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What the FDA is considering in its emergency approval of a Covid-19 vaccine

Should the FDA have moved even faster on vaccine approval?

A sign for the Food and Drug Administration is seen outside of the headquarters on July 20, 2020, in White Oak, Maryland.
An advisory committee to the Food and Drug Administration is meeting today to consider the emergency use authorization request from Pfizer and BioNTech for their Covid-19 vaccine.
Sarah Silbiger/Getty Images
Umair Irfan is a correspondent at Vox writing about climate change, Covid-19, and energy policy. Irfan is also a regular contributor to the radio program Science Friday. Prior to Vox, he was a reporter for ClimateWire at E&E News.

The United States is on the verge of granting emergency approval to its first vaccine for Covid-19, in what will be the culmination of the fastest vaccine development effort in history. But with 3,000 Americans dying a day (as of December 9) from the disease, the wait has been nonetheless agonizing.

The Food and Drug Administration is meeting Thursday to consider the emergency use authorization (EUA) request from Pfizer and BioNTech for their mRNA vaccine for people aged 16 and older. The two companies have reported that their vaccine candidate is 95 percent effective at preventing disease, with no serious safety concerns. The FDA committee evaluating the vaccine has scheduled a vote on the EUA for Thursday afternoon. To support their application, Pfizer and BioNTech revealed critical details about their vaccine for the first time, which the FDA made available to the public on December 8.

The agency has also scheduled an EUA evaluation on December 17 for the Covid-19 vaccine developed by Moderna, which has also reported about 95 percent efficacy. Both the Moderna and the Pfizer/BioNTech vaccines require two doses spaced several weeks apart.

If granted an EUA, the first doses of the Pfizer/BioNTech vaccine could begin rolling out to health workers and long-term care facility residents and staff — the two groups deemed the top priority by an advisory group to the Centers for Disease Control and Prevention — in the US within days. The United Kingdom and Canada have already granted limited approval to this vaccine, with hospitals in the UK starting to immunize people against Covid-19 this week. Pfizer and BioNTech expect to produce 50 million doses of their vaccine globally, enough for 25 million people, before the end of the year.

It’s likely the FDA will follow suit, but its lag behind the UK highlights the difficult balancing act of gathering enough information about a new vaccine that will be administered to millions of people amid the screaming urgency of a pandemic that’s killing thousands per day. Some researchers have criticized the FDA for sticking to its timeline despite early data about the efficacy of the Pfizer/BioNTech vaccine being available for weeks.

And there are still some important concerns beyond efficacy that will shape how the vaccine will be distributed and the role it will play in drawing down the pandemic. Here is some of the new information about the Pfizer/BioNTech vaccine that was revealed this week and some of the questions that remain.

What we learned this week about the Pfizer/BioNTech Covid-19 vaccine

The FDA’s Vaccines and Related Biological Products Advisory Committee is going over Pfizer and BioNTech’s vaccine clinical trial in a public meeting Thursday for the first time to consider their application for an EUA.

Until recently, the only information about the vaccine available to the public came from press releases. On Tuesday, the FDA published a 52-page briefing from the companies about their vaccine, revealing more detailed information about their clinical trial. The trial recruited more than 43,000 participants across a wide range of demographics. The results so far are striking and promising, and FDA experts expect that an EUA will likely be granted shortly after the committee votes on it.

One revelation this week was that the vaccine (also known as BNT162b2) begins to offer protection against Covid-19 after just one dose, although it seems to take some time to build up immunity. The trial detected 178 Covid-19 cases among its participants, with just nine in the group that received the vaccine and most of those occurring between the first and second doses. The second dose of the vaccine was administered 21 days after the first and getting both doses seems to confer stronger protection.

A graph comparing a placebo group to the treatment group in the Pfizer-BioNTech Covid-19 vaccine clinical trial.
Cases mounted quickly in the placebo group (red) and remained low in the vaccine group (blue).

The FDA also revealed more information about the demographics of the participants in the trial. The companies recruited people across a variety of ages and ethnic groups, as well as people with existing health conditions like obesity, diabetes, and chronic pulmonary disease.

Chart showing the demographics of the Pfizer-BioNTech Covid-19 vaccine clinical trial.
Pfizer and BioNTech recruited a variety of participants for their clinical trials.

Across the board, the vaccine seems to shield people against Covid-19, but within specific subsets of the population, it’s harder to gauge efficacy since there are so few cases to compare between the treatment and placebo groups.

For instance, older adults face some of the highest risks of dying from Covid-19. While there were more than 800 people in each of the placebo and treatment groups over the age of 75, there were five detected Covid-19 cases in the placebo group and none in the group that received the vaccine. That demonstrates 100 percent efficacy in that age bracket, but it’s only based on a difference of five cases. Consequently, the reported confidence interval for that age bracket is massive.

