The Food and Drug Administration on Friday evening granted an emergency use authorization (EUA) to the Covid-19 vaccine developed by Pfizer and BioNTech, making it the first Covid-19 vaccine in the United States to begin distribution outside of clinical trials.
The first 6.4 million doses could ship within days.
The announcement came after an advisory committee to the Food and Drug Administration, the Vaccines and Related Biological Products Advisory Committee, voted 17 to 4, with 1 abstention, to recommend and EUA for the Pfizer-BioNTech vaccine. The committee specifically voted on whether the benefits of the Pfizer-BioNTech vaccine outweigh the risks in people aged 16 years and older.
The highly anticipated regulatory green light means health workers facing high exposure to the disease and residents of long-term care facilities can now start receiving the first doses of the two-dose vaccine.
That a vaccine for a disease only discovered late last year would be ready so quickly is already an unmatched scientific feat, but the fact that it’s also based on a new technology that yielded 95 percent efficacy in preventing disease makes the announcement all the more remarkable.
“The tireless work to develop a new vaccine to prevent this novel, serious, and life-threatening disease in an expedited timeframe after its emergence is a true testament to scientific innovation and public-private collaboration worldwide,” said FDA Commissioner Stephen Hahn in a statement.
The approval of the Pfizer/BioNTech vaccine in the US follows green lights from regulatory agencies in Canada and the United Kingdom. Next week, the vaccine advisory committee will consider another EUA for the Covid-19 vaccine using a similar approach developed by Moderna.
But an EUA is only one step forward.
The vaccine must then be shipped to health facilities and administered in two doses. These steps present their own challenges, ranging from keeping the vaccine at the frigid temperatures it requires to getting patients to come back for a follow-up shot. Meanwhile, many of the health systems administering shots are struggling to care for a huge surge of hospitalized Covid-19 patients.
This rollout will be part of the largest vaccination effort in history. But there will not be enough doses for everyone at the outset, even for people placed at the front of the line. Pfizer and BioNTech expect to produce 50 million doses of their vaccine around the world before the end of the year, enough for 25 million people — half of which has been pledged for the US. The first doses to roll out will be a crucial test of the vaccine distribution system in the United States, as well as a test of public acceptance and of the integrity of the clinical trial process.
The Pfizer/BioNTech vaccine is cleared for emergency approval. Now what?
One of the first challenges for the Pfizer/BioNTech vaccine is getting it where it needs to go. That’s complicated by the fact that the vaccine requires temperatures of minus 70 degrees Celsius (minus 94 degrees Fahrenheit) or lower, some of the coldest temperature constraints of any Covid-19 vaccine under development. Maintaining the cold chain from factories to distribution hubs to hospitals is crucial; otherwise, the vaccine may spoil and become ineffective.
Pfizer has developed its own temperature-controlled shipping containers that use dry ice to maintain the recommended temperatures for their vaccine for up to 10 days. But longer storage will require ultra-cold freezers, and not many clinics have the requisite hardware, so timing the shipments will be key. There may also be shortages of dry ice.
The next hurdle is figuring out who gets the vaccine first. The 6.4 million doses available at the outset are nowhere near enough to quench the raging Covid-19 pandemic that is still reaching new peaks in daily hospitalizations and fatalities.
An advisory committee to the Centers for Disease Control and Prevention voted at the beginning of this month on a set of guidelines that prioritize health care personnel, as well as staff and residents of long-term care facilities. But these groups alone add up to about 24 million people, so states and local governments and health groups are having to narrow these groups further.
Pfizer and BioNTech’s vaccine also has to be administered as two doses spaced 21 days apart. That poses a problem because experiences with other vaccines show that people are really bad at getting follow-up shots. As many as half of patients failed to get their second dose of the hepatitis B vaccine, for example. For the Covid-19 vaccine, side effects from the first dose, scheduling conflicts, or supply shortages may inhibit recipients from getting the second dose.
The good news is that the Pfizer/BioNTech vaccine may offer some protection against Covid-19 from the first dose, although it takes a few days for the shielding to build up. In fact, some experts, including former FDA commissioner Scott Gottlieb, argued that the entire allotment of doses should be given to as many people as possible, as fast as possible, rather than withholding injections to give to people as second shots.
