FDA Insight: Episode 6 – Transcript
>> Anand Shah: Welcome back to another episode of FDA Insight. I'm Dr. Anand Shah, the Deputy Commissioner for Medical and Scientific Affairs here at the FDA. Thank you so much for joining us for our sixth episode. This is part two of our discussion on COVID-19 vaccines. And I'm pleased to reintroduce Dr. Peter Marks, Director of FDA Center for Biologics Evaluation and Research, or CBER. Dr. Marks, welcome back to FDA Insight.
>> Peter Marks: Thanks very much for having me back.
>> Anand Shah: Indeed, last week, we talked about vaccine basics. But this week, let's dive right into something I'm sure our audience is thinking about. Right now, there are many different vaccines under development for a COVID-19, but if multiple vaccines are approved, or licensed or authorized, how will Americans know which vaccine to pick?
>> Peter Marks: I think the simplest answer will be you'll speak with your physician or your health care provider. And that's because they'll be able to look at the information that FDA will put into the product insert, the information about the given vaccine that will tell that health care provider more about which populations that vaccine may be most appropriate for. It's actually a wonderful thing that we have multiple vaccines in development, because it may be that some of the vaccines will work better in older people, some may be more effective in younger people, some may have fewer side effects in certain populations. And all of that information, one of FDA's jobs is to take that information and make it available in an accessible format to health care providers so they can digest that information and then make the right recommendation to a patient for which vaccine they should receive.
>> Anand Shah: Dr. Marks, many Americans have heard about Operation Warp Speed. If vaccines are indeed being developed faster, how can the public be confident that they're safe? Does that mean that we at FDA change our standards?
>> Peter Marks: No, and in fact, that's the exact point here, is that there will be no change in our standards for approval here, that vaccines will have to be safe and they'll have to show efficacy. What's happening here in Operation Warp Speed is that vaccine development is normally a very linear process. And that's because it moves from step to step to step in order to essentially de-risk the cost of making a vaccine. Because when one goes from step to step to step, one doesn't unnecessarily invest money in something that might fall out of development.
In Operation Warp Speed, what has been done is multiple steps are being done simultaneously without sacrificing the safety or the determination of efficacy in order to be able to produce a vaccine for use more quickly. So, it's just a matter of here, the benefit of having a vaccine is so great that it's worthwhile putting the additional resources in to do things at the same time rather than one step after another so that we can end up with a vaccine more quickly. Obviously, at the end of the day, we have to make sure that all of the boxes are checked and that we have a safe, effective, high quality vaccine that people are able to receive.
>> Anand Shah: Dr. Marks, you mentioned efficacy and safety. Can you explain a bit about how a vaccine is developed? There's a lot of information available about different phases of vaccine trials. What does that really mean?
>> Anand Shah: So, there are various stages of vaccine development, as you know. The first part doesn't involve even using people; the first part involves using one of the known vaccine platforms or developing a new vaccine platform. Having that particular vaccine, that one makes, then tested in animals in order to understand how animals form immune responses to the vaccine. And for many infectious diseases, and thankfully, also for something like COVID-19, there are animal models that we can use to help tell us whether the vaccine is likely or not to cause an immune response in a human. It doesn't tell us for sure, but it gives us some insight. And once we have that data and we feel comfortable and we also see that it appears like the animals have not been adversely affected from the standpoint of safety, we go into a first in-human study, which is often called a phase one study.
And there what we're looking to do is to see if the vaccine is safe when you give it at a given dose. Is it safe in the people who it's given to? And then it generally progresses if it's safe to a phase two trial, that's where one looks, not only is it safe, but also can we find the dose at which it has a has a protective effect. And oftentimes in that case, we'll use something that might not be the final end point that we're going to use in the clinic, but we'll look at whether it causes an immune response in the individuals.
And then once something passes that test that it causes an immune response in the individuals and it's safe, then it moves on to phase three. Phase threes are usually large. What I mean, in vaccines, it's usually tens of thousands of individuals where either half or two-thirds of the people get the vaccine and half or a third for half the people get a placebo. And one looks to see if the vaccine protects against the infectious disease.
For those who might not be so familiar with the term placebo, placebo just means an inert substance. So, something that's not active. So, the idea is to make sure there's a difference between the vaccine and that non-active placebo to see if there is an effect. And then that way unambiguously, without any doubt at the end, one can see that the vaccine has the kind of efficacy that we need to see to approve or authorize a vaccine for use. Those large trials in phase three also provide us with very large sets of safety data that also help us feel comfortable then that they meet the standard that we can either authorize for license, both vaccines.
And then there's actually even what's really like a fourth stage of development. Sometimes it's called phase four. But in this case, it's what happens after the vaccine is approved, which is that sometimes we ask manufacturers to do additional work, to look in special populations, or we ask them to do studies, to look at even larger numbers of people to make sure that we really understand how the vaccine works in either specific populations or that we understand any specific side effects that we think might be associated with the vaccine.
