Print BCTV: Biodefense Bulwarks -- BARDA, FDA on what has been created with $5.6B spent on biodefense

Biodefense Bulwarks

Transcript of BioCentury This Week TV Episode 140




Dr. Robin Robinson, Director of the Biomedical Advanced Research and Development Authority (BARDA)


Dr. Luciana Borio, FDA Assistant Commissioner for Counterterrorism Policy and Director of FDA's Office of Counterterrorism and Emerging Threats



Health and Human Services

National Institutes of Health

Secretary of Health and Human Services

Department of Defense

Project BioShield

Centers for Disease Control

Homeland Security

Strategic Investor entity

Veteran's Administration


Strategic National Stockpile



Steve Usdin, Senior Editor




STEVE USDIN: The United States has spent billions of bio-defense since 9/11. Are we any safer? An update from two leaders of America's bio-defense enterprise. I'm Steve Usdin. Welcome to BioCentury This Week.


NARRATOR: Your trusted source for biotechnology information and analysis, BioCentury This Week.


STEVE USDIN: The world got a wakeup call about bio-terrorism in 2001 when anthrax killed five Americans. Natural and man-made medical threats, the possibility of pandemic influenza, exposure to radiation, bio-terrorist attacks, and the specter of chemical war are back in the news. And questions are being asked again.


Are we safe? Is the investment in medical countermeasures being managed properly? The United States government has poured billions into bio-defense over the last decade. But counter measures against chemical, biological, and radioactive threats are only available for a few of the lethal agents that would likely be used in an attack. Vaccines and drugs for anthrax and smallpox have been stockpiled along with drugs to treat botulism and radiation exposure.


The effort to develop and procure medical countermeasures is led by BARDA, the Biomedical Advanced Research and Development Authority. Recently, Congress reauthorized the law that created BARDA. The Pandemic All-Hazards Preparedness Act has $2.8 billion should be set aside for a five-year special reserve fund to buy countermeasures.


The Obama administration doesn't agree. It's asked Congress to fund BARDA on a year-by-year basis, starting with $250 million for fiscal 2014. Without longer-term commitments, companies worry they won't be rewarded for massive investments needed to create countermeasures. Meanwhile, critics are questioning the government's decisions to purchase and stockpile large quantities of expensive vaccines and drugs.


Today, we ask the nation's top defense leaders to answer the critics, BARDA director Robin Robinson and the Luciana Borio, FDA's assistant commissioner for counter-terrorism policy. I'm pleased to be joined today by Robin Robinson, director of BARDA. Dr. Robinson, I want to start, taxpayers have spent about $5.6 billion over the last nine years to develop and procure biodefense agents. What have they gotten for that money?


ROBIN ROBINSON: Well, thank you, Steven. Thank you for the opportunity to be here on BioCentury. I want to first say that by the end of 2013 fiscal year, in September, that the taxpayers will have new products instituting the national stockpile, 11 in fact that were not there in 2004. These are for smallpox, anthrax, botulinum, clean radiation and nuclear treatments, and chemical antidotes that are new.


STEVE USDIN: So how does what we've got in the stockpile now and what you've got in late-stage development match up against the threat?


ROBIN ROBINSON: Good question. The Department of Homeland Security is responsible for providing material threat determinations for 13 different threats that we have. With the exceptional of only one, BARDA has product in development or delivered products for 12 of those. The NIH and Department of Defense have candidates that are for viral hemorrhagic fever, Marburg, Ebola, that are in development that may be promising to come to us in one to two years.


STEVE USDIN: So the progress that you've made so far has been based on a model where you had a big pile of money, two different piles. At two different times we had $2.8 billion. And manufacturers were able to see that that money was going to be there. If they developed the drugs according to BARDA's specifications and needs, there would be money for them there now.


What biodefense companies are telling me now that they're very concerned about is that you're switching to an annual appropriation and it's a smaller one. And they're concerned that the money might not be there when they develop products. What would be your response to them?


ROBIN ROBINSON: Well, first, Congress with the Pandemic and All Hazards Preparedness Act when it was reauthorized this year showed an affirmation in what BARDA's done, both in advance development and in Project Bioshield, and authorized $2.8 billion to be spent in this special reserve fund for these biodefense medical countermeasures.


