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Voices of HHS

Dr. Peter Marks: Operation Warp Speed

Thursday, July 2, 2020

On this episode of “Learning Curve,” Caputo joins the Director of the FDA’s Center for Biologics, Evaluation, and Research, Dr. Peter Marks, to chat about what types of products the Center oversees, the role personal responsibility plays in the spread of the virus, and the genesis of Operation Warp Speed.

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Michael Caputo: This is Michael Caputo; I am the Assistant Secretary for Public Affairs at the United States Department of Health and Human Services. The COVID-19 pandemic is a new experience for almost every American. Few of us have personal experience with any infectious disease threat like this. Protecting our families, our communities, and our country requires learning: learning about the virus, how we can prevent its spread, and how we can protect the most vulnerable. So far, as the president and many Trump administration leaders have said, Americans have done an incredible job educating themselves about the virus and taking smart steps to protect themselves. This hard work has to continue. The president's aggressive response has also pushed his administration into uncharted territory. How can states and the private sector take -- you know, make testing even faster and more accessible? How quickly can we get therapeutics and vaccines to the American people? And once we know what works, how can we get as many as we need and deploy these tools as quickly as possible? These are the kinds of questions that lots of Americans want to know the answers to. Providing answers to questions like these, being radically transparent about where we're headed and what we're learning -- that's the aim of this HHS podcast. This is Learning Curve. I'm Michael Caputo, and I've got a lot of people to introduce you to here at HHS.

So this week on Learning Curve we have Peter Marks. Dr. Marks is the director for the Center for Biologics, Evaluation, and Research. The acronym is CBER, and he is at the Food and Drug Administration. The Center for Biologics is responsible for ensuring the safety and effectiveness of biological products like vaccines, you know, allergenic products, blood and blood products, and cellular tissue, and gene therapies, and if that sounds like everything in the pharmaceutical arena, it really is. Dr. Marks, your job is all-encompassing, isn't it?

Peter Marks: Well so, we don't do small molecules. We don't do monoclonal antibodies. There are certain things we don't do, but we do have a tremendous range of products and it's quite an interesting range of products. It ranges from things that nearly nobody gets, like certain gene therapies that are for very, very rare disorders, to things that nearly everybody gets, like vaccines that protect us against things like measles, influenza, and other infectious diseases.

MC: So you really, as the leader of the Center for Biologics at the Food and Drug Administration, you're at ground zero of COVID response, aren’t you?

PM: We feel like it. [laughs]

MC: Well you are. I mean, honest to God.

PM: Yeah, exactly.

MC: Every reporter -- I mean, everybody knows -- I'm still relatively new here, but every reporter who has covered HHS and covered pharmaceuticals for quite some time -- they all know you. Everybody knows Dr. Peter Marks who's in this industry, who is -- you're on the front line of all of this.

PM: I think that's because we have both some therapeutic things in our center, like convalescent plasma, hyperimmune globulin, and some variations thereof, plus we have the vaccines. And in addition to those things, we cover blood donation policies, so we've made some changes to those during this period to help adjust to the COVID-19 crisis, which actually I think those are a great example of how some things -- good comes out of bad situations sometimes, where I think we've advanced policies in some ways for the better, for the long term.

MC: There are those who are out there saying, you know, because of whatever reasons -- distrust, basic distrust, whatever political reasons -- are talking about how, you know, the safety and efficacy of the therapeutics and vaccines that may come out of the months ahead are something to be mistrusted. I want people to understand -- I didn't understand -- how big is the Center for Biologics? How many scientists are there? How many people are keeping an eye on this for the American people?

PM: So we have a center of about 1,200 people as full-time equivalent, plus a couple hundred of contractors in addition to that. The office of vaccines which handles vaccines review, we have an office of blood products, an office of tissues, and advance therapies, they handle the cellular therapies and the gene therapies. Scientists, Ph.D. scientists, MD scientists, support staff that are all absolutely committed to ensuring the safety of the products that we regulate -- the safety and effectiveness. And I think people come to work every day really committed to that. I think when we do employee surveys, people -- we are over 95 percent generally, on people being absolutely committed to the mission of making sure that the products that we regulate are safe and effective for what they say that they're going to do.

MC: Quite literally a legion of scientists who are standing between the American people and great ideas and some bad ideas on therapeutics and vaccines. A legion of scientists.

PM: Right.

MC: And I think one thing that struck me when I first met you, and -- is that, you know, you're enthusiastic about your job. How long have you been at it?

