The FDA Really Did Have to Take This Long

After months of anticipation, Americans have a fully licensed COVID-19 vaccine. Today, the FDA announced the approval of Pfizer-BioNTech’s shot for people 16 and older—the first complete thumbs-up among the three vaccines available in the U.S.

The pervasive mood has been: Finally. Pfizer’s shot was given its emergency use authorization—the vaccine’s training wheels—back in December, and the company submitted its application for full approval in May. While America’s emergency-use vaccination rollout has saved an untold number of lives, many institutions, including some universities and hospitals, have been waiting for formal approval to mandate vaccinations. Health officials have expressed hope that approval will help convince people who are vaccine-hesitant to get a shot.

Especially as COVID-19 cases skyrocket and hospitals strain under the Delta variant, the FDA has to stop “dragging its feet” on vaccine approvals, many people have argued. Lives are at stake. The urgency, the medical scientist Eric Topol recently wrote in The New York Times, “cannot be overstated.”

Except this hasn’t been the only mood. While the approval timeline for Pfizer has felt like forever to many, less than four months from application to full FDA approval is much faster than usual for a completely new type of drug—even a priority vaccine ordinarily takes up to eight. The timeline has been so fast, in fact, that a group of scientists recently called for the agency to slow down in the name of safety. “If the FDA listens to us, they won’t give serious consideration to approving a covid-19 vaccine until 2022,” the group said.

Some people want the FDA to speed up. Others want it to be more cautious. All of this can be head-spinning for anyone who just wants the agency to do whatever actually works to get us out of this horrendous pandemic. If one thing has defined America’s vaccination rollout, it’s exactly these competing pressures. There’s a fundamental tension between the right to get access to a drug people are desperate for and the right to protection from dangerous failures of quality. The first demands speed; the second requires time.

Today’s Pfizer approval relieves some of this tension, but there’s far more pushing and pulling to come. Similar debates persist over the Moderna and Johnson & Johnson vaccines and, even more pressing, over emergency use authorization for vaccinating young children, who are returning to schools amid outbreaks without any access to shots. For many people, the reflexive position remains: Get vaccines into arms. If the FDA doesn’t hurry up, it is killing Americans. But imagine the cost of the agency taking a controversial safety shortcut. For full FDA approval to bring all the benefits it could, people need to trust that such approval means something.

The full FDA approval of America’s three available vaccines has long been a foregone conclusion. The shots are impressively powerful, the safety data after hundreds of millions of injections are colossal, and COVID-19 certainly hasn’t lost its teeth. So why wait? The recent push to fast-track full approval for these vaccines is based on two premises. First, the FDA has been taking unreasonably long. The agency has already reviewed the initial data for the vaccines as they rolled in, there have been massive global scientific scrutiny of and consensus about them, and signing off on the latest longer-term data shouldn’t take months, the argument goes. Second, the vaccines’ emergency-use status has been a dam wall holding back a flood of vaccination that could help turn the pandemic around.

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We have good reason to be cautious about both assumptions. Let’s start with the FDA. The agency’s full approval is more than just a formality. Yes, the vaccines are a tremendous success. But while early, publicly available data have now been thoroughly scrutinized, the agency has access to enormous amounts of more recent information that needs to be combed over for any surprises or signs of possible undetected issues. On a press call about the approval announcement, Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, said that the agency reviewed hundreds of thousands of pages of new data from Pfizer. Even for an agency as well resourced as the FDA, thorough analysis and consideration of so much information is a heavy lift, especially for multiple vaccines at once; Moderna’s application for full approval arrived hot on the heels of Pfizer’s, on June 1. (In response to questions on the call, Marks declined to comment on the timeline of a full approval for Moderna.)

And it’s not just a lot of data from the clinical trials of the vaccine. The trials and other studies by the manufacturers established the vaccine’s efficacy and basic safety, along with common and not-so-common possible reactions. Now that it’s been rolled out, though, the regulators have to look for signals of very rare issues that wouldn’t show up even in trials of tens of thousands of people.

We’ve already seen how crucial this effort can be. When Pfizer submitted its application for full approval, the link between the currently available mRNA vaccines and some cases of heart inflammation hadn’t been established. The CDC informed us about this potential risk in mid-May. A safety issue particularly affecting younger people was a serious development in the regulatory process of a vaccine approval that includes 16- and 17-year-olds. The small amount of early data for that age group had been a sticking point back at the emergency-use-authorization stage. Now investigating whether the incidence of this potential side effect might be higher for Moderna’s vaccine than for Pfizer’s is reportedly the reason Moderna still hasn’t received emergency use authorization for adolescents.

Then there’s the quality-control side of the task. One of Pfizer’s drug specialists recently described the company’s earliest attempt at manufacturing a COVID-19 vaccine as an “absolute and utter failure.” By the end of this year, Pfizer will have produced an estimated 3 billion doses, the most of any company. That lightning-fast progress is awe-inspiring—and a little nerve-racking. You really want to be confident that regulators are on top of this. The FDA has to be thorough, especially with the first of a new type of drug with completely new production processes, like this mRNA vaccine. It’s not enough that the vaccine used in trials was safe: We must be assured that the shots we’ll get in the arm have the same quality. That quality is not simply baked in. Last winter, for example, the European Medicines Agency, the European Union’s equivalent of the FDA, reported that the contents of some batches of the BioNTech-Pfizer vaccine they had tested weren’t all the same, and the source of the discrepancies had to be resolved before the agency authorized it for rollout.

