FDA Has Broad Regulatory Options for Mixing Covid Boosters

Oct. 19, 2021, 1:36 AM

U.S. vaccine regulators have broad authority to allow mix-and-match Covid-19 vaccine boosters under their emergency powers, even if Johnson & Johnson and other companies don’t apply for it.

The Food and Drug Administration appears poised to clear heterologous boosting, which would allow someone who’s eligible for a booster to get an additional shot that’s different from their original vaccine. Preliminary results from a National Institutes of Health study indicate mixing Covid-19 vaccines as a booster can produce the same or even more antibodies compared with using the same vaccine for all shots. The study found the strongest antibody response by combining J&J’s one-shot vaccine with a booster from an mRNA vaccine developed by Pfizer Inc. or Moderna Inc.

It’s less clear what regulatory pathway the FDA will take to make heterologous boosting—or mixing and matching boosters—available. The emergency use authorizations for Covid-19 vaccines so far have stemmed from submissions from the companies themselves. But they’ve only applied for homologous boosting, or boosting a shot of the same vaccine originally administered.

“That raises some interesting questions because, generally speaking, the sponsor of the EUA would be the party in charge of determining which booster could be used,” James A. Boiani, an FDA regulatory attorney with Epstein Becker & Green PC, said.

J&J executives pushed back on the idea of mixing and matching boosters at an FDA advisory panel last week, saying the antibody level only told part of the study and that they prefer homologous boosting. Pfizer spokesperson Jerica Pitts indicated the company was open to the possibility of mixing boosters: “While this study was not conducted by Pfizer and BioNTech, we welcome the data that supports giving eligible populations more flexibility to receive a booster shot across vaccine regimens that will increase levels of protective antibodies.”

The FDA will likely ask vaccine makers to apply for a mix-and-match booster authorization voluntarily, Boiani said.

“The way it would generally work would be for FDA to informally request that. They might tell the sponsor, ‘We’d really like you to ask us for this authorization,’” he said.

The FDA could also make a public health requirement to require mixing and matching of booster shots, but Boiani said that’s a step that hasn’t happened before.

“It’s an odd situation, and it does sort of depend on how much FDA wants to try and push the envelope in terms of forcing this on parties that would want it right now,” he said. “I think the first instance will be FDA is going to try and encourage them and CDC would probably try and publicly pressure manufacturers to voluntarily allow for this.”

The statute that makes EUAs possible allows the Department of Health and Human Services to revoke or revise an authorization for several reasons, including circumstances that “make such revision or revocation appropriate to protect the public health.”

That statutory language gives the FDA a lot of flexibility to make changes to an EUA, even if a company hasn’t necessarily requested those changes, Patricia J. Zettler, an associate professor of law at Ohio State University who specializes in FDA regulation, said.

“I don’t see a reason to expect that companies would not request that revision if the data and information are there,” she said. “But if it’s the case that we really need those mix-and-match boosters, and companies are unwilling to request that revision, I think FDA has the legal flexibility to make those kinds of mix-and-match boosters available, potentially by revising EUAs.”

EUAs mean providers can’t go off-label like they would for a fully approved medical product, but the FDA could opt not to enforce that part of the EUA, essentially allowing mixing and matching of boosters by exercising enforcement discretion, Zettler and Boiani both said.

The Centers for Disease Control and Prevention also could act as a sponsor to request heterologous boosting, Boiani said. This wouldn’t be unprecedented since the CDC acted a sponsor for Zika tests and the HHS’s Office of the Assistant Secretary for Preparedness and Response sponsored emergency requests for convalescent plasma and the now-revoked EUA for hydroxychloroquine. But he said such an approach would be an odd move by the agency.

“It’s highly unusual for FDA to do something on its own without having the sponsor come to it,” Boiani said. “This is unusual for them to add on different medications when a sponsor’s saying that’s not what we’re asking for authorization for, and you’re expanding it without our consent. That just doesn’t happen.”

To contact the reporter on this story: Jeannie Baumann in Washington at jbaumann@bloombergindustry.com

To contact the editors responsible for this story: Alexis Kramer at akramer@bloomberglaw.com; Karl Hardy at khardy@bloomberglaw.com

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