The regulatory approval of COVID-19 vaccines towards the end of 2020 and start of 2021 coincided with the detection of new SARS-CoV2 strains in the UK, South Africa and Brazil. The ACCESS consortium has released a document detailing the regulatory approach for updating authorised coronavirus vaccines to target new strains.
The mutation first reported in Brazil has been found to contain mutations in the spike gene. Mutations and deletions in the spike protein are of particular concern as current vaccines are targeted to this structure which may lead to them becoming less effective. Consequently, updating COVID-19 vaccines to make them effective against emerging mutations is a potentially efficient way to deal with these variants. This approach is similar to the seasonal influenza vaccine and as such, the regulatory strategy for updated COVID-19 vaccines will be similar. The document released by the ACCESS consortium details key considerations for vaccine manufacturers.
Pharmaceutical quality considerations revolve around companies providing the manufacturing process (along with appropriate batch analyses and stability data), the virus sequence and its history.
Non-clinical considerations concern toxicology data (the absence of which must be justified), immunogenicity data (both humoral and cellular) and protection data from a suitable challenge model.
Clinical considerations are more extensive and depend on the nature of the vaccine. For those using a viral vector, antibodies against the viral vector should be measured. Regardless of the vaccine mechanism, clinical efficacy studies are not required prior to approval. However, immunogenicity and safety data will need to be provided which requires an immunogenicity and reactogenicity study. Such a study may include both vaccine-naïve and already vaccinated subjects. A plan for a post-approval effectiveness study must also be included in the submission, as well as an updated Risk Management Plan (RMP) to cover the required pharmacovigilance and risk minimisation activities for the proposed vaccine.
The guidance also includes information on certain aspects which may be applied to unapproved COVID-19 vaccines which are currently under development. Further considerations are included as part of the consortium’s pandemic preparedness, detailing how the guidance may be adapted to deal with future novel coronaviruses unrelated to SARS-CoV2.
A final section of the document is specific to the United Kingdom (UK) and details Medicines and Healthcare product Regulatory Agency (MHRA) considerations such as the use of human challenges studies as a valid alternative method of studying an updated vaccine candidate.
Click here to view the full guidance document.