FDA Outlines Data Required for Modifying COVID-19 Vaccines Against Viral Variants
The FDA has published draft guidance letting COVID-19 vaccine developers that modify authorized vaccines against new viral variants know what they need to present to the agency for amending Emergency Use Authorizations (EUAs), noting that it doesn’t expect large-scale trials will be needed for the altered versions.
The agency said it expects trials for modified vaccines will take approximately two to three months and consist of “a few hundred individuals,” though Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), cautioned he could not give exact figures.
For clinical data, determination of effectiveness for modified vaccines should be supported by data from clinical immunogenicity studies that compare the variant immune response induced by the modified version with the immune response granted by the original authorized vaccine. The guidance also encourages vaccine-makers to include both nonvaccinated participants and those previously vaccinated with the authorized vaccine in trials for amended EUAs.
In addition, the guidance includes recommendations for safety assessments that should be done to support an amended EUA for a modified vaccine. For example, evaluating solicited local and systemic adverse events daily for at least a week after each vaccination done as part of the trial of the modified vaccine, in addition to assessing serious and other unsolicited adverse events during the immunogenicity evaluation period, may be enough to support an amended EUA.
However, the agency’s new guidance says that evaluating the modified version in a larger safety database than initially planned for immunogenicity studies may be necessary if safety signals appear following a booster shot given during the trial for the amended EUA, noting that those studies should also plan for longer-term assessments of serious and other medically attended adverse events.
Generally, the agency believes required manufacturing information will remain the same for an authorized vaccine and its modified version, the guidance says.
The agency said it believes that the vaccines authorized to date are still effective against the SARS-CoV-2 strains circulating in the U.S., but it is urging vaccine-makers to prepare for future strains that could render inoculations less effective.
“We need to have the studies conducted to facilitate potential strain changes sooner rather than later so that if we need to swap something in, we can do it in a relatively quick manner,” said Marks. “These variants can sometimes move through the population very quickly, so we want to be prepared for them and that’s what I think the manufacturers are already starting to gear up to do.”
Also on Monday, the agency published a draft guidance on developing COVID-19 monoclonal antibody products that includes recommendations on efficiently generating nonclinical, clinical and chemistry, manufacturing and controls (CMC) data in support of an EUA for variant-tailored monoclonal antibodies.
“Fortunately, there are a lot of monoclonals in the pipeline,” said Acting FDA Commissioner Janet Woodcock. “We have a lot of ways we can fairly easily understand their performance against different variants, so we have a lot of prior knowledge about this to work on.”
In addition, the FDA put out a revised guidance, first issued in May 2020, that outlines in a broader sense its recommendations for phase 2 and 3 clinical trials for drugs and biological products being developed for treating or preventing COVID-19, excluding vaccines, monoclonal antibodies and convalescent plasma products.
The guidance, which includes advice on patient population, trial design, efficacy endpoints, safety considerations and statistical considerations, was updated to reflect “the evolving landscape of COVID-19 drug development, including the emergence of SARS-CoV-2 variants and the availability of authorized COVID-19 vaccines,” the agency said.
For example, the guidance advises sponsors to characterize drug resistance pathways and the potential for cross-resistance to other drugs using both clinical and nonclinical studies. The agency explained that changes in the virus could impact the effectiveness of antiviral drugs. In addition, the use of antivirals to treat COVID-19 could contribute to the emergence of variants that have reduced susceptibility to antivirals or other drugs.
“The reason for these guidances is that any of these products might be impacted by changes to the virus, particularly their efficacy or performance,” Woodcock said. “Therefore, we need to identify official ways to modify the products that are either in the pipeline or are EUA products to address these variants. We actually need to make sure the products that are marketed under EUA are monitored to ensure that if their performance is altered, we know about it and manufacturers know about it right away.”
Read the COVID-19 vaccine guidance here: www.fdanews.com/02-22-21-EUAVaccinesPreventCOVID19.pdf.
Read the COVID-19 monoclonal antibody guidance here: www.fdanews.com/02-22-21-AddressingImpactEmergingVariants.pdf.
Read the COVID-19 drugs and biological products guidance here: www.fdanews.com/02-22-21-COVID19.pdf. — James Miessler