The Federal Aviation Administration (FAA) said Saturday it had approved the use of the Pfizer-BioNTech COVID-19 vaccine by pilots and air traffic controllers.
The U.S. aviation regulator said pilots and controllers must not fly or conduct safety-related duties for 48 hours after receiving doses. The FAA said it will “monitor the patient response to Pfizer-BioNTech vaccine and may adjust this policy as necessary to ensure aviation safety.”
Top U.S. Food and Drug Administration regulators said on Saturday that most Americans with allergies should be safe to receive the COVID-19 vaccine developed by Pfizer Inc and Germany’s Biotech SE.
The FDA, which authorized the nation’s first COVID-19 vaccine on Friday night, said that only people who have previously had severe allergic reactions to vaccines or ingredients in this particular vaccine should avoid getting the shot.
“We’re telling people that unless they’ve had a severe allergic reaction to the vaccine, or one of its components, they can receive it,” Dr. Peter Marks, director of the FDA division that authorized the vaccine, said at a press conference.
After Britain began inoculations this week, two people with severe allergies reported side effects and the British medicine regulator advised that anyone with a history of anaphylaxis to a medicine or food should not get the Pfizer-BioNTech vaccine.
“About 1.6% of the population has had a severe allergic reaction of some sort or another to a food or some environmental aspect and we would really not like to have that many people not be able to receive the vaccine,” Marks said.
The vaccine is seen as a key tool in stemming the coronavirus pandemic that has killed nearly 300,000 people in the United States.
The FDA advised people with allergies to consult with their doctors to make sure that they are not allergic to any of the component of the vaccine.
Pfizer executives said on Friday that there had been no cases of severe allergic reactions to the vaccine during its nearly 44,000 volunteer late-stage clinical trial. That trial excluded people with a history of severe allergic reactions to any vaccine or to the Pfizer-BioNTech vaccine’s ingredients.
They said there were no anaphylactic episodes related to the vaccine in the trial, which did include about 6,000 participants respectively in both the vaccine and placebo groups with a range of allergic conditions such as pollen allergies and food allergies. Those participants had a history of symptoms including anaphylaxis.
Pfizer Inc. was months from proving its Covid-19 vaccine would even work when Chief Executive Albert Bourla got into a tense WebEx debate with his head of manufacturing.
It was a warm day in June and Pfizer was racing to develop a radical new vaccine based on a technology that had never been approved before. Mr. Bourla and his team were so optimistic they had committed hundreds of millions of dollars to build a global manufacturing network.
Mr. Bourla, speaking from his suburban New York home during one of Pfizer's twice-weekly meetings on the project, told the team he wanted them to increase commercial production at least 10-fold.
"Why can't we make more and why can't we make it sooner?" Mr. Bourla demanded.
Mike McDermott, who oversees Pfizer's global manufacturing network, pushed back. His team already was working furiously, he said.
"What we're doing already is a miracle," he said he told Mr. Bourla. "You're asking for too much."
Even for jaded pharmaceutical scientists, what happened next was little short of miraculous. U.S. health regulators Friday night authorized the Covid-19 vaccine developed by Pfizer and its German partner BioNTech SE. The shot is already in U.K. use and will be the first given in the U.S., capping the fastest vaccine development ever in the West.
How the drugmakers pulled off the feat, cutting the typical time from more than 10 years to under one, partly stems from their bet on the gene-based technology.
As the inside story shows, it was also the product of demanding leadership, which bordered on the unreasonable. From urging vaccine researchers to move fast to pressing the manufacturing staff to ramp up, Mr. Bourla pushed employees to go beyond even their own ambitious goals to meet Covid-19's challenge.
Pfizer couldn't meet every target set by its chief executive. Mr. Bourla wanted the vaccine done by October and as many as 100 million doses by year's close, enough for 50 million people. Instead about half that will be produced.
Yet the company, which has spent more than $2 billion on the effort, achieved more, faster, than outside experts and even its employees thought possible. In a series of interviews over more than seven months, senior Pfizer executives and other managers shed new light on how the vaccine project took shape.
Early in the pandemic, U.S. health officials cautioned the first vaccines wouldn't be ready until 2021. Pfizer's vaccine researchers initially forecast the middle of next year at the earliest.
Previously, the quickest vaccine development program was the four years it took to make the mumps vaccine, licensed in 1967. After getting Mr. Bourla's go-ahead, Pfizer researchers figured they could shorten the timeline to a year, give or take.
Crucial to what they considered an ambitious forecast: the unproven gene-based technology honed by BioNTech, a small biotech company based in Mainz, Germany, already in partnership with the big drugmaker to develop a flu shot.
