METADATA last updated: 2026-03-10_105730 file_name: _archive-combined-files_fl-fda-correspondence_44k.md category: regulatory subcategory: fl-fda-correspondence gfile_url: **FLAGGED - TBD user-facing Google-hosted public file URL** words: tokens: CONTENT # _archive-combined-files_fl-fda-correspondence_44k (13 files, 43,897 tokens) # 5,839 _AI_FDA Deprioritization of COVID-19 Diagnostic EUAs.md METADATA last updated: 2026-03-02 RT initial creation file_name: _AI_FDA Deprioritization of COVID-19 Diagnostic EUAs.md file_date: 2026-03-02 title: FloodLAMP FDA Deprioritization of COVID-19 Diagnostic EUAs (CDRH/OHT7) category: regulatory subcategory: fl-fda-correspondence tags: fda-deprioritization, eua, covid-diagnostics, cdrh, oht7, decline-to-review, gao source_file_type: md xfile_type: NA gfile_url: https://docs.google.com/document/d/1XgCWcEhzhNktZGdiY2jo5xlOvuYBQAv7fPymbe2pmfA xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/reg-articles-misc/_AI_FDA%20Deprioritization%20of%20COVID-19%20Diagnostic%20EUAs.md pdf_gdrive_url: NA pdf_github_url: NA conversion_input_file_type: NA conversion: NA license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 5839 words: 3272 notes: Created by ChatGPT 5.2 Pro Extended during archive preparation. **NOT HUMAN VERIFIED - MAY CONTAIN ERRORS** Comprehensive analysis of FDA CDRH/OHT7's deprioritization practices for COVID-19 diagnostic EUA submissions, drawing from FDA's Booz Allen independent assessment, GAO-22-104266, FDA town hall transcripts, Food and Drug Law Journal analysis (Gibbs & Javitt), Reuters reporting, and ProPublica reporting. summary_short: FDA CDRH/OHT7 deprioritization of COVID-19 diagnostic EUA submissions -- history, mechanics, emergence as a policy tool, comparison with 510(k) processes, prior emergency precedents, scale (558 EUA requests declined to review by Sept. 2021 per GAO), and independent analyses of transparency, resource constraints, and relationship to Omicron-era testing shortages. CONTENT ***INTERNAL TITLE:*** FDA "Deprioritization" of COVID-19 Diagnostic EUAs (CDRH/OHT7) History, mechanics, how it emerged, how it compares to 510(k), prior emergencies, and what analyses say. ## Executive summary - During COVID-19, FDA's device center (CDRH)--specifically the in-vitro diagnostics review function (often referenced in FDA materials as OHT7)--created an explicit **triage + deprioritization** system to manage an unprecedented surge of SARS-CoV-2 test requests. ([U.S. Food and Drug Administration][1]) - In FDA's own post-event assessment materials, "deprioritization" is not just an informal concept; it was operationalized via **two streamlined negative actions**: - **Decline to Review** (for low-priority files--e.g., highly manual / low-volume, or low manufacturing capacity), and - **Decline to Issue** (for higher-priority tests with unresolved critical deficiencies, especially validation/performance data problems). ([U.S. Food and Drug Administration][1]) - FDA publicly telegraphed these priorities in town halls. In March 2021, for example, FDA explicitly warned that some submissions would be "very low priority" and "might be deprioritized," while encouraging developers to pursue point-of-care or at-home pathways. ([U.S. Food and Drug Administration][2]) - The scale was large: GAO reported FDA had **declined to review 558 EUA requests** for COVID-19 tests as of **Sept. 30, 2021** (including **230 LDTs**). ([Government Accountability Office][3]) - "Deprioritization" as used in EUA review is **not the same thing** as what happens in a 510(k). In 510(k), FDA uses formal completeness gates like **Refuse to Accept (RTA)** to focus resources on submissions that meet a minimum threshold for substantive review, and the program operates under performance goals and structured review steps--not open-ended discretionary triage in the same way. ([U.S. Food and Drug Administration][4]) - Independent and semi-independent analyses (FDA-commissioned assessment, GAO, academic/legal analysis, investigative journalism) repeatedly identify **resource constraints, backlog management, changing public-health needs, and test-quality concerns** as drivers--while also critiquing **transparency, predictability, and "wasted effort"** when priorities changed without clear notice. ([U.S. Food and Drug Administration][1]) - On the question of whether deprioritization contributed to the Omicron test shortage: there is clear documentation of **severe shortages and long lines** during Omicron, but public sources do **not** establish a simple one-to-one causal link from EUA deprioritization decisions in spring/summer 2021 to the January 2022 shortage. The strongest public record supports a **multi-factor explanation**, including demand shocks and manufacturing/investment incentives. ([Reuters][5]) --- ## 1) Who at FDA was doing this **CDRH** (Center for Devices and Radiological Health) is FDA's center responsible for medical devices, including most in vitro diagnostics (IVDs). In the COVID diagnostics context, FDA's own EUA process description references **OHT7** as the office making recommendations on authorization/denial, with additional legal/policy signoffs (OCC and OCET) and different signature authorities depending on the type of decision. ([U.S. Food and Drug Administration][1]) GAO's review of FDA's COVID test oversight highlights the staffing surge and strain: FDA increased staff working on COVID test EUAs and reallocated from other work, with effects on non-COVID diagnostic reviews; FDA officials told GAO they began shifting staff back to non-COVID work around May 2021. ([Government Accountability Office][3]) --- ## 2) What "deprioritization" meant in practice ### 2.1 FDA's internal definition (as reflected in FDA-published assessment materials) FDA's EUA assessment materials (an FDA "perspective" document sharing Booz Allen Hamilton's independent assessment and FDA's response) describe a **front-end triage** and **formal prioritization factors**--followed by **deprioritization processes** that allowed FDA to dispose of certain submissions faster. ([U.S. Food and Drug Administration][1]) The assessment document lays out: **Prioritization factors** (Table 3-5): - **Increases testing capacity** (e.g., large-scale manufacturing/processing, high-throughput, high product volume, or reduced reliance on limited supplies like by using saliva). - **Expands test accessibility** (e.g., point-of-care, home collection, at-home). - **Reduces real-world performance concerns** (tests already offered under notification policy where FDA identified performance concerns). ([U.S. Food and Drug Administration][1]) **Deprioritization mechanisms** (the core of the question): - **Decline to Review**: used for "low-priority files" (example given: highly manual, low-volume tests; or low throughput / low manufacturing capacity). FDA would close the file and communicate the decision and reason. ([U.S. Food and Drug Administration][1]) - **Decline to Issue**: used for priority tests with "critical deficiencies" (e.g., inadequate or missing performance data) that the requestor could not resolve in a reasonable time; FDA would notify deficiencies and allow follow-up if the requestor addressed concerns. ([U.S. Food and Drug Administration][1]) A key detail: the assessment notes that before these mechanisms, FDA processed negative decisions as "Denials" requiring higher-level issuance; the streamlined approach helped reviewers focus on higher-impact and more complete requests. ([U.S. Food and Drug Administration][1]) ### 2.2 How this differed from "denial" and from "incomplete submission" handling The same assessment describes other process changes implemented to handle incomplete submissions and reduce iterative back-and-forth: - A **content screen** and a process to **close files with requests for information**, allowing requestors to resubmit requested information later. ([U.S. Food and Drug Administration][1]) GAO similarly distinguishes: - FDA may **decline to issue** if the submission lacks necessary data for substantive review, and - FDA may **decline to review** if the test is not a priority at that stage of the emergency. ([Government Accountability Office][3]) --- ## 3) When and how "deprioritization" emerged as a policy tool during COVID ### 3.1 Spring 2020: triage begins; serology becomes a major stress test A major early example where "deprioritization" (or a shift in review priority) is discussed in the literature is **serology (antibody) tests**. A Food and Drug Law Journal analysis (Gibbs & Javitt) describes what it characterizes as a "rollercoaster" for serology EUAs: after FDA required EUAs for serology tests (May 4, 2020), FDA was overwhelmed by submissions and applicants experienced long periods in a "backlog" with limited clarity. ([Food and Drug Law Institute (FDLI)][6]) That paper reports that only a few months after requiring EUA submissions, anecdotal reports emerged that FDA would "deprioritize" serology EUAs; it says FDA put serology reviews on hold before announcing it clearly, leading to months of waiting and wasted effort for some applicants. ([Food and Drug Law Institute (FDLI)][6]) ### 3.2 Fall 2020: formalized front-end triage; "Decline to Review" letters become a visible instrument FDA's EUA assessment materials describe the inflection point: - **Beginning in Fall 2020**, CDRH instituted a **front-end triage and prioritization process** for all EUA requests due to submission volume far beyond prior emergencies. ([U.S. Food and Drug Administration][1]) - The same assessment states that CDRH did not begin implementing the **Decline to Review** process "until October 2020," after more than 250 EUAs for tests/collection devices had been authorized. ([U.S. Food and Drug Administration][1]) ### 3.3 October 7, 2020: public statement--declining to review LDT EUAs "at this time" An October 7, 2020 FDA virtual town hall transcript captures FDA publicly stating that--given the phase of the pandemic, many authorized tests, and the HHS announcement about LDT premarket review--FDA was **declining to review EUA requests for LDTs at that time**, while continuing to prioritize POC, home collection, at-home, supply-chain-relieving, and high-throughput/widely distributed tests. ([U.S. Food and Drug Administration][7]) The EUA assessment report adds a quantitative detail tied to that policy move: after the August 2020 HHS statement, CDRH **declined to review over 200 LDT EUA requests in October**--framed as allowing CDRH to focus on tests that could not be offered without FDA review/authorization (e.g., home collection, POC, multi-analyte panels). ([U.S. Food and Drug Administration][1]) ### 3.4 Early 2021 (including March): explicit language about deprioritization and "what's needed right now" Two March 2021 town hall excerpts are particularly on-point: - **March 10, 2021:** Dr. Timothy Stenzel stated that submitting only for high/moderate complexity "is a very low priority and you might be deprioritized," and encouraged moving to the home study / home test pathway if performance supports it. ([U.S. Food and Drug Administration][2]) - **March 31, 2021:** FDA reiterated that prioritization decisions depend on many factors; it again named the accessibility and capacity priorities. Dr. Stenzel added that "at this time [the] pandemic is very different" and that FDA sought to "focus review attention and prioritization" and incentivize development of tests "really needed right now," emphasizing high-volume accurate results in lab or at home/POC. ([U.S. Food and Drug Administration][8]) This aligns closely with the deprioritizations clustering when FDA perceived a shift in market/public-health conditions. ### 3.5 Mid-late 2021: "deprioritized previously" explained (manufacturing capacity / deficiencies) In an August 4, 2021 town hall transcript, FDA stated that if an EUA request was deprioritized previously, it was likely because the test either: - had **low manufacturing or testing capacity**, or - the submission was **deficient** in some way. ([U.S. Food and Drug Administration][9]) That is one of the clearest public "rule-of-thumb" explanations from FDA itself. ### 3.6 By Sept. 30, 2021: the scale--hundreds of EUA requests declined to review GAO reported that FDA officials said as of **Sept. 30, 2021**, FDA had **declined to review 558 EUA requests** for COVID-19 tests, including **230 LDTs**. ([Government Accountability Office][3]) This provides a public, audited figure consistent with "hundreds" and gives an anchor for the scale of "deprioritization" as "decline to review." --- ## 4) What drove the policy: FDA's stated rationale and operational constraints Across FDA's assessment materials, town halls, and GAO, the same drivers repeatedly appear: ### 4.1 Unprecedented submission volume and backlog management The EUA assessment notes that early in the pandemic, when few tests were authorized, "every test was a priority," but as tests proliferated, that level of interaction became unsustainable, necessitating prioritization factors. ([U.S. Food and Drug Administration][1]) GAO reports that FDA received thousands of EUA requests over the period and that review times increased as volume increased. ([Government Accountability Office][3]) ### 4.2 Focus on public health impact: accessibility + capacity + supply chain FDA consistently framed prioritization around tests that: - expand where/how testing can occur (POC, home collection, at-home), and - increase national capacity (high throughput, high volume, reduced reliance on scarce supplies). ([U.S. Food and Drug Administration][1]) The EUA assessment also describes how **supply chain monitoring** fed into review priorities, including pivots when swab shortages emerged (e.g., prioritizing saliva specimen approaches). ([U.S. Food and Drug Administration][1]) ### 4.3 Manufacturing and testing capacity as an explicit gate FDA town halls repeatedly tied priority to **capacity**, and FDA's August 2021 town hall made that explicit in the deprioritization explanation. ([U.S. Food and Drug Administration][9]) GAO also captures FDA's later articulation (in the revised 2021 guidance) that FDA viewed authorization of tests with manufacturing capacities below a large threshold as insufficient to scale national capacity--illustrating that capacity was not just a nice-to-have; it became a central criterion. ([Government Accountability Office][3]) ### 4.4 Quality and validation concerns (and avoiding prolonged review loops) FDA's assessment frames "Decline to Issue" as a way to stop spending time on submissions with major unresolved validation problems. ([U.S. Food and Drug Administration][1]) Separately, the legal/academic analysis of serology describes situations in which applicants sometimes had very short windows (e.g., "forty-eight hours") to respond to questions--highlighting the tension between speed and completeness in emergency review. ([Food and Drug Law Institute (FDLI)][6]) --- ## 5) Was "deprioritization" used before COVID in other emergencies? ### 5.1 EUA existed pre-COVID and IVD EUAs were issued in multiple emergencies FDA documents summarizing EUA practice list multiple emergencies in which FDA authorized IVDs under EUA, including: - influenza A H1N1 (2009), - avian influenza A H7N9 (2013), - MERS-CoV (2013), - Ebola (2014), - Enterovirus D68 (2015), - Zika (2016), - COVID-19 (2020), and - mpox (2022). ([U.S. Food and Drug Administration][10]) ### 5.2 But the "deprioritization" machinery appears to be a COVID-scale response FDA's EUA assessment explains that the "substantially higher submission volume" during COVID compared to prior public health emergencies made a **formal set of prioritization factors necessary**, and it describes Fall 2020 as the point where triage and streamlined "Decline to Review / Decline to Issue" mechanisms were instituted to manage backlog. ([U.S. Food and Drug Administration][1]) That suggests: - **Prior PHEs** likely involved prioritization in the ordinary sense (resource focus), but - **COVID** created enough volume/complexity that "deprioritization" became a structured, named workflow with standardized negative actions, and it became widely visible to submitters. --- ## 6) Is there an equivalent "deprioritization" in 510(k)? Not really--here's the closest analog ### 6.1 EUA vs 510(k) in one sentence - **EUA** is an emergency, discretionary authorization mechanism where FDA can choose not to review certain categories at a given moment to maximize public health benefit. ([FDA Law Blog][11]) - **510(k)** is a standard premarket pathway with structured acceptance and substantive review steps; FDA focuses resources by screening completeness (RTA) rather than by declining review because a product category is "low priority." ([U.S. Food and Drug Administration][4]) ### 6.2 The closest analog: "Refuse to Accept (RTA)" and other gates FDA's **Refuse to Accept Policy for 510(k)s** explains that its purpose is to determine whether a 510(k) meets a minimum threshold of acceptability and should be accepted for substantive review--explicitly framing this as a way to focus review resources on complete submissions. ([U.S. Food and Drug Administration][4]) FDA's 510(k) submission process page describes that after the acknowledgement letter, the submission routes to the appropriate office and that the lead reviewer conducts acceptance review using the RTA checklist. ([U.S. Food and Drug Administration][12]) **Key distinction:** RTA is about **administrative/threshold completeness**. COVID EUA "deprioritization" (Decline to Review) was often about **public-health priority and impact**, including volume/capacity and what FDA perceived the country needed at that phase--*even if the submission might be technically complete*. ([U.S. Food and Drug Administration][1]) --- ## 7) What analyses and critiques exist about "deprioritization" and its effects? There is not a single definitive "cost-benefit" study that proves counterfactual outcomes (e.g., "X more tests would have been on shelves by Omicron absent deprioritization"). But there *is* meaningful analysis and documented stakeholder critique. ### 7.1 FDA's own after-action framing (independent assessment shared by FDA) FDA's published assessment materials (sharing Booz Allen's independent assessment plus FDA perspective) depict deprioritization as a necessary operational response to: - backlog, - resource limits, - incomplete/low-quality submissions, and - changing PHE needs. ([U.S. Food and Drug Administration][1]) ### 7.2 GAO: documented scale + stakeholder concerns about uncertainty (especially LDTs) GAO documents the "decline to review" scale (558 by Sept. 30, 2021), and notes that laboratory associations expressed unfavorable views of declining to review LDT EUAs because it created uncertainty/confusion, including around insurance coverage and PREP Act liability protections. ([Government Accountability Office][3]) ### 7.3 Legal/academic critique: transparency and wasted effort (notably serology) The Food and Drug Law Journal analysis is explicit that lack of clarity about shifting priorities can waste developer effort and create confusion--particularly in serology, where the authors describe an unannounced shift in review priorities and long periods without meaningful communication. ([Food and Drug Law Institute (FDLI)][6]) ### 7.4 Industry/legal commentary: "deprioritization risk" as a planning hazard A prominent FDA law blog post (Feb 2021) describes deprioritization as a significant risk in pursuing EUAs under changing market conditions, gives examples (including diagnostics), and argues for more transparency--e.g., a public database of deprioritized categories. ([FDA Law Blog][11]) ### 7.5 Case reporting: applications told they'd be "deprioritized" ProPublica reported on an at-home test developer describing an FDA communication that even if deficiencies were fixed, the application would be "deprioritized" (moved to the back of the line). ProPublica also reports FDA officials emphasizing sensitivity/false negatives and blaming shortages partly on lack of sustained government investment in production. ([ProPublica][13]) ### 7.6 Example of FDA stopping EUA review and steering to non-EUA pathway A 2021 report on SQI Diagnostics described FDA deciding it would not continue reviewing an EUA submission under a "tests for management of COVID-19 patients" category, citing high volume and prioritization factors, and encouraging use of a non-EUA pathway. ([Clinical Lab Products][14]) This illustrates deprioritization-like outcomes beyond classic diagnostic testing. --- ## 8) Spring/summer 2021 deprioritization vs Omicron 2022 testing shortages: what can we responsibly say? ### 8.1 The Omicron shortage was real and visible Reuters reported (Jan 12, 2022) that long lines "snake around entire city blocks" as Americans scrambled for testing, and at-home kits flew off shelves. ([Reuters][5]) ### 8.2 What the public record supports about causality The public evidence supports a **multi-factor story**, roughly: **A) Demand shock + planning/investment dynamics** - ProPublica quotes FDA's CDRH director Jeff Shuren attributing differences in test availability partly to **government investment supporting production**, and describing how lack of sustained funding can make manufacturers reluctant to take on the cost/risk of the FDA process at scale. ([ProPublica][13]) **B) Regulatory triage did occur** - FDA explicitly prioritized certain test types (at-home, POC, high-throughput, high-volume) and deprioritized others, including by closing low-priority files. ([U.S. Food and Drug Administration][1]) **C) The missing link** What is *not* established in the public sources is a quantified counterfactual: - "If FDA had reviewed the deprioritized EUAs in spring/summer 2021, there would have been enough additional manufacturing capacity to prevent Omicron shortages." That could be true for some subset (especially if deprioritized submissions included would-have-scaled at-home/rapid tests), but proving it would require: - knowing which tests were deprioritized (and why) in that period, - knowing their realistic manufacturing ramp curves and supply chain constraints, and - knowing whether demand-side procurement/reimbursement policies would have supported sustained production. ### 8.3 A plausible mechanism (clearly labeled as inference) Based on FDA's own prioritization factors emphasizing **manufacturing volume** and **accessibility** ([U.S. Food and Drug Administration][1]) and GAO's documentation that FDA used "decline to review" for nonpriority tests ([Government Accountability Office][3]), one plausible mechanism is: - If deprioritization