First published December 9, 2020.
On 8 December 2020, the US Food and Drug Administration published its staff review of the Pfizer–BioNTech COVID-19 vaccine. The document found that the two-dose vaccine was about 95 percent effective at preventing symptomatic COVID-19 in its large clinical trial and raised no specific safety concern that would block emergency use. Two days later an outside advisory panel voted in favour, and on 11 December the FDA issued the first emergency use authorisation for a COVID-19 vaccine in the United States.
Headlines at the time said the vaccine had received an "A+" from the FDA. The agency does not hand out grades. That phrase came from a Yale immunologist commenting on the data. Here is what the review actually said, what the numbers meant, and how the picture developed once millions of people had been vaccinated.
What the FDA review was
When a company asks the FDA for an emergency use authorisation, agency scientists reanalyse the trial data rather than relying on the company's summary. For the Pfizer–BioNTech vaccine, they released a briefing document of about 50 pages ahead of a public meeting of the Vaccines and Related Biological Products Advisory Committee, a panel of independent doctors, statisticians and infectious disease specialists.
The review concluded that the trial showed "no specific safety concerns identified that would preclude issuance of an EUA." It also found that protection was consistent across age groups, sexes, racial and ethnic groups, and people with conditions that raise the risk of severe COVID-19, such as obesity or diabetes.
Akiko Iwasaki, an immunologist at Yale University, summed up the reaction of many scientists when she told The New York Times: "This is what an A+ report card looks like for a vaccine." It was praise from an outside expert, not a rating from the regulator.
From panel vote to authorisation
The advisory committee met on 10 December 2020 and voted 17 to 4, with one abstention, that the benefits of the vaccine outweighed its risks for people aged 16 and over. Some members felt the data on 16- and 17-year-olds was thin, and several noted that follow-up was still short. The panel also discussed two severe allergic reactions reported among health workers in the UK on the first day of its rollout.
The FDA authorised the vaccine the next day. The UK had already become the first country to approve it, and Britain's mass vaccination campaign began on 8 December 2020, the same day the FDA review appeared.
What "95 percent effective" means
The trial enrolled more than 40,000 volunteers, half given the vaccine and half a placebo. Researchers then counted who developed confirmed COVID-19 with symptoms. Far fewer cases appeared in the vaccinated group, which produced an efficacy estimate of 95 percent.
That figure is often misread. It does not mean 95 percent of vaccinated people became immune, or that 5 percent were left unprotected. It means that vaccinated participants had about 95 percent less risk of symptomatic illness than unvaccinated ones during the trial period. The trial was not designed to show how well the vaccine blocked silent infection or transmission, or how long protection would last.
Later experience answered some of those questions. Protection against infection faded over months and fell further with new variants such as Omicron, which is why booster doses were introduced. Protection against severe disease and death held up much better.
Side effects seen in the trial and afterwards
The most common reactions in the trial were pain at the injection site, tiredness, headache, muscle aches, chills and sometimes fever, usually more noticeable after the second dose and generally gone within a day or two. These are signs of the immune system responding.
A trial of tens of thousands of people cannot detect very rare events, and some appeared only after rollout. Severe allergic reactions (anaphylaxis) occurred in roughly 11 cases per million doses, mostly within 15 minutes, which is why people are observed briefly after vaccination. A rare risk of heart inflammation, myocarditis, was later identified, mainly in young men after the second dose; most cases were mild. Anyone with a history of serious allergies or other concerns should talk to a doctor before vaccination.
So the claim, repeated widely in December 2020, that there were "absolutely no serious reactions" went further than the evidence. The review found no safety signal that outweighed the benefit, which is a different and more careful statement.
How mRNA vaccines work
Traditional vaccines usually contain a weakened or inactivated virus, or a piece of one. The Pfizer–BioNTech vaccine instead carries messenger RNA, a set of instructions wrapped in tiny fat particles called lipid nanoparticles. Once inside cells, the instructions are used to make a harmless copy of the coronavirus spike protein, the structure the virus uses to enter cells.
The immune system recognises the spike as foreign and builds antibodies and T cells against it, so it can respond quickly if it meets the real virus. The mRNA itself breaks down within days and does not enter the cell nucleus or alter DNA. The drawback in 2020 was storage: the vaccine had to be shipped at about −80 to −60 °C, which made distribution difficult.
How it compared with other vaccines
Moderna's mRNA vaccine reported similar efficacy, around 95 percent, and was authorised in the US a week later. The Oxford–AstraZeneca vaccine, which uses a modified cold virus, reported an average of 70 percent in interim results, combining 62 and 90 percent from groups given different doses. Its big advantage was that it could be kept in an ordinary refrigerator, and the UK approved it on 30 December 2020. A very rare clotting disorder was later linked to it, and AstraZeneca withdrew the vaccine worldwide in 2024 as demand shifted to updated vaccines.
When the FDA review came out, the pandemic was at a grim stage. More than 280,000 people in the United States had died of COVID-19, far more than the roughly 58,000 Americans killed in the Vietnam War, and the UK's toll stood at between about 60,000 and 70,000 depending on how deaths were counted.
From emergency use to full approval
The emergency authorisation was a temporary step. On 23 August 2021 the FDA granted full approval to the Pfizer–BioNTech vaccine, sold as Comirnaty, for people aged 16 and older, making it the first fully approved COVID-19 vaccine in the US. Use in younger age groups and booster doses followed through later authorisations, and the vaccine has since been updated to match newer variants.
The December 2020 review remains a useful example of how regulators work under pressure: independent reanalysis, a public advisory meeting, and continued safety monitoring once a product reaches millions of people.
Sources: The New York Times, 8 December 2020 (Iwasaki and FDA review); RAPS, 11 December 2020: advisory committee vote; Wikipedia: Pfizer–BioNTech COVID-19 vaccine; Wikipedia: Oxford–AstraZeneca COVID-19 vaccine.
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