FDA authorization of COVID-19 vaccines would set off a scramble

Several steps remain between approval and distribution — here's what to expect

A sign at the entrance to a pharmacy in Burbank, Calif., tells customers that a COVID-19 vaccine is not yet available. While multiple possible vaccines are nearing approval, several steps remain before they could be distributed. (Robyn Beck/AFP via Getty Images)
A sign at the entrance to a pharmacy in Burbank, Calif., tells customers that a COVID-19 vaccine is not yet available. While multiple possible vaccines are nearing approval, several steps remain before they could be distributed. (Robyn Beck/AFP via Getty Images)
Posted November 30, 2020 at 9:26am

The Trump administration's pledge to start shipping COVID-19 vaccines “within 24 hours” of a green light from the Food and Drug Administration will lead to a multi-step scramble during the time between authorization and the first shots going into arms.

Any thumbs-up from the FDA would kickstart the distribution of 6.4 million vaccine doses among 64 states, territories and major cities, based on population, Gen. Gustave Perna said Tuesday. Perna co-leads Operation Warp Speed, the Trump administration's initiative on COVID-19 vaccines and treatments.

[Moderna vaccine shows high efficacy as questions about uptake remain]

Here’s what to expect over the next few weeks.

FDA review

The first step is a scientific review by the FDA.

FDA’s evaluations will likely happen quickly because as part of the administration’s efforts to accelerate the process, the agency is already accepting data on a rolling basis. But the applications for emergency use authorization, like any standard application, will likely be thousands of pages long, FDA Commissioner Stephen Hahn confirmed to USA Today Tuesday.

FDA official Peter Marks, who leads the career scientists reviewing the data, has said people should expect the process to take a few weeks. On Nov. 20, Pfizer and its partner BioNTech were the first to finish submitting all of their data. Moderna Inc. announced it will file its request Monday.

[Deep freezers and dry ice for Pfizer vaccine may face shortages]

For a COVID-19 vaccine, "we'll only be thinking about issuing [an emergency use authorization] if it's demonstrated clear and compelling efficacy in a large, well-designed, phase 3 clinical trial similar to that which would be required to support an approval. And that's because it's potentially going to be administered to millions of individuals, including healthy people,” Marks said on an FDA podcast last month.

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FDA also provides the data to a panel of independent experts, the Vaccines and Related Biological Products Advisory Committee, which advises the agency on vaccine approvals. Although the committee’s advice is non-binding, FDA follows most VRBPAC recommendations.

The VRBPAC meeting to discuss Pfizer and BioNTech’s vaccine candidate — which can be watched via livestream — is scheduled for Dec. 10.

Experts emphasize the meeting will be important for establishing trust.

At an earlier meeting in October, the group expressed concerns about whether there would be enough follow-up safety data, and whether the vaccines will prevent severe COVID-19 cases.

Experts say the early evidence shared by the drugmakers seems promising, though.

“The size of these trials is the size of any trial that would be submitted for [standard approval]. The only difference is the length of the study is much shorter,” said committee member Paul Offit, co-developer of the rotavirus vaccine. “But then again, it has to be. You’re not going to study these vaccines for two or three years for a virus that’s killed 250,000 people this year.

“So the question is have we reduced a critical amount of uncertainty?" Offit said. “We’ll drill down on these data to see what the story is.”

Hahn said after the advisory committee makes its recommendation, FDA may take a few days to digest the advice and decide whether to authorize the vaccine. Operation Warp Speed co-lead Moncef Slaoui has indicated authorization could happen the same day as the VRBPAC meeting.

Prioritizing populations

The Advisory Committee on Immunization Practices, which guides the CDC on vaccine schedules, also would vote on how to prioritize populations in vaccination. Like VRBPAC, the ACIP typically holds its meetings openly with opportunities for public comments. That could boost confidence in the process.

An ACIP working group on COVID-19 vaccines already spelled out broad goals: maximizing benefits and minimizing harms, promoting justice, mitigating racial and economic inequities, and ensuring transparency. The working group said health care personnel, essential workers, adults with high-risk medical conditions and adults 65 years old or older should be first in line for shots.

But the full ACIP would vote on more detailed recommendations on who receives priority specific to each FDA-authorized vaccine.

These meetings typically occur after FDA's determination, but Department of Health and Human Services Secretary Alex Azar indicated he wants to speed things up.

“I'm working directly with CDC Director Robert Redfield on how we could convene the ACIP, hopefully, concurrent with the FDA review,” Azar said. “Every hour, every day matters.”

Vanderbilt University infectious diseases expert William Schaffner, who has been affiliated with ACIP for 25 years, said it’s good to ensure the FDA and ACIP can simultaneously “chew on the data.”

But Schaffner said if ACIP issues recommendations early, conditional on a vaccine’s authorization, that could risk undermining FDA’s authority.

“ACIP has always been very careful in their discussions to say, ‘This preliminary data is in process of being investigated by the FDA, and we all have to remember this vaccine hasn’t been approved yet,’” Schaffner.

Azar said he doubted ACIP's recommendations would significantly change states’ plans on where to send the vaccine, and does not expect the meeting to be a time-consuming step. Azar noted that ACIP's recommendation on any COVID-19 vaccine is important for reimbursement. Under the 2010 health care law, private insurance companies must cover vaccines recommended by ACIP without a copay.

Meanwhile, states are already operating off earlier recommendations by the National Academies of Science, Engineering and Medicine.

“The final say will be up to our governors,” Azar said. “We are not dependent on any delay from ACIP in terms of helping to advise states on prioritization.”

But if the clinical trial data shared with ACIP indicates the vaccine is less effective in some populations, as is sometimes the case with older people, that could mean big differences between what states are planning and what ACIP recommends.

Depending on where you live, any COVID-19 vaccine may need to surmount one more hurdle before distribution. Some states, including New York, plan to independently review the clinical data.

Even critics of the FDA under Trump question this step.

“There are likely hundreds of career staff who touch a candidate drug as it courses its way through the regulatory system. No hurriedly assembled state committee can reproduce this process,” said former FDA official Peter Lurie, president of the Center for Science in the Public Interest, in a recent editorial. “But these shadow committees carry an unintended danger: They could reinforce public distrust.”

Distributing doses

After all this, Operation Warp Speed officials say a vaccine would go immediately to sites that public health departments designate through a new software system called “Tiberius.”

“Every jurisdiction will have access immediately,” said Perna.

One red flag is that some health systems say they aren't prepared to distribute vaccines continually stored in frigid temperatures such as the Pfizer one.

Perna said Operation Warp Speed has begun running drills on how to administer the Pfizer vaccines, but these drills have only been completed with 10 of the total 64 vaccine jurisdictions such as states and cities. The CDC published more guidance on storing and handling COVID-19 vaccines this week, which public health departments awaited for months.

Public health departments also are still billions short of the funding they want for the unprecedented challenge. Redfield testified to Congress that an estimated $6 billion is needed, while health departments are seeking $8 billion.

Asked whether broad immunity is possible without that distribution funding, Sen. Patty Murray, D-Wash., said, “I highly doubt it.”