. The first test performed on the indicated day and the second test performed 48 hours later.  
3 Tests = three (3) tests performance an average of 48 hours apart. The first test performed on the indicated day, the second test performed 48 hours later, and a final test performed 48 hours after the second test.

#### 4. Fact Sheets
The Fact Sheet for Healthcare Providers (HCPs) and Fact Sheet for Patients and Fact Sheet for Individuals will be updated by FDA consistent with this revision, and FDA will provide them to you.

#### 5. Electronic Applications (e.g., Cell Phone Apps)
Electronic applications (apps) should include a prominently placed warning for the requirement of repeat testing after a negative test result. App related software should be updated to accommodate the following minimal information:

- Test interpretation as outlined in section 3. a. i. above.
- How to Use This Test as outlined in section 3. a. ii. above
- Warning Statements:
   - In the USA, this product has not been FDA cleared or approved, but has been authorized by FDA under an Emergency Use Authorization. This product has been authorized only for the detection of proteins from SARS-CoV-2, not for any other viruses or pathogens. The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.
   - **Serial testing should be performed in individuals with negative results at least twice over three days (with 48 hours between tests) for symptomatic individuals and three times over five days (with at least 48 hours between tests) for asymptomatic individuals. You may need to purchase additional tests to perform this serial (repeat) testing.**
   - There is a higher chance of false negative results with antigen tests than with laboratory-based molecular tests due to the sensitivity of the test technology. This means that there is a higher chance this test will give a false negative result in an individual with COVID-19 as compared to a molecular test, especially in samples with low viral load.
   - All COVID-19 antigen test negative results are presumptive and confirmation with a molecular assay may be necessary. If you continue to have symptoms of COVID-19, and both your first and second tests are negative, you may not have COVID-19, however you should follow-up with a healthcare provider.
   - This test is read visually and has not been validated for use by those with impaired vision or color-impaired vision.
   - A link to an FAQ document as described in section 3. a. v. above.

---

[^1]: U.S. Department of Health and Human Services, *Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3*. 85 FR 7316 (February 7, 2020)
[^2]: In Vitro Diagnostics EUAs: [FDA](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas)
[^3]: [Performance of Screening for SARS-CoV-2 Using Rapid Antigen Tests to Detect Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infection: findings from the Test Us at Home prospective cohort study](https://www.medrxiv.org/content/10.1101/2022.08.05.22278466v1)
[^4]: Generally, the authorized uses of antigen tests are described in, among other locations, the “indication” discussion and “authorized product detail” section in the letters of authorization, and in an “intended use” section in the authorized labeling.
[^5]: Authorized labeling impacted by the additional condition of authorization established by this letter includes some combination of the following documents: Instructions for Use (IFU), Quick Reference Instructions (QRI), laboratory Standard Operating Procedures (SOPs), electronic labeling and applications, and Fact Sheets. Note that the Fact Sheets are generated by FDA who will update these documents after it receives the supplement request to update the test’s other labeling consistent with this revision.
[^6]: [Performance of Screening for SARS-CoV-2 using Rapid Antigen Tests to Detect Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infection: findings from the Test Us at Home prospective cohort study](https://www.medrxiv.org/content/10.1101/2022.08.05.22278466v1)
[^7]: [Please see the following link for currently authorized Antigen IVD devices for SARS-CoV-2](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-antigen-diagnostic-tests-sars-cov-2)
[^8]: As discussed in footnote 4, generally the authorized uses of antigen tests are described in, among other locations, an “intended use” section in the authorized labeling. If such uses are discussed elsewhere in the authorized labeling, you must also make appropriate updates to that labeling to reflect the revised authorized uses.


# 394  2022-11-01_FDA Website - Antigen EUA Revisions for Serial Repeat Testing.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2022-11-01_FDA Website - Antigen EUA Revisions for Serial Repeat Testing.md
file_date: 2022-11-01
title: FDA Website - Antigen EUA Revisions for Serial Repeat Testing
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tokens: 394
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notes: date converted 2024-04-05
web_url: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-antigen-diagnostic-tests-sars-cov-2#SerialTesting
summary_short: The Antigen EUA Revisions for Serial Repeat Testing summarizes FDA’s November 1, 2022 revision updating authorized uses and labeling for all authorized SARS-CoV-2 antigen tests to emphasize repeat testing after a negative result. It sets new serial-testing instructions—at least twice over three days for symptomatic use and at least three times over five days for asymptomatic use, with 48 hours between tests—and requires EUA holders to submit supplemental requests with updated labeling. The revision also adds one new Condition of Authorization and removes one that FDA determined was no longer needed.


CONTENT

On November 1, 2022, the FDA revised the authorized uses and required updates to product labeling regarding repeat, or serial, testing, for all currently authorized SARS-CoV-2 antigen tests.  The revised Letter of Authorization establishes one additional Condition of Authorization and also eliminates one Condition of Authorization that is no longer needed.

This action is in response to available data about the performance of COVID-19 antigen tests showing that repeat testing after a negative COVID-19 antigen test result increases the chance of an accurate result in people with and without symptoms and could help prevent people from unknowingly spreading the SARS-CoV-2 virus to others. The FDA communicated recommendations consistent with this revision in the August 11, 2022, Safety Communication: [At-Home COVID-19 Antigen Tests-Take Steps to Reduce Your Risk of False Negative](https://www.fda.gov/medical-devices/safety-communications/home-covid-19-antigen-tests-take-steps-reduce-your-risk-false-negative-results-fda-safety). 

The November 1, 2022 revision requires test developers in the scope of the revision to take certain actions, including submitting a supplemental EUA request to the FDA with updated labeling to reflect the revised authorized uses, as follows:

Where a test was previously authorized for testing of symptomatic individuals (for example, within the first [number specific to each test] days of symptom onset), the test is now authorized for use at least twice over three days with at least 48 hours between tests.
Where a test was previously authorized for testing of asymptomatic individuals (for example, individuals without symptoms or other epidemiological reasons to suspect COVID-19), the test is now authorized for use at least three times over five days with at least 48 hours between tests. 
[Repeat Testing Revision Letter - November 1, 2022](https://www.fda.gov/media/162799/download?attachment)


# 2,432  2022-11-17_FDA Website - At Home COVID-19 Antigen Tests-Take Steps.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2022-11-17_FDA Website - At Home COVID-19 Antigen Tests-Take Steps.md
file_date: 2022-11-17
title: FDA Website - At Home COVID-19 Antigen Tests-Take Steps
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: website
xfile_type: NA
gfile_url: NA
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conversion_input_file_type: docx
conversion: manual cut and paste
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tokens: 2432
words: 1537
notes: date converted 2024-06-04
web_url: https://www.fda.gov/medical-devices/safety-communications/home-covid-19-antigen-tests-take-steps-reduce-your-risk-false-negative-results-fda-safety
summary_short: The FDA safety communication on at-home COVID-19 antigen tests explains that negative results can miss infections—especially early or in asymptomatic people—and recommends serial (repeat) testing 48 hours apart to reduce false negatives. It outlines practical testing schedules (two tests if symptomatic; three tests if exposed without symptoms), notes antigen tests are generally less sensitive than molecular PCR, and cites FDA-required follow-up studies and NIH-supported data that informed EUA labeling revisions on November 1, 2022.


CONTENT

November 17, 2022, Update: The FDA took an additional action related to the need for repeat testing following a negative COVID-19 test result on COVID-19 antigen tests -- revising the emergency use authorizations (EUAs) of all authorized COVID-19 antigen tests on November 1, 2022. For details, see [FDA Actions](https://www.fda.gov/medical-devices/safety-communications/home-covid-19-antigen-tests-take-steps-reduce-your-risk-false-negative-results-fda-safety#actions) below.

Date Issued: August 11, 2022 (Updated November 17, 2022)

The U.S. Food and Drug Administration (FDA) is advising people to perform repeat testing, also called serial testing, following a negative result on any at-home COVID-19 antigen test, to reduce the risk an infection may be missed (false negative result) and to help prevent people from unknowingly spreading the SARS-CoV-2 virus to others. The FDA recommends repeat testing following a negative result whether or not you have COVID-19 symptoms.

At-home COVID-19 antigen tests detect proteins, called antigens, from the SARS-CoV-2, the virus that causes COVID-19. At-home COVID-19 antigen tests are less likely to detect the SARS-CoV-2 virus than molecular tests, such as polymerase chain reaction (PCR) tests. This is especially true early in an infection or in people who do not have COVID-19 symptoms. Currently, all at-home COVID-19 antigen tests are FDA-authorized for repeat use. This means people should use multiple tests over a certain time period, such as 2-3 days, especially when the people using the tests don't have COVID-19 symptoms. Today, the FDA is highlighting the continued need for repeat testing when people get a negative result with an at-home COVID-19 antigen test, including recommending additional testing over a longer period of time.

Over the course of the COVID-19 pandemic, public health scientists have continued to learn about the SARS-CoV-2 virus and the impact of variants on diagnostic tests that detect SARS-CoV-2. Today's recommendations are based on the latest study results from people with likely omicron infection showing that repeat testing after a negative at-home COVID-19 antigen test result increases the chance of an accurate result. COVID-19 diagnostic testing remains a cornerstone of our nation's fight against COVID-19. At-home COVID-19 antigen tests, while not perfect, provide a fast and convenient COVID-19 testing option.

Recommendations:
Before you use a COVID-19 antigen test:
Be aware that at-home COVID-19 antigen tests are less accurate than molecular tests. COVID-19 antigen tests may not detect the SARS-CoV-2 virus early in an infection, meaning testing soon after you were exposed to someone with COVID-19 could lead to a false-negative result, especially if you don't have symptoms. This is the reason why repeat testing is important.
If you plan to use at-home COVID-19 antigen tests, have several tests on hand so you can test more than once. You do not need to use the same brand of test each time for repeat testing. Visit [At-Home OTC COVID-19 Diagnostic Tests](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/home-otc-covid-19-diagnostic-tests) for a list of all FDA-authorized home tests and for more information about who can use a test and for what ages.
Be aware the FDA expects similar performance with Point of Care (POC) COVID-19 antigen tests performed at a clinic or doctor's office. A negative POC COVID-19 antigen test result should also be followed up with repeat testing and an at-home test could be used.
When you use an at-home COVID-19 antigen test:
Follow the test's step by step instructions exactly to perform the test and to read the test's results.

After you use an at-home COVID-19 antigen test:
If you receive a positive result initially or after a repeat test, this means the test detected the SARS-CoV-2 virus and you most likely have COVID-19.
Follow the [Centers for Disease Control and Prevention (CDC) guidance](https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/index.html) for people with COVID-19, including to stay home, isolate from others, and seek follow-up care with a health care provider to determine the next steps.
If you receive a negative result, the test did not detect the SARS-CoV-2 virus at the time of that test.
If you have [COVID-19 symptoms](https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html), test again 48 hours after the first negative test, for a total of at least two tests.
If you get a negative result on the second test and you are concerned that you could have COVID-19, you may choose to test again 48 hours after the second test, consider getting a laboratory molecular-based test, or call your health care provider.
If you do not have COVID-19 symptoms and believe you have been exposed to COVID-19, test again 48 hours after the first negative test, then 48 hours after the second negative test, for a total of at least three tests.
If you get a negative result on the second test, test again 48 hours after the second test.
If you get a negative result on the third test and you are concerned that you could have COVID-19, you may choose to test again using an antigen test, consider getting a laboratory molecular-based test, or call your health care provider.
If you get a positive result on any repeat test with an at-home COVID-19 antigen test, you most likely have COVID-19 and should follow the CDC guidance for people with COVID-19.
Background
[COVID-19 diagnostic tests](https://www.fda.gov/consumers/consumer-updates/covid-19-test-basics) detect the SARS-CoV-2 virus. There are at-home COVID-19 diagnostic tests that are [FDA-authorized](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization) for self-testing at home, or anywhere. The FDA has authorized both molecular and antigen COVID-19 diagnostic tests for home use.

Overall performance of at-home COVID-19 antigen tests
Most at-home COVID-19 tests are antigen tests and do not detect the SARS-CoV-2 virus as well as molecular tests, most of which are laboratory-based such as polymerase chain reaction (PCR) tests. Molecular COVID-19 tests are generally expected to detect the SARS-CoV-2 virus at least 95% of the time when someone is infected. However, at-home COVID-19 antigen tests are generally expected to detect the SARS-CoV-2 virus at least 80% of the time when someone is infected.

When you perform an at-home COVID-19 antigen test, and you get a positive result, the results are usually accurate. However, if you perform an at-home COVID-19 antigen test, you could get a false negative result. This means that the test may not detect the SARS-CoV-2 virus that is in your nasal swab sample. This could happen if you test soon after you get an infection, especially if you don't have [COVID-19 symptoms](https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html). If you receive a false negative test result, you may unknowingly spread the SARS-CoV-2 virus to others.

Studies to better understand at-home COVID-19 antigen test performance
When at-home COVID-19 antigen tests were initially FDA-authorized, the FDA knew that for people to get accurate results, test instructions would need to include directions for repeat testing. The FDA believed the best way to better understand COVID-19 infections and evaluate test accuracy was to require test developers to perform follow up studies with their tests. The studies would need to assess how well COVID-19 antigen tests could detect the SARS-CoV-2 virus, especially in people without COVID-19 symptoms. Therefore, the FDA required each at-home COVID-19 antigen test manufacturer to assess how well their test works when used by people with and without COVID-19 symptoms following repeat testing instructions.

In parallel, the FDA collaborated with the National Institutes for Health (NIH) and the University of Massachusetts Chan Medical School and together they designed a [comprehensive study](https://www.medrxiv.org/content/10.1101/2022.08.04.22278274v1) to assess at-home COVID-19 antigen test performance. The study was funded by the NIH's Rapid Acceleration Diagnostics (RADx) Program and included more than 7,000 participants. The results of the study would be available as a resource to all at-home COVID-19 antigen test manufacturers.

The study participants collected their nasal sample and performed an at-home COVID-19 antigen test. Participants who got a negative test result performed repeat testing every 48 hours, over 14 days. All participants also collected their nasal sample using a home collection kit and then sent the sample to a clinical laboratory for testing with an FDA-authorized molecular test. The study compared the performance of at-home COVID-19 antigen tests to performance of a laboratory-based molecular test. [Results from this study](https://www.medrxiv.org/content/10.1101/2022.08.05.22278466v1) show that repeat testing over a longer timeframe improves test performance and increases the likelihood that an at-home COVID-19 antigen test will detect an infection. These results have further guided the FDA's thinking that repeat testing after a negative result with an at-home COVID-19 antigen test reduces the risk of a false negative result.

FDA Actions
On November 1, 2022, based on the data discussed in this safety communication, the FDA revised the authorized uses and required updates to the labeling for all currently authorized COVID-19 antigen tests regarding repeat testing after a negative COVID-19 test result. 

For additional information about the EUA revision, visit: [Antigen EUA Revisions for Serial (Repeat) Testing](https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-antigen-diagnostic-tests-sars-cov-2#SerialTesting)

For additional information about at-home tests, visit: [At-Home OTC COVID-19 Diagnostic Tests](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/home-otc-covid-19-diagnostic-tests)

The FDA is committed to assuring appropriately accurate and reliable at-home COVID-19 diagnostic tests for all Americans and will keep the public informed if significant new information about COVID-19 antigen test performance becomes available. 

Reporting Problems with Your Device
If you think you had a problem with your COVID-19 test, the FDA encourages you to report the problem through the [MedWatch Voluntary Reporting Form](https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home).

Health care personnel employed by facilities that are subject to the FDA's user facility reporting requirements should follow the reporting procedures established by their facilities.

Questions?
If you have questions, email the Division of Industry and Consumer Education (DICE) at DICE@FDA.HHS.GOV or call 800-638-2041 or 301-796-7100.


# 8,029  2023-01-12_FDA Guidance - COVID IVD Test Developers v7.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2023-01-12_FDA Guidance - COVID IVD Test Developers v7.md
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title: FDA Guidance - COVID IVD Test Developers v7
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conversion_input_file_type: pdf
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license: Public Domain
tokens: 8029
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notes: 
summary_short: The FDA “Policy for Coronavirus Disease-2019 Tests (Revised)” (7th edition, January 12, 2023) outlines FDA’s EUA review priorities and enforcement policies for COVID-19 diagnostic and serology tests during the section 564 emergency declaration. It explains when tests may be distributed or offered during FDA review, what disclosures and performance information should accompany non-authorized tests, and how high-complexity CLIA labs can make certain modifications to EUA-authorized molecular tests without a new EUA if validated and limited to that lab.


CONTENT

***INTERNAL TITLE:*** Policy for Coronavirus Disease-2019 Tests (Revised)*
Guidance for Developers and Food and Drug Administration Staff

Document issued January 12, 2023.

This document supersedes “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised): Guidance for Developers and Food and Drug Administration Staff” issued September 27, 2022.

U.S. Department of Health and Human Services  
Food and Drug Administration  
Center for Devices and Radiological Health  

*This is the seventh edition of this guidance, which originally issued February 29, 2020, and was subsequently revised on March 16, May 4, May 11, 2020, November 15, 2021, and September 27, 2022.*

## Preface
### Public Comment
Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to [https://www.regulations.gov](https://www.regulations.gov). All comments should be identified with the docket number FDA-2020-D-0987 and complete title of the guidance in the request.

### Additional Copies
Additional copies are available from the FDA webpage titled “COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders,” available at [https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders](https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders), and the FDA webpage titled “Search for FDA Guidance Documents,” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents](https://www.fda.gov/regulatory-information/search-fda-guidance-documents). You may also send an e-mail request to [CDRH-Guidance@fda.hhs.gov](mailto:CDRH-Guidance@fda.hhs.gov) to receive an additional copy of the guidance. Please include the document number GUI00020010 and complete title of the guidance in the request.

### Questions
For questions about this document, contact [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov).


## Table of Contents
I. Introduction ............................................................................................................................. 4  
II. Background ............................................................................................................................ 5  
III. Scope ..................................................................................................................................... 6  
IV. Policy .................................................................................................................................... 7  
   A. Review of EUA Requests for COVID-19 Tests ............................................................... 7  
   B. State Authorization of High-Complexity CLIA-Certified Laboratories ......................... 8  
   C. Distribution and Offering of SARS-CoV-2 Diagnostic and Serology Tests During FDA Review .......................................................................................................................... 10  
      1. FDA Review of EUA Requests .................................................................................. 10  
      2. Recommendations Regarding Test Reports and Other Information for Tests Offered During FDA Review of EUA Requests .................................................................... 11  
   D. Modifications to EUA-Authorized Diagnostic COVID-19 Tests .................................. 11  
      1. Modifications Made After Issuance of this Updated Guidance ................................. 12  
      2. Certain Modifications Made Before Issuance of this Updated Guidance .................. 13  
V. Validation ............................................................................................................................. 14  
VI. Availability of EUA Templates and Inquiries Regarding Validation .................................. 15  

## I. Introduction
FDA plays a critical role in protecting the United States from threats such as emerging infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support response efforts to this pandemic.

FDA is issuing this guidance to provide FDA’s review priorities and enforcement policies regarding novel coronavirus (COVID-19) tests. Rapid detection of COVID-19 cases in the United States requires wide availability of testing to control the spread of this highly contagious infection.

The policies in this guidance are intended to remain in effect only for the duration of the declaration under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) by the Secretary of Health and Human Services (HHS) on February 4, 2020, declaring that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the novel coronavirus (2019-nCoV).[^1] FDA continues to assess the evolving situation and intends to update this guidance as appropriate.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word _should_ in Agency guidance means that something is suggested or recommended, but not required.

## II. Background
There is currently a pandemic of respiratory disease caused by a novel coronavirus. The virus has been named “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) and the disease it causes has been named “Coronavirus Disease 2019” (COVID-19). On January 31, 2020, the Secretary of HHS issued a declaration of a public health emergency under section 319 of the Public Health Services Act related to COVID-19 and mobilized the Operating Divisions of HHS.[^2] On February 4, 2020, the Secretary of HHS issued a declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of SARS-CoV-2 based on the HHS Secretary’s public health emergency determination under section 564(b)(1)(C) of the FD&C Act.[^3] In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19.[^4]

Under section 564 of the FD&C Act, the FDA Commissioner may authorize the use of unapproved medical products, or unapproved uses of approved medical products, in certain emergency circumstances, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use, to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by chemical, biological, radiological, and nuclear (CBRN) threat agents when certain criteria are met. The Emergency Use Authorization (EUA) authorities allow FDA to help strengthen the nation’s public health protections against CBRN threats by facilitating the availability and use of medical countermeasures needed during certain public health emergencies.

As of August 15, 2022, FDA has issued EUAs for more than 439 tests for COVID-19, including more than 354 diagnostic and 85 serology or other immune response tests. Further, two molecular diagnostic COVID-19 tests have been granted marketing authorization through the traditional device premarket review pathways. In the context of a public health emergency involving pandemic infectious disease, it is critically important that tests are validated because false results not only can negatively impact the individual patient but also can have a broad public health impact. False positive results for diagnostic tests, for example, can lead to unnecessary quarantine and potential further spread when presumed positive individuals are quarantined together, wasted contact tracing and testing resources, and delay in accurate diagnosis and appropriate treatment for the individual. False negative results can lead to lack of appropriate treatment for the individual and further spread of the disease.

Previous versions of this guidance described policies regarding the distribution and offering of certain tests for clinical use prior to or without an EUA. These policies were issued to help quickly increase availability of tests in the early stages of the pandemic. Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under the Clinical Laboratory Improvement Amendments (CLIA), section 353 of the Public Health Service Act (42 USC 263a), use of that test is limited to laboratories that are certified under CLIA, and meet the requirements to perform tests of high complexity, and at the point-of-care (POC) when covered by such a laboratory’s CLIA certificate. Throughout this guidance, references to “high-complexity CLIA-certified laboratories” are referring to laboratories that are certified under CLIA and meet the requirements to perform tests of high complexity. These policies did not apply to at-home tests or tests with home specimen collection.

FDA has updated these policies when appropriate in response to the changing landscape of this pandemic. The previous update on November 15, 2021, explained FDA’s intent to review EUA requests for certain types of tests that FDA believed would be most beneficial at that stage of the pandemic. In addition, in the November 15, 2021, version, FDA revised the previous enforcement policies to reflect that, at that stage of the pandemic, the Agency generally expected COVID-19 tests to have been issued an EUA prior to the tests being distributed or offered.

FDA has continued to closely monitor the COVID-19 testing landscape and believes it is again appropriate to update its policies to reflect the current needs of the pandemic. As explained throughout this guidance, FDA intends to review the EUA requests for a small subset of tests based on the review priorities described in Section IV. A. Traditional marketing pathways remain available to all developers and FDA encourages developers of tests that fall outside the scope of the priorities outlined in this guidance to pursue those routes. In sum, in the September 27, 2022, update, FDA revised this guidance to update the types of COVID-19 tests for which the Agency intends to review EUA requests, to discuss the use of the traditional premarket review pathways for other types of COVID-19 tests for which the Agency does not intend to review EUA requests, and to make minor updates to the enforcement policies. In the current version of this guidance, FDA has revised the duration for which the policies in this guidance are intended to remain in effect.

## III. Scope
This guidance applies to diagnostic and serology tests for COVID-19.[^5] The policies and recommendations described in this guidance are intended to facilitate availability of tests for COVID-19 that FDA believes will be most beneficial at the current stage of the public health emergency.

FDA notes that the enforcement policies in this guidance do not address medical device reporting (MDR) under 21 CFR Part 803 for tests offered prior to authorization as described in the guidance. Developers offering such tests are expected to comply with applicable MDR requirements, including reporting of medical device events that reasonably suggest that their device may have caused or contributed to a death or serious injury, and malfunctions that would be likely to cause or contribute to a death or serious injury if they were to recur. Moreover, unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to high-complexity CLIA-certified laboratories, including testing at the point-of-care when the site is covered by the laboratory’s CLIA certificate for high complexity testing.

## IV. Policy
### A. Review of EUA Requests for COVID-19 Tests
The issuance of an EUA is discretionary. FDA’s decision to review and process an EUA request, and ultimately issue an EUA if the relevant statutory criteria are met, is based on a determination, on a case-by-case basis, that such action is necessary to protect the public health in an emergency. It is an authorization that the government “may” issue when necessary to protect the public health in an emergency (see section 564(a)(1) of the FD&C Act (21 U.S.C. 360bbb-3(a)(1)), which states, in relevant part, “subject to the provisions of this section, the Secretary may authorize the introduction into interstate commerce…a drug, device, or biological product intended for use in an actual or potential emergency”). FDA’s January 2017 guidance, *Emergency Use Authorization of Medical Products and Related Authorities,* describes factors that FDA intends to use in its prioritization of EUA requests, such as the public health need for the product, the availability of the product, the availability and adequacy of the information concerning the likelihood that the product may be safe and effective in preventing, treating, or diagnosing the condition, and whether the product is included in government stakeholder stockpiles.

Given the need to address urgent public health priorities, FDA has and continues to prioritize among the EUA requests it receives for COVID-19 tests.

At this stage of the pandemic, FDA intends to prioritize its review of EUA requests and supplemental EUA requests from experienced developers for diagnostic tests that are likely to have a significant public health benefit (e.g., employ innovative technology) or are likely to fulfill an unmet need (e.g., diagnosing infection with a new variant or subvariant).