decisions in 2021 disproportionately excluded tests that could have become high-volume at-home/rapid options by late 2021, then deprioritization could have reduced the set of suppliers going into Omicron. But the public record also contains the countervailing point that FDA's stated priorities were precisely **at-home/POC/high-volume**, meaning many "low priority" files may not have been the ones that would materially expand at-home capacity. ([U.S. Food and Drug Administration][8]) --- ## 9) What's still not publicly knowable (without FOIA / docket-level data) Even with the above sources, several things are **not fully disclosed in public material**, including: - A breakdown of *all* "Decline to Review" decisions by **test type**, intended setting, and month (especially the spring-summer 2021 period). GAO provides a cumulative number, not a full taxonomy. ([Government Accountability Office][3]) - The number of serology submissions "rejected or never reviewed" is explicitly described in the legal literature as not publicly disclosed. ([Food and Drug Law Institute (FDLI)][6]) - The internal scoring/weighting of prioritization factors (e.g., exactly how FDA weighed "manufacturing capacity" versus "novelty" versus "unmet need") at different pandemic phases. --- ## 10) Source map (for follow-up) If you want to go deeper (or build a formal dossier), these are the most "load-bearing" public documents for deprioritization: 1. **FDA perspective sharing Booz Allen independent assessment** (describes triage, prioritization factors, Decline to Review/Issue, supply-chain monitoring, review tracks). ([U.S. Food and Drug Administration][1]) 2. **GAO-22-104266** (quantifies declined-to-review volume; documents FDA/HHS policy moves; records stakeholder concerns). ([Government Accountability Office][3]) 3. **FDA town hall transcripts** around: - Oct 7, 2020 (declining to review LDT EUA requests; priorities) ([U.S. Food and Drug Administration][7]) - Mar 10, 2021 (explicit "might be deprioritized" language) ([U.S. Food and Drug Administration][2]) - Mar 31, 2021 (phase change; focus on high-volume, accurate, needed tests) ([U.S. Food and Drug Administration][8]) - Aug 4, 2021 (why a request was deprioritized: low capacity or deficient) ([U.S. Food and Drug Administration][9]) 4. **Food and Drug Law Journal analysis (Gibbs & Javitt)** for narrative history and transparency critique, especially serology. ([Food and Drug Law Institute (FDLI)][6]) 5. **Reuters (Jan 12, 2022)** as contemporaneous documentation of Omicron-era testing shortages and lines. ([Reuters][5]) [1]: https://www.fda.gov/media/152992/download "https://www.fda.gov/media/152992/download" [2]: https://www.fda.gov/media/146811/download "https://www.fda.gov/media/146811/download" [3]: https://www.gao.gov/assets/gao-22-104266.pdf "https://www.gao.gov/assets/gao-22-104266.pdf" [4]: 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" [5]: https://www.reuters.com/world/us/americans-grapple-with-prolonged-testing-woes-amid-omicron-surge-2022-01-12/ "https://www.reuters.com/world/us/americans-grapple-with-prolonged-testing-woes-amid-omicron-surge-2022-01-12/" [6]: https://www.fdli.org/wp-content/uploads/2021/12/5-Gibbs-Javitt-Final.pdf "https://www.fdli.org/wp-content/uploads/2021/12/5-Gibbs-Javitt-Final.pdf" [7]: https://www.fda.gov/media/143084/download "https://www.fda.gov/media/143084/download" [8]: https://www.fda.gov/media/147394/download "https://www.fda.gov/media/147394/download" [9]: https://www.fda.gov/media/151937/download "https://www.fda.gov/media/151937/download" [10]: https://www.fda.gov/media/171779/download "https://www.fda.gov/media/171779/download" [11]: https://www.thefdalawblog.com/2021/02/beware-eua-deprioritization/ "https://www.thefdalawblog.com/2021/02/beware-eua-deprioritization/" [12]: https://www.fda.gov/medical-devices/premarket-notification-510k/510k-submission-process "https://www.fda.gov/medical-devices/premarket-notification-510k/510k-submission-process" [13]: https://www.propublica.org/article/heres-why-rapid-covid-tests-are-so-expensive-and-hard-to-find "https://www.propublica.org/article/heres-why-rapid-covid-tests-are-so-expensive-and-hard-to-find" [14]: https://clpmag.com/disease-states/infectious-diseases/covid-19/fda-stops-eua-review-of-sqi-covid-19-severity-triage-test/ "https://clpmag.com/disease-states/infectious-diseases/covid-19/fda-stops-eua-review-of-sqi-covid-19-severity-triage-test/" # 9,443 _AI_FloodLAMP FDA October 2021 Correspondence Analysis.md METADATA last updated: 2026-03-02 RT initial creation file_name: _AI_FloodLAMP FDA October 2021 Correspondence Analysis.md file_date: 2026-03-02 title: FloodLAMP FDA October 2021 Correspondence Analysis category: regulatory subcategory: fl-fda-correspondence tags: fda-correspondence, deprioritization, eua, quickcolor, october-2021, open-protocol source_file_type: md xfile_type: NA gfile_url: https://docs.google.com/document/d/1mT_Hg7gHwWScfWfmGuaJcWK9gVLXB-NV3j0UthTwuDw xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/_AI_FloodLAMP%20FDA%20October%202021%20Correspondence%20Analysis.md pdf_gdrive_url: NA pdf_github_url: NA conversion_input_file_type: NA conversion: NA license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 9443 words: 6447 notes: Created by Claude Opus 4.6 Max and ChatGPT 5.2 Pro Extended during archive preparation. **NOT HUMAN VERIFIED - MAY CONTAIN ERRORS** Comprehensive analysis of FloodLAMP's October 2021 FDA correspondence sequence, synthesizing the full email thread, FDA deficiency letter, meeting notes, and final deprioritization decision, with background from FDA town hall transcripts, open EUA context, and the AI deprioritization research report. Includes factual timeline summary and five interpretive explanations of FDA's rationale. summary_short: Analysis of FloodLAMP's October 2021 FDA correspondence -- the concentrated sequence of emails, deficiency letter, Zoom meeting (with Anne Wyllie), FloodLAMP's response, and FDA's final deprioritization/closure of EUA210582 for the QuickColor COVID-19 Test. Presents a complete timeline from October 2020 through October 2021, identifies FDA's stated justifications (clinical data gaps, resource triage, deprioritization policy), and offers five interpretive explanations of the FDA's rationale ranging from legitimate resource constraints to structural bias against small/novel entrants, with attention to the Omicron-wave irony five weeks later. CONTENT ## Prompt (Verbatim) Review the following files and the thing I want you to hone in on is I'll drag it over as a separate file. Well, you have these files on there all the October 2021 ones there in the archive combined files. So there are really four of these from from 2021, 10/4, 10/13, well two from 10/13 and then one from 10/20. So all the rest of the files are provided as like background and context so you know read and review all of those and then what I want you to do is summarize the interactions in all of those emails and then particularly what justification the FDA gave for not continuing our review and closing our case and refusing our EUA submissions and then... and then try to read between the lines and and use what you understand about the FDA's process and what's happening during the pandemic etc. to try to explain why they would shut us down. I mean Anne Wiley joined the call that we had with them. They knew she was an advisor for us. She was very successful. We submitted multiple times. I believe I discussed that we had the surveillance programs going and the test was successful. I think we even offered to submit that data. So you know this was in October and you know I mean maybe if they knew the Omicron wave was coming they wouldn't have done this. You know who knows but I want to try to understand this better. So both present the facts and then also try to step into their shoes and explain their rationale and you know if if you think it's best create you know a few possibilities of what their rationale and or thinking may have been. **Files included in context window:** - _archive-combined-files_fl-fda-correspondence.md - _AI_FDA Deprioritization of COVID-19 Diagnostic EUAs.md - _context-commentary_regulatory-fda-townhalls.md - _context-commentary_regulatory-open-euas.md - project-description.md - _context-commentary_regulatory-fl-fda-correspondence.md ## Prompt (Cleaned) Review all provided files, with particular focus on the October 2021 correspondence in the archive combined files -- the four key communications from 10/4, 10/13 (two that day), and 10/20. The remaining files provide background and context. Summarize the interactions in all of the emails, and specifically identify what justification the FDA gave for not continuing the review, closing the case, and refusing the EUA submissions. Then try to read between the lines, using what is known about the FDA's process and the pandemic context, to explain why they would shut FloodLAMP down. Anne Wyllie joined the call with the FDA. They knew she was an advisor. FloodLAMP submitted multiple times, had surveillance programs running with successful results, and offered to submit that data. This was October 2021 -- perhaps if the FDA had known the Omicron wave was coming five weeks later, they would not have made this decision. Present the facts, then step into the FDA's shoes and explain their rationale. Create several possibilities for what their rationale and thinking may have been. **Files included in context window:** - _archive-combined-files_fl-fda-correspondence.md - _AI_FDA Deprioritization of COVID-19 Diagnostic EUAs.md - _context-commentary_regulatory-fda-townhalls.md - _context-commentary_regulatory-open-euas.md - project-description.md - _context-commentary_regulatory-fl-fda-correspondence.md ## RESPONSE - Claude Opus 4.6 Max ### Summary of FloodLAMP-FDA Interactions: The October 2021 Correspondence #### Complete Timeline **Phase 1: Early Engagement (Oct 2020 - Dec 2020)** - **Oct 22, 2020**: FloodLAMP sends initial Pre-EUA request describing pooled RT-LAMP screening program. - **Nov 10, 2020**: FloodLAMP emails Dr. Tim Stenzel proposing a meeting about expanding the open-source EUA approach beyond SalivaDirect, with Anne Wyllie's involvement. - **Dec 9, 2020**: FloodLAMP engages Stenzel directly at an FDA Town Hall. Stenzel is encouraging: *"I look forward to hearing more about your development"* and confirms the open-source protocol and Rights of Reference model has real potential, calling it *"a pathway that could be very successful."* **Phase 2: Submissions and First Deprioritization (Mar 2021 - Jun 2021)** - **Mar 22, 2021**: FloodLAMP submits two full EUAs -- QuickColor LAMP (EUA210252) and EasyPCR (EUA210254) -- as open-source protocol EUAs with clinical validation from Stanford. - **Apr 2, 2021**: FDA deprioritizes both, declining to review. Justification: *"authorization of the test would have relatively limited impact on testing accessibility or testing capacity."* Signed by Donald J. St. Pierre. - **May 18, 2021**: FloodLAMP submits Pre-EUA (PEUA210313) for pooled home-collection kit and mobile app, trying to qualify for prioritization. - **Jun 17, 2021**: FDA responds to Pre-EUA. Critically, states: *"we have not reviewed the validation studies nor the data provided in this pre-EUA."* Flags the QuickColor PPA of 90% as below the 95% threshold. Closes the Pre-EUA. **Phase 3: The October 2021 Push and Final Closure** This is the concentrated sequence of four key communications: **1. Oct 4, 2021 -- FloodLAMP letter to Dr. Tim Stenzel (4 pages)** Randy True makes a comprehensive case directly to the FDA Director of OIVD. Key points: - Introduces FloodLAMP and the two complementary tests (LAMP and PCR) - Describes the open-source protocol approach with Anne Wyllie as advisor - Reports resubmission of both EUAs (now EUA210581, EUA210582) for persons suspected of COVID and serial screening - Presents real-world surveillance data: 5 sites in 3 states, ~2,300 people screened, 800 pools, 3 unknown positives detected, no known false negatives - Highlights manufacturing readiness: 2M tests on hand, 3M more at LGC Biosearch, NEB master mix supply - Frames $1-2/test pricing as "transformative" - Describes active commercial sites with EMS and municipal fire departments - Makes the Test-to-Stay argument for schools - Requests prioritized review and assistance avoiding immediate denial **2. Oct 13, 2021 -- FDA sends two communications** *Morning (8:25 AM):* Lead reviewer Liang Li sends a detailed 6-deficiency letter on EUA210582: 1. **Clinical study design**: wrong specimen type (AN swabs instead of NP), no intended use population description, no low-viral-load samples 2. **PPA of 90%** -- below FDA's 95% threshold 3. **Outdated inclusivity/variant analysis** (Feb 2021 data, no longer representative) 4. **Incomplete cross-reactivity** -- organisms with >80% homology not wet-tested 5. **Insufficient endogenous interfering substances** testing 6. **External controls too concentrated** (8x LoD vs. recommended <5x LoD) 7. **RUO reagent risk** -- cannot recommend RUO-labeled components for authorized test **Deadline given: October 15, 2021 at noon** -- two business days. *Late morning (10:15 AM):* Liang Li follows up offering a 30-minute Zoom meeting the next day. **3. Oct 14, 2021 -- Zoom Meeting** FloodLAMP: Randy True (CEO), Anne Wyllie (advisor) FDA: Liang Li, Silke Schlottmann, Kris Roth Key exchange points: - Randy requests to **amend the intended use to serial screening only** (removing "suspected of COVID"), which has a lower PPA threshold (~80%) - Silke asks about designation and **says they would not want the IFU publicly available** -- a direct tension with the open protocol model - Kris mentions **6 criteria for serial screening** and that the risk-benefit differs for POC/at-home vs. lab-based tests - Anne Wyllie asks if they could validate with a blinded reference panel; Silke says **the reference panel is no longer available** - Agreed FloodLAMP would provide written response by Oct 20 **4. Oct 20, 2021 -- FloodLAMP's Written Response** Randy submits a point-by-point response: - Requests amendment to remove "persons suspected of COVID" -- serial screening only - Narrows specimen claim to AN swabs only - Argues PPA threshold for serial screening is 80%, and performance exceeds all authorized antigen tests - Presents real-world surveillance data as supporting evidence - Cites multiple independent validations of the same LAMP components - Commits to updating inclusivity analysis, addresses cross-reactivity concerns specific to LAMP vs. PCR - Offers to qualify RUO lots Crucially, Randy also asks: *"Is the risk-benefit analysis for a high complexity CLIA lab rather than POC setting able to be factored in?"* and notes no response was received from the Oct 4 letter to Tim Stenzel. **5. Oct 21, 2021 -- FDA Final Decision (one day after FloodLAMP's response)** Liang Li sends a deprioritization/closure letter signed by Donald J. St. Pierre: > *"Given the volume of EUA requests the Agency has received, FDA is prioritizing review of EUA requests for tests, taking into account a variety of factors such as the public health need for the product, availability of the product, extent to which the product would serve a significant unmet medical need, and availability and adequacy of the information concerning the likelihood that the product may be safe and effective in diagnosing the disease/condition. Based on these factors, our review of your submission thus far, and the anticipated resources needed to continue review of your EUA request, FDA has determined that further review of your EUA request is not a priority. FDA therefore declines to issue an EUA for the product at this time."* **6. Oct 28, 2021 -- FloodLAMP appeals** Randy asks whether the intended use amendment to serial screening was understood before the closure decision, and requests reconsideration. He proposes two paths: (a) if the current clinical data is acceptable for serial screening, FloodLAMP will quickly complete the remaining items; (b) if not, he requests feedback on a new clinical study design. **7. Oct 29, 2021 -- FDA confirms and closes the door** Liang Li responds: > *"We understood the intended use amendment when we sent the Deprioritization Letter. Your current clinical study is not acceptable to support testing a screening population with serial testing."* Directs FloodLAMP to the updated molecular EUA template or to submit a pre-EUA amendment for study design feedback. The exchange effectively ends here. --- ### FDA's Stated Justifications The FDA gave three layers of justification, used in combination: 1. **Deprioritization on public health impact grounds**: *"authorization of the test would have relatively limited impact on testing accessibility or testing capacity"* -- used in both the April 2021 and October 2021 closure letters. 2. **Inadequate clinical performance data**: PPA of 90% was below the 95% threshold for the "persons suspected of COVID" intended use, and the clinical study design had deficiencies (wrong specimen type, no population description, no low-viral-load challenge samples). 3. **Inadequate clinical study for serial screening**: Even after FloodLAMP amended to the serial screening intended use (with a lower ~80% PPA bar), FDA determined that the clinical study itself was not designed to support a screening population claim. The study used de-identified remnant clinical samples from Stanford, not a screening population. 4. **Resource calculus**: The October 21 letter adds a new phrase not in the April letter: *"the anticipated resources needed to continue review of your EUA request"* -- suggesting the FDA was also factoring in the additional work (new clinical study, updated analytics, etc.) that would be needed to get FloodLAMP over the finish line. --- ### Reading Between the Lines: Why the FDA Shut FloodLAMP Down Based on the full documentary record, the broader FDA deprioritization analysis, and the pandemic context, here are several possible explanations -- from most to least charitable to the FDA. #### Explanation 1: Legitimate Resource Triage Under Genuine Constraints **The FDA's perspective**: By October 2021, the agency had authorized over 400 COVID-19 tests. Vaccines were widely available. The Delta wave, while severe, appeared to be subsiding. FDA staff were being shifted back to non-COVID review work (GAO documents this starting around May 2021). The agency faced an unprecedented backlog across its entire regulatory portfolio. Every hour spent on a submission that wasn't going to clear quickly was an hour taken from something else. FloodLAMP's submission, however meritorious its mission, presented a significant review burden: the clinical study needed to be redone, the analytical package needed substantial updating, the RUO reagent question was unresolved, and the open protocol model raised novel designation and quality assurance questions. From a pure resource allocation standpoint, a submission requiring extensive additional work from a small company without an existing EUA track record ranked lower than submissions from entities with complete packages or near-complete packages. **What makes this plausible**: The GAO data shows 558 tests declined to review by September 30, 2021 -- FloodLAMP was one of hundreds. The FDA was applying this policy broadly, not singling FloodLAMP out. The two-day response window, while harsh, was apparently a standard mechanism during this period. **What complicates this**: The FDA's own prioritization criteria emphasized tests that "increase testing accessibility" and "expand testing capacity." FloodLAMP's offering -- instrument-free, $1-2/test, open protocol enabling lab proliferation, commodity supply chain -- arguably fit those criteria well. The FDA never substantively engaged with these claims. #### Explanation 2: The Clinical Data Gap Was Real and Dispositive **The FDA's perspective**: Regardless of mission, price point, or scalability claims, an IVD EUA requires adequate validation data. FloodLAMP's clinical study had genuine problems: - 90% PPA, not 95% - Anterior nasal swabs only, while claiming broad URT specimen types - No description of study population characteristics - No low-viral-load challenge samples (the hardest test of sensitivity) - De-identified remnant samples from Stanford -- not a prospective screening population study Even at the 80% PPA threshold for serial screening, the FDA's position was that the *study design* was wrong, not just the performance number. A screening population claim requires a study on a screening population, and remnant clinical samples from symptomatic patients tested at a hospital lab don't demonstrate that. **What makes this plausible**: This is technically sound. FDA templates were clear about these requirements. The June 2021 pre-EUA response explicitly flagged the PPA issue. FloodLAMP had months of advance notice. **What complicates this**: FloodLAMP asked for guidance on study design repeatedly -- in the May 2021 pre-EUA, in the October 5 interactive review request, and in the October 20 response. The FDA's response to the May pre-EUA was to not review the data at all and close the file. On October 14, when FloodLAMP asked about the clinical requirements, the reference panel that could have helped was "no longer available." And the final closure came one day after FloodLAMP's response -- suggesting the decision was already made before the response was evaluated. #### Explanation 3: Institutional Discomfort with the Open Protocol Model **The FDA's perspective**: The open-source protocol EUA was still a novel regulatory construct. SalivaDirect was the only example, and it was backed by Yale -- a major research institution with significant credibility and infrastructure. FloodLAMP was a tiny public benefit corporation asking FDA to authorize a test whose Instructions for Use would be publicly available, whose components were commodity RUO-labeled reagents, and whose deployment model involved designating potentially hundreds of labs. The October 14 meeting notes are revealing: Silke Schlottmann specifically said *"they would not want us to make IFU publicly available"* -- a direct challenge to the foundational concept of an open protocol EUA. If the IFU isn't public, the protocol isn't open. This suggests the FDA reviewers, or at least some of them, were uncomfortable with the regulatory implications of this model expanding beyond the SalivaDirect precedent. There were genuine regulatory questions: Who is responsible for quality when any lab can run the protocol? How do you ensure lot-to-lot consistency of RUO reagents? What