STEVE USDIN: But they haven't-- but the president's not asking for that money, right?


ROBIN ROBINSON: The president is asking in the FY14 budget $250 million. We submitted a five-year budget to the administration for the $2.8 billion from FY14 to FY18 that would accommodate the purchase of a dozen new medical countermeasures going forward. In budget austere times and the fact that the money would come out of the department, it was seen that $2.8 billion in one year is just not possible.


STEVE USDIN: So you mentioned budget austere times. If you're sitting in the board room of a company and you've got to make a decision, are you going to develop a drug for cancer, are you going to develop a drug for a rare disease, are you going to develop a biodefense drug and you're not really confident that the government might have the money, is that going to be a deterrent to your being able to get the drugs that we need and the vaccines?


ROBIN ROBINSON: Well, first the administration has been committed to biodefense. And this was presented in the State of the Union in 2010. And it still is committed to that. And every time we've asked the President for funds, they've said yes. And going forward, they told us that they were very much aware of what's needed and that when we come back with annual appropriation requests, that we would receive that.


STEVE USDIN: So one of the things that you didn't receive is BARDA and the administration asked Congress to include in the re-authorization something called a Strategic Investor to create a kind of venture fund for biodefense. You still asked for money for it for this year. Can you describe first very briefly what is Strategic Investor?


ROBIN ROBINSON: First, we think that hopefully the Congress will reconsider authorization for the strategic investor this year and subsequent years so that we can utilize the $20 million that we did ask for in the FY14 budget. The strategic investor is a not-for-profit organization that would be administered, managed, and guided by BARDA to develop new medical countermeasures that either would re-purpose or find multi-purpose usage of products that have a commercial usage as well as a biothreat.


STEVE USDIN: So very quickly, you mentioned $20 million. Is that really enough to move the needle when we're talking about developing drugs for biodefense needs?


ROBIN ROBINSON: Yeah. That's the seed money. That starts it. That would get you the incubator. And we and others have actually estimated about $200 million is what would be needed and certainly in our five-year budget have indicated that would be the amount of money needed for that particular initiative.


STEVE USDIN: Well, thank you. We're going to be right back with Dr. Robin Robinson, director of BARDA.


NARRATOR: You're watching BioCentury This Week.




STEVE USDIN: I'm joined again by Dr. Robin Robinson, director of BARDA. Dr. Robinson, one of the big frustrations of people watching the bio-defense enterprise in the United States, has been the failure to develop a second-generation anthrax vaccine. What's happening?


DR. ROBIN ROBINSON: So first of all, I can tell you that we do have a licensed anthrax vaccine that can be used. Instead of the five doses it took several years ago, we're down to three doses. Our goal is to actually have it in one. We're moving forward with that, what we call enhanced anthrax vaccine by the older method.


But we do have a next generation anthrax vaccine program that has four candidates in it right now. Two of them are legacy products that we have supported for a number of years, and two of them are actually came out of our innovation program with new platform technologies.


STEVE USDIN: And what will be the criteria for getting a second-generation anthrax vaccine? I mean, there isn't any point in just creating one that's the same as the one that's now, or even slightly better. What are you looking to get?


DR. ROBIN ROBINSON: Yeah, so in 2012 we took a long look at this and came up with a new strategy for that very reason. We don't want another me too vaccine that's similar to our licensed vaccine. We want vaccines that have fewer doses, has a longer shelf life, is easy to administer, that actually is cheaper than the vaccine that we have now, and has greater manufacturing capabilities. Those were large things to do, but we think that we have some candidates that can do that.


STEVE USDIN: And you mentioned cheaper, and you mentioned shelf life, that's another thing that's been a criticism, or maybe it's just a concern about BARDA and about the bio-defense effort. You're procuring drugs, you're paying for the development of drugs that might cost hundreds, or even thousands of dollars a dose. And in some cases, they have relatively short shelf lives. It's immense amounts of money. Is that sustainable?