“We should get as many shots in our arms as possible right away,” he told USA Today on Monday. “The idea that we need to cut (the doses) in half and give half of it now and hold onto it, so we have supply in January to get the second dose … I just fundamentally disagree with that.”
But other experts say there isn’t yet enough data on a single dose to know whether it will provide enough protection from the virus for the broader population.
Meanwhile, the FDA is likely to authorize another Covid-19 vaccine in the coming weeks, clearing the way for the distribution of 25 million doses of the Moderna vaccine, enough for 12.5 million people on the two-dose regimen.
Moncef Slaoui, the scientific lead for Operation Warp Speed, the program from the Department of Health and Human Services to accelerate and deploy Covid-19 vaccines, said he expects 20 million Americans will be vaccinated in December, 30 million more in January, and 50 million more in February as more vaccines with promising early results are approved.
The clinical trials for Covid-19 vaccines must continue, but they’re going to get harder to complete as placebo participants leave to get vaccinated
An EUA is a critical step, but it’s not full approval, and it signals that the FDA still wants answers to key questions, like long-term safety. The standards for an EUA for a vaccine is that there is an urgent public health need, the proposed vaccine may have a beneficial effect, and that there are no approved alternatives. The FDA also set a minimum threshold of 50 percent efficacy for a Covid-19 vaccine, a line that several vaccines have completely vaulted.
So far, Pfizer and BioNTech are only reporting two months of observational safety for their phase 3 clinical trial, although the companies have committed to continue monitoring their more than 43,000 trial participants.
But at the same time, Covid-19 is spreading rampantly in the United States, and more than 20,000 people in Pfizer and BioNTech’s trial have received a placebo rather than the actual vaccine, leaving them vulnerable to the disease. Of the 178 reported cases of Covid-19 in the trial pool, 169 were in the placebo group. Of those, 9 in the placebo group and 1 in the vaccine group experienced severe Covid-19. As time goes on, more people in the placebo group will likely get sick and some will fall severely ill, requiring hospitalization. Without intervention, some of these people in the placebo group may die.
The EUA now presents a huge dilemma for the clinical trial. People in the placebo group may be at risk of Covid-19, but if they receive the vaccine, it would diminish the value of the trial and make it harder to answer questions about safety and efficacy, particularly in vulnerable subgroups like older adults.
And since this is a double-blind clinical trial, neither the recipients nor the companies know who received the vaccine and who received the placebo. Vaccinating the placebo group would require breaking this blind, and if participants find out which group they’re in, they could change their behavior. People who received the vaccine may engage in riskier behavior while people in the placebo group may end up taking more precautions if they decide not to get vaccinated themselves. Those changes in behavior will make it harder to isolate the effects of the vaccine.
William C. Gruber, senior vice president for vaccine clinical research and development for Pfizer, told the FDA vaccine advisory committee on Thursday that the company has an ethical obligation to inform trial participants that the vaccine has received an EUA, but they are working on coming up with ways to maintain the integrity of the trial as much as possible.
“Eligible participants in the placebo group will have the option to receive the vaccine,” Gruber said. “We are currently in discussions with the FDA about the best way to vaccinate placebo recipients.”
Gruber added that the study will continue for 24 months regardless, with ongoing monitoring of the trial participants. This sort of large-scale and long-term follow-up is key because there may be rare complications that emerge that weren’t detected over a shorter time frame or were not present in the selected pool of participants in the trial.
Already, the rollout of the Pfizer/BioNTech vaccine in the UK has revealed that people with severe allergies could face complications.
“[T]he expectation would be that subjects with known severe reaction — allergic reaction — should not take the vaccine until we understand exactly what happened here,” Slaoui told reporters on Wednesday.
More people receiving this inoculation will further clarify any problems and concerns. But it will take months before the vaccine will start to constrain new Covid-19 cases since tens of millions of people would need to have immunity before the spread starts to slow down. And while the Pfizer/BioNTech vaccine has demonstrated effectiveness against disease, it’s still not clear how well it prevents asymptomatic infection. Scientists don’t yet know if people who are vaccinated could still transmit the virus to other people without getting sick themselves.
That means that until there is widespread vaccination, hospitals will still be battling severe Covid-19 as case numbers reach grim new heights. And handwashing, social distancing, and mark-wearing will remain the orders of the day for months to come, even for people lucky enough to receive a vaccine.