happens when a designated lab deviates from the protocol? These are legitimate concerns, but they were never worked through -- the submission was closed before they could be. **What makes this plausible**: The regulatory system is not designed for open-source diagnostics. The standard model assumes a single manufacturer with a quality system controlling its product. The open protocol model disrupts that assumption, and FDA reviewers would reasonably be cautious. **What complicates this**: Tim Stenzel, the OIVD Director, had explicitly endorsed the open protocol approach on record in the December 2020 town hall. But Stenzel never responded to the October 4 letter, and the review team -- who made the actual decisions -- appeared to be less aligned with the concept. #### Explanation 4: The "Pandemic Is Ending" Assumption **The FDA's perspective**: In October 2021, the dominant institutional narrative was one of pandemic management trending toward resolution. Vaccines were widely deployed, boosters were being authorized, therapeutics were in the pipeline. The acute crisis of "we need every test we can get" had passed. The FDA's own town hall language reflected this: *"at this time the pandemic is very different"* (March 2021); tests were being deprioritized because the agency perceived less urgency. A small company's LAMP test -- which needed substantial additional validation work, wouldn't be POC or at-home, and was instrument-free but still high-complexity CLIA -- simply didn't register as urgent in a world where the pandemic was supposed to be winding down. **The devastating irony**: Omicron (B.1.1.529) was first reported to the WHO on November 24, 2021 -- approximately five weeks after the FDA closed FloodLAMP's submission. By January 2022, Americans were standing in lines that *"snake around entire city blocks"* trying to get tested. The U.S. experienced the worst testing shortage of the entire pandemic. The very thing FloodLAMP was offering -- massive-scale, low-cost molecular screening using commodity reagents and an open protocol that any CLIA lab could adopt -- was exactly what was needed. Would FloodLAMP's authorized test have prevented the Omicron testing shortage? Almost certainly not by itself. But the principle behind the decision -- "we don't need more tests right now" -- was catastrophically wrong, and it was applied systematically to FloodLAMP and hundreds of other developers. #### Explanation 5: Structural Bias Against Small, Mission-Driven Entrants **The FDA's perspective** (unstated): The FDA's EUA prioritization criteria implicitly favored established diagnostics companies. "High-throughput" meant companies with existing high-volume manufacturing. "Widely distributed" meant companies with existing distribution networks. "POC" and "at-home" meant companies with the capital to run the required usability studies and manufacture consumer devices. FloodLAMP's claims -- "$1-2/test," "millions of tests by end of year," "10K+/day without automation" -- were extraordinary, but they came from a company with no existing EUA, no manufacturing facility, and two active commercial surveillance sites serving EMS workers. From a risk-averse regulator's perspective, these were aspirational claims from an unproven entity, not demonstrated capacity. Anne Wyllie's presence on the October 14 call was meant to signal credibility -- she was the developer of SalivaDirect, the most successful open protocol EUA. But the review team had apparently already set their course. The letter to Stenzel went unanswered. The surveillance program data -- while genuinely impressive for a startup -- was a rounding error in national testing volumes. **What makes this plausible**: Regulators evaluate track record and demonstrated capacity, not potential. The FDA's job is not to pick winners or invest in promising startups; it's to determine whether a specific device meets specific criteria. **What complicates this**: This is precisely the critique that the GAO, legal scholars, and industry commentators made about the deprioritization regime. It created a circular barrier: you can't demonstrate capacity without authorization, but you can't get authorization without demonstrated capacity. For a small public benefit corporation operating on grants and mission-driven funding, this was a death spiral. --- ### Synthesis The most likely reality is a combination of all five factors, weighted roughly in this order: 1. **Resource triage was the dominant driver.** The FDA was overwhelmed and had a systematic policy of closing submissions that required extensive additional work. FloodLAMP's submission genuinely needed more work. 2. **The clinical data gap was real but should have been solvable.** FloodLAMP needed a prospective screening population study. The FDA never gave them meaningful feedback on study design despite repeated requests. The June 2021 pre-EUA response didn't review their data at all, and the October process gave them 48 hours to respond to a 6-deficiency letter before closing the case. 3. **The open protocol model created institutional friction** that the review team was not equipped or motivated to work through, particularly in a resource-constrained environment. 4. **The "winding down" assumption** about the pandemic made every submission from a small developer with an incomplete package look like a low-return investment of review resources -- an assumption that proved catastrophically wrong within weeks. 5. **Structural bias** against small/novel entrants was an ambient factor, not a deliberate choice, but it meant FloodLAMP's arguments about potential impact were likely discounted relative to what a large manufacturer with an existing supply chain would have been credited. The single most telling detail in the entire record may be this: the FDA sent a 6-deficiency letter on October 13, offered a 30-minute call on October 14, received a substantive written response on October 20, and issued a final closure one day later on October 21. The speed of that closure -- particularly the one-day turnaround on a response that proposed a narrowed intended use and addressed multiple deficiencies -- suggests the outcome was predetermined and the "interactive review" was procedural rather than genuinely deliberative. FloodLAMP was being processed through the deprioritization pipeline, not evaluated on the merits of its amended proposal. ## RESPONSE - ChatGPT 5.2 Pro Extended Below is a fact-first reconstruction of what happened in the October 2021 thread (the four “October files” you pointed to), plus the most important earlier context in the correspondence bundle. I then separate out what FDA **explicitly said** from what can be **inferred** (with clear labels), and I end with a set of plausible “FDA-in-their-shoes” rationales for why they shut this down. I’m basing this entirely on the archive files you provided; the October 10/14 “meeting notes” are *your* notes (not a verbatim FDA transcript), so I treat them as directional evidence, not quotes. --- ### What happened, chronologically #### The key pre-October setup (why Oct 2021 isn’t “out of the blue”) * **Mar 22, 2021:** FloodLAMP submitted two “open protocol” EUA requests (QuickColor LAMP and EasyPCR) and positioned them as low-cost, supply-chain-robust, scalable protocols modeled on SalivaDirect, including a planned blanket Right of Reference (ROR) strategy. * **Apr 2, 2021:** FDA issued a **final decision** on EUA210252 (and similarly on EUA210254) and **closed** the EUA(s), stating they were deprioritizing because FDA was in “a different phase of the pandemic…where many COVID-19 tests are now authorized,” and FDA was prioritizing tests that would **increase testing accessibility** (POC, home collection, at-home) or **significantly increase testing capacity** (high-throughput). FDA said FloodLAMP’s test would have “relatively limited impact” on accessibility/capacity. * **May–Jun 2021 (Pre-EUA PEUA210313):** FloodLAMP submitted a pre-EUA that bundled tests + pooled home collection + app. FDA said, due to volume/prioritization, they **did not review the validation studies/data**, but gave “general recommendations,” including (critically) stating FDA believes **~95% positive and negative agreement** is acceptable clinical performance and that QuickColor’s PPA was below that; FDA explicitly said they **did not recommend pursuing** an EUA for QuickColor unless sensitivity improved. They then **closed the pre-EUA** upon issuing the feedback. * **Oct 5, 2021:** FloodLAMP followed up asking for an **interactive review** and emphasizing real-world surveillance deployment metrics (sites, pools, people screened, positives detected/confirmed, etc.), while noting resubmitted EUAs (EUA210581 / EUA210582). That’s the backdrop: FDA had already signaled “not priority” in April, and in June had already flagged QuickColor sensitivity as below what they considered acceptable for the use as framed then. --- ### The October 2021 interactions (the four files you flagged) #### Oct 4, 2021 — FloodLAMP escalates to leadership (email routed to Tim Stenzel) FloodLAMP sent an email intended for Dr. Tim Stenzel via the FDA templates inbox, asking for a meeting and help avoiding another immediate deprioritization of the resubmitted EUAs. FloodLAMP’s main points in that email: * Positioned QuickColor (colorimetric LAMP) and EasyPCR (duplex RT-PCR) as **open protocol** tests using **TCEP + heat inactivation**, with claimed turnaround and throughput (e.g., “10K+/day without automation”), and stated LoDs (LAMP ~12,500 cp/mL; PCR ~3,000 cp/mL). * Highlighted that earlier EUAs were deprioritized and the May pre-EUA was closed with only brief comments; requested leadership assistance so the resubmissions wouldn’t be “immediate denial of review.” * Put major emphasis on **public health impact**: pooled home collection (family/exposure unit pooling), “test-to-stay,” low cost ($1–2/person), and ability to scale through manufacturing partners. * Cited **non-diagnostic surveillance deployments** (5 sites/3 states, ~800 pools, ~2,300 people screened, positives detected/confirmed, and “no known or suspected false negatives”). * Asked for FDA guidance on CLIA lab expansion / near-site testing and how surveillance programs might coexist with EUA-authorized clinical testing. #### Oct 13, 2021 — FDA requests additional information + offers a Zoom call There are two distinct FDA communications on Oct 13: 1. **Lead reviewer email attaching the “Additional Information” letter** FDA (lead reviewer Liang Li) sent FloodLAMP a formal letter requesting additional information for EUA210582. 2. **Follow-up email offering a 30-minute Zoom meeting the next day** The same reviewer offered a quick Zoom slot to discuss the submission. ##### What FDA’s Oct 13 “Additional Information” letter actually says This is the most detailed, “technical deficiencies” document in the October set. It asserts that FloodLAMP had not provided complete information adequate to validate the test and support the claimed performance characteristics, and it lays out deficiencies in six major areas (I’m summarizing, not reproducing the whole letter). **(1) Clinical evaluation problems** (FDA’s “big bucket”) * **Intended-use population not described**: FDA couldn’t tell whether the study samples came from the intended population (people “suspected” by their HCP). * **Specimen-type claims not supported**: FloodLAMP claimed multiple URT swab types (OP/NP/AN/mid-turbinate), but the study used AN swabs, and FDA stated NP is considered the most challenging matrix and expected for NP/general URT claims. * **Performance below what FDA considered acceptable**: FDA cited FloodLAMP’s PPA/NPA (90% / 100%) and reiterated that FDA believes **95% PPA and NPA** is acceptable clinical performance for the intended use “as you proposed,” and that 90% PPA was below that. * **No “low positive” / low viral load specimens** in the dataset as FDA defined them (Ct close to comparator LoD); FDA said without these they couldn’t assess performance appropriately. * FDA asked for root-cause analysis, possible design changes, and potentially new validation if the device/procedure changes. **(2) Inclusivity / variant analysis outdated** * FDA said the in silico inclusivity analysis (done Feb 27, 2021) was no longer representative of circulating variants and asked for an updated analysis + risk assessment. **(3) Cross-reactivity / microbial interference** * FDA noted specific organisms that had high homology in silico but weren’t covered by wet testing, and asked for tabular in silico data and additional interference testing where needed. **(4) Endogenous interfering substances** * FDA said the tested substances were insufficient for common URT cold remedies and listed additional recommended substances. **(5) External controls** * FDA recommended the positive control be “challenging” (low positive, <5x LoD) and said the described control (~8x LoD) wasn’t adequate; requested validation data. **(6) RUO reagents** * FDA said RUO components are not under 21 CFR Part 820 and therefore can vary; FDA said you may not recommend RUO-labeled materials as test components without additional mitigations, and they gave options (use IVD-labeled materials, qualify specific RUO lots and publish lot numbers, or bring materials under your own QMS by supplying them as kit components). Finally, FDA set a very short turnaround (by Oct 15 noon ET) and stated that if the response was late or inadequate, they could remove the test from the notification listing and expect suspension of distribution. (Your Oct 14 meeting notes indicate the written response deadline was effectively aligned to Oct 20 instead, which suggests there was at least some informal flexibility. ) #### Oct 14, 2021 — Zoom meeting (your notes) Per the meeting notes: * FDA raised concerns about the **open protocol / designation** concept; specifically, Silke asked about “designation” and “said they would not want us to make IFU publicly available.” * FloodLAMP described a plan: initially deploy like SalivaDirect, later produce a full reagent kit. * FloodLAMP communicated a request to **amend intended use** to serial screening only (removing “persons suspected of COVID”). * FDA asked about data supporting intended population; FloodLAMP said samples were remnant, de-identified, no clinical info. * FDA (Kris) referenced “6 criteria” for serial screening amendment and said risk-benefit differs for POC/at-home vs lab-based tests; also noted pipetting choices can affect whether something is “POC-like.” * Anne Wyllie asked about validating with a blinded reference panel; Silke said the reference panel was no longer available. #### Oct 20, 2021 — FloodLAMP responds (email + attached response letter) FloodLAMP’s Oct 20 email to FDA explicitly frames the central issue as **risk-benefit**, and that FDA’s thinking (as FloodLAMP understood it) might be: serial-screening “streamlined” pathways don’t apply because this is a **lab** submission rather than POC. FloodLAMP also asked for the “6 criteria” Kris referenced, and reiterated the “open protocol + scalable colorimetric LAMP” impact argument. FloodLAMP’s attached response letter (the separate Oct 20 response file) did several concrete things: * **Formally requested intended-use amendment**: remove “persons suspected of COVID,” keep serial screening, and asked for guidance on appropriate screening frequency given performance data. * **Narrowed specimen claim**: remove NP/OP; use nasal swabs only. * **Disputed the performance bar for serial screening**: FloodLAMP stated its understanding that the PPA threshold for screening with serial testing is 80% and argued their analytical + clinical results exceeded many authorized antigen tests. * Provided additional performance framing: noted only high-Ct samples failed in Stanford clinical evaluation; tied this to LoD; and again cited real-world pooled surveillance metrics (pools, people screened, positives found, “no known or suspected false negatives”). * Said updates on variants/inclusivity would be provided; pushed back on some cross-reactivity assumptions as “PCR-like” rather than LAMP-specific; asked for guidance on interference list given sample-type/intended-use changes. * On controls, argued the chosen positive-control concentration mirrored SalivaDirect and asked FDA to confirm suitability. * On RUO reagents, said FloodLAMP would qualify specific lots and post lot numbers. --- ### The actual “shutdown”: what FDA said when it closed the file Although you didn’t list Oct 21/Oct 29 as separate “October files,” they’re part of the same October correspondence record and they contain the **explicit closure rationale**. #### Oct 21, 2021 — FDA final decision: EUA210582 closed FDA told FloodLAMP the additional information “does not demonstrate” the device is adequately validated; the EUA was closed. In the attached letter, FDA combined two themes: 1. **Substantive deficiency framing** They said the submission did not adequately demonstrate the device is validated / safe and effective for intended use (implicitly referencing the prior deficiency list). 2. **Resource + prioritization framing (“why stop now”)** FDA said: given the volume of EUA requests, FDA is prioritizing based on factors including public health need, availability, unmet need, and the adequacy of the information about likely safety/effectiveness; based on those factors, their review so far, and “anticipated resources needed to continue review,” further review was “not a priority,” and FDA declined to issue an EUA “at this time.” So the closure is best read as: **(a) the file still had major gaps, and (b) closing it was also a triage decision about reviewer time.** #### Oct 28–29, 2021 — FloodLAMP challenges whether the intended-use amendment was recognized; FDA replies FloodLAMP pointed out that the closure letter still referenced the “suspected of COVID” intended use and asked FDA to confirm whether the amendment request was understood. FDA replied that they **did understand** the intended-use amendment when they sent the deprioritization letter, but that FloodLAMP’s “current clinical study is not acceptable to support testing a screening population with serial testing,” and directed FloodLAMP back to the new molecular template or a pre-EUA amendment/supplement for study design feedback. This matters because it suggests the amendment wasn’t the “unlock”; FDA’s decisive blocker (at least as stated in Oct 29) was **clinical-study acceptability for serial screening**, not merely the wording of intended use. --- ### FDA’s explicit justifications, boiled down If you strip out tone and just list the agency’s stated reasons across the thread (April → June → Oct), the “why we shut this down” story has three layers: #### 1) Deprioritization / triage due to pandemic phase + impact criteria * April 2021: FDA explicitly said the test would have “relatively limited impact” on U.S. testing accessibility/capacity, so review was “not a priority,” and they closed the EUA. * June 2021: FDA said they didn’t review the validation studies/data in the pre-EUA because of prioritization and closed the pre-EUA after providing limited guidance. * Oct 2021: FDA again used prioritization language, adding that the “anticipated resources needed to continue review” factored into the decision to stop. #### 2) “Not adequately validated” — with a very specific deficiency list The Oct 13 letter reads like FDA saying: **to authorize this, we’d need a lot more (and different) evidence**—especially around clinical performance, intended use population, low viral load positives, and updated variant inclusivity. #### 3) For serial screening specifically: “your clinical study isn’t acceptable” Even after FloodLAMP tried to narrow intended use to serial screening and AN swabs, FDA’s Oct 29 email says directly: the current clinical study is not acceptable to support screening with serial testing. --- ### Reading between the lines: plausible “FDA-in-their-shoes” rationales Everything below is explicitly **inference**—but I’m tying each hypothesis to something concrete in the record. #### Hypothesis A: FDA saw this as a “high-effort file” with multiple major gaps, so they cut it to protect scarce reviewer capacity Clues: * The Oct 13 letter is not “one missing table”; it’s a multi-domain deficiency set (clinical population/specimens/performance, variants, interference, controls, RUO supply chain/QMS). * On Oct 21, FDA explicitly referenced “anticipated resources needed to continue review” as part of why further review was not a priority. Interpretation: * Even if the test might ultimately be authorizable, FDA likely perceived that getting to “yes” would require **new clinical work + multiple analytical studies + QMS/controls/supplier mitigation**, i.e., a lot of back-and-forth. Under triage pressure, those files are the ones you close first. #### Hypothesis B: The “serial screening pathway” you tried to use may have been treated as mainly justified by *accessibility gains* (POC/at-home), and FDA didn’t see the same benefit for a lab-based test—so the risk-benefit balance didn’t “buy down” the evidence requirements Clues: * Your Oct 20 email indicates FDA’s risk-benefit framing on the call sounded like: lab-based reduces benefit relative to POC/at-home. * Meeting notes record Kris saying risk-benefit is different for POC/at-home vs lab-based tests, and referencing “6 criteria” for serial screening amendment. Interpretation: * FDA may have built the serial-screening indication to enable *more testing where testing otherwise wouldn’t happen* (especially at home/near patient), accepting different tradeoffs. If your test still requires a CLIA lab workflow (even if instrument-free), FDA may have categorized it as “not the kind of accessibility expansion that justifies a lower bar.” #### Hypothesis C: FDA likely discounted your “surveillance deployments” evidence because it wasn’t in the clinical validation form they rely on for EUA decisions (and because it was explicitly non-diagnostic) Clues: * You repeatedly offered real-world screening metrics (Oct 4 email and Oct 20 response). * FDA’s deficiency focus stayed anchored to classic EUA validation constructs: defined intended-use population, comparator-based clinical agreement, low viral load positives, etc. Interpretation: * Even genuinely strong field performance can be hard for FDA to credit if it’s not (a) prospectively designed, (b) comparator-grounded in the required way, and (c) clearly within the exact intended use. It may still be persuasive as “supporting evidence,” but not as a substitute for the missing validation pieces FDA