PM: I've been at FDA for a bit over eight years.

MC: From my perspective, it really was definitive for me to talk to you about this because it felt to me, and it still feels to me of course, that you take your job so seriously, you have like a solemn commitment to it. To me it's beyond ethics. I've been really remarkably impressed by the people in your operation.

PM: Thank you. I think all of us are very committed to doing the right thing by public heath, which means following the science, looking at the data, understanding the data, and then doing the right thing. The right thing will be following those data, making sure that anything that we do is to the best of our ability to know that if we look at something, that it's appropriately safe and it has the appropriate efficacy to meet our standards.

MC: And with that in mind, the solemn nature of the commitment of your people to making sure that therapeutics and vaccines and biologics are safe, that commitment really spreads across a lot of this coronavirus response. I want to talk about therapeutics and then vaccines because -- well actually, let's do it the other way around. Let's talk about vaccines first because that's what everybody's talking about. They, you know, the American people believe that without a vaccine we will never go back to normal, ever. Now, I've learned that's not quite true, but going back to normal in many ways can be hastened along by the vaccine and more importantly, by people accepting the vaccine. Tell us what the regulator's role, the Center for Biologics' role is in the vaccine development.

PM: So, we have a couple different roles that we play. As the vaccines are being developed, as they're going through the process of having manufacturers take a concept and bring it through testing and into people, and then take it from a small number of people into a large number of people, we provide advice to them on the most efficient way to get to a robust answer. An answer that will tell us in a manner that we can feel comfortable with, that the vaccine is safe for deployment in large populations and it has efficacy at a level that makes sense to use in a large population.

MC: It's interesting because really when it comes to vaccine development, it's a pretty long timeline typically, isn't it?

PM: It is. It's normally years, and a lot of what's trying to happen here is compressing that into the shortest time possible to get the data that's needed in terms of safety and effectiveness to be able to make a determination that the vaccine is deployable to help prevent COVID-19.

MC: And that's what caused you -- I think principally you but some of your colleagues as well, to develop the concept of Operation Warp Speed. I mean, what people don't know, even though the president announced it and it comes out of the Trump administration and it's something that the secretary of HHS Alex Azar and the secretary of the Department of Defense co-chair, appointees of Donald Trump -- Operation Warp Speed was designed by scientists -- was designed by you.

PM: It initially came at a point towards -- actually it came about towards March of this year when it became clear that perhaps we weren't pursuing trying to get towards a vaccine as diligently as we might. Or I think people almost had a fatalistic viewpoint that it's going to take a long time, we're going to have to live through this for a while, and many of the vaccine timelines were not seeing a vaccine come to market for a year and a half to two years. And --

MC: We couldn't wait that long.

PM: Well, you know, the idea would be we shouldn't wait that long if there's some way around it, right?

MC: And you saw a way.

PM: Right, right. Well, I think the way that we thought we could reduce the time is having worked in the pharmaceutical industry and worked on drug development, it's very clear that there's a lot of dead space in drug development. Sometimes, there are ways to eliminate dead space. When it has it do with resources or money, in this case, not having a vaccine is obviously costing a heck of a lot more than anything that would go into eliminating dead space. What do I mean by that? We normally -- one finishes one phase of a clinical trial and then starts another phase of a clinical trial. One has preclinical data and then one proceeds in a very orderly fashion through preclinical data phase one, phase two, phase three. Now that's not to say you can just jumble them all up, but you can eliminate time between things. And then additionally, most of the time for vaccines, one doesn't start to manufacture the vaccine until you know you've got something that's going to work. Unfortunately here if one does that, one delays things by months and months. So here, I think probably if there's any, you know, stroke of really insight here it's that look, you can start making the thing at risk in large quantity.

MC: Meaning at risk, as a financial risk?

PM: As a financial risk, not as a [laughs] --

MC: Right, right.

PM: -- as a financial risk, thank you for making sure that's clear. It's a financial risk because the worst thing that happens is if in phase three trials it turns out not to work. You throw it away. On the other hand, it would be kind of really sad is if at the end of phase three, you showed that the thing really worked but it was going to take another three or four months while literally thousands and thousands and thousands of people contracted COVID-19 while you were manufacturing the stuff to make it, right?

MC: Right.

PM: So this way, if there's something that turns up that we determine is safe and effective, there will hopefully be supplies ready to be deployed and to people who need it.