FDA generally intends to focus its review on EUA requests and supplemental EUA requests for tests that are within these priorities. In addition to the above priorities, FDA also intends to focus its review on EUA requests that are from or supported by a U.S. government stakeholder, such as tests funded by the Biomedical Advanced Research and Development Authority (BARDA) or the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx). FDA intends to notify test developers of its intent by email if FDA declines to review or otherwise decides not to authorize a test/modification in an EUA request or supplemental EUA request.

In general, FDA believes these priorities are appropriate to address the public health needs at the current stage of the public health emergency based on the available information and may adjust these priorities as public health needs change. Specifically, there is generally sufficient availability of authorized high-throughput laboratory-based diagnostic tests intended for use with pooled samples and authorized home-use antigen tests that are available for over-the-counter (OTC) or prescription use.

FDA believes that the number of EUA requests that fall within FDA’s current review priorities described in this guidance are likely limited and generally encourages developers to submit COVID-19 tests through traditional premarket review pathways. If you are unsure whether your test may be prioritized for review, we encourage you to reach out to CDRH-EUA-Templates@fda.hhs.gov; however, at this stage, FDA strongly encourages developers of new tests and existing tests for which modifications are sought to pursue traditional pre-market pathways.

### B. State Authorization of High-Complexity CLIA-Certified Laboratories
Versions of this guidance prior to November 15, 2021, described a policy regarding States and territories that authorize laboratories within their State or territory to develop their own COVID-19 tests and perform specimen testing, where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA.

Under such policy, a State or territory choosing to authorize laboratories within that State or territory to develop and perform a test for COVID-19 would do so under authority of its own State law, and under a process that it established, and FDA did not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation was not submitted to FDA and the laboratory did not submit an EUA request to FDA, and where instead the State or territory took responsibility for COVID-19 testing by laboratories in its State during the COVID-19 outbreak. This policy applied only to tests designed, developed, and used within a single, high-complexity, CLIA-certified laboratory. The policy did not apply to at-home tests or tests with home specimen collection, or any testing outside of a high-complexity CLIA-certified laboratory.

In versions of this guidance prior to November 15, 2021, FDA requested that the State or territory notify us if it chose to use this flexibility to expedite COVID-19 testing. FDA indicated that it would not be reviewing the process adopted by the State or territory. FDA expected that such States and territories as part of their oversight process would require laboratories developing SARS-CoV-2 tests to validate those tests prior to use. FDA encouraged laboratories that developed and performed a test for COVID-19 that was authorized by a State or territory to notify FDA that they have started clinical testing by sending an email to that effect to CDRH-EUA-Templates@FDA.HHS.GOV, and provide information on testing capacity.

In the November 15, 2021, version of this guidance, FDA revised this policy such that FDA no longer intended to apply the policy to any additional States or territories going forward. The FDA is maintaining the policy in Section IV.B. of the November 15, 2021, policy, without further revision. For the States and territories listed on the notification list on FDA’s website prior to November 15, 2021, that are continuing to authorize laboratories within their State or territory to develop and perform a test for COVID-19, FDA does not intend to object to the use of such tests for specimen testing where notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request, and where instead the State or territory takes responsibility. This policy applies only to tests designed, developed, and used within a single, high-complexity CLIA-certified laboratory. This policy does not apply to at-home tests or tests with home specimen collection, or any testing outside of a high-complexity CLIA-certified laboratory.

FDA notes that laboratories should be aware of requirements to report test results to appropriate federal, state, and local public health agencies in accordance with applicable federal, state, and local laws.  

### C. Distribution and Offering of SARS-CoV-2 Diagnostic and Serology Tests During FDA Review
Previous versions of this guidance document described enforcement policies where FDA generally did not intend to object to developers distributing and offering certain tests prior to FDA authorization, as described in the policies. Those policies were updated in the November 15, 2021, version of the guidance, and FDA is generally continuing those updated policies and clarifying them, as discussed below.

#### (1) FDA Review of EUA Requests
For the following tests, FDA does not intend to object to the continued distribution or offering of the test while FDA reviews the EUA request for the test:

- Tests on one of the [notification lists](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/notifications-and-emergency-use-authorizations-faqs-testing-sars-cov-2) on FDA’s website at the time of issuance of this updated guidance; and,
- Laboratory developed tests (LDTs) offered following the HHS August 2020 Web Statement entitled, “Rescission of Guidances and Other Informal Issuances Concerning Premarket Review of Laboratory Developed Tests” (“August 2020 HHS Announcement”) and prior to November 15, 2021, where an EUA request was submitted to FDA as described in Section IV.C.2 of the November 15, 2021 version of this guidance document.

For tests described in this section, FDA intends to notify test developers by email if FDA declines to review, declines to issue, or otherwise decides not to authorize the test for any reason, including lack of response or a determination that there is a lack of adequate data to support authorization. If so notified, FDA generally expects developers to cease distributing, marketing, and offering their tests within 15 calendar days. Moreover, if FDA identifies a significant problem or concern with a test, based either on the provided information or external reports, FDA generally would expect the developer to take appropriate steps to address such problems, which could include conducting a recall of the test and/or notification concerning corrected test reports indicating prior test results may not be accurate.

#### (2) Recommendations Regarding Test Reports and Other Information for Tests Offered During FDA Review of EUA Requests
FDA continues to recommend the following:

1. Test reports should prominently disclose that the test has not been reviewed by FDA. Until the test is authorized by FDA, any statements in the test reports and other labeling that expressly state or imply that the test has been authorized by FDA would be false. Similarly, any statements in the test reports and other labeling that state or imply that EUA issuance or FDA authorization are imminent or pending could be misleading.

2. Developers should make publicly available on their website the instructions for use for the test and data about the test’s performance characteristics, including a summary of assay performance.

3. Instructions for use and patient test reports for serology tests should include information that helps users and patients understand the test results, including the following:

   - Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct (i.e., diagnostic) testing for SARS-CoV-2 is necessary.
   - Results from antibody testing should not be used to diagnose or exclude acute SARS-CoV-2 infection.
   - Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E.

In addition, as noted in previous versions of this guidance and earlier in this updated guidance, unless and until an EUA is issued that authorizes additional testing environments for a specific test, under CLIA, use of that test is limited to high-complexity CLIA-certified laboratories, including testing at the POC when the site is covered by such a laboratory’s CLIA certificate.

### D. Modifications to EUA-Authorized Diagnostic COVID-19 Tests
Throughout the course of the pandemic, FDA has issued various policies with respect to modifications and, as discussed further below, FDA is updating these policies. The policies in this section do not apply to at-home tests or tests with at-home specimen collection.

In order to provide transparency, when a developer is distributing or offering a test that is a modification of an EUA-authorized diagnostic test prior to or without authorization of the modified test, as discussed in this section, the recommendations in Section IV.C.2 of this updated guidance apply. FDA further recommends that the developer post data about the modified test’s performance characteristics on the developer’s website, and that the instructions for use or test protocol and the test reports accurately reflect the modification and prominently disclose that the test has been modified since authorization by FDA and that the modified test has not been reviewed by FDA.

If FDA identifies a significant problem or concern with a modified test, based either on the provided information or external reports, that cannot be addressed in a timely manner, FDA generally would expect the developer to cease distribution, marketing and offering the modified test and address such problem, which could include conducting a recall of the modified test and/or notification concerning corrected test reports indicating prior test results may not be accurate.

#### (1) Modifications Made After Issuance of this Updated Guidance
In addition to the priorities above, FDA intends to review supplemental EUA requests that fulfill a condition of an EUA. For other supplemental requests, such as those that are beyond the priorities outlined above, FDA encourages developers to consider including the modification in a submission through a traditional premarket review pathway. In general, FDA expects such modified tests to be authorized under an EUA or pursuant to a traditional premarket review pathway before being distributed or offered.

When a high-complexity CLIA-certified laboratory is modifying an authorized COVID-19 molecular diagnostic test, including one for which such laboratory is not the developer of the original, EUA-authorized test, and the modifications do not change the indication for use set forth in the EUA (e.g., including new/different extraction kits or instruments that would not be expected to change the indication for use) and do not change the analyte specific reagents (e.g., the modifications do not change the PCR primers and/or probes), FDA does not intend to object to implementation of the modification to the diagnostic test without notification to FDA or a new or amended EUA where the laboratory has validated the modification and confirmed that the performance of the modified test is equivalent to the performance of the authorized test, and use of the test is limited to the high-complexity CLIA-certified laboratory in which the modification was made.

In such cases, where the laboratory modifying and performing the test is not the developer of the original, EUA-authorized test, FDA encourages the laboratory to collaborate with the developer of the authorized test so that validation data supporting the modifications can be submitted by the original developer to FDA in a supplemental EUA request or incorporated into a future submission through the traditional premarket review pathways.

#### (2) Certain Modifications Made Before Issuance of this Updated Guidance
Under previous versions of this guidance, when a commercial manufacturer made certain modifications to its EUA-authorized COVID-19 diagnostic test, and where validation data supporting the modification had been submitted in a supplemental EUA request, FDA stated that it did not intend to object to implementation of the modification while FDA conducted its review, except for modifications to add specimen types that have not been previously authorized with another test of the same technology. For such modifications made and implemented as discussed in the policies in the previous version of the guidance, FDA does not intend to object to such commercial manufacturers continuing to implement the modification while FDA conducts its review.

Under previous versions of the guidance, when a high-complexity CLIA-certified laboratory modified an EUA-authorized COVID-19 diagnostic test[^20] prior to November 15, 2021, for use with a new specimen type, where the new specimen type has been previously authorized for another test of the same technology[^21] and where the laboratory had validated the test for the new specimen type, FDA stated that it did not intend to object to the use of such a modified test without notification to FDA or a new or amended EUA. For all other types of modifications made by the high-complexity CLIA-certified laboratory prior to November 15, 2021, for an EUA-authorized COVID-19 diagnostic test, in previous versions of the guidance, FDA stated that it did not intend to object to the use of the test by high-complexity CLIA-certified laboratories, without notification to FDA or a new or amended EUA, where the modified test is validated using a bridging study to the EUA-authorized test.

For high-complexity CLIA-certified laboratories that modified an authorized COVID-19 molecular diagnostic test after November 15, 2021, but before issuance of the September 27, 2022, version of the guidance, including one for which such laboratory is not the developer of the original, EUA-authorized test, and the modifications do not change the indication for use set forth in the EUA (e.g., including new/different extraction kits or instruments that would not be expected to change the indication for use) and do not change the analyte specific reagents (e.g., the modifications do not change the PCR primers and/or probes), FDA stated that it did not intend to object to implementation of the modification to the diagnostic test without notification to FDA or a new or amended EUA where the laboratory has validated the modification and confirmed that the performance of the modified test is equivalent to the performance of the authorized test, and use of the test is limited to the high-complexity CLIA-certified laboratory in which the modification was made.[^23]

For such modifications made and implemented by high-complexity CLIA-certified laboratories as discussed in the policies in the previous versions of the guidance, FDA does not intend to object to such laboratories continuing to offer any of those modified tests.

In such cases, where the laboratory performing the modified test is not the developer of the original, EUA-authorized test, FDA encourages the laboratory to share its validation data with the developer of the original, EUA-authorized test so that the developer of the original, EUA-authorized test can use the validation data in support of a supplemental EUA request to add the modification or can incorporate it into a future submission through the traditional premarket review pathways.

## V. Validation
All clinical tests should be validated using clinical specimens and an appropriate comparator test prior to use.

In the context of a public health emergency, it is critically important that tests be validated prior to use because false results not only can negatively impact the individual patient but also can have a broad public health impact. However, FDA also generally accepts a lower level of evidence of validation for an EUA than for traditional premarket review pathways. FDA has provided recommendations regarding testing that should be performed to ensure analytical and clinical validity to the level of evidence expected for an EUA, including descriptions of appropriate comparators for different types of tests, in the EUA templates available through download from our website.[^24] Depending on the characteristics of a developer’s test, additional validation studies may be recommended.

Because the level of evidence required for authorization under traditional premarket review pathways is higher than that required for an EUA, the recommendations in the EUA templates may not be sufficient for developers seeking marketing authorization of their tests through traditional premarket review pathways. FDA can provide recommendations specific to a test developer’s situation through inquiries to [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) or through pre-submission interactions.[^25]

Developers can use alternative approaches. FDA encourages developers to discuss any alternative technological approaches to validating their test with FDA through [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV).

Additionally, FDA continues to expect certain serology tests to be independently evaluated by NIH/NCI,[^26] prior to authorization, when requested by the FDA. When performed, this additional testing can assist FDA in determining whether the EUA issuance criteria in section 564 of the FD&C Act have been met and whether FDA should authorize the test. This independent evaluation may also be used to assist FDA in determining whether the criteria for marketing authorization have been met for tests submitted through traditional premarket review pathways.

## VI. Availability of EUA Templates and Inquiries Regarding Validation
FDA has made available through download from our website[^27] a series of templates that developers may choose to use to facilitate the preparation and submission of an EUA request for various types of COVID-19 tests. The templates reflect FDA’s current thinking on validation recommendations for SARS-CoV-2 tests and the data and information that developers should submit to facilitate the EUA process. The templates provide information and recommendations, and FDA plans to update them as appropriate as more is learned about COVID-19 and more experience is gained with the EUA process for the various types of COVID-19 tests. Developers may use alternative approaches. Developers who are considering alternative approaches should consider seeking FDA’s feedback.

FDA can provide validation recommendations specific to a test developer’s situation both for those seeking EUA and for those seeking marketing authorization through traditional review pathways. Developers can send simple inquiries to [CDRH-EUA-Templates@fda.hhs.gov](mailto:CDRH-EUA-Templates@fda.hhs.gov) or submit a pre-EUA or pre-submission for more complex inquiries.[^28] For tests seeking marketing authorization through traditional premarket review pathways, FDA may recommend validation studies or supportive evidence in addition to the recommendations in the EUA templates.

Members of the public can submit questions about the templates to [CDRH-EUA-Templates@FDA.HHS.GOV](mailto:CDRH-EUA-Templates@FDA.HHS.GOV), or they can submit comments regarding the templates to the public docket established for this guidance.

---

[^1]: See 85 FR 7316; available at [https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency](https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency).
[^2]: Secretary of Health and Human Services, Determination that a Public Health Emergency Exists (originally issued on Jan. 31, 2020, and subsequently renewed), available at [https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx](https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx).
[^3]: 85 FR 7316; available at [https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency](https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency).
[^4]: Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak (Mar. 13, 2020), available at [https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/](https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/). On February 24, 2021, there was a Presidential Declaration continuing the national emergency concerning the COVID-19 pandemic beyond March 1, 2021. See Continuation of the National Emergency Concerning the Coronavirus Disease 2019 (COVID-19) Pandemic (February 24, 2021), available at [https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic](https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic).
[^5]: Throughout this guidance, the term “diagnostic test” is generally used to refer to molecular or antigen tests, both of which can be used to diagnose infection with the SARS-CoV-2 virus. Diagnostic tests may be designed for use in various settings, such as in a CLIA-certified laboratory, at the point of care at a site covered by a laboratory’s CLIA certificate, or at home. Screening tests, which are used for testing individuals without symptoms or other reasons to suspect COVID-19, are a subset of diagnostic tests. Molecular tests detect the presence of viral RNA and antigen tests detect the presence of viral proteins that are part of the SARS-CoV-2 virus. There may also be diagnostic tests that incorporate different technologies, such as breath tests, that have a reasonable expectation of technical and clinical success. While the principles in this guidance are generally still applicable to such tests, there are fewer available, so different approaches may be appropriate. Therefore, FDA recommends that developers of such tests contact FDA at CDRH-EUA-Templates@fda.hhs.gov to discuss the best approach for their test.
[^20]: This applies to modifications to any EUA-authorized diagnostic test, including a laboratory’s own test with an EUA or a purchased kit from a commercial manufacturer with an EUA, but does not apply to modifications of authorized home collection kits.
[^21]: For the purposes of this guidance, all nucleic acid amplification tests are considered to have the same technology.
[^22]: Other modifications, including new specimen types, test settings (e.g., point-of-care, home testing), and new patient populations (e.g., asymptomatic individuals), among others, do not fall under this policy.
[^23]: FDA generally considers equivalent performance to be where the LoD of the modified test (using the same validation material used in the LoD study described in the authorized test’s Instructions For Use (IFU)) is within 3x of the LoD established in the authorized test’s IFU or that the LoD of the modified test is within 3x of the LoD of the authorized test in a direct comparison LoD study.
[^24]: [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas)
[^25]: See FDA Guidance document “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program,” available at: [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program).
[^26]: The FDA is working with the NIH, the Centers for Disease Control and Prevention (CDC), and BARDA to assess the performance of certain commercial manufacturers’ serology tests. As part of this project, the FDA, working with partnering agencies, has designed a performance assessment protocol that offers a mechanism for an independent evaluation of certain lateral flow and certain enzyme-linked immunosorbent assay (ELISA) or similar technology-based SARS-CoV-2 antibody tests in a laboratory environment. Under this protocol, each test evaluated at the NIH/NCI will be evaluated with a well-characterized sample panel consisting of positive and negative plasma and/or serum samples. The approach represents a balanced attempt to provide a reasonable understanding of the potential performance of a significant number of the tests within a short time period. Performance results are considered during FDA’s review of an EUA request for the test.
[^27]: [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas)
[^28]: See FDA Guidance document “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program,” available at: [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program).


# 483  2023-03-24_FDA Website - Transition Plan for Medical Devices.md
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last updated: 2026-03-04 by BA
file_name: 2023-03-24_FDA Website - Transition Plan for Medical Devices.md
file_date: 2023-03-24
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web_url: https://www.fda.gov/medical-devices/covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2
summary_short: The FDA announces final March 24, 2023 guidances that lay out how medical devices covered by COVID-19 enforcement policies or issued COVID-19 EUAs should transition back to normal regulatory operations. It highlights FDA recommendations to create a transition implementation plan, prepare and submit an appropriate marketing submission, and take other follow-on actions, with links to the guidances and an April 18, 2023 webinar for stakeholders.


CONTENT

March 24, 2023 - The FDA has finalized two guidances: [Transition Plan for Medical Devices That Fall Within Enforcement Policies Issued During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-fall-within-enforcement-policies-issued-during-coronavirus-disease) and [Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-issued-emergency-use-authorizations-euas-related-coronavirus-disease). The guidances outline the FDA's general recommendations to transition from certain policies adopted and operations implemented during the COVID-19 pandemic to normal operations, including the FDA's recommendations for:

Developing a transition implementation plan,
Submitting a marketing submission, and
Taking other actions with respect to these devices.
The FDA encourages stakeholders to review the two final guidances, view the webinar, and reach out to the FDA if they have questions or concerns. In particular, for manufacturers planning to seek marketing authorization for their devices, the FDA recommends beginning work on a marketing submission, including a transition implementation plan, as described in the guidances.

Additional Resources:
[Transition Plan for Medical Devices That Fall Within Enforcement Policies Issued During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-fall-within-enforcement-policies-issued-during-coronavirus-disease)
[Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-issued-emergency-use-authorizations-euas-related-coronavirus-disease)
[Webinar on Guidances on COVID-19 Transition Plans for Medical Devices - April 18, 2023](https://www.fda.gov/medical-devices/medical-devices-news-and-events/webinar-guidances-covid-19-transition-plans-medical-devices-04182023)


# 12,172  2023-03-27_FDA Guidance - Transition Plan for Medical Devices Issued EUAs.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2023-03-27_FDA Guidance - Transition Plan for Medical Devices Issued EUAs.md
file_date: 2023-03-27
title: FDA Guidance - Transition Plan for Medical Devices Issued EUAs
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summary_short: The FDA “Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to COVID-19” (March 27, 2023) describes how manufacturers should transition devices from EUA status to normal regulatory pathways after EUA declarations are terminated. It outlines expectations for marketing submissions, continued or discontinued distribution, labeling updates, and disposition of already distributed devices, with special provisions for in vitro diagnostics, CLIA categorization, and life-supporting or reusable equipment.


CONTENT

***INTERNAL TITLE:*** Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19)
Guidance for Industry, Other Stakeholders, and Food and Drug Administration Staff

Document issued on March 27, 2023.

The draft of this document was issued on December 23, 2021.

For questions about this document, contact the Regulation, Policy, and Guidance Staff at [RPG@fda.hhs.gov](mailto:RPG@fda.hhs.gov). For general questions about emergency use authorizations, contact the Office of the Commissioner/Office of the Chief Scientist/Office of Counterterrorism and Emerging Threats at [AskMCMi@fda.hhs.gov](mailto:AskMCMi@fda.hhs.gov).

## Preface
### Public Comment
You may submit electronic comments and suggestions at any time for Agency consideration to [https://www.regulations.gov](https://www.regulations.gov). Submit written comments to the Dockets Management Staff, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. Identify all comments with the docket number FDA-2021-D-1149. Comments may not be acted upon by the Agency until the document is next revised or updated.

### Additional Copies
Additional copies are available from the Internet. You may also send an email request to [CDRH-Guidance@fda.hhs.gov](mailto:CDRH-Guidance@fda.hhs.gov) to receive a copy of the guidance. Please include the document number GUI00020042 and complete title of the guidance in the request.

## Table of Contents
I. Introduction ......................................................................................................................... 1  
II. Background ......................................................................................................................... 2  
III. Scope ................................................................................................................................... 5  
IV. Guiding Principles .............................................................................................................. 5  
V. Transition Plan for Devices Authorized Under an EUA .................................................... 6  
   A. “Notifications of Intent” for Certain Reusable Life-Supporting or Life-Sustaining Devices ............................................................................................................................ 8  
   B. Devices distributed after the EUA termination date ....................................................... 9  
      1. Recommendations for “Transition Implementation Plan” ......................................... 10  
      2. Enforcement policy for devices with a marketing submission under review by FDA 12  
      3. Additional considerations for EUA-authorized in vitro diagnostics – Clinical Laboratory Improvement Amendments of 1988 (CLIA) categorization and waivers ........ 14  
   C. Devices not distributed after the EUA termination date ............................................... 16  
   D. Discontinuing distribution of a device .......................................................................... 17  
   E. Quality System considerations ...................................................................................... 18  
   F. Laboratory developed tests (LDTs) ............................................................................... 18  
VI. Examples ........................................................................................................................... 19  
   Example 1 ........................................................................................................................... 19  
   Example 2 ........................................................................................................................... 20  
   Example 3 ........................................................................................................................... 21  
   Example 4 ........................................................................................................................... 22  

## I. Introduction
FDA plays a critical role in protecting the United States (U.S.) from threats such as emerging infectious diseases, including Coronavirus Disease 2019 (COVID-19). FDA is committed to providing timely guidance to support response efforts to the COVID-19 pandemic. FDA recognizes that it will take time for device manufacturers, device distributors, healthcare facilities, healthcare providers, patients, consumers, and FDA to adjust from policies adopted and operations implemented during the COVID-19 pandemic to “normal operations.” To provide a clear policy for all stakeholders and FDA staff, the Agency is issuing this guidance to describe FDA’s general recommendations for this transition process with respect to devices issued emergency use authorizations (EUAs) related to COVID-19, including recommendations regarding submitting a marketing submission, as applicable, and taking other actions with respect to these devices.

FDA is concurrently issuing a companion transition guidance to describe FDA’s recommendations for devices that fall within certain enforcement policies issued during the COVID-19 public health emergency (PHE). FDA believes these transition guidances will help prepare manufacturers and other stakeholders for the transition to normal operations and foster compliance with applicable requirements under the FD&C Act and its implementing regulations.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should* in Agency guidances means that something is suggested or recommended, but not required.

## II. Background
In 2019, an outbreak of respiratory disease caused by a novel coronavirus began. The virus has been named “SARS-CoV-2,” and the disease it causes has been named “Coronavirus Disease 2019” (COVID-19). On January 31, 2020, the Secretary of Health and Human Services (HHS) issued a declaration of a PHE related to COVID-19 in accordance with section 319 of the Public Health Service Act (PHS Act) and mobilized the Operating Divisions of HHS. In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19. On February 9, 2023, the HHS Secretary renewed the section 319 PHE declaration related to COVID-19, effective February 11, 2023. The section 319 PHE declaration related to COVID-19 is anticipated to expire at the end of the day on May 11, 2023.

FDA has authorized the emergency use of devices under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Section 564 of the FD&C Act authorizes FDA, after the HHS Secretary has made a declaration of emergency or threat justifying authorization of emergency use (an “EUA declaration”), to authorize the emergency use of an unapproved product or an unapproved use of an approved product for certain emergency circumstances. FDA may issue an EUA to allow a product to be used to diagnose, treat, or prevent a serious or life-threatening disease or condition referenced in the EUA declaration, when the statutory criteria are met, including FDA’s determination that, based on the totality of scientific evidence, the product may be effective for such use, the known and potential benefits outweigh the known and potential risks for such use, and that there are no adequate, approved, and available alternatives.

An EUA issued under section 564 of the FD&C Act remains in effect for the duration of the relevant EUA declaration, unless FDA chooses to revoke the EUA because the criteria for issuance are no longer met or revocation is appropriate to protect public health or safety. An EUA declaration under section 564 of the FD&C Act is distinct from, and is not dependent on, a declaration by the HHS Secretary of a PHE under section 319 of the PHS Act. The device EUAs related to COVID-19 remain in effect until the relevant EUA declaration under section 564 of the FD&C Act is terminated or FDA otherwise revokes a specific EUA, [^14] even if the section 319 PHE declaration related to COVID-19 expires before then. [^15]

Given the magnitude of the response to the COVID-19 pandemic, including the number of devices issued EUAs, FDA recognizes that stakeholders may need time to adjust after the termination of the device EUA declarations to help ensure an orderly and transparent transition to normal operations. Further, FDA is taking into account that the manufacture, distribution, and use of devices in the context of the COVID-19 pandemic raises unique considerations. These unique considerations include, for example, the manufacturing of devices by non-traditional manufacturers to address supply issues and the distribution and use of capital or reusable equipment (e.g., ventilators, extracorporeal membrane oxygenation systems) under EUAs.

