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FDA Issues Covid-19 Variant Regulatory Guidance

Covid-19 testing


22 Feb. 2021. Food and Drug Administration is updating its regulatory guidance for Covid-19 drugs and diagnostics to cover emerging mutations in the SARS-CoV-2 virus. The agency’s guidance on viral variants is reflected in two new and two updated guidance documents for developers of vaccines, infection tests, and therapies when seeking emergency use authorizations.

The new guidance released for comment, says FDA, reflects the agency’s current scientific consensus for developers arising from the emergence of mutations in the SARS-CoV-2 virus, and remains in effect during the medical emergency brought on by the Covid-19 pandemic. The agency also encourages drug, biologic, and diagnostic developers to keep monitoring genomic databases for further variants that may become prevalent and affect their companies’ products.

“By issuing these guidances,” says acting FDA commissioner Janet Woodcock in an agency statement, “we want the American public to know that we are using every tool in our toolbox to fight this pandemic, including pivoting as the virus adapts. We need to arm health care providers with the best available diagnostics, therapeutics, and vaccines to fight this virus.”


For vaccine developers, FDA added an appendix on new variants to its guidance document issued in October 2020. While early findings from clinical trials of vaccines already authorized or near agency review show the vaccines protect against B.1.1.7 (U.K.) and B.1.351 (South Africa) variants, efficacy rates, particularly against B.1.351, are lower than the original strain. In addition, lab studies of blood serum from clinical trial participants immunized with authorized vaccines show uneven results against the variants.

The updated guidance calls for developers of vaccines already authorized by FDA to provide clinical study findings of safety and immune reactions to vaccines altered for emerging variants compared to results from trials of the original vaccine. The results should show relative efficacy of primary vaccine and booster shots against the variants in generating immune responses. Developers are also encouraged to test its modified vaccines in people previously vaccinated as well as non-vaccinated individuals. In addition, developers should be prepared to discuss the need for annual updates to their vaccines, as well as clinical trials to test annual updates.


For diagnostic test developers, FDA issued new guidance providing policies and recommendations for identifying Covid-19 infections in patients as new variations emerge. The document notes that most of today’s Covid-19 diagnostics are based on the original SARS-CoV-2 viral sequence from Wuhan, China. But performance of diagnostics can be affected by mutations in the virus, and if the test is not updated to reflect those mutations, it could give false negative results.

The document recommends molecular test developers, including so-called gold standard RT-PCR tests, design their tests to minimze effects of mutations on test performance. Molecular test designers are also asked to routinely monitor for mutations that can affect test performance, and describe any limitations from new variants in the test’s package labeling and literature.

For antigen and blood serum test developers, FDA also recommends developers take new variants into account during design of the diagnostics. The agency recognizes, however, that antigen and blood serum tests are not as directly affected by emerging mutations as molecular tests. Nonetheless, developers are encouraged to obtain samples of variants and show with simulations or lab tests their effects on test performance. Test developers are also asked to indicate where the presence of viral variants reduces test performance by five percent or more from previous benchmarks.


For developers of Covid-19 therapeutics, FDA issued one new and one updated guidance document. The new guidance addresses monoclonal antibodies, synthetic proteins that act like natural antibodies in the immune system to fight Covid-19 infections. The document notes that the emergence of SARS-CoV-2 variants may require a faster than usual response from FDA, which calls for more streamlined data reporting by developers and expedited reviews. The agency advises developers to expect requests by FDA to test combinations of monoclonal antibody treatments to address these variants, and encourages collaborations, or at least sharing of information, among developers.

FDA also updated a current guidance document, originally issued in May 2020, covering development of drugs and biologics overall to prevent or treat Covid-19 infections. The document focuses on design of mid- and late-stage, or phase 2 and 3, clinical trials testing therapy candidates, and adds an appendix calling for a plan to evaluate resistance to therapies arising from SARS-CoV-2 variants. The appendix asks developers to identify steps to identify the chemistry of variants in the targets, and design trial outcomes to highlight their effects. Developers also need to watch as well for cross-resistance to other drugs with the same target or mechanism of action.

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