FDA Lists 27 Current COVID-19 Tests that May Not Detect Omicron

Are the current COVID-19 tests available in the US market capable of detecting the new Omicron (B.1.1.529) variant? That’s the burning question that test producers, policy makers and providers have been asking since the World Health Organization (WHO) declared the new Omicron mutation a “variant of concern.” While many leading makers of COVID-19 diagnostic tests have declared their products ready for Omicron, the FDA seems less confident. On Dec. 3, the agency updated its website by listing 27 tests “whose performance may be impacted by mutations in the SARS-CoV-2 Omicron variant.”

FDA Rules on Impact of Viral Mutation on Test Performance

FDA has issued Emergency Use Authorization (EUA) for hundreds of assays detecting SARS-CoV-2; but not a single one of these tests was designed for the Omicron variant of the virus. Of course, the agency has anticipated this challenge and continually warned labs and health care providers to consider the potential impact of viral mutations on COVID-19 test performance. This fall, it issued new rules requiring producers of molecular, serology and antigen SARS-CoV-2 tests that have received EUA to take additional steps to account for viral variants.

New FDA Variant Requirements for EUA COVID-19 Tests

Although FDA has required makers of EUA tests to account for how mutations of the SARS-CoV-2 virus might impact test performance from the beginning of the public health emergency, this fall it implemented new rules requiring test makers to take three additional measures.

1. Updated Labeling Requirements: Test makers must revise their authorized labeling and submit the updated labeling to FDA as a supplement to the EUA within three months.
2. Performance Evaluation Requirements: FDA also required 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.
3. Additional Labeling Update Requirements: If requested by FDA, test makers must update their 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.

The Omicron Response

In late November and early December, many of the leading providers of EUA COVID-19 tests, both polymerase chain reaction (PCR) and rapid antigen, have stated that analysis of actual Omicron samples confirms that their assays can detect the new variant. That includes Abbott, Hologic, Thermo Fisher Scientific, Qiagen, Lucira Health, PerkinElmer and Becton Dickinson.

Less assuring is the FDA’s newly published list of 27 tests from 24 manufacturers whose performance might be impacted by Omicron based on the agency’s bioinformatics analysis suggesting that one genetic target will have significantly reduced sensitivity due to a mutation in Omicron. Many of the listed tests are produced by smaller labs. Only one major test manufacturer has products on the list.

FDA Listed COVID-19 Tests Potentially Impacted by Omicron Variant

Source: FDA website

The listed assays will still be able to detect SARS-CoV-2 infection. “Since these tests are designed to detect multiple genetic targets, the overall test sensitivity should not be impacted,” according to the FDA. However, the agency warns lab staff and providers that use the listed tests to be aware of the potential of S-gene target failure (SGTF). SGTF is a specific deletion in the spike (S) gene (Δ69-70) resulting in an S-gene dropout that causes the portion of the test targeting the S-gene to not detect the virus.

Furthermore, as SGTF is typically not observed in the Delta variant, specimens “with an S-gene dropout detection pattern may potentially be Omicron variants and should be prioritized for sequencing confirmation,” the FDA said.