FDA Redux? CDRH Policy and EUA Templates for Monkeypox Tests Following Public Health Emergency Declaration Mirror FDA’s COVID-19 Approach

On August 9, 2022, the Secretary of the Department of Health and Human Services (HHS) declared the outbreak of monkeypox virus a public health emergency (see announcement here).  On September 7, 2022, the Secretary of HHS declared that “circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of infection with the monkeypox virus, including in vitro diagnostics that detect and/or diagnose infection with non-variola Orthopoxvirus,” thereby opening the door for submission of requests for emergency use authorization (EUAs) of monkeypox tests.

On the same day, September 7, CDRH published a policy for monkeypox tests.  CDRH has also published templates for EUA requests.

This policy and the EUA templates mirror the approach taken by FDA for COVID-19.  With COVID-19, CDRH was forced to “build the plane while flying it,” in that it had to create the administrative infrastructure and related guidance and templates while simultaneously issuing the first round of EUAs.  This led to delays in releasing a uniform policy and templates for COVID-19, as well as many other problems (see blog post chronicling some of the challenges here).  Now that FDA has worked out an approach to EUAs through COVID-19, it seems the agency has more easily launched a similar framework for monkeypox on the same day as the HHS declaration permitting EUAs for IVDs.

The monkeypox test policy describes how FDA will prioritize review of EUA requests for monkeypox tests, stating that FDA intends to focus on requests for high-throughput tests, tests with home specimen collection, or rapid diagnostic tests, all from experienced developers with high manufacturing capacity.

We note that this policy defines an “experienced developer” more narrowly than the COVID-19 policy.  For monkeypox, an experienced developer is one who has “successfully been issued an EUA” or received approval or clearance for a diagnostic test.  For COVID-19, an experienced developer is one who has only “interacted with FDA through an EUA request or pre-EUA submission,” regardless of success.  This narrower definition of experienced developer may make it more difficult for new companies to break in compared to COVID-19, where many novice companies submitted EUAs.

Additionally, to be subject to prioritized review, test developers are advised to send preliminary information to FDA by email within 30 days after publication of this policy to indicate their intent to submit an EUA request for a monkeypox test.  The preliminary information should include a description of the test technology; manufacturing capacity; test throughput; expected timeline for development, validation, and submission of an EUA request; and any available validation data.  FDA intends to respond to developers by email to indicate whether they intend to prioritize the proposed test.  As with COVID-19, “prioritization” simply means that FDA will review the EUA; if the test is not a priority, FDA will decline to review.

This process for submitting preliminary information to FDA appears to be one area where CDRH is applying a lesson-learned from its approach to COVID-19.  With COVID-19, CDRH has similar criteria for priority review.  However, it was not always clear to developers, prior to submission of an EUA request, whether their test would satisfy the priority criteria.  This led to many developers spending the time and money to validate a test and prepare an EUA request, only for it to be rejected – or languish in regulatory limbo – as a non-priority.  With this new monkeypox policy, it appears test developers will have the opportunity to learn prior to completion of validation whether their test will be granted to priority review.

The policy states that FDA, at this time, does not intend to object to monkeypox tests developed and performed in a high-complexity, CLIA-certified laboratory “to address immediate capacity needs.”  Additionally, if a high-complexity, CLIA-certified laboratory modifies a cleared or authorized monkeypox test, and the modifications do not change the indications for use or change the analyte specific reagents, FDA does not intend to object to implementation of the modification without a new 510(k) or EUA.

The policy also addresses serology tests.  Incorporating some insights gained from its initial policy for COVID-19 serology tests, FDA is approaching monkeypox serology tests in a more restrictive manner.  The policy cautions that serology tests “can provide information that may further our understanding of the disease process,” but cannot diagnose infection and “are not tests of immunity.”  FDA does not intend to object to the use of monkeypox serology tests that are developed and performed by high-complexity, CLIA-certified laboratories that are “part of an entity that conducts research on diseases and is integrated into the direct medical care of the patient” (i.e., academic medical center laboratories).  Such laboratories are not required to submit an EUA, so long as they submit a notification to FDA and include disclaimer statements in test reports (exact language in the policy), which clarify that the test results are not for diagnosis.

Finally, the policy emphasizes the importance of validation data, and states that FDA is providing EUA templates.  While the policy notes that “recommendations in the templates are voluntary,” we have learned from experience with COVID-19 EUAs that CDRH will likely adhere closely to the template guidelines and will be resistant to deviate from the FDA-recommended approach to validation.  Compared to the COVID-19 templates, the monkeypox EUA template appears to include more detail about what is expected, and includes many check-the-box responses from lists of options (e.g., for interfering substances) rather than open-ended prompts in which developers can draft descriptive summaries.  This format may lead to more uniformity in initial EUA submissions, which may cut down on interactive requests from EUA reviewers for clarifying information.

As we have learned from COVID-19, CDRH’s monkeypox policy and EUA templates will likely evolve over time as CDRH begins to receive EUAs and learns more about the unique validation issues that may arise with monkeypox tests.  That said, monkeypox test developers are starting with much more guidance from CDRH compared to COVID-19, which will hopefully lead to submission of EUAs that are more likely to meet CDRH’s expectations, and in turn, lead to faster roll-out of high-quality tests.