The U.S. Food and Drug Administration issued 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.
“The FDA is committed to identifying efficient ways to modify medical products that either are in the pipeline or have been authorized for emergency use to address emerging variants,” said Acting FDA Commissioner Janet Woodcock, M.D. “We know the country is eager to return to a new normal and the emergence of the virus variants raises new concerns about the performance of these products. By issuing these guidances, we want the American public to know that we are using every tool in our toolbox to fight this pandemic, including pivoting as the virus adapts. We need to arm health care providers with the best available diagnostics, therapeutics and vaccines to fight this virus. We remain committed to getting these life-saving products to the frontlines.”
The FDA has anticipated the possible emergence of SARS-CoV-2 variants and has already been prepared to address changes in the virus, informed by the agency’s experience with evolving infectious diseases, such as influenza and HIV. While the FDA has already been communicating with individual medical product sponsors to provide information and scientific advice as they evaluate the impact of SARS-CoV-2 variants on their products, in the spirit of transparency and to continue to encourage public input on this important topic, the agency published this suite of guidances.
As with any evolving situation, the FDA will be continuously monitoring the situation and updating its plans as more information becomes available. The agency is committed to communicating with the public as the FDA determines the best paths forward. The FDA urges Americans to continue to get tested, get their vaccines to prevent COVID-19 and follow important health measures—wash your hands, wear a mask and maintain social distance.
Vaccines
The FDA updated its October 2020 guidance, Emergency Use Authorization for Vaccines to Prevent COVID-19, 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, available information suggests that the FDA-authorized vaccines remain effective in protecting the American public against currently circulating strains of SARS-CoV-2. 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 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.
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 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 FDA 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, 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. The guidance also provides recommendations to test developers, such as considering the potential for future viral genetic mutations when designing their test, and conducting their own 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.
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. 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 new guidance provides recommendations for developers of SARS-CoV-2-targeting monoclonal antibodies during the COVID-19 public health emergency. Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses, like SARS-CoV-2. The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged. This guidance provides recommendations on efficient approaches to the generation of non-clinical, clinical, and chemistry, manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.
The revised guidance covering drugs and biological products more broadly, originally published in May 2020, describes the FDA’s current recommendations regarding phase 2 and phase 3 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. Today, 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.
