FDA unveils plans to tackle COVID variants

Regulatory NewsRegulatory News | 22 February 2021 |  By 

The US Food and Drug Administration (FDA) on Monday unveiled recommendations for vaccine, drug and diagnostic test developers to address the impact of COVID-19 variants on the efficacy and performance of their products.
The recommendations are made across four new and updated guidances targeting vaccines, drugs and biologics, monoclonal antibodies and diagnostic tests.
“The purpose of these guidances is to address the emergence and potential future emergence of variants of SARS-CoV-2, the virus that causes COVID-19. The reason for these guidances is any of these products might be impacted by changes to the virus, particularly their efficacy or performance. Therefore, we need to identify efficient ways to modify the products that are either in the pipeline or are [emergency use authorization] EUA products to address these variants,” Acting FDA Commissioner Janet Woodcock said during a press conference. Woodcock also said that authorized or approved products for COVID-19 should be monitored to ensure that if performance is altered, the agency and manufacturers are aware right away.
Several variants of the SARS-CoV-2 virus, including those first identified in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (B.1.1.28), have raised international concern as they appear to be more transmissible and may diminish the efficacy of certain treatments or vaccines. FDA has also warned that some genetic variants of the virus may confound the results of molecular tests, potentially leading to false negatives.
The release of the new and updated guidance comes weeks after Woodcock announced that such guidance would be forthcoming. The European Medicines Agency (EMA) has also said that it will provide its own guidance up adapting vaccines for COVID-19 variants. (RELATED: Woodcock: FDA plans guidance to address new COVID-19 variants, Regulatory Focus 5 February 2021; EU plan to tackle COVID variants features flu vaccine-like pathway, Regulatory Focus 17 February 2021).
While the guidance was released publicly on Monday, Woodcock said that FDA “has already been communicating with the individual medical product sponsors to provide information and scientific advice as they evaluate the impact of these variants on their products,” and that the agency is releasing the guidances as a matter of transparency and to gather feedback.
Woodcock also emphasized that containing the virus and new variants will require a global effort. “The virus, wherever it is replicating, is mutating, and so as long as there’s a large amount of infection around the world, probably additional virus variants will emerge. We need a global approach to this global pandemic,” she said.
FDA has so far authorized vaccines developed by Pfizer-BioNTech and Moderna for emergency use and is set to review Johnson & Johnson’s single-shot vaccine at a Vaccines and Related Biological Products Advisory Committee meeting later this week.
“At this time, as you know, available data suggests the FDA-authorized vaccines are effective in protecting the American public against circulating strains of SARS-CoV-2; however, if there’s an emergence of variants in the United States that are moderately or fully resistant to the antibody response elicited by the current generation of COVID-19 vaccines, it may be necessary to modify vaccines or the vaccination regimen,” Woodcock said.
In an update to its guidance on EUAs for COVID-19 vaccines, FDA details the nonclinical, clinical and chemistry, manufacturing and controls (CMC) data needed to support an amendment to an EUA.
“Assuming the prototype vaccine has been authorized under an EUA it is expected that the modified COVID-19 vaccine against a SARS-CoV-2 variant made by the same manufacturer and process as the prototype COVID-19 vaccine would be authorized through an EUA amendment to the EUA for the prototype COVID-19 vaccine,” FDA writes in a new appendix in the guidance. FDA notes that the guidance does not address how it will be determined that an updated vaccine will be needed, which protein sequences should be expressed or the follow-up of modified vaccines, nor does it address multivalent COVID-19 vaccines. (RELATED: FDA updates EUA guidance, addressing vaccines against COVID variants, Regulatory Focus 22 February 2021).
Therapeutics and monoclonal antibodies
For therapeutics, FDA has updated its existing guidance on developing drugs and biologics for COVID-19 and issued a new guidance specifically tailored to the development of monoclonal antibodies to address the emergence of variants.
“We have updated this guidance, since a lot has happened over the last months to address the evolving landscape of COVID-19 drug development, including the emergence of variants and the availability of authorized COVID-19 vaccines,” Woodcock said.
The guidance now includes an appendix on conducting drug resistance analysis, including recommendations for drug developers to continuously monitor for emerging SARS-CoV-2 variants. “We will do this as well,” Woodcock said, “We will continuously monitor the situation and update our plans as more information becomes available.”
In FDA’s new guidance on developing monoclonal antibodies for COVID-19, FDA details the approaches to generating nonclinical, clinical and CMC data to support an EUA for antibody products that neutralize specific variants of the virus.
“We know that some of the monoclonal antibodies that are currently authorized are less active against some of the SARS-CoV-2 variants that have emerged and are prevalent in some parts of the world,” Woodcock said. “Fortunately, there are a lot of monoclonals in the pipeline … we can fairly easily understand their performance against different variants, so we have a lot of prior knowledge about this to work on.”
In the guidance, FDA “strongly recommends” that monoclonal antibodies be developed with the expectation that they will be combined with one or more other monoclonal antibodies that bind to different epitopes to minimize the risk of losing activity against new variants. FDA also recommends that sponsors monitor genomic databases for emerging variants and evaluate the neutralizing activity of monoclonal antibodies against circulating variants.
In a new guidance, FDA sets out its policy for evaluating the impact of viral mutations on COVID-19 tests.
“There’s a lot of tests out there and we need the manufacturers to be vigilant and make sure that their tests are not impacted adversely by changes to the virus,” Woodcock said.
The guidance provides specific recommendations for assessing the impact of viral mutations on molecular diagnostics, antigen tests and serology tests and explains that FDA is considering including a condition of authorization for test developers in EUAs that would require them to evaluate the impact of virus mutations on test performance. The guidance also discusses design considerations for making tests more robust against changes in the virus. (RELATED: COVID test developers get variant-related FDA guidance, Regulatory Focus 22 February 2021).


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