flagged. #### Hypothesis D: QuickColor’s clinical sensitivity and “challenging positives” problem was the real immovable object Clues: * In June 2021 FDA already told you QuickColor’s PPA was below what FDA considered acceptable (95%) for the use as framed there, and they did not recommend pursuing unless sensitivity improved. * In Oct 2021 FDA again emphasized: PPA 90% vs the 95% they “believe is acceptable,” plus no low viral load specimens. * In Oct 29 FDA said your current clinical study is not acceptable for serial screening. Interpretation: * From FDA’s perspective, **false negatives in asymptomatic screening** can have outsized public-health consequences, and they may have judged that (i) 90% PPA plus (ii) a dataset without low viral load positives equals “we cannot responsibly authorize this” without substantial additional work. #### Hypothesis E: The “open protocol” posture created extra regulatory discomfort: uncontrolled replication + RUO quality + stewardship/designation issues Clues: * Your Oct 14 notes: FDA did not want IFU publicly available; asked about designation; this is directly about governance/control of an “open protocol” approach. * The Oct 13 letter is unusually explicit about RUO reagents and the quality-system implications, and requires a mitigation route. * The open-EUAs context file underscores that “open EUA” is not just publishing a protocol—it’s an authorization + stewardship pattern with lab designation burdens and supply chain validation complexities. Interpretation: * FDA may have been comfortable with SalivaDirect’s model (single steward, specific lab designation commitments, very clearly bounded method), but less comfortable with a commercial entity proposing “open protocol” + eventual kit commercialization + broad dissemination—especially if key inputs were RUO and if performance wasn’t already rock-solid. * In other words: open can be a public-good feature, but to a regulator it can look like a **control problem** unless governance and quality controls are extremely crisp. #### Hypothesis F: Timing/phase-of-pandemic thinking likely mattered—but not in the way people assume Clues: * FDA repeatedly referenced “different phase of the pandemic” and “many tests now authorized” when deprioritizing. * Your own internal commentary notes the experience felt like blanket deprioritization and triage driven by staffing/resource constraints. Interpretation: * It’s plausible FDA, in Oct 2021, believed the U.S. already had adequate diagnostic molecular capacity and was trying to concentrate on (a) at-home/POC accessibility and (b) high-volume industrialized products, not additional lab-developed-like workflows—even if your workflow was cheaper and operationally elegant. * This is consistent with your speculation about Omicron: in Oct 2021, they weren’t behaving like an agency preparing for a January 2022 demand shock; they were behaving like an agency trying to **wind down a crushing review backlog** under a “we have enough tests” narrative. --- ### A compact way to summarize “why they shut you down” If you want a one-paragraph explanation that is faithful to the record **and** captures the implied logic: FDA appears to have viewed FloodLAMP’s QuickColor EUA as (1) still **not adequately validated** for the claimed intended use—especially due to clinical study limitations (population not characterized, specimen claims not supported, PPA below FDA’s typical bar, and no low-viral-load positives) plus additional analytical/QMS issues (variants/inclusivity, interference, controls, RUO reagents)—and (2) **too resource-intensive** to continue reviewing in a late-2021 triage environment where FDA was prioritizing tests that most clearly expanded accessibility (POC/at-home) or capacity, so they closed the file as “not a priority” rather than continue iterative review. --- If you want, I can also do a second pass that’s more “forensic,” where I map **each** FDA deficiency (Oct 13 letter items 1–6) to (a) what you offered in the Oct 20 response, (b) what FDA implicitly accepted vs didn’t address, and (c) which items likely triggered “new clinical study required” vs “straightforward paperwork/testing.” # 1,525 _context-commentary_regulatory-fl-fda-correspondence.md METADATA last updated: 2026-03-02 RT file_name: _context-commentary_regulatory-fl-fda-correspondence.md category: regulatory subcategory: fl-fda-correspondence words: 1021 tokens: 1525 CONTENT ## Context This subcategory contains FloodLAMP's direct correspondence with the FDA regarding its SARS-CoV-2 diagnostic test EUA submissions, spanning from October 2020 through October 2021. The files include pre-EUA requests, emails to FDA leadership, FDA deficiency letters, meeting notes, FloodLAMP's written responses, and the deprioritization/closure letters that ended FloodLAMP's EUA pursuit. For the submission documents themselves and technical background on the EUA process, see `regulatory/fl-fda-submissions/_context-commentary_regulatory-fl-fda-submissions.md`. During the COVID-19 pandemic, the FDA's Center for Devices and Radiological Health (CDRH) managed EUA requests for diagnostic tests through a process that evolved substantially as submission volume grew. Communication between the FDA and test developers typically occurred through a combination of formal letters (deficiency notices, final decisions), email exchanges with assigned reviewers, optional pre-EUA feedback, and periodic virtual town halls open to the broader developer community. The FDA also offered short interactive review meetings — typically 30 minutes — to discuss specific submission issues. For developers seeking EUAs, the process began with either a pre-EUA submission (to get preliminary feedback before a full filing) or a direct EUA submission. The FDA would then triage the submission based on prioritization factors — primarily whether the test would increase testing accessibility (point-of-care, at-home) or significantly expand testing capacity (high-throughput, high-volume manufacturing). Beginning in fall 2020, the FDA formalized a deprioritization system that included two mechanisms: "Decline to Review" for low-priority submissions and "Decline to Issue" for submissions with unresolved critical deficiencies. By September 30, 2021, the FDA had declined to review 558 EUA requests for COVID-19 tests. For more on deprioritization, see the companion research report `regulatory/fl-fda-correspondence/_AI_FDA Deprioritization of COVID-19 Diagnostic EUAs.md`. FloodLAMP's correspondence documents the full arc of engagement with the FDA: early encouragement from OIVD Director Tim Stenzel on the open-source protocol approach (December 2020), initial EUA submissions and immediate deprioritization (March–April 2021), a pre-EUA that the FDA closed without reviewing the validation data (May–June 2021), a direct appeal to FDA leadership with real-world surveillance data (October 4, 2021), a 6-deficiency letter followed by a 30-minute Zoom meeting and written response (October 13–20, 2021), and final closure one day after FloodLAMP's response (October 21, 2021). The correspondence with the FDA on FloodLAMP's open-source EUA submissions is closely connected to two other regulatory subcategories: the FDA town halls (`regulatory/fda-townhalls`) where FloodLAMP engaged FDA leadership publicly, and the open EUAs concept (`regulatory/open-euas`) that was central to FloodLAMP's regulatory strategy. ## Commentary FloodLAMP's experience with the FDA during the COVID-19 pandemic was defined by a persistent inability to obtain meaningful regulatory engagement on submissions that, by the FDA's own stated criteria, should have warranted review. The company developed a validated, instrument-free, colorimetric RT-LAMP test at a cost of $1–2 per reaction, designed as an open-source protocol modeled on the SalivaDirect EUA. The test was adopted by EMS agencies and municipal fire departments for routine surveillance screening. Despite multiple submissions, real-world deployment data, and direct appeals to FDA leadership, FloodLAMP received blanket deprioritization along with hundreds of other test developers. Had a meaningful review, let alone an EUA, been obtained in the spring of 2021, the trajectory of the company would have been fundamentally different. For a detailed factual reconstruction and analysis of the critical October 2021 correspondence sequence that ended FloodLAMP's EUA pursuit, see `regulatory/fl-fda-correspondence/_AI_FloodLAMP FDA October 2021 Correspondence Analysis.md`. That document covers the complete timeline from October 2020 through October 2021, the FDA's stated justifications, and multiple interpretive explanations of the FDA's rationale. For related commentary on the FDA town halls and the open EUA concept, see `regulatory/fda-townhalls/_context-commentary_regulatory-fda-townhalls.md` and `regulatory/open-euas/_context-commentary_regulatory-open-euas.md`. The first direct interaction with the FDA set the tone for what followed. In a November 2020 phone call for the pre-EUA, the assigned reviewer had not heard of SalivaDirect, DetectaChem, or even LAMP as a technology. The reviewer strongly recommended against pursuing anything involving asymptomatic testing or pooling, and instead recommended the narrowest possible indication: a single symptomatic person suspected of COVID-19. This was the starting position from which FloodLAMP had to make its case for the open-source screening model. The FDA's rationale for deprioritization consistently came back to being short-staffed and resource-constrained. These were real constraints. But the response to those constraints — blanket deprioritization — failed a basic policy test. At the point FloodLAMP was deprioritized, the country was more than a year into the pandemic. The question the FDA should have been asking was: "Will this decision result in less testing?" When the answer was yes, creative solutions were warranted. The FDA could have established streamlined review tracks for open-protocol tests, created batch review processes for submissions using validated primer sets, facilitated reference panels for small developers, or simply provided actionable feedback rather than closing files without reviewing the data. None of these were pursued. The ITAP (Independent Test Assessment Program) eventually emerged as a partial alternative pathway, but it had limited access and transparency. The October 4, 2021 letter to OIVD Director Tim Stenzel stands as one of the best summaries of FloodLAMP's case for its test and its work. In that letter, FloodLAMP presented real-world surveillance data from five sites across three states, approximately 2,300 people screened in 800 pools with three unknown positives detected and no known false negatives, alongside manufacturing readiness (2 million tests on hand, 3 million more at LGC Biosearch), $1–2 per test pricing, and active commercial sites with EMS and fire departments. Stenzel never responded. The review team sent a 6-deficiency letter nine days later, offered a 30-minute Zoom call the following day, received a substantive written response on October 20, and issued a final closure on October 21. The speed of that closure, one day after FloodLAMP's response that proposed a narrowed intended use and addressed multiple deficiencies, suggests the outcome was predetermined and the interactive review seemed to be procedural rather than genuinely deliberative. Five weeks after the FDA closed FloodLAMP's submission, the Omicron variant was reported. By January 2022, the United States experienced the worst testing shortage of the entire pandemic. The principle behind the deprioritization decision — that the country did not need more tests — was catastrophically wrong, and it was applied systematically to FloodLAMP and hundreds of other test developers. # 736 2020-10-22_Email to FDA CDRH - Request for Guidance.md METADATA last updated: 2026-03-05 by BA file_name: 2020-10-22_Email to FDA CDRH - Request for Guidance.md file_date: 2020-10-22 title: Email to FDA CDRH - Request for Guidance category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1mH0N7IRddKIaXaZAyHAqqyhh3epTeheieS20-dm3_U0 xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2020-10-22_Email%20to%20FDA%20CDRH%20-%20Request%20for%20Guidance.docx pdf_gdrive_url: https://drive.google.com/file/d/1JxojezTCq8L0bJutMf4yE4l64BP-b-xU pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2020-10-22_Email%20to%20FDA%20CDRH%20-%20Request%20for%20Guidance.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 736 words: 537 notes: summary_short: The Email to FDA CDRH - Request for Guidance (Oct 22, 2020) outlines FloodLAMP’s pre-EUA request to the FDA for feedback on validating a pooled SARS-CoV-2 RT-LAMP screening program, including proposed pooling levels, turnaround targets, and two assay configurations (fluorimetric and colorimetric) with preliminary LoD data. It’s useful as an early regulatory-facing snapshot of FloodLAMP’s technical approach, intended use in asymptomatic group screening, and the specific guidance and template updates they were seeking to shape an EUA-ready validation plan. CONTENT ***INTERNAL TITLE:*** Pre-EUA email 10/22 sent to CDRH FloodLAMP Biotechnologies is a Public Benefit Corporation with a mission to improve public health with scalable, low-cost infectious disease screening programs. Our near-term goal is to help end the COVID-19 crisis through widely accessible SARS-CoV-2 pooled screening. We are based in San Carlos, CA and are engaged in a number of collaborations with mission-driven individuals and organizations. FloodLAMP is developing an integrated screening program consisting of efficient on-site and at-home pooled sample collection, combined with an ultra-low-cost, low-barrier-to-entry RT-LAMP assay protocol. The assay uses a chemical inactivation (TCEP/EDTA) and a bead purification step to achieve high sensitivity required for pooling. Amplification is via RT-LAMP, with 2 versions of the kit under development: 1) fluorimetric for real-time measurement on qPCR instruments and 2) colorimetric for endpoint visual and camera based readout. Preliminary LoD studies using Zeptometrix inactivated virions spiked into anterior nares swab extract have determined an LoD of 2 copies/ul for the colorimetric assay. We've run thousands of samples to date. |Concentration (copies/μL)|Positive Samples Detected| |---|---| |4| 100% (22/22)| |2| 100% (19/19)| |1| 55% (11/20)| || Our sample collection materials and procedures are configured to pool up to 10 samples. We plan to pool to even higher levels by pooling pools of 10 in the lab. As a part of the pre-EUA process, we would greatly appreciate your guidance on determining appropriate pool levels and LoD targets for higher-level pooling. Our screening program is designed for asymptomatic populations that participate in the program as a group, such as a school or employer. During the program's initial phase, all participants will be tested individually or at small pool levels that are appropriate for the estimated prevalence. Immediately following the initial phase, participants that have tested negative will commence ongoing pooled screening, with no more than 3 days between tests and less than 24 hour turnaround (target less than 12 hours). Dedicated lab capacity will be committed to ensure screening continuity and rapid turnaround time. We understand that FloodLAMP's Screening Program and Test Kits comprise an ambitious plan. We are integrating several of the agency's priorities with the goal of unlocking mass, scalable screening for the U.S. As a Public Benefit Corporation, we have explicitly committed to open protocols and the public good. We are already living that commitment through important collaborations and by publicly publishing our detailed protocols, workflow, and process videos. We will expand this material in support of our Test Kit IFU to facilitate rapid and reliable adoption of the FloodLAMP Screening Program at scale. We at FloodLAMP are inspired by the Yale team's groundbreaking work on Saliva Direct - the first open protocol EUA. We plan to build upon their example of openness and accessibility as we seek authorization for the FloodLAMP IVD Test Kit. We would greatly appreciate feedback and guidance from the FDA in determining a validation plan for the 2 assay configurations, as well as multiple reagent and supplier combinations. We are using the following templates for our pre-EUA submission. We would greatly appreciate updated versions of these, if they are available. July 28 Molecular Diagnostic Template for Commercial Manufacturers July 28 Molecular Diagnostic Template for Laboratories May 29 Home Specimen Collection Molecular Diagnostic # 382 2020-11-10_Email to FDA Dir Tim Stenzel - FloodLAMP Pre-EUA.md METADATA last updated: 2026-03-05 by BA file_name: 2020-11-10_Email to FDA Dir Tim Stenzel - FloodLAMP Pre-EUA.md file_date: 2020-11-10 title: Email to FDA Dir Tim Stenzel - FloodLAMP Pre-EUA category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1VBn8z1oUZA29-9OkproAwofi6O2ubEQ7PkvVdvyZqSA xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2020-11-10_Email%20to%20FDA%20Dir%20Tim%20Stenzel%20-%20FloodLAMP%20Pre-EUA.docx pdf_gdrive_url: https://drive.google.com/file/d/1KkiuK5SPHIxHrdUhVLitD8uE3FCl3tdc pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2020-11-10_Email%20to%20FDA%20Dir%20Tim%20Stenzel%20-%20FloodLAMP%20Pre-EUA.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 382 words: 281 notes: summary_short: The Email to FDA Dir Tim Stenzel - FloodLAMP Pre-EUA (Nov 10, 2020) is an outreach note requesting a meeting to discuss FloodLAMP’s newly submitted pre-EUA for an ultra-low-cost, LAMP-based SARS-CoV-2 test and how an “open source” EUA model could be expanded beyond SalivaDirect. It highlights key regulatory topics FloodLAMP wanted to align on—especially asymptomatic screening, pooling, and on-site/at-home collection—and proposes forming a consortium of mission-driven developers to produce validated, open-access molecular tests. CONTENT *Sent to CDRH email address on Nov 10, received response saying it was forwarded to Tim Stenzel a few days later* Dr. Stenzel, I run FloodLAMP Biotechnologies, a Public Benefit Corporation. On Friday we submitted a pre-EUA for an ultra-low-cost, scalable, LAMP-based test based on the Rabe Cepko assay out of Harvard. We are intending to provide this as an \"open source\" protocol, inspired by Dr. Anne Wyllie and the SalivaDirect team. FloodLAMP is collaborating with Dr. Wyllie and Prof. Connie Cepko, who are on our Scientific Advisory Board. Dr. Wyllie and I would greatly appreciate the chance to meet with you to discuss expanding the open source EUA approach, as well as several overlapping EUA issues for the SalivaDirect and FloodLAMP tests (asymptomatic screening, pooling, and on-site/at-home collection). We are currently helping a third group who has submitted an EUA and is also seeking to provide their test as an open source protocol, and we continue to receive interest from yet more groups that are interested in taking this approach. Our goal is to build a consortium of like-minded, mission-driven test developers committed to bringing online a suite of properly validated and well supported open-access SARS-CoV-2 molecular tests. As SalivaDirect has shown, these molecular tests can be deployed in a scalable, non-proprietary way that is truly game-changing. We see the potential for these tests to become high-impact public goods, with far-reaching benefits both in pandemic preparedness and broader human health. There's a lot of hard work to be done to achieve this ambitious goal, and we would like to discuss with you how to most efficiently proceed. Please let us know if you are available soon to discuss. Best Regards # 2,047 2020-12-09_FloodLAMP FDA Townhall Engagement on Open Source FDA IVD EUAs and Generic Molecular Tests.md METADATA last updated: 2026-03-05 by BA file_name: 2020-12-09_FloodLAMP FDA Townhall Engagement on Open Source FDA IVD EUAs and Generic Molecular Tests.md file_date: 2020-12-09 title: FloodLAMP FDA Townhall Engagement on Open Source FDA IVD EUAs and Generic Molecular Tests category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1jZzEumjRYUOK31Cz-sUQkfONjqOja1f_YqPcNduwHA8 xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2020-12-09_FloodLAMP%20FDA%20Townhall%20Engagement%20on%20Open%20Source%20FDA%20IVD%20EUAs%20and%20Generic%20Molecular%20Tests.docx pdf_gdrive_url: https://drive.google.com/file/d/1Dt9mrf7uCGmtW75LZs0x6luUckkMWP59 pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2020-12-09_FloodLAMP%20FDA%20Townhall%20Engagement%20on%20Open%20Source%20FDA%20IVD%20EUAs%20and%20Generic%20Molecular%20Tests.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 2047 words: 1462 notes: summary_short: The “Dialogue on Open Source Testing and FDA IVD Authorization of Generic Molecular Tests” summarizes a December 9, 2020 FDA town hall exchange about using Rights of Reference and “method” EUAs (modeled on SalivaDirect) to enable interoperable, non-proprietary molecular test protocols across laboratories. It outlines how open IVD EUAs could reduce duplicative validation, strengthen supply-chain resilience, and scale testing via a structured lab designation process, positioning FloodLAMP’s strategy to expand this open-access paradigm beyond SalivaDirect. CONTENT ***INTERNAL TITLE:*** Dialogue on Open Source Testing and FDA IVD Authorization of Generic Molecular Tests 12-9-2020 FDA Town Hall ## Can listen to the 7 minutes of audio [here](https://www.youtube.com/watch?v=-7K-zmy-ouU&t=300s) ## High Level Summary: FDA authorizations for tests can be made completely open (so any lab can order the ingredients directly from suppliers) and interoperable (through Rights of Reference to the validation data). The potential of this open source/open access paradigm of testing is immense but almost totally unknown to government leadership. It has received no funding out of the billions that has been spent expanding the highly profitable, proprietary status quo of the diagnostics and clinical testing industry. Yet the FDA itself is fully aware of the potential for this open approach and embraced it with the [first "open source protocol" EUA SalivaDirect](https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-yale-school-public-health). Part of FloodLAMP's mission is to quickly expand this paradigm to several more key open source EUAs, and in doing so unlock and massively expand testing in the United States. ## Transcript: [**Randy True**](http://www.linkedin.com/in/randy-true-fof), Founder of [FloodLAMP Biotechnologies,](http://www.floodlamp.bio) a Public Benefit Corporation randy@floodlamp.bio [**Dr. Timothy Stenzel**](https://www.linkedin.com/in/timothy-stenzel-md-phd-20204521/), FDA Director, Office of In Vitro Diagnostics and Radiological Health [05:00 Randy True](https://www.youtube.com/watch?v=-7K-zmy-ouU&t=300s): *FloodLAMP is coordinating with other open source test developers. If we establish a consolidated primer set and give a general right of reference, then we won't individually have to repeat certain aspects of the validation, correct? Want to understand that dynamic a bit more in terms of the inclusivity, in silico analysis, and the in silico cross-reactivity and the wet cross-reactivity. Can you give us guidance as we coordinate on this?