FDA developed this guidance to describe a transition plan, among other things, to help avoid disruption in device supply and help facilitate compliance with applicable FD&C Act requirements after the termination of the relevant EUA declaration related to COVID-19 under section 564(b) of the FD&C Act.

Section 564 of the FD&C Act provides a statutory framework describing the circumstances in which an EUA declaration shall terminate and the process for such termination. [^16] Under section 564(b) of the FD&C Act, the HHS Secretary is required to provide advance notice that an EUA declaration will be terminated and to publish such notice in the Federal Register. [^17] When an EUA declaration is terminated, all EUAs issued under that declaration also terminate. After an EUA declaration terminates, it ceases to be in effect and the emergency use of all products under the EUA declaration are no longer authorized.

Pursuant to section 564(b)(2)(B) of the FD&C Act, when an EUA for an unapproved product ceases to be effective as a result of the termination of an EUA declaration, FDA must consult with the manufacturer of such product with respect to the appropriate disposition of the product. FDA believes that by issuing this guidance in draft with a proposed transition policy and requesting public comment (including from manufacturers of EUA-authorized devices), the Agency has satisfied the requirement to consult with manufacturers, while also efficiently managing Agency resources. To address any unique considerations or other issues related to disposition of product that are not otherwise discussed in this guidance, FDA recommends engagement with the Agency as soon as possible. [^18]

HHS intends to publish the advance notice of termination of each EUA declaration [^19] pertaining to devices in the Federal Register 180 days before the day on which the EUA declaration is terminated. The advance notice of termination of each device EUA declaration may occur simultaneously or at different times, depending on whether the circumstances underlying such declarations continue to exist. [^20] For purposes of this guidance, FDA refers to the date on which an EUA is terminated as the “EUA termination date.” During the time between the advance notice of termination of an EUA declaration and the EUA termination date, manufacturers of devices with EUAs issued pursuant to such an EUA declaration and others [^21] must continue to comply with the terms of the devices’ respective EUAs, including applicable conditions of authorization [^22] identified in the EUA letters of authorization for the devices.

FDA recommends that manufacturers of devices authorized under EUAs plan their post-EUA regulatory and disposition strategies now. When an EUA declaration is terminated, the Agency intends to promptly publish notice of termination of the associated EUAs in the Federal Register and an explanation of the reasons for the termination. [^23]

## III. Scope
This guidance applies to devices that have been issued an EUA under section 564 of the FD&C Act on the basis of a device EUA declaration related to COVID-19. [^24]

Current good manufacturing practice deviations authorized under section 564A(c) of the FD&C Act are outside the scope of this guidance.

This guidance does not apply to devices for which FDA has revoked the EUA under section 564(g)(2)(B)-(C) of the FD&C Act because the criteria under section 564(c) of the FD&C Act were no longer met or because other circumstances made such revocation appropriate to protect the public health or safety.

## IV. Guiding Principles
In developing this guidance, and its companion transition guidance regarding devices that fall within certain enforcement policies issued during the COVID-19 PHE, several guiding principles were followed. Some derive from existing policies and are widely known, and others are key to understanding the approach set forth in this guidance. Thus, anyone using this guidance should bear in mind the following guiding principles:

- This guidance is intended to help facilitate continued patient, consumer, and healthcare provider access to devices needed in the prevention, treatment, and diagnosis of COVID-19.
- FDA believes the policies and recommendations in this guidance will help to ensure an orderly and transparent transition for devices that fall within the scope of this guidance. FDA’s policies and recommendations in this guidance are consistent with the Agency’s statutory mission to both protect and promote the public health. [^25]
- FDA’s policies and recommendations follow, among other things, a risk-based approach with consideration of differences in the intended use and regulatory history of devices, including whether the device is life-supporting or life-sustaining, [^26] capital or reusable [^27] equipment, a single-use device, [^28] and whether another version of the device is FDA-cleared or -approved.
- As always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type. This may include FDA revising or revoking an EUA, [^29] requesting a firm initiate a recall (see 21 CFR 7.45), [^30] or taking other actions, including an enforcement action. Moreover, FDA may revise the enforcement policies and recommendations in the guidance, as appropriate.

## V. Transition Plan for Devices Authorized Under an EUA
As previously stated, FDA recognizes that it will take time for device manufacturers, device distributors, healthcare facilities, healthcare providers, patients, consumers, and the Agency to adjust from policies adopted and operations implemented during the COVID-19 pandemic to normal operations. FDA seeks to encourage and facilitate an appropriate transition period to help, among other things, avoid exacerbating product shortages and supply chain disruptions. This transition plan takes into account the advance notice(s) of termination of the EUA declarations pertaining to devices, and the discussion below contains recommendations regarding the preparation and submission of marketing submissions (including the timing of such submissions), manufacturers' actions if they do not wish to continue distributing their product after the EUA termination date, and the distribution of devices within the scope of this guidance.

For purposes of this guidance, devices are considered to be "already distributed" if they are finished devices that are labeled and are in distribution in the U.S. supply chain or are in the possession of the end user. For purposes of this guidance, FDA would generally consider devices to be "in distribution" to mean those finished, labeled devices that are no longer in the manufacturer's possession that are in transit to or held in a third party’s device inventory not on behalf of the manufacturer, in a federal, state, or other governmental stockpile, or at a location where devices are then offered for direct sale to the end user.

During the time between the advance notice of termination of an EUA declaration and the EUA termination date, manufacturers of devices with EUAs issued pursuant to such an EUA declaration and others must continue to comply with the terms of the devices’ respective EUAs, including applicable conditions of authorization identified in the EUA letters of authorization for the devices.

FDA understands that there may be scenarios that are not specifically addressed in this guidance, but generally believes that the policies and recommendations described, regardless of the specific scenario for a manufacturer, will help avoid disruptions in critical devices and allow FDA to best manage its resources for review of marketing submissions. To address any unique considerations or other issues not otherwise discussed in this guidance, manufacturers may wish to initiate discussions with the Agency through the Q-Submission Program, including requesting feedback in Pre-Submissions. Manufacturers should submit any Pre-Submissions with the understanding that their device will no longer be authorized for emergency use beginning on the EUA termination date. If the manufacturer’s intent is to continue to distribute its device after the EUA declaration for the device has been terminated, the manufacturer should promptly start preparing, and FDA intends to help facilitate acceptance of, a marketing submission before the EUA termination date. For details on the Q-Submission Program, refer to the guidance “[Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program](https://www.google.com/url?q=https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program&sa=D&source=apps-viewer-frontend&ust=1734725789006654&usg=AOvVaw23XJU5bUWWiOVI7qzWrNcE&hl=en).”

### A. “Notifications of Intent” for Certain Reusable Life-Supporting or Life-Sustaining Devices
Given the public health significance of certain reusable life-supporting or life-sustaining devices that have been issued an EUA, FDA requests that manufacturers of such devices submit to FDA information regarding whether or not they intend to submit a marketing submission to FDA and continue distributing their product after the EUA termination date. This information will assist the Agency in resource planning for marketing submission review and providing support to manufacturers. This request applies to EUA-authorized devices with a product code listed in Table 1:

| Product Code | Device Type                                             | Classification Regulation |
|--------------|---------------------------------------------------------|---------------------------|
| BSZ          | Gas-machine, anesthesia                                 | 21 CFR 868.5160           |
| CAW          | Generator, oxygen, portable                             | 21 CFR 868.5440           |
| BTT          | Humidifier, respiratory gas, (direct patient interface) | 21 CFR 868.5450           |
| QAV          | High flow/high velocity humidified oxygen delivery device | 21 CFR 868.5454          |
| CBK          | Ventilator, continuous, facility use                    |  21 CFR 868.5895                         |
| MNT          | Ventilator, continuous, minimal ventilatory support, facility use | 21 CFR 868.5895                      |
| NOU          | Continuous, ventilator, home use                        | 21 CFR 868.5895           |
| MNS          | Ventilator, continuous, non-life-supporting             | 21 CFR 868.5895                        |
| ONZ          | Mechanical ventilator                                   | 21 CFR 868.5895                         |
| BTL          | Ventilator, emergency, powered (resuscitator)           | 21 CFR 868.5925           |
| QOO          | Ventilator tubing and accessories                       | No corresponding CFR section |
||

Manufacturers of the devices identified in Table 1 should submit the following information to the CDRH Document Control Center as soon as possible after issuance of this guidance:

- General information about the manufacturer, including contact information, name and place of business, and email address;
- EUA request number;
- Submission number(s) for related premarket submissions;
- A list of all model numbers or other device identifying information;
- Whether the manufacturer plans to submit a marketing submission; and
- If not planning to submit a marketing submission, the manufacturer should discuss, as applicable, its plans to discontinue distribution of the device, to restore the device to an FDA-cleared or -approved version, to provide a physical copy and/or electronic copy of updated labeling, and any other efforts to address or mitigate potential risks of devices already distributed as of the EUA termination date.

The manufacturer should submit this information designated with the EUA request number as an “EUA report.” FDA recommends that manufacturers notate the following on the cover letter of the submission: “Attention: Notification of Intent.” To the extent the Notification of Intent contains trade secret information or confidential commercial or financial information, FDA will handle that information in accordance with applicable laws, including 21 CFR 20.61.

### B. Devices distributed after the EUA termination date
For manufacturers of devices authorized under an EUA seeking the required marketing authorization for their devices, please refer to the recommendations and policies in the subsections below. FDA recommends that these manufacturers submit their marketing submissions to FDA with sufficient time for the submission to be accepted by FDA before the EUA termination date. The marketing submission should be administratively complete in that it includes all of the information necessary for FDA to conduct a substantive review. FDA understands there may be extenuating circumstances that may make doing so difficult (e.g., ongoing clinical trial or longer term non-clinical studies). Manufacturers in such circumstances should engage with the Agency early in the transition period.

FDA is taking into account that the use of devices during the COVID-19 pandemic may allow manufacturers to utilize a variety of data sources in their marketing submission. As such, FDA anticipates many manufacturers may wish to reference data from related marketing authorizations and submissions, and use real-world data obtained as a result of device use during the COVID-19 pandemic. FDA recommends that marketing submissions include in the cover letter a statement that the device is/was previously authorized under an EUA and the EUA request number, as well as submission number(s) for related premarket submissions. This information will help FDA track devices that are transitioning from an EUA to the required marketing authorization, facilitate review of the submission, and help ensure that transitioning devices can be appropriately considered in light of the policy described in Section V.B.(2) of this guidance.

#### (1) Recommendations for “Transition Implementation Plan”
FDA anticipates that some marketing submissions will include changes or updates to the device and/or its labeling compared to the product that has been distributed under the EUA. For example, a manufacturer may have distributed a singleplex in vitro diagnostic assay under an EUA, and the manufacturer intends to submit a marketing submission for a multiplex in vitro diagnostic assay; or a manufacturer may have distributed a remote monitoring device under an EUA, and the manufacturer intends to submit a marketing submission for such remote monitoring device with an additional, new indication. In addition, in some cases, a manufacturer may not receive a positive decision from FDA on its marketing submission.

To help address all of these situations efficiently, FDA recommends that manufacturers include in the cover letter of their marketing submission a “Transition Implementation Plan” that addresses the manufacturers’ plans for dealing with devices already distributed in the case of a positive decision as well as in the case of a negative decision on the marketing submission. To the extent the Transition Implementation Plan contains trade secret information or confidential commercial or financial information, FDA will handle that information in accordance with applicable laws, including 21 CFR 20.61.

FDA recommends that the Transition Implementation Plan include the following information, as applicable:

- Estimated number of devices under an EUA that are currently in U.S. distribution;
- An explanation of the manufacturer’s benefit-risk based plan for disposition of already distributed product in the event of a negative decision on the marketing submission. If the manufacturer is proposing to leave already distributed product in place, the plan should address the rationale for doing so and considerations such as the following, where relevant:
  - Process for notifying patients, consumers, healthcare facilities, healthcare providers, and device distributors of the device’s regulatory status;
  - Process and timeline for restoring already distributed devices to an FDA-cleared or -approved version;
  - Process and timeline for providing a physical and/or electronic copy of updated labeling that accurately describes the product features and regulatory status (e.g., that the product lacks FDA clearance, approval, or authorization) for reusable devices. To help ensure accessibility to updated labeling for reusable life-supporting/life-sustaining devices, FDA recommends that stakeholders be provided an opportunity to request a physical copy of updated labeling, and after such request, be provided the requested labeling without additional cost; and
  - A description of the maintenance plan for already distributed devices.

- An explanation of the manufacturer’s plans for addressing already distributed product in the event of a positive decision on the marketing submission, including considerations such as the following, where relevant:
  - Process for notifying patients, consumers, healthcare facilities, healthcare providers, and device distributors of the device’s regulatory status; and
  - Process and timeline for providing to users of already distributed devices updated labeling or components for the cleared or approved device, including updated labeling or components to reflect any cleared/approved changes to the already distributed device.

FDA encourages manufacturers to collaborate with device distributors, healthcare facilities, healthcare providers, patients, and consumers, as appropriate, regarding their Transition Implementation Plan to assist all stakeholders with transition planning.

Depending on FDA’s evaluation of the marketing submission, FDA may engage with the manufacturer during the Agency’s review of the submission to discuss the appropriate disposition of already distributed devices described in the Transition Implementation Plan. For marketing submissions that include changes to the device compared to the product that has been distributed under the EUA (e.g., modifications to address a cybersecurity concern), the manufacturer should discuss possible correction or removal with FDA regarding devices already distributed to the end user, as needed. As always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type (e.g., requesting a firm initiate a recall (see 21 CFR 7.45) or taking other actions, including an enforcement action).

#### (2) Enforcement policy for devices with a marketing submission under review by FDA
As previously stated, FDA recognizes that it may take time for device manufacturers, including non-traditional device manufacturers, to adapt and adjust from their operations during the COVID-19 pandemic to normal operations. As such, at this time, FDA does not intend to object to the continued distribution of devices within the scope of this guidance after the EUA termination date where:

- The manufacturer has submitted a marketing submission to FDA and it is accepted by FDA before the EUA termination date; and
- FDA has not taken a final action on the marketing submission.

For these same devices, while the device is under FDA review, FDA does not intend to object to the devices not bearing a Unique Device Identification (UDI) (see 21 CFR Part 801 Subpart B and Part 830) or complying with other applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as previously authorized under the EUA. As always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type.

The enforcement policy in this section (Section V.B.(2)) relates to FDA marketing authorization (e.g., 510(k) clearance), UDI, and certain labeling requirements. It does not apply to other legal requirements (such as registration and listing, Quality System (QS), and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806, respectively) that may apply after the EUA termination date. Moreover, it does not apply after FDA has taken a final action on the marketing submission for a device. At that time, FDA expects manufacturers to comply with all applicable regulatory requirements for the device/manufacturer. Following the device’s marketing authorization, this includes labeling updates (see 21 CFR Part 801), compliance with UDI requirements (see 21 CFR Part 801 Subpart B and Part 830), and any applicable updates to registration and listing information, including the submission number (see 21 CFR Part 807 Subparts B-D). After marketing authorization, manufacturers also should follow the steps outlined in their Transition Implementation Plan.

In addition, and as always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type. This may include FDA revising or revoking an EUA, requesting a firm initiate a recall (see 21 CFR 7.45), or taking other actions, including an enforcement action. Moreover, FDA may revise the enforcement policies and recommendations in the guidance, as appropriate.

As mentioned previously, FDA recommends that marketing submissions include in the cover letter a statement that the device is/was previously authorized under an EUA and the EUA request number, as well as submission number(s) for related premarket submissions. This information will help FDA track devices that are transitioning from an EUA to the required marketing authorization, facilitate review of the submission, and help ensure that transitioning devices can be appropriately considered in light of the policy described in this section (Section V.B.(2) of this guidance).

In addition, during this transition period and after the EUA termination date, FDA may receive questions from stakeholders (e.g., other Agencies, governmental stockpilers, healthcare providers) about a device’s regulatory status for devices distributed as described in this section (Section V.B.(2)) while the marketing submission is under review by FDA. Typically, if a device has an EUA or conventional marketing authorization (e.g., 510(k) clearance), this information would be publicly available. The existence of a marketing submission under review is not typically disclosed unless certain circumstances apply, such as when the device is on the market. As such, for devices distributed as described in this section, FDA may share that a manufacturer is distributing such device as described in the policy in this guidance, which could indirectly reveal that the manufacturer has a marketing submission under review by FDA.

#### (3) Additional considerations for EUA-authorized in vitro diagnostics – Clinical Laboratory Improvement Amendments of 1988 (CLIA) categorization and waivers
In vitro diagnostics (IVDs) authorized under an EUA are generally authorized for use in specific settings, such as those certified as laboratories under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), that meet the requirements to perform high or moderate complexity tests, or for use at the point-of-care (POC), i.e., in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation. FDA’s determination that an EUA-authorized IVD is deemed to be in a particular category of examinations and procedures under CLIA is effective only while the relevant declaration under section 564(b) of the FD&C Act is in effect. Outside of EUAs, CLIA categorization typically is determined by FDA after FDA has cleared or approved a marketing submission. Prior to a CLIA categorization as moderate complexity or waived, an IVD is considered to be high complexity and, under CLIA, use of that test is limited to laboratories that are certified under CLIA, and that meet the requirements to perform tests of high complexity.

For IVDs authorized under an EUA for use in laboratories certified under CLIA that meet the requirements to perform moderate complexity tests, FDA intends to categorize the test’s complexity immediately following FDA’s final action on the marketing submission, per FDA’s typical categorization process.

For IVDs authorized under an EUA for use in patient care settings operating under a CLIA Certificate of Waiver, FDA intends to accept marketing submissions under the Dual 510(k) and CLIA Waiver by Application pathway, or Dual De Novo and CLIA Waiver marketing submissions modeled after the 510(k) and CLIA Waiver by Application pathway, as appropriate. Manufacturers intending to submit a Dual Submission are encouraged to consider the recommendations in the guidance “Recommendations for Dual 510(k) and CLIA Waiver by Application Studies,” for information on the process and content of Dual Submissions. Consistent with the recommendations in that guidance, data regarding actual use of the IVDs in CLIA-waived settings for comparison and reproducibility studies will be helpful in making a CLIA waiver determination. FDA anticipates that, in many cases, manufacturers will be able to reference data from related marketing authorizations and submissions, including the EUA request, and real-world data obtained as a result of use of the IVD under the EUA may be submitted in support of a CLIA Waiver by Application. As described in the guidance “Recommendations for Dual 510(k) and CLIA Waiver by Application Studies,” FDA recommends submitting a Pre-Submission to discuss planned study designs for comparison and reproducibility studies that support the marketing submission and the CLIA waiver, and the Dual Submission should be submitted following a Pre-Submission.

For IVDs authorized under an EUA for home use, if a marketing submission for such test is subsequently cleared, approved, or authorized for home use, the test will be waived by regulation under 42 CFR 493.15(c), meaning that the test will be categorized as waived without the need for a CLIA Waiver by Application.

FDA recommends that any marketing submission that may necessitate a CLIA categorization decision (e.g., tests intended for use in moderate complexity laboratories or in CLIA Certificate of Waiver settings) be submitted as soon as possible to facilitate FDA’s review of the marketing submission and CLIA categorization request (or CLIA Waiver by Application) prior to the termination of the EUA declaration to reduce the potential for disruption in distribution and use.

For IVDs authorized under an EUA for use in high complexity, moderate complexity, and waived settings where, as described in Section V.B.(2) of this guidance, the manufacturer has submitted a marketing submission to FDA and it is accepted by FDA before the EUA termination date, and FDA has not taken a final action on the marketing submission or made a determination on CLIA categorization, at this time, FDA does not intend to object to the continued distribution and use of such tests consistent with the policy described in Section V.B.(2) of this guidance and in a manner consistent with the EUA that was in effect prior to the EUA termination date.

### C. Devices not distributed after the EUA termination date
When a manufacturer does not intend to continue to distribute its device beyond the EUA termination date, at this time, FDA does not intend to object to the disposition and use[^67] of already distributed devices (i.e., FDA does not intend to request market removal[^68]) as follows:

1. Single-use, non-life-supporting/non-life-sustaining devices (e.g., face masks), including IVDs, that were distributed before the EUA termination date are used by the end user prior to the product expiration date,[^69] as applicable.
2. Reusable, non-life-supporting/non-life-sustaining devices (e.g., non-invasive remote patient monitoring devices) that were distributed before the EUA termination date are used by their end user and either:
   a. Are restored[^70] by the manufacturer to an FDA-cleared or -approved version of the device,[^71] or
   b. Have[^72] a physical and/or electronic copy of updated labeling that accurately describes the product features and regulatory status (e.g., that the product lacks FDA clearance, approval, or authorization).
3. Reusable life-supporting/life-sustaining devices (e.g., ventilators, extracorporeal membrane oxygenation systems, continuous renal replacement therapy systems) that were distributed before the EUA termination date are restored[^73] by the manufacturer to an FDA-cleared or -approved version of the device[^74] so that they may be used by their end user. If not restored, a physical and/or electronic copy of updated labeling that accurately describes the product features and regulatory status (e.g., that the product lacks FDA clearance, approval, or authorization) should be provided,[^75] and such devices are not to be used.[^76][^77] To help ensure accessibility to updated labeling, FDA recommends that stakeholders be provided an opportunity to request a physical copy of updated labeling, and after such request, be provided the requested labeling without additional cost.

Manufacturers that do not intend to distribute their devices after the EUA termination date should also refer to relevant information included in this guidance in other sections (though note that recommendations in Section V.B. are intended only for manufacturers that intend to distribute their device after the EUA termination date). In addition, manufacturers should be aware of any applicable legal requirements for their device, such as adverse event reporting under 21 CFR Part 803, and are expected to comply with such requirements for the duration in which they are applicable, which may extend beyond the cessation of distribution.

For IVDs authorized under an EUA for use in high complexity, moderate complexity, and waived settings that were already distributed before the EUA termination date, at this time, FDA does not intend to object to the continued use of such tests prior to the product expiration date in a manner consistent with the EUA that was in effect prior to the EUA termination date.[^78]

Manufacturers may also voluntarily withdraw their devices from the market. For manufacturers that do not intend to continue distributing their devices and that intend to voluntarily withdraw their devices from the market, FDA recommends completing withdrawal of the devices from the market prior to the EUA termination date; otherwise, if withdrawal of the devices from the market is not completed prior to the EUA termination date, FDA recommends restoring and/or updating labeling for reusable non-life-supporting/non-life-sustaining devices and for reusable life-supporting/life-sustaining devices as outlined in the policy above prior to the EUA termination date. Manufacturers should be aware of any applicable legal requirements for their device, such as adverse event reporting under 21 CFR Part 803, and continue to comply with such requirements for the duration in which they are applicable, which may extend beyond the cessation of distribution or withdrawal. Generally, it is anticipated that, over time, legal requirements will no longer apply when the manufacturer’s device withdrawal activities are completed.

FDA encourages manufacturers that do not intend to continue to distribute their devices after the EUA termination date to communicate with device distributors, healthcare facilities, healthcare providers, patients, and consumers, as appropriate, regarding their product disposition to assist all stakeholders with transition planning. In addition, thinking through elements of the “Transition Implementation Plan” outlined in Section V.B.(1) of this guidance may help manufacturers and stakeholders with this process.

### D. Discontinuing distribution of a device
FDA expects manufacturers to discontinue distribution of a device within the scope of this guidance:

1. On the EUA termination date, if the manufacturer has not submitted a required marketing submission[^79] for its device and had it accepted by FDA before the EUA termination date; or
2. On the date the manufacturer receives a negative decision on its marketing submission as FDA’s final action, or on the date the manufacturer withdraws its submission or fails to provide a complete response to an FDA request for additional information[^80] within the allotted time identified in FDA’s letter.

In addition, manufacturers should be aware of any applicable legal requirements for their device, such as adverse event reporting under 21 CFR Part 803, and continue to comply with such requirements for the duration in which they are applicable, which may extend beyond the cessation of distribution. Generally, to help determine the applicable legal requirements after cessation of distribution, FDA expects manufacturers of devices and others[^81] to review terms of the devices’ respective EUAs, including the conditions of authorization[^82] that were included in the EUA letters of authorization for the devices.

FDA encourages manufacturers to communicate with device distributors, healthcare facilities, healthcare providers, patients, and consumers, as appropriate, regarding their product disposition to assist all stakeholders with transition planning.

### E. Quality System considerations
FDA recognizes that there may be situations that raise unique compliance considerations, particularly regarding QS requirements. For example, non-traditional device manufacturers that previously operated under different quality standards or requirements may face challenges that take more time to address in transitioning to a system that fully complies with 21 CFR Part 820. FDA intends to take such considerations into account when making case-by-case compliance and enforcement decisions. Some manufacturers who intend to continue distributing their devices after the EUA termination date may choose to request an exemption or variance from a device QS requirement as outlined in 21 CFR 820.1(e) and section 520(f)(2) of the FD&C Act. Any such exemption or variance should be requested within 90 days of publication of the advance notice of termination of the EUA declaration pertaining to the device at issue to help ensure FDA considers your request in time.

