COVID Weekly Recap: A significant change to FDA’s authority over laboratory tests. New guidance on FDA inspections. FDA clarity on diagnostic and face mask policies.


Top stories: HHS unveils new approach for FDA’s oversight of laboratory developed tests. FDA releases details about its facility inspections during COVID. Congress wants more information about HHS’ LDT policy change. FDA authorizes novel saliva-based COVID-19 diagnostic. Diagnostics lab meeting highlights continued confusion about “non-laboratory” and “at-home” testing. Legal experts offer recommendations for FDA COVID-19 response.

Welcome to our COVID Weekly Recap, AgencyIQ’s weekly wrap-up of the top regulatory developments related to COVID-19. The following analysis was available to AgencyIQ subscribers earlier this week as part of our daily regulatory intelligence briefings, as well as dozens of other pieces of analysis. Contact us to find out how you can become a subscriber to AgencyIQ.

HHS scales back FDA’s regulatory authority over laboratory developed test (LDTs) during the pandemic

By Laura DiAngelo, MPH

August 19, 2020


In a notice published on August 19, the Department of Health and Human Services (HHS) issued a notice that the FDA “will not require” laboratory-developed tests to submit premarket submissions, including Emergency Use Authorizations (EUAs).

  • How Things Work Now: Laboratory developed tests (LDTs) are diagnostics that are developed by clinical laboratories, rather than manufacturers. They are historically intended to be used within a single laboratory or health system and are generally not required to gain authorization for market access from the FDA, instead falling under the regulatory authority of the Centers for Medicare and Medicaid Services (CMS). However, during times of increased public health risk—including the COVID-19 pandemic—the FDA has asserted its regulatory authority over these products.
  • What’s New: A new notice published by HHS states that the FDA “will not require” any LDT to submit a premarket submission. This includes both regular process device submissions and Emergency Use Authorizations (EUA), which are the type of application used to authorize products during a public health emergency.
  • Impact: While the FDA does not require pre-market submissions for LDTs in non-emergent situations, the notice represents a significant change in policy for the COVID-19 public health emergency. Clinical laboratories have had some flexibility in submitting EUAs for certain diagnostics during the public health emergency—for example, the FDA does not require certain laboratories to submit an EUA for serological tests—but the agency has typically directed clinical laboratories to submit EUAs for molecular and antigen tests during the pandemic.
  • Our full analysis of this development is available to AgencyIQ subscribers. This is just the executive summary.


Foreign facilities could slow approvals during COVID, FDA says in new guidance

By Alexander Gaffney, MS, RAC

August 19, 2020


New guidance published this week by the FDA explains the processes through which the agency plans to oversee drug quality, manufacturing and inspections in the midst of the COVID-19 pandemic.

  • How things work now: In March 2020, the FDA announcedthat it would postpone most foreign and domestic inspections due to the pandemic. Some inspections would be conducted on a case-by-case basis if they were found to be critical, but most would not. Then, on July 10, 2020, the FDA announced that it planned to soon resume inspections of domestic manufacturing facilities. The agency said it planned to employ a risk-based framework (the COVID-19 Advisory Rating System) that takes national and state data into account when scheduling a planned inspection.
  • What’s new: Now the FDA has released a new final guidance document explaining the way in which it plans to conduct inspections of domestic and foreign facilities. FDA notes that for pre-approval inspections, it intends to “continue using other tools and approaches where possible. The guidance also makes clear that foreign inspections are the ones most likely to see delays under its current guidelines, especially if they are not deemed “mission critical” (defined in the guidance). Sponsors also “will not automatically receive a complete response letter if FDA cannot conduct an inspection,” but will instead be assessed against a “totality of the information” assessment.
  • What’s next: FDA’s guidance makes clear the risks ahead for some companies as they seek approval for new drugs. Historically, having foreign-based manufacturing facilities could be an asset due to lower tax rates, lower labor costs of production and greater advanced notice of FDA inspections. Now, the opposite may be true: Foreign facilities could be a liability if they prevent a company from obtaining FDA approval.
  • Our full analysis of this development is available to AgencyIQ subscribers. This is just the executive summary.