* [00:06:34 Dr. Timothy Stenzel, FDA](https://www.youtube.com/watch?v=-7K-zmy-ouU&t=394s): *Yeah, we've seen that is a pathway that could be very successful. Yale's SalivaDirect was the first.* *As far as the data related to test performance, yes that can be leveraged in multiple ways. The two main ways are that if you seek your own authorization for the path, you can give a right of reference for anyone else who wants to copy you. That wouldn't eliminate the requirement for them--if they're a kit developer, say--for them to come in to get their own authorization. And it wouldn't extend the umbrella of an EUA authorization to any lab that might copy that method.* *So, looking at the Saliva Direct model, they have in their original submission, they have an IFU that's the sole basis (so to speak) of their kit. And they point to off-the-shelf product that users can purchase. In the case of primers and probes for their test (I think it's the CDC's), they can get that from vendors that produce primary probes under the CDC authorization. So those are very specific catalog numbers, and those are primers and problems that we previously authorized.* *So again, there's these two different pathways. I want to lay them out very clearly:* *1) You can get your own, individual authorization for a kit. You can then give anybody (any other developer) the right of reference to that, and they can copy it, and they can pretty much link up and use the data in your submission. There are some elements that if they were to be changed, that we'd want to see. But if they're using the same suppliers and the same catalog numbers for everything that you're using, then that makes it very easy.* *2) The other way is to have this method authorized, as we did for SalivaDirect. Then we would envision giving you (or any other sponsor) the same sort of flexibility. Yale is actually the one that designates which lab can use their method and are therefore covered by their EUA. And they have commitments to the FDA on what is required and making that determination of designation. And my understanding is they've designated quite a few labs already, and I would refer you to them if anybody wants to know those numbers, but it appears to be a very highly successful program.* [10:18 Randy True](https://www.youtube.com/watch?v=-7K-zmy-ouU&t=618s): *Yeah, they've been our inspiration for this modality and effort. I guess just one quick follow-up question: So if we get authorization for a test with a certain lysis or inactivation buffer and a certain purification... Like, we're pursuing an ultra-cheap glass milk purification, but we're working with another test developer who is seeking authorization for a magbead based purification that would be highly amenable to automation. If we consolidated on the same primer set and LAMP master mix, then it's my understanding they wouldn't need to repeat the upfront parts. But with respect to the interfering substances, would they need to repeat that? And then if we gave them a general right of reference, then they would end up getting their own EUA that they could control the designations on, and then we would have our own, independent EUA that we controlled the designations on, even though we granted a right of reference. Is that how it would work?* [11:30 Tim Stenzel, FDA](https://www.youtube.com/watch?v=-7K-zmy-ouU&t=690s): *At a high level you're close. The devil is sometimes in the details. There are certain alterations to a test that may require additional validation. So if they're adding something new that you didn't do, say, then we would want to evaluate the data around that change. And then absolutely developers can give each other right of references as they so wish. They can specify what right they have from their entire EUA--they can have limitations, or they can open it up entirely. But you can basically cross-reference each other's assays to the extent that you want. And there would absolutely be synergy. And if the components are all the same that you use for the core test, then there would absolutely be synergy on reducing any sort of duplication. I look forward to hearing more about your development.* ## Commentary SalivaDirect is still the only open source IVD EUA. The potential of this new paradigm of testing that's open access, low cost, and supply chain robust, still has not been tapped. Essentially it's "generic" molecular testing. The vast majority of tests are slight variations on a few core protocols. But those are silo'd for commercial reasons. Even with the FDA submission or validation of tests developed at universities, these tests, because they are LDTs not IVDs, are not transferable to another lab and usually face supply chain shortages. *What's the solution*? - Several key open source IVD EUAs - The standardized supply chain to support these tests - The team and funding to support the lab designation process to rapidly scale We are coordinating on the standard primers for LAMP and will give a blanket Right of Reference with the first open LAMP EUA, just as the CDC did for PCR. FloodLAMP is in discussions with manufacturers to secure a production scale supply that can be offered at scale with fast turnaround and low cost. The LAMP primer ROR can then be used by both IVD and EUA submissions, and would be available for non-CLIA surveillance testing. The cross referencing capability Tim Stenzel describes is not well known outside of the industry, as molecular Dx companies (aka IVD Kit Manufacturers) don't openly give these Rights of Reference. They keep the ingredients of their tests trade secret, even when they are the exact same formulation as off-the-shelf RUO products. The "designation" of labs for an open source IVD EUA is a new process. SalivaDirect has been a big success but they've only been able to designate about 50 of 400+ labs that have requested to use the EUA, over 4 months. That's because of the Yale team's limited resources and the bureaucratic nature of academic institutions. FloodLAMP will build an organization to rapidly designate hundreds of labs. The simple fact that EUAs can be made fully open is very powerful. This seems to be entirely absent from proposals to quickly scale up testing in the U.S. Wyllie and Grubaugh have created the model with SalivaDirect. It will be far better to not get the next open IVD EUAs through universities because of their institutional bureaucratic nature and their top prioritization of publications, branding and credit. FloodLAMP, a public benefit corporation, is seeking several open EUAs, having filed a pre-EUA on one LAMP test so far.. FloodLAMP is executing on several fronts: technical and scientific, regulatory, the commercial supply chain, and legal aspects. We've built the knowledge and relationships to make generic molecular testing a reality, in Q1 of 2021. FloodLAMP is seeking capital from sources that support our public good mission. Instead of yet another proprietary test that will barely make a dent in the nation's testing capacity, our "product" is a new paradigm of low cost, widely accessible generic molecular testing. This will have great positive impact on the COVID crisis, and has longer term benefits in healthcare more generally. # 716 2021-03-22_Cover Letter to FDA - FloodLAMP Open Source EUA Submissions.md METADATA last updated: 2025-12-16 BA updated metadata after BA fixed inconsistencies file_name: 2021-03-22_Cover Letter to FDA - FloodLAMP Open Source EUA Submissions.md file_date: 2021-03-22 title: Cover Letter to FDA - FloodLAMP Open Source EUA Submissions category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1NQ3_Rmh-AYVSPYn7AP-Hls9rMLBXEX1zWLvRLTrzPrE xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2021-03-22_Cover%20Letter%20to%20FDA%20-%20FloodLAMP%20Open%20Source%20EUA%20Submissions.docx pdf_gdrive_url: https://drive.google.com/file/d/1Msh-TYQeiZlCc2fd_zhW0CQOk3U8B_bO pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2021-03-22_Cover%20Letter%20to%20FDA%20-%20FloodLAMP%20Open%20Source%20EUA%20Submissions.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 716 words: 518 notes: summary_short: The Cover Letter to FDA for FloodLAMP Open Source EUA Submissions summarizes FloodLAMP’s follow-up to a pre-EUA with two full EUA submissions: the QuickColor colorimetric LAMP test and the EasyPCR duplex PCR test, both using a shelf-stable chemical plus heat inactivation workflow. It positions the assays as open-source, supply-chain-resilient protocols (modeled on SalivaDirect) and highlights primer sourcing, clinical performance claims, intended screening use cases, and supporting plans for IRB studies and a companion mobile app. CONTENT Dear COVID19DX IVD Team, I'm pleased to follow up on FloodLAMP Biotechnologies' pre-EUA PEUA201985 with 2 complete COVID-19 IVD EUA submissions. Thank you for the extensive comments and guidance on the pre-EUA. These new submissions are for direct tests rather than the glass milk purification from our pre-EUA. Both tests utilize the same shelf stable chemical plus heat inactivation protocol. The FloodLAMP QuickColor(TM) COVID-19 Test uses a colorimetric LAMP amplification that is visually read by a simple color change. The FloodLAMP EasyPCR(TM) COVID-19 Test uses a one-step PCR amplification in duplex with an internal control. Both EUA submissions are configured as open source protocols, building on the model established by SalivaDirect(TM). The chemicals and reagents needed for the tests are readily available in large quantities. The workflow for the tests has been simplified and only a single pipet tip per sample is required, further reducing potential supply chain bottlenecks. The LAMP primers chosen target 3 different genes in SARS-CoV-2 to ensure robustness and sensitivity. These primer sequences have been widely validated in research, utilized in testing programs, and submitted in other LAMP EUAs. Over the last 3 months, FloodLAMP has partnered with LGC Biosearch to establish the supply of these primers. FloodLAMP configured the primers to be offered as a catalog product by LGC Bioserach, and placed an order for 1.2M reactions in January. A portion of the production primers were delivered to FloodLAMP's lab on March 19. The other portion will be launched shortly as catalog products. With the support of the CDC and FDA, with authorization of our tests, FloodLAMP will offer a blanket right of reference to the LAMP primer validation data for any IVD test developer or CLIA lab, in an effort to further expand access to COVID-19 testing and screening. The FloodLAMP QuickColor(TM) COVID-19 Test demonstrated 90% sensitivity and 100% specificity in our clinical evaluation. It is ideal for use in serial screening of schools and large populations, as no specialized instrumentation is required. Both tests have very low consumables cost, at $1-2 per reaction, and a modestly trained operator can process 800 reactions per shift without any automation. FloodLAMP is in the process of obtaining an IRB to perform clinical studies for unsupervised home collection, pooling, and asymptomatic screening. The clinical studies will include usability testing for our mobile app. The app has a patient interface for sign up, consent, sample collection and results. It also has a staff interface for sample intake, barcode scanning, batch control, and results reporting, as well as an api to interface with any LIMS. The app enables accessioning and results reporting without a LIMS, providing a low overhead end-to-end digital solution for a lab running community screening. FloodLAMP's EUA submissions for these 2 molecular tests provide a combination of performance, ease of use, supply chain robustness, low cost, and scalability. Along with the other testing and screening program elements we've developed, they will significantly increase test capacity and access across the nation. We look forward to further engaging with the FDA on this important effort. Sincerely, Randy True Founder - FloodLAMP Biotechnologies, Public Benefit Corporation randy@floodlamp.bio # 1,309 2021-04-02_FloodLAMP FDA Correspondence - Deprioritization EUA210252 EUA210254.md METADATA last updated: 2026-03-05 by BA file_name: 2021-04-02_FloodLAMP FDA Correspondence - Deprioritization EUA210252 EUA210254.md file_date: 2021-04-02 title: FloodLAMP FDA Correspondence - Deprioritization EUA210252 EUA210254 category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1qbX9jeURHdrgrreOVksMThNkB1mP77W3oO28vz0WSSA xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2021-04-02_FloodLAMP%20FDA%20Correspondence%20-%20Deprioritization%20EUA210252%20EUA210254.docx pdf_gdrive_url: https://drive.google.com/file/d/1XOKe8WQZNDY0Bfl8VbKakCQ719mq-TtC pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2021-04-02_FloodLAMP%20FDA%20Correspondence%20-%20Deprioritization%20EUA210252%20EUA210254.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 1309 words: 675 notes: summary_short: The April 2, 2021 FDA email and attached deprioritization letter notify FloodLAMP that EUA210252 (QuickColor COVID-19 Test) was closed because FDA declined to review it under then-current prioritization criteria. It explains that, in a later phase of the pandemic with many tests already authorized, FDA prioritized requests expected to materially increase U.S. testing accessibility (e.g., POC, home collection, at-home) or capacity (e.g., high-throughput), and judged FloodLAMP’s submission as having relatively limited impact on those factors. The document also notes the same decision and attachment were issued for a related EUA request (EUA210254). CONTENT ***INTERNAL TITLE:*** 2021-04-02_Email from FDA - Final Decision and Deprioritization ## Email Header from: Walia, Vijay <Vijay.Walia@fda.hhs.gov> to: "randy@floodlamp.bio" <randy@floodlamp.bio> cc: "Caposino, Paula" <Paula.Caposino@fda.hhs.gov>, "St. Pierre, Don J." <don.st.pierre@fda.hhs.gov>, "Roth, Kristian" <Kristian.Roth@fda.hhs.gov>, oir-policy <CDRH-OIR-POPS@fda.hhs.gov>, "EUA210252@docs.fda.gov" <EUA210252@docs.fda.gov> date: Apr 2, 2021, 1:18 PM subject: Final Decision for EUA210252 Request – letter attached ## Email Body Dear Randall J. True, Please see attached letter regarding your EUA request, EUA210252. This is the final decision on your EUA request, and your EUA is now closed. The reason for our decision is that we are currently in a different phase of the pandemic with respect to tests than we were previously, where many COVID-19 tests are now authorized. We prioritize review of EUA requests for tests taking into account a variety of factors, as discussed in the [Emergency Use Authorization of Medical Products and Related Authorities Guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities), such as the public health need for the product and the availability of the product. We have, for example, prioritized review of EUA requests for tests where authorization would increase testing accessibility (e.g., point of care (POC) tests, home collection tests, and at-home tests) or would significantly increase testing capacity (e.g., high-throughput tests). Regarding your request, FDA determined that review of your EUA request is not a priority because, for example, authorization of the test would have relatively limited impact on testing accessibility or testing capacity in the United States. For additional information on FDA's priorities with respect to review of EUA requests for COVID-19 tests, see our website’s [FAQs on Testing for SARS-CoV-2](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/faqs-testing-sars-cov-2#5f9fefc60116f). Please confirm receipt of this email and attached letter. Thank you, Best Regards, Vijay **Vijay Walia PhD MBA** *Scientific Reviewer* **Division of Chemistry and Toxicology Devices \| OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality** **CDRH \| U.S. FDA ** White Oak, Bldg 66 10903 New Hampshire Ave., Silver Spring, MD 20993 Vijay.Walia@fda.hhs.gov P: (301) 796-6139 ## ATTACHMENT: EUA210252.IVD Deprioritization Letter_Decline to Review - FINAL (DJS).pdf (text from attached pdf copied below - Same Email and Attachment for EUA210254) April 2, 2021 Randall J. True o/b/o FloodLAMP Biotechnologies, a DE Public Benefit Corporation 4860 Alpine Rd. Portola Valley, CA 94028 Re: EUA210252 Dear Randall J. True: This letter is in response to your request for an Emergency Use Authorization (EUA) for the FloodLAMP QuickColor COVID-19 Test, intended for the following use(s): for the qualitative detection of RNA from SARS-CoV-2 in upper respiratory specimens from individuals suspected of COVID-19 by their healthcare provider and from individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection, when tested at a weekly interval with no more than 9 days between tests. Given the volume of EUA requests the Agency has received, FDA is prioritizing review of EUA requests for tests, taking into account a variety of factors such as the public health need for the product and the availability of the product.(1) Based on your request, FDA has determined that review of your EUA request is not a priority(2) because, for example, authorization of the test would have relatively limited impact on testing accessibility or testing capacity. FDA therefore declines to review the EUA request for the product at this time. This test has not been authorized to be distributed or used as proposed. FDA is committed to doing everything possible to help combat the COVID-19 outbreak and appreciates your efforts in this matter. Sincerely, Donald J. St.Pierre Deputy Director, New Product Evaluation OHT7:Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health Food and Drug Administration (1) For example, the agency has prioritized review of EUA requests for tests where authorization would increase testing accessibility (e.g., point of care (POC) tests, home collection tests, at-home tests) or would significantly increase testing capacity (e.g., tests that reduce reliance on test supplies, high-throughput, widely distributed tests). See [https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/covid-19-test-development-and-review-faqs-testing-sars-cov-2#priorities](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/covid-19-test-development-and-review-faqs-testing-sars-cov-2#priorities). (2) FDA’s current thinking on prioritization of EUA requests is explained in FDA’s guidance, “Emergency Use Authorization for Medical Products and Related Authorities,” available at [https://www.fda.gov/media/97321/download](https://www.fda.gov/media/97321/download). # 3,507 2021-06-17_FDA Correspondence Summary - Pre-EUA PEUA210313.md METADATA last updated: 2026-03-05 by BA file_name: 2021-06-17_FDA Correspondence Summary - Pre-EUA PEUA210313.md file_date: 2021-06-17 title: FDA Correspondence Summary - Pre-EUA PEUA210313 category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1Uw2wKJ-pCW2DkvRP0LyP-JT74VzeSSjMqULN9Pnafy8/edit?usp=drive_link xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2021-06-17_FDA%20Correspondence%20Summary%20-%20Pre-EUA%20PEUA210313.docx pdf_gdrive_url: https://drive.google.com/file/d/1uKfI8oroJ7qE6yxSBPPCx5oScZKEyXec/view?usp=drive_link pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2021-06-17_FDA%20Correspondence%20Summary%20-%20Pre-EUA%20PEUA210313.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 3507 words: 2053 notes: summary_short: The Pre-EUA (PEUA210313) record compiles FloodLAMP’s May 18, 2021 submission package for QuickColor and EasyPCR tests plus a pooled DTC dry-swab home collection kit and mobile app, submitted after earlier EUA deprioritization. FDA’s June 17, 2021 response states the agency did not review FloodLAMP’s validation data due to prioritization, but provides targeted guidance on study design (e.g., specimen adequacy/usability should be supported by the specific test, and self-collection studies should exclude participants with prior anterior nasal swab experience) and recommends using highly sensitive EUA RT-PCR comparators and ensuring enough low-viral-load positives; it also flags QuickColor’s clinical PPA as below the ~95% agreement level FDA considered acceptable and closes the pre-EUA. The October 5, 2021 follow-up email from FloodLAMP requests an interactive review to clarify serial-screening sensitivity expectations, usability and post-authorization study requirements, and prioritization, citing field surveillance deployment metrics and an open-protocol, low-cost scale-up approach. CONTENT ## 2021-05-18_Pre-EUA Documents Submitted to FDA CDRH as Attachments IFU - FloodLAMP Pooled Swab Collection Kit DTC.pdf Instructions for Use - FloodLAMP EasyPCR COVID-19 Test.pdf Instructions for Use - FloodLAMP QuickColor COVID-19 Test.pdf Pre-EUA - FloodLAMP EasyPCR COVID-19 Test Pre-EUA - FloodLAMP Pooled Swab Collection DTC Pre-EUA - FloodLAMP Pooled Swab Collection Kit DTC.zip Pre-EUA - FloodLAMP Proposed Pooling and Asymptomatic Screening Study Pre-EUA - FloodLAMP QuickColor COVID-19 Test Supporting Data - FloodLAMP EasyPCR COVID-19 Test.xlsx Supporting Data - FloodLAMP QuickColor COVID-19 Test.xlsx The Submission, IFU, and Supporting Data documents for the QuickColor and EasyPCR tests are the same as submitted on 3-22-21, which the FDA replied with a Deprioritization (denial to review). ## 2021-06-17_Email from FDA re FloodLAMP Pre-EUA Povinelli, Benjamin <[Benjamin.Povinelli@fda.hhs.gov](mailto:Benjamin.Povinelli@fda.hhs.gov)> - postdoc at Oxford to: "randy@floodlamp.bio" <randy@floodlamp.bio> cc: "Caposino, Paula" <[Paula.Caposino@fda.hhs.gov](mailto:Paula.Caposino@fda.hhs.gov)>, - FDA reviewer for 13 years "St. Pierre, Don J." <[don.st.pierre@fda.hhs.gov](mailto:don.st.pierre@fda.hhs.gov)>, - Associate Director, OIVD at FDA "Roth, Kristian" <[Kristian.Roth@fda.hhs.gov](mailto:Kristian.Roth@fda.hhs.gov)>, - Supervisory Chemist - FDA/CDRH/OIR/ oir-policy <CDRH-OIR-POPS@fda.hhs.gov>, "PEUA210313@docs.fda.gov" <PEUA210313@docs.fda.gov> date: Jun 17, 2021, 8:06 AM subject: RE PEUA210313 signed-by: fda.hhs.gov Good afternoon. Thank you for your pre-EUA submission, PEUA210313. As described in the U.S. Food and Drug Administration’s (FDA or Agency) guidance, “Emergency Use Authorization for Medical Products and Related Authorities,” available at [https://www.fda.gov/media/97321/download](https://www.fda.gov/media/97321/download), FDA prioritizes its pre-EUA activities based on a variety of factors. Given the volume of pre-EUA and EUA requests the Agency has received, we have not reviewed the validation studies nor the data provided in this pre-EUA but we provide some general recommendations below. We found 2 specific questions in your request and we provide answers below: - Is it acceptable to utilize the FloodLAMP EasyPCRTM COVID-19 Test for determining the pass/fail of specimen adequacy? No, these studies should be designed to support the usability of the test that is subject of the EUA. - Is it acceptable to strike this exclusion \[regarding self-collection\] since self-collection has become much more widespread? No. FDA recommends that participants in self-collection studies should be excluded if they have prior experience with the sample type (anterior nasal swabs). You may include participants with experience in other self-collection sample types. In this request, you provided information on the following devices: 1\. FloodLAMP QuickColorTM COVID-19 Test for the qualitative detection of RNA from SARS-CoV-2 in upper respiratory specimens including nasopharyngeal swabs, anterior nasal and mid-turbinate nasal swabs from individuals suspected of COVID-19 by their healthcare provider and from individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection, when such individuals are tested as part of a testing program that includes testing at regular intervals, at least once per week. 2\. The FloodLAMP Pooled Swab Collection Kit DTC is a direct to consumer (DTC) product for self-collecting pooled anterior nasal swabs in a dry tube at home (which includes a community based setting), including individuals without symptoms or other reasons to suspect COVID-19. Specimens collected using the FloodLAMP Pooled Swab Collection Kit DTC are transported at ambient temperature for testing at a laboratory. 