>> Anand Shah: Dr. Marks, I want to pivot to a question that I know is being discussed at many water coolers and dinner tables across America. It's probably something you can't answer. But how soon do you think a vaccine can be authorized or licensed at the current pace of development?
>> Peter Marks: This is this is like a question like the rock upon which the thousand ships have gone down on, but I'll give it my shot here. Just to try and work through this for people, the large clinical trials that will be starting this summer, it takes a period of time to get the large number of individuals enrolled into the trial. After the trial is enrolled, the patients all have to receive the vaccinations. Then it actually takes several months to see if there are any differences that arise that indicate that the vaccine may be effective.
And so because we're talking about these things that take on the order of several months, I think the earliest we could be seeing a vaccine is a number of months from now. I can't put a number on that because it would -- I'm certain to be wrong. I know what I can say is that basically no one is delaying anything, and all the stops are being pulled out to try to move the clinical trials forward. And I can say from the standpoint of what will happen after those trials are completed, we're at FDA prepared to pull out all the stops to assure that once a vaccine does show efficacy in a trial and shows that it's safe, we're ready to help let it get deployed either through an authorization or through an approval as absolutely quickly as possible.
>> Anand Shah: So, Dr. Marks, once that authorization or approval happens, how quickly will patients be actually able to get that vaccine?
>> Peter Marks: So, the groups around the government, it's cross government, are working together here to make sure that it's really going to be a matter of weeks from the time that we get data to the point that that vaccine can start to be deployed. Now, how much of it will be deployed and how long that will take I can't answer today, but I know there are teams working on that and they're trying to make that as quick as possible and to make it make as much sense as possible so that the first vaccine that's ready to go goes out to the people who need it most and that ultimately everyone who wants to get vaccinated get vaccinated.
>> Anand Shah: So, patients and consumers will have to make a decision about whether to seek a vaccine or not. And in the news, we often hear about a term known as herd immunity in the context of COVID-19. What exactly is that? And why is herd immunity important?
>> Peter Marks: So, herd immunity is a situation which we have in the United States for certain infectious diseases. When we keep, for instance, our measles, mumps, rubella vaccine rates up high enough where [unintelligible] enough children are vaccinated, we don't see those infectious diseases anymore because so many people are vaccinated that there's no room for the infectious disease to find a toehold to move from person to person because if the average person that someone meets is immune to it.
So even if you happen to have measles for some reason, you can't spread it because everyone around you is immune. That's the concept of herd immunity that you have enough people in the population that can't get the disease, that the disease has nowhere to go if it shows up. That's exactly what we'd like to ultimately see with a really effective vaccine, one that might have, I think, we estimate at least 70 percent efficacy that would have that same effect where if you had 70, 80 percent efficacy and enough of the population is vaccinated with it, COVID-19 will have nowhere to go, and it will just go away. That's what happened for smallpox. It's what happened for measles, with the exception of the occasional times we've had re-importation. It's what's happened with polio. And so, this is an incredibly important thing. And so I would view it as almost a civic responsibility. Once we have vaccines to go out and get vaccinated because if we all do this, we're doing it for each other to protect each other in the long run and help us all get back to normal lives.
>> Anand Shah: Dr. Marks, is there a process in place to help evaluate the vaccine when it's used broadly?
>> Peter Marks: So, once the vaccine will be used broadly, we already are putting in place, in conjunction with our colleagues at the Centers for Disease Control and Prevention, systems so that we'll be able to monitor not only the safety, but also the efficacy of this in the large population.
So, we will be making sure that after the vaccine is out there and getting used, any vaccine that we are keeping tabs on what's happening in terms of its safety, we'll be making sure that there aren't some rare adverse events that pops up that we didn't see before. And we'll also may be looking at its efficacy, seeing in large, large populations, millions of individuals. Is it doing what it's supposed to be doing? And so, I think that's a very important component of what we're able to do. And if you ask me what's different now than 10 years ago, I would say that is one of the major differences is our ability now through having excellent electronic medical record systems, claims-based databases that we can use as tools after a vaccine is deployed to understand their safety and their efficacy profile.
>> Anand Shah: Dr. Marks, I really appreciate you coming in now two weeks in a row to discuss COVID-19 vaccines. We're all very hopeful that a safe and effective vaccine is developed soon.
>> Peter Marks: Thanks so much for having me on your show, and we have the same hope.
>> Anand Shah: Thanks to our audience for joining us again on FDA Insight. As always, we'll be providing you insight in plain language to help you understand the products that we regulate, the issues that we face and the processes that we follow. We hope you enjoyed this episode of FDA Insight. Please subscribe on your favorite podcast app of choice, such as Apple Podcasts, Google Play, and others. See you next week.
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