MC: And the way you designed Operation Warp Speed is that the development would happen in parallel to the manufacturing, in parallel to the design of the distribution system. And you're going to have multiple vaccine candidates to deal with, and so you're basically setting up manufacturing and distribution systems in parallel that we're going to end up not using. Any private company that did that, their investors would fire the entire C suite if they did that.

PM: Right, right. But when you think about it, when you have an economy that lost -- I'm not an economist but I don’t know how many -- it was how many trillions of dollars like happened with our last shutdown? So if you're talking about a trillion dollars versus a couple billion dollars to make some vaccine at risk, that the worst thing that's going to happen is you're not going to use it, but the best thing that happens is --

MC: You save lives. Yeah.

PM: You save lives. You save lives not just -- and that's not just from preventing COVID-19, it's from allowing people to get back so they get screened for their colon cancers, they get their childhood vaccines, so that we can restore our country back to order. The true toll of COVID-19 is not just -- ultimately when we look back years from now, it's not going to just be on people who died of COVID-19 or who were harmed by COVID, it will be all of the other people who were harmed by not having their routine healthcare that would have prevented them from dying of a heart attack, or colon cancer, or something that would have been easily preventable. Getting the society back moving is an important piece of why we need a vaccine here.

MC: And the United States government -- a government is uniquely positioned to take the risk, to accept the risk, to even tolerate the loss, because loss of life is far more expensive than loss of dollars.

PM: Right, right, exactly. I think this here -- this was the whole idea here is that look, a couple billion dollars that might go down the drain here, and we don't know -- the point is that it's just we don't know it's going to go down the drain. It could actually be lifesaving, right?

MC: Right.

PM: So, it's a good investment.

MC: It's a worthy bet. It really is, and sorry -- you set this up with your colleagues and you were inside for a while, and you stepped out to regulate the process. I know that you really -- that you love your job as a chief regulator. I absolutely trust you; I mean, I can tell the American people as I sit here on the Learning Curve podcast that Dr. Peter Marks is someone you can trust. And I've found that this is the rule rather than the exception among the regulators who work in the, you know, in the health arena. I think what people need to understand -- we saw an opinion article in the New York Times a couple of weeks ago. I don't want to mention the authors, but both men were -- both of the authors were doctors in the public health system and they wrote an op-ed that theorized that Donald Trump, who they clearly hate, is going to come up with an October surprise that would bring a bad, unsafe vaccine to market so that he could be reelected and then a bunch of people, millions are going to die. I saw that as number one, a real attempt to undermine confidence in the public health system. I don't want you to criticize these individuals. What I want you to do is help me set aside the idea that the Food and Drug Administration regulators would ever let something like that happen.

PM: Yeah, so I, you know, I have to say, I love what Warp Speed is doing. I think they're doing a great job. I stepped away from it because in order to actually do my job, I can't be -- you can't be developing something and then regulating it.

MC: Right.

PM: We have to be able to have that separation. And I stepped aside early enough so that it was -- there's enough air space there so that --

MC: But it might not exist if you weren't there.

PM: Right, well I appreciate [laughs] -- I appreciate getting it started --

MC: But anybody in this space who knows what's going on knows that you played a pivotal role.

PM: But what's really important to me is the regulatory aspect of this and, you know, I just -- just to make sure people understand. What we will do is we will look at the data that comes in to us from the manufacturers. The goal is it's not to do something for one person or another, it's to do something for our responsibility to the American people to make sure that if we say that a vaccine is safe and effective that we do so. If we say that the preponderance of evidence is such that we feel that a vaccine could be deployed, for instance, under emergency use authorization, it's because we have looked carefully and we've looked at the benefits and the risks, and we truly believe that this vaccine is going to save lives. We're not going to do something for another reason, and our folks just can't do that. They won't do that because they care too much. They care too much about their responsibility to every one of the people of this country not to fall down on the job.

MC: When lives are at stake on the decisions that you make, you tend to look at things a little differently than let's say, a politician or a critic.