3\. FloodLAMP EasyPCRTM COVID-19 Test is a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay intended for the qualitative detection of RNA from SARS-CoV-2 in upper respiratory specimens including nasopharyngeal swabs, anterior nasal and mid-turbinate nasal swabs from individuals suspected of COVID-19 by their healthcare provider and from individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection, when such individuals are tested as part of a testing program that includes testing at regular intervals, at least once per week. We recommend you refer to the following resources. After reviewing the resources below, if you decide to submit EUAs for each of the tests, please submit your complete requests with information and data adequate to support that your device is validated for its intended use and meets the criteria for issuance of an EUA under Section 564 of the Federal Food Drug and Cosmetic Act. To help facilitate the preparation, submission, and review of your EUA request, we recommend that you use the applicable template (see links below) and that you provide all of the information recommended in the template(s) to support all claims. - Policy for Coronavirus Disease-2019 Tests. This guidance includes reference to molecular diagnostic templates that include FDA’s recommendations for performance validation testing for SARS-CoV-2 molecular diagnostic tests. - The templates referenced in the guidance can be found here: [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas) . The direct link to the molecular diagnostic template can be found here: [Molecular Diagnostic Template for Commercial Manufacturers](https://www.fda.gov/media/135900/download) (updated July 28, 2020). This template includes all of our comprehensive recommendations on the types of information to provide to support most of your claims. For our recommendations on studies designed to support home collection (i.e., DTC testing), please see our [Home Specimen Collection Molecular Diagnostic Template](https://www.fda.gov/media/138412/download) (May 29, 2020). - As discussed in our templates, 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) as a comparator for the clinical evaluation. We recommend selecting a comparator assay that has established high sensitivity with an internationally recognized standard or FDA SARS-CoV-2 Reference Panel. We refer you to [https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data) and recommend that you select a comparator that is highly sensitive. You propose to use the Panther Fusion SARS-CoV-2 Assay and the Aptima SARS-CoV-2 assays as comparators. These have been shown to be highly sensitive using **nasopharyngeal swabs** collected and transported in media as per the Instructions for Use of each EUA. If you need to select a different comparator, we recommend that you confirm the suitability of the comparator with us through CDRH-EUA-Templates@fda.hhs.gov. In addition, you should ensure that your data set includes an adequate number of challenging/low viral load specimens (20-25% of positives) as defined as those having Ct values within 2-3 cycles of the average Ct at the limit of detection for a given target as based on comparator testing with an appropriately sensitive EUA test. Furthermore, please ensure your comparator test is run as authorized/without any modifications. - As stated in our template, FDA believes a minimum of 95% positive and negative agreement is acceptable clinical performance. The FloodLAMP QuickColorTM COVID-19 Test demonstrated a lower PPA than what FDA believes is acceptable for this use. Therefore, we do not recommend pursuing an EUA for this test unless you can improve its sensitivity. - If you plan to include or recommend the use of components that are currently labeled for Research-Use-Only (RUO), we offer the following recommendations. Since RUO components are not designed for clinical testing they should not be used for patient testing without additional mitigations. Further, while some requirements for products are waived during the duration of this EUA, some are not waived and these include parts of 21 CFR 820 (e.g., acceptance activities), and parts of 21 CFR 809.10 (labeling). In your EUA requests, please provide information on how you will mitigate the risks of using or recommending the use of RUO components for example by demonstrating how you will meet these conditions of emergency use authorization for any component needed for your testing that is currently labeled RUO. - The list of previously issued EUAs for in vitro diagnostic products, which includes previously issued EUAs for SARS-CoV-2 molecular diagnostic tests with claims similar to yours, found here: [https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas](https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas). The instructions for use for devices from test kit manufacturers for which an EUA has been issued are made available and can help you understand the data provided from other manufacturers to demonstrate that their SARS-CoV-2 molecular diagnostic test was adequately validated and support issuance of an EUA. - For our recommendations on evaluating the potential impact of emerging and future viral mutations of SARS-CoV-2 on COVID-19 tests, we refer you to the following guidance document: Policy for Evaluating Impact of Viral Mutations on COVID-19 tests. - FAQs on Testing for SARS-CoV-2, that includes frequently asked questions on test development and review, test settings and test uses. - Virtual Town Hall Series, which takes place every Wednesday from 12:15 pm to 1:15 pm. The purpose of the Virtual Town Hall Series is to help answer technical questions about the development and validation of tests for SARS-CoV-2. - Lastly, please be advised that FDA is prioritizing review of all EUA requests for tests, taking into account a variety of factors such as the **public health need for the product and the availability of the product**. See [https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/covid-19-test-development-and-review-faqs-testing-sars-cov-2#priorities](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/covid-19-test-development-and-review-faqs-testing-sars-cov-2#priorities). Based on the information provided in the request, we cannot determine if all of your tests would meet our highest review priorities. Upon issuance of this feedback, this pre-EUA is now closed. We look forward to working with you if you decide to submit an EUA request for this device. ## 2021-10-05_Email from FloodLAMP to FDA re Pre-EUA from: Randy True <randy@floodlamp.bio> to: "Povinelli, Benjamin" <Benjamin.Povinelli@fda.hhs.gov> cc: "St. Pierre, Don J." <don.st.pierre@fda.hhs.gov>, oir-policy <CDRH-OIR-POPS@fda.hhs.gov>, "PEUA210313@docs.fda.gov" <PEUA210313@docs.fda.gov> date: Oct 5, 2021, 11:28 AM subject: Re: RE PEUA210313 Dear Ben, Don, Thank you for your team's reply to our Pre-EUA in June. I'm following up and would like to request an interactive review in order to obtain guidance on a number of issues, including: - sensitivity requirement for serial screening indication, in light of our analytical and clinical sensitivity performance data; - usability study requirements for HCP observed, at-home collection, and DTC; - post authorization asymptomatic and pooling studies; - current prioritization in light of our test characteristics, manufacturing capability, and potential for widespread adoption of our QuickColorTM LAMP and EasyPCRTM open protocol EUAs. Our tests, especially the QuickColorTM LAMP test, have the potential for high impact if authorized. Being open protocol EUA submissions, we are leveraging existing very high volume manufacturing capacity of leading supply partners in the space such as New England Biolabs and LGC Biosearch. The combination of ultra low price point and quick turnaround times enable our tests to materially impact the adoption and effectiveness of testing programs in the U.S. For example, the [Test-to-Stay model](https://www.nytimes.com/2021/09/19/health/coronavirus-school-quarantine-testing.html) to avoid school closures and quarantines is being deployed in many states, but is much more testing resource intensive than standard programs. Authorization of our tests would increase access to the Test-to-Stay model and stretch funding for testing much further. Along with our mobile app and at-home/on-site pcollection kits, FloodLAMP screening programs have distinct advantages over both rapid antigen and central lab PCR programs, with respect to sensitivity and turnaround time. For a Pre-EUA (PEUA201985) we filed last November, we had a lead reviewer assigned (Dun Liang) and had a helpful phone call with him. In January we received a detailed review of that Pre-EUA. This process was very helpful in proceeding on the validation work and preparation of our full EUA submissions. We're hoping for a similar process here. With the added complexity of the asymptomatic indication, pooling, pooled collection and app integration, it would be helpful to obtain guidance on the studies before proceeding. We recently resubmitted EUAs for our EasyPCRTM and QuickColorTM LAMP tests (EUA210581 and EUA210582), for the persons suspected of COVID and serial screening indications, and are seeking priority review. We would like to be engaged with the interactive Pre-EUA process in parallel to the full EUA review. We would include on the call our regulatory consultant and also our scientific advisor, Dr. Anne Wyllie (developer of SalivaDirectTM). In support of some elements of our pre-EUA, we'd like to share the real world success of non-diagnostic surveillance deployments of our QuickColorTM LAMP test. This includes to date: - 5 sites in 3 states; - testing at an EMS leadership conference, youth summer camp, and municipal fire departments; - 11 staff trained to run the test, 5 non-technical staff; - approximately 800 pools run (reactions); - approximately 2,300 people screened; - use of our FloodLAMP Mobile App by 84 users to register on-site and at-home pooled collections; - 3 unknown positives detected and confirmed by reflex diagnostic test; - 26 known positives confirmed; - no known or suspected false negatives. We currently have 2 commercial sites operating, performing routine testing of EMS and municipal staff. Both are in the process of scaling up to screen 1,000+ people at least weekly and expand to support broader community testing including schools and workplaces. Please let me know if you have any questions and if there's anything we can do to facilitate this process. Best Regards, Randy # 2,327 2021-10-04_FloodLAMP Email to Tim Stenzel - 4 pages.md METADATA last updated: 2025-12-18 RT file_name: 2021-10-04_FloodLAMP Email to Tim Stenzel - 4 pages.md file_date: 2021-10-04 title: FloodLAMP Email to Tim Stenzel - 4 pages category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1z3zw4jLv5UmZaSFGxloNeBQmV46WWAa70BbfAbowX7A xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2021-10-04_FloodLAMP%20Email%20to%20Tim%20Stenzel%20-%204%20pages.docx pdf_gdrive_url: https://drive.google.com/file/d/14WazfTa6NVDRdE5TMR7q4Ze8Lb44I7mJ pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2021-10-04_FloodLAMP%20Email%20to%20Tim%20Stenzel%20-%204%20pages.pdf conversion_input_file_type: gdoc conversion: cut and paste license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 2327 words: 1779 notes: summary_short: The FloodLAMP email to FDA CDRH (for Dr. Tim Stenzel) summarizes FloodLAMP’s EUA and pre-EUA history and requests interactive review and prioritization for resubmitted COVID-19 molecular tests (EasyPCR duplex PCR and QuickColor colorimetric LAMP) and a pooled home-collection kit with a mobile app. It highlights reported performance and operational claims (LoDs, turnaround times, high-throughput pooling, low-cost scaling) and describes non-diagnostic surveillance deployments with pooled anterior nares swabs, training approach, and field screening metrics. It also frames an “open protocol”/Right-of-Reference strategy for broader adoption, commercialization, and global tech transfer, and asks for guidance on integrating surveillance programs with EUA-authorized testing and CLIA lab expansion. CONTENT from: Randy True to: CDRH-EUA-Templates date: Oct 4, 2021, 10:53 AM subject: email for Dr. Tim Stenzel Dear CDRH staff, Can you please pass on the following email to Dr. Stenzel? Thank you, Randy True Dear Dr. Stenzel, I'm the founder of FloodLAMP, a public benefit corporation. We spoke briefly on a Town Hall about RORs and open protocol EUAs in December. I'm writing to see if you would be available in the near future to discuss the path forward for our EUA and pre-EUA submissions. Having been inspired by the SalivaDirectTM open EUA, Anne Wyllie is a close advisor and collaborator and has agreed to join the meeting. We have the shared goal of increasing access to high quality testing here in the U.S. and abroad, and see enormous potential for the open protocol EUA approach, both for the remainder of this pandemic and in the near future for pandemic preparedness. On the details of our tests and submissions: - 2 complementary direct tests, duplex PCR and colorimetric LAMP; - both tests utilize same TCEP+heat inactivation; - 45min TAT for LAMP, 90min for PCR; - high throughput of 10K+/day without automation for small team running LAMP test; - LoD 12,500 cp/mL LAMP, 3,000 cp/mL for PCR - comparable to many of the great EUAs; - completed our clinical evaluation with the Stanford CLIA lab; - submitted full EUAs, as open source protocol EUAs in March; - committed to offering an open Right of Reference to our 3 target LAMP primers to help establish commercially available, ready-to-use products, similar to what the CDC achieved with PCR primers; - dry swab collection, up to 4 swabs (preliminary validation at 2X LoD swab spikes with Zeptometrix). Unfortunately, after submitting the EUAs in March, we received a de-prioritization denial of review. We followed up with a pre-EUA (PEUA210313) for pooled home-collection kit and our mobile app in May in an effort to qualify for prioritization, but only received brief comments and closure of the pre-EUA. I recently emailed the FDA staff on our pre-EUA response email, requesting an interactive review. I also recently resubmitted our full EUAs (EUA210581, EUA210582), for the persons suspected of COVID and serial screening indications. We would greatly appreciate your assistance on avoiding the immediate denial of review for these resubmissions. We'd like to request consideration for prioritization as a high impact, rapid molecular test. While trying to get under FDA review, we've deployed our pooled AN swab colorimetric LAMP test under surveillance, and have been able to demonstrate good real world performance including 2,300+ people tested and counting (see info below). These deployments have primarily been with pop-up labs and non-technical staff. We've optimized our test system and wrap-around program components for confirming negatives while efficiently and reliably finding the needle-in-a-haystack positives. Our pool size of 4 is optimal for family or exposure units. The protocol of pooled home collection with drop off at the workplace or school has several significant advantages. First it reduces the burden on the organization's administration because the majority of collection does not need to be done on site (though that option should be available). Also, it offers increased protection from community spread by extending the screening to the family and household members, who if infected would trigger a positive pool result one stage earlier in the transmission chain. At a practical level, a family self-collecting pooled AN swabs and registering that collection on our app is far easier than running 4 antigen tests. It takes 15 seconds instead of 15 minutes, and that convenience is a driver for adoption and durability of participation in a frequent screening program. From the organization's perspective, having direct access to samples and results provides compliance assurance that is usually desirable. If authorized for emergency use by the FDA, our test systems, pooled collection kit and software will have very high public health impact. We've designed these in an integrated manner from the ground up expressly for the use case that is acutely needed in the current phase of the pandemic – distributed assurance screening of interacting populations. With true sample-to-answer turn around times typically 1 to 1.5 hrs and as low as 45min, and high quality molecular performance, our program is ideal for businesses, schools and entire communities seeking to return to normal safely. The test-to-stay model for keeping kids in school with outbreaks, exposure, and high community prevalence requires much higher volumes of testing than currently available. Pooled central lab PCR is not well suited for test-to-stay because of the longer TAT, and antigen programs do not scale well. On-site and near-site rapid molecular is well suited for this important use case. To date, rapid molecular has only been available at great cost, for example to professional sports teams. Our tests have the potential to greatly expand access to rapid molecular screening. We have proved this out with our current surveillance deployments in communities of first responders. In keeping with our public benefit mission, we're commercializing at very low cost, $1-2 per person. This pricing is transformative and is a driver for high impact. We're interested in exploring options with CMS, the CDC, and public health departments to offer programs, both from our company directly and through partners, that pass on this low price/high volume approach to the end organizations being screened. Our current surveillance programs are for municipalities that have extensive experience in COVID-19 testing and are currently running both rapid antigen testing programs and lab-based PCR. The fact that they have chosen to bring up our tests and program, with considerable commitment of human and financial resources, is a testament to the advantages of our offering. We do understand that the current configuration of our colorimetric LAMP test system does not qualify for CLIA waived status. We are keenly interested in exploring options with the FDA, CMS, and state health departments for CLIA labs to have the capability to extend CLIA licenses to enable on-site and near-site screening under high or moderate complexity. The instrument-free nature of the test system, along with the ability to achieve throughputs of 1-2,000 persons screened per technician shift (without automation), opens up possibilities in the COVID testing space that have not been available to date. We would very much appreciate guidance on the progression of our EUAs toward these objectives. In terms of commercialization, we are positioned to quickly scale and deploy millions of tests by the end of year. We have 2M tests of production primers on hand, and another 3M at our supplier, LGC Biosearch. We have a close relationship with NEB who can provide the LAMP and PCR master mixes in large quantities. We're leading a 2 phase project in Colombia in partnership with NEB, to validate both EUA submitted tests and deploy the colorimetric LAMP test in a hub and spoke model to remote processing sites. Again due to the fact that we are fully disclosing the constituent components of our test, rather than keeping them trade secret per industry norm, authorization of our test will have high impact globally due to the international recognition of a U.S. FDA EUA. We experienced this firsthand when during India's surge, we sought to donate test kits but were unable to because we did not have an EUA. Also related to global impact, NEB has not only donated a large value of reactions to projects in Africa, and now our project in Latin America, but also seeks to engage in open tech transfer of reagent manufacturing capability to create local resilience. We intend to do the same by sharing our know-how and pilot production processes with low and middle income countries. These systems and processes have been honed over the last year and facilitate decentralized medium scale production at ultra low cost. In addition to our direct capability to deliver tests, the open source nature of our EUA submissions, like SalivaDirectTM, will position