Congress calls for more information about HHS change on FDA diagnostic policy

By Laura DiAngelo, MPH

August 20, 2020


House Committee on Energy and Commerce (E&C) Chairman Frank Pallone is calling for Alex Azar, the Secretary of the Department of Health and Human Services (HHS), to brief the Committee on a quietly-issued policy from August 19 that exempted certain diagnostics from FDA review.

  • The HHS announcement statedthat the FDA “will not require” premarket review for a certain kind of in vitro diagnostic (IVD) called laboratory developed tests (LDTs). This applies to all types of premarket submissions, including authorizations for emergency use during the COVID-19 pandemic.
  • Pallone’s reaction: “This week’s announcement from HHS that lab developed COVID-19 tests no longer need review by FDA prior to coming to market is deeply concerning and suggests that the Trump Administration is once again interfering with FDA’s regulation of medical products. Given the importance of testing for our ability to control the spread of COVID-19 and the Administration’s past blunders with serological tests, I do not believe that now is the time to reduce oversight of COVID-19 tests.”
  • Laboratory Developed Tests (LDTs) have traditionally operated under enforcement discretion from the FDA. This means that while the agency has maintained that LDTs are medical devices, it has declined to exercise its regulatory authority over these products due to their limited distribution and low risk profile. Historically, LDTs have been developed and intended for use within a single clinical laboratory or health systems, which means that they often don’t enter into interstate commerce.
  • In high-risk situations, like a pandemic, the FDA has asserted authority over LDTs. As with the Zika virus outbreak in 2016, the FDA has been requiring emergency use authorization (EUA) submissions for LDTs during the COVID-19 pandemic. According to the agency, the public health situation warrants heightened FDA scrutiny of the tests. However, the FDA has not required pre-market submissions for LDTs since the mid-1970s when the device regulations were established.
  • The history of FDA’s oversight of LDTs is long and complex. AgencyIQ has an extensive explainer on the topic available to our subscribers.

FDA authorizes novel saliva-based COVID-19 diagnostic

By Laura DiAngelo, MPH

August 17, 2020


The FDA on Saturday authorized a new and unique diagnostic that uses saliva as a sample. This comes less than a week after Center for Device and Radiological Health (CDRH) officials indicated that their thinking on saliva as a matrix was still undefined.

  • SalivaDirect is a real-time reverse transcription polymerase chain reaction (rRT-PCR) test for SARS-CoV2 developed by the Yale School of Public Health. The test garnered some public attention from a June announcement that its efficacy would be studied in players in the National Basketball Association (NBA). That research, on identifying its ability to identify cases in asymptomatic individuals, is ongoing.
  • The test is the fifth to be authorized for use with saliva, but the first to be authorized with saliva alone and with reduced reliance on regular diagnostic accessories.
  • Reduced supply chain pressures have been a significant priority for the FDA recently. CDRH diagnostics chief Tim Stenzel asserted in a recent town hall meeting that diagnostics that don’t rely on products in shortage—like reagents or viral transport media—would see faster review and increased attention from the agency.
  • Unlike most other diagnostics for COVID-19,SalivaDirect does not require the use of a nasopharyngeal swab, which are in significant shortage due to the global pandemic. In addition, the test does not require the saliva sample to be collected in any specific type of transport container. Any sterile container will do. Additionally, SalivaDirect’s testing methodology was authorized for use with “different combinations of commonly used reagents and instruments,” meaning that the test can be run even in areas experiencing shortage or scarcity.
  • “The data on saliva is evolving,”FDA officials said last week. A key issue has been the complexity of saliva as a matrix, as well as its stability. CDRH diagnostic chief Tim Stenzel had noted that his office had “found saliva to be an incredibly unpredictable and challenging substrate” for diagnostics. “We’ve seen and we’ve denied some saliva submissions because of performance,” he added.
  • Performance in saliva-based tests appears to be variable, which is acknowledged in the FDA’s press announcementon SalivaDirect. FDA’s thinking on this matrix will continue to evolve as more data becomes available.
  • What’s next. This diagnostic will be made available with an “open source” protocol to laboratories, which means that tests can be assembled from commercially available components rather than purchased directly from Yale.