PM: Yeah, I think that's right. I think nobody here is going to take any chances that what we do is done without the most extreme care. That doesn't mean that we can't make a mistake. Mistakes, you know, no matter how good we are, there's always a chance that mistakes can be made. But our goal is to do our absolute best not to make mistakes; our absolute best to make sure that if we do put a vaccine out there, we're going to have the right safety surveillance system there. There will be post-marketing, or post-deployment will be looking at what's going on to make sure that anything that's put out there, as we would with any new vaccine. It doesn’t matter whether it's COVID or if whether it's a vaccine against shingles, or a vaccine against pneumococcus, or even a seasonal influenza vaccine. Every time we put a vaccine out there, we look at the safety after it's deployed to make sure that nothing is going on that we didn't expect. We'll do the same thing here. We have an absolute -- I mean our mission, our absolute obligation here is to make sure that we do our absolute best to make sure that what goes out there is doing what it's supposed to.

MC: It's interesting, because -- well, I don't want to get into the politics of this because this is more a public health question than it is a political question. But in the end, vaccines are politics for many people. There are people who believe in vaccines; there are people who don't believe in vaccines. And in the end, we really have to have a certain number of people that accept this vaccine in order to reach what I heard when I first got here was herd immunity. To me as someone who grew up with a grandfather who raised cattle, I know that had a certain implication to me. What is herd immunity?

PM: So, herd immunity is when enough people are immune to a disease that it -- the best way I can describe it is enough people in a population are immune to a disease that the disease can't get a toehold to start spreading because it can't find a host to start spreading from to. It's just not worth it to it, essentially. It's why we like to have our measles vaccination rates up so high in this country, or other childhood illnesses. If we have our vaccination rates up high enough, the pathogen just -- the microorganism doesn't have a toehold to spread from person to person. And so that's one of the reasons why we have to make sure that we do our job well enough that people feel confident that when they get these vaccines, that they're going to do what they say they're going to do. And I should be clear: every medical intervention that you do potentially has side effects. And it's true, I don't -- every year I get the influenza vaccine. I go around for a day or so. I always have an achy arm and sometimes it's a little red, sometimes it's a little achy -- more achy than others. So, we do see side effects, but I think what's important for people to understand is that when we deploy these, it's because we really see their benefit in the population and that as a population, you know, I don't know that you can deny that vaccines work. Vaccines clearly, you know, we've -- smallpox would not have been eliminated without a vaccine. Measles would not nearly be --

MC: Right, well some people think that the earth is flat, so…

PM: Right. No, and that's right, you know, I mean I think, you know, there are just certain things in public health that just happen to be that way. If you don't believe in vaccines, maybe you don't believe that you should have your drinking water and your septic system separate.

MC: Right.

PM: Is that as crazy? No one would say that's crazy right? No one's going to, like, have their -- I mean, I used to live in Connecticut. I had a well, and you made sure that the well and the septic fields, they were code, they were a certain way separated apart, right? Nobody -- I don't think anyone's going to like, argue with me on that one, that that's a good idea, right? But people get -- and that's a basic public health measure, right?

MC: Right.

PM: That was actually determined -- that actually -- the basis for that came from studies done in England back several centuries ago, right? That it's good to have your water supply and your sewer supply separate, right? So, basic public health measure. You've got that.

MC: Right.

PM: No one's going to -- I don't think there's a lot of people that'll argue with you the same way that people will argue about vaccines. Vaccines have more mystery about them, and they've come to have more mystery in part because we are, as human beings, are -- we always are looking to associate cause and effect. Unfortunately, vaccines have gotten a bad rap often because of the cause and effect. Now, there is probably some very real cause and effect. You get that influenza vaccine; the next day your arm's kind of red and it hurts. That is true. That's related to it. Unfortunately, what's happened is, okay, a few weeks later, you develop -- you get a cold. Oh, the influenza vaccine gave me the cold. Or in children, it's the same thing with, you know, with children developing developmental disorders. It's hard to -- for people to understand that those just happen in children at a certain age and they also so happens that the vaccination series goes through a certain age. And so, I don't -- you know, I feel so for parents who -- my heart goes out to everyone who has these things that happen in their lives. But having cause and effect -- our goal, our job at FDA is to help tease apart things, and that's why we do what we can to tease apart what actually relates to a vaccine and what doesn't. That's why I hope people can have confidence that what we'll do is we'll do our job to make sure that when we put a vaccine out there, it's going to be something that is safe and that people can feel comfortable with. That means -- for us, what that means is that it's going to actually be in clinical trials in thousands of people before it's deployed widely, and that's just part of what the manufacturers who are currently doing vaccine trials are going to have to do. They're going to have to study it in thousands of people. And to be honest, we're not even satisfied with that because that's why after the vaccine is approved, we'll want to see what it does in millions of people.

MC: Right. Right. And I think I heard -- actually, I asked Dr. Fauci. Certainly, a certain percentage of people have to take the vaccine in order to reach herd immunity so that we can, you know, so that we can box out the virus. We don't know what that percentage is now, do we?

PM: We don't. I think there is estimates, and part of it depends on how effective the vaccine is. So, we -- but if you hear, I think Dr. Fauci's said, you know, it needs to be probably roughly 70 percent --

MC: Effective.

PM: -- in that range.

MC: Seventy percent.

PM: Seventy percent of people need to take the vaccine --

MC: Ah okay, right.

PM: -- to be able to get towards herd immunity with a vaccine that has a reasonable efficacy.

MC: And what about people who have gotten the disease? How do they play into herd immunity?

PM: Well, yeah. The good news is they will be -- they're immune for the disease for as long as their immune systems keep them immune. Now, this is one of the unknowns, and this is why every day as a scientist I come to work, and I learn something. Because we still don't know with COVID-19, when you've gotten the disease, how long you're immune afterwards. Because some diseases, once you've had it, you're immune pretty much forever. I mean, usually until older age. Whereas other diseases, the -- your immunity goes -- it wanes. And that has to do with the complexity of our immune systems have both a component where the cells of the immune system make a response and we also make antibodies, the molecules -- the proteins that attack the microorganisms. And so there's some mix of that, and for some microorganisms, we make a robust response that protects you for most of your life and others, it only can -- you might only be protected for months. We still don't know yet how long one will be protected against COVID-19. Why? Because it was just last December. So we don't know whether it's going to be months, years, and we'll see with the vaccine ultimately -- we'll see with the vaccine and we'll see with individuals how long that lasts. The good news is we don’t see reports right now of people being re-infected who have been infected previously. So we know it --

MC: And that’s good news.

PM: That's good. That's good news because it means that at least you're making antibodies, and at least for a few months, we know you're protected. But we don't know how long.

MC: And I want to get with that, that's very interesting, because the antibodies lead into your other job. If -- like, I've learned that watching vaccines in development is kind of like watching grass grow. Even when the grass is growing at warp speed, it's still -- it's a slow process. It is. And in fact because it's going to take that long -- if vaccines were a film, they would be a feel-good holiday movie. That's what they would. People will be really encouraged by what they hear in the holiday season. But under the same line, therapeutics are a blockbuster summer film. I mean, the news that we're getting out of therapeutics -- it's going to happen now and one of the things we have, you know, we've heard about the impact of remdesivir, which we just announced today. We've secured a supply of remdesivir that's going to help America heal of -- Americans who catch COVID heal through the summer and into the fall, a half a million doses secured. But in addition to that we've looked at steroids that are helpful and helping people recover, and other things, but one thing that I've heard a lot about is plasma-based, and we were just talking about how someone's antibodies -- if you've got -- if you've had COVID, then God bless you for surviving, but you should go and donate blood right now. Donate plasma right now because that plasma, it's really remarkable, isn’t it?

PM: Yeah, so we're -- there's currently studies going on. We don't know for sure yet, but there is some promising data that suggests that if you take the plasma, which is the liquid portion of blood, from an individual who's had COVID-19 and you give it to someone who's in the throes of being pretty ill with COVID-19, you could potentially help make them better more quickly or prevent them perhaps even from dying of this. Now, we don't know definitively yet, we don't know definitely, but there are quite a number of randomized trials going on. There's a very large expanded access program which is currently being analyzed to see if we can understand whether we can -- whether there's really definitive efficacy there or more definitive efficacy. But in the meantime, I think given what we see of promise in this area, we certainly would encourage anyone who's had COVID-19 who's gotten better, who feels up to it, to go out and donate at a blood collection center or at a plasma collection center because you can make a really big difference.

MC: You can. In fact, that's what makes it the summer's, you know, blockbuster hit. Because right now we're seeing a rise in cases; some people are saying it's because we're testing a lot more, but it's also because there's asymptomatic spread. We're finding out now --governors are telling us, that their increased testing is finding COVID-positive cases in young people, 35 and younger. Now, many of them are asymptomatic, meaning they're not showing any symptoms, but they test positive for COVID. You know, first of all they should thank God they didn't get any symptoms, but the next thing they should do is call the Red Cross and donate their plasma. Don't you agree?

