ACCESS Consortium guidance on strain changes in authorised COVID-19 vaccines
A regulatory approach for updating authorised coronavirus vaccines should mutations at any time make them less efficacious due to insufficient cross-reactivity.
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This document is only applicable to COVID-19 vaccines which have already been authorised, based on adequate data on pharmaceutical quality, safety and efficacy from pivotal clinical trials.
On public health and scientific considerations, Regulatory Authorities do not consider an updated coronavirus vaccine to be an entirely novel product with the resulting requirement for lengthy full-blown clinical studies.
Rather, a regulatory approach like for seasonal updates for influenza vaccines can be taken. Evidence gathered by the large pivotal clinical studies for initial authorisation and by mass vaccination campaigns is a strong foundation for this approach, as is ongoing research on the “correlate of protection” (i.e what immunological readouts correlate with clinical protection from COVID-19 disease).
It is considered that, in a rapidly evolving pandemic and public health need, international harmonisation of both the definition on key virus variants and regulatory requirements are desirable but not a prerequisite for moving ahead in effective and enabling regulation of vaccine updates.
From a pharmaceutical quality perspective, details of the virus sequence, its history and any updates to the already established manufacturing process should be provided, supported by appropriate batch analyses and stability data.
From a non-clinical perspective, non-clinical immunogenicity data, both humoral and cellular, in a relevant animal model can be of support for an application.
From a clinical perspective, clinical efficacy studies prior to approval are not required. Regulatory Authorities request bridging data on immunogenicity from a sufficient number of individuals; an immunogenicity and reactogenicity study may include both vaccine-naïve and subjects already vaccinated with the current vaccine version. For a vaccine using a viral vector, antibodies against the viral vector should be measured.
An updated Risk Management Plan (RMP) would have to be submitted for review to ensure that the pharmacovigilance and risk minimisation activities for both variant and prototype vaccine are in place.
For COVID-19 vaccines which are not yet authorised where an update to the SARS-CoV2 strain is considered, some considerations of this document may apply. Such scenarios will depend on the stage of development, the format of the vaccine, and on the evidence on immunogenicity, safety and efficacy already gathered at the time of updating the SARS-CoV2 sequence. Any concept should be discussed with Regulatory Authorities.
Read our press release for further information on our how modified COVID-19 vaccines will be fast-tracked.