### F. Laboratory developed tests (LDTs)
For laboratory developed tests (LDTs)[^83] in general, FDA has generally exercised enforcement discretion, meaning that FDA generally does not exercise its authority to enforce the regulatory requirements for these devices, although it maintains that authority. FDA has not applied this general enforcement discretion approach to, among other LDTs, those used for declared emergencies under section 564 of the FD&C Act. As such, following termination of the EUA declaration for COVID-19 IVDs, FDA intends to have the same enforcement approach for COVID-19 LDTs as it does for other LDTs.

## VI. Examples
The following hypotheticals are intended to illustrate the transition policy outlined above. To exemplify the timeline of the Transition Implementation Plan outlined in this section (Section VI. of this guidance), for purposes of the examples, FDA set the hypothetical advance notice of termination date for the EUA declaration pertaining to the device at issue as July 1 in Year 1, and the EUA termination date as January 1 in Year 2. This date is not intended to propose an actual advance notice of termination or EUA termination date; it is hypothetical and for illustrative purposes only. Note that these generalized examples do not account for every possible detail, risk, or consideration a manufacturer should evaluate or that may be relevant to FDA decisions regarding a particular device.

### Example 1
A single-use surgical mask that is intended for use in healthcare settings by healthcare personnel as personal protective equipment to provide a physical barrier to fluids and particulate materials was authorized for emergency use under an umbrella EUA for surgical masks. The manufacturer does not intend to continue distributing the surgical mask after the EUA is no longer in effect.

On July 1, the advance notice of termination of the relevant EUA declaration is published. After July 1, the manufacturer continues to distribute the surgical masks and continues to comply with all conditions of authorization.

On the EUA termination date (January 1), the relevant EUA declaration is terminated and the umbrella EUA is no longer in effect. On January 1, the manufacturer ceases distribution of the surgical mask. Before January 1, the manufacturer had recently sold surgical masks directly to retailers and device distributors. Some of the surgical masks are in transit to these customers, and others are being held in device distributors’ warehouses in the U.S.

The policies included in this guidance relate to the following actions by the device manufacturer and others:
- The surgical masks in transit or in device distributors’ warehouses remain distributed (they were already distributed by the EUA termination date), and they are used by the end user prior to their expiration date.
- If on January 1, some of the surgical masks are in the manufacturer’s possession, the surgical masks in the manufacturer’s possession are not subsequently distributed (they were not already distributed by the EUA termination date).
- The manufacturer does not update the labeling of the already distributed surgical masks (they are single-use, non-life-supporting/non-life-sustaining devices).
- User exhaustion of already distributed surgical masks is described in Section V.C. of this guidance.
- Even after the cessation of distribution, the manufacturer continues to submit any adverse event reports of which it becomes aware to FDA consistent with 21 CFR Part 803.

### Example 2
A continuous ventilator was authorized under the umbrella EUA for ventilators and ventilator accessories to support patients who develop respiratory distress due to COVID-19.

On July 1, the advance notice of termination of the relevant EUA declaration is published. Before August 1, to help FDA plan for transition-related premarket review activities, the manufacturer submits an “EUA report” to the CDRH Document Control Center with “Attention: Notification of Intent” on the cover letter of the submission to inform FDA that it does not intend to pursue marketing authorization. This EUA report includes the information outlined in Section V.A. of this guidance, which includes the manufacturer’s plans to have already distributed ventilators remain distributed.

On the EUA termination date (January 1), the relevant EUA declaration is terminated and the umbrella EUA is no longer in effect. On January 1, the manufacturer ceases distribution of the ventilator. FDA does not intend to object if the manufacturer implements a plan (that was included in the Notification of Intent) for the already distributed ventilators to remain distributed (e.g., ventilators in device distributors’ warehouses), including ventilators in the possession of end users (e.g., ventilators in healthcare facilities). As part of the plan, the manufacturer interacts with affected stakeholders, such as healthcare facilities, to determine the stakeholders’ interest in keeping distributed ventilators. The ventilator manufacturer updates the electronic labeling as outlined in Section V.C. of this guidance, and emails a copy of the electronic labeling to affected stakeholders that have expressed an interest in keeping the ventilators.

The policies included in this guidance relate to the following actions by the device manufacturer and others:
- The already distributed ventilators are not used.
- Should healthcare facilities wish to retain the ventilator that lacks FDA clearance, approval, or authorization for use in the future, the future use of the device would be subject to the regulatory requirements of any future authorization, including marketing authorization or EUA.
- For governmental stockpilers that wish to retain a device that lacks requisite FDA clearance, approval, or authorization for use in the future, FDA recommends engaging with the Agency to discuss the public health need for future deployment and/or use of the device in specific circumstances (e.g., regional natural disaster, localized disease outbreaks).
- Even after the cessation of distribution, the manufacturer continues to submit any adverse event reports of which it becomes aware to FDA consistent with 21 CFR Part 803.

### Example 3
A non-traditional device manufacturer worked with a traditional device manufacturer (original equipment manufacturer (OEM)) to produce, as a contract manufacturer, ventilators that were designed by the traditional device manufacturer. Such devices were authorized under the umbrella EUA for ventilators and ventilator accessories and distributed by the OEM during the COVID-19 pandemic.

On July 1, the advance notice of termination of the relevant EUA declaration is published. Before August 1, to help FDA plan for transition-related premarket review activities, the OEM submits an “EUA report” to the CDRH Document Control Center with “Attention: Notification of Intent” on the cover letter of the submission to inform FDA that it intends to pursue marketing authorization. This EUA report includes the information outlined in Section V.A. of this guidance.

On October 1, the OEM submits a marketing submission to FDA. In its marketing submission, the OEM includes a “Transition Implementation Plan” for already distributed ventilators in the case of a positive decision as well as in the case of a negative decision on the marketing submission. On October 10, the marketing submission is determined to be administratively incomplete because it is missing a test report for a biocompatibility endpoint; the marketing submission is not accepted for review (an “RTA1 decision”). The OEM resolves the acceptance review deficiency by including the missing test report for the biocompatibility endpoint and resubmits the marketing submission on November 1. On November 8, the marketing submission is accepted for substantive review.

On the EUA termination date (January 1), the relevant EUA declaration is terminated and the umbrella EUA is no longer in effect. The OEM has submitted a marketing submission and it was accepted by FDA. Under these circumstances, FDA does not intend to object to the continued distribution of the ventilators before FDA takes a final action on the marketing submission (see Section V.B.(2) of this guidance). Additionally, the OEM has kept the device labeling as described in the EUA-authorized device labeling. Under these circumstances, FDA does not intend to object to the device labeling not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as previously authorized under the EUA while the marketing submission is under FDA review (see Section V.B.(2) of this guidance).

In this scenario, in the course of FDA’s substantive review, FDA identifies a potential control software issue that could result in patient harm. FDA issues a request for additional information and informs the OEM that the marketing submission is being placed on hold pending receipt of a response to the deficiency. The OEM updates its software, performs the appropriate testing, and provides additional information and a response to the deficiency.

On July 10, the OEM receives a positive decision as part of FDA’s final action on the marketing submission. FDA and the OEM engage on the manufacturer’s Transition Implementation Plan to address already distributed devices, which includes the manufacturer updating software for already distributed ventilators and providing updated electronic labeling to the relevant stakeholders in accordance with the FDA-cleared version of the ventilator. The OEM continues to submit any adverse event reports of which it becomes aware to FDA consistent with 21 CFR Part 803.

### Example 4
A molecular diagnostic test kit manufactured by a commercial manufacturer was issued an individual EUA for the qualitative detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens in authorized laboratories. [^88]

On July 1, the advance notice of termination of the relevant EUA declaration is published. On October 1, the manufacturer submits a marketing submission to FDA, which is accepted by the Agency. In its marketing submission, the manufacturer includes a “Transition Implementation Plan” for already distributed molecular diagnostic test kits in the case of a positive decision as well as in the case of a negative decision on the marketing submission.

On the EUA termination date (January 1), the relevant EUA declaration is terminated and the EUA for the device is no longer in effect. The manufacturer has submitted a marketing submission and it was accepted by FDA. Under these circumstances, FDA does not intend to object to the continued distribution of the device before FDA takes a final action on the marketing submission (see Section V.B.(2) of this guidance). Additionally, the manufacturer has kept the device labeling as described in the EUA-authorized device labeling. Under these circumstances, FDA does not intend to object to the device labeling not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as previously authorized under the EUA while the marketing submission is under FDA review (see Section V.B.(2) of this guidance).

#### a) Positive Decision
In this scenario, the manufacturer receives a positive decision on February 20, as part of FDA’s final action on the marketing submission. FDA and the manufacturer engage on the manufacturer’s Transition Implementation Plan to address already distributed devices. The manufacturer does not update the device labeling for already distributed devices (these devices are single-use, non-life-supporting/non-life-sustaining devices); however, the manufacturer updates the device labeling for devices that are in production and those in its possession in accordance with the FDA-cleared version of the molecular diagnostic test kit. No outstanding issues were identified during FDA review that would result in a correction or removal of the molecular diagnostic test kits that were already distributed. The manufacturer continues to submit any adverse event reports of which it becomes aware to FDA consistent with 21 CFR Part 803.

#### b) Negative Decision
In this scenario, the manufacturer receives a negative decision on March 1, as part of FDA’s final action on the marketing submission. FDA and the manufacturer engage on the manufacturer’s Transition Implementation Plan to address already distributed devices. During FDA’s substantive review, FDA found that specific lots of the molecular diagnostic test kit had a high number of false positive reports, which may lead to a delay in both the correct diagnosis and treatment for the actual cause of a person’s illness. The manufacturer issues a voluntary recall for the affected lots of the molecular diagnostic test kit by informing relevant stakeholders to dispose of the affected lots.

The policies included in this guidance relate to the following actions by the device manufacturer and others:

- For unaffected lots of the molecular diagnostic test kit that are not subject to the recall and are already distributed, the devices remain distributed with device distributors and retail sellers who have already purchased the devices so that they may be used prior to the product expiration date.
- The manufacturer has a small number of unaffected lots of the molecular diagnostic test kit that are not subject to the recall in its possession; the manufacturer does not distribute these devices.
- The manufacturer does not update the device labeling of already distributed devices (these devices are single-use, non-life-supporting/non-life-sustaining devices); however, the manufacturer does communicate publicly about the recall about the affected lots of the molecular diagnostic test kit.
- Even after the cessation of distribution, the manufacturer continues to submit any adverse event reports of which it becomes aware to FDA consistent with 21 CFR Part 803.

---

[^14]: See sections 564(f)-(g) of the FD&C Act.
[^15]: See the HHS “Fact Sheet: COVID-19 Public Health Emergency Transition Roadmap,” (February 9, 2023), available at [link](https://www.hhs.gov/about/news/2023/02/09/fact-sheet-covid-19-public-health-emergency-transition-roadmap.html).
[^16]: Section 564(b)(2) of the FD&C Act.
[^17]: Sections 564(b)(3) and (4) of the FD&C Act.
[^18]: FDA recommends that manufacturers engage with the Agency through the Q-Submission Program, including requesting feedback in Pre-Submissions, to discuss the appropriate disposition of their product. For details on the Q-Submission Program, refer to the guidance “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program,” available at [link](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program).
[^19]: See footnote 10.
[^20]: See section 564(b)(2)(A) of the FD&C Act.
[^21]: Certain EUAs include conditions of authorization for parties other than the manufacturer, such as healthcare facilities or distributors.
[^22]: See section 564(e) of the FD&C Act.
[^23]: See section 564(h)(1) of the FD&C Act.
[^24]: See footnote 10.
[^25]: See section 1003(b) of the FD&C Act.
[^26]: Life-supporting or life-sustaining devices are defined in 21 CFR 860.3. A list of life-supporting or life-sustaining devices can be found by searching FDA’s product classification database: [link](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm).
[^27]: A reusable device is intended for repeated use either on the same or different patients, with appropriate cleaning and other reprocessing between uses. For additional information see the guidance “Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling” available at [link](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-medical-devices-health-care-settings-validation-methods-and-labeling).
[^28]: A single-use device is a device that is intended for one use or on a single patient during a single procedure. For additional information see the guidance “Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling.”
[^29]: See sections 564(f)-(g) of the FD&C Act.
[^30]: 21 CFR 7.45(a) states that FDA “may request a firm to initiate a recall when the following determinations have been made: (1) That a product that has been distributed presents a risk of illness or injury or gross consumer deception. (2) That the firm has not initiated a recall of the product. (3) That an agency action is necessary to protect the public health and welfare.”
[^67]: FDA recognizes that not all use would necessarily be violative (see, e.g., section 564(f)(2) of the FD&C Act). To the extent such use is violative, FDA generally does not intend to object as described herein.
[^68]: FDA uses the term “removal” consistent with the definition in 21 CFR 806.2(j).
[^69]: For IVDs that were authorized under EUA, this is the product expiration date listed as of the EUA termination date. Extension of the expiration date cannot be authorized after the EUA is terminated.
[^70]: In situations where manufacturers do not believe restoration is possible or in the best interest of public health, FDA recommends additional engagement with the Agency on the appropriate disposition of a product if it is not otherwise discussed in this guidance.
[^71]: For example, an FDA-cleared or -approved version may include an earlier software version, component replacement, or different labeling that removes information related to the use of the device under the EUA.
[^72]: The manufacturer should provide labeling to the original purchaser, and collaborate with the original purchaser to ensure that labeling is distributed to relevant stakeholders, including device distributors, healthcare facilities, healthcare providers, patients, consumers, etc.
[^73]: See footnote 70.
[^74]: See footnote 71.
[^75]: See footnote 72.
[^76]: FDA recognizes that not all use would necessarily be violative (see, e.g., section 564(f)(2) of the FD&C Act).
[^77]: Should healthcare facilities wish to retain a device that lacks FDA clearance, approval, or authorization for use in the future, the future use of the device would be subject to the regulatory requirements of any future authorization, including marketing authorization or EUA, as applicable. For governmental stockpilers that wish to retain a device that lacks requisite FDA clearance, approval, or authorization for use in the future, FDA recommends engaging with the Agency to discuss the public health need for future deployment and/or use of the device in specific circumstances (e.g., regional natural disaster, localized disease outbreaks).
[^78]: Laboratories using such tests should consider whether CLIA requirements administered by CMS may apply.
[^79]: See, e.g., sections 510(k), 513(f)(2), 515, and 520(m) of the FD&C Act.
[^80]: For more information on FDA requests for additional information (i.e., deficiency letters) and how to respond, see the guidance “Developing and Responding to Deficiencies in Accordance with the Least Burdensome Provisions,” available at [FDA guidance documents](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/developing-and-responding-deficiencies-accordance-least-burdensome-provisions).
[^81]: Certain EUAs include conditions of authorization for parties other than the manufacturer, such as healthcare facilities or distributors.
[^82]: See section 564(c) of the FD&C Act.
[^83]: An LDT is a type of IVD that is designed, manufactured, and used within a single site laboratory certified under CLIA that meets the requirements to perform tests of high complexity.
[^88]: Available at [FDA Guidance](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-2#individual-molecular).


# 17,421  2023-03-27_FDA Guidance - Transition Plan for Medical Devices That Fall Within Enforcement Policies.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2023-03-27_FDA Guidance - Transition Plan for Medical Devices That Fall Within Enforcement Policies.md
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summary_short: The FDA “Transition Plan for Medical Devices That Fall Within Enforcement Policies Issued During the COVID-19 Public Health Emergency” (March 27, 2023) lays out a phased, 180-day wind-down for devices that were marketed under COVID-era enforcement discretion guidance. It specifies Phase 1–3 compliance expectations (e.g., MDR reporting, corrections/removals, registration/listing), when marketing submissions should be submitted and accepted to keep distributing after the policies end, and when FDA may continue enforcement discretion while a submission is under review. It also includes Notification of Intent requests for certain reusable life-supporting/sustaining devices and recommends a Transition Implementation Plan to manage already-distributed products under both positive and negative FDA decisions.


CONTENT

***INTERNAL TITLE:*** Transition Plan for Medical Devices That Fall Within Enforcement Policies Issued During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency
Guidance for Industry, Other Stakeholders, and Food and Drug Administration Staff

Document issued on March 27, 2023.

The draft of this document was issued on December 23, 2021.

For questions about this document, contact the Regulation, Policy, and Guidance Staff at [RPG@fda.hhs.gov](mailto:RPG@fda.hhs.gov).


## Preface  
### Public Comment  
You may submit electronic comments and suggestions at any time for Agency consideration to [https://www.regulations.gov](https://www.regulations.gov). Submit written comments to the Dockets Management Staff, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. Identify all comments with the docket number FDA-2021-D-1118. Comments may not be acted upon by the Agency until the document is next revised or updated.

### Additional Copies
Additional copies are available from the Internet. You may also send an email request to [CDRH-Guidance@fda.hhs.gov](mailto:CDRH-Guidance@fda.hhs.gov) to receive a copy of the guidance. Please include the document number GUI00021011 and complete title of the guidance in the request.

## Table of Contents  
I. Introduction ....................................................................................................................... 1  
II. Background ....................................................................................................................... 3  
III. Scope ................................................................................................................................ 5  
IV. Guiding Principles .......................................................................................................... 6  
V. Phased Transition Plan for Devices That Fall Within COVID-19 Enforcement Policies Described in Guidances in List 1 ............................................................................................. 7  
   A. Devices not distributed after Phase 2 ........................................................................... 11  
   B. Phase 1 .......................................................................................................................... 13  
   C. Phase 2 .......................................................................................................................... 13  
      (1) “Notifications of Intent” for Certain Reusable Life-Supporting or Life-Sustaining Devices ............................................................................................................................. 14  
   D. Phase 3 .......................................................................................................................... 15  
      (1) Enforcement policy for devices with a marketing submission under review by FDA 16  
      (2) Recommendations for “Transition Implementation Plan” ........................................ 18  
   E. Discontinuing distribution of a device ......................................................................... 20  
   F. Quality System considerations ..................................................................................... 21  
VI. Examples ......................................................................................................................... 21  
   Example 1 .......................................................................................................................... 21  
   Example 2 .......................................................................................................................... 23  
   Example 3 .......................................................................................................................... 24  
   Example 4 .......................................................................................................................... 25  

## I. Introduction
FDA plays a critical role in protecting the United States (U.S.) from threats such as emerging infectious diseases, including Coronavirus Disease 2019 (COVID-19). FDA is committed to providing timely guidance to support response efforts to the COVID-19 pandemic. FDA recognizes that it will take time for device[^1] manufacturers,[^2] device distributors, healthcare facilities, healthcare providers, patients, consumers, and FDA to adjust from policies adopted and operations implemented during the COVID-19 public health emergency (PHE) to “normal operations.”[^3] To provide a clear policy for all stakeholders and FDA staff, the Agency is issuing this guidance to describe FDA’s general recommendations for a phased transition process with respect to devices that fall within certain enforcement policies issued during the COVID-19 PHE, including recommendations regarding submitting a marketing submission, as applicable, and taking other actions with respect to these devices.

FDA is concurrently issuing a companion transition guidance to describe FDA’s recommendations for devices issued emergency use authorizations (EUAs) related to COVID-19.[^4] The companion transition guidance does not include phases as described in this transition plan for devices that fall within enforcement policies and instead relies on the advance notice(s) of termination process required under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act). FDA believes that these transition guidances will help prepare manufacturers and other stakeholders for the transition to normal operations and foster compliance with applicable requirements under the FD&C Act and its implementing regulations.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word *should* in Agency guidances means that something is suggested or recommended, but not required.

## II. Background
In 2019, an outbreak of respiratory disease caused by a novel coronavirus began. The virus has been named “SARS-CoV-2,” and the disease it causes has been named “Coronavirus Disease 2019” (COVID-19). On January 31, 2020, the Secretary of Health and Human Services (HHS) issued a declaration of a PHE related to COVID-19 in accordance with section 319 of the Public Health Service (PHS) Act (hereinafter referred to as “section 319 PHE declaration”) and mobilized the Operating Divisions of HHS.[^5] In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19.[^6] On February 9, 2023, the HHS Secretary renewed the section 319 PHE declaration related to COVID-19, effective February 11, 2023. The section 319 PHE declaration related to COVID-19 is anticipated to expire at the end of the day on May 11, 2023.[^7]

In response to the COVID-19 pandemic, the device supply chain has been stressed because the demand for certain devices has exceeded available supply. FDA recognized early in the COVID-19 pandemic the importance of maintaining the availability of certain devices. FDA’s policies have helped facilitate the availability of devices intended to diagnose, treat, and prevent COVID-19 and associated conditions – including mitigating exposure to the SARS-CoV-2 virus – and to help address manufacturing limitations or supply chain issues due to disruptions caused by the COVID-19 pandemic.

FDA issued various guidance documents that describe enforcement policies for certain devices that are intended to support the emergency response to the COVID-19 pandemic.[^8] These policies have helped to facilitate the availability of devices such as in vitro diagnostics, personal protective equipment intended for medical purposes, and ventilators. Additionally, FDA issued guidance to help expand the availability and remote monitoring capabilities of certain devices, including infusion pumps and non-invasive remote patient monitoring devices, to reduce the risk of exposure for patients, healthcare providers, and other healthcare professionals to individuals diagnosed with COVID-19.

Generally, the guidances that set forth COVID-19-related enforcement policies for certain devices initially stated that they were intended to remain in effect only for the duration of the section 319 PHE declaration. As FDA announced in the Federal Register on March 13, 2023, many of these guidance documents – the guidances in List 1 (see below) – have been revised to state that they are intended to continue in effect for 180 days after the section 319 PHE declaration expires unless a different intended duration is set forth in the finalized version of this guidance.9,10 A different intended duration is _not_ being set forth in this guidance – as described in Section V., the implementation date is the date the section 319 PHE declaration expires and the guidances are intended to continue in effect for 180 days after that date. FDA recommends reviewing the cover page for the relevant List 1 guidance to help determine the transition period for your device.

Given the magnitude of the response to the COVID-19 pandemic, FDA recognizes that a phased approach may help to ensure an orderly and transparent transition from the policies and recommendations in the List 1 guidances to normal operations. Further, FDA is taking into account that the manufacture, distribution, and use of devices in the context of the COVID-19 pandemic raises unique considerations. These unique considerations include, for example, the manufacturing of devices by non-traditional manufacturers to address supply issues and the distribution and use of capital or reusable equipment (e.g., ventilators, extracorporeal membrane oxygenation systems) that fall within enforcement policies.

FDA developed this guidance to describe a phased approach, as set forth in Section V., among other things, to help avoid disruption in device supply and help facilitate compliance with applicable legal requirements after the enforcement policies are no longer in effect. This phased approach will allow FDA to better understand the landscape of devices that fall within the relevant enforcement policies, provide support to manufacturers, and assist the Agency in resource planning for marketing submission review.

## III. Scope
This guidance applies to devices that fall within the enforcement policies described in the guidances identified in List 1 below.11

**List 1**
- [Enforcement Policy for Remote Digital Pathology Devices During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-remote-digital-pathology-devices-during-coronavirus-disease-2019-covid-19-public)
- [Enforcement Policy for Imaging Systems During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-imaging-systems-during-coronavirus-disease-2019-covid-19-public-health-emergency)
- [Enforcement Policy for Non-Invasive Fetal and Maternal Monitoring Devices Used to Support Patient Monitoring During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-non-invasive-fetal-and-maternal-monitoring-devices-used-support-patient)
- [Enforcement Policy for Telethermographic Systems During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-telethermographic-systems-during-coronavirus-disease-2019-covid-19-public-health)
- [Enforcement Policy for Digital Health Devices for Treating Psychiatric Disorders During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-digital-health-devices-treating-psychiatric-disorders-during-coronavirus-disease)
- [Enforcement Policy for Extracorporeal Membrane Oxygenation and Cardiopulmonary Bypass Devices During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-extracorporeal-membrane-oxygenation-and-cardiopulmonary-bypass-devices-during)
- [Enforcement Policy for Remote Ophthalmic Assessment and Monitoring Devices During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-remote-ophthalmic-assessment-and-monitoring-devices-during-coronavirus-disease-2019-covid-19-public)
- [Enforcement Policy for Infusion Pumps and Accessories During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-infusion-pumps-and-accessories-during-coronavirus-disease-2019-covid-19-public)
- [Enforcement Policy for Face Shields, Surgical Masks, and Respirators During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-face-shields-surgical-masks-and-respirators-during-coronavirus-disease-covid-19-public)
- [Enforcement Policy for Gowns, Other Apparel, and Gloves During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-gowns-other-apparel-and-gloves-during-coronavirus-disease-covid-19-public-health)
- [Enforcement Policy for Sterilizers, Disinfectant Devices, and Air Purifiers During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-sterilizers-disinfectant-devices-and-air-purifiers-during-coronavirus-disease)
- [Enforcement Policy for Ventilators and Accessories and Other Respiratory Devices During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-ventilators-and-accessories-and-other-respiratory-devices-during-coronavirus)
- [Enforcement Policy for Modifications to FDA Cleared Molecular Influenza and RSV Tests During the COVID-19 Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-modifications-fda-cleared-molecular-influenza-and-rsv-tests-during-covid)
- [Coagulation Systems for Measurement of Viscoelastic Properties: Enforcement Policy During the COVID-19 Public Health Emergency (Revised)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/coagulation-systems-measurement-viscoelastic-properties-enforcement-policy-during-coronavirus)
- [Enforcement Policy for Viral Transport Media During the COVID-19 Public Health Emergency (Revised)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-viral-transport-media-during-coronavirus-disease-2019-covid-19-public-health)

## IV. Guiding Principles
In developing this guidance, and its companion transition guidance regarding device issues EUAs related to COVID-19, several guiding principles were followed. Some derive from existing policies and are widely known, and others are key to understanding the approach set forth in this guidance. Thus, anyone using this guidance should bear in mind the following guiding principles:

- This guidance is intended to help facilitate continued patient, consumer, and healthcare provider access to devices needed in the prevention, treatment, and diagnosis of COVID-19.
- FDA believes the policies and recommendations in this guidance will help to ensure an orderly and transparent transition for devices that fall within the scope of this guidance. FDA’s policies and recommendations in this guidance are consistent with the Agency’s statutory mission to both protect and promote the public health.
- FDA’s policies and recommendations follow, among other things, a risk-based approach with consideration of differences in the intended use and regulatory history of devices, including whether the device is life-supporting or life-sustaining, capital or reusable equipment, a single-use device, and whether another version of the device is FDA-cleared or -approved.
- As always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type. This may include requesting a firm initiate a recall (see 21 CFR 7.45), or taking other actions, including an enforcement action. Moreover, FDA may revise the enforcement policies and recommendations in the guidance, as appropriate.

