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  6. Transcript - Research Post 9/11 – FDA’s Work on Medical Countermeasures: Presentation by Luciana Borio, M.D.
  1. MCM Issues

Transcript - Research Post 9/11 – FDA’s Work on Medical Countermeasures: Presentation by Luciana Borio, M.D.

Science Writers Symposium
Day: September 11, 2012
Session: Luciana Borio

Luciana Borio:

And I look forward to your questions at the end of our presentation. I was invited to provide a bit of a background on a fairly young initiative at FDA. It's called the Medical Countermeasures initiative, what we call the MCMi.

And I think the invitation was partially prompted by today's date, September 11. For us, for my staff and for many whom we work with, the events of 911 are something that we think about every single day.

Today in homes, schools and businesses throughout the country, Americans mark the moment when 11 years ago the planes struck. The experience of 911, the Anthrax attack that soon followed, and the need to more aggressively support the development of medical countermeasures have given rise to a problem that I'll talk about today.

In 2010, FDA launched its MCMi to respond to a request by the President and by Secretary Sebelius, to significantly expand countermeasure activities at FDA.

FDA has always been involved in efforts to prepare for and to respond to emergencies. But during the past two years our efforts have dramatically increased.

Under MCMi, thanks to the commitment of the administration and thanks to strong bipartisan support in Congress, FDA's receiving additional resources to foster development and availability of drugs, vaccines, diagnostic devices, and other equipment to counter threats involving a chemical, biological, nuclear, or radioactive agent, what we call a CBRN agent. And to respond to emerging infectious diseases like pandemic influenza.

MCMi is an FDA-wide initiative involving the biologics, drug, and device product centers, (or CBER, CDER, and CDRH) − I'm sure you're familiar with them − and their offices as needed.

And we're working very closely with other federal agencies, especially within the Department of Health and Human Services and the Department of Defense, with academia, and of course with product developers.

And my office, the Office of Counterterrorism and Emerging Threats, or OCET, within the Office of the Chief Scientist, is leading and managing the initiative.

But before talking about where we are today, I thought it might be helpful to think about where we were about 11 years ago when the anthrax attacks occurred.

In 2001, I was working at the John's Hopkins Center for Civilian Bio-Defense Studies. And even though Bio-Security was the very focus of our work, we were all taken very much by surprise when it actually happened.

And there was a lot of uncertainty about so many things at the time. It was no easy time.

  • We didn't have a test that could quickly identify who had been exposed and who needed antibiotics.
  • We didn't know for sure how long prophylactic antibiotics were needed or who might develop disease after discontinuing antibiotic treatment.
  • We had a limited supply of vaccine.
  • And we could see that the state and local public health system and CDC were being very thoroughly tested.

During my work at Hopkins, I had the opportunity to interact with many science writers like you on a topic that, up to that point, had been quite theoretical. But it became frighteningly real as some news outlets became targets of the Anthrax attacks. And I received many calls from journalists who sought advice about their own personal safety. We were extremely lucky that more attacks did not come.

So how do things look today? We are certainly much better prepared. We have more safe and effective products for the strategic national stockpile. And we just approved Levaquin for treatment of plague, including in pediatric patients. Nevertheless, we still face many scientific challenges and uncertainties. From a drug development perspective we're dealing with the scientific issues that are very complicated.

Another sizable challenge is that many of the companies doing development work in this area are new to the business, and they need help with funding, with the science, and with navigating a regulatory framework that was not created with the complexities or urgencies of medical countermeasure development in mind.

Despite these challenges, we have no choice. We must continue to improve our ability to prepare and respond to public health emergencies no matter the origin.

And these threats appear unexpectedly from anywhere. Think of SARS, the Fukushima nuclear accident, the rise in incidence around the US of West Nile Virus, the CDC health advisory just last week on the hanta virus associated cabins in Yosemite National Park, and the recent reports from Ohio of the first death from H3N2 variant influenza.

And we must also protect our soldiers, especially those working in areas of the world that are frequent sites for emergent infectious diseases. Think about Chikungunia virus in Southeast Asia.

So I'm sure you can imagine that such a dynamic and ever evolving effort like preparing for pandemic influenza and other public health emergencies require an amazing commitment. And I can tell you with great confidence that FDA fully embraces that commitment.

This initiative serves as a good example. Currently, there are more than 70 medical countermeasure candidates in the development pipeline. And these represent billions of dollars in federal investment.

Most of these products are in the early clinical development stage and require FDA's rigorous and long-term engagement to foster their development. The FDA is critical to the success of these products.

But as I mentioned before, the world of countermeasure development is very different from that of a typical drug product. In many cases we will have very limited human data. Meaning that we must obtain data using other approaches, including development under the animal rule.

But drug development and regulatory review using the animal rule is difficult. This is mostly due to the complexities of identifying appropriate animal models and the significant difficulty in bridging animal data to humans. At times, there is not even a suitable animal model that mimics human disease.

And generally, products pursuing approval under the animal rule require much more frequent and early interactions between FDA and developer compared to products for traditional indications.

And because our product review processes are not completely amenable to the complexities of MCM development, we're focusing on identifying and addressing the choke points that can slow development, review, and approval.

