Developing vaccines and therapeutics for virus variants: FDA releases new guidance
Vaccines: EUA amendment
The FDA says that authorized vaccines (Pfizer and Moderna) appear to remain effective against strains circulating in the US. “However, if there is an emergence of SARS-CoV-2 variant(s) in the US that are moderately or fully resistant to the antibody response elicited by the current generation of COVID-19 vaccines, it may be necessary to tailor the vaccines to the variant(s),” it notes.
A question for regulators globally is how they will treat amended or new versions of vaccines that are developed against new virus strains. They could, for example, be treated in the same way as seasonal flu vaccines are regulated; but most jurisdictions have not yet set out a clear policy.
In the US, the FDA says that – assuming the initial vaccine has been authorized under an EUA - it expects that a modified COVID-19 vaccine against a SARS-CoV-2 variant (made by the same manufacturer and process as the initial COVID-19 vaccine) would be authorized through an EUA amendment for the initial vaccine.
The updated guidance outlines the FDA’s current scientific recommendations for modifications to authorized vaccines.
“For example, the FDA expects that manufacturing information will remain generally the same for an authorized vaccine and a modified vaccine candidate from the same manufacturer. For clinical data, the guidance recommends that a determination of effectiveness be supported by data from clinical immunogenicity studies, which would compare a recipient’s immune response to virus variants induced by the modified vaccine against the immune response to the authorized vaccine.
“Manufacturers are also encouraged to study the modified vaccine in both naïve (non-vaccinated) individuals and in individuals previously vaccinated with the authorized vaccine.”
As with an initial EUA, manufacturers would be expected to provide information on chemistry, manufacture and controls; non-clinical and clinical data, among other considerations.
“Currently, it is not known whether SARS-CoV-2 variants are more virulent than the original SARS-CoV-2 virus, whether the immunogenicity and safety profile of vaccines against the SARS-CoV-2 variants will be comparable to those of vaccines against the original SARS-CoV-2 virus and whether regular (e.g., annual) updates will be needed,” notes the FDA advice.
“Thus, manufacturers should generate the data to support authorization of a modified COVID-19 vaccine as outlined [in the guidance]. Further discussions will be necessary to decide whether in the future, modified COVID-19 vaccines may be authorized without the need for clinical studies.
“Developers are encouraged to perform exploratory studies regarding the ability of modified vaccines to boost immune responses to an appropriate level, even if the viral sequence being evaluated may not ultimately be selected for use in a modified vaccine. Such studies may provide important dose-finding and safety information. If a manufacturer plans to develop a modified monovalent vaccine against a variant, it will be important to ensure that the modified vaccine can be clearly distinguished from vaccines made by the manufacturer that target the original virus.”
Similarly, the FDA has set out advice on development of monoclonal antibody products targeting the virus.
“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged," it notes. "This guidance provides recommendations on efficient approaches to the generation of 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 variants.”
The agency calls on companies to collaborate to maximise efficacy against variants.
“FDA strongly recommends that individual monoclonal antibody products be developed with the expectation that they will be combined with one or more monoclonal antibody products that bind to different epitopes to minimize the risk of losing activity against emergent variants. FDA encourages collaborations between sponsors of individual monoclonal antibody products to address this unmet medical need.
“Sharing of information regarding SARS-CoV-2 variants among sponsors, consortia, or other partnerships may help expedite the development of therapeutics to address these variants.”