March 09, 2021

Vaccines, Federal Regulation, and Compensation—and What that Means for COVID-19

By Dorit Reiss

It’s not an overstatement to call the COVID-19 pandemic a national trauma (certainly not the first or only one). Over the past year, practically everyone’s life was impacted by the pandemic, and for some, the impact was dramatic. Hundreds of thousands of people in the United States have died. Millions more were sickened or hospitalized. Businesses were closed, or impacted in other ways, having to cut operations, dismiss employees, cut salaries. Other businesses—like Amazon—benefitted financially from the increase in delivery.

Vaccines are an important and essential part of our way out of the pandemic. This article examines COVID-19 vaccines, addressing two separate but related issues. First, the process the vaccines went through, with an emphasis on the legal framework within which they are created, the monitoring apparatus, and the Emergency Use Authorization (EUA) process.  Second, options for compensation when a vaccine causes harm, and the differences when it comes to Covid-19 vaccines.

How Vaccines Work

Vaccines work with our immune system, teaching it to recognize and fight off a germ without the risks of a disease. There are several ways vaccines could do that, including by introducing into our body a weakened version of the germ, an inactivated version of it, or a partial version—for example, one or more proteins that our body learns to make an immune response to. The first vaccines authorized for COVID-19 take a different approach: these are mRNA vaccines, which use an mRNA fragment to tell some of our cells to create a copy of the spike protein of the COVID-19 virus. Identifying this protein as foreign, our immune system makes a response to it—and that immune response includes creating memory cells, setting us up for both short term and longterm immunity to the germ. We do not know how long immunity from the vaccines will last; but the data so far suggests that mRNA vaccines trigger a strong immune response in most people.

Vaccines are biologics, subject to regulation under both the Public Health Service Act of 1944 and the general framework the FDA applies to drugs under the Food, Drug and Cosmetics Act. This means that to license a vaccine, a manufacturer has to submit a biological license application (BLA). To be approved, a manufacturer has to show both that the vaccine is “safe, pure, potent and effective” through large clinical trials in humans, and that the manufacturing plant meets standards.

Current mRNA COVID-19 vaccines manufacturers have not yet applied for—and certainly not been granted—a BLA. They went a different route, and were authorized through an Emergency Use Authorization (EUA). The process to getting there was, itself, involved.

Working Quickly

The new coronavirus was identified at least by January 2020. Work on creating vaccines for it started almost immediately. To give one example, the sequence for Moderna’s vaccine, was, according to its site, finalized in January 13, and the first vaccine batch created by February 7, 2020. Other manufacturers in the United States and abroad were also working on vaccines at that point. Because this article addresses the United States regulatory process, it focuses on vaccines destined for the United States market (other vaccines were developed in China and Russia).

By March, the FDA allowed several companies to proceed to human trials, and phase 1 trials started. Usually, the FDA requires extensive evidence from animal studies and toxicology to allow this to proceed. Because of the emergency created by the pandemic, some companies moved to this stage before completing animal trials—but the animal trials did continue, and were completed. This was one of several shortcuts that allowed COVID-19 vaccines to be developed substantially faster than the usual vaccine development process, which takes years or decades.

Phase I trials involve comparing the vaccine to a placebo in a small group of healthy volunteers, to establish the correct vaccine dose and schedule, to examine whether the vaccine generates an immune response, and to look for safety concerns (because the group is small, a safety problem would have to be common to be identified at that stage). Most vaccines fail phase I trials. Several COVID-19 vaccine candidates showed sufficient promise in these trials to proceed to large trials.

In addition, on March 26, 2020, Congress allocated money for vaccine development, and in the following weeks the Department of Health and Human Services awarded funding to several companies with vaccine candidates. In April 29, 2020 the federal government announced Operation Warp Speed, a public-private partnership aimed at developing Covid-19 vaccines. Operation Warp Speed oversaw providing funding to certain company both to support vaccine development and to prepare for manufacturing (though distribution, apparently, was not sufficiently emphasized or prepared for).

