The US Food and Drug Administration (FDA) has issued guidances and revised previously published guidances for medical product developers, specifically covering vaccines, diagnostics and therapeutics products, to address the emergence and potential future emergence of variants of SARS-CoV-2, the virus that causes COVID-19.

Vaccines

The FDA updated its guidance, Emergency Use Authorization for Vaccines to Prevent COVID-19, originally published in October 2020, to provide recommendations to vaccine developers, including those who have already received emergency use authorization (EUA) for their COVID-19 vaccines and are seeking to amend their EUA to address new variants. At this time (as reported on February 22, 2021), the agency says available information suggests that the FDA-authorized vaccines remain effective against currently circulating strains of SARS-CoV-2. 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).

The updated guidance outlines the 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. 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. 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.

Therapeutics

To address the impact of emerging variants of SARS-CoV-2 on the development of monoclonal antibody products targeting the virus, the FDA has issued a new guidance, Development of Monoclonal Antibody Products Targeting SARS-CoV-2, Including Addressing the Impact of Emerging Variants, During the COVID-19 Public Health Emergency, to provide recommendations for developers of SARS-CoV-2-targeting monoclonal antibodies during the COVID-19 public health emergency. The guidance provides recommendations on approaches to the generation of non-clinical, clinical, and chemistry, manufacturing and controls (CMC) data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.

FDA has also revised a second guidance covering drugs and biological products more broadly for COVID-19, COVID-19: Developing Drugs and Biological Products for Treatment or Prevention. The revised guidance covering drugs and biological products more broadly, originally published in May 2020, describes the FDA’s current recommendations regarding Phase II and Phase III clinical trials for drugs and biological products under development to treat or prevent COVID-19, including the patient population, trial design, efficacy endpoints, safety considerations, and the statistical considerations for such trials and more. This guidance was updated to address the evolving landscape of COVID-19 drug development, including the emergence of SARS-CoV-2 variants and the availability of authorized COVID-19 vaccines.

With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.

COVID-19 Tests

The FDA issued a new guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests. The guidance 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 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 FDA identified a few tests that are known to be impacted by emerging viral mutations, though at this time, the agency says that the impact does not appear to be significant.

Source: US Food and Drug Administration