## V. Phased Transition Plan for Devices That Fall Within COVID-19 Enforcement Policies Described in Guidances in List 1
As previously stated, FDA recognizes that it will take time for device manufacturers, device distributors, healthcare facilities, healthcare providers, patients, consumers, and the Agency to adjust from policies adopted and operations implemented during the COVID-19 PHE to normal operations. FDA seeks to encourage and facilitate an appropriate transition period to help, among other things, avoid exacerbating product shortages and supply chain disruptions. This transition plan takes into account that the guidances in List 1 will no longer be in effect after the 180-day transition period discussed in this guidance ends. The discussion below contains recommendations regarding the preparation and submission of marketing submissions (including the timing of such submissions), manufacturers’ actions if they do not wish to continue distributing their product after the end of Phase 2, and the distribution of devices that fall within the scope of this guidance.

For purposes of this guidance, devices are considered to be “already distributed” if they are finished devices that are labeled and are in distribution in the U.S. supply chain or are in the possession of the end user. For purposes of this guidance, FDA would generally consider devices to be “in distribution” to mean those finished, labeled devices that are no longer in the manufacturer’s possession that are in transit to or held in a third party’s device inventory not on behalf of the manufacturer, in a federal, state, or other government stockpile, or at a location where devices are then offered for direct sale to the end user.

Given the duration of the COVID-19 pandemic and the need to safeguard the public health in a post-pandemic environment, FDA is implementing a 180-day transition period that will begin on the “implementation date” (see discussion below regarding this date). The guidances in List 1 will no longer be in effect after the 180-day transition period ends. FDA believes a phased transition over the 180 days following the implementation date as set forth in this guidance will help foster compliance with applicable legal requirements. This approach consists of three phases as described later in this section and outlined in Table 2.

The implementation date is the date the COVID-19 section 319 PHE declaration expires or 45 days after the finalization of this guidance, whichever comes later. Because the COVID-19 section 319 PHE declaration is anticipated to expire at least 45 days after the finalization of this guidance, or May 11, 2023, the implementation date is that date. The guidance documents identified in List 1 will no longer be in effect after the 180-day transition period ends, or after November 7, 2023.

A timeline for this process is provided in Figure 1.

_Timeline diagram showing the three-phase transition period: Phase 1 begins on implementation date (May 11, 2023), Phase 2 starts 90 days later (August 9, 2023), and Phase 3 starts 180 days later (November 7, 2023), when enforcement policies in List 1 expire._

**Figure 1. Transition Timeline. Implementation date occurring on the date the COVID-19 section 319 PHE declaration expires.**

In the bullets below, FDA describes our transition period expectations and recommendations for all manufacturers that distributed devices as described in an enforcement policy in a guidance in List 1, both for those who do and do not pursue marketing authorization for their devices. FDA believes these expectations and recommendations will help facilitate a smooth and consistent transition to normal operations.

A summary of the three phases are as follows:

- **Phase 1**: Begins on the implementation date. If not already doing so, manufacturers should follow 21 CFR Part 803 (i.e., adverse event reporting requirements) in order to prepare for Phase 3.

- **Phase 2**: Begins 90 days after the implementation date. Before the start of Phase 2 and in order to prepare for Phase 3, if not already doing so, manufacturers should: (1) follow 21 CFR Part 806 (i.e., reports of corrections and removals requirements), and (2) if planning to continue to distribute their devices after Phase 2, should also follow 21 CFR Part 807 Subparts B-D (i.e., registration and listing requirements).

- **Phase 3**: Begins 180 days after the implementation date. After the 180-day transition period ends, the guidances in List 1 will no longer be in effect. At this time, FDA does not intend to object to continued distribution of devices within the scope of this guidance where a required marketing submission has been submitted and accepted[^35^] by FDA before the start of Phase 3 and FDA has not taken a final action[^36^] on the marketing submission. In addition, for these same devices, while the device is under FDA review, FDA does not intend to object to the devices not complying with certain Unique Device Identification (UDI) requirements (see 21 CFR Part 801 Subpart B) and other applicable labeling requirements (see 21 CFR Part 801) (see Section V.D.(1) of this guidance). This enforcement policy does not apply to other legal requirements (such as registration and listing, Quality System (QS), and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806, respectively).

The three phases of the transition plan, including additional considerations and recommendations related to each phase, are described in more detail below.

FDA recommends manufacturers submit a “Transition Implementation Plan” with their marketing submission that addresses the manufacturers’ plans for dealing with devices already distributed in the case of a positive decision as well as in the case of a negative decision on the marketing submission (see Section V.D.(2) of this guidance). The marketing submission should be administratively complete in that it includes all of the information necessary for FDA to conduct a substantive review.[^37^] FDA understands there may be extenuating circumstances that make doing so difficult (e.g., ongoing clinical trial or longer term non-clinical studies). Manufacturers in such circumstances should engage with the Agency early in the transition period.[^38^]

FDA understands there may be other circumstances that are not specifically addressed in this guidance, but generally believes that the policies and recommendations described in Table 2, regardless of the specific scenario for a manufacturer, will help avoid disruptions in critical devices and allow FDA to best manage its resources for review of marketing submissions. To address any unique considerations or other issues not otherwise discussed in this guidance, manufacturers may wish to initiate discussions with the Agency through the Q-Submission Program, including requesting feedback in Pre-Submissions. If the manufacturer’s intent is to continue to distribute its device after Phase 2, the manufacturer should promptly start preparing, and FDA intends to help facilitate acceptance of, a marketing submission before Phase 3 begins. For details on the Q-Submission Program, refer to the guidance “[Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program)”[^39^]

### A. Devices not distributed after Phase 2
When a manufacturer that has been distributing its device as described in an enforcement policy in a guidance in List 1 does not intend to continue to distribute its device after Phase 2, at this time, FDA does not intend to object to the disposition and use[^40^] of already distributed devices (i.e., FDA does not intend to request market removal[^41^]) as follows:

1. Single-use, non-life-supporting/non-life-sustaining devices (e.g., face masks) that were distributed before the end of Phase 2 are used by the end user prior to the product expiration date, as applicable.

2. Reusable, non-life-supporting/non-life-sustaining devices (e.g., infusion pumps) that were distributed before the end of Phase 2 are used by their end user and either:
   a. Are restored[^42^] by the manufacturer to an FDA-cleared or -approved version of the device,[^43^] or
   b. Have[^44^] a physical and/or electronic copy of updated labeling that accurately describes the product features and regulatory status (e.g., that the product lacks FDA clearance, approval, or authorization).

3. Reusable life-supporting/life-sustaining devices (e.g., ventilators, extracorporeal membrane oxygenation systems) that were distributed before the end of Phase 2 are restored[^45^] by the manufacturer to an FDA-cleared or -approved version of the device[^46^] so that they may be used by their end user. If not restored, a physical and/or electronic copy of updated labeling that accurately describes the product features and regulatory status (e.g., that the product lacks FDA clearance, approval, or authorization) should be provided,[^47^] and such devices are not to be used.[^48^,^49^] To help ensure accessibility to updated labeling, FDA recommends that stakeholders be provided an opportunity to request a physical copy of updated labeling, and after such request, be provided the requested labeling without additional cost.

Manufacturers that do not intend to distribute their devices after Phase 2 should also refer to relevant information included in other sections of this guidance (though note that recommendations in Section V.D.(1) are intended only for manufacturers that intend to distribute their device after the end of Phase 2). In addition, manufacturers should be aware of any applicable legal requirements for their device, such as adverse event reporting under 21 CFR Part 803, and are expected to comply with such requirements for the duration in which they are applicable, which may extend beyond the cessation of distribution.

Manufacturers may also voluntarily withdraw their devices from the market. For manufacturers that do not intend to continue distributing their devices and that intend to voluntarily withdraw their devices from the market, FDA recommends completing withdrawal of the devices from the market prior to the withdrawal of the guidances in List 1; otherwise, if withdrawal of the devices from the market is not completed prior to the withdrawal of the guidances in List 1, FDA recommends restoring and/or updating labeling for reusable non-life-supporting/non-life-sustaining devices and for reusable life-supporting/life-sustaining devices as outlined in the policy above prior to the withdrawal of the guidances in List 1. Manufacturers should be aware of any applicable legal requirements for their device, such as adverse event reporting under 21 CFR Part 803, and continue to comply with such requirements for the duration in which they are applicable, which may extend beyond the cessation of distribution or withdrawal. Generally, it is anticipated that, over time, legal requirements will no longer apply when the manufacturer’s device withdrawal activities are completed.

FDA encourages manufacturers that do not intend to continue to distribute their devices after Phase 2 to communicate with device distributors, healthcare facilities, healthcare providers, patients, and consumers, as appropriate, regarding their product disposition to assist all stakeholders with transition planning. In addition, thinking through elements of the “Transition Implementation Plan” outlined in Section V.D.(2) of this guidance may help manufacturers and stakeholders with this process.

### B. Phase 1
Phase 1 starts on the implementation date, as described above. In order to prepare for Phase 3, if not already doing so, manufacturers should follow adverse event reporting requirements[^50] under 21 CFR Part 803. Manufacturers should submit any adverse event reports that were stored (e.g., because of pandemic-related high employee absenteeism) and should refer to applicable FDA guidance regarding adverse event reporting during a pandemic.

During (and preferably before the start of) this phase, manufacturers that intend to continue distribution of their devices after Phase 2 should begin preparation of any required marketing submission to help avoid disruptions in critical devices and allow FDA to best manage its resources for review of marketing submissions. While preparing a marketing submission, manufacturers can use the [FDA Guidance Search Tool](https://www.fda.gov/regulatory-information/search-fda-guidance-documents) to identify relevant guidance documents that may be helpful in preparing the submission.

FDA is taking into account that the use of devices during the COVID-19 pandemic may allow manufacturers to utilize a variety of data sources in their marketing submission. As such, FDA anticipates many manufacturers may wish to reference data from related marketing authorizations and submissions, and use real-world data obtained as a result of device use during the COVID-19 pandemic.[^52] FDA recommends that marketing submissions include in the cover letter a statement that the device was distributed as described in an enforcement policy, as well as submission number(s) for related premarket submissions. This information will help FDA track devices that are transitioning to the required marketing authorization,[^53] facilitate review of the submission, and help ensure that the transitioning devices can be appropriately considered in light of the policy described in Section V.D.(1) of this guidance.

### C. Phase 2
Phase 2 begins 90 days after the implementation date. Before the start of Phase 2 and in order to prepare for Phase 3, if not already doing so, manufacturers should follow correction and removal requirements under 21 CFR Part 806. Before the start of Phase 2, manufacturers that intend to continue to distribute their devices after Phase 2 should also register their establishments and list[^54] their device(s) or update existing registration and listing (R&L) if they have not already done so. For manufacturers that register and list by the start of Phase 2, FDA recommends that manufacturers utilize the term “enforcement” (as a shorthand for “enforcement policy”) in the premarket submission field if a submission number is not yet available. If the device subsequently receives marketing authorization, FDA expects manufacturers to comply with all applicable registration and listing requirements, which may require updating the listing information.

As discussed above, manufacturers that intend to continue to distribute their devices after Phase 2 should continue preparation of any required marketing submission[^55] as FDA expects such manufacturers to submit a marketing submission to FDA and have it accepted before the start of Phase 3 to help avoid disruptions in critical devices and allow FDA to best manage its resources for review of marketing submissions.

In addition, FDA recommends that manufacturers of certain life-supporting or life-sustaining devices within the scope of this guidance – regardless of whether they intend to continue distribution of their devices after Phase 2 – submit a “Notification of Intent” to FDA as described in Section V.C.(1) of this guidance.

#### (1) “Notifications of Intent” for Certain Reusable Life-Supporting or Life-Sustaining Devices
Given the public health significance of certain reusable life-supporting or life-sustaining devices, FDA requests that manufacturers of such devices submit to FDA information about whether or not they intend to submit a marketing submission to FDA and continue distributing their product after Phase 2. This information will assist the Agency in resource planning for marketing submission review and providing support to manufacturers. This request applies to devices that fall within the scope of this guidance and that have a product code listed in Table 1:

| Product Code | Device Type                                                | Classification Regulation |
|--------------|------------------------------------------------------------|---------------------------|
| BSZ          | Gas-machine, anesthesia                                    | 21 CFR 868.5160           |
| CAW          | Generator, oxygen, portable                                | 21 CFR 868.5440           |
| BTT          | Humidifier, respiratory gas, (direct patient interface)    | 21 CFR 868.5450           |
| QAV          | High flow/high velocity humidified oxygen delivery device  | 21 CFR 868.5454           |
| CBK          | Ventilator, continuous, facility use                       | 21 CFR 868.5895                          |
| MNT          | Ventilator, continuous, minimal ventilatory support, facility use | 21 CFR 868.5895           |
| NOU          | Continuous, ventilator, home use                           | 21 CFR 868.5895                          |
| MNS          | Ventilator, continuous, non-life-supporting                | 21 CFR 868.5895                          |
| ONZ          | Mechanical ventilator                                      | 21 CFR 868.5895                          |
| BTL          | Ventilator, emergency, powered (resuscitator)              | 21 CFR 868.5925           |
||

Manufacturers of the devices identified in Table 1 should submit the following information to the CDRH Document Control Center[^56] before the start of Phase 2:[^57]

- General information about the manufacturer, including contact information, name and place of business, and email address;
- Title of the relevant enforcement policy guidance;
- Submission number(s) for related premarket submissions;
- A list of all model numbers or other device identifying information;
- Whether the manufacturer plans to submit a marketing submission; and
- If not planning to submit a marketing submission, the manufacturer should discuss, as applicable, its plans to discontinue distribution of the device, to restore the device to an FDA-cleared or -approved version, to provide a physical copy and/or electronic copy of updated labeling, and any other efforts to address or mitigate potential risks of devices that remain distributed after Phase 2.

If another version of the device is FDA-cleared or -approved and a modified version is/was distributed as described in a policy in a guidance in List 1, the manufacturer should submit this information in a premarket notification (i.e., 510(k)) or PMA “amendment” for the cleared or approved device.[^58] FDA recommends that manufacturers notate the following on the cover letter of the submission: “Attention: Notification of Intent.” To the extent the Notification of Intent contains trade secret information or confidential commercial or financial information, FDA will handle that information in accordance with applicable laws, including 21 CFR 20.61.

### D. Phase 3
Phase 3 begins 180 days after the implementation date. After the 180-day transition period ends, the guidances in List 1 will no longer be in effect. Before the start of Phase 3, any required marketing submission[^59] is expected to be submitted to and accepted by FDA if the manufacturer intends to continue distribution of the device after Phase 2. Where possible, FDA strongly encourages manufacturers to work to complete such submissions well in advance of the start of Phase 3 to avoid potential delays created by a large influx of new submissions and to best serve the public health.

#### (1) Enforcement policy for devices with a marketing submission under review by FDA
As previously stated, FDA recognizes that it may take time for device manufacturers, including non-traditional device manufacturers, to adapt and adjust from their operations during the COVID-19 PHE to normal operations. As such, at this time, FDA does not intend to object to the continued distribution of devices within the scope of this guidance after the guidances in List 1 are no longer in effect where:

- The manufacturer has submitted a marketing submission to FDA and it is accepted by FDA before the start of Phase 3; and
- FDA has not taken a final action on the marketing submission.

For these same devices, while the device is under FDA review, FDA does not intend to object to the devices not complying with certain UDI requirements (see 21 CFR Part 801 Subpart B) or other applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as described in the relevant List 1 guidance. As always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type.

The enforcement policy in this section (Section V.D.(1)) relates to FDA marketing authorization (e.g., 510(k) clearance), and certain UDI and other applicable labeling requirements. It does not apply to other legal requirements (such as registration and listing, QS, and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806, respectively) that may apply. Moreover, it does not apply after FDA has taken a final action on the marketing submission for a device. At that time, FDA expects manufacturers to comply with all applicable regulatory requirements for the device/manufacturer. Following the device’s marketing authorization, this includes labeling updates (see 21 CFR Part 801), compliance with UDI requirements (see 21 CFR Part 801 Subpart B and Part 830), and any applicable updates to registration and listing information, including the submission number (see 21 CFR Part 807 Subparts B-D). After marketing authorization, manufacturers also should follow the steps outlined in their Transition Implementation Plan.

In addition, and as always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type. This may include FDA requesting a firm initiate a recall (see 21 CFR 7.45) or taking other actions, including an enforcement action. Moreover, FDA may revise the enforcement policies and recommendations in the guidance, as appropriate.

As mentioned previously, FDA recommends that marketing submissions include in the cover letter a statement that the device is/was distributed as described in an enforcement policy, and submission number(s) for related premarket submissions. This information will help FDA track devices that are transitioning to the required marketing authorization, facilitate review of the submission, and help ensure that transitioning devices can be appropriately considered in light of the policy described in this section (Section V.D.(1) of this guidance). The marketing submission should be administratively complete in that it includes all of the information necessary for FDA to conduct a substantive review. FDA understands there may be extenuating circumstances that may make doing so difficult (e.g., ongoing clinical trial or longer term non-clinical studies). Manufacturers in such circumstances should engage with the Agency early in the transition period.

In addition, during this transition period and after the start of Phase 3, FDA may receive questions from stakeholders (e.g., other Agencies, governmental stockpilers, healthcare providers) about a device’s regulatory status for devices distributed as described in this section (Section V.D.(1)) while the marketing submission is under review by FDA. Typically, if a device has an EUA or conventional marketing authorization (e.g., 510(k) clearance), this information would be publicly available. The existence of a marketing submission under review is not typically disclosed unless certain circumstances apply, such as when the device is on the market. As such, for devices distributed as described in this section, FDA may share that a manufacturer is distributing such device as described in the policy in this guidance, which could indirectly reveal that the manufacturer has a marketing submission under review by FDA.

#### (2) Recommendations for “Transition Implementation Plan”
FDA anticipates that some marketing submissions will include changes or updates to the device and/or its labeling compared to the product that was distributed as described in the relevant guidance in List 1. For example, a manufacturer may have distributed fetal dopplers as described in an enforcement policy, and the manufacturer intends to submit a marketing submission for such fetal dopplers with an additional, new indication. In addition, in some cases, a manufacturer may not receive a positive decision from FDA on its marketing submission.

To help address all of these situations efficiently, FDA recommends manufacturers include in the cover letter of their marketing submissions a “Transition Implementation Plan” that addresses the manufacturers’ plans for dealing with devices already distributed in the case of a positive decision as well as in the case of a negative decision on the marketing submission. To the extent the Transition Implementation Plan contains trade secret information or confidential commercial or financial information, FDA will handle that information in accordance with applicable laws, including 21 CFR 20.61.

FDA recommends the Transition Implementation Plan include the following information, as applicable:

- Estimated number of devices that fall within the policies outlined in any of the guidances referenced in List 1 above that are currently in U.S. distribution;
- An explanation of the manufacturer’s benefit-risk based plan for disposition of already distributed product in the event of a negative decision on the marketing submission. If the manufacturer is proposing to leave already distributed product in place, the plan should address the rationale for doing so and considerations such as the following, where relevant:
  - Process for notifying patients, consumers, healthcare facilities, healthcare providers, and device distributors of the device’s regulatory status;
  - Process and timeline for restoring already distributed devices to an FDA-cleared or -approved version;
  - Process and timeline for providing a physical and/or electronic copy of updated labeling that accurately describes the product features and regulatory status (e.g., that the product lacks FDA clearance, approval, or authorization) for reusable devices. To help ensure accessibility to updated labeling for reusable life-supporting/life-sustaining devices, FDA recommends that stakeholders be provided an opportunity to request a physical copy of updated labeling, and after such request, be provided the requested labeling without additional cost; and
  - A description of the maintenance plan for already distributed devices.
- An explanation of the manufacturer’s plans for addressing already distributed product in the event of a positive decision on the marketing submission, including considerations such as the following, where relevant:
  - Process for notifying patients, consumers, healthcare facilities, healthcare providers, and device distributors of the device’s regulatory status; and
  - Process and timeline for providing to users of already distributed devices updated labeling or components for the cleared or approved device, including updated labeling or components to reflect any cleared/approved changes to the already distributed device.

FDA encourages manufacturers to collaborate with device distributors, healthcare facilities, healthcare providers, patients, and consumers, as appropriate, regarding their Transition Implementation Plan to assist all stakeholders with transition planning.

Depending on FDA’s evaluation of the marketing submission, FDA may engage with the manufacturer during the Agency’s review of the submission to discuss the appropriate disposition of already distributed devices described in the Transition Implementation Plan. For marketing submissions that include changes to the device compared to the already distributed device (e.g., modifications to address a cybersecurity concern), the manufacturer should discuss possible correction or removal with FDA regarding devices already distributed to the end user, as needed. As always, FDA will make case-by-case decisions regarding the enforcement of legal requirements in response to particular circumstances and questions that arise regarding a specific device or device type (e.g., requesting a firm initiate a recall, see 21 CFR 7.45), or taking other actions, including an enforcement action.

### E. Discontinuing distribution of a device
FDA expects manufacturers to discontinue distribution of a device within the scope of this guidance:

1) Before the start of Phase 3, if the manufacturer has not submitted a required marketing submission for its device and had it accepted by FDA before the start of Phase 3; or
2) On the date the manufacturer receives a negative decision on its marketing submission as FDA’s final action, or on the date the manufacturer withdraws its submission or fails to provide a complete response to an FDA request for additional information within the allotted time identified in FDA’s letter.

In addition, manufacturers should be aware of any applicable legal requirements for their device, such as adverse event reporting under 21 CFR Part 803, and continue to comply with such requirements for the duration in which they are applicable, which may extend beyond the cessation of distribution.

FDA encourages manufacturers to communicate with device distributors, healthcare facilities, healthcare providers, patients, and consumers, as appropriate, regarding their product disposition to assist all stakeholders with transition planning.

### F. Quality System considerations
FDA recognizes that there may be situations that raise unique compliance considerations, particularly regarding QS requirements. For example, non-traditional device manufacturers that previously operated under different quality standards or requirements may face challenges that take more time to address in transitioning to a system that fully complies with 21 CFR Part 820. FDA intends to take such considerations into account when making case-by-case compliance and enforcement decisions. Some manufacturers who intend to continue distributing their devices beyond Phase 2 may choose to request an exemption or variance from a device QS requirement as outlined in 21 CFR 820.1(e) and section 520(f)(2) of the FD&C Act. Any such exemption or variance should be requested within 90 days of the announcement of the implementation date for this guidance to help ensure FDA considers your request in time.

## VI. Examples
The following hypothetical examples are intended to illustrate the phased transition plan outlined above. To exemplify the timeline of the phased transition plan outlined in Section V. of this guidance, for purposes of the examples, FDA set the implementation date for all devices that fall within this enforcement policy as the implementation date, May 11, 2023, consistent with the timeline shown in Figure 1. The dates outlined in each example follow this example phased transition plan timeline. Note that these generalized examples do not account for every possible detail, risk, or consideration a manufacturer should evaluate or that may be relevant to FDA decisions regarding a particular device.

### Example 1
A 510(k)-cleared fetal doppler was modified to add Bluetooth functionality as described in the policies in the guidance, “[Enforcement Policy for Non-Invasive Fetal and Maternal Monitoring Devices Used to Support Patient Monitoring During the COVID-19 Public Health Emergency.](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-non-invasive-fetal-and-maternal-monitoring-devices-used-support-patient)”

#### a) Manufacturer who intends to continue distributing beyond Phase 2 and receives a positive decision on its marketing submission

**Phase 1 (May 11, 2023)**
In the above-referenced guidance, FDA describes its intent not to object to modification of certain fetal dopplers in certain circumstances without marketing authorization by FDA. The enforcement policy in the guidance does not address other requirements, including adverse event reporting, reports of corrections and removals, and QS requirements. The manufacturer continues to comply with requirements under 21 CFR Parts 803, 806, and 820.

**Phase 2 (August 9, 2023)**
As an indication of its intent to market its device beyond Phase 2, the fetal doppler manufacturer updates its existing listing under 21 CFR Part 807 Subparts B-D, as applicable. On October 1, 2023, the manufacturer submits a marketing submission to FDA, which is accepted by the Agency. Along with its marketing submission, the manufacturer includes a “Transition Implementation Plan” for already distributed fetal dopplers in the case of a positive decision as well as in the case of a negative decision on the marketing submission.