Also in April, the CDC’s Advisory Committee on Immunization Practices (ACIP) created a workgroup to oversee the vaccines’ development. The workgroup included forty-two people, including external experts, CDC scientists, and other people, including industry representatives. In a set of emergency meetings over the summer, ACIP reviewed data provided from the workgroup, closely following the vaccines’ trials.

In July and August 2020 large clinical trials, with over 30,000 people in each, started for the vaccines candidates. Very early, it was clear that the vaccines manufacturers would likely apply for an Emergency Use Authorization (EUA) before filing for a Biologics License Application and full approval.

Emergency Use Authorization

The act setting the framework for an Emergency Use Authorization was passed in 2004. The purpose of the mechanism was to address the fact that in an emergency, waiting for completion of the general risk/benefit evaluation process can have very high costs in lives and harms. The EUA allowed a path to permit use of a product on an emergency basis with less evidence than full approval requires.  To get an EUA, a product had to meet four criteria. It had to be for a “serious or life-threatening illness or condition”; there has to be “reasonable belief that the product may be effective in diagnosing, treating, or preventing” the illness or condition; its known and potential benefits had to outweigh its known and potential risks; and there is no “adequate approved, available alternative.” This is substantially less than required to give a BLA license to a vaccine.

Since its creation, only one limited EUA was granted for a vaccine (EUAs were used for other products, including tests and treatments.).  The EUA allowed using an already approved vaccine against anthrax for inhalation anthrax in United States military members.

An EUA for vaccines for the whole population is unprecedented. The leadup to granting the vaccine EUA discussion raised concerns. Among other things, the FDA approved an EUA for hydroxychloroquine that did not have good evidence behind it—and ended up retracting it. FDA improved its process in relation to the EUA for convalescent plasma, and announced an intent to hold vaccines to a higher standard—an “EUA-plus” standard. The EUA-plus standard, as described by Peter Marks, head of the FDA’s Center for Biologics Evaluation and Research (the unit that oversees vaccines approval and monitoring), was closer to full approval than the regular standard for an EUA. The agency faced some pressure from the administration to relax its guidelines, but held fast, and both the FDA’s review team and its expert advisory committee—populated with experts from outside the agency—were to follow these new, more demanding standards.

In the event, the decision was easier than expected, because the data supporting the first two requests for an EUA, for Pfizer and Moderna’s mRNA vaccines, was extremely strong. After two months of clinical trials, both vaccines were over 94% effective at preventing disease, and no serious safety concerns appeared. That does not mean everything about the vaccines is known. Latent effects—problems that emerge months or more later—are very unusual for vaccines, so the risk of those is small, but since clinical trials only have tens of thousands of people, they cannot identify side effects that are extremely rare—one in a hundred thousand or one in a million. But that problem would be true for a vaccine that went through the full approval process too. Other open questions for the vaccines are whether they will reduce transmission—they may, but the initial trials were not geared to measure that—and how long will immunity last. But the data presented to the FDA’s scientific review staff and the FDA and CDC’s expert advisory committees was strong, making authorizing the vaccines relatively straightforward.

Identifying Side Effects

In the time since, the vaccines were found to have a higher rate of severe allergic reactions than routine vaccines. For routine vaccines, the rate of allergic reaction is about one severe allergic reaction per million doses. For COVID-19 mRNA vaccines, the rate of anaphylaxis, after over fifteen million doses, was found to be 4.7 per million for Pfizer and 2.5 per million for Moderna, all within the first fifteen minutes, none fatal. This is higher than routine vaccines, but still very low. mRNA vaccines also have a high rate of unpleasant but temporary side effects; they may leave recipients feeling very bad, ill—even incapacitated—for a day, or two, or three. These temporary side effects mean the immune system is working, and are not likely to cause longterm harms. No other serious safety signals were identified as of February 2021, though unsurprisingly, there are online rumors and stories of things that happen after vaccines. This was inevitable, as Dr. Derek Lowe reminded us:

“…if you take 10 million people and just wave your hand back and forth over their upper arms, in the next two months you would expect to see about 4,000 heart attacks. About 4,000 strokes. Over 9,000 new diagnoses of cancer. And about 14,000 of that ten million will die, out of usual all-causes mortality. No one would notice. That’s how many people die and get sick anyway.