We're devoting considerable time and resources to advancing science, what we call regulatory science: the knowledge and tools needed to more efficiently develop the countermeasures and to facilitate our, FDA's, evaluation of product safety, efficacy, quality, and performance.

And experience shows that regulatory uncertainties that stall development are largely driven by gaps in scientific knowledge. So, to remediate that, we have launched a rigorous science program to help build the necessary science base for countermeasure development and review.

This past June, we hosted a regulatory science symposium where we presented a number of scientific research projects underway at FDA that support development and approval of countermeasures. You can find out more about this symposium on our MCMi Website.

But I'd like to highlight a few of the projects just to give you a little flavor of how we fit into this equation.

As some of you may know, US Government efforts to develop next generation Anthrax vaccines have been hindered by the poor stability of the protective antigen in the vaccine.

To address this problem, FDA scientists are examining the scientific basis for this instability. And are using proton engineering to stabilize the antigen.

In yet another example, Prussian Blue is a countermeasure approved in 2003 to treat internal radiation contamination. But under certain pH conditions in the gut, Prussian Blue may release small amounts of cyanide. And this may raise safety concerns for very small children. They have a different gut pH than adults. FDA scientists are assessing the chemical properties that may affect the safety and efficacy profiles and the usability of this product in very small children.

Vancomycin is an important antibiotic that may prove crucial for treating certain types of bacterial pneumonia that may affect patients with severe influenza.

In 2010, reports questioning the quality and efficacy of generic Vancomycin products appeared in the scientific literature. FDA scientists conducted very sophisticated analysis, including developing new assays and methods. They confirmed that generic Vancomycin products available in North America meet stringent quality standards. This type of research would not have been possible without the additional resources we received under this initiative because it required some sophisticated equipment.

FDA scientists are working on new approaches for measuring the quality of next generation Small Pox vaccines. And FDA is developing new methods for evaluating the purity and (sterility) of novel cell substrates used to produce certain medical products.

We're also busy validating the more rapid methods to determine product sterility, which can take a couple of weeks, up to 14 days following manufacture − a rapid method to ensure product sterility is particularly important during public health emergencies when quick access to countermeasure will save lives. Each day counts. And to encourage manufacturers to adopt the methods that can bring the time down to more or less three to four days, FDA published a direct final rule earlier this year.

And you'll soon learn about the work being done at the Center for Biologics Evaluation and Research; Doctor Hana Golding is here. She'll talk about the development of new screening tools to assess the potential for adverse reactivity and to assess any potential added value of novel vaccine adjuvants and the quality of the new responses against vaccines.

Finally, protecting children is one of our highest priorities. In many cases we do not know the correct dosing for children for many of the countermeasures in development. Or even those already approved for use in adults.

And because children are not just small versions of adults, determining the appropriate dosing is crucial. However, it will not always be possible to study these products in children in advance of an emergency. So, FDA scientists are exploring sophisticated modeling tools to determine appropriate dosing for these countermeasures in children.

Work like this really paid off during the 2009 H1N1 flu pandemic, when FDA developed pediatric dose recommendations, not only for the approved antiviral medication, oseltamivir, but also for intravenous peramivir, an investigational antiviral medication that was used under an emergency authorization. This work allowed very small children who were critically ill access to these important medications.

To support all of these activities we're also evaluating existing statutes, regulations, and policies to identify ways to make sure countermeasures, even sometimes before they're fully approved, could be made readily available to local communities in emergencies if we believed the benefits outweighed the risks.

And essentially we are trying to think outside the box about new, innovative pathways for evaluating the products for use should they be needed. Because of statutory context we operate in is so important, we recently developed a set of legislative proposals that are now being considered as part of Congress's reauthorization of the Pandemic and All Hazards Preparedness Act. The proposals provide enhanced clarity and flexibility for activities related to pre-event planning and positioning of medical products. They provide for enhanced rapid deployment and clarify that certain actions taken by state and local public health officials to prepare for or respond to an emergency will not violate our laws and regulations.

Although we’ve made substantial progress, this FDA initiative requires extensive collaboration and commitment over the long-term. Planning is essential to its success. So we are constantly looking ahead to the next year and beyond. A very important goal for 2013 is reissuing the animal rule guidance to assist developers in successfully navigating product development under the animal rule.

And other exciting efforts are on the horizon. For example, FDA will soon be announcing a scientific collaboration with the Department of Defense and academia to develop lung, bone marrow, and gut biomimetic models to support the screening of medical countermeasures to treat acute radiation syndrome.

These models sometimes referred to as organs on a chip are models that mimic the complex interactions of living tissues within an organ.

This and similar technologies may enable us to test novel molecules on actual human tissue, without the human. This holds great promise in terms of developing and testing countermeasures and in reducing the use of animals.

So, before I take your questions, I want to pause for a moment to balance what may have sounded like some initial pessimism with some real optimism. I feel personally very privileged to work with such wonderful staff and to have the opportunity to lead FDA's MCM initiative. I feel like I'm in the right place at the right time.

Sometimes, it's not easy, and I do have some restless nights. But I believe that FDA can make a difference; FDA IS making a big difference.

Thank you for your attention this morning, and I look forward to your questions.

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