Agency Tells EUA SARS-CoV-2 Test Makers to Account for Viral Mutations

On Sept. 23, FDA issued a letter requiring producers of SARS-CoV-2 tests with Emergency Use Authorization (EUA) to take additional steps to account for viral variants. 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 don’t cover EUAs for authorized IL-6 assays, standalone specimen collection devices, or standalone home collection kits. Nor do they cover 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

FDA wants test makers to update their authorized labeling and submit it to the agency 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:

The performance of this test was established based on the evaluation of a limited number of clinical specimens. Clinical performance has not been established with all circulating variants but is anticipated to be reflective of the prevalent variants in circulation at the time and location of the clinical evaluation. Performance at the time of testing may vary depending on the variants circulating, including newly emerging strains of SARS-CoV-2 and their prevalence, which change over time.

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: The following language must be added 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?”:

The performance of this test was established based on the evaluation of a limited number

of clinical specimens. The clinical performance has not been established in all

circulating variants but is anticipated to be reflective of the prevalent variants in

circulation at the time and location of the clinical evaluation. Performance at the time of

testing may vary depending on the variants circulating, including newly emerging strains

of SARS-CoV-2 and their prevalence, which change over time.

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?”:

The performance of this test was established based on the evaluation of a limited number

of clinical specimens. The clinical performance has not been established in all

circulating variants but is anticipated to be reflective of the prevalent variants in

circulation at the time and location of the clinical evaluation. Performance at the time of

testing may vary depending on the variants circulating, including newly emerging strains

of SARS-CoV-2 and their prevalence, which change over time.

2. Performance Evaluation

FDA is also requiring test makers to perform ongoing evaluation of SARS-CoV-2 viral mutations impact on test performance. Multianalyte test evaluation must address how mutations impact all analytes. Viral mutations that affect the expected performance of the test must be relayed to the agency by email, CDRH-EUA-Reporting@fda.hhs.gov).

3. Additional Labeling Updating

If requested by FDA, labeling must be updated within seven calendar days to include

any additional labeling risk mitigations that the agency identifies regarding the impact of

viral mutations on test performance.

Molecular Tests Cited by FDA as Being Potentially Affected by Viral Mutations

In addition to the letter, FDA published a list of molecular tests whose performance could be impacted by viral mutations:

FDA suggested that mutation impact on these tests “does not appear to be significant” for overall sensitivity and that it is providing the information “out of an abundance of caution.”

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Here are some of the key new FDA EUAs and clearances announced in September 2021:

New FDA Emergency Use Authorizations (EUAs) & Approvals (NEW)

New CE Marks & Global Certifications

Notable European CE certifications announced during the period:

NEW CE MARKINGS IN EUROPE

Other international clearances announced during the period: