More than eight months ago, large studies found that both the Pfizer-BioNTech and Moderna COVID-19 vaccines reduced the risk of illness by more than 90%. Yet the U.S. Food and Drug Administration has not yet granted them full approval, to the dismay of public-health officials eager to boost vaccination rates as the delta variant sends infections skyward.
So what's the holdup?
Part of the reason, according to experts in drug regulation, may be simply that the agency can afford to take the time.
In December, the FDA authorized the first two vaccines for emergency use, and did so for a third in February. Those authorizations, though based on extensive, rigorous research, are temporary in nature. Before granting permanent approval ("licensure"), the agency can spend months to make triply sure that all regulatory requirements are met, given that the vaccines are available for all who want them in the meantime.
"Any decision to grant such an approval is a potential precedent in the future, so you don't want to rush something through," said Adam Muchmore, a law professor at Pennsylvania State University.
Still, with the emergence of the highly transmissible delta variant of the coronavirus, public-health officials are eager for the agency to move forward, contending that full approval may pave the way for more people to be vaccinated.
That could happen in two ways. Physicians hope that if the agency licenses the drugs, some who are hesitant about vaccination may become more receptive. Even if not, more businesses and institutions may decide they have a legal basis for requiring the shots, said Greer Donley, an assistant professor at the University of Pittsburgh Law School.
Hundreds of universities already have instituted vaccine mandates for students enrolling this fall, in one case surviving a challenge in federal court. And on Monday, the U.S. Department of Veterans Affairs announced it would require the shots for 115,000 frontline medical workers. But with full approval, Donley said, employers seeking to require the vaccines may feel they are on even firmer legal ground.
Either way, FDA's career civil servants, accustomed to carrying out their careful reviews in relative obscurity, are under public pressure like never before.
"If it were to move too fast, that would be evidence that skeptics would use, that the FDA is acting politically, not acting based on science," Donley said. "The FDA is walking on this tightrope to make sure it is acting as quickly as possible but also following all its protocols."
What is emergency use?
The FDA's power to authorize drugs for emergency use is relatively new, enacted by Congress in 2004 in response to the anthrax attacks of 2001.
The agency can grant such an approval if it is "reasonable to believe" that the product may be effective, and that its "known and potential benefits" exceed its "known and potential risks," according to the statute.
But vaccines are not like most drugs, in that they are administered to healthy people to prevent illness, not to treat it. So when the FDA issued guidance on what it would require before authorizing vaccines against COVID-19, the agency went beyond the letter of the law.
Drug makers learned they would need to enroll tens of thousands of participants, randomly assigning some to receive the vaccine and others to get a placebo. In short, they needed to run the type of large, well controlled trial that is required for regular approval of any vaccine, said biostatistician Susan S. Ellenberg, a professor emerita at the University of Pennsylvania's Perelman School of Medicine.
On Nov. 9, the partnership of Pfizer and BioNTech announced that its vaccine prevented more than 90% of cases of COVID-19, far exceeding most expectations.
Similar results came a week later from Moderna Inc., and by the middle of December, the FDA had authorized emergency use of both.
What more do they need?
Before granting the emergency authorizations, the FDA analyzed the rates of any side effects for two months following administration of the vaccines.
Any side effects caused by vaccines tend to arise within a month, and physicians generally agreed that two months' of safety data was more than sufficient — especially given the urgency of curbing the pandemic during the wintertime surge.
The evidence on the COVID-19 vaccines was promising, with some participants reporting temporary consequences such as a fever, headache, or sore arm — nothing serious or long-lasting.
But for full approval of the vaccines, the agency has gone even further, saying that trial participants must be monitored for an additional four months (that is, a total of six months following full vaccination).
Health systems under pressure to require vaccines for employees
It also is reviewing any adverse events in the general population. Those have included rare cases of myocarditis (a type of heart inflammation) in people who have received the Pfizer and Moderna vaccines, and rare cases of blood clots in those who got a vaccine made by Johnson & Johnson.
Infectious-disease specialists generally agree that these risks are small, especially when balanced against the potential for much greater consequences from a case of COVID-19.
Still, the FDA is well within its rights to exercise caution, said Ellenberg, who once worked for the agency. Regulators also conduct a careful review of a drug-maker's manufacturing processes.
"I think the regulators feel the intense external pressure to complete the full approval, and have to balance that against the concern they always have about new products, about missing something," she said.
Will it make a difference?
In June, a group of Indiana University students filed a lawsuit against the school, contending that it was violating their constitutional rights by requiring vaccination for those enrolling in the fall.
In a preliminary ruling this month, federal judge Damon Leichty found in favor of the school, writing that the university had a rational basis for protecting the public health in a pandemic. He acknowledged legal precedents that establish a person's right to refuse unwanted medical treatment in certain circumstances — yet stressed that vaccines protect not just the recipient, but the community at large.
"Vaccines address a collective enemy, not just an individual one," he wrote.
What's more, the students were not being forced to get the vaccines, the judge noted. They have the option of requesting a medical or religious exemption, or they can go to school elsewhere.
Others have come to a similar conclusion on the law. Also this month, the U.S. Justice Department found that public and private entities may require vaccines that are authorized for emergency use.
Assuming the FDA grants full approval for the vaccines in the coming months, the case would become even stronger.(c)2021 The Philadelphia Inquirer Distributed by Tribune Content Agency, LLC.