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An FDA advisory committee voted to recommend the Pfizer-BioNTech mRNA COVID-19 vaccine candidate (BNT162b2) for use in individuals age 16 or older, though there was some late-breaking drama at the end of the meeting.

Based on the totality of scientific evidence available, the 162nd meeting of the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) ended in a 17-4-1 vote that the benefits of the vaccine outweigh risks in individuals age 16 and older, meaning the vaccine would qualify for FDA emergency use authorization (EUA).

Over 15,000 viewers watched the meeting via the FDA's YouTube channel, and it was also streamed on the FDA's Twitter account, as well as broadcast and live-streamed on C-SPAN 3.

The age of the individuals involved generated the most discussion at the end of a meeting largely free of rigorous debate. Committee member Cody Meissner, MD, of Tufts University School of Medicine in Boston, brought up lack of data among those ages 16-17 in the trial, saying he was "uncomfortable" with the voting question as written, citing insufficient data for the younger group. He said he wanted to make the recommendation for adults age 18 and older.

Several committee members shared his concern about lack of data, but they were met with equal resistance from other committee members, as well as FDA staff. Temporary voting member Ofer Levy, MD, PhD, of Boston Children's Hospital, noted how excluding this group could hamper data-gathering if the vaccine was eventually to seek a pediatric indication.

"If we take away 16- and 17-year-olds, we lose an effort to climb down in age, and might lose one of our tools to conquer this pandemic," he said.

Ultimately, the FDA had no appetite for revising the voting question after 5 p.m., noting that agency laws and regulations permit extrapolating data to younger age groups. They asked the committee to vote on the question "as is." Meissner was ultimately the vote's one abstention.

VRBPAC acting chair Arnold Monto, MD, of the University of Michigan in Ann Arbor, then abruptly closed the meeting without giving committee members a chance to discuss their vote, as it had already gone more than a half-hour over time.

Until then, the meeting was a little more than a formality. Peer-reviewed data was in the New England Journal of Medicine (interestingly, the journal's editor-in-chief Eric Rubin, MD, PhD, of Harvard Medical School in Boston, joined the advisory committee as a temporary voting member and voted yes). Vaccine efficacy at least 7 days after the second vaccine dose was 95% overall (95% CI 90.3%-97.6%) and 66% against severe COVID-19 (three cases in the control group; one in the vaccine group) albeit with a wide and nonsignificant confidence interval (95% CI -124.8% to 96.3%) given the small number of events.

Similar to data presented in FDA briefing documents, safety data was comparable across groups, with injection site reactions, fatigue, and headache as the most common adverse events. Mild-to-moderate reactogenicity was reported more frequently in participants younger than age 55.

The committee and FDA staff focused most of their attention on the of anaphylaxis in two vaccinated participants in the United Kingdom.

FDA staff said they were working with Pfizer to include individuals with severe allergic reactions under known contraindications on the vaccine fact sheet, saying they will "state this vaccine should not be administered to individuals with a known history of severe allergic reactions to any components of Pfizer's vaccine."

But Paul Offit, MD, of The Children's Hospital of Philadelphia, worried about the tens of millions of Americans with a history of severe allergic reactions who would not get the COVID-19 vaccine, and recommended a separate trial of individuals with severe allergies who would receive the vaccine under careful observation to prove it was safe to do so.

"This issue is not going to die until we have better data," he said.

The issue of unblinding participants also arose, with Pfizer recommending offering vaccine to placebo participants who become eligible for the vaccine "according to local or national recommendations" at the time of an EUA. Alternatively, subjects not meeting these recommendations would be offered vaccination at 6 months.

A separate presentation by Steven Goodman, MD, PhD, of Stanford University in California, proposed ways to continue blinding of vaccine studies, including alternate trial designs such as blinded crossover designs (where all participants are re-vaccinated, but placebo recipients receive vaccine and vaccine recipients receive placebo) or active control designs once vaccines are approved.

He ultimately said that for now, Pfizer's recommendation was a compromise offering some benefit to the placebo group: that they could get the vaccine first within their own priority group, but not immediately once an EUA was issued.

"I don't think the ethical calculus is such ... that they are necessarily owed that just by virtue of being in the trial, but they do get a benefit," Goodman said.

When Monto closed the meeting, he reminded committee members they will "have a chance to do this again," likely referring to the next VRBPAC meeting slated for Dec. 17, which will discuss the EUA application for Moderna's mRNA vaccine against COVID-19.

The FDA is not required to follow the advice of the advisory committee, but it often does.

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