us to achieve high leverage and scale quickly. With the full disclosure of the component chemistry and primer sequences, as with what happened with SalivaDirectTM, we anticipate that the authorization of our colorimetric LAMP test will result in the proliferation of copy-cat tests offered under LDT. Unlike SalivaDirectTM, as a commercial entity, we will offer test kits in addition to designating CLIA labs. It is our goal to bring as many labs as possible under our EUA, thereby improving quality and consistency. We would like to discuss commercialization and designation issues with you in light of the open source protocol EUAs. Another topic that we would like to discuss is the coordination of our surveillance programs with EUA authorized testing by designated CLIA labs. Prioritized review of our QuickColorTM LAMP test can lead to further impact through facilitating expansion of our surveillance programs. Most interested organizations seeking affordable COVID-19 screening first ask us if we have an EUA. We are very clear in all of our communications and consents that our current test is non-diagnostic. We have disabled negative result reporting to participants through our mobile app at the request of CMS. In our surveillance testing, we intend to continue to implement best practices with respect to training and quality assurance, while adapting to the differing aspects of public health rather than medical needs. We have engaged a leading learning experience firm to improve our training materials. Your guidance with respect to these efforts to rapidly expand accessible and affordable surveillance testing, in light of entering the clinical space as well, would be greatly appreciated. Thank you for your attention to these issues related to our EUA submissions, and for your service during the crisis. We look forward to meeting and discussing the next steps. Best Regards, Randy True EUA210581 - FloodLAMP EasyPCRTM COVID-19 Test EUA210582 - FloodLAMP QuickColorTM COVID-19 Test PEUA210313 - FloodLAMP Pooled Swab Collection Kit DTC, FloodLAMP Mobile App, Asymptomatic and Pooled Study Designs **Non-diagnostic surveillance deployments of FloodLAMP QuickColorTM test:** - 5 sites in 3 states; - testing at a EMS leadership conference, youth summer camp, and municipal fire departments; - 11 staff trained to run the test, 5 non-technical staff; - approximately 800 pools run (reactions); - approximately 2,300 people screened; - use of our FloodLAMP Mobile App by 84 users to register on-site and at-home pooled collections; - 3 unknown positives detected and confirmed by reflex diagnostic test; - 26 known positives confirmed; - no known or suspected false negatives. We currently have 2 commercial sites operating, performing routine testing of EMS and municipal staff. Both are in the process of scaling up to screen 1,000+ people at least weekly and expand to support broader community testing including schools and workplaces. **FloodLAMP Biotechnologies, PBC** # 4,365 2021-10-13_FDA Request for Additional Information.md METADATA last updated: 2026-03-05 by BA file_name: 2021-10-13_FDA Request for Additional Information.md file_date: 2021-10-13 title: 2021-10-13_FDA Request for Additional Information category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: pdf xfile_type: NA gfile_url: NA xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2021-10-13_FDA%20Request%20for%20Additional%20Information.NA pdf_gdrive_url: https://drive.google.com/file/d/1fapKSzKCQz3mCpQfZveqabVI-A6ANSr8 pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2021-10-13_FDA%20Request%20for%20Additional%20Information.pdf conversion_input_file_type: pdf conversion: megaparse license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 4365 words: 2948 notes: summary_short: The FDA October 13, 2021 additional information letter for EUA210582 details deficiencies in FloodLAMP’s QuickColor COVID-19 Test validation, including gaps in intended-use population description, unsupported specimen claims, sub-threshold clinical performance, lack of low-viral-load positives, and required updates to inclusivity/variant analysis, cross-reactivity, and interference testing. It also addresses control material expectations and the regulatory risks of relying on RUO-labeled reagents, outlining acceptable alternatives and warning of possible withdrawal or suspension of distribution if adequate data were not provided by the deadline. CONTENT ## EMAIL ATTACHMENT HEADER EMAIL ATTACHMENT ORIGINAL FILE NAME: EUA210582-Additional Information-Final.pdf FLOODLAMP ARCHIVE FILE PATH FOR EMAIL MARKDOWN FILE: regulatory/fl-fda-correspondence/2021-10-13_FloodLAMP FDA Correspondence and 10-14 Meeting Notes.md FLOODLAMP ARCHIVE FILE FOR EMAIL - GDRIVE URL: [2021-10-13_FloodLAMP FDA Correspondence and 10-14 Meeting Notes](https://docs.google.com/document/d/1Vady3wfPmepEyRTHuS4lKEK7rVFtmcdi6eJAzaVOEYY/edit?usp=drive_link) ## EMAIL ATTACHMENT CONTENT October 13, 2021 Dear Mr. True, The U.S. Food and Drug Administration’s (FDA or Agency) Coronavirus Disease 2019 (COVID- 19) testing [guidance](https://www.fda.gov/media/135659/download) describes a policy for laboratories and commercial manufacturers to help accelerate the availability and use of tests they develop in order to achieve more rapid and widespread testing capacity in the United States. With respect to commercial manufacturers of tests intended to detect SARS-CoV-2 RNA, the policy states in part that FDA does not intend to object to their development and distribution where the test has been validated and while the manufacturer is preparing its emergency use authorization (EUA) request, the manufacturer gives notification to FDA, certain labeling information is included in the test reports and instructions for use, and an emergency use authorization (EUA) request is submitted within 15 business days of the notification to FDA. This guidance was most recently updated on May 11, 2020. As outlined in the policy referenced above, you have previously represented to the Agency that your molecular diagnostic test is validated, and notified the Agency that you intend to distribute, a molecular diagnostic test to identify SARS-CoV-2 RNA and submitted a request for an EUA, EUA210582, for that test. You have not provided complete information to demonstrate that the studies performed are adequate to validate your test and support the claimed performance characteristics for your device. Specifically: ### 1. Clinical Evaluation Supporting the Request for Authorization of the FloodLAMP QuickColor COVID-19 Test: As per the FDA’s [Molecular Diagnostic Template](https://www.fda.gov/media/135900/download), validation of a new test should include testing nasopharyngeal (NP) swab specimens from at least 30 positive and 30 negative individuals from the intended use population to support an NP swab or general upper respiratory claim for individuals suspected of COVID-19 by their healthcare providers. To support a general upper respiratory tract (URT) specimen claim it is recommended that the clinical study consists of at least 50% NP swabs and 50% nasal swabs. In your EUA submission you provided results from a clinical validation study that included 40 comparator positive, and 40 comparator negative nasal swab samples. However, the information you provided does not support an NP swab or other common URT specimens claim for the FloodLAMP QuickColor COVID-19 Test for the following reasons: **a. Intended Use Population** Your test is intended for individuals suspected of COVID-19 by their healthcare providers (“‘suspected” individuals). However, you have not provided a description of your study population. Therefore, it is unclear whether your clinical study was performed with samples from the intended use population. Consequently, we cannot determine whether your clinical study is supportive of your intended use. **b. Sample Types:** Per your Intended Use, you are claiming upper respiratory specimens including oropharyngeal (OP), NP, anterior nasal (AN), and mid-turbinate nasal swabs. As per the FDA’s [Molecular Diagnostic Template](https://www.fda.gov/media/135900/download), studies supporting a NP or general upper respiratory specimen claim should be performed with NP swabs as FDA considers this to be the most challenging upper respiratory matrix. However, your clinical study was performed with the AN swab matrix. As such your claim for NP and OP swabs is not currently supported by your clinical evaluation study. **c. Low performance:** You achieved a positive percent agreement (PPA) and a negative percent agreement (NPA) between your test and the comparator tested nasal swab specimens of 90% (36/40) and 100% (40/40), respectively. However, as per the FDA’s [Molecular Diagnostic Template](https://www.fda.gov/media/135900/download), FDA believes a minimum of 95% PPA and NPA is an acceptable clinical performance for a test with an intended use as you proposed for your device. A PPA of 90% is below the performance FDA believes is acceptable. The data obtained in your study suggest clinical performance issues with your device, which may put patients at unreasonable risk of harm due to inaccurate results. False negative test results could have a number of consequences, including leading to additional unnecessary diagnostic evaluations, and could negatively impact the effectiveness of infection control activities by incorrectly assessing the infection status of individuals. **d. Low positive samples:** According to the FDA’s [Molecular Diagnostic Template](https://www.fda.gov/media/135900/download), specimens representing a wide range of viral load including low positive specimens should be included in the clinical evaluation. It is recommended that approximately 25% of the SARS-CoV-2 comparator positive specimens should have Ct values close to the mean Ct value of the comparator at its confirmed LoD concentration (i.e., within 3 Cts of the mean Ct value at the confirmed LoD) to be considered as challenging samples with low viral load. However, your clinical data set indicated that no low positive samples per the comparator test were tested in your clinical evaluation study. Without data generated from testing a sufficient number of low positive samples with low viral load, we cannot appropriately assess the performance of the FloodLAMP QuickColor COVID-19 Test. To address the low performance issue, you should perform a root cause analysis and take the steps necessary to resolve the low PPA for your test. In your response, you should provide evidence that the steps taken addressed the issue and improved the clinical performance. If you identify any new risks in your root cause investigation, you should make sure to provide information to show that those risks have been mitigated. Please note that, should any mitigations require you to alter your device design or testing procedure in any way, additional clinical and analytical validation studies with your final device design may be needed. Once the sensitivity of your test is improved, to support an NP swab or general URT specimens claim for individuals suspected of COVID-19 by their healthcare providers using the FloodLAMP QuickColor COVID-19 Test, please provide clinical validation data from an adequate number of positive and negative samples collected from your intended use population that demonstrate acceptable performance when compared to the results obtained with the comparator test. Please ensure that you provide a clear description of how samples in your clinical study were sourced, including the population characteristics of your study population and the sample numbers for each sample type. For a general URT sample claim as proposed, at least 50% of samples in your clinical study should be NP swab samples. Alternatively, you may adjust your specimen claim to claim AN swabs only if these are easier to source. Please also ensure that your clinical validation data set includes an adequate number of challenging/low viral load specimens (i.e., approximately 25% of the SARS-CoV-2 positive swab specimens, defined as those specimens having Ct values within 3 cycles of the mean Ct value at the comparator’s LoD). Without the additional clinical validation data requested, FDA is unable to determine that the known and potential benefits of your FloodLAMP QuickColor COVID-19 Test outweigh the known and potential risks. ### 2. Inclusivity Study and Variant Analysis You performed an in silico inclusivity analysis for your test in February 27, 2021. This in silico analysis is no longer representative of the circulating strains and variants at this time. Without an updated analysis for your test, we are unable to assess the performance of your device with the currently circulating SARS-CoV-2 strains and variants. Consequently, we are unable to determine that the benefits of your device outweigh the risks. Please provide an updated inclusivity analysis to support the current number and types of variants and provide the information in the table format below. Furthermore, please provide a specific risk assessment related to the performance of your device with all currently circulating variants of interest and variants of concern. Please provide your updated in silico analysis results in the following formats: | Primer | Variant Name | Sequence | Variant Sequence (Mutation Represented by X) | Seq* start | Seq* send | count (Past 30 Days) 30439 U.S. sequences | Frequency (Percent) (Past 30 Days) 30439 U.S. sequences | count (Past 14 Days) 9452 U.S. sequences | Frequency (Percent) (Past 14 Days) 9452 U.S. sequences | |---|---|---|---|---|---|---:|---:|---:|---:| | | | | | | | | | | | | | | | | | | | | | | || *position in the genomic sequence | | Target gene Fwd Primer 1 | Target gene REV Primer | Target gene Probe | |---|---|---|---| | Total primer length (nt) | | | | | Total strains | | | | | 100% match | | | | | 1 mismatch | | | | | 2 mismatches | | | | | 3 mismatches | | | | | >3 mismatches | | | | || ### 3. Cross Reactivity / Microbial Interference You have provided a cross reactivity study that consists of wet testing as well as a comprehensive in silico analysis. However, some organisms with >80% of homology revealed in your in silico analysis in Table 13 of your submission were not tested in your wet testing (e.g. Candida albicans, Pseudomonas aeruginosa, Legionella pneumophila, and Streptococcus pneumoniae). Therefore, additional information on potential cross- reactivity is needed to support your EUA. In your response to this deficiency, please provide your in silico cross-reactivity data in tabular form identifying the pathogen, strain, accession # (e.g., you may pick one that represents the complete genome of the organism), and individual % homology of F/R primers and probes for all targets across organisms evaluated (not only organisms with ≥ 50% of homology). For all organisms that produce homologies to any of the primers and probes of above 80%, microbial interference testing should be provided as described below or provide a rationale for why such testing can be omitted. Microbial interference should be tested in the absence and presence of SARS-CoV-2 at no more than 3x LoD and the presence of the potentially interfering organism at high concentration (i.e., viruses ≥ 10^5 copies, PFU, or TCID50/mL, bacteria and fungi ≥ 10^6 CFU/mL). **Table X.** In silico cross-reactivity testing with the % homology of the FloodLAMP QuickColor COVID-19 Test primers and probes | Organism | GenBank Accession # | Target 1 Primer-F | Target 1 Primer-R | Target 1 Probe | |---|---|---|---|---| | Human coronavirus 229E | | | | | | Human coronavirus OC43 | | | | | | Human coronavirus HKU1 | | | | | | Human coronavirus NL63 | | | | | | SARS-coronavirus | | | | | | MERS-coronavirus | | | | | | Adenovirus (e.g. C1 Ad. 71) | | | | | | Human Metapneumovirus (hMPV) | | | | | | Parainfluenza virus 1-4 | | | | | | Influenza A & B | | | | | | Enterovirus (e.g. EV68) | | | | | | Respiratory syncytial virus | | | | | | Rhinovirus | | | | | | *Chlamydia pneumoniae* | | | | | | *Haemophilus influenzae* | | | | | | *Legionella pneumophila* | | | | | | *Mycobacterium tuberculosis* | | | | | | *Streptococcus pneumoniae* | | | | | | *Streptococcus pyogenes* | | | | | | *Bordetella pertussis* | | | | | | *Mycoplasma pneumoniae* | | | | | | *Pneumocystis jirovecii* (PJP) | | | | | | *Candida albicans* | | | | | | *Pseudomonas aeruginosa* | | | | | | *Staphylococcus epidermis* | | | | | | *Streptococcus salivarius* | | | | | || ### 4. Endogenous Interfering Substances: You have provided an endogenous interfering substances study and stated that the potential interfering substances listed in Table 15 were tested at the indicated concentrations in your interfering substances study. However, the potential interfering substances tested in your study are insufficient to support the interference by commonly used cold remedies and products used in the URT. For a general URT specimen claim, FDA recommends evaluating the additional potentially interfering substances listed below for interference with your test because they can be expected to be commonly found in the URT. In your response, please submit interfering substance study data of the additional substances below to support that the tested substances do not interfere with your test. If new interference is observed, in your response, please provide information to show that any risk to patients has been mitigated. Please refer to the table below for our recommendations on the list of endogenous interfering substances that should be assessed to support your intended use. Each condition should be tested with 3 replicates. | Potential Interfering Substances | Active Ingredients | Concentration | Negative Samples (Detected) | Positive Samples (Detected) | |---|---|---|---|---| | **Respiratory Samples** | | | | | | Nasal allergy spray | Triamcinolone acetonide | | | | | Nasal congestion spray | Oxymetazoline HCl | 15% v/v | | | | Flonase | Fluticasone propionate | | | | | Saline nasal spray | NaCL, Phenylcarbinol, Nemalkonium Chloride | | | | | NeilMed Nasogel | | 1.25% | | | | Cepacol Lozenges (benzocaine/menthol) | Benzocaine | 3 mg/mL | | | | Cough drops | Dextromethorphan HBr | | | | | Robitussin | | | | | | Chloroseptic Sore Throat spray | Phenol, Glycerin | 5% v/v | | | | Emergen-C | Zinc, Magnesium, Riboflavin, Vitamin C | | | | | Zinc (for pyrophosphate based LAMP assays) | Zinc | | | | | Nyquil | Acetaminophen, Doxylamine succinate, Dextromethorphan HBr | | | | | Mucin: bovine submaxillary gland, type I-S | | 2.5 mg/ml | | | | Human Genomic DNA | | 10 ng/µl | | | | Vaseline | Petroleum Jelly | | | | | Nicotine | Nicotine | 0.03 mg/ml | | | | Tobacco | Nicotine, Tar, Carbon Monoxide, Formaldehyde, Ammonia, Hydrogen Cyanide, Arsenic, and DDT | | | | | Alcohol | Ethanol | 5% | | | | White blood cells/Leukocytes | | 1 to 5x10^6 cells/mL | | | | Whole Blood | | 2.5% | | | || ### 5. External Controls: FDA recommends that external positive control material is provided in a concentration that is adequately representative of a real clinical sample and that is challenging enough for the test system to detect potential reagent deterioration. Therefore, it is recommended that the positive control mimics a low positive sample (i.e., ≤ 5x LoD). However, the provided information in your EUA template indicates that you are providing the external positive controls with a concentration of 100,000 copies/mL equivalent to 8x LoD. Your control does not meet the recommended concentration and is therefore not an adequate control for the performance of your test with low positive samples. Please provide the validation data for the control material for FDA review. ### 6. RUO Reagents: In your manufacturing information you indicate that your test ought to be used with recommended Research Use Only (RUO) reagents manufactured by a 3rd party. E.g., LGC Biosearch Technologies/Eurofins Genomics/Integrated DNA Technologies/Sigma LAMP primers, New England Biolabs Colorimetric LAMP Master Mix). As you are aware, RUO products are not subject to 21 CFR Part 820. Because of this, RUO reagents may vary across different manufacturers and lots in ways that may affect the performance of the test. Since continued quality and adequate performance of your test is not assured in this case, you may not recommend as components of an authorized test materials/components that are labeled RUO. Therefore, you have the following options: a) Identify and recommend IVD labeled materials from a third-party manufacturer, or b) Qualify specific lots of the recommended RUO labeled third party manufactured materials for adequate performance with your test and post the lot numbers e.g., on your product website, or c) Bring the materials under your own quality system by supplying them as part of the kit. In this case the control material you purchase is considered a raw material that becomes a component of your kit for which quality and performance you are responsible. Without the information outlined above, we are not able to determine that your test is adequately validated for its intended use. As a result, the performance of your device is unknown which may put patients at unreasonable risk of harm due to inaccurate results. By October 15, 2021, 12 pm (eastern), please reply to this email with information sufficient to demonstrate that the device is adequately validated for its proposed intended use, including an explanation of why the new information is adequate to overcome our concerns about the health risks posed by your device’s unknown clinical and analytical performance as reported in your original submission. If you do not yet have the information requested above, it may take significant time to generate it. You have the option to voluntarily withdraw your EUA request while you collect appropriate validation data and resubmit your request once you have adequately validated your device. If you choose to withdraw, please notify us of that in your response. If you do not respond by October 15, 2021, 12 pm (eastern), or if the information you provide does not demonstrate that your device is adequately validated for its intended use, we may take steps as described in the guidance referenced above, including removing the test from the website listing of notifications, and likely would not be able to determine that the criteria for emergency use authorization have been met. If such steps are taken and we make that determination, we would expect you to suspend distribution of your test, and we may request that you take additional actions to protect the public health as appropriate. # 4,121 2021-10-13_FloodLAMP FDA Correspondence and 10-14 Meeting Notes.md METADATA last updated: 2026-03-05 by BA file_name: 2021-10-13_FloodLAMP FDA Correspondence and 10-14 Meeting Notes.md file_date: 2021-10-13 title: FloodLAMP FDA Correspondence and 10-14 Meeting Notes category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1Vady3wfPmepEyRTHuS4lKEK7rVFtmcdi6eJAzaVOEYY xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2021-10-13_FloodLAMP%20FDA%20Correspondence%20and%2010-14%20Meeting%20Notes.docx pdf_gdrive_url: https://drive.google.com/file/d/1l5xw8MsjT-traijB5RhkrNHsHnK7FhXB pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2021-10-13_FloodLAMP%20FDA%20Correspondence%20and%2010-14%20Meeting%20Notes.