Selected Announcements: COVID-19 Vaccines – Announcements/Regulatory Actions/Deployment

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Selected Announcements: COVID-19 Vaccines – Announcements/Regulatory Actions/Deployment

ICMRA COVID-19 Virus Variants Workshop
Co-chairs: Marion Gruber (FDA, US) and Marco Cavaleri (EMA, EU)
International Coalition of Medicines Regulatory Authorities [ICMRA]
10 February 2021
… The ICMRA works hop was organised in light of the possible spread of these new variants globally and the need to consider rapid updates of current vaccines. The objectives were to discuss current surveillance activities to monitor the spread of the variants, and minimal elements of data that would be required to swiftly approve updated versions of available vaccines against emerging variants of SARS-CoV-2…
3. Vaccines: Possible minimal requirements for regulatory approval, or updated versions, of already-approved vaccines
The focus of the discussion was on the generation of monovalent vaccines containing the spike protein from an emerging variant recognized to pose a significant public health threat because it has shown to escape immunity from current vaccines.  Multivalent vaccines against SARS-CoV-2 variants were not considered in this workshop.


There was consensus that large safety and efficacy studies, similar to those required for initial approval of COVID-19 vaccines, are not feasible and would not be compatible with the timeframe for a rapid regulatory decision responsive to public health needs.

Authorization under emergency use approval and approval of variant COVID-19 vaccines against a SARS-CoV-2 variant expressing the spike protein and made by the same manufacturer and process as the prototype COVID-19 vaccine shown to be safe and effective in clinical trials, could be considered based on clinical data bridging the immune response of the variant vaccine to the prototype parent vaccine for which efficacy has been demonstrated in clinical disease endpoint efficacy studies.

Assuming that much of the manufacturing process and controls, as well as the facilities for vaccine production, for the variant COVID-19 vaccine would be identical to that of the prototype COVID-19 vaccine and depending on platform specific aspects, data to be generated may be confined to critical aspect of product characterization, potency assay and stability.

In general, it was agreed that additional non-clinical safety studies would not be required. Data derived from animal challenge/protection studies in a relevant model could be considered supportive. However, clinical immunogenicity and safety data would provide primary evidence for determining the suitability of the variant vaccines.

Inference of efficacy would need to be supported by conducting clinical non-inferiority immunogenicity studies comparing the immune responses induced by a variant COVID-19 vaccine against the SARS-CoV-2 variant of concern to the immune responses induced by the prototype vaccine for which clinical studies demonstrated efficacy and when administered according to the authorized dose and dosing regimen.

Studies in seronegative adults showing non-inferiority after a primary series of the new variant vaccine against the variant strains compared to prototype vaccine against ancestral strain were discussed as critical evidence for inferring efficacy of the variant vaccine.


In addition, booster studies would provide evidence to support the use of the variant vaccine when administered as a booster to individuals who were already vaccinated with the prototype vaccine as a primary series according to the authorized dose and dosing regimen. In this case, one option would be to demonstrate non-inferiority of the variant booster response against the variant strain versus the immune response of the primary series of the prototype vaccine against the ancestral strain.

As no correlate of protection for COVID-19 vaccines has been established to date, immune markers best suited for inferring protection were briefly discussed. The majority view was that neutralizing antibodies would constitute the most suitable immune marker for conducting immuno-bridging studies despite the complexity of comparing results from assays against different strains.

T-cell responses are considered an important component of the immune response elicited by different vaccines contributing to protection, but it would not be feasible to measure them due to lack of currently available validated assays.

The size of the studies would be driven by pre-specified statistical success criteria and endpoints.  Safety data should be collected covering both solicited and unsolicited adverse events as part of the immunogenicity studies. The safety of the variant vaccine would likely not differ significantly from that of the prototype, however, should unexpected safety signals arise, the safety database may have to be extended.


The importance of post-authorization studies evaluating safety and effectiveness of the variant COVID-19 vaccines was stressed…