PM: Yeah, no, I think it's something they should certainly think about doing. There's some interesting things here. It looks like people who have actually been the sickest with COVID-19 probably have the highest antibody titers, so if you've been sick with it and you can donate, it's great for you to do it. But because we can actually measure the amount of antibodies in the plasma that's donated, even if you haven't been sick with it, you should go and donate because we can test it anyway.

It turns out that, believe it or not, we still need plasma even if your plasma can't be used for treating someone with COVID-19. We have a blood shortage anyway going on, so it's just a good thing to go and donate blood anyway. So people going to donate blood, plasma -- those are really good things to be able to be doing now because our blood donation goes down to --summertime's a challenge for blood donation anyway because people tend not to go as much. We can use blood donors who just need to donate blood, so we keep our blood supply going. Plus if you've been diagnosed with COVID-19, it's a great way to try to help others. And each donation can actually help potentially help several people, so each donation --

MC: So you go donate plasma, you -- there could be multiple people who benefit from it.

PM: Right, so there could be three people who benefit from that donation of plasma.

MC: Isn't that something? And they call this convalescent plasma, right?

PM: Right. Convalescent because you've gotten better from the -- convalescent because you've convalesced, you've gotten better from the disease when you donate it.

MC: See, that's why I think it's tremendous to actually, as somebody who learned everything he knows about healthcare from the Obamacare website, I don't -- I came in here -- I'm not a specialist, but I am just -- it's remarkable to me how big these therapeutics can be. Because this is a remarkably infectious disease and there are so many people who have had it and don't even know, and they have a viral load and they're giving it to people. If you're 35 or below and you've been to a bar and it was crowded, you better take your butt to the testing center like right now. Am I right?

PM: Yeah, well I think probably it's -- more testing is good, because the more people who have been in high risk situations who know that they've had this or they have it, then can shield themselves from bringing it home to their parents or grandparents, that's really the -- the problem really is, you know, with young people who have COVID-19, there are two things that I would say to them. First of all, sometimes people don't know that they have complicating things like asthma or lung disease, and so there are the occasional young person who may have been cavalier who gets this and succumbs to it. They die of it. And so, it's not totally a free lunch. It's not like everyone who's below 30 who gets COVID-19 gets away with a get out of jail free pass. But the other thing is that most of us have social networks that include people older than ourselves.

MC: Or more ill.

PM: Or more ill than ourselves, exactly.

MC: With these comorbidities that get terribly bad.

PM: Right, exactly. So even if you think that you're not going to see grandma or grandpa, you may actually have a friend who has cystic fibrosis, or -- and they may not be -- because of how well things are meant or are currently managed with some chronic diseases now, people don't always say that, "Oh, I have type-1 diabetes, or I have…" and they can be pretty young. You don't want to be spreading this, so that's the reason --

MC: And you don't know that they're sick. You don't know.

PM: Exactly.

MC: That’s what Secretary Azar has been saying.

PM: That's the reason to take precautions if you're younger, because you don't want to be spreading this stuff.

MC: That's right, and that's what Secretary Azar has been saying about your personal responsibility. The government can shut down the economy. The government can tell you to wear a mask. The government can do this, and that, and the other thing. But in the end, it's yours and it's our responsibility to our grandparents and to our friends who we may not even know are managing a comorbidity.

PM: Yeah, I would say that everyone -- you can be your own leader. I know that my wife and I, we always go out of the -- we wear our masks reproducibly and because of that, originally my kids were like on and off, but since they see us doing it all the time, they do it all the time. And they actually insist that their friends when they're -- so, you can actually start your own trend by just doing the right thing.

MC: You know, you and I have been around each other a bit, and I just got to tell the audience that I rarely see Dr. Marks' face.

PM: [laughs]

MC: He and I are in situations where he's wearing a mask. He's wearing a mask; I'm learning from the doctors that I need to wear a mask in certain situations. I told friends of mine this weekend that if you're not wearing a mask, if you can't socially distance, you need to wear a face covering. If you're not wearing a face covering and you're not socially distance, then you are part of the problem.

PM: [affirmative]

MC: Then you are one of the reasons why this is spreading. And you may not care, but do you care about your grandpa or your grandma? I mean, to me, that's a no-brainer. I don't want to preach about it but, what's interesting to me is the fact that these therapeutics are always good news. They're so rarely bad news, especially when all we're getting seems to be bad news -- about how this is, you know, moving up in places like Houston and Vegas and Florida. But you have -- I want to tell the listeners what an IND is. An IND -- it's really the first step toward discovering new therapies, isn't it?

