The FDA on Monday issued new guidance confirming that drugmakers will not have to perform large-scale trials for new COVID-19 vaccines or booster shots developed to combat new variants of SARS-CoV-2. "At this time, available information suggests that the FDA-authorised vaccines remain effective in protecting the American public against currently circulating strains," the agency said, but developers may need to modify their products to provide protection against any potential new variants in the US should they fail to elicit immune response in their current form.
"Preliminary reports from clinical trials evaluating COVID-19 vaccine candidates in multiple countries, including South Africa, have added to concerns that vaccine efficacy against the B.1.351 variant may be lower than against the original virus," the agency noted, referring to the strain found in that country, so "there is an urgent need to initiate development and evaluation of vaccines against these SARS-CoV-2 variants."
According to the FDA, the latest guidance would clear the new vaccines as an amendment to a company's originally approved emergency-use application. The agency expects that the manufacturing information of a modified vaccine candidate would "remain generally the same" as its authorised counterpart if produced by the same manufacturer. However, it said companies should submit new clinical immunogenicity studies, similar to what is done for annual vaccines against influenza. These studies would have to demonstrate that a recipient's immune response to SARS-CoV-2 variants induced by the modified candidate are comparable to what was produced following vaccination with an authorised product against the initial strains. Manufacturers are also "encouraged" to study the updated candidate in both non-vaccinated individuals and those previously vaccinated with authorised vaccines, the FDA said. It also recommended monitoring subjects for adverse events for at least seven days following each study vaccination.
The agency is trying to allow drugmakers to make the change with a minimal amount of extra data needed, according to Peter Marks, director of the FDA's Center for Biologics Evaluation and Research. The type of trial the agency wants "might take a few months, whether it be two or three…I can't say exactly how long, but again, that type of the scale of the amount of time," he said.
The US has so far issued emergency-use authorisations (EUAs) for Pfizer and BioNTech's BNT162b2 and Moderna's mRNA-1273, both two-dose mRNA-based vaccines that were greenlighted in December. The FDA is also in the process of reviewing Johnson & Johnson's single-dose adenovirus viral vector-based candidate Ad26.COV2.S, with an advisory panel meeting scheduled to discuss the filing this Friday. "Further discussions will be necessary to decide whether in the future, modified COVID-19 vaccines may be authorised without the need for clinical studies," the FDA said.
The FDA also issued guidance Monday containing recommendations for developers of SARS-CoV-2-targeting monoclonal antibodies. The US has authorised three such therapies to date for COVID-19 patients at high risk of worsening to severe disease, including Eli Lilly's bamlanivimab, both alone and in combination with etesevimab, as well as Regeneron Pharmaceuticals' REGN-COV2, which is the co-administration of casirivimab plus imdevimab.
The FDA said it "is aware that some of [these] are less active against some of the SARS-CoV-2 variants that have emerged." According to the regulator, the new guidance gives recommendations on "efficient approaches" to generating non-clinical, clinical, and chemistry, manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging strains.
"By issuing these guidances, 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," stated acting FDA commissioner Janet Woodcock. Meanwhile, the European Medicines Agency is also preparing guidance aimed at helping vaccine manufacturers tackle SARS-CoV-2 mutations, and said it plans to fast-track variant-modified COVID-19 vaccines.
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