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 category: regulatory subcategory: fda-policy tags: source_file_type: pdf xfile_type: docx gfile_url: https://docs.google.com/document/d/1ldfbrQXievTqNcIeQi0-BVkwlGu1P4e8 xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fda-policy/2020-02-29_FDA%20Guidance%20-%20COVID%20IVD%20Test%20Developers%20v1.docx pdf_gdrive_url: https://drive.google.com/file/d/1uoLP2EJrJEjgMtdMmsUOSn4HZ0XZp_x5 pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fda-policy/2020-02-29_FDA%20Guidance%20-%20COVID%20IVD%20Test%20Developers%20v1.pdf conversion_input_file_type: pdf conversion: claude license: Public Domain tokens: 2610 words: 1961 notes: 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.