The First Authorized COVID-19 Vaccine in the U.S. Has Arrived

Late in the evening on Dec. 11, the U.S. Food and Drug Administration (FDA) authorized the first COVID-19 vaccine for use in the country. The emergency use authorization means that doses of the vaccine—made by Pfizer/BioNTech—can be shipped at any time; certain Americans could be vaccinated as soon as next week.

In a statement, FDA commissioner Dr. Stephen Hahn said “The FDA’s authorization for emergency use of the first COVID-19 vaccine is a significant milestone in battling this devastating pandemic that has affected so many families in the United States and around the world.” In the same press release, Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, noted that “efforts to speed vaccine development have not sacrificed scientific standards or the integrity of our vaccine evaluation process.”

The authorization for the two-dose vaccine comes a day after an FDA advisory committee voted 17-4 (with one abstention) to greenlight the vaccine after reviewing data on the shot’s safety and efficacy.

“We have received the great news that the FDA has authorized the emergency use of our COVID-19 vaccine for people 16 or older,” Albert Bourla, Pfizer Chairman and CEO, said in a Dec. 11 video statement announcing the authorization. Bourla said the company is ready to begin shipping doses “immediately” throughout the U.S. from its three manufacturing facilities in Andover, Mass.; Kalamazoo, Mich.; and St. Louis, Mo. The vaccine has already received approval in the UK and health officials began vaccinating people there on Dec. 8; it has also been approved in Canada, where the first shots are expected next week.

”It is a wonderful feeling because for the first time outside of clinical trials, we see something that was developed in our lab that could reach people and could change that vaccinated person’s life,” Ugur Sahin, co-founder of BioNTech, tells TIME. “The understanding that it will make a difference to many, many, many people and all of their families is an extremely powerful and energizing feeling.”

In the U.S., the CDC has said health care workers and older people living in long-term care centers will get the first of the expected 2.9 million or so doses—which Pfizer has already produced—that will be distributed to the U.S. public. Another 3 million doses or so will be reserved to ensure that all those who are vaccinated during this initial round will get their second dose 21 days later.

By next spring, the company expects to ship 100 million doses to fulfill its first order from the U.S. government. The CDC’s Advisory Committee on Immunization Practices, which makes immunization recommendations for the U.S. population, met on Dec. 11 and will meet again on Dec.13 to iron out the final details of who should be vaccinated first, based on the EUA.

During the day-long meeting of the FDA’s Vaccines and Related Biologics Products Advisory Committee on Dec 10, the 22 voting members heard a presentation from Pfizer scientists detailing the 44,000-person study that showed the vaccine was 95% effective in protecting against COVID-19 disease, as well as an analysis from FDA scientists of that data and earlier trials of the shot. Pfizer’s data showed that the vaccine was equally effective across different age groups, among people from different racial and ethnic backgrounds and among people with underlying health conditions—critical data since Black and Latinx populations have been disproportionately affected by the disease, as have those with chronic health conditions. “There were no specific safety concerns identified in the analysis of [these] subgroups,” said Dr. Susan Wollersheim, medical officer in Center for Biologics Evaluation and Research at the FDA, who presented the agency’s analysis.

The Dec. 11 EUA means that the vaccine could be distributed like any other approved shot, with an important caveat. EUAs are granted only under public health emergencies, and so require manufacturers to report follow up data on safety and effectiveness on a shorter time frame than usual. Pfizer and BioNTech will continue the studies they began in six countries (the U.S., Argentina, Brazil, Germany, South Africa and Turkey) and follow participants for two years to collect more information on how long the immunity provided by the vaccines lasts, and whether any serious side effects occur over time. Already, days after the UK began vaccinating some citizens with the Pfizer/BioNTech shot, the health regulatory agency there issued a warning that people with allergies severe enough to require them to carry epinephrine should not get vaccinated after two health care workers with allergies developed severe reactions to the shot.

Pfizer and FDA scientists have received more information on the two cases in the UK that prompted the warning, and the EUA specifies that anyone with allergies to any of the components of the vaccine should not get the shot. The EUA also requires that any location offering the vaccine keep on hand emergency medications to treat allergic reactions.