PM: So, an investigational new drug application is what a person who wants to study a new drug has to put on file with the FDA, whether it's a drug or a biologic, and there's actually even an equivalent for certain types of devices. What it does is it makes sure that we know, and we can look at before we allow it to proceed. That that drug, or biologic, or in some cases device, is being made in a manner that -- we can't say it's absolutely not going to harm anyone because you don't know until you've tried it, but it's being made in a manner that's according to certain regulations so that we know that it's being manufactured in a safe manner that's not going to harm people and that it's a quality product. Then, that it's being studied in a manner that will give us data that will hopefully be generalizable knowledge. In other words, you can't just like say, "Oh I'm just going to give it to the first person who comes across the street." You have to have a plan that you're actually going to study in a systematic way to then be able to tell whether the thing is safe and whether it works. It generally proceeds through stages where you first understand is it safe? Then you understand what's the right dose. And then you understand is this really effective or even better than something that's already out there? That's what the IND process does.

MC: But what's after the IND? If you got an IND and you’ve gone through the process, what's next?

PM: What happens after you've gotten all your data, you've put it all together, you come into the agency and you talk to us about how you're going to submit it. And you file something that’s either a new drug application or a biologics license application if it's a biologic product, and that's where you collect all the data that you got from animal studies, all the data that you've gotten from other non-clinical studies, all the data you've gotten in the clinic, all the stuff you've done for manufacturing. Not just how you manufacture, but how you make sure it's a quality product; that what you do for quality measures on the manufacturing. You say what you're going to do after it's approved to make sure that it's safe in terms of your post-market plan. All that's put together into that biologics license application or the new drug application. It comes to the agency. It's usually thousands upon thousands of pages. We then have teams of reviewers: reviewers who have expertise in manufacturing, in quality, in clinical development, in the science of what's going on, and regulatory specialists. That those teams get together, they look over those applications. It usually takes a few months because they're so big. Our statisticians go through and they repeat the statistical analyses, they'll do additional statistical analyses, and at the end of the day, we look at all of the safety data and all of the efficacy data and say oh, this looks good. This might not look good. Sometimes then we'll take to an external advisory meeting, particularly if it's a first-in-class. Probably just like we'll probably take the first-in-class COVID-19 vaccine to an advisory committee so that there's a transparent public process. We do that for any -- generally we do that for many new products that are first-in-class. We don't do it for something that’s, you know, another member of a class of drugs or biologics that have been approved necessarily, unless there's some --

MC: None of them would be [unintelligible]

PM: Right, unless there's some reason to. But the idea is to have as transparent a process as we can. And at the end of the day, we put together reviews that are actually publicly available. You can go to our website and see after we review a product, there's something called the summary basis of regulatory action that you can go to and see how we reviewed a product.

MC: Now, what's interesting to me is how many therapeutics come out of an IND process and go onward? I mean, a lot of them fail, right?

PM: Right so --

MC: The process is there to choose winners.

PM: The process is there to choose -- right. It depends on where you are. Very early on, there's a very high chance for failure. Probably on average, you know, a tenth of what makes it into the beginning of the pipeline, only a tenth to a twentieth of what makes it into clinical trials ultimately makes it into an approved product. So there's a lot that falls out, and it falls out -- sometimes it falls out because it's just not effective enough, sometimes it falls out because of safety, sometimes there are other commercial reasons why it falls out. It's a pretty -- I mean that's -- it's not a very efficient process, but it's one that works.

MC: So, if one tenth or one twentieth might make it out, between one twentieth and one tenth might make it all the way through into the commercial marketplace, into the public health system, and I don't want to trap you in this because I know you're a scientist and you don't like saying these things -- how many COVID-19 therapeutics have an IND right now?

PM: I can't, you know I can't even --

MC: Is it over 100?

PM: There are literally -- there are hundreds.

MC: Hundreds of them.

PM: Right, yeah. I mean, I can't give you an exact number, but it's certainly when you take them all together, it's certainly over 100.

MC: It's over 100. Let's just say 100.

PM: Right.

MC: So, 10 percent of those are going to make it through? This is -- we don't know, but let's just say that there's 100 and a certain number of them -- what the American people have here is hope.

PM: Yeah, well I think the idea here that's important to get through is that enough people are working on this that one of the great things that we have going for us in the United States is our just sheer ingenuity.

MC: Right.

