Sept. 2, 2021 -- Many Americans are clamoring for a booster dose of a COVID-19 vaccine after reports of rising numbers of breakthrough infections, and demand only shot up after the Biden administration said they would begin offering those shots on Sept. 20.

That plan, which was first announced on Aug. 18, has raised eyebrows because it comes in advance of regulatory reviews by FDA and CDC, , which are required to determine whether third doses of these vaccines would be effective or even safe. The move could have important legal ramifications for doctors and their patients, too.

On Tuesday, two high-level officials in the FDA’s office of Vaccines Research and Review at the FDA abruptly resigned, amid reports that they were angry that the White House was making decisions that should be left up to the agency.

So far, data shows that the vaccines remain highly effective at preventing the most severe consequences of COVID-19 — hospitalization and death — even against the Delta variant. The World Health Organization has also urged wealthy nations like the United States not to offer boosters so that the limited supply of vaccines can be directed to countries with fewer resources.

White House Supports Boosters

In a recent press briefing, Jeff Zients, the White House COVID-19 Response coordinator, defended the move.

“You know, the booster decision, which you referenced … was made by and announced by the nation’s leading public health officials,” including CDC Director Rochelle Walensky, MD, Anthony Fauci, MD, the chief medical officer to President Joe Biden, Surgeon General Vivek Murthy, MD, acting FDA Commissioner Janet Woodcock, MD, Francis Collins, MD, the director of the National Institutes of Health, and others, Zients said,

“And as our medical experts laid out, having reviewed all of the available data, it is in their clinical judgment that it is time to prepare Americans for a booster shot,” he said.

Zietns said the announcement of a Sept. 20 target date was to give states and vaccine providers time to prepare, and that the move to give boosters was meant to help the U.S. stay ahead of a rapidly changing virus. Zients added that starting boosters on Sept. 20 would still depend on the FDA’s and CDC’s go ahead.

“Booster doses are going to be handled the same way all vaccines are handled,” said Kristen Nordlund, a CDC spokesperson. “Companies will have to provide data to FDA. FDA will have to make a decision and authorize the use of those, and [the CDC’s] ACIP will have to look at the evidence as well and make recommendations on top of FDA's regulatory action,” she said.

Nordlund agreed that the planned Sept. 20 start date for boosters was aspirational, and not necessarily set.

Historically, the FDA has needed at least 4 months to review a change to a vaccine’s approval, even on an accelerated schedule. Reviewers use that time to scrutinize data down to the level of individual patients involved in a study, to review raw data, and essentially check a drug company’s math and conclusions.

After the FDA approves, the CDC’s Advisory Committee on Immunization Practices must meet to review the evidence and make recommendations on the use of the boosters in the U.S.

Pfizer says it completed its submission for a supplemental Biologics License Application (sBLA) to the FDA on Friday, Aug. 27. To meet a Sept. 20 timeline, the entire process has to be completed within 3 weeks, meaning the Biden administration’s timeline would shorten the review period from months to just a few weeks.

“FDA in a Very Difficult Position”

“I don't think that was handled, you know, ideally,” said Peter Lurie, MD, president of the Center for Science in the Public Interest and former FDA associate commissioner of public health strategy and analysis.

“It puts FDA in a very difficult position,” Lurie said. “It's almost as if the decision has been made and they're just checking a box and that is, you know, contrary to the what FDA -- at least the internal people at FDA -- have been trying to do for ages.”

He said the agency took great pains with the both the emergency use authorizations (EUAs) and the full approvals of the vaccines to work as rapidly but thoroughly as possible. They did not skip steps.

“I think all of that reflected very well on the agency,” Lurie said. “And I think it worked out well in terms of trust in the vaccines.”

Though additional doses of vaccine are expected to be safe, there’s little known about side effects or adverse events after a third dose.

“It’s critical to wait for additional data and regulatory allowance for booster doses,” said Sara Oliver, MD, a member of the CDC’s epidemic intelligence service in an Aug. 30th presentation to the Advisory Committee on Immunization Practices, the group charged with making recommendations for use of all vaccines in the U.S.

Boosters Already Being Given

But after the announcement by the White House that boosters were on the way, many people are not waiting.

Many health care providers and pharmacies have already been giving people third doses of vaccines, even if they don’t fall under the umbrella of immunocompromised — the group of people who are currently approved for the shots.

“You can walk into a pharmacy and ask for a third dose. Depending on which pharmacy you go to, you may get it,” said Helen Talbot, MD, an associate professor of medicine at Vanderbilt University in Nashville and a member of ACIP.

She says he has a friend who recently went for a checkup and was offered a third dose because his doctor is already giving extra doses to everyone who is over age 65.

Talbot said that in fairness, pharmacies are throwing away vaccine doses in the U.S. because they are expiring before they get used.

“Many of us may or may not be ready to give a third dose, but would rather give someone a third dose, than throw a vaccine away,” she said.

Consequences of a Third Shot

But giving or getting a third dose before they are approved by the FDA may have legal consequences.

In Monday’s ACIP meeting, Demetre Daskalakis, MD, who leads vaccine equity efforts at the CDC, cautioned that doctors who give extra doses of the vaccine before the FDA and CDC have signed off may be in violation of provider agreements with the federal government, and might not be covered by the federal Public Readiness and Emergency Preparedness Act.  Better known as the PREP Act, the law provides immunity against lawsuits for people who administer COVID-19 vaccines, and compensates patients in the event of injury.

“Many of us gasped when he said that,” Talbot said, “because that’s a big deal.”

The ACIP signaled that it might be looking at recommending boosters for a much narrower slice of the American population than the Biden administration has suggested.

They said that so far, the data only points to the need for boosters in seniors, who are most likely to experience breakthrough infections that require hospitalization, and health care workers, who are needed now more than ever and cannot work if they’re sick. 

In a White House news briefing Monday, Walensky was asked about ACIP’s conclusions and whether she believed there was enough data to recommend booster shots for most Americans 8 months after their last dose.

“The ACIP did not review international data that actually has led us to be even more concerned about increased risk of vaccine effectiveness waning against hospitalization, severe disease, and death.  They will be reviewing that as well,” she said.