Diagnostics lab meeting highlights continued confusion about “non-laboratory” and “at-home” testing

By Laura DiAngelo, MPH

August 19, 2020


At the twenty second weekly town hall on COVID-19 diagnostics, Center for Device and Radiological Health (CDRH) in vitro diagnostic (IVD) leads Tim Stenzel and Toby Lowe answered industry questions about the ongoing review backlog of diagnostic test, what “non-laboratory testing” actually means, and what their office is prioritizing during the pandemic.

  • “Non-laboratory” testing is simply CDRH’s new terminology for at-home testing, according to Lowe. “We got some questions last week” about the change in terminology, she said, and “we may have caused some more confusions, so we’re working to clarify that.” Non-laboratory testing does not mean testing that does not involve a laboratory with a certificate under the Clinical Laboratory Improvement Amendments (CLIA), but “the non-lab [EUA] template is really for self-tests,” which is typically called home use, where there is “no need to install an instrument.”
  • The agency updated the terminology in deference to public desire to test individuals for COVID-19 in less-traditional areas, like airports or schools. “Someone at a school or a sporting event, for example, could hand an individual a test,” she clarified, but that individual wouldn’t be involved in collecting the sample or running the test.
  • Speaking of CLIA, Lowe noted that their office had been in conversation with CMS about their expectations for CLIA certificates in schools. “CMS would expect a school to have a certificate of waiver to provide testing,” said Lowe, but noted that CMS has been considering CLIA certificates of waiver on a school district level, rather than individually.
  • The review backlog is still a concern for many, although Stenzel and Lowe provided some details about the way that they triage tests for priority review. “Anything that’s point-of-care” will be moved to the top of the queue, Stenzel said. Point-of-care tests, notably, can’t use the agency’s “notification pathway,” which allows a test to be distributed after validation but before EUA authorization, “so those are the ones in greatest need.”
  • FDA review capacity is still a significant issue according to Stenzel: “Our reviewers, obviously, their desks and plates are very full” with submissions.
  • Stenzel called for more point-of-care diagnostic tests, stating at the top of the call that he wanted to “basically encourage the further development of point-of-care tests.” There are only three direct antigen tests that have been authorized by the agency so far, although the antigen test EUA template was published in May“We look forward to more submissions and more authorizations” of these diagnostics, he said.

Legal experts offer recommendations for FDA COVID-19 response

By Charles Friend

August 19, 2020


On Tuesday, legal experts from various universities and other organizations released a report assessing government responses to COVID-19 and offering recommendations on how government leaders can better respond to COVID-19 and future pandemics. The report recommendations for the FDA, including:

  • Communication regarding EUAs: The report states that the FDA and other government leaders should clearly communicate and reiterate that emergency use authorizations (EUA) are not approvals and that they do not include determinations that the FDA has deemed a product to be safe and effective for its intended purpose. This need for reiteration is attributed to mistaken media reports of products authorized under EUA being approved.
  • Transparency on decision-making: The report states that the FDA should be as transparent as possible and product authorization decisions on based on best available public health and scientific evidence, as this will aid in promulgating public trust and understanding about the agency’s actions in response to the COVID crisis. The report also recommends that Congress and the FDA should consider mandating additional transparency measures such as requiring the FDA to proactively release detailed information about the reasoning behind its EUA decisions.
  • FDA should issue EUAs judiciouslyas some EUAs are not appropriate for public health. The report suggests that the FDA should also actively and carefully review EUAs already issued and revoke them when necessary. Results of said reviews, along with summary analysis and data, should be made public as soon as they are completed. FDA should consider routinely requiring patient registries for products that are issued EUAs to help gather information about patient outcomes and any disparities in access as well as conduct post-market reviews of said products as often as weekly.
  • FDA should decline to authorize EUAs for COVID-19 vaccines. If the agency does consider issuing an EUA for a COVID vaccine, it should be for voluntary use amongst the populations at highest risk from the disease. The report suggests issuance of an EUA for a vaccine across the entire population may cause unnecessary risks to healthy individuals and that Congress consider appropriate legal revisions to the FDA’s authority to issue EUAs under Section 564 of the Food, Drug, and Cosmetic Act.
  • State Governments: The report recommends that state health officials and agencies also join the FDA in communicating the difference between EUAs and FDA approval, as well discouraging off-label use of products to treat COVID-19 unless strong evidence supports their use.