**Phase 3 (November 7, 2023)**
The above-referenced guidance is no longer in effect after the 180-day transition period ends, and FDA has not yet taken a final action on the manufacturer’s marketing submission. Under these circumstances, FDA does not intend to object to the continued distribution of the fetal doppler before FDA takes a final action on the marketing submission (see Section V.D.(1) of this guidance). The manufacturer continues to comply with all other legal requirements applicable to the device (such as registration and listing, QS, and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806). Additionally, the manufacturer has kept the device labeling as described in the labeling recommendations provided in the above-referenced guidance. Under these circumstances, FDA does not intend to object to the device labeling not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as described in the relevant List 1 guidance while the marketing submission is under FDA review (see Section V.D.(1) of this guidance).

The manufacturer receives a positive decision on its marketing submission on December 29, 2023 (90 days after submission), although outstanding software anomalies were identified and modifications to the device were made during FDA’s premarket review. Based on the Transition Implementation Plan included with the marketing submission, FDA is aware of the number of already distributed devices that may have these anomalies and engages with the manufacturer on how to address these issues with the already distributed devices and provide updated electronic labeling to the relevant stakeholders. The manufacturer initiates a correction to address the software anomalies in the fetal dopplers that were distributed prior to the positive marketing decision.

Additionally, as part of its Transition Implementation Plan, the manufacturer updates its website to add the updated device labeling. All devices distributed after receiving the positive decision will have the updated labeling.

#### b) Manufacturer who intends to continue distribution beyond Phase 2 and receives a negative decision on its marketing submission

**Phase 1 (May 11, 2023)**
In the above-referenced guidance, FDA describes its intent not to object to modification of certain fetal dopplers in certain circumstances without marketing authorization by FDA. The enforcement policy in the guidance does not address other requirements, including adverse event reporting, reports of corrections and removals, and QS requirements. The manufacturer continues to comply with requirements under 21 CFR Parts 803, 806, and 820.

**Phase 2 (August 9, 2023)**
As an indication of its intent to market its device beyond Phase 2, the fetal doppler manufacturer updates its existing listing under 21 CFR Part 807 Subparts B-D, as applicable. On October 1, 2023, the manufacturer submits a marketing submission to FDA, which is accepted by the Agency. Along with its marketing submission, the manufacturer includes a “Transition Implementation Plan” for already-distributed fetal dopplers in the case of a positive decision as well as in the case of a negative decision on the marketing submission.

**Phase 3 (November 7, 2023)**
The above-referenced guidance is no longer in effect after the 180-day transition period ends, and FDA has not yet taken a final action on the manufacturer’s marketing submission. Under these circumstances, FDA does not intend to object to the continued distribution of the fetal doppler before FDA takes a final action on the marketing submission (see Section V.D.(1) of this guidance). The manufacturer continues to comply with all other legal requirements applicable to the device (such as registration and listing, QS, and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806). Additionally, the manufacturer has kept the device labeling as described in the labeling recommendations provided in the above-referenced guidance. Under these circumstances, FDA does not intend to object to the device labeling not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as described in the relevant List 1 guidance while the marketing submission is under FDA review (see Section V.D.(1) of this guidance).

The manufacturer receives a negative decision on its marketing submission on January 15, 2024 (90 days after submission), due to outstanding software anomalies that were identified and could not be addressed by the manufacturer during FDA’s premarket review. As described in the Transition Implementation Plan included with the marketing submission, the manufacturer initiates a correction to restore the fetal doppler to the FDA-cleared version. In addition, the manufacturer ceases distributing the modified device.

### Example 2
A FDA-cleared diagnostic x-ray system was modified to become portable and falls within the enforcement policy described in the guidance [“Enforcement Policy for Imaging Systems During the COVID-19 Public Health Emergency.”](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-imaging-systems-during-coronavirus-disease-2019-covid-19-public-health-emergency)

**Phase 1 (May 11, 2023)**
In the above-referenced guidance, FDA describes its intent not to object to modifications to certain imaging systems in certain circumstances without marketing authorization by FDA. The enforcement policy in the guidance does not address other requirements, including requirements in 21 CFR Parts 803, 807 Subparts B-D, 806, 820, and 830. The manufacturer continues to comply with these requirements.

**Phase 2 (August 9, 2023)**
As an indication of its intent to market its device beyond Phase 2, the portable x-ray system manufacturer updates its existing listing, under 21 CFR Part 807 Subparts B-D, as applicable. On September 29, 2023, the manufacturer submits a marketing submission to FDA, which is accepted by the Agency. In its marketing submission, the manufacturer includes a “Transition Implementation Plan” for already-distributed portable x-ray systems in the case of a positive decision as well as in the case of a negative decision on the marketing submission.

**Phase 3 (November 7, 2023)**
The above-referenced guidance is no longer in effect after the 180-day transition period ends, and FDA has not yet taken a final action on the manufacturer’s marketing submission. Under these circumstances, FDA does not intend to object to the continued distribution of the portable x-ray system before FDA takes a final action on the marketing submission (see Section V.D.(1) of this guidance). The manufacturer continues to comply with all other legal requirements applicable to the device (such as registration and listing, QS, and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806). Additionally, the manufacturer has kept the device labeling as described in the labeling recommendations provided in the above-referenced guidance. Under these circumstances, FDA does not intend to object to the device labeling not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as described in the relevant List 1 guidance while the marketing submission is under FDA review (see Section V.D.(1) of this guidance).

The manufacturer does not respond to a request from FDA for additional information within the specified timeframe identified in the Agency’s deficiency letter. FDA issues a notice of withdrawal as the Agency’s final action on the marketing submission on March 15, 2024. FDA and the manufacturer engage regarding the manufacturer’s Transition Implementation Plan to address already distributed devices. The diagnostic x-ray is a reusable, non-life-supporting/non-life-sustaining device; as such, the manufacturer, following the Transition Implementation Plan, updates its website to accurately describe the product features and regulatory status of the already distributed, modified devices. FDA may request the firm initiate a recall of such devices in certain circumstances if a recall has not already been initiated (see 21 CFR 7.45). In addition, the manufacturer ceases distributing the modified device.

### Example 3
A FDA-cleared ventilator was modified to make material changes to components in the gas pathway to accommodate supplier shortages and falls within the enforcement policy described in the guidance, [“Enforcement Policy for Ventilators and Accessories and Other Respiratory Devices During the COVID-19 Public Health Emergency.”](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-ventilators-and-accessories-and-other-respiratory-devices-during-coronavirus)

**Phase 1 (May 11, 2023)**
In the above-referenced guidance, FDA describes its intent not to object to modifications to ventilators in certain circumstances without marketing authorization by FDA. The enforcement policy in the guidance does not address other requirements, including requirements in 21 CFR Parts 803, 807 Subparts B-D, 806, and 820, and 830. The manufacturer continues to comply with these requirements.

**Phase 2 (August 9, 2023):** 
As an indication of its intent to market its device beyond Phase 2, the ventilator manufacturer updates its existing listing, under 21 CFR Part 807 Subparts B-D, as applicable. On October 1, 2023, the ventilator manufacturer also submits an amendment to the manufacturer’s previously cleared marketing submission to the CDRH Document Control Center with “Attention: Notification of Intent” on the cover letter of the submission to describe the manufacturer’s intent to submit a marketing submission. This submission amendment includes the information outlined in Section V.C.(1) of this guidance. In its marketing submission that was accepted by the Agency on December 20, the manufacturer includes a “Transition Implementation Plan” for already distributed ventilators in the case of a positive decision as well as in the case of a negative decision on the marketing submission.

**Phase 3 (November 7, 2023):** 
The above-referenced guidance is no longer in effect after the 180-day transition period ends, and FDA has not yet taken a final action on the manufacturer’s marketing submission. Under these circumstances, FDA does not intend to object to the continued distribution of the ventilator before FDA takes a final action on the marketing submission (see Section V.D.(1) of this guidance). The manufacturer continues to comply with all other legal requirements applicable to the device (such as registration and listing, QS, and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806). Additionally, the manufacturer has kept the device labeling as described in the labeling recommendations provided in the above-referenced guidance. Under these circumstances, FDA does not intend to object to the device labeling not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as described in the relevant List 1 guidance while the marketing submission is under FDA review (see Section V.D.(1) of this guidance).

The ventilator manufacturer receives a positive decision on its marketing submission on January 2, 2024. The manufacturer continues to distribute the modified ventilator with updated labeling. In addition, the manufacturer communicates with users of the modified ventilator, distributed as described in the above-referenced guidance, apprising them of the regulatory status of the device and providing updated electronic labeling.

### Example 4
A new telethermographic system that has not been FDA-cleared and is intended for adjunctive diagnostic screening by providing an initial body temperature assessment for triage use, falls within the enforcement policy described in the guidance, “Enforcement Policy for Telethermographic Systems During the COVID-19 Public Health Emergency.”[^83]

#### a) Manufacturer who intends to continue distribution beyond Phase 2
**Phase 1 (May 11, 2023):** 
In the guidance, FDA describes its intent not to object to the distribution and use of certain telethermographic systems without submission of a 510(k), reports of corrections and removals, registration and listing, and compliance with the QS regulation and UDI, and other applicable labeling requirements in certain circumstances. The enforcement policy in the guidance does not address other requirements, including requirements in 21 CFR Part 803. The manufacturer continues to comply with 21 CFR Part 803.

**Phase 2 (August 9, 2023):** 
As an indication of its intent to market its device beyond Phase 2, the telethermographic system manufacturer registers and lists, consistent with 21 CFR Part 807 Subparts B-D, as applicable. On October 5, 2023, the manufacturer submits a marketing submission to FDA, which is accepted by the Agency. In its marketing submission, the manufacturer includes a “Transition Implementation Plan” for already distributed telethermographic systems in the case of a positive decision as well as in the case of a negative decision on the marketing submission.

**Phase 3 (November 7, 2023):** 
The above-referenced guidance is no longer in effect after the 180-day transition period ends, and FDA has not yet taken a final action on the manufacturer’s marketing submission. The manufacturer complies with all other legal requirements applicable to the device (such as registration and listing, QS, and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806). Additionally, the manufacturer has kept the device labeling as described in the labeling recommendations provided in the above-referenced guidance. Under these circumstances, FDA does not intend to object to the device labeling not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as described in the relevant List 1 guidance while the marketing submission is under FDA review (see Section V.D.(1) of this guidance).

The manufacturer receives a “not substantially equivalent” decision on January 3, 2024, after FDA’s review of the manufacturer’s marketing submission. The manufacturer ceases distributing the telethermographic system. FDA and the manufacturer engage regarding the manufacturer’s Transition Implementation Plan to address already distributed devices. FDA may request the firm initiate a recall of such devices in certain circumstances if a recall has not already been initiated (see 21 CFR 7.45).

#### b) Manufacturer who does not intend to continue distribution beyond Phase 2
A new telethermographic system that has not been FDA-cleared and is intended for adjunctive diagnostic screening by providing an initial body temperature assessment for triage use was distributed under the enforcement policy described in the guidance, “[Enforcement Policy for Telethermographic Systems During the COVID-19 Public Health Emergency.](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-telethermographic-systems-during-coronavirus-disease-2019-covid-19-public-health)”[^84]

**Phase 1 (May 11, 2023):** 
In the above-referenced guidance, FDA describes its intent not to object to the distribution and use of a certain telethermographic system without submission of a 510(k), reports of corrections and removals, registration and listing, and compliance with the QS regulation, UDI, and other applicable labeling requirements in certain circumstances. The enforcement policy in the guidance does not address other requirements, including 21 CFR Part 803. The manufacturer continues to comply with 21 CFR Part 803.

**Phase 2 (August 9, 2023):** 
The manufacturer decides that it does not want to continue to market and distribute the device beyond Phase 2. The manufacturer ceases distributing the device on November 1, 2023. The telethermographic system is a reusable, non-life-supporting/non-life-sustaining device. Devices that were distributed before the end of Phase 2 remain distributed. In addition, the manufacturer continues to report adverse events that it becomes aware of, even after the manufacturer has ceased distributing the telethermographic system.

**Phase 3 (November 7, 2023):** 
The above-referenced guidance is no longer in effect after the 180-day transition period ends. Prior to the start of Phase 3, the manufacturer provides updated electronic labeling for the telethermographic system, and such labeling accurately describes all product features and notes that the product is not FDA-cleared, -approved, or -authorized for marketing. The manufacturer leaves already distributed telethermographic systems in the field. The manufacturer continues to engage in adverse event reporting to FDA concerning the device.

**Table 2. Summary of Recommendations for a Phased Transition**
| **PHASE** | 1 | 2 | 3 |
|-----------|---|---|---|
| **STARTING TIME** | 0 days (implementation date – May 11, 2023) | 90 days after the implementation date – August 9, 2023 | 180 days after the implementation date – November 7, 2023 |
| **ACTIONS** | Manufacturers should, if not already doing so, follow adverse event reporting requirements under 21 CFR Part 803. Manufacturers should submit any stored adverse event reports and should refer to applicable [FDA guidance](#) regarding adverse event reporting during a pandemic. Manufacturers that intend to continue distribution of their devices after Phase 2 should begin to prepare their required marketing submissions. | Before the start of Phase 2, manufacturers that intend to continue to continue to distribute their devices after Phase 2 should register their establishments and list their device(s), or update their existing registration and listing, under 21 CFR Part 807 Subparts B-D, as applicable. Before the start of Phase 2, if not already doing so, manufacturers should submit reports of corrections and removals consistent with 21 CFR Part 806 (regardless of whether they intend to continue distribution of their devices after Phase 2). Manufacturers of devices under the product codes listed in Table 1 of this guidance should send a Notification of Intent to FDA (regardless of whether they intend to continue distribution of their devices after Phase 2). Manufacturers that intend to distribute their devices after Phase 2 should continue to prepare to submit a marketing submission to FDA and have it accepted by FDA before the start of Phase 3. | After the 180-day transition period ends, the List 1 guidances containing COVID-19 related enforcement policies will no longer be in effect. Before the start of Phase 3, if manufacturers submit a marketing submission(s), and that submission is accepted by FDA, at this time, FDA does not intend to object to the continued distribution of the device after Phase 2 as described in Section V.D.(1) of this guidance. With the marketing submission, the manufacturer should include a "Transition Implementation Plan" that addresses the manufacturer's plans for devices already in distribution in the case of a positive decision or a negative decision on the marketing submission. FDA recommends that the Transition Implementation Plan include the information in Section V.D.(2) of this guidance, as applicable. Moreover, for devices for which FDA has accepted a marketing submission prior to the start of Phase 3, FDA does not intend at this time to object to the devices not complying with certain UDI and other applicable labeling requirements where they are labeled as described in the relevant List 1 guidance. This enforcement policy does not apply to other applicable legal requirements (such as registration and listing, QS, and reports of corrections and removals requirements under 21 CFR Parts 807, 820, and 806, respectively). |
||
---

[^1]: Section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act provides that the term “device” means: “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is—
    (A) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
    (B) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
    (C) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. The term ‘device’ does not include software functions excluded pursuant to section 520(o)” of the Federal Food, Drug, and Cosmetic Act.
[^2]: Throughout this guidance, when describing policies for devices that fall within enforcement policies issued during the COVID-19 public health emergency declared under section 319 of the Public Health Service Act, FDA uses the term “manufacturer” to refer to any person who designs, manufactures, fabricates, assembles, or processes a finished device. See 21 CFR 820.3(o). Other entities, including those that introduce such devices into commercial distribution, such as initial importers and certain distributors, should ensure they understand, and where applicable, they should follow, the recommendations that pertain to such devices.
[^3]: Throughout this guidance, FDA refers to “normal operations” as a shorthand for the circumstances when the declaration of the PHE related to COVID-19 under section 319 of the Public Health Service Act has expired and/or the relevant device emergency use declarations related to COVID-19 under section 564 of the Federal Food, Drug, and Cosmetic Act are terminated.
[^4]: The guidance “Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19),” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-issued-emergency-use-authorizations-euas-related-coronavirus-disease](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-issued-emergency-use-authorizations-euas-related-coronavirus-disease), will be referred to as the “companion transition guidance” in the remainder of this guidance.
[^5]: Secretary of Health and Human Services, Determination that a Public Health Emergency Exists (originally issued on January 31, 2020, and subsequently renewed), available at [https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx](https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx).
[^6]: Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak (March 13, 2020), available at [https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/](https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/). On February 24, 2021, there was a Presidential Declaration continuing the national emergency concerning the COVID-19 pandemic beyond March 1, 2021. See Continuation of the National Emergency Concerning the Coronavirus Disease 2019 (COVID-19) Pandemic (86 FR 11599), available at [https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic](https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic).
[^7]: See the HHS “Fact Sheet: COVID-19 Public Health Emergency Transition Roadmap,” (February 9, 2023), available at [https://www.hhs.gov/about/news/2023/02/09/fact-sheet-covid-19-public-health-emergency-transition-roadmap.html](https://www.hhs.gov/about/news/2023/02/09/fact-sheet-covid-19-public-health-emergency-transition-roadmap.html).
[^8]: For links to the COVID-19-related FDA guidances, see the webpage “COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders,” available at [https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders](https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders).
[^35^]: For more information regarding FDA’s acceptance policies for marketing submissions, see the guidances “Refuse to Accept Policy for 510(k)s,” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/refuse-accept-policy-510ks](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/refuse-accept-policy-510ks), “Acceptance and Filing Reviews for Premarket Approval Applications (PMAs),” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-and-filing-reviews-premarket-approval-applications-pmas](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-and-filing-reviews-premarket-approval-applications-pmas), and “Acceptance Review for De Novo Classification Requests,” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-review-de-novo-classification-requests](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-review-de-novo-classification-requests).
[^36^]: For purposes of this guidance, FDA uses the term “final action” to mean a Medical Device User Fee Amendments (MDUFA) decision, which can include positive decisions, negative decisions, and notices of withdrawals, consistent with the: 510(k) Actions/Clock guidance, available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-premarket-notification-510k-submissions-effect-fda-review-clock-and-goals](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-premarket-notification-510k-submissions-effect-fda-review-clock-and-goals); De Novo Actions/Clock guidance, available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-de-novo-classification-requests-effect-fda-review-clock-and-goals](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-de-novo-classification-requests-effect-fda-review-clock-and-goals); PMA Actions/Clock guidance, available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-premarket-approval-applications-pmas-effect-fda-review-clock-and-goals](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-premarket-approval-applications-pmas-effect-fda-review-clock-and-goals).
[^37^]: See footnote 35.
[^38^]: FDA recommends that manufacturers engage with the Agency through the Q-Submission Program, including requesting Pre-Submissions, to discuss extenuating circumstances. For details on the Q-Submission Program, refer to the guidance “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program,” available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program).
[^39^]: Available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program).
[^40^]: FDA recognizes that not all uses would necessarily be violative. To the extent such use is violative, FDA generally does not intend to object as described herein.
[^41^]: FDA uses the term “removal” consistent with the definition in 21 CFR 806.2(i).
[^42^]: In situations where manufacturers do not believe restoration is possible or in the best interest of public health, FDA recommends additional engagement with the Agency on the appropriate disposition of a product if it is not otherwise discussed in this guidance.
[^43^]: For example, an FDA-cleared or -approved version may include an earlier software version, component replacement, or different labeling that removes information related to the use of the device as described in an enforcement policy.
[^44^]: The manufacturer should provide labeling to the original purchaser, and collaborate with the original purchaser to ensure that labeling is distributed to relevant stakeholders, including device distributors, healthcare facilities, healthcare providers, patients, consumers, etc.
[^45^]: See footnote 42.
[^46^]: See footnote 43.
[^47^]: See footnote 44.
[^48^]: FDA recognizes that not all use would necessarily be violative.
[^49^]: Should healthcare facilities wish to retain a device that lacks FDA clearance, approval, or authorization for use in the future, the future use of the device would be subject to the regulatory requirements of any future authorization, including marketing authorization or EUA, as applicable. For governmental stockpilers that wish to retain a device that lacks requisite FDA clearance, approval, or authorization for use in the future, FDA recommends engaging with the Agency to discuss the public health need for future deployment and/or use of the device in specific circumstances (e.g., regional natural disaster, localized disease outbreaks).
[^50]: For more information on adverse event reporting requirements under 21 CFR Part 803, see the guidance “Medical Device Reporting for Manufacturers,” available at [FDA guidance document](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-device-reporting-manufacturers).
[^51]: Available at [FDA guidance document search](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/).
[^52]: Data derived from real-world sources may be submitted in support of a marketing submission. See the guidance titled “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices,” available at [FDA guidance document](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-evidence-support-regulatory-decision-making-medical-devices).
[^53]: See, e.g., sections 510(k), 513(i)(2), 515, and 520(m) of the FD&C Act.
[^54]: 21 CFR Part 807, Subparts B-D.
[^55]: See, e.g., sections 510(k), 513(i)(2), 515, and 520(m) of the FD&C Act.
[^56]: The mailing address for the CDRH Document Control Center can be found in 21 CFR 807.90(a)(1) and 814.104(d)(1). FDA encourages manufacturers to submit Notifications of Intent as eCopies. Information about the eCopy program can be found in the guidance “eCopy Program for Medical Device Submissions,” available at [FDA guidance document](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-device-submissions).
[^57]: Submitting this information as soon as possible after issuance of this guidance is encouraged because it will assist the Agency in resource planning, help to avoid any supply disruptions, and otherwise help to ensure a smooth transition for these devices after the guidances in List 1 are no longer in effect.
[^58]: FDA recommends that the information be submitted as an “amendment” to the 510(k) or PMA file to facilitate efficient tracking of the “Notification of Intent” submissions.
[^59]: See, e.g., sections 510(k), 513(f)(2), 515, and 520(m) of the FD&C Act. For devices that are class I or II and exempt from premarket notification (e.g., shoe covers, face shields), no 510(k) submission is required unless the limitations of exemption are exceeded (see, e.g., 21 CFR 878.9).
[^60]: This includes a marketing submission for the device within the scope of the guidances in List 1, or a marketing submission for a device that is a derivative of, or the next generation of, the device within the scope of the guidances in List 1.
[^61]: Manufacturers that do not have an accepted marketing submission before the start of Phase 3 should refer to the policy described in Section V.A. of this guidance.
[^62]: See footnote 36.
[^63]: For example, if a manufacturer made modifications to the labeling of a cleared fetal doppler as described in the “Enforcement Policy for Non-Invasive Fetal and Maternal Monitoring Devices Used to Support Patient Monitoring During the COVID-19 Public Health Emergency” guidance, FDA generally does not intend to object to the manufacturer not complying with applicable labeling requirements (see 21 CFR Part 801) where the device continues to be labeled as described in that guidance while the marketing submission for the modified device is under review.
[^64]: Based on comments received on this draft guidance, as well as the companion transition guidance, FDA understands that updating the labeling of these devices while they are under FDA review, and then again if they are subsequently cleared, approved, or authorized, would be challenging for manufacturers. This policy takes those comments into account and is least burdensome for manufacturers and FDA. As noted elsewhere, manufacturers should engage with the Agency if they have questions specific to their device (e.g., regarding updating the device labeling to acknowledge that the device is currently under FDA review when the FDA review is expected to take an extended period of time).
[^65]: For manufacturers that register and list by the start of Phase 2, FDA recommends that manufacturers utilize the term “enforcement” in the premarket submission field if a submission number is not yet available. If the device subsequently receives marketing authorization, FDA expects manufacturers to comply with all applicable registration and listing requirements, which may require updating the listing information.
[^66]: For more information regarding FDA regulatory requirements for a specific device and FDA policies related to those requirements, manufacturers can use the FDA Guidance Search Tool to identify relevant guidance documents: [FDA Guidance Search](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/). After the start of Phase 3, FDA will look to any other applicable compliance policies and otherwise apply our general risk-based approach in making compliance and enforcement decisions. For more information, see the guidance “Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions,” available at [Factors to Consider](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-regarding-benefit-risk-medical-device-product-availability-compliance-and).
[^67]: 21 CFR 7.45(a) states that FDA “may request a firm to initiate a recall when the following determinations have been made: (1) That a product that has been distributed presents a risk of illness or injury or gross consumer deception. (2) That the firm has not initiated a recall of the product. (3) That an agency action is necessary to protect the public health and welfare.”
[^68]: See, e.g., sections 510(k), 513(f)(2), 515, and 520(m) of the FD&C Act.
[^69]: For more information regarding FDA’s acceptance policies for marketing submissions, see the guidances “Refuse to Accept Policy for 510(k)s,” available at [Refuse to Accept Policy](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/refuse-accept-policy-510ks), “Acceptance and Filing Reviews for Premarket Approval Applications (PMAs),” available at [Acceptance and Filing Reviews](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-and-filing-reviews-premarket-approval-applications-pmas), and “Acceptance Review for De Novo Classification Requests,” available at [Acceptance Review for De Novo Classification Requests](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-review-de-novo-classification-requests).
[^70]: FDA recommends that manufacturers engage with the Agency through the Q-Submission Program, including requesting Pre-Submissions, to discuss extenuating circumstances. For details on the Q-Submission Program, refer to the guidance “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.”
[^71]: See, e.g., 21 CFR 807.95(a)(1).
[^72]: To the extent the marketing submission contains trade secret information or confidential commercial or financial information, FDA will handle that information in accordance with applicable laws, including 21 CFR 20.61.
[^83]: Available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-telethermographic-systems-during-coronavirus-disease-2019-covid-19-public-health](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-telethermographic-systems-during-coronavirus-disease-2019-covid-19-public-health).
[^84]: Available at [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-telethermographic-systems-during-coronavirus-disease-2019-covid-19-public-health](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-telethermographic-systems-during-coronavirus-disease-2019-covid-19-public-health).


