Locke Lord QuickStudy: Approving New Vaccines in the Time of COVID-19

The full weight of the federal government (and obvious public support) is being brought to bear on the development and approval of a vaccine for COVID-19. But what are the steps involved in that process?

What is a vaccine?
A vaccine is a biological preparation designed to sensitize a person’s adaptive immune system to future disease, here the COVID-19 virus. New vaccines contain a novel agent that resembles the disease in some way. The goal is to train the body to attack the novel agent and later the virus itself.

How are vaccines regulated?
The Director of the National Vaccine Program within the Department of Health and Human Services—currently, Dr. Bruce Gellin—is required by statute to facilitate the development of new vaccines. Dr. Gellin is tasked to coordinate with:
    •the National Institutes of Health (NIH),
    •the Office of Biologics Research and Review of the Food and Drug Administration (FDA),
    •the Department of Defense, and
    •the Agency for International Development
to develop the techniques needed to produce safe and effective vaccines and provide for safety and efficacy testing of vaccines. 42 U.S.C. §300aa-2(2)-(3). FDA and NIH, in particular, are involved in vaccine development.

Presumably, a pandemic and national health emergency will cut through a lot of red tape generated by the multiple federal agencies. But even with immediate regulatory review, it is still in everyone’s best interest to require that a vaccine be safe and effective.

Safety and Efficacy
Demonstrating safety and efficacy for an approved vaccine runs from inspecting the factories where vaccines are made to reviewing and approving the instructions that are provided to the doctors and nurses who administer the vaccine. But how do we determine safety and efficacy for a new vaccine?

There is a balance between safety and efficacy for vaccines. A vaccine is efficacious if it triggers an immune response and activates the immune system to the virus. But, a vaccine is not safe if it triggers too much of an immune response (e.g. anaphylactic shock).

Testing efficacy of a vaccine is somewhat complicated. Clinical trials measure people not getting sick by comparing disease rates between people who are vaccinated to people who are not vaccinated. Results can be difficult to interpret. If a vaccinated subject does not get sick, it can mean that he or she was not exposed to the disease. If a vaccinated subject does get sick, it can mean that he or she was exposed to the disease before his or her body had time to develop immunity. It is, of course, unethical to test vaccines in people more directly—i.e. to give a person a vaccine and then purposefully infect them with the disease—although this step must be done earlier in development with cells or animals.

Timing and clinical trials
The regulatory step before human testing of a new vaccine is typically filing an investigational new drug application (IND) with FDA. An IND includes the basic research, cell and animal studies, and manufacturing information that suggests a vaccine will be safe and effective in humans.

It appears that NIH has already cleared that hurdle in the U.S. NIH and Moderna started the first COVID-19 clinical trial yesterday, March 16, 2020—a Phase 1 trial with mRNA-1273. The study is enrolling 45 healthy adult volunteers for a six-week open-label study to test different doses of an mRNA-based vaccine to the spike protein of SARS-CoV-2, the virus that causes COVID-19. The study is based in Seattle, one of the hotbeds of COVID-19 in the U.S., so participants have a higher chance of coming into contact with the virus. Each participant will receive two doses, spaced 28 days apart, of 25 microgram (mcg), 100 mcg, or 250 mcg of the vaccine (15 people each). Doctors are testing initial safety by dosing limited subjects with the lower doses before using the higher 250 mcg dose.

Other efforts are ongoing. Pfizer and BioNTech expect to start clinical testing by the end of April on another mRNA vaccine. And the European Union is supporting efforts by CureVac to develop a third mRNA vaccine, with initiation of expected clinical testing by June.

mRNA vaccines use the body’s own cells to produce the protein that is meant to activate the immune system. They are typically thought to be easier to produce and more rapid in development. However, to date, no mRNA vaccine has been approved by FDA.

Clinical trials are conducted in multiple steps. As evidenced above, Phase 1 is the initial safety study conducted on a small number of people. Phase 2 is a larger study or studies that involves hundreds of subjects and explores the same or additional doses. Phase 3 involves thousands of subjects and is used to determine effectiveness. After Phases 1-3, an applicant submits a Biologics License Application (BLA) for review and final approval by FDA.

With COVID-19, significant efforts are being made to speed-up the process. Regulatory review is being fast-tracked. Recruiting subjects for clinical trials—normally a time consuming process—is unlikely to be a problem with the current heightened public interest in developing a vaccine. Clinical trial stages may even overlap to save time.

But could there be a sacrifice of safety or efficacy for time? Given the seemingly high rate of infection but limited mortality in healthy subjects, it would be irresponsible at best to provide an ineffective or unsafe vaccine and tell people to resume their normal lives. Fortunately, medical professionals are quite dedicated and driven, and can do quite a bit to accelerate the process.

Can all this be done safely in a short period of time? Time will tell.

Visit our COVID-19 Resource Center often for up-to-date information to help you stay informed of the legal issues related to COVID-19.