FDA Face Mask meeting highlights ongoing confusion among developers, health systems

By Laura DiAngelo, MPH

August 18, 2020


Representatives from FDA’s Center for Device and Radiological Health (CDRH), as well as CDC offices, held a call with industry on August 18 to answer questions about the new Umbrella EUA for surgical face masks. However, questions raised by industry representatives during the webinar indicate that there is still significant confusion about the FDA’s policies for both developers and the health systems who need to purchase Personal Protective Equipment (PPE).

  • A quick refresher: Surgical masks are a Class II device intended to cover a user’s nose and mouth provide a physical barrier to fluids and particulate materials, but are not appropriate for use in aerosolizing procedures. Face masks are a Class I 510(k)-exempt device that cover a user’s nose and mouth but may not meet fluid barrier or filtration efficiency levels. They are intended for use by the general public. Face filtering respirators (FFR), like N95s, are disposable half-face non-powered air-purifying particulate respirators that reduce exposures to pathogenic biological airborne particulates.
  • In May the FDA issued a policy of enforcement discretionallowing sponsors of certain surgical masks to market products without a 510(k) submission or certain post-market requirements (e.g., registration and listing).
  • The new Umbrella EUA, issued on August 4th, allows developers to submit their surgical mask for authorization by the agency for market access.
  • PPE developers and providers have expressed significant confusion about the pathways to market, their appropriate uses and post-market requirement differences between the EUA and enforcement discretion policy.
  • So, what isthe difference between the pathways? Medical claims. As CDRH’s Cynthia Chang clarified during today’s call: “Under the enforcement policy, you are not to make any” claims related to particle size filtration. Under the EUA, certain claims related to the testing and evaluation of the mask can be made, based on the FDA’s review of the evidence submitted. Fully cleared face masks must meet additional evidentiary standards, such as biocompatibility testing on the finished product rather than the raw materials.
  • Post-market policies are also different. Masks marketed under the enforcement discretion are exempt from regular post-market medical device requirements like the quality system regulations (QSR) and registration and listing. Surgical masks marketed under the EUA are also exempt from the QSR, though it’s not yet clear if they’re also exempt from the registration and listing requirements. While it’s not specifically spelled out in the EUA, “that doesn’t mean that it isn’t waived, it’s just not annotated within the EUA” noted CDRH officials.
  • Registration and consternation. Health system representatives were also confused about the waiving of registration and listing requirements. CDRH officials explained that masks marketed under the enforcement discretion could voluntarily register and list, but that the FDA’s databases will flag these surgical masks as marketed under an “enforcement discretion” tag.
  • Also of concern:a transition plan. “After the pandemic ends… there’s going to need to be a transition plan,” said CDRH’s Benita Asher. “And there’s some efforts on what that transition [plan] is going to be.” However, there aren’t yet any details on such a plan. The emergency enforcement discretion guidance documents clearly states that these policies are in effect “only for the duration of the public health emergency related to COVID-19 declared by the Secretary of Health and Human Services (HHS)” under section 319 of the Public Health Services Act. Unlike the authority for the FDA to issue EUAs, this emergency declaration must be renewed regularly.

Data points: 

966: The number of foreign drug facility inspections conducted in 2019. The FDA today published a new guidance document indicating that foreign facilities may not be able to be inspected during COVID, which could delay or prevent approvals


6 months: The immunization duration endpoint being sought by Chinese regulators. Like the US FDA, China’s National Medical Products Administration is also seeking a 50% efficacy endpoint.


“You have to decide where your red line is, and that’s my red line. I would feel obligated (to resign) because in doing so, I would indicate to the American public that there’s something wrong.”


CBER’s Peter Marks, in an interview with Reuters, describing how he would resign if he felt that he was under political pressure to approve a vaccine. Marks apparently made the same promise to resign on a call with government officials earlier this month.

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