# 655  2023-04-18_FDA Website - Webinar on Guidances on COVID-19 Transition Plans.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2023-04-18_FDA Website - Webinar on Guidances on COVID-19 Transition Plans.md
file_date: 2023-04-18
title: FDA Website - Webinar on Guidances on COVID-19 Transition Plans
category: regulatory
subcategory: fda-policy
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license: Public Domain
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notes: date converted 2024-04-05
web_url: https://www.fda.gov/medical-devices/medical-devices-news-and-events/webinar-guidances-covid-19-transition-plans-medical-devices-04182023
summary_short: The Webinar on Guidances on COVID-19 Transition Plans summarizes FDA’s April 18, 2023 stakeholder webinar explaining two final guidances for transitioning COVID-19-related medical devices from EUA/enforcement-policy flexibilities back to normal regulatory operations. It highlights recommendations on marketing submissions, timing, and a 180-day transition period with examples, along with Q&A addressing manufacturer and stakeholder implementation issues.


CONTENT

Summary
On April 18, 2023, the U.S. Food and Drug Administration (FDA) hosted a webinar for stakeholders interested in learning more about the two final guidances on the Coronavirus Disease 2019 (COVID-19) transition plans for medical devices. 

During this webinar, the FDA:

Helped prepare manufacturers and other stakeholders for the orderly and transparent transition to normal operations.
Described recommendations regarding submitting a marketing submission and the timeline for doing so.
Provided examples to illustrate the transition policies and exemplify the 180-day transition period timeline.
Answered your questions about the guidances on the COVID-19 transition plans.
Background
In response to the COVID-19 pandemic, the device supply chain has been stressed because the demand for certain devices has exceeded available supply. As such, since the beginning of the COVID-19 pandemic, FDA took a number of proactive steps to help facilitate the availability of critical medical devices, including issuing emergency use authorizations (EUAs), which has enabled access to medical devices to help diagnose, treat, or prevent COVID-19. In addition, FDA issued guidances to help expand the availability of certain devices to help patients, health care providers, and other health care professionals access devices for COVID-19-related uses.

Given the magnitude of the COVID-19 pandemic, the FDA recognizes that stakeholders may need time to adjust to help ensure an orderly and transparent transition to normal operations. Further, the FDA is taking into account that the manufacture, distribution, and use of devices in the context of the COVID-19 pandemic raises unique considerations. These considerations include, for example, the manufacturing of devices by non-traditional manufacturers to address supply issues and the distribution and use of capital or reusable equipment that fall within enforcement policies issued during the COVID-19 public health emergency (PHE) declared under section 319 of the Public Health Service Act or under relevant device EUA declarations related to COVID-19 issued under section 564 of the Federal Food, Drug, and Cosmetic Act.

To provide clarity to manufacturers, the FDA issued two guidance documents to provide recommendations to manufacturers that may or may not want to continue to distribute certain medical devices after the PHE declaration expires and certain enforcement policies issued during the COVID-19 PHE are no longer in effect, or the relevant EUA declaration related to COVID-19 terminates.

See the guidances for more information: 
[Transition Plan for Medical Devices That Fall Within Enforcement Policies Issued During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-fall-within-enforcement-policies-issued-during-coronavirus-disease)
[Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-issued-emergency-use-authorizations-euas-related-coronavirus-disease)

Meeting Materials
The presentation, printable slides, and transcript are available at CDRH Learn under “Specialty Technical Topics”, sub-section “ COVID-19 Transition Policy”.


# 4,124  2023-09-23_FDA Response Letter - To Compliant regarding FDA Reference Panel from Dec 2020.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2023-09-23_FDA Response Letter - To Compliant regarding FDA Reference Panel from Dec 2020.md
file_date: 2023-09-23
title: FDA Response Letter - To Compliant regarding FDA Reference Panel from Dec 2020
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: pdf
xfile_type: NA
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conversion_input_file_type: pdf
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notes: Unsure about license
summary_short: The FDA letter dated September 29, 2023 responds to an Information Quality Act request from a law firm seeking removal of the FDA SARS-CoV-2 Reference Panel Comparative Data, claiming it was inaccurate and harmed EUA test developers. FDA explains the reference panel and protocol were scientifically sound for comparing relative limits of detection across assays, that participation and public posting were conditions of EUA authorization, and that variability in posted results supports the panel’s validity rather than a systemic flaw. It notes FDA later stopped distributing the reference panel when materials reached effective expiration and removed the comparative data from its website as outdated, denying requests for a public statement blaming accuracy concerns or for additional validation data publication.


CONTENT

September 29, 2023

Via Email

James P. Ellison 
Jeffrey N. Gibbs 
Gail H. Javitt 
Michael D. Shumsky 
Hyman Phelps & McNamara, P.C. 
700 13th Street NW, Suite 1200 
Washington, DC 20005

Dear Mr. Ellison, Mr. Gibbs, Ms. Javitt, and Mr. Shumsky:

This letter responds to your letter dated December 22, 2020, requesting that the U.S. Food and Drug Administration (FDA) remove FDA SARS-CoV-2 Reference Panel Comparative Data for COVID-19 molecular diagnostic assays contained on FDA’s website. Your request is based on your allegation that the data are inaccurate and misleading and, as a result, do not meet the statutory, Office of Management and Budget (OMB), Department of Health and Human Services (HHS), and FDA guidelines under the Information Quality Act (IQA), Pub. L. No. 106-554 (2000).

For the reasons set forth below, part of your request is now moot and we are denying the other parts of your request.


## I. Introduction
You assert that you are writing on behalf of unidentified clients who hold Emergency Use Authorization (EUA) for their tests and have participated in the Reference Panel program, which is a condition of authorization. You claim that your clients generated data for their tests using the FDA reference panel materials and instructions, and that the reference panel data generated by your clients do not correlate with the Limit of Detection (LoD) they previously established for their tests. You allege that your clients have been subject to “direct harm” because their tests are “being inaccurately presented as having a low sensitivity.” You also allege that health care practitioners and the public are being misled about critical information regarding these diagnostic assays. As a result of these alleged inadequacies, you contend that FDA’s disclosure of the FDA SARS-CoV-2 Reference Panel data violates the 2000 IQA.

Your letter requests that FDA (1) remove the SARS-CoV-2 Reference Panel Comparative Data from its website “until such time as all the information it contains is accurate,” (2) issue a public statement explaining that the data was removed “because of concerns regarding the accuracy of the data,” and (3) publish the data demonstrating “the validity of the reference panel and protocol.”

As discussed below, we have determined that the FDA SARS-CoV-2 Reference Panel and protocol instructions, which are used to generate the SARS-CoV-2 Reference Panel Comparative Data, are scientifically sound for their intended purpose of providing a relative LoD that can be used to establish a comparison of analytical test performances. Accordingly, we are denying your request.

We note that FDA stopped use of the FDA SARS-CoV-2 Reference Panel when it determined the reference panel materials it was providing test developers had, in effect, reached their expiration date. FDA has also removed the SARS-CoV-2 Reference Panel Comparative Data from its website as part of its regular review and updating of COVID-related information because that data has become outdated.


## II. Information Quality Act
In 2002, the Office of Management and Budget issued Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility and Integrity of Information Disseminated by Federal Agencies (Guidelines). As you note in your letter, the principles and core values underlying these Guidelines were updated and reinforced recently through the OMB Memorandum, Improving Implementation of the Information Quality Act (Apr. 24, 2019).1 FDA issued its agency-specific guidelines on September 30, 2002 (FDA Guidelines).2 You stated that “FDA does not appear to have updated its guidelines recently” in response to the OMB 2019 Memorandum. Although the updated guidelines have not yet been reflected on the HHS website, FDA has implemented the guidelines and complies with the latest guidelines. FDA’s practices are consistent with the Memorandum.


## III. Reference Panel and Protocol
The Reference Panel and its protocol provide both the material and procedure to be used to evaluate the analytical sensitivity or relative LoD of an assay used to detect SARS-CoV-2.

### A. Limit of Detection for SARS-CoV-2 Tests
Establishing the analytical sensitivity of a test, often referred to as the LoD (i.e., the lowest quantity or concentration of a component that can be reliably detected with a given assay in at

1 OMB, Memorandum, Improving Implementation of the Information Quality Act (Apr. 24, 2019)1, https://www.whitehouse.gov/wp-content/uploads/2019/04/M-19-15.pdf. 2 HHS Office of the Assistant Secretary for Planning and Evaluation, HHS Guidelines for Ensuring and Maximizing the Quality, Objectivity, and Integrity of Information Disseminated to the Public (HHS Guidelines) (Oct. 1, 2002), https://aspe.hhs.gov/report/hhs-guidelines-ensuring-and-maximizing-quality- objectivity-utility-and-integrity-information-disseminated-public.

U.S. Food & Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 FDA.GOV least 19/20 replicates), is a standard analytical procedure. For SARS-CoV-2 molecular tests, FDA has provided an EUA template with recommendations for determining the LoD.3 The template is updated as appropriate as we learn more about the COVID-19 disease and gain experience with the EUA process for the various types of COVID-19 tests.

The EUA template also provides recommendations to establish an assay clinical sensitivity. Clinical sensitivity is the probability that the test will identify as positive a clinical specimen that has been identified with a reference method. Clinical specimens are the preferred material for determining performance. Since natural clinical specimens were not available to test developers in the early phases of the COVID-19 pandemic, FDA authorized tests based on available data from contrived samples generated from a range of SARS-CoV-2 material sources for analytical and clinical performance evaluation. “Contrived” means that developers could “spike” some specified materials (e.g., viral RNA or inactivated virus) into a clinical matrix (e.g., BAL fluid, sputum, or nasopharyngeal swab). However, this approach is less likely than use of natural patient specimens to accurately characterize test performance.

The LoD, which is required in the labeling for each EUA-authorized test, was therefore based on the material and methodology used by the test developer, and these vary across the hundreds of EUA-authorized tests. As of the end of December 2020, when you had sent your letter, FDA had issued EUAs to over 230 nucleic acid-based tests (NATs) for SARS-CoV-2. Many of these tests (59) were developed and EUA-authorized based only on contrived specimens in the early phases of the pandemic, before clinical specimens were available to the test developers. As clinical specimens became available, FDA recommended that developers obtain and use patient specimens to validate their tests. In addition, FDA recommended evaluating the performance of the test with a comparator test by using clinical specimens. For the analytical performance, a quantified known positive clinical specimen, as determined by an EUA-authorized test, could also be used to create dilutions in clinical matrix for LoD determination. As of July 14, 2023, 277 NATs for SARS-CoV-2 were authorized for emergency use.

Since the LoD of the 230-plus molecular tests was determined using samples spiked with different types of materials, the performance of these tests, as reflected in the labeling originally authorized under the EUAs, cannot be directly compared. In addition, when clinical samples became available, different developers did not utilize the same samples and therefore results obtained with clinical specimens cannot be directly compared across assays either. Use of the same reference material across test developers is thus critical to allow a determination and direct comparison of the relative LoD of NATs for SARS-CoV-2.

For the analytical sensitivities of different tests to be compared, the clinical matrix must be spiked with the same material that has the different targets at the ratios found in the original virus. The material must be the same for different labs and be stable during transport and under the conditions stored prior to testing. Panels developed at the FDA laboratory produced the amount needed to fulfill testing for hundreds of assays, and to achieve consistency of the viral titer, sample composition, and targets present. For these reasons, FDA supplied the FDA SARS-CoV-2 Reference Panel with recommended handling procedures so that each lab would be assured that the material remained functional. Results of the testing to determine LoD were then checked with the blinded panel. This is a robust and efficient procedure to compare analytical sensitivities of a large number of different assays.

Recognizing that the availability of well-characterized reference reagents that all molecular tests can be compared against is critical to performance standardization of EUA-authorized assays during a pandemic, FDA had included in the EUA Letters of Authorization for every molecular-based test a requirement that the test developer would evaluate its test with an FDA- recommended reference material when such material was made available, and would update the test’s labeling to include the results of that additional data. This requirement is set forth in the following Condition of Authorization:

“You will evaluate the analytical limit of detection and assess traceability* of your product with any FDA-recommended reference material(s). After submission to and concurrence with the data by FDA, you will update your labeling to reflect the additional testing. Such labeling updates will be made in consultation with, and require concurrence of, DMD/OHT7- OIR/OPEQ/CDRH.” * Traceability refers to tracing analytical sensitivity/reactivity back to an FDA- recommended reference material.”

Thus, from the beginning, test developers submitting an EUA request for a SARS-CoV-2 NAT knew not only that they would be required to participate in testing with an FDA-recommended reference material but also that the data from that testing would be made publicly available for their EUA-authorized test. Data from evaluation of tests using the same reference panel provide more accurate information on the relative performance of different tests, allowing comparative studies that will give the FDA, professionals, laboratories, and patients a better understanding of the relative sensitivity of the various tests. The FDA SARS-CoV-2 Reference Panel also includes an additional coronavirus allowing the evaluation of cross- reactivity to MERS-CoV.

### B. Development and Validation of the Reference Panel
FDA began distributing the FDA SARS-CoV-2 Reference Panel in May 2020. To develop the FDA SARS-CoV-2 Reference Panel, FDA obtained live virus in February 2020. The SARS- CoV-2 strain used in this panel was cultivated, heat-inactivated, sequenced, and genetically characterized by the Center for Biologics Evaluation and Research (CBER) to produce reference reagents.

FDA appropriately validated the Reference Panel and protocol. In developing, producing, and characterizing the Reference Panel for SARS-CoV-2, CDRH/CBER followed the same scientific approach, methods, and principles used in the development and production of reference reagents for Zika virus tests, which are described in detail in the published articles “Production and characterization of Zika virus RNA reference reagents as a response to a public health emergency,” Transfusion, volume 58, September 2018, and “A Zika Reference Panel for Molecular-Based Diagnostic Devices as a US Food and Drug Administration Response Tool to a Public Health Emergency,” The Journal of Molecular Diagnostics, Vol. 21, No. 6, November 2019. The value of reference materials containing heat-inactivated SARS- CoV-2 virus has also been recognized in international studies; see, e.g., “RNA reference materials with defined viral RNA loads of SARS-CoV-2—A useful tool towards a better PCR assay harmonization,” PLoS ONE 17(1): e0262656 (January 20, 2022) available at https://doi.org/10.1371/journal.pone.0262656.

For Zika virus, CDRH used a variation of the CBER-developed reference reagents to create a reference panel for Zika virus tests suitable to in vitro diagnostics developers. CDRH created the reference panel known as Zika FDA-RP using dilutions of the culture media virus stocks in defibrinated human plasma. The stocks were diluted to various concentrations of NAT- detectable units (NDU), or NDU/mL. A single NDU is the minimum level of target that will result in a positive PCR result, which is not interchangeable with viral copy number/mL. The methodology for production of reagents and preparation of the reference panel, as well as the designs for the LoD range finding study, LoD confirmation study, and LoD blinded validation, are described in detail in the above-referenced article, “A Zika Reference Panel for Molecular- Based Diagnostic Devices as a US Food and Drug Administration Response Tool to a Public Health Emergency.” Those details will not be repeated here but can be found in the attached article. Articles are accepted for publication in The Journal of Molecular Diagnostics only after external scientific review. The FDA reference panel for Zika virus tests, developed and studied as described in this published article, was used to evaluate the performance of Zika virus diagnostic assays before they received an EUA.

Although the details about the preparation of the reference reagents, and the production and validation of the FDA SARS-CoV-2 Reference Panel, have not yet been published4, FDA followed the same scientific approach and methodology that was described in detail in the peer-reviewed, published articles describing the Zika FDA-RP, which was used successfully to evaluate Zika virus assays prior to granting an EUA. In addition, to further evaluate both the material and the protocol, FDA conducted a pilot study with several commercial manufacturers and laboratories prior to sending the FDA SARS-CoV-2 Reference Panel to all developers of EUA-authorized tests. The results of this pilot study supported the quality and utility of this specific FDA SARS-CoV-2 Reference Panel as well as the clarity of its protocol, providing additional external confirmation of the scientific validity of the FDA SARS-CoV-2 Reference Panel prior to distributing it to developers of EUA-authorized tests.

Furthermore, results obtained using the FDA SARS-CoV-2 Reference Panel show a wide distribution of values that further support that the reference panel was of appropriate quality for its use at the time the IQA complaint was submitted (12/22/2020). If the design of the Reference Panel were flawed, it should have resulted in all devices showing high LoD values with no expected dispersion.

4 FDA is developing a manuscript with information on the SARS-CoV-2 Reference Panel, but it has not been internally reviewed and cleared.

You have not provided any data or evidence to support your claim that the Reference Panel or protocol were flawed, or that use of the Reference Panel or protocol led to the FDA SARS- CoV-2 Reference Panel Comparative Data being unreliable. In contrast, existing data and information supports that the development, validation and use of the Reference Panel was appropriate for its stated purpose.


## IV. The FDA SARS-CoV-2 Reference Panel Comparative Data Is Not “Influential”
In your letter, you assert that the FDA SARS-CoV-2 Reference Panel Comparative Data constitute “influential” information as that term is used in the context of the IQA. The OMB Guidelines state that “influential” “means that the agency can reasonably determine that dissemination of the information will have or does have a clear and substantial impact on important public policies or important private sector decisions.” As explicitly contemplated by the OMB’s Guidelines, FDA’s Guidelines further explain this term in light of FDA’s areas of responsibility, stating:

For purposes of this guidance, influential information is defined as disseminated information that results from or is used in support of agency actions that are expected to have an annual effect on the economy of $100 million or more or will adversely affect in a material way the economy, a sector of the economy, productivity, competition, jobs, the environment, public health or safety, or State, local or tribal governments or communities. It should be noted that the definition applies to “information” itself, not to decisions that the information may support. Even if a decision or action by FDA is itself very important, a particular piece of information supporting it may or may not be “influential.”

In asserting that the information is “influential,” you base this on your view that FDA intends it to be influential because FDA has said that this type of comparison information has been “shown to be useful to healthcare providers and laboratories using these tests.” When a person or firm is deciding which authorized COVID molecular test to use, the comparative performance information can be useful. To the extent such information is considered, however, it is one of a wide range of considerations. The SARS-CoV-2 Reference Panel Comparative Data can help people understand the relative performance of authorized molecular tests, but relative performance is, and should be, just one consideration along with many other considerations, such as the indication a test is authorized for, test availability, test throughput, and cost. FDA is not aware of any information that shows, or even suggests, that healthcare providers and labs rely solely or even heavily on the posted relative performance information and, even if they did, they would merely be choosing one FDA-reviewed and authorized molecular test over another. In short, although this information can be useful, it is not “influential” as that term is used in the OMB and FDA Guidelines.


## V. Conclusion
Your request that FDA remove the SARS-CoV-2 Reference Panel Comparative Data from its website “until such time as all the information it contains is accurate,” is moot because FDA subsequently removed that information as part of its regular review and updating of COVID-

U.S. Food & Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 FDA.GOV

related information because it had become outdated. For the reasons stated above, FDA denies your request that it issue a public statement explaining that the data was removed “because of concerns regarding the accuracy of the data” and that FDA publish data demonstrating the validity of the Reference Panel and protocol.

Thank you for your interest in the quality of information disseminated by FDA. If you do not agree with FDA’s decision about your complaint (including any corrective action), you may send a request for reconsideration within 30 days of receipt of our decision. You may use any of the Procedures for Submitting Complaints described in the FDA specific guidelines contained in the HHS Information Quality Guidelines available at: https://aspe.hhs.gov/reports/hhs-guidelines-ensuring-maximizing-quality-objectivity-utility- integrity-information-disseminated. A request for reconsideration should state the reasons why you believe the response is inadequate, should be designated as an “Information Quality Appeal,” and sent to the following address:

Food and Drug Administration Office of Ombudsman 10903 New Hampshire Avenue WO Building 32, Room 4260 Silver Spring, MD 29993 Email: Ombuds@OC.FDA.gov

A request for reconsideration should include a copy of your original request and the Agency’s decision. The Agency will respond to all requests for appeals within the time frame specified in the procedure you use. Where a procedure does not specify a time frame for a response to your appeal, we will respond in a timely manner, in accordance with OMB and HHS Guidelines.

Sincerely,
Ellen J. Flannery 
Deputy Center Director for Policy 
Director, Office of Policy 
Center for Devices and Radiological Health

cc: Jeffrey Shuren, M.D., J.D. 
Timothy Stenzel, M.D., Ph.D. 
Mark Raza, J.D. 
Laurie Lenkel


# 507  2023-11-08_FDA Website - In Vitro Diagnostics EUAs.md
METADATA
last updated: 2026-03-04 by BA
file_name: 2023-11-08_FDA Website - In Vitro Diagnostics EUAs.md
file_date: 2023-11-08
title: FDA Website - In Vitro Diagnostics EUAs
category: regulatory
subcategory: fda-policy
tags: 
source_file_type: website
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gfile_url: NA
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notes: date converted 2024-04-05
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summary_short: The In Vitro Diagnostics EUAs page explains FDA’s COVID-19 IVD EUA framework after the May 11, 2023 expiration of the HHS public health emergency and the end of certain COVID-19 enforcement-policy guidances. It clarifies that the PHE’s end did not eliminate FDA’s authority to keep existing EUAs in effect or issue EUAs under FD&C Act section 564, and it directs manufacturers to FDA’s EUA transition-plan guidance and related FAQs for expectations when EUA declarations eventually end.


CONTENT

November 8, 2023 - The COVID-19 public health emergency (PHE) declared under section 319 of the Public Health Service (PHS) Act [expired](https://www.hhs.gov/about/news/2023/02/09/fact-sheet-covid-19-public-health-emergency-transition-roadmap.html) on May 11, 2023. The COVID-19 enforcement policy guidances within scope of the [Transition Plan for Medical Devices That Fall Within Enforcement Policies Issued During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency]((https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-fall-within-enforcement-policies-issued-during-coronavirus-disease)) are no longer in effect.

The end of the COVID-19 PHE and certain COVID-19 enforcement policy guidances no longer being in effect do not impact the FDA's ability to authorize devices, including tests, for emergency use. Existing emergency use authorizations (EUAs) for devices relating to COVID-19 remain in effect under section 564 of the Federal Food, Drug, and Cosmetic Act. The FDA encourages manufacturers of devices issued EUAs related to COVID-19 to review the guidance: [Transition Plan for Medical Devices Issued Emergency Use Authorizations(EUAs) Related to Coronavirus Disease 2019 (COVID-19)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-issued-emergency-use-authorizations-euas-related-coronavirus-disease) and [Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19)](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transition-plan-medical-devices-issued-emergency-use-authorizations-euas-related-coronavirus-disease), which outlines the FDA's recommendations and expectations to such manufacturers to transition to normal operations when the declarations that allowed for FDA to issue EUAs under section 564 of the Federal Food, Drug, and Cosmetic Act end. Additional information is provided on the page [FAQs: What happens to EUAs when a public health emergency ends?](https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/faqs-what-happens-euas-when-public-health-emergency-ends)


# 6,657  FDA SARS-CoV-2 Reference Panel Comparative Data - Complied by Matt McFarlane.md
METADATA
last updated: 2026-03-04 by BA
file_name: FDA SARS-CoV-2 Reference Panel Comparative Data - Complied by Matt McFarlane.md
file_date: 2021-01-11
title: FDA SARS-CoV-2 Reference Panel Comparative Data
category: regulatory
subcategory: fda-policy
tags: 
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xfile_type: xlsx
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notes: Missing date, unsure about license
summary_short: The FDA SARS-CoV-2 Reference Panel Comparative Data spreadsheet compiles EUA-reported LoDs and FDA reference panel LoDs for many authorized molecular tests, enabling side-by-side comparison of relative analytical sensitivity across developers and platforms. It includes test names, developers, notes on data-release wave and versioning caveats, and a calculated FDA/EUA LoD ratio to highlight discrepancies between EUA-submitted LoD claims and reference-panel results.