The EUA is historic for a number of reasons. For one, it would be the first vaccine based on mRNA technology to receive authorization in the country. mRNA is a genetic material that codes for proteins; the Pfizer/BioNTech vaccine is built around the mRNA coding for the COVID-19 virus’s spike protein, which is encased in a fatty lipid particle and injected into the body, where immune cells recognize it as foreign and target the viral material for attack.

Because all that’s required to create an mRNA vaccine is the genetic sequence of the virus, these shots can be developed relatively quickly compared to more traditional methods. The genetic sequence of the COVID-19 virus, called SARS-CoV-2, was released in January, and by May the companies injected the first volunteer in its human trials. That speed could set a new precedent for developing vaccines not just against emerging infectious diseases but also for influenza; Pfizer and BioNTech’s partnership began, in fact, with a program to develop an mRNA-based flu vaccine.

Because the technology is new, however, the vaccine advisory committee members raised a lot of questions about how regulators would monitor its safety, especially among younger people for whom there is less data (Pfizer expanded enrollment to include adolescents after the trial began). One panel member, Dr. Cody Meissner, professor of pediatrics at Tufts University School of Medicine, abstained from voting due to his discomfort with including teens 16 and 17 years old in the EUA. “I do not believe there is sufficient data on 16- to 17-year olds. I would prefer to say [the EUA is for] use in 18 year olds and older,” he said, adding that “16- and 17-year olds do not get very sick, they are seldom hospitalized, and I bet they are a very small number of deaths.”

Pfizer and the FDA responded to the concern by outlining plans to continue studying younger populations (the current ongoing study now includes children as young as 12). Under the EUA, Pfizer agreed to continue monitoring potential side effects among all those who are vaccinated. Those data will be added to government-based monitoring programs, which include a new text-based system for contacting people who are vaccinated, and which those individuals can use to report any potential side effects, along with established systems for doctors and hospitals to report adverse events.

Another concern about the Pfizer/BioNTech vaccine is that it needs to be stored and shipped at -70°C (-94°F), far below normal freezer temperatures. Pfizer is shipping the shots using its own specially designed thermal packaging, which will maintain these ultra-cold temperatures with dry ice for up to 15 days. Each pizza-sized box will contain around 95 vials of frozen vaccine; each vial will need to be thawed and then diluted with 1.8 ml of a provided sterile solution to make five doses of vaccine. Once diluted, a vial can be stored in the refrigerator or at room temperature for up to six hours.

Pfizer says its containers are equipped with both tracking devices that will allow them to monitor the whereabouts of every package, and temperature sensors to ensure the doses stay frozen. If the vaccines deviate from their target destination, or if the vials get too warm, the company is alerted.

Now that the vaccine is authorized, regulators and the manufacturer must decide whether the people in the placebo group in the studies should get vaccinated when they are eligible. Bourla said Pfizer plans to allow placebo recipients to get vaccinated when they qualify according to CDC recommendations of priority groups. But during the advisory committee meeting, panel members expressed concern that doing so would diminish the power of the study to continue tracking effectiveness and side effects, which the manufacturers had been planning to do for two years. One way that panel members discussed to retain the validity of the trials is to switch everyone in the placebo group to vaccine, and everyone in the vaccine group to placebo; it’s not clear yet how the manufacturers will proceed on this question.

The EUA also raises the question about whether it’s still ethical to ask people to join trials for vaccines that are planned in coming months and potentially receive placebo — if they can get an authorized vaccine on their own, outside of the trial. That issue will likely be discussed in more detail by the panel next week, when it will vote on the second COVID-19 vaccine EUA request, from Mass.-based Moderna.

Hospitals around the country are gearing up to administer the shot to their health care workers; many have trained staff on how to properly store and manage the special thermal shippers that the vials will come in, and some have ordered ultra cold freezers to house the doses. CVS and Walgreens have also entered into agreements with the U.S. government to administer the vaccines in long term care facilities.