Tracking the FDA advisory panel meeting on Covid-19 booster shots

Do most Americans already need Covid-19 booster shots, or at least will they soon? Those questions have been hotly debated in the public square over the past few weeks. But today, they’ll be debated in a formal setting where the discussion may affect whether the Biden administration carries through on an announced plan to offer adults booster jabs several months after they received their second shot of vaccine.

The debate will play out among members of the Food and Drug Administration’s vaccine expert panel, the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, which is meeting to review an application from Pfizer and BioNTech for a third dose of their messenger RNA vaccine, to be given six months after the second dose. While today’s discussion relates specifically to the Pfizer vaccine, it has implications for the future of boosters in general in this country.

In regulatory terms, the administration put the cart well out in front of the horse when it declared in August that a national campaign to administer third shots would begin the week of Sept. 20 — that’s next week — before the FDA had approved the Pfizer application and before the other two manufacturers supplying the United States had applied for the right to market a booster.


Now the horse is scrambling to assume its rightful position, beginning with VRBPAC. Next week, the Centers for Disease Control and Prevention’s equivalent panel, the Advisory Committee on Immunization Practices, is scheduled to meet for a day and a half to explore the issue. Since ACIP advises the CDC on whether it should recommend use of vaccines the FDA has approved, one might conclude that the planning scenario is premised on the FDA approving the Pfizer application sometime between the end of today’s meeting and the start of the ACIP meeting next Wednesday.

If it doesn’t, it will put the regulatory and public health agencies at odds with the administration and place acting FDA Commissioner Janet Woodcock and CDC Director Rochelle Walensky in highly awkward positions. They publicly signed off on the administration’s booster shot plan in August.


Different people see different things in the data that have been amassed so far on the efficacy of the mRNA vaccines — the Pfizer shot and the one made by Moderna, which has also applied for a booster license.

There is no argument that the remarkably strong protection against all infections that these vaccines exhibited in their Phase 3 trials has waned. Some people who are fully vaccinated are contracting Covid. But the vast majority of them have only mild or moderate symptoms. It’s still overwhelmingly true that the people who are being hospitalized or dying from Covid are people who are unvaccinated.

Many experts — including two FDA high-ranking officials who will be involved in today’s meeting — argue it’s not yet time to boost in this country. And the World Health Organization has been highly critical of the idea of boosting in affluent countries while most people in developing countries haven’t yet received a dose of vaccine.

Today’s proceedings — which can be viewed online here — are going to be really interesting. We’ll be live-blogging the hearing, which is scheduled to run from 8:30 a.m. to 4:45 p.m. EDT. The back-and-forth among the 19 panelists and data wranglers — the Pfizer representatives and the FDA staff — begins at 1:40 p.m. If there are going to be fireworks, they may start then.

Updates and analysis will be posted below in reverse chronological order.

— Helen Branswell

The question

8:45 a.m.: So the FDA has posted what it is calling Question 1. As there is only one question posted online at this time, that name begs the question: Does the FDA expect to need to ask additional questions?

It may well. Because Question 1 is: “Do the safety and effectiveness data from clinical trial C4591001 support approval of a COMIRNATY booster dose administered at least 6 months after completion of the primary series for use in individuals 16 years of age and older?”

The vote is a yes or no option.

If members of the committee object to giving boosters to 16- and 17-year-olds — given there are no data supporting the need or exploring the risks for this group at this point — they could vote this down, prompting the FDA to ask if the panel believes boosters are warranted for a narrower age group.

Pfizer and BioNTech applied for a booster authorization for people 16 and older.

— Helen Branswell

Reading some tea leaves

7 a.m.: Matt and I are not in the predictions business. But there are a few observations we thought we could make that might point to where this discussion may end up.

Matt: A lot of data that one would normally expect for an FDA advisory panel are not available. For one thing, the immunogenicity data being used to argue for booster shots are from a comparatively small study. There were no recipients under 18, even though Pfizer is requesting authorization for boosters for those 16 and up. Participants over 65 received the booster along with Pfizer’s pneumococcal vaccine, Prevnar. The FDA says such extrapolation is allowed as long as “no age group-specific safety or effectiveness considerations would preclude such extrapolation.” So that could be a point of debate.

Normally, the FDA relies on what’s called regulatory quality data that it has had the opportunity to comb through and re-analyze. But for many of the studies being analyzed, briefing documents say, “FDA has not independently reviewed or verified the underlying data or their conclusions.” Still, the data all point in a similar direction, to some waning of immunity.