CONTENT

***INTERNAL TITLE*** FDA SARS-CoV-2 Reference Panel Comparative Data
*Compiled by Matt McFarlane*

## Data
| Test                                 | EUA LOD (/3ml swab)   |   FDA Panel LOD (/3ml swab) | FDA/EUA LOD   | DataNote         | Developer                                                                       | Full Test                                                                           |                                                                    |
|--------------------------------------|-----------------------|-----------------------------|---------------|------------------|---------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|----------------------------------------------------------------------------|
| PerkinElmer                          | 28                    |                         540 | 19.28571429   | 1st data release | PerkinElmer, Inc.                                                               | PerkinElmer New Coronavirus Nucleic Acid Detection Kit                              |                                                                            |
| ScienCell                            | 9600                  |                        1620 | 0.16875       | 1st data release | ScienCell Research Laboratories                                                 | ScienCell SARS-CoV-2 Coronavirus Real-time RT-PCR (RT-qPCR) Detection Kit           |                                                                            |
| BioCore                              | 1500                  |                        1800 | 1.2           | 1st data release | BioCore Co., Ltd.                                                               | BioCore 2019-nCoV Real Time PCR Kit                                                 |                                                                            |
| DiaCarta (4 1plex wells)             | 600                   |                        1800 | 3.0           | 1st data release | DiaCarta, Inc                                                                   | QuantiVirus SARS-CoV-2 Test kit                                                     | Results were obtained with the version of the test authorized on 4/08/2020 |
| DiaCarta (duplex)                    | 300                   |                        1800 | 6.0           | 1st data release | DiaCarta, Inc                                                                   | QuantiVirus SARS-CoV-2 Multiplex Test Kit                                           |                                                                            |
| Hologic (Panther RTqPCR)             | 600                   |                        1800 | 3.0           | 1st data release | Hologic, Inc.                                                                   | Panther Fusion SARS-CoV-2 Assay                                                     |                                                                            |
| Hologic (TMA)                        | 638                   |                        1800 | 2.821316614   | 1st data release | Hologic, Inc.                                                                   | Aptima SARS-CoV-2 assay                                                             |                                                                            |
| Seasun (PCR)                         | 3000                  |                        1800 | 0.6           | 1st data release | SEASUN BIOMATERIALS                                                             | U-TOP COVID-19 Detection Kit                                                        |                                                                            |
| PrivaPath (letsgetchecked)           | 600                   |                        2160 | 3.6           | 1st data release | PrivaPath Diagnostics, Inc.2                                                    | LetsGetChecked Coronavirus (COVID-19) Test                                          |                                                                            |
| BD Max (2 duplex)                    | 120                   |                        5400 | 45.0          | 1st data release | Becton, Dickinson & Company (BD)                                                | BioGX SARS-CoV-2 Reagents for BD MAX System                                         |                                                                            |
| CirrusDx                             | 1170                  |                        5400 | 4.615384615   | 1st data release | CirrusDx Laboratories                                                           | CirrusDx SARS-CoV-2 Assay                                                           |                                                                            |
| EuroImmun                            | 450                   |                        5400 | 12.0          | 1st data release | Euroimmun US, Inc.                                                              | EURORealTime SARS-Cov-2                                                             |                                                                            |
| Helix (PCR)                          | 3000                  |                        5400 | 1.8           | 1st data release | Helix OpCo LLC (dba Helix)                                                      | Helix COVID-19 Test                                                                 |                                                                            |
| LabGenomics                          | 60000                 |                        5400 | 0.09          | 1st data release | LabGenomics Co., Ltd.                                                           | LabGun COVID-19 RT-PCR Kit                                                          |                                                                            |
| Quest Diagnostics                    | 408                   |                        5400 | 13.23529412   | 1st data release | Quest Diagnostics Infectious Disease, Inc.                                      | Quest SARS-CoV-2 rRT-PCR                                                            |                                                                            |
| Rheonix                              | 1875                  |                        5400 | 2.88          | 1st data release | Rheonix, Inc.                                                                   | Rheonix COVID-19 MDx Assay                                                          |                                                                            |
| Roche                                | 138                   |                        5400 | 39.13043478   | 1st data release | Roche Molecular Systems, Inc. (RMS)                                             | cobas SARS-CoV-2                                                                    |                                                                            |
| Applied DNA                          | 3750                  |                        7500 | 2.0           | 1st data release | Applied DNA Sciences, Inc.                                                      | Linea COVID-19 Assay Kit                                                            |                                                                            |
| Abbott (m2000)                       | 120                   |                        8100 | 67.5          | 1st data release | Abbott Molecular                                                                | Abbott RealTime SARS-CoV-2 assay                                                    |                                                                            |
| Fulgent                              | 15000                 |                       10800 | 0.72          | 1st data release | Fulgent Therapeutics, LLC                                                       | Fulgent COVID-19 by RT-PCR Test                                                     |                                                                            |
| Enzo                                 | 840                   |                       10800 | 12.85714286   | 1st data release | Enzo Life Sciences, Inc.                                                        | AMPIPROBE SARS-CoV-2 Test System                                                    |                                                                            |
| Access Bio                           | 1286                  |                       16200 | 12.59720062   | 1st data release | Access Bio, Inc.                                                                | CareStart COVID-19 MDx RT-PCR                                                       |                                                                            |
| Applied BioCode                      | 0.017 TCID50/ml       |                       16200 |               | 1st data release | Applied BioCode, Inc.                                                           | BioCode SARS-CoV-2 Assay                                                            |                                                                            |
| Assurance Sci.                       | 15000                 |                       16200 | 1.08          | 1st data release | Assurance Scientific Laboratories                                               | Assurance SARS-CoV-2 Panel                                                          |                                                                            |
| BD Max (triplex)                     | 120                   |                       16200 | 135.0         | 1st data release | Becton, Dickinson & Company                                                     | BD SARS-CoV-2 Reagents for BD MAX System                                            | Results were obtained with the version of the test authorized on 9/23/2020 |
| BioFire Defense                      | 990                   |                       16200 | 16.36363636   | 1st data release | BioFire Defense, LLC                                                            | BioFire COVID-19 Test                                                               |                                                                            |
| Boston Heart                         | 750                   |                       16200 | 21.6          | 1st data release | Boston Heart Diagnostics                                                        | Boston Heart COVID-19 RT-PCR Test                                                   |                                                                            |
| Cepheid                              | 750                   |                       16200 | 21.6          | 1st data release | Cepheid                                                                         | Xpert Xpress SARS-CoV-2 test                                                        |                                                                            |
| ChromaCode                           | 3000                  |                       16200 | 5.4           | 1st data release | ChromaCode Inc.                                                                 | HDPCR SARS-CoV-2 Assay                                                              |                                                                            |
| Ethos                                | 60000                 |                       16200 | 0.27          | 1st data release | Ethos Laboratories                                                              | Ethos Laboratories SARS-CoV-2 MALDI-TOF Assay                                       |                                                                            |
| GeneMatrix                           | 7500                  |                       16200 | 2.16          | 1st data release | GeneMatrix, Inc                                                                 | NeoPlex COVID-19 Detection Kit                                                      |                                                                            |
| Hackensack Uni MC                    | 12000                 |                       16200 | 1.35          | 1st data release | Hackensack University Medical Center (HUMC) Molecular Pathology Laboratory      | CDI Enhanced COVID-19 Test                                                          |                                                                            |
| Kogene                               | 12000                 |                       16200 | 1.35          | 1st data release | KogeneBiotech Co., Ltd.                                                         | PowerChek 2019-nCoV Real-time PCR Kit                                               |                                                                            |
| Luminex (NxTAG)                      | 15000                 |                       16200 | 1.08          | 1st data release | Luminex Molecular Diagnostics, Inc.                                             | NxTAG CoV Extended Panel Assay                                                      |                                                                            |
| Patients Choice                      | 300000                |                       16200 | 0.054         | 1st data release | Patients Choice Laboratories, LLC                                               | PCL SARS-CoV-2 Real-Time RT-PCR Assay                                               |                                                                            |
| CDC (inf+CoV2)                       | ?                     |                       17100 |               | 1st data release | Centers for Disease Control and Prevention (CDC)                                | Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay                                      |                                                                            |
| DiaSorin                             | 1500                  |                       18000 | 12.0          | 1st data release | DiaSorin Molecular LLC                                                          | Simplexa COVID-19 Direct assay                                                      |                                                                            |
| Quidel                               | 2400                  |                       18000 | 7.5           | 1st data release | Quidel Corporation                                                              | Lyra SARS-CoV-2 Assay                                                               |                                                                            |
| Seasun (LAMP, 1 duplex)              | 21000                 |                       18000 | 0.8571428571  | 1st data release | Seasun Biomaterials, Inc                                                        | AQ-TOP COVID-19 Rapid Detection Kit                                                 |                                                                            |
| Sherlock BioSci                      | 20250                 |                       18000 | 0.8888888889  | 1st data release | Sherlock BioSciences, Inc.                                                      | Sherlock CRISPR SARS-CoV-2 Kit                                                      |                                                                            |
| UNC                                  | 2640                  |                       18000 | 6.818181818   | 1st data release | University of North Carolina Medical Center                                     | UNC Health SARS-CoV-2 real-time RT-PCR test                                         |                                                                            |
| Exact Sciences                       | 7800                  |                       18075 | 2.317307692   | 1st data release | Exact Sciences Laboratories                                                     | SARS-CoV-2 (N gene detection) Test                                                  |                                                                            |
| CDC                                  | 9500                  |                       54000 | 5.684210526   | 1st data release | Centers for Disease Control and Prevention (CDC)                                | CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel (CDC)                               |                                                                            |
| Acupath                              | 75000                 |                       54000 | 0.72          | 1st data release | Acupath Laboratories, Inc                                                       | Acupath COVID-19 Real-Time (RT-PCR) Assay                                           |                                                                            |
| Avellino Lab USA                     | 165000                |                       54000 | 0.3272727273  | 1st data release | Avellino Lab USA, Inc.                                                          | AvellinoCoV2 test                                                                   |                                                                            |
| Color                                | 2250                  |                       54000 | 24.0          | 1st data release | Color Genomics, Inc.2                                                           | Color Genomics SARS-CoV-2 RT-LAMP Diagnostic Assay                                  | Results were obtained with the version of the test authorized on 8/28/2020 |
| Eli Lilly                            | 3000                  |                       54000 | 18.0          | 1st data release | Eli Lilly and Company                                                           | Lilly SARS-CoV-2 Assay                                                              |                                                                            |
| Gravity (CDC Primers)                | 7200                  |                       54000 | 7.5           | 1st data release | Gravity Diagnostics, LLC                                                        | Gravity Diagnostics COVID-19 Assay                                                  |                                                                            |
| HealthQuest                          | 60000                 |                       54000 | 0.9           | 1st data release | HealthQuest Esoterics                                                           | HealthQuest Esoterics TaqPath SARS-CoV-2 Assay                                      |                                                                            |
| Boston CH                            | 6900                  |                       54000 | 7.826086957   | 1st data release | Infectious Diseases Diagnostics Laboratory (IDDL), Boston Children's Hospital   | Childrens-Altona-SARS-CoV-2 Assay                                                   |                                                                            |
| Psomagen                             | 3000                  |                       54000 | 18.0          | 1st data release | Psomagen, Inc.                                                                  | Psoma COVID-19 RT Test                                                              |                                                                            |
| Yale                                 | 6000                  |                      540000 | 90.0          | 1st data release | Diatherix Eurofins Laboratory                                                   | SARS-CoV-2 PCR Test                                                                 |                                                                            |
| Luminex (Aries)                      | 999                   |                      540000 | 540.5405405   | 1st data release | Luminex Corporation                                                             | ARIES SARS-CoV-2 Assay                                                              |                                                                            |
| Qiagen                               | 1500                  |                      540000 | 360.0         | 1st data release | QIAGEN GmbH                                                                     | QIAstat-Dx Respiratory SARS-CoV-2 Panel                                             |                                                                            |
| Abbott (ID Now)                      | 313                   |                       15000 | 47.92332268   | 1st data release | Abbott Diagnostics Scarborough, Inc.                                            | ID NOW COVID-19                                                                     |                                                                            |
| Quidel (LyraDirect)                  | 5120                  |                       27000 | 5.2734375     | 1st data release | Quidel Corporation                                                              | Lyra Direct SARS-CoV-2 Assay                                                        |                                                                            |
| Bio-Rad                              | 450                   |                        1800 | 4.0           | 2nd data release | Bio-Rad Laboratories, Inc                                                       | Bio-Rad SARS-CoV-2 ddPCR Test                                                       |                                                                            |
| Altru                                | 1875                  |                        5400 | 2.88          | 2nd data release | Altru Diagnostics, Inc.                                                         | Altru Dx SARS-CoV-2 RT-PCR assay                                                    |                                                                            |
| OPTI                                 | 2700                  |                        5400 | 2.0           | 2nd data release | OPTI Medical Systems, Inc.                                                      | OPTI SARS-COV-2 RT PCR Test                                                         |                                                                            |
| Roche (infA/B+CoV2, Cobas)           | 182                   |                        5400 | 29.67032967   | 2nd data release | Roche Molecular Systems, Inc.                                                   | cobas SARS-CoV-2 & Influenza A/B                                                    |                                                                            |
| Illumina                             | 3000                  |                       16200 | 5.4           | 2nd data release | Illumina, Inc.                                                                  | Illumina COVIDSeq Test                                                              |                                                                            |
| NeuMoDx                              | 450                   |                       16200 | 36.0          | 2nd data release | NeuMoDx Molecular, Inc.                                                         | NeuMoDx SARS-CoV-2 Assay                                                            |                                                                            |
| ZhuHai Sinochips                     | 7500                  |                       16200 | 2.16          | 2nd data release | ZhuHai Sinochips Bioscience Co., Ltd                                            | COVID-19 Nucleic Acid RT-PCR Test Kit                                               |                                                                            |
| Columbia Uni.                        | 840                   |                       18000 | 21.42857143   | 2nd data release | Columbia University Laboratory of Personalized Genomic Medicine                 | TRIPLEX CII-SARS-CoV-2 rRT-PCR TEST                                                 |                                                                            |
| 1drop                                | 600                   |                       54000 | 90.0          | 2nd data release | 1drop Inc.                                                                      | 1copy COVID-19 qPCR Multi Kit                                                       |                                                                            |
| BioMérieux                           | 1140                  |                       54000 | 47.36842105   | 2nd data release | BioMérieux SA                                                                   | SARS-COV-2 R-GENE                                                                   |                                                                            |
| Cedars-Sinai                         | 30000                 |                       54000 | 1.8           | 2nd data release | Cedars-Sinai Medical Center, Department of Pathology and Laboratory Medicine    | SARS-CoV-2-Assay                                                                    |                                                                            |
| Curative                             | 600                   |                       54000 | 90.0          | 2nd data release | KorvaLabs Inc.                                                                  | Curative-Korva SARS-Cov-2 Assay                                                     |                                                                            |
| Phosphorus Dx                        | 15000                 |                       54000 | 3.6           | 2nd data release | Phosphorus Diagnostics LLC                                                      | Phosphorus COVID-19 RT-qPCR Test                                                    | 4                                                                          |
| Ultimate Dx                          | 300                   |                       54000 | 180.0         | 2nd data release | Ultimate Dx Laboratory                                                          | UDX SARS-CoV-2 Molecular Assay                                                      |                                                                            |
| Ipsum                                | 25500                 |                      540000 | 21.17647059   | 2nd data release | Ipsum Diagnostics, LLC                                                          | COV-19 IDx assay                                                                    | Results were obtained with the version of the test authorized on 4/01/2020 |
| Thermo Fisher                        | 750                   |                      540000 | 720.0         | 2nd data release | Thermo Fisher Scientific, Inc.                                                  | TaqPath COVID-19 Combo Kit                                                          |                                                                            |
| PreciGenome                          | 1714                  |                      540000 | 315.0525088   | 2nd data release | PreciGenome LLC3                                                                | FastPlex Triplex SARS-CoV-2 detection kit (RT-Digital PCR)                          |                                                                            |
| MicroGen DX                          | 300                   |                      540000 | 1800.0        | 2nd data release | Southwest Regional PCR Laboratory LLC. dba MicroGen DX                          | COVID-19 Key                                                                        |                                                                            |
| SDI                                  | 1500                  |                      540000 | 360.0         | 2nd data release | Specialty Diagnostic (SDI) Laboratories                                         | SDI SARS-CoV-2 Assay                                                                |                                                                            |
| Boston Medical                       | 3000                  |                     1800000 | 600.0         | 2nd data release | Boston Medical Center                                                           | BMC-CReM COVID-19 Test                                                              |                                                                            |
| Viracor Eurofins                     | 219                   |                         540 | 2.465753425   | 3rd data release | Viracor Eurofins Clinical Diagnostics                                           | Viracor SARS-CoV-2 assay                                                            |                                                                            |
| Zymo                                 | 750                   |                        1350 | 1.8           | 3rd data release | Zymo Research Corporation1                                                      | Quick SARS-CoV-2rRT-PCR Kit                                                         |                                                                            |
| Fast Track                           | 0.0069 TCID50/ml      |                        1620 |               | 3rd data release | Fast Track Diagnostics Luxembourg S.á.r.l. (a Siemens Healthineers Company)     | FTD SARS-COV-2                                                                      |                                                                            |
| UMass                                | 12000                 |                        5400 | 0.45          | 3rd data release | UMass Memorial Medical Center                                                   | UMass Molecular Virology Laboratory 2019-nCoV rRT-PCR Dx Panel                      |                                                                            |
| Texas DSHS                           | 60                    |                        5400 | 90.0          | 3rd data release | Texas Department of State Health Services, Laboratory Services Section          | Texas Department of State Health Services (DSHS) SARS-CoV-2 Assay                   |                                                                            |
| Nationwide CH                        | 94                    |                        5400 | 57.44680851   | 3rd data release | Nationwide Children's Hospital                                                  | SARS-CoV-2 Assay (CH)                                                               |                                                                            |
| Maccura                              | 3000                  |                        5400 | 1.8           | 3rd data release | Maccura Biotechnology (USA) LLC                                                 | SARS-CoV-2 Fluorescent PCR Kit                                                      |                                                                            |
| Cormeum                              | 6000                  |                        5400 | 0.9           | 3rd data release | Cormeum Laboratory Services                                                     | Cormeum SARS-CoV-2 Assay                                                            |                                                                            |
| CSI Labs                             | 18750                 |                        5400 | 0.288         | 3rd data release | CSI Laboratories                                                                | CSI SARS-CoV-2 RT PCR Test                                                          |                                                                            |
| Biocollections                       | 3000                  |                        5400 | 1.8           | 3rd data release | Biocollections Worldwide, Inc.                                                  | Biocollections Worldwide SARS-Co-V-2 Assay                                          |                                                                            |
| BayCare                              | 138                   |                        5400 | 39.13043478   | 3rd data release | BayCare SARS-CoV-2 RT PCR Assay                                                 | BayCare SARS-CoV-2 RT PCR Assay                                                     |                                                                            |
| Tempus                               | 750                   |                        7200 | 9.6           | 3rd data release | Tempus Lab, Inc.                                                                | iC SARS-CoV2 Test                                                                   |                                                                            |
| Gencurix                             | 18000                 |                        8100 | 0.45          | 3rd data release | Gencurix, Inc.                                                                  | GenePro SARS-CoV-2 Test                                                             |                                                                            |
| BGI genomics                         | 450                   |                        9000 | 20.0          | 3rd data release | BGI Genomics Co. Ltd                                                            | Real-Time Fluorescent RT-PCR Kit for Detecting SARS-CoV-2                           |                                                                            |
| Guardant Health                      | 375                   |                       16200 | 43.2          | 3rd data release | Guardant Health, Inc.2                                                          | Guardant-19                                                                         |                                                                            |
| ClearDx                              | 6000                  |                       16200 | 2.7           | 3rd data release | Clear Labs, Inc.                                                                | Clear Dx SARS-CoV-2 Test                                                            |                                                                            |
| Sandia                               | 18750                 |                       16200 | 0.864         | 3rd data release | Sandia National Laboratories                                                    | SNL-NM 2019 nCoV Real-Time RT-PCR Diagnostic Assay                                  |                                                                            |
| Roche (infA/B+CoV2, Liat)            | 36                    |                       16200 | 450.0         | 3rd data release | Roche Molecular Systems, Inc.                                                   | cobas SARS-CoV-2 & Influenza A/B Nucleic Acid Test for use on the cobas Liat System |                                                                            |
| Optolane                             | 15000                 |                       16200 | 1.08          | 3rd data release | OPTOLANE Technologies, Inc.                                                     | Kaira 2019-nCoV Detection Kit                                                       |                                                                            |
| LumiraDx                             | 1500                  |                       16200 | 10.8          | 3rd data release | LumiraDx UK Ltd.                                                                | LumiraDx SARS-CoV-2 RNA STAR                                                        |                                                                            |
| BioSewoom                            | 18750                 |                       16200 | 0.864         | 3rd data release | BioSewoom, Inc.                                                                 | Real-Q 2019-nCoV Detection Kit                                                      |                                                                            |
| InBios                               | 3300                  |                       18000 | 5.454545455   | 3rd data release | InBios International, Inc.                                                      | Smart Detect SARS-CoV-2 rRT-PCR Kit                                                 |                                                                            |
| BioFire (RP)                         | 480                   |                       18000 | 37.5          | 3rd data release | BioFire Diagnostics, LLC                                                        | BioFire Respiratory Panel 2.1 (RP2.1)                                               |                                                                            |
| Diagnostic Solutions                 | 10                    |                       54000 | 5400.0        | 3rd data release | Diagnostic Solutions Laboratory, LLC                                            | DSL COVID-19 Assay                                                                  |                                                                            |
| SolGent                              | 600                   |                       54000 | 90.0          | 3rd data release | SolGent Co., Ltd                                                                | DiaPlexQ Novel Coronavirus (2019-nCoV) Detection Kit                                |                                                                            |
| Miami Baptist                        | 6000                  |                       54000 | 9.0           | 3rd data release | Pathology/Laboratory Medicine Lab of Baptist Hospital Miami                     | COVID-19 RT-PCR Test (Miami)                                                        |                                                                            |
| Vela (v1, 2 duplex wells per sample) | 1680                  |                       54000 | 32.14285714   | 3rd data release | Vela Operations Singapore Pte Ltd                                               | ViroKey SARS-CoV-2 RT-PCR Test                                                      |                                                                            |
| MD Anderson                          | 15000                 |                       54000 | 3.6           | 3rd data release | University of Texas MD Anderson Cancer Center, Molecular Diagnostics Laboratory | MD Anderson High-throughput SARS-CoV-2 RT-PCR Assay                                 |                                                                            |
| Stanford                             | 3000                  |                       54000 | 18.0          | 3rd data release | Stanford Health Care Clinical Virology Laboratory                               | Stanford SARS-CoV-2 assay                                                           |                                                                            |
| T2 Biosystems                        | 6000                  |                       54000 | 9.0           | 3rd data release | T2 Biosystems, Inc.                                                             | T2SARS-CoV-2 Panel                                                                  |                                                                            |
| Gene By Gene                         | 18750                 |                       54000 | 2.88          | 3rd data release | Gene By Gene                                                                    | Gene By Gene SARS-CoV-2 Detection Test                                              |                                                                            |
| AIT Labs                             | 3000                  |                       54000 | 18.0          | 3rd data release | AIT Laboratories                                                                | SARS-CoV-2 Assay (AIT)                                                              |                                                                            |
| Gravity (ThermoPrimers)              | 3000                  |                       54000 | 18.0          | 3rd data release | Gravity Diagnostics, LLC                                                        | Gravity Diagnostics SARS-CoV-2 RT-PCR Assay                                         |                                                                            |
| Solaris                              | 30000                 |                       54000 | 1.8           | 3rd data release | Solaris Diagnostics                                                             | Solaris Multiplex SARS-CoV-2 Assay                                                  |                                                                            |
| Biomeme                              | 5400                  |                       54000 | 10.0          | 3rd data release | Biomeme, Inc.                                                                   | Biomeme SARS-CoV-2 Real-Time RT-PCR Test                                            |                                                                            |
| Visby                                | 3336                  |                      162000 | 48.56115108   | 3rd data release | Visby Medical, Inc.                                                             | Visby Medical COVID-19                                                              |                                                                            |
| Primerdesign                         | 990                   |                      162000 | 163.6363636   | 3rd data release | Primerdesign Ltd.3                                                              | Primerdesign Ltd COVID-19 genesig Real-Time PCR assay                               |                                                                            |
| GenMark (Panel)                      | 750                   |                      540000 | 720.0         | 3rd data release | GenMark Diagnostics, Inc.                                                       | ePlex Respiratory Pathogen Panel 2                                                  |                                                                            |
| UTMG                                 | 100 PFU               |                      540000 |               | 3rd data release | UTMG Pathology Laboratory2                                                      | UTHSC/UCH SARS-CoV-2-RT-PCR Assay                                                   |                                                                            |
| Omnipathology                        | 3690                  |                      540000 | 146.3414634   | 3rd data release | Omnipathology Solutions Medical Corporation                                     | Omni COVID-19 Assay by RT-PCR                                                       |                                                                            |
| LCT                                  | 609                   |                      540000 | 886.6995074   | 3rd data release | Laboratorio Clinico Toledo                                                      | Laboratorio Clinico Toledo SARS-CoV-2 Assay                                         |                                                                            |
| Express Gene                         | 2400                  |                      540000 | 225.0         | 3rd data release | Express Gene LLC, DBA: Express Gene Molecular Diagnostics Laboratory            | Express Gene 2019-nCoV RT-PCR Diagnostic Panel                                      |                                                                            |
| Alpha Genomix                        | 12000                 |                      540000 | 45.0          | 3rd data release | Alpha Genomix Laboratories3                                                     | Alpha Genomix TaqPath SARS-CoV-2 Combo Assay                                        |                                                                            |
| BioTNS                               | 11145                 |                     1620000 | 145.3566622   | 3rd data release | TNS Co., Ltd (Bio TNS)                                                          | COVID-19 RT-PCR Peptide Nucleic Acid (PNA) kit                                      |                                                                            |
| Cue Health                           | 40                    |                        3000 | 75.0          | 3rd data release | Cue Health Inc.a                                                                | Cue COVID-19 Test                                                                   |                                                                            |
| Atila BioSystems                     | 3500                  |                        9000 | 2.571428571   | 3rd data release | Atila BioSystems, Inc.                                                          | iAMP COVID-19 Detection Kit                                                         |                                                                            |
||

## Chart
_Scatter Plot showing EUA tests with EUA LOD on y axis and FDA Panel LOD on x axis. Above the line = Developer obtained worse LOD in original EUA than with FDA panel_