FDA Requires EUA SARS-CoV-2 Test Developers to Account for Viral Mutations

New rules from the U.S. Food and Drug Administration (FDA) require producers of SARS-CoV-2 tests that have received Emergency Use Authorization (EUA) to take additional steps to account for viral variants. Specifically, FDA is requiring test makers to update test labeling and evaluate the impact of variants on test performance. Here is a quick briefing on the new rules.

FDA Authority to Revise EUA Conditions of Authorization

The legislation giving FDA authority to issue EUA to clear diagnostic tests to detect SARS-CoV-2, Section 564 of the Federal Food, Drug, and Cosmetic Act, also allows the agency to establish additional Conditions of Authorization for those products. On Sept. 23, FDA issued a letter setting forth new Conditions of Authorization requiring test makers to account for new genetic variants of the virus to maintain the test’s EUA status.

Which Tests the Revisions Affect

The new Conditions of Authorization apply to certain molecular, antigen and serology tests that have already received EUA for SARS-CoV-2 diagnosis and detection. They do not apply to EUAs for authorized IL-6 assays, standalone specimen collection devices, or standalone home collection kits. Nor do they apply to EUAs that include substantially equivalent viral mutation Conditions of Authorization.

The New EUA Requirements

The revisions require test makers to take three steps to account for genetic variants:

1. Updated Labeling Requirements

You must revise your authorized labeling and submit the updated labeling to FDA as a supplement to the EUA within three months. The letter includes a pair of Appendices setting forth detailed instructions. Appendix A requires test makers to add the following specific limitation language to their IFU/Laboratory SOP and/or EUA Summary:

Appendix B of the letter sets out limitation language that must be added to the Fact Sheet for Healthcare Providers, depending on the type of test:

Molecular and Antigen Tests: At the end of the section of the Fact Sheet titled “What does it mean if the specimen tests negative for the virus that causes COVID-19?,” you must add the following paragraph:

Serology Tests: The following paragraph must be added to the end of the Fact Sheet section called “What does it mean if the specimen tests negative for antibodies against virus that causes COVID-19?”:

2. Performance Evaluation Requirements

FDA is also requiring test makers to evaluate the impact of SARS-CoV-2 viral mutations on test performance. Evaluation for multianalyte tests must address the impact of SARS-CoV-2 viral mutations and all other target analytes. Evaluations must be performed on an ongoing basis and include any additional data analysis that the agency requests in response to performance concerns. You must also immediately notify FDA of any viral mutations that affect the expected performance of the test via email: CDRH-EUA-Reporting@fda.hhs.gov).

3. Additional Labeling Update Requirements

If requested by FDA, you must update your labeling within seven calendar days to include any additional labeling risk mitigations that the agency identifies with regard to the impact of viral mutations on test performance. You must make such updates will be made in consultation with, and secure the concurrence of the FDA Division of Microbiology (DMD), Office of Health Technology 7 (OHT7), Office of In Vitro Diagnostics and Radiological Health (OIR), Office of Product Evaluation and Quality (OPEQ), and Center for Devices and Radiological Health (CDRH).