Chart comparing Covid-19 cases in the Pfizer-BioNTech Covid-19 vaccine phase 3 trial.
Most of the Covid-19 cases in the Pfizer-BioNTech clinical trial occurred in people between the ages of 18 and 64.

And there were also groups that were excluded from the trial completely, including people under the age of 16, pregnant women, and people with certain immunological conditions.

The task for regulators will be determining how much they can extrapolate from the limited information they have in order to come up with recommendations for how to deploy this vaccine, especially in these high-risk groups.

The data this week also showed a range of side effects. “The most common solicited adverse reactions were injection site reactions (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%),” according to the briefing.

However, one key side effect this week was revealed from outside the clinical trial. Two patients in the UK reported allergic reactions to the vaccine. It’s not yet clear what component of the vaccine triggered the reactions, but the UK’s National Health Service issued new guidelines saying that people with a history of significant allergies should not receive this vaccine.

The new documents this week also acknowledged some of the important unanswered questions in the vaccine trial.

These include how long protection lasts; the effectiveness in people at high risk for severe Covid-19, such as people with HIV/AIDS; effectiveness in people previously infected with Covid-19; effectiveness in children; effectiveness against mild or asymptomatic infection; effectiveness against transmission of the virus; effectiveness against mortality; effectiveness against mutated versions of the virus; and potential long-term complications.

The answers to these questions will influence how the vaccine will be distributed on a larger scale and will shape the ultimate decline of Covid-19 in the population.

Could, and should, the FDA have moved faster on a Covid-19 vaccine?

Americans may be watching with envy as the first doses of the Pfizer/BioNTech Covid-19 vaccine roll out in other countries and wondering why the US couldn’t get there sooner.

Writing in The Dispatch, Marty Makary, a professor of surgery at Johns Hopkins University, said regulators could have done more to speed up the process, especially given the urgency of the pandemic, and he argued that delays were political maneuvers:

Americans have a right to ask why an American vaccine has been approved by the British but not by Americans. Some sympathetic to the FDA career staff have suggested that the U.K. was careless in approving the vaccine quickly, but the real story is how the American government bureaucracy wasted time.


As the FDA career staff ponder the safety of known transient side effects like fatigue, they should consider the thousands of Americans dying each day they sit on the application.

But other experts said that the FDA is already working as fast as it can without cutting corners. Jesse Goodman, a former chief scientist at the FDA who’s now a professor of medicine at Georgetown University, noted that the UK’s health regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA), conducts its reviews differently from the FDA.

The MHRA looks at trial data on a rolling basis, evaluating it as it comes in, while the FDA evaluates more completed results. He also noted that both the Pfizer/BioNTech vaccine and the Moderna vaccine use a technology that has never been approved for widespread use before. Not only does that introduce new scientific questions, it also raises concerns about how well these companies will be able to manufacture the vaccines at scale while maintaining a high level of quality.

“The public needs to understand that these are new technologies that have never been used to scale up to millions of doses before,” Goodman said. “Those factors mean to me a three-week review of all that is exceptionally fast.”

Another factor to consider is public trust. This is a vaccine that has to be administered to millions of people, but short of a government mandate, it has to be voluntary. But without a massive uptake of the vaccine, the pandemic will persist. The early days of distribution of the vaccine are especially critical: We’ll never have a second chance for the first rollout.

Getting people to get their shots requires assuring them that the vaccine is safe and effective and that the approval came without any political influence.

“The way you do that is you have everything transparent, get all the data published and discussed,” said Eric Topol, a professor of molecular medicine at the Scripps Research Translational Institute. That’s a big reason why the FDA is making its evaluations of the vaccine public, unlike the UK.

And while it’s true that the US is now squarely in the worst days of the Covid-19 pandemic, with hospitalizations and daily deaths reaching new records, many of these effects are baked in for the time being. A vaccine prevents disease, but it does little to help people who are already sick and may do little for people who are already infected. Since the virus that causes Covid-19 can take up to two weeks before causing symptoms, with hospitalizations and deaths following after that, there is little a vaccine can do to reverse the incoming surge.

To begin to interrupt transmission of the virus, millions of people would have to receive the vaccine, and that could take months. “The vaccine isn’t going to stop deaths until we get further into this,” Topol said.

As the FDA noted in its briefing document, it’s still not clear how well the Pfizer/BioNTech vaccine can prevent deaths. “A larger number of individuals at high risk of COVID-19 and higher attack rates would be needed to confirm efficacy of the vaccine against mortality,” according to the document. “Benefits in preventing death should be evaluated in large observational studies following authorization.”

That means that until everyone that wants a vaccine can get one, the best ways to stall the Covid-19 pandemic remain what they’ve always been: handwashing, social distancing, wearing masks indoors with people outside your household and outdoors in crowds, and limiting unnecessary exposures. Meanwhile, the clinical trial of this vaccine will still need to continue in order to resolve crucial unknowns. But with a powerful tool like a vaccine in hand, the path out of the pandemic is the clearest it has ever been.