Data is at the Heart of Booster Shot Approvals

Sept. 22, 2021 Update: FDA amended its EUA for the Pfizer vaccine to allow a single booster dose to be administered at least six months after completion of the primary series for individuals 65 and older; individuals, ages 18 to 64, who are at high risk of COVID-19; and individuals 18 to 64 who are frequently exposed to SARS-CoV-2, which puts them at high risk.

The public has been awaiting next steps in COVID-19 vaccination efforts amid emerging variants and possible booster shots to vaccinated individuals. But before boosters can be issued, the Food and Drug Administration has to approve them, and doing so comprises a close data-oriented evaluation of immune responses.

In August, FDA fully approved the first COVID-19 vaccine to have received authorization on an emergency-use basis, Pfizer-BioNTech. Other vaccines that were approved on an emergency basis are still waiting on full approval in addition to boosters.

FDA has a lot of flexibility to enact emergency use authorizations to vaccine manufacturers, but to receive a fully approved license, manufacturers have to prove that they can consistently produce the vaccine in the same manner, noted Dr. Peter Marks, director of FDA’s Center for Biologics Evaluation and Research (CBER), during the Sept. 15 Research!America’s 2021 National Health Research Forum.

This includes inspection of facilities that are being used for production as well as analysis of data regarding patient safety, all of which take time.

“We waited after a period where we had data on 12,000 individuals who had been followed for at least six months. That gave us a more robust safety data set,” Marks said. “FDA is one of the few regulatory agencies globally that actually goes through patient-level data and we do our own analyses — we don’t just look at summary data.”

As new COVID-19 variants emerge, FDA has been conducting laboratory and field studies to analyze how the current generation of vaccines are faring with new mutations. Marks said FDA is confident that the current vaccines are adequately addressing the delta variant, particularly within the first few months after an individual is vaccinated.

“The amount of antibodies that our bodies make against these spike proteins on the surface of coronavirus … those antibody levels can be used in assays against the different coronavirus variants to see how well we’re going to be able to fight them off,” Marks said. “The lucky thing is that the current vaccines do a pretty good job against the delta variant.”

As vaccine immunity decreases with time and other variants emerge that might not respond as well to the current vaccines, the mRNA structure could serve as a solid foundation for future iterations.

“If this ever strays far enough that the current generation of vaccines are not able to produce good immune responses, we have a plan forward whereby we, probably with these vaccines, can switch over in a matter of weeks to a few months … That’s because we’re not going to need the large clinical trials that we needed up front. We’ll need a much smaller amount of data to make this switch to address these variants if they come along,” Marks said.

With the Biden Administration’s call for booster shots by Sept. 20 overdue, FDA is ensuring it has a solid handle on the evidence first before approving the recommendation for a broader population, Marks said. One possibility could be that, instead of “boosters,” the vaccine could evolve to have a second or third dose in the primary series.

“We want to make sure that we’re doing the right thing here in protecting our population. We don’t want to see people starting to get sick again from COVID-19 after a number of months,” Marks said. “Delta variant may need a very robust antibody response to protect against it. The combination of a waning immunity and the delta variant is what has led us to consider this need for boosters or third doses.”

As of Sept. 17, FDA’s Vaccines and Related Biological Products Advisory Committee recommended boosters for those vaccinated individuals who are 65 and older and those with underlying conditions.

“Our internal drive here is that we want to bring this pandemic to an end as rapidly as possible and save as many American lives as we possibly can. So, that is what drives us to get to a decision here as quickly as possible because data suggest that if you need a third dose, it’s probably better to get there sooner,” Marks said.