DR. ROBIN ROBINSON: You're exactly right. Those are not sustainable in that paradigm. So we have put huge amounts of efforts in our advanced development to actually having products with longer shelf life; example, lypholized products that not only have a longer shelf life but are easier to administer. Secondly, can we have commercial-scale production that actually lowers the price of the overall product?


And lastly, this is a realization that these products, when compared to their commercial counter parts -- a monoclonal antibody for, say, rheumatoid arthritis verses one that may be used for anthrax, they're very comparable in fact. It's just that when you buy millions of doses of these it's a large bill.


STEVE USDIN: Yeah. The difference is nobody who is worried about rheumatoid arthritis is going to stockpile a million doses and then have them go bad and have to stockpile new ones again. One of the other criticisms, or concerns that people have raised, is the size of the stockpile. For example, for smallpox, the United States is one of only three countries in the whole world that thinks it has to have enough smallpox vaccine stockpiled for the entire population. How do you make those decisions, and at some point will you say, we just can't afford that?


DR. ROBIN ROBINSON: That's a good point. The threat assessments come from the Department of Homeland Security who say, if an event occurs under these scenarios, these would be the number of casualties that would occur. Then at HHS, we're responsible for actually looking at how can we intervene with medical countermeasures to mitigate those events and come up with a plan that actually has enough of this medical countermeasure.


One of the problems that we face with the amount of money that we've had is that we may not be able to meet all the demands for that particular medical countermeasure for that particular threat. And how can we spread that over all the different threats that we have with viable medical countermeasures. That's a balancing act that we, across the entire department, and the enterprise, which includes Department of Defense, Homeland Security, VA and USDA tried to actually come up and prioritize expenditures of the Strategic National Stockpile fund, and also Project BioShield.


STEVE USDIN: How do you balance and make decisions about whether you're going to develop a therapeutic against a biological threat or a vaccine? And one example is tularemia, which is considered to be one of the more serious threats that the United States faces. My understanding is that you're developing a therapeutic but not a vaccine.


DR. ROBIN ROBINSON: That's correct. What you see is a big difference between Department of Defense with the smaller numbers with their workforce that is in the theater of action versus the entire United States being our theater of action for a threat. And one of the things is being able to treat individuals or be able to protect them in a prevention mode ahead of time.


What we've seen in the past when we try to use smallpox vaccines for the general population, or anthrax vaccines, is that it didn't go so well if you remember from early 2000. What we do know, though, is that treatments, such as antibiotics for tularemia, there are antibiotics available, but they're also ones that we have in development that may be better, and then we can actually get the antibiotics out to the individuals very rapidly.


STEVE USDIN: So going to the smallpox example, you didn't have very much success because people didn't see a real threat. The thing that I'm worried about with, for example, tularemia is if you were actually have an attack with tularemia sure, you have to go in and treat people with antibiotics very quickly, but then there's going to be an enormous demand for vaccines to be able to protect people against the second wave. Is that a concern? Is it realistic that you're going to be only able handle everything simply with treatment?


DR. ROBIN ROBINSON: So with the antibiotics that we have available they would be able to treat the scenarios that have been proposed to us, including the second wave. So the modeling has been done for that would be able to address that. Certainly there are others that actually think that the only way you can handle that is vaccines. And one of the things that we do routinely is we actually go through these threat analyses and see if there are better ways to actually address these.


STEVE USDIN: And when you're talking about the threats also there's -- I know that there's this list that you're working off from DHS -- is that sort of like looking under the lamppost for your keys? I mean, isn't there a concern that you're going to have evolving threats that haven't been identified now?


DR. ROBIN ROBINSON: So the Department of Homeland Security actually goes through their list periodically, not only to add things, but actually to take things off. And actually that did happen a couple years ago when the Hunan viruses were removed from the list because it was no longer thought to be a threat.


STEVE USDIN: Great. Thank you very much, Dr. Robinson. We will be joined in just a moment by Dr. Luciana Borio, Head of Countermeasures at FDA.




NARRATOR: Now back to BioCentury This Week.


STEVE USDIN: Although BARDA gets far more attention, FDA is actually a key national security agency. By law, BARDA can only procure countermeasures that FDA is likely to approve within eight years. To approve a countermeasure for a bioterror attack or pandemic, FDA must determine that it's safe and effective. Most biodefense products can't be studied in humans, so FDA allows manufacturers to test them in animals.