There is also the worry of myocarditis and pericarditis, a side effect that is very rare and has appeared mostly in young men. The clinical trials are not big enough to give information about this risk, but it is exactly the kind of risk-benefit calculus that FDA panels normally perform.

It would be surprising if the panel doesn’t back boosters for anyone, but it seems very possible they will try to identify groups that should or should not get the booster shots. That’s a key point of discussion to watch for. But, then again, that decision isn’t entirely the FDA’s job: it’s supposed to decide if the product meets the bar for authorization, not how to roll out boosters.

Helen: Indeed, the hard job on the booster question doesn’t necessarily rest with VRBPAC. It probably falls to the ACIP. That’s the group that actually maps out how approved vaccines should be used. The final step in that process requires the CDC director to sign off on the ACIP’s recommendation, but that is generally a pro forma thing.

Should VRBPAC recommend that the FDA approve the Pfizer booster, they could do so with the knowledge that that doesn’t commit the country to offering everyone who got the Pfizer vaccine a third dose. ACIP will decide whether everyone needs to be boosted, or whether the program should start in a more targeted fashion, with elderly Americans — especially those living in nursing homes — and front-line health care workers. Those two groups were the first vaccinated and are also the people at highest risk, either because they are frequently exposed to SARS-CoV-2 (health workers) or because their aging immune systems don’t generate robust responses to vaccines (the elderly).

A special ACIP meeting for next Wednesday and Thursday was announced this week. Someone must have thought they’d have something to discuss.

ACIP has already met twice to discuss boosters in general terms. The committee hasn’t exactly sounded bullish on the need for them, and there have certainly been rumblings about members of the committee feeling that the White House got over its skis by announcing the booster program before boosters had been green lit by the FDA and CDC.

But there’s been a fair amount of turnover on ACIP over the past couple of months. The committee has a new chair and two new members, with a third in the wings, awaiting final approval of his or her appointment. (There are typically 15 members, including the chair.) It’s harder right now to predict how ACIP will come down on the issue because those new members don’t have a voting track record.

— Helen Branswell and Matthew Herper

Some booster background

7 a.m.: Good morning.

In order to understand today’s discussions, a bit of a vaccinology primer might be helpful.

Vaccines teach the immune system to recognize disease threats. They do so in a variety of ways, for example by injecting into our systems killed viruses or genetic coding that will prompt our cells to pump out versions of a protein found on the surface of a virus, triggering production of immune weapons that specifically target that particular threat.

Most vaccines are given in a series of two, three, or more shots. The first primes the immune system to recognize a threat; the subsequent shot or shots boost that initial response to generate (hopefully) long-lasting protection.

It’s not uncommon to space the first and the last shots in a series over several months. But both Pfizer and Moderna spaced their jabs out over a tight interval — three and four weeks, respectively — to try to vaccinate people quickly in the face of the pandemic threat.

Evidence from the United Kingdom, which used longer intervals between shots, suggests that a vaccinology truism — a longer interval is a more effective interval — probably is true here as well.

Experts argue about whether a booster is needed now. But most believe one may eventually be needed. And most acknowledge that people who get a third shot of the mRNA vaccines will have better, more long-lasting protection.

“I think having a late boost is going to make this a much better vaccine,” Barney Graham, who designed the structure for the vaccines made by Moderna and a number of other producers while he was deputy director of the Vaccine Research Center at the National Institutes of Health, said in a recent interview.

“Giving a boost to people would make them more protected and would reduce transmission. Now the question, I guess, is do you need to boost and what incremental value is there in boosting? Or do we have enough memory and a rapid enough … response that we’d be protected relatively well? And honestly, as the viruses are evolving and making more rapid transit from the upper to lower airway, I’m not sure the memory we have is going to be sufficient.”

As the last part of Graham’s remark implies, much of the thinking about the need to boost is steeped in the disquiet generated by the Delta variant — a highly transmissible form of the virus that has swept the globe in recent months.

At 68, Graham said, “I don’t know how well I would do if I get exposed to the Delta virus.” He added: “What I know is that the boost would work. We know now in humans and animals that a boost really pushes the antibody levels even higher than they were after the second dose.”

As for the WHO’s argument that a third dose for Americans delays first doses in low-income countries, Graham proposed a different way of thinking about the issue. If these vaccines truly are three-dose shots — if the third dose is critical to getting lasting protection — the world needs to know that, he said.

But Paul Offit, director of the Children’s Hospital of Philadelphia’s Vaccine Education Center and co-inventor of the rotavirus vaccine, has publicly stated he thinks it’s premature to be giving all adults booster shots at this point.

Offit is on VRBPAC. He’s unlikely to bite his tongue here.

— Helen Branswell

Source: STAT