FDA Commissioner Discusses Requirements for COVID-19 Vaccine Approval

John Whyte, MD, MPH; Stephen M. Hahn, MD


October 08, 2020

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  • FDA experts evaluate three main areas for all vaccines, including for COVID-19: safety, effectiveness, and manufacturing quality.

  • Before a COVID-19 vaccine is approved, the FDA will review safety and effectiveness data from at least one well-designed and -performed clinical trial that shows data that are "clear and compelling."

  • The FDA is looking for a COVID-19 vaccine that has a minimum of 50% efficacy but is hoping for higher.

  • The FDA is requiring a "very robust" program to continue to look at safety data after a COVID-19 vaccine is approved, as well as an "aggressive" postmarketing assessment program.

This transcript has been edited for clarity.

John Whyte, MD, MPH: You're watching Coronavirus in Context. I'm Dr John Whyte, chief medical officer at WebMD. Today I am joined by Dr Stephen Hahn. He's the commissioner of the US Food and Drug Administration (FDA). Dr Hahn, thanks for joining me.

Stephen M. Hahn, MD: John, thank you. I really appreciate the opportunity. It's great to be part of this webcast.

Whyte: Let's start with the obvious: How is this [COVID-19 vaccine] process going to be transparent when a large number of the public is more interested in these particular products than they would be in perhaps a diabetes medicine or a medicine for the heart?

Hahn: As you know, we have experts at FDA in our vaccine division in the Center for Biologics Evaluation and Research who do this for a living. They are great scientists, doctors, nurses, pharmacists, statisticians. They look at the primary information, the raw data that come from clinical trials on vaccines, and they make a decision based on three factors: safety, effectiveness, and information about the manufacturing. There's a number of different acronyms we use for that, but that's not really important. What is important is, are we confident that the manufacturing is of high quality and that every vaccine that comes off the manufacturing plant has a high level of consistency and quality associated with it?

Those are the data that we would look at, regardless of whether it's an emergency use authorization (EUA) or a biological license application. With a vaccine, it's a little different from a therapy because this is going to be given to people who are presumably healthy and don't actually have COVID-19. That changes the balance somewhat for us.

We've listed a couple of criteria that recently came out in vaccine guidance. One is that we will need to see effectiveness and safety data from at least one well-designed and -performed clinical trial that is robust and that shows data that are clear and compelling. We've already said that we would look at a floor of 50% efficacy. Now remember, that's a floor, not a ceiling. Of course, we want to see high efficacy if possible, but the floor will be 50%.

Whyte: Give people a reference for that. Is 50% good? Is it consistent with many other vaccines? Maybe compare it to influenza. We know that for pneumonia, Pneumovax can be 90% effective. So explain to us about 50% because I think people get confused by that.

Hahn: We (our scientists) felt that for this public health emergency, the most appropriate floor was 50%. That should give you some perspective on that.

With respect to safety, what we said was that from the last dose of vaccine — in some cases there are two doses of vaccine; in some cases there is one — we would need to see follow-up data of a minimum of 2 months after the last dose of the vaccine in at least 50% (in the median) of the volunteers who are on the trial.

Whyte: And 15,000 people — is that right?

Hahn: Exactly right. It's a trial of 30,000 people; 15,000 receive placebo, 15,000 receive the active vaccine. Now, we added something else just to make sure that we can ensure safety. That is, we require a very robust program to look at additional safety after, or if, a vaccine is approved or authorized. So, in this case in the EUA, we want to see this minimum amount of safety data. Then we're going to be very close in terms of our observation of any additional safety events.

Whyte: How does that play in the role of safety? In our survey on WebMD, people are very concerned about getting the vaccine in the first 3 months. Everyone's saying, "I'll let you, Dr Hahn, get it and see how you do." We all can't be doing that.

Hahn: A couple of things: One is that our safety database isn't just from the randomized clinical trial. Remember, for some of these vaccines, which started in humans back in the spring, we have safety data from those individuals as well. We'll look at the totality of data. The other thing that we're going to do, obviously, is this very active postmarketing assessment program. We're going to do a very aggressive approach to that.

Remember, this won't be given to 100 or 300 million people in the first 3-6 months. There will be a rollout plan associated with this as the manufacturing runs up. And so what we'll want to do — and again, I don't want to prejudge that this is going to happen; it all depends upon the data. Remember, the data are going to be looked at by our scientists and a vaccine advisory committee. Given the fact that we do have a robust safety database up until now, plus the size of these trials (which are larger than many trials for vaccines in the past), and the surveillance afterward, our scientists feel that we can have confidence around the safety.

Now, that being said, we really do have to look at the data and look at it very closely. If you look at the current situation, anywhere between 800 and 1000 people are dying per day in the United States, let alone worldwide, from COVID-19. If there is a highly effective vaccine that appears safe in this dataset that we're talking about, we will consider authorization — and I'm not saying we'll do it — in order to prevent additional deaths associated with COVID-19, if the data suggest it.

Now, I will not prejudge, and this is not my saying that we will do it. I'm just saying that this is what FDA does. If we do not feel that the data are supportive enough of safety, we won't authorize. That is for sure.

Whyte: I think that's an important message. Finally, tell us about the morale. And let's be honest: I'm sure it can be challenging if one feels that there is an attack on science, if one reads that it's a political hit job, in terms of trying to put out good information. How are people feeling?

Hahn: Throughout this pandemic, our folks at FDA, 17,000-plus ─ you know them yourself personally — have been absolutely remarkable. They have stepped up to the plate to serve the American public. Our workload has doubled during this pandemic. Not only are we working on COVID-19, but all of our regular work (eg, cancer drug approvals, cardiac drugs), all of our user-fee deadlines — we're meeting those parameters and those deadlines. We're doing our regular work, and at the same time, we're responding to the public health crisis. These are remarkable public servants. They have not looked back. They have stepped up to the plate and they've done tremendous work.

Of course, everyone is tired. There's a large workload. We're trying to stay focused on the public health commitment that we all have. I think the externalities that we always hear in the press and elsewhere do take a toll. There's no question about it. One thing I can tell you, though, that I am incredibly proud of is the amazing resiliency of our folks. We spent a lot of time — the leadership, center directors — focusing on how we can help build resiliency, but also on how we can best support our incredible staff at FDA.

I want to tell your listeners and the entire American public that America's FDA is there and has been there for them. They do nothing except use science and data to make decisions. They've done that up until now. We will continue to do that. I have absolute confidence and faith in them. And I am incredibly proud of them as a workforce.

Whyte: I want to clarify to our audience that there were no questions that were off-limits in our discussion today. You've been very gracious with your time. And I want to thank you for clarifying and providing answers for what's on people's minds, as well as for the dedicated work that you and the thousands of people who work at FDA are doing, literally all over the globe. So, thank you, Dr Hahn.

Hahn: John, thank you, and I really appreciate you and your organization asking these questions. We talked a little bit about what increases trust: transparency. It's being able to answer the questions that need to be answered. I appreciate that you're doing that. Thank you.

Whyte: Thank you.

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