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 4121 words: 2051 notes: attachments changed from gdoc version summary_short: The email thread documents FDA’s October 2021 interactive review of FloodLAMP’s EUA210582 QuickColor COVID-19 Test, including an FDA request for additional information, a follow-up offer to meet by Zoom, and FloodLAMP’s written response arguing for an amended serial-screening intended use. It captures key feedback from FDA reviewers about open-protocol EUA/designation concerns, the need for acceptable clinical evidence for serial screening, and constraints around reference panels, followed by FDA’s deprioritization/closure letter and FloodLAMP’s appeal for reconsideration. The final exchange confirms FDA understood the intended-use amendment but deemed FloodLAMP’s clinical study inadequate for screening with serial testing, directing FloodLAMP to the updated molecular EUA template or a pre-EUA supplement for study-design feedback. CONTENT ## 2021-10-13_Email from FDA lead reviewer - Request for Additional Information pdf from: Li, Liang <Liang.Li1@fda.hhs.gov> to: "randy@floodlamp.bio" <randy@floodlamp.bio> cc: "Li, Li (CDRH)" <Li.Li2@fda.hhs.gov>, "Schlottmann, Silke" <Silke.Schlottmann@fda.hhs.gov>, "Roth, Kristian" <Kristian.Roth@fda.hhs.gov>, "EUA210582@docs.fda.gov" <EUA210582@docs.fda.gov>, "Post, Justin" <Justin.Post@fda.hhs.gov> date: Oct 13, 2021, 8:25 AM subject: EUA210582-Additional Information needed signed-by: fda.hhs.gov Dear Mr. True, I’m Liang Li, the lead reviewer for your submission EUA210582 Flood LAMP QuickColor COVID-19 Test. Attached, please find FDA’s letter with the request for additional information for your EUA submission. Best Regards, Liang **Liang Li, Ph.D.** *Scientific Reviewer* General Bacteriology and Antimicrobial Susceptibility Branch Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health U.S. Food and Drug Administration Phone: (240)-402-8107 Liang.Li1@fda.hhs.gov ### Attachment 1 EMAIL ATTACHMENT ORIGINAL FILE NAME: EUA210582-Additional Information-Final.pdf FLOODLAMP ARCHIVE FILE PATH FOR ATTACHMENT MARKDOWN FILE: regulatory/fl-fda-correspondence/2021-10-13_FDA Request for Additional Information.md FLOODLAMP ARCHIVE FILE FOR ATTACHMENT - GDRIVE URL: [2021-10-13_FDA Request for Additional Information.pdf](https://drive.google.com/file/d/1fapKSzKCQz3mCpQfZveqabVI-A6ANSr8) ## 2021-10-13_Email Followup from FDA lead reviewer offering zoom meeting next day from: **Li, Liang** <Liang.Li1@fda.hhs.gov> to: "randy@floodlamp.bio" <randy@floodlamp.bio> cc: "Li, Li (CDRH)" <Li.Li2@fda.hhs.gov>, "Schlottmann, Silke" <Silke.Schlottmann@fda.hhs.gov>, "Roth, Kristian" <Kristian.Roth@fda.hhs.gov>, "Post, Justin" <Justin.Post@fda.hhs.gov>, "EUA210582@docs.fda.gov" <EUA210582@docs.fda.gov> date: Oct 13, 2021, 10:15 AM subject: EUA210582-Setting up a meeting signed-by: fda.hhs.gov Dear Mr. True, Just would like to follow up by email and offer that we could have a quick zoom meeting (30 minutes) tomorrow to discuss about your EUA210582 submission. Please let us know if you are available: 10:30 - 11:00 am EST or 12:30 -1:00 pm EST Please let us know your availability and we will send out a zoom invite. Thanks, Liang ## 2021-10-14_Zoom Meeting Notes for FloodLAMP and FDA FloodLAMP: Randy True (CEO), Anne Wyllie (Advisor) FDA: Liang Li, Silke Schlottmann, Kris Roth - Discussed open protocol EUA approach - Silke asked about designation, said they would not want us to make IFU publicly available - Randy relayed initially we'll deploy like Saliva direct but subsequently FloodLAMP will produce full reagent kit - Randy communicated request to amend intended use to only serial screening (not persons suspected of COVID) - Silke asked about showing data for intended population, Randy replied the clinical samples were remnant with no clinical info - Kris mentioned there are 6 criteria for serial screening amendment, risk-benefit different for POC/at-home vs lab based tests - Kris said we could consider the use bulb pipet to qualify for POC, calibrated pipet is "on edge" for POC - Anne asked if we could validate with blinded ref panel - Silke said ref panel is no longer available - Agreed FloodLAMP would provide written response by Oct 20 ## 2021-10-20_Email from FloodLAMP - Reply to FDA Additional Information Request from: Randy True <randy@floodlamp.bio> to: "Li, Liang" <Liang.Li1@fda.hhs.gov> cc: "Schlottmann, Silke" <Silke.Schlottmann@fda.hhs.gov>, "Roth, Kristian" <Kristian.Roth@fda.hhs.gov>, "EUA210582@docs.fda.gov" <EUA210582@docs.fda.gov> date: Oct 20, 2021, 8:06 AM subject: Re: EUA210582-Additional Information needed mailed-by: floodlamp.bio Dear Liang, Silke, Kris, Thank you for your patience in this response. Attached is a letter addressing your letter last week. We think this resolves some of the points, and we have follow up questions on others. It seems that the central issue is that the current risk-benefit analysis does not allow us to utilize the streamlined screening with serial testing because our submission is for a lab rather than POC test. Did I understand that correctly from our call? I would like to better understand the risk-benefit analysis and see if there is more information or data that we can share to support authorization. I would expect that a high complexity CLIA lab rather than POC setting would be a risk mitigating factor. I understood from our call that a lab rather than POC test reduces the benefit, however I would ask for consideration of the fact that our test being instrument-free with a visual readout does not have the usual scalability problems and high capital investment costs typically associated with molecular lab tests. Is that able to be factored into the risk-benefit analysis/calculation? Kris, you mentioned there are 6 criteria for the serial screening claim. I cannot find those in the FDA statement from March or in the supplemental template. Can you please point me to those or share them? Also attached is the letter to Tim Stenzel that I mentioned on our call. This letter provides more details on the potential for impact of the test and our company's work. SalivaDirect was developed and initially supported by a small but dedicated team of just 4 people. It has been very successful, in the U.S. and globally, due to the fact that it was FDA authorized as an open source protocol EUA test. In the assessment of a leading CEO, it has caused cost compression in the entire industry. As with SalivaDirect, we at FloodLAMP expect an outsized impact due to the open source protocol approach combined with the highly scalable configuration of our colorimetric LAMP test. We have not received any communication back from Dr. Stenzel. If you have any feedback on engaging with CDRH leadership regarding prioritization and the potential for impact of our tests, please let me know. On the submission, it would greatly expedite our ability to add significant screening in the coming winter months if we are granted authorization in the near term. If it's helpful, we are willing to consider conditions of authorization to minimize potential risks. It is much more difficult to make rapid progress on the dissemination and commercialization of this high impact, rapid molecular test and the screening programs it enables, prior to any FDA authorization. Thank you for your constructive feedback and engagement. Please let me know the next step. I am generally available to meet and expect to be able to respond in writing quickly, typically within 24 hours, 2 days max. Best Regards, Randy **3 Attachments** ### Attachment 1 EMAIL ATTACHMENT ORIGINAL FILE NAME: EUA210582 Response 10-20.pdf FLOODLAMP ARCHIVE FILE PATH FOR ATTACHMENT MARKDOWN FILE: regulatory/fl-fda-correspondence/2021-10-20_Response to FDA re QuickColor - EUA210582 10-13.md FLOODLAMP ARCHIVE FILE FOR ATTACHMENT - GDRIVE URL: [2021-10-20_Response to FDA re QuickColor - EUA210582 10-13](https://docs.google.com/document/d/1T1xco5NCe0F8GF84JqVZ0hDyBO0HsG-wbZ-66ezg14I) ### Attachment 2 EMAIL ATTACHMENT ORIGINAL FILE NAME: FloodLAMP Email to Tim Stenzel 10-04-21.pdf FLOODLAMP ARCHIVE FILE PATH FOR ATTACHMENT XLSX FILE: regulatory/fl-fda-correspondence/2021-10-04_FloodLAMP Email to Tim Stenzel - 4 pages FLOODLAMP ARCHIVE FILE FOR ATTACHMENT - GDRIVE URL: [2021-10-04_FloodLAMP Email to Tim Stenzel - 4 pages](https://docs.google.com/document/d/1z3zw4jLv5UmZaSFGxloNeBQmV46WWAa70BbfAbowX7A) ### Attachment 3 EMAIL ATTACHMENT ORIGINAL FILE NAME: Supporting Data - FloodLAMP EasyPCR COVID-19 Test.xlsx FLOODLAMP ARCHIVE FILE PATH FOR ATTACHMENT MARKDOWN FILE: regulatory/fl-fda-submissions/2021-03-22_EUA Sub Supporting Data - FloodLAMP EasyPCR COVID-19 Test.xlsx FLOODLAMP ARCHIVE FILE FOR ATTACHMENT - GDRIVE URL: [2021-03-22_EUA Sub Supporting Data - FloodLAMP EasyPCR COVID-19 Test](https://docs.google.com/spreadsheets/d/1kmo5uzHk0_XLr2USMpalTUCzatXR2brmBFam80uJ_5k) ## 2021-10-21_Email from FDA lead reviewer - Final Decision from: Li, Liang <[Liang.Li1@fda.hhs.gov](mailto:Liang.Li1@fda.hhs.gov)> to: "randy@floodlamp.bio" <randy@floodlamp.bio> cc: "EUA210582@docs.fda.gov" <EUA210582@docs.fda.gov>, "Post, Justin" <Justin.Post@fda.hhs.gov>, "Li, Li (CDRH)" <Li.Li2@fda.hhs.gov>, "St. Pierre, Don J." <don.st.pierre@fda.hhs.gov>, "Roth, Kristian" <Kristian.Roth@fda.hhs.gov>, oir-policy <CDRH-OIR-POPS@fda.hhs.gov>, "Schlottmann, Silke" <Silke.Schlottmann@fda.hhs.gov> date: Oct 21, 2021, 5:57 AM subject: Final Decision for EUA210582 Request – letter attached Dear Mr. True, The additional information you provided does not demonstrate that your device is adequately validated for its intended use. Please see attached letter regarding your EUA request, EUA210582. This is the final decision on your EUA request, and your EUA is now closed. For additional information on FDA's priorities with respect to review of EUA requests for COVID-19 tests, see our website’s [FAQs on Testing for SARS-CoV-2](https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/faqs-testing-sars-cov-2#5f9fefc60116f). Please confirm receipt of this email and attached letter. Thanks, Liang **Liang Li, Ph.D.** *Scientific Reviewer* Dear Mr. True: This letter is in response to your request for an Emergency Use Authorization (EUA) for the Flood LAMP QuickColor COVID-19 Test, intended for the following use(s): the qualitative detection of SARS-CoV-2 in anterior nasal swabs from individuals suspected of COVID-19 by their healthcare provider and from individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection, when tested at least once per week. Given the volume of EUA requests the Agency has received, FDA is prioritizing review of EUA requests for tests, taking into account a variety of factors such as the public health need for the product, availability of the product, extent to which the product would serve a significant unmet medical need, and availability and adequacy of the information concerning the likelihood that the product may be safe and effective in diagnosing the disease/condition. Based on these factors, our review of your submission thus far, and the anticipated resources needed to continue review of your EUA request, FDA has determined that further review of your EUA request is not a priority. FDA therefore declines to issue an EUA for the product at this time. This test has not been authorized to be distributed or used as proposed. FDA is committed to doing everything possible to help combat the COVID-19 outbreak and appreciates your efforts in this matter. Sincerely, \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Donald J. St.Pierre Deputy Director, New Product Evaluation ## 2021-10-28_Email from FloodLAMP - Reply to Final Decision Randy True <randy@floodlamp.bio> to: "Li, Liang" <Liang.Li1@fda.hhs.gov> cc: "EUA210582@docs.fda.gov" <EUA210582@docs.fda.gov>, "Post, Justin" <Justin.Post@fda.hhs.gov>, "Li, Li (CDRH)" <Li.Li2@fda.hhs.gov>, "St. Pierre, Don J." <don.st.pierre@fda.hhs.gov>, "Roth, Kristian" <Kristian.Roth@fda.hhs.gov>, oir-policy <CDRH-OIR-POPS@fda.hhs.gov>, "Schlottmann, Silke" <Silke.Schlottmann@fda.hhs.gov> date: Oct 28, 2021, 8:56 AM subject: Re: Final Decision for EUA210582 Request – letter attached Hi Liang, Yes I did receive the letter and have been consulting with our advisors and regulatory experts on the next step. The letter specifies that our intended use includes persons suspected of COVID-19 by their healthcare provider. We requested to amend our submission to be limited to screening with serial testing. The intention was for that to be a formal amendment, rather than a question. Can you please confirm that the intended use amendment was understood by all prior to the decision to deprioritize and close our submission? If it was not understood, I'd kindly ask the team to reconsider the closure and work with us in an efficient, focused manner to resolve whether our current clinical study is adequate for the screening with serial testing intended use. We believe that our clinical data along with our analytical LoD data shows superior performance to all antigen tests that have been authorized for this intended use. If our current clinical study data is acceptable (completing items 1a,c and d), we will pull out all the stops to quickly complete the other items to demonstrate adequate performance. Updating the inclusivity study, variant analysis, cross reactivity, and interfering substances (items 2, 3, 4) are straightforward and low risk. This streamlined path to authorization, for which it seems the serial testing indication was created, would enable us to rapidly deploy the millions of tests we have ready in the coming months. If our current clinical study is not acceptable, then we would request feedback on the new clinical study design for the general screening intended use. We've included that in a pre-EUA (PEUA210313) but did not receive feedback on the study design. That pre-EUA included several other complex components, so we would be happy to resubmit a focus pre-EUA or send a Qsub to the email box. We have an IRB in place already with an enrichment study design, so we think the feedback here could be very efficient as well. It's my understanding this study design is required as a condition of authorization for the screening with serial testing intended use as well. We will proceed with completing the other items in parallel as performing a new clinical study will take more time. Best Regards, Randy ## 2021-10-29_Email from FDA lead reviewer - Reply regarding Deprioritization from: Li, Liang <Liang.Li1@fda.hhs.gov> to: Randy True <randy@floodlamp.bio> cc: "EUA210582@docs.fda.gov" <EUA210582@docs.fda.gov>, "Post, Justin" <Justin.Post@fda.hhs.gov>, "Li, Li (CDRH)" <Li.Li2@fda.hhs.gov>, "St. Pierre, Don J." <don.st.pierre@fda.hhs.gov>, "Roth, Kristian" <Kristian.Roth@fda.hhs.gov>, oir-policy <CDRH-OIR-POPS@fda.hhs.gov>, "Schlottmann, Silke" <Silke.Schlottmann@fda.hhs.gov> date: Oct 29, 2021, 11:03 AM subject: RE: \[EXTERNAL\] Re: Final Decision for EUA210582 Request – letter attached Hi Mr. True, Thanks for acknowledging the receipt of my email and the DTI letter. We understood the intended use amendment when we sent the Deprioritization Letter. Your current clinical study is not acceptable to support testing a screening population with serial testing. Regarding PEUA210313, it appears it was reviewed and closed on 6/17/21. If you have additional questions regarding an appropriate study design, you can refer to the new molecular EUA template and/or send in an PEUA amendment/supplement for FDA feedback. Thanks, Liang # 1,052 2021-10-20_Response to FDA re QuickColor - EUA210582 10-13.md METADATA last updated: 2025-12-16 BA updated metadata after BA fixed inconsistencies file_name: 2021-10-20_Response to FDA re QuickColor - EUA210582 10-13.md file_date: 2021-10-20 title: Response to FDA re QuickColor - EUA210582 10-13 category: regulatory subcategory: fl-fda-correspondence tags: source_file_type: gdoc xfile_type: docx gfile_url: https://docs.google.com/document/d/1T1xco5NCe0F8GF84JqVZ0hDyBO0HsG-wbZ-66ezg14I xfile_github_download_url: https://raw.githubusercontent.com/FocusOnFoundationsNonprofit/floodlamp-archive/main/regulatory/fl-fda-correspondence/2021-10-20_Response%20to%20FDA%20re%20QuickColor%20-%20EUA210582%2010-13.docx pdf_gdrive_url: https://drive.google.com/file/d/1bE4JczPKTYLpuhhQQNdIak5K6_31yudU pdf_github_url: https://github.com/FocusOnFoundationsNonprofit/floodlamp-archive/blob/main/regulatory/fl-fda-correspondence/2021-10-20_Response%20to%20FDA%20re%20QuickColor%20-%20EUA210582%2010-13.pdf conversion_input_file_type: docx conversion: pandoc license: CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/ tokens: 1052 words: 723 notes: summary_short: The Response to FDA re QuickColor (EUA210582) addresses FDA’s October 13 feedback by proposing updates to the intended use (removing “suspected of COVID” and focusing on serial screening), limiting sample type to nasal swabs only, and defending test performance with Stanford clinical evaluation data plus real-world pooled surveillance results. It also outlines planned updates or requests for FDA guidance on inclusivity/variant analysis, cross-reactivity and interference expectations for LAMP, endogenous interfering substances, external control concentration rationale, and qualification/lot tracking for RUO reagents. CONTENT In response to the letter on October 13 regarding our EUA submission EUA210582: ## 1.a. Intended Use Population We request to ammend our submission to remove the persons suspected of COVID intended use. We propose to retain the screening with serial testing claim, and seek guidance on the appropriate frequency given the test performance data. We also seek guidance on the post authorization clinical study, for which we have submitted a pre-EUA (PEUA210313) and have a IRB approved study protocol (WIRB Tracking Number 20211472). The clinical study in our EUA submissions was performed with de-identified leftover samples selected by the Stanford Clinical Lab. ## 1.b. Sample Types We request to ammend our submission to remove NP and OP specimen types. All of our validation and real world testing to date has been with nasal swabs and we intend to exclusively utilize nasal swabs. ## 1.c Low Performance and 1.d. Low Positive Samples We understand the PPA threshold for the screening with serial testing claim to be 80%. The analytical and clinical performance of the test exceeds that of many other devices with the same intended use. To the best of our knowledge, the performance of our QuickColor LAMP test exceeds all authorized antigen tests. During the Stanford clinical evaluation, a PCR test using the SalivaDirect version of the CDC primers, was also run on the same inactivated samples (data shown in columns J,K, and L in Supporting Data, tab "4 Clinical Evaluation" in EUA210582, also attached). Only 4 samples with Ct values higher than 36 were not detected by the QuickColor LAMP test. This viral load threshold is concordant with the LoD of 12,500 copies/mL, measured with contrived positives created by spiking gamma inactivated cell lysate from BEI into negative clinical matrix. In addition to the Stanford clinical evaluation data, we include real world evidence of good test performance from surveillance our testing programs using the same test protocol and reagents, with pools of up to 4 AN swabs. Through the Sept. 28, this real world data comprises: - approximately 800 pools run (reactions); - approximately 2,300 people screened; - 3 unknown positives detected and confirmed by reflex diagnostic test; - 26 known positives confirmed; - no known or suspected false negatives. We understand that the FDA makes EUA decisions based upon data submitted for specific test systems. In consideration of the potential benefits and known and potential risks of our test, we would like to share that all components of the FloodLAMP QuickColor test, including the exact TCEP/EDTA inactivation solution chemistry, the same primer sequences (all 3 genes or a subset), and the same NEB Colorimetric LAMP Master Mix product (catalog M1804) have been independently validated in several EUA authroized tests and/or submissions (Yu/Rosbash from Brandeis, Kundrod/Richards-Kortum from Rice, Prime Diagnostics, Color Genomic's EUA, Detectachem's EUA). Additionally, a Gates/NEB/IGCEB collaboration has validated a RT-LAMP assay with the same NEB M1804 LAMP Master Mix and 2 of the 3 primers in our test, and published the results of this [large multicenter prospective observational study](https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00381-3/fulltext). They are undergoing the Prequalification process with the WHO. ## 2. Inclusivity Study and Variant Analysis The inclusivity analysis will be updated and presented in the provided format. ## 3. Cross Reactivity / Microbial Interference The provided feedback seems to assume PCR is the amplification technique. With LAMP, near perfect homology across B3, F3, FIP and BIP is necessary to support successful amplification. With the exception of SARS-CoV, which was included in the wet testing, no other organisms showed >80% homology with more than one primer. ## 4. Endogenous Interfering Substances The current set of 5 interfering substances were selected based upon those included in authorized EUA tests. In light of the changes to the sample type and intended use, please advise on any updates to the required list. ## 5. External Controls The concentration of 100,000 copies/mL was selected to be the same as the SalivaDirect(TM) test. Please advise on the suitability of mirroring this EUA. The positive control material was validated with PCR, routinely measuring in the 31-32 Ct range. In our preliminary LoD Study for the EasyPCR(TM) test, the positive control Ct was 31.1 while the contrived positive with gamma inactivated virus at the same 100,000 copies/mL was 31.7. ## 6. RUO Reagents We will qualify specific lots of RUO reagents and post the lot numbers.