PM: If you would have told me -- so I was a young doctor and I was a medical student at the time when HIV was just coming on the scene. If you would have told me that people today would be able to take one pill a day and basically become essentially asymptomatic from HIV, become viral-load free, not be able to sexually transmit it -- if you told me that in 1990, I would have said you've got to be smoking something, right? But look at the ingenuity and the scientific development that went into that, that went into Hepatitis-C, other infectious diseases. Now, we're not that lucky with every infectious disease, but I think by putting our minds to it, you know, we usually can find solutions. The difference for COVID-19 is we're trying to find them as fast as we possibly can.

MC: Right. Without --

PM: Without sacrificing any issues with safety or effectiveness. That's exactly correct. We've got to check the boxes. Every time we say it's great actually that you're the one that's slowing me down as a regulator we're about that, because what we need to be doing here is making sure that we want to move as quickly as possible, but we can't forget -- we can never forget to check all the boxes that we need to for making medical products that are safe and effective and that meet our standards.

MC: And we will not skip any of the boxes during the Operation Warp Speed process, will we?

PM: Yeah, I can say -- I can't -- I'm not in Warp Speed now, but I can say when they come over the fence to us, we're going to check every box that we need to, to make sure that it meets our regulatory standards for whatever the purpose is. Now, the standard for an emergency use of a product is different for the standard for the approval of a product. But to be honest, for vaccines, for COVID-19 vaccines, they're going to be pretty similar because they're going to have to be products -- the vaccines are going to have to be studied in large populations of patients and they're going to have to clearly show efficacy so it's not like I think people should -- the anxiety level here that something is going to just kind of get given to people and repeat mistakes of the past where something's given too quickly, I don't think that's going to happen. I hope that we've learned enough from past issues that we know to do what's right here.

MC: You do. And I want the American people to know Dr. Peter Marks here is my guest. He's the head of the Center for Biologics, Evaluation, and Research at the FDA. He is the front line of regulation of every vaccine or therapeutic that comes out of Operation Warp Speed so that America can heal itself of the coronavirus. And I can tell you, apparently there are well over a thousand of Dr. Peter Marks's out there working on this stuff. And if anybody tells you that we're going to declare some October surprise or rush something to market just for any other reason than healing America, I'm here to tell you, I advise you, dear listener, to call them exactly what they are. They're liars. It's just a fact. We have too many people here at HHS and all the different regulatory divisions of this organization who are completely devoted in a solemn manner to never giving up the standards of their work. And even though we're all in a rush, we all want to heal, we want our grandmothers and grandfathers to be safe, our friends with diabetes and other comorbidities to be safe, it really is up to us. It's our personal responsibility to think of other people. But at the same time, if there is one thing the Center for Biologics is, in the midst of a pandemic, it's hope. It really is hope. And there is hope for all of us. You know, things are tough, and they're going to continue to be tough until we get to more therapeutics and vaccines. Those are coming, aren't they, Doctor?

PM: Yeah. The Center for Drugs is the other center that has the monoclonal antibodies and the small molecule antivirals. It's actually Dr. Patrizia Cavazzoni is currently the acting director of that, and they're working really hard on there. I think, you know, people are working -- our folks I can tell you, the amount of work that our folks are doing, I can't thank them enough because they're not getting overtime. They're working overtime, they're working nights, weekends, because they care so much about this and that's whether it’s the Center for Biologics, the Center for Drugs, or the Center for Devices. They're all working their hardest to make sure that the medical products the people need here get developed and get the appropriate regulatory review so that the ones that work get to people. They're really committed to that. They're committed to making sure they do their jobs right. That's what I think is what people should understand. We're here to do our jobs, which means we have to make sure that the products that we approve are safe and effective. The products that we authorize are doing -- if they're via an emergency use authorization, that they are doing what they are supposed to be doing.

MC: Dr. Peter Marks, head of the Center for Biologics at the FDA, thanks a lot for being a guest on Learning Curve today. Listen, if vaccines are the feel-good holiday film --

PM: [laughs]

MC: -- it is going to be good news, then the therapeutics that come out of the research that is going on being regulated by the FDA, this is the blockbuster summer film. The blockbuster summer movie. Pay attention, they're coming, these therapeutics, they're coming more and more, all through the summer. Pay attention.

Listen, this is Michael Caputo, I'm assistant secretary for Public Affairs at HHHS, that is the United States department of Hope, Health, and Human Services. Thanks a lot, we'll talk to you next week.

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