But if you took those ten million people and gave them a new vaccine instead, there’s a real danger that those heart attacks, cancer diagnoses, and deaths will be attributed to the vaccine. I mean, if you reach a large enough population, you are literally going to have cases where someone gets the vaccine and drops dead the next day (just as they would have if they *didn’t* get the vaccine). It could prove difficult to convince that person’s friends and relatives of that lack of connection, though.”

Sorting out real signals from coincidences is not easy. We may eventually identify real but rare side effects linked to COVID-19 vaccines, things that only happen in one per million cases or one per hundred thousand. But that’s just it: At this point, we have very strong data to suggest that any serious harms will be extremely rare. In contrast, we already know COVID-19 is harmful. Close to 3% of people who get COVID-19 are hospitalized—and that does not include people who are sick at home for a few weeks but do not need hospitalization. About 1:200 die, on average, and the risk increase with age. And we still do not know the extent of longterm harms from it.

If these numbers seems low, compare it to polio, a past scourge: polio paralyzes about 1 in 200 people who get it. That meant tens of thousands of cases each year in the United States during the 20th century, until the vaccine. A 1:200 risk of dying from a disease is a high risk. Measles, the most serious of rash diseases, kills about one person per thousand in developed countries.

These are not close numbers. We can say with some confidence that serious risks of mRNA COVID-19 vaccines are small absolutely and substantially smaller than the risks of COVID-19 itself. If you are one of the people who suffers a rare harm, are your costs compensated? Right now, the answer is “maybe”.

COVID-19 Vaccines Injury Compensation

In February 2020, the Secretary of Health issued a Public Readiness and Emergency Preparedness (PREP) Act declaration for “medical countermeasures” against COVID-19. What this means in practice is that unless additional measures are taken, until 2024—when the declaration expires—manufacturers and administrators of vaccines (and treatments) for COVID-19 are immune from liability if the product causes harm unless they engaged in “willful misconduct”—a high bar. The protection is broad, covering “manufacturers and distributors,” program planners and anyone who administers the vaccine.

Those who suffer a serious adverse reaction to a COVID-19 vaccine cannot, therefore, sue the manufacturers. They can, instead, turn to a no-fault government compensation program, the Countermeasures Injury Compensation Program. But that program is hard to use: compensation requires showing that the harm was the “direct result” of the vaccine with “compelling, reliable, valid, medical and scientific evidence.” The program also requires filing a year from getting the vaccine. Since its creation in 2010 the program has compensated only twenty-nine claims.

Obviously, this is not an ideal solution. To encourage manufacturing during an emergency, liability protections make sense. There is, further, logic in providing compensation for vaccines harms through a no-fault program. Unlike medicines, vaccines offer—ideally—a double benefit. They protect the recipients, but they also protect others through the mechanism of herd immunity: if enough people are vaccinated, the disease cannot spread in the community. Because getting vaccinated is not just a private good but also a social good, there is an argument for having society cover the rare cases of harm. Proving fault—whether negligence or a product defect—can be difficult, and requiring claimants to go through the regular courts means some harmed by vaccine will not be compensated, since they would be unable to show fault. This argument is why Germany adopted a no-fault approach to vaccine injury compensation in 1953, and why other countries also follow a no-fault model. But the other side of compensating those participating in a social good and encouraging fast action in an emergency should be a compensation system that is relatively easy and generous—and CICP is not.

We do have another option. For vaccines given to children and pregnant women, the United States uses a different compensation scheme: the Vaccine Injury Compensation Program. The standard in the program is less demanding, and compensation easier. Congress should legislate to place COVID-19 vaccines under this easier to use program.

Dorit Reiss is a professor of law at the University of California Hastings Law School. Her research and activities include a focus on legal and policy issues related to vaccines. She writes about school mandate, policy responses to non-vaccinating, tort issues and administrative issues related to vaccines.