BioNTech wanted to make vaccines out of messenger RNA, or mRNA, the molecules that carry genetic instructions telling cells what proteins to make.
The German company's researchers thought they could use the genetic sequence of the coronavirus, which had recently been published, to synthesize mRNA that would instruct cells to make a harmless version of the spike protein that protrudes from the surface of the virus.
The defanged spike proteins would prompt a person's immune system to produce antibodies that could fight off the real virus.
Unlike the months it takes to cultivate a vaccine in test tubes, designing an mRNA vaccine would be quick. BioNTech simply plugged the genetic code for the spike protein into its software. On Jan. 25, BioNTech Chief Executive Ugur Sahin designed 10 candidates himself.
The company's researchers would create 10 more different potential coronavirus vaccines for a total of 20, each slightly different in the event one design worked better and more safely than the others.
But BioNTech, founded in 2008 and with just 1,000 employees when the pandemic hit, needed a big partner to manufacture the vaccines for human trials and potentially for people around the world.
During a March 1 phone call, Dr. Sahin proposed a coronavirus vaccine collaboration with Kathrin Jansen, Pfizer's vaccine-research chief.
Many in pharma were skeptical of mRNA, which had been long in the making but never the basis for an approved product. Dr. Jansen, known in the industry for helping develop Merck & Co's cervical-cancer shot Gardasil, saw promise, in large part because mRNA vaccines appeared to produce stronger immune responses than older shots.
"This is a disaster, and it's getting worse," Dr. Jansen told Dr. Sahin. "Happy to work with you."
Mr. Bourla gave his go-ahead a week later, at one of Pfizer's first leadership meetings on the program. When vaccine researchers at a follow-up meeting in mid-March forecast a coronavirus vaccine in the middle of 2021, Mr. Bourla spoke up.
"Sorry, this will not work," he said. "People are dying."
Mr. Bourla demanded a vaccine by October, when it looked like a second wave of the pandemic would be peaking.
Growing up in Greece, Mr. Bourla never envisioned a career running one of the world's biggest drugmakers. He trained to be a veterinarian. At Pfizer, Mr. Bourla gained a reputation for his friendliness and achievements, brightly chatting up colleagues and rescuing troubled products. He took the helm of Pfizer in 2019.
"I'm a true believer that people, they don't really know their limits," Mr. Bourla said in an interview. "And usually, they have the tendency to underestimate what they can produce."
Pfizer's leadership held hour-long meetings Mondays and Thursdays on the vaccine program. The WebEx calls lacked a formal agenda so that discussions could flow freely. Dr. Jansen and the two dozen other colleagues who joined grew accustomed to Mr. Bourla urging fast progress.
Pfizer and BioNTech researchers collaborating via video sought to narrow down the number of vaccine candidates from 20. In test tubes, they examined various doses and looked for molecular signs of effectiveness and safety. BioNTech also tested the candidates in mice.
The whittling was especially tough, because mRNA vaccines weren't tried-and-true commodities. Researchers wanted to collect as much data as they could to inform their judgments. They also had to move fast.
Vaccines normally are tested in three stages, with the first test on a limited number of people to ensure they are safe. To save time, the researchers took unorthodox steps. In April, they filed their plans for testing a candidate with regulators, but the paperwork was littered with holes for data they would need to fill in. Pfizer also combined the second and third stages. And then they decided they should test more than one version of the vaccine. The company sent the U.S. Food and Drug Administration updated batches of data almost daily.
By April 12, the scientists eliminated 16 candidates. They didn't know how to choose among the remaining four. Normally, researchers would take years and finish animal testing before injecting any doses into a human. Pfizer didn't have that kind of time. It still tested the vaccines in monkeys, but simultaneously with humans. "We needed speed, and with speed, you have to rethink how you normally go," said Dr. Jansen, who leads a team of 650.
On April 23, they started trying the four candidates on a small number of human volunteers in Germany. Within two days of getting two of the shots, some subjects developed fevers and chills, signs the vaccines wouldn't be well tolerated.
The companies went ahead with testing the other two experimental vaccines in the U.S. One directed cells to produce a partial-spike protein, while the other generated a full-spike protein. Researchers tested different doses and determined either version would require two shots to deliver maximum immunity.
On Sunday, June 7, researchers emailed Dr. Jansen the first results from the early-stage trial of the first vaccine candidate. Dr. Jansen, preparing a presentation in her Manhattan apartment, brightened.
The findings showed the experimental shot produced an antibody response in study subjects, a good sign it could protect against Covid-19.
"Really, really encouraging," she replied to the researchers by email. "When can I see the next data?"
