On November 15, HHS announced that it was withdrawing the prior administration’s policy that prevented FDA from requiring premarket review of laboratory developed tests (LDTs) without notice and comment rule making. See the prior post on this policy here. This statement comes at least six months after the policy was removed from the HHS website without any public notice (a copy of the prior policy is available here for reference). Although we were surprised to learn that the prior policy had vanished from the HHS website at least six months ago, we were not surprised that the Biden Administration had reversed the prior policy.
The announcement is light on details, simply stating that the policy was withdrawn and that “HHS no longer has a policy on LDTs that is separate from FDA’s longstanding approach in this area.” This suggests that the LDT status quo ante has been restored. As our readers know, our firm has long been critical of this status quo (see our prior posts here, here, here, here, and here, just to name a few).
The rationale for withdrawal appears to have been that the prior policy allowed LDTs with “poor performance” to enter the market without prior FDA review. This rationale is weak, at best. In the past, when pushed to provide examples, FDA has struggled to provide examples or evidence of poorly performing LDTs. Nevertheless, FDA has said that in its review of 125 EUAs applications for COVID-19 LDTs, 82 contained design or validation issues that the agency believed needed to be resolved before an EUA could be authorized.[1] Further, the prior HHS policy was supported by a legal analysis concluding that FDA could regulate LDTs only after notice and comment rulemaking. (legal memo available here). It is unclear whether HHS revised this analysis prior to reversing the August 2020 policy.
The HHS announcement was accompanied by a corresponding statement from FDA as to how this change will affect its review of LDTs. In relevant part, the FDA announcement states, “the FDA now generally expects newly offered COVID-19 tests, including LDTs, to have an EUA or traditional marketing authorization such as a granted De Novo or cleared 510(k), prior to clinical use.” (emphasis added). The announcement goes on to say that the notification pathway available for certain tests intended for use in CLIA high-complexity laboratories had led to “some poorly performing testing being offered prior to FDA review.” See our prior post on the notification pathway here. Thus, the FDA states that it is “ending those notification policies going forward” and revised its COVID testing guidance, available here, and added new Q&As to its FAQs for SARS-CoV-2 Testing.
No doubt many questions will be raised regarding the rationale, legality, and impact of HHS and FDA’s actions, but two threshold questions for clinical laboratories are: what does this mean for COVID-19 LDTs they are currently offering or may seek to offer going forward?; and what impact will HHS’ removal of constraints on FDA’s oversight of LDTs mean for laboratories performing non-COVID LDTs? We discuss each of these key questions below.
What do these announcements mean for Labs performing COVID-19 LDTs?
If the lab has obtained an EUA for its COVID-19 LDT, which many did because of the PREP Act protections afforded by the authorization, there is nothing more for the lab to do because the only change introduced by the policy is the need for an EUA. Certain modifications to the LDT could, however, require the submission of an amendment to the EUA.
If a lab is performing a COVID-19 LDT that is not subject to an authorized or pending EUA and that is not included in one of FDA’s notification lists (see our discussion of the notification list below), the Guidance states that the laboratory should either submit an EUA within 60 calendar days of November 15, 2021 (i.e., Friday, January 14, 2022) or cease marketing on or before this date. FDA notes that it plans to review all LDT EUA submissions. If FDA declines to issue an EUA after such review, a lab will need to cease offering the test within 15 calendar days of being notified by FDA.
FDA’s decision to again require EUAs for COVID-19 LDTs raises a serious question of capacity. OHT7 is already unable to perform its normal functions, such as reviewing pre-submissions for non-COVID diagnostic devices. It is unclear why FDA would choose to devote resources to reviewing COVID-19 LDTs that are on the market instead of providing feedback to companies that have new types of diagnostic devices or reviewing IVD submissions in a timely manner.
It is also unclear why FDA would take steps that could reduce the availability of COVID-19 testing. Even if the Agency believes that there is sufficient access nationwide, LDTs have played an important role in filling local needs. The sudden loss of access to a laboratory is bound to be disruptive to institutions, physicians, patients, employers, and schools, among others, who have relied upon testing at that facility.
What does the withdrawal of the notification pathway mean for COVID-19 tests?
If a lab is performing a COVID-19 LDT that was added to the notification list and for which an EUA submission is pending, then the consequences depend on whether the EUA was submitted before or after February 1, 2021. If the EUA was submitted after February 1, 2021, there is nothing for the lab to do as FDA does not intend to object to offering of such tests while the EUA is under review. If the EUA was submitted prior to February 1, 2021, a lab must notify FDA on or before December 30, 2021, as described in the Guidance, letting FDA know that:
- the developer wants FDA to continue reviewing its EUA request;
- the EUA request is for the current version of the test; and
- either the developer does not have additional data to add, or the developer submits updated information to FDA within that same timeframe including, if not previously provided, validation with clinical specimens using an appropriate comparator.
The Guidance indicates that if a lab needs to submit additional information under item 3, it should also explain how the test falls within the test priorities for the “current stage of the public health emergency and the tests for which FDA will be prioritizing review.”
As many on the notification list know, FDA review of certain EUAs has been slow, with many ultimately being “deprioritized.” FDA’s revised guidance states that, for tests on the notification list, “FDA intends to notify test developers by email if FDA declines to issue or otherwise decides not to authorize a test for any reason,” (emphasis added) and the test manufacturer will be required to cease marketing within 15 calendar days of such declination. The language “for any reason” raises significant questions, e.g., what if FDA declines to review an EUA because it is deprioritized? Will these tests need to be taken off the market? There is a difference, after all, between FDA determining that a test may not perform well and deciding that a test is low priority. It is unclear how the deprioritization process affects the new call for EUAs. The lack of clarity here underscores, once again, the uncertainty surrounding various aspects of the LDT process.
What do these announcements mean for non-COVID LDTs?
FDA’s press release and guidance give no hint as to the FDA’s intentions with respect to the hundreds of thousands of LDTs being performed for conditions other than COVID-19. As we noted above, HHS appears to have restored the status quo ante for LDTs – in other words, a general policy of enforcement discretion with exceptions (e.g., for companion diagnostics, direct-to-consumer tests). But certain actions taken by HHS during the last administration arguably create “facts on the ground” that may have implications for FDA’s next steps. For example, the prior HHS policy revoked all LDT guidance documents. The latest notice makes no mention of the status of such guidance documents. Furthermore, as noted above, the previous General Counsel prepared a memorandum for then FDA Commissioner Hahn that called into question the scope of FDA’s authority over LDTs and unequivocally concluded that FDA is legally required to engage in rulemaking before regulating LDTs. How, if at all, will the current administration respond to the legal arguments laid out in this memorandum?
HHS’ policy reversal and FDA’s guidance updates raise numerous practical questions that laboratories offering, or contemplating whether to offer, COVID-19 LDTs are now scrambling to address. These laboratories must decide whether to withdraw, submit, or update their LDTs, taking into account whether additional data will be needed to supplement their EUAs and whether their tests are likely to be authorized given FDA’s new test priorities. The impact of FDA’s resumption of COVID-19 LDT regulation on laboratories and the public remains to be seen.
[1] COVID-19 Tests Highlight Need for Strengthened FDA Oversight and Diagnostics Legislation, PEW Charitable Trusts (May 19, 2021), https://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2021/05/covid-19-tests-highlight-need-for-strengthened-fda-oversight-and-diagnostics-legislation [https://ift.tt/317swcw].