It’s so easy to take the rigors of our current systems for granted. We are used to them preventing disasters. In the 1950s, a world without the FDA’s current level of caution, the manufacturing failure that derailed the 1950s polio-vaccine campaign led to the deaths of 11 people and sickened far more. Today, we worry about millions of vaccine doses being discarded because they might have been contaminated, but those shots don’t get as far as people’s arms. Ensuring that these kinds of issues are identified and smoothed out is the everyday business of drug regulation. It’s not always fast or predictable. No agency can always get everything right, of course, including the FDA. They can go too fast, and they can go too slow. But having a system in which pharmaceutical companies knew that scrutiny would be relatively superficial would be tempting fate: Lowering oversight can be a quick path to lowering standards.

Both the European Medicines Agency and Health Canada are releasing the complete data packages that companies submit with their applications. All of that data plus what’s in publicly reported safety-monitoring systems will be combed over by many others down the line, including some who will be trying to discredit the vaccines. If there are problems, we need the FDA to spot them first and deal with them. Confidence in specific vaccines and in the system that regulates them is a very long game.

Now for the second case for fast-tracking vaccine approvals. People arguing that full FDA approval will supercharge vaccination point to two factors: more vaccine mandates, and removing the reason for a substantial proportion of vaccine hesitancy.  

The Pfizer approval is indeed a green light for significant vaccine mandates at a range of institutions. The Pentagon announced today that it would go forward with mandating vaccination for America’s 1.4 million active-duty service members. New York City will now require every employee of its Department of Education to be vaccinated. Major pushes like these could make a substantial difference for vaccination numbers. At the same time, we can’t predict all reactions to mandates, especially in parts of the country where they have been strongly resisted. Back in 2015, school vaccine mandates were strengthened after measles outbreaks linked to Disneyland hit California and surrounding states. Researchers have called the groundswell of opposition to the removal of nonmedical vaccine exemptions at the time a turning point in the U.S.—it led to the mainstreaming of anti-vaccine sentiment and a shift to a highly politicized civil-liberties focus for the movement. It’s a volatile issue.

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I wouldn’t rush to predict the impact of full approval on general vaccine hesitancy, either. People have been noting the results of a Kaiser Family Foundation poll suggesting that three out of 10 unvaccinated Americans say they are more likely to get vaccinated after full FDA approval. But as the poll’s authors point out, that might just be a stand-in for safety concerns—most of the respondents either thought the vaccines were already “approved” or weren’t sure what their status was. We don’t really know how common the concern is, or how much it would affect behavior.

At the moment, arguing that the vaccines aren’t actually FDA-approved is an easy tactic used to try to convince people that the vaccines are still experimental or were never properly tested. Anti-vaccine arguments can shape-shift pretty quickly, though. The claim could indeed be retired after today, at least for Pfizer, but expect some to simply pivot to saying that the vaccines are still experimental because the trials aren’t over yet. (Although Pfizer’s trials have delivered the answers we needed to start using the vaccine, they technically won’t be complete until the last collection of follow-up data on the participants.) Indeed, that the trials are still following people well into 2022 is the foundation of the argument from some scientists that FDA approval shouldn’t be granted now at all.

None of this is to advocate for the idea that approvals should be slow for the sake of it. Being slow, after all, isn’t a guarantee that corners aren’t cut. The FDA needs to be able to maintain its standards, uncompromised by political or other pressures, because community confidence in its approvals has to be solid. That doesn’t mean it shouldn’t be questioned or challenged. This process of emergency use authorization for vaccines for the general population was a first, and the system could surely be improved for the future.

One of the areas that could be improved straightaway is greater transparency for the fraught issue of vaccinating young children. Unlike adults merely waiting by choice on full approval, kids under 12—one of the country’s largest unvaccinated populations—have no access to COVID-19 vaccines. Emergency authorization of Pfizer’s vaccine for this age group is expected, but the timeline for this still is unclear, even though America is experiencing  a pediatric outbreak of COVID-19 as children are returning to school. On top of this, we’re not getting the same detailed information from pharmaceutical companies that we got for the big Phase 3 trials. For those, the protocols were public, providing blueprints of how the trials would be run. The ones for the children’s trials aren’t.

[Read: The school year is going to be a mess—again]

Again, push and pull. The journalist Michelle Goldberg spoke to many people’s concerns when she wrote that she “can hardly overstate the frantic helplessness” she feels over the “bureaucratic caution” that’s stopping vaccines getting to kids under 12. Yet some scientists are arguing that we should completely forgo early emergency use authorization for them, and wait the extra months it will take to gather the longer-term safety data needed for full FDA approval.

I don’t think there is a solid justification for denying young children access to vaccination on the same emergency-use basis as adults. But we can expect the arguments about EUAs and vaccination for children to get far more intense: Even for COVID-19, children are the prime focus of anti-vaccine activism. Pressure from parents in favor of vaccination is likely to increase too. Now that Pfizer’s vaccine is fully approved, the door is open for doctors to prescribe it “off label”—that is, using it outside the specific parameters that the FDA has approved. This could ratchet up the pressure to vaccinate even before the data and the EUA are in—perhaps even before we know how low a dose is enough for the very young. (In the FDA’s press briefing, the acting commissioner, Janet Woodcock, said that preemptively vaccinating children “would be a great concern.”)

We’ve gotten used to the emergency-use-authorization world. We can’t predict for sure what open season on marketing for the vaccines will be like. Some things may be simpler, but others may get more complicated. What is certain: We need widespread confidence on efficacy, safety, and the reliability of vaccine quality. The FDA’s job is to make sure that confidence is well placed and difficult to undermine. Even when it seems as though the agency is lumbering along, a perception that corners were cut under pressure would only make things worse.