FDA’s Third Party Review Program is Ready for the Next Pandemic, not the LDT Final Rule

FDA recently released 510(k) Third Party Review Program and Third Party Emergency Use Authorization (EUA) Review which finalizes the draft guidance of the same title issued in December 2023.  We previously discussed the Third Party Review Program in a blog post last year when FDA mentioned its expansion as part of its plan to address the resource gap for review of laboratory developed tests (LDTs) under the LDT final rule.  The final guidance appears not to make any meaningful changes that are actually likely to support or incentivize its increased utilization, which is disappointing, although not unsurprising.

The final guidance looks much like the prior draft and is intended to satisfy FDA’s obligation to issue final guidance on consultations with persons under section 565(i) of the FD&C Act and also to provide clarity on use of third party emergency use authorization (EUA) review. The guidance also addresses FDA’s obligation to provide considerations on third party compensation, information sharing, and conflicts of interest.

Discussion of the early interaction (EI) consult policy and details of a third party review memo, which were previously described on the website, are now included within the guidance.  The guidance also clarifies the criteria for re-recognition of third party 510(k) review organizations and the suspension or withdrawal of recognition and discusses how FDA will audit the Third Party 510(k) Review Program as part of ongoing audit plans under the Quality Management and Organizational Excellence (QMOE) Program which are all Medical Device User Fee Amendments (MDUFA) IV and V commitments.

The Third Party Review Program for EUAs looks different compared to the Third Party Review Program for 510(k)s.  Whereas applicants interact directly with third party 510(k) review organizations, for EUAs, FDA will generally contract with the third party review organization and will send submissions it receives to the third party for review.  FDA may, in certain emergency situations, determine that in vitro diagnostic device EUAs may be submitted directly to the third party EUA review organization.  EUAs may only be submitted following a relevant declaration under section 564 of the FD&C Act justifying emergency use authorization of a product and, because such emergencies are not known, FDA will identify and contract with third parties based on expertise and skills needed in anticipation of or at the time of an emergency declaration.

While FDA may utilize third parties to review EUAs to lessen the burden on internal FDA resources during a public health emergency, this might not offer much in the way of advantage or assistance to a new Sponsors or FDA as compared to other programs put in place during the recent COVID-19 public health emergency.  In April 2020, the National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx) to speed innovation in the development, regulatory authorization, commercialization, and implementation of EUA COVID-19 testing.  Sponsors who applied to the program were put through a highly competitive, rapid three-phase selection process to identify the best candidates for at-home (over-the-counter) or point-of-care in vitro diagnostic COVID-19 tests. All proposals underwent an initial technical, clinical, commercial, and regulatory review before receiving funding and in-kind service support.  Sponsors were provided a RADx interdisciplinary consulting team, including a regulatory consultant who worked closely with the FDA to ensure Sponsors were meeting the Agency’s expectations.  This was especially advantageous to Sponsors who had not previously taken a product through the FDA market authorization process.  The purpose of the RADx project team was to help Sponsors quickly accelerate past development hurdles, provide them with close partnerships with other regulatory agencies (e.g., FDA), and to generate data in a format that would streamline FDA’s review. The program led to 18 over-the-counter COVID-19 EUAs, 2 multiplex COVID/Flu EUAs, and supported De Novo and 510(k) submissions for over-the-counter COVID-19 and multiplex COVID/Flu assays.  A similar support program, instead of or in combination with third party review, could be instrumental in assisting manufacturers of LDTs to validate tests and de-risk regulatory authorizations.

As we have previously discussed, the Third Party 510(k) Review Program is not widely used.  We noted in last year’s post that in Fiscal Years 2018 – 2022, fewer than 100 510(k)s went through the Third Party Review Program annually. Fiscal Year 2023 showed similar performance.  The Agency has reportedly been trying to improve the program, as we discussed in 2018 and 2020.  However, the new final guidance does not appear to do anything to enhance the program or change it in a way that would be likely to lead to increased use by industry.  This appears to be yet another failed attempt to remediate a program that has long underperformed its potential.  As the Agency looks towards reviews of LDTs, a program similar to RADx may provide a better approach to assist manufactures and FDA in meeting the challenges to allow for review and authorization of LDTs.