Pfizer announced the full findings July 1. The second, or full-spike, candidate wouldn't finish its own study for a few weeks. Without that data, the companies weren't sure which of the two to take into the large, final trial that regulators would use to determine whether to authorize the shot or not.
Most of the results didn't arrive until July 23, the day before Pfizer told the FDA it would name a candidate.
Like its cousin, the second candidate also generated a strong immune response. Yet subjects reported fewer cases of fevers and chills than the first vaccine candidate, so it was considered more tolerable.
The choice was tough because the candidates were so close, Pfizer officials said. On July 24, Pfizer and BioNTech agreed to go with the second vaccine candidate.
"I started to relax a little bit, which I haven't really done since the beginning of all of this." Dr. Jansen recalled a week later. "It is just a major, major, major decision to make."
As the researchers zeroed in on a vaccine selection, Pfizer's manufacturing team geared up to make the shots with BioNTech. Given the urgent need for a vaccine, the companies planned to make supplies for testing, but also to begin making vaccines for real-world use even before the final study finished.
One problem: Pfizer didn't have the equipment to make an mRNA vaccine, a new and different manufacturing process.
Pfizer Inc. and partner BioNTech SE received authorization from the Food and Drug Administration on Friday to begin distributing their Covid-19 vaccine. As the shot goes into use across the U.S., here's what we know and don't know.
Who is authorized to receive the vaccine?
The FDA authorized the vaccine to be administered to people 16 and older to prevent Covid-19.
How did the FDA decide?
FDA staff evaluated the results that Pfizer and BioNTech provided to the agency from a clinical trial of about 44,000 people, which tested whether the vaccine safely protected people from Covid-19. FDA staff concluded the vaccine met success criteria by reducing the risk of contracting Covid-19 and becoming symptomatic. The FDA also considered the input and recommendations from a committee of outside advisers, which voted Thursday 17 to 4, with one abstention, that the vaccine's benefits outweighed its risks in people 16 and older.
When can I get the vaccine?
Federal officials have allocated an initial supply of about 6.4 million doses of the Pfizer vaccine to become available after authorization. Of these, 2.9 million doses are expected to be shipped immediately, and another 2.9 million held back and shipped about three weeks later so the initial vaccine recipients can receive the second of two doses. Federal officials are holding 500,000 doses of the initial supply in reserve in case any problems arise. Health officials have recommended this limited supply -- plus additional doses expected this month -- should go to health-care workers and residents of nursing homes and other long-term-care facilities. As supplies increase in January and February, additional high-priority groups will be vaccinated, including essential workers like police and teachers, adults 65 and older, and people with high-risk medical conditions. The order of these groups may vary by state. The general U.S. population outside those categories may not get access to a vaccine until spring or summer.
How can I get one?
Hospitals will vaccinate their workers and, in some cases, health workers from the surrounding community. Pharmacy chains will vaccinate staff and residents at nursing homes and other long-term-care facilities. As supplies increase, the wider population will be able to get vaccinated at local health departments, doctors' offices, urgent-care centers and pharmacies.
How do we know the vaccine protects against the virus?
In the large clinical trial, the vaccine was shown to be 95% effective at preventing Covid-19 cases with certain symptoms, including severe cases.
How does the vaccine work?
The vaccine uses messenger RNA, or mRNA, technology, which doesn't contain the coronavirus itself, but rather a genetic code associated with the virus that triggers the desired immune response. The mRNA is engineered to teach human cells to make something resembling the spike protein found on the surface of the coronavirus. This induces an immune response that shores up defenses if a vaccinated person is later exposed to the real virus. The vaccine is given in two injections, three weeks apart.
Is the vaccine safe?
The FDA said it identified no specific safety concerns that would preclude authorization. Common side effects in the large study included injection-site pain, fatigue, headache, chills and joint and muscle pain. Such symptoms were generally mild or moderate, and happened more frequently after the second dose.
Can the vaccine cause allergic reactions?
In the U.K., which authorized the vaccine on Dec. 2, two health-care workers had allergic reactions shortly after vaccination, prompting the U.K. health regulator to advise that people with a history of allergic reactions not receive the vaccine. The FDA said there was a higher rate of hypersensitivity reactions among vaccine recipients than in people who had received a placebo in the large study. But the overall rate of such events was less than 1% of all study subjects.
What don't we know about the vaccine?
It is not yet known whether the vaccine prevents asymptomatic cases or transmission of the virus. The FDA said it didn't have enough data to make conclusions about the safety of the vaccine in children younger than 16, pregnant or lactating women, and immunocompromised people. We also don't yet know the duration of protection afforded by the shots.