Mice aren't furry little humans, however. It's difficult, sometimes impossible to produce results in animals that can be directly extrapolated to humans. The Pandemic All Hazards Preparedness Reauthorization Act instructs FDA to work intensively with companies to develop new animal models and other ways to overcome these regulatory challenges. The law also changes the way FDA authorizes the use of unapproved drugs, vaccines, and diagnostic tests to cope with emergencies.


Under the old law, FDA had to wait until an emergency was declared. This made it difficult to deploy countermeasures ahead of the H1N1 flu pandemic in 2009. The new law allows the Secretary of Health and Human Services to declare a potential emergency. The FDA has already used its new power to grant emergency use authorization for diagnostics to test for the H7N9 avian influenza strain that's circulating in China.


In 2010, Congress gave FDA a one-time appropriation of $170 million for countermeasures. Now the agency's Countermeasures Oversight Program receives over $20 million a year. The FDA's program is headed by Luciana Borio, Assistant Commissioner for Counterterrorism Policy.


FDA isn't usually thought of as a key player in national security, but when it comes to biodefense, FDA is on the front lines. To discuss FDA's evolving role, I'm pleased to be joined by Dr. Luciana Borio, Assistant Commissioner for Counterterrorism Policy at FDA. Dr. Borio, the PAHPA Bill reauthorization gave FDA new powers to declare emergency use authorization in advance, before an emergency. That sounds like kind of an obscure thing. But you've actually had an opportunity to do it already, haven't you?


DR. LUCIANA BORIO: That's right, Steve. So after cases of H7N9, avian influenza, were detected in China, CDC began to work to develop a diagnostic test to detect H7N9 in patients, in the event cases were to occur in the US. So the Secretary of Health and Human Services was able to declare, make a declaration for the potential for an emergency, which is new in PAHPRA.


So based on this declaration, that there is a potential for an emergency, FDA was able to review CDC's diagnostic test submission, and issue an emergency use authorization. So the diagnostic tests can be forward deployed to state health laboratories and be used for surveilling the detection of cases, were they to occur in the US.


STEVE USDIN: And that's something that wouldn't have been able to happen under the old authorization, because you had to have an emergency already in place. I wanted to ask you about some other things in the new bill, and generally about FDA's activities and countermeasures development.


One is the role that FDA plays in trying to help validate and to develop drugs based on animal models. When FDA first announced that it was going to approve countermeasures based on animal models, there was a lot of enthusiasm. People thought that we're going to see a flood of applications and approvals. It's turned out to be a lot harder than that, hasn't it?


DR. LUCIANA BORIO: It certainly has. And the Animal Rule is a tool that we have. It's a regulatory tool. And in this instance, I believe the regulatory tool was ahead of the science. All of FDA's assessments of products are based on a risk-benefit analysis, and that's scientifically informed. And at the time the rule was developed, there were very few, if any, animal models developed that was suitable for product evaluation.


And since then, there have been many, many efforts and steps taken to close that gap. We've worked closely with NIH, and also BARDA to help them develop the animal models that are required for product evaluation. And recently, we launched a program called Animal Model Qualification Program, where developers or our government partners can submit to the FDA a file to be reviewed on the suitability of the animal model to be used as product development tools. And it's a very early program, but we are excited about it.


STEVE USDIN: So how far along are we? Because Doctor Robinson talked about having products either in advanced development or procurement for most of the threats that are on the Department of Homeland Security list. But those aren't going to be able to actually get FDA approval unless there are animal models that are accepted. Do you have animal models for things like Marburg, and Ebola and Tularemia that would be acceptable, right now, for approval of those products?


DR. LUCIANA BORIO: Well I can't say that we have, because that would be misleading. But traditionally, developers would have to develop their own models. And they would have to submit, for review, their product, the product they're interested in developing, and the animal model, as well. So it's very, very labor intensive, resource intensive, for the developer to have to work on validating, basically, two different things, the product and the model.


STEVE USDIN: And the testing, yeah.


