Modifying Vaccines, Tests Due to Variants: Woodcock
FDA has issued a updated guidance for currently authorized Covid-19 vaccines that could be modified with limited data to address emerging variants. In announcing the guidance, FDA acting commissioner Janet Woodcock said the document will allow FDA and developers to pivot as the virus adapts. “At this time, available information suggests that the FDA-authorized vaccines remain effective in protecting the American public against currently circulating strains of SARS-CoV-2,” the agency says. “However, if there is an emergence of SARS-CoV-2 variant(s) in the U.S. 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).”
The guidance, Emergency Use Authorization for Vaccines to Prevent COVID-19, outlines FDA’s 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,” the agency says. For clinical data, instead of large controlled trials, it recommends that an effectiveness determination 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,” FDA says. “Additionally, the guidance outlines the FDA’s recommendations for assessments of safety to support an EUA for a modified vaccine. Finally, the guidance states that further discussions will be necessary to decide whether in the future, modified Covid-19 vaccines may be authorized without the need for clinical studies.”
For Covid test developers, a new guidance, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, provides information on evaluating the potential impact of emerging and future viral genetic mutations, which may be the basis of viral variants, on Covid-19 tests, including design considerations and ongoing monitoring. “The FDA has already issued a safety alert to caution that the presence of viral genetic mutations in a patient sample can potentially change the performance of a diagnostic test,” the agency says, adding that it has identified a few tests that are known to be impacted by emerging viral mutations, though at this time the impact does not appear to be significant.
“The clinical impact of viral genetic mutations on a test’s performance is influenced by various factors,” FDA continues, “such as the sequence of the variant, the design of test (for example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to the effects of genetic variation than tests designed to detect a single genetic target), and the prevalence of the variant in the patient population. The guidance describes the FDA’s activities to better understand the public health impact of new virus variants and the impact on test performance, such as monitoring publicly available genomic databases for emerging SARS-CoV-2 genetic mutations and monitoring the potential effects of genetic variation on molecular tests that have been issued an EUA.”
Additionally, the guidance provides recommendations to test developers, such as considering the potential for future viral genetic mutations when designing their test, and conducting routine monitoring to evaluate the potential impact of new and emerging viral genetic mutations, which may be the basis of viral variants, on the performance for molecular, antigen and serology SARS-CoV-2 tests.