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FDA’s Booster OK Puts Pfizer on Data Hunt, Muddles Off-Label Use

Sept. 23, 2021, 4:43 PM

The FDA’s decision to authorize boosters on an emergency basis for a fully approved Covid-19 vaccine opens the door to rolling out more third doses while putting Pfizer Inc. on the hook for more data and complicating avenues for broader, off-label use.

Pfizer has the green light from the Food and Drug Administration to offer a single booster of its vaccine to older and high-risk populations after the agency amended the company’s emergency use authorization late Wednesday. The expanded EUA applies to those who are at least six months out of getting their second Pfizer dose. It also only applies to adults 65 and older; 18 to 64 at high risk of severe disease; or 18 to 64 with high risk of serious complications due to their job or institutional setting, such as a homeless shelter or prison.

Pfizer is the only company with a fully approved coronavirus vaccine in the U.S., along with additional emergency authorizations for teenagers, third shots for immunocompromised individuals, and boosters for older and high-risk populations. It will now have to navigate the varying FDA pathways to figure out what additional data it needs to support full licensure of boosters.

“It’s interesting. It’s complicated,” Heather H. Pierce, senior director and regulatory counsel at the Association of American Medical Colleges, said in an interview.

“But as each segment of either the population or dose or whoever it is moves from the EUA to a BLA, it just gets a little bit cleaner and a little bit easier to interpret,” she said. Full approval is known as a biologics license application, or BLA.

The FDA’s latest decision to grant emergency authorization versus full approval also makes it more difficult for populations outside of those listed who may want to get a booster—given that providers must comply with the terms and limits of the EUA. Some people, including those younger than age 65 and who are not at high risk, have been seeking out boosters on their own ahead of the FDA’s authorization, immunologist Gigi Kwik Gronvall said.

“I’ve talked to people who thought that boosters were already allowed now because they were going off at the White House with statements about it,” said Gronvall, senior scholar at the Johns Hopkins Center for Health Security and an associate professor at the Johns Hopkins Bloomberg School of Public Health. The White House first announced a plan a month ago to make boosters available, which it said was contingent upon clearance from the FDA and the Centers for Disease Control and Prevention.

The regulatory complexities involved in making the first set of boosters available likely won’t affect the rollout of those third shots, however.

“I don’t think for patients who are going to get boosters or the doctors who are prescribing them, it will really mean anything,” Kalah Auchincloss, a former FDA deputy chief of staff who’s now executive vice president of regulatory compliance and deputy general counsel at FDA regulatory consulting firm Greenleaf Health, said. “From a practical perspective, it shouldn’t necessarily have many implications.”

The FDA announced the EUA expansion in the middle of a two-day CDC advisory committee meeting on how best to administer vaccines. The agenda for Thursday remained largely open when the meeting began Wednesday as the committee awaited the FDA’s decision.

Evolving Data

The FDA’s emergency use authorization mechanism makes products available more quickly in a public health emergency. Once the health and human services secretary rescinds that authority, those EUAs cease to become effective, Pierce said.

“The biggest difference is not going to be for individuals who are eligible for a booster under the EUA. It will be for the future when the public health emergency is declared over,” she said.

Pfizer will have to work with the FDA to “determine what data will be required to convert the booster portion of the EUA” to a supplemental biologics license application for full approval, Barbara A. Binzak Blumenfeld, an FDA regulatory attorney with Buchanan Ingersoll & Rooney PC, wrote in an email.

Auchincloss said she expects the FDA will need more data from Pfizer for the agency to grant a broad approval for boosters, based on the deliberations of the FDA advisory panel last week. “It sounded like there was some pretty big skepticism about whether there was enough evidence,” from both an efficacy and safety standpoint, she said.

“There’s some utility, obviously, for boosters in an older patient population, and maybe even there’s utility for boosters in the younger age population—if there’s additional data that can show that to us. But that’s certainly in question at this point,” Auchinloss said.

FDA leaders left that door open. “This pandemic is dynamic and evolving, with new data about vaccine safety and effectiveness becoming available every day. As we learn more about the safety and effectiveness of COVID-19 vaccines, including the use of a booster dose, we will continue to evaluate the rapidly changing science and keep the public informed,” Acting Commissioner Janet Woodcock said in a statement.

Off-Label Implications

The EUA for boosters also complicates the issue of potential off-label use, which had been seen as most likely to happen for booster shots and children following full approval of Pfizer’s vaccine last month.

Access to products under an EUA requires that providers stick to the terms of that authorization. Once approved, prescribers generally have more flexibility to offer a medical product for a reason not listed on the label.

“Because the vaccine is available through a BLA, providers would be able to provide it off label whether that’s for boosters or in theory for children,” Pierce said.

But to use a medical product under an EUA—which Pfizer has for boosters—providers must sign agreements with the CDC saying they’ll adhere to the terms of the authorization, she said. “That provides a strong disincentive for off-label use in any way of the approved vaccine.”

Pfizer had initially requested for an expansion to its BLA to allow third shots for everyone 16 and over who was inoculated with its vaccine.

“This first FDA authorization of a COVID-19 vaccine booster is a critical milestone in the ongoing fight against this disease,” Pfizer CEO Albert Bourla said in a statement. “We believe boosters have an important role to play in addressing the continued threat of this disease, alongside efforts to increase global access and uptake among the unvaccinated.”

Future Vaccine Regulation

The regulatory pathways Pfizer is following may provide a general roadmap for Moderna Inc. and Johnson & Johnson, Binzak Blumenfeld said. “However, each vaccine will be evaluated, and will rise and fall, on its own merits.”

Moderna in August said it completed the application process for full approval of its Covid-19 vaccine. J&J said it also intends to seek full approval. But at the moment these vaccines are only available through the EUA mechanism.

“If I were competitors, I would not put my money or my focus on boosters at this point, I would be looking at full approval,” Auchinloss said, adding she would focus on the younger population of children under 12 “who have nothing right now.”

Gronvall echoed the need to prioritize making vaccines available for younger children. “Why are we talking about boosters when we have all these unvaccinated children? That should really be the priority No. 1.”

However the drugmakers decide, future combinations of approvals—whether on an emergency, full, or supplemental basis—will depend in part on the order in which each sponsor seeks authorization and/or approval for younger age groups or boosters, Binzak Blumenfeld said. Advisory committee recommendations and actions from both the FDA and CDC also will play a role.

“This vaccination regulatory landscape is poised to continue to rapidly evolve,” she said.

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

To contact the editor responsible for this story: Alexis Kramer at akramer@bloomberglaw.com

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