DR. LUCIANA BORIO: So we're hoping that by separating this somewhat, by have an Animal Model Qualification Program, we can develop these models that any sponsor can take advantage of. So there are different models in different stages of development. A lot of them were developed with a particular product in mind, so they might be more advanced than others. But we would like to see them being submitted to the FDA for a product qualification.


STEVE USDIN: And is that going to be a public process? Will we know when these animal models get qualified?


DR. LUCIANA BORIO: We were hoping to, to the extent feasible, to be able to share this information. I know BARDA is also willing to do that. And they have established an Animal Model Core Program to be able to use publicly funded resources to develop those animal models to the point of qualification.


STEVE USDIN: Thank you, Dr.Borio. We'll be back in just a moment to talk more about FDA's work on medical countermeasures.






STEVE USDIN: Now we're going to get some final thoughts from Dr. Luciana Borio. So Dr. Borio, this idea of the animal model, it's more complicated than just coming up with a good model for the disease, isn't it? Because, it has to be a model where the drug is actually going to work in it.


DR. LUCIANA BORIO: That's correct. So even though we had some recent successes, recently we had a botulinum antitoxin approved under the Animal Rule. We had an anthrax antitoxin approved under the Animal Rule. There are products that they are so specific to be used in humans, that even if you have the perfect disease model qualified, you won't be able to study the product in that perfectly qualified animal model.


STEVE USDIN: So then, what are you going to do?


DR. LUCIANA BORIO: And I think that that's when we have to be really creative, and flexible, as well. We have an initiative where we are working to support development of what we call bio-pneumatic models, or organs on a chip. We try to get clinical data where we can. And for some of these products it's possible. Some products are for Acute Radiation Syndrome, and they have, sometimes, utility in cancer patients. So we have to, basically, filter the puzzle with different sources of data.


STEVE USDIN: And that also suggests, ultimately, that you have to accept some level of uncertainty, doesn't it? That when an emergency happens and these products need to be used, they might not work.


DR. LUCIANA BORIO: That's right. And that happens even with the products that are the gold standard based on Phase III clinical trials. We see products every day that go into the market and, for some reason or another, they have to be recalled. And there's always uncertainty in product development. But we have to be prepared to take risks. And our job is to close the gaps to the extent they're feasible. But, at the end of the day, we have to establish a pathway that is viable for developers to develop their products.


STEVE USDIN: So do you have, also, any concern about the kind of closeness? You've got FDA working closely with BARDA, with NIH, with product developers, much closer than you do with typical products. Typically, there's much more of an arm's length relationship. Do you have any concerns about conflict of interest, or kind of a lack of objectivity, because you're working so closely in the development process?


DR. LUCIANA BORIO: This is something that I think people struggled early on. And I think, first of all, it has to be a collaborative process. The FDA has to be working very closely with its partners. The reviewers must be fully informed about the context of this review. It's very different from the usual normal product.


But I think it's OK, because, at the end of the day, we have the role and a responsibility to play. And as long as we remember that, and this a very distinct role we play, the regulator role. So we can do both. We can be in partnership and, as long as, remember that we have a very clear role and responsibility in this arena, and regulate appropriately.


STEVE USDIN: And one of the other issues, of course, with normal drugs, is that there's a post market experience. You're going to learn about these drugs after they're used. Is there anything that's in place to be able to learn about countermeasures after they might have to be used?


DR. LUCIANA BORIO: Absolutely. As a matter of fact, under the Animal Rule, if a product they approved under the Animal Rule, there's a requirement that a field study needs to be done, if there is an emergency, to assess its clinical benefit. Now that is extraordinarily challenging. For a lot of these products, the manufacturer won't have full control of how these products are used, because the government is going to dictate, to some extent, how they're used and who they go to. So there are many, many plans in government, right now. We're discussing how to do that in a way that it's viable and efficient.


STEVE USDIN: Well, thank you, very much. That's this week's show. I'd like to thank Luciana Borio and Robin Robinson. Thank you for watching. Remember, you can share your thoughts about today's show on Twitter. Just use the hashtag #BioCenturyTV. I'm Steve Usdin, and I'll see you next week.