> DEPARTMENT OF HEALTH AND HUMAN SERVICES
>
> FOOD AND DRUG ADMINISTRATION
>
> FDA SCIENCE BOARD ADVISORY
>
> COMMITTEE MEETING
>
> Thursday, November 6, 2003
>
> 8:00 a.m.
>
> Room 1066
>
> 5630 Fishers Lane
>
> Rockville, Maryland
>
> PARTICIPANTS
>
> Michael P. Doyle, Ph.D., Chair
>
> Jan Johannessen, Ph.D. Executive Secretary
>
> MEMBERS
>
> Robert M. Nerem, Ph.D.
>
> Martin Rosenberg, Ph.D.
>
> Jose C. Principe, Ph.D.
>
> Cecil B. Pickett, Ph.D.
>
> Jim E. Riviere, D.V.M., Ph.D.
>
> Cato T. Laurencin, M.D., Ph.D.
>
> Katherine M.J. Swanson, Ph.D.
>
> John A. Thomas, Ph.D.
>
> FDA
>
> Mark B. McClellan, M.D., Ph.D.
>
> Norris E. Alderson, Ph.D.
>
> Margaret Glavin
>
> Joseph A. Levitt, Esq.
>
> Robert L. Buchanan, Ph.D.
>
> Daniel Casciano, Ph.D.
>
> Kathryn Carbone, M.D.
>
> Linda D. Youngman, M.S., Ph.D.
>
> Subhas G. Malghan, Ph.D.
>
> Anne M. Kirchner, J.D.
>
> C O N T E N T S
>
> Call to Order:
>
> Michael P. Doyle, Ph.D. 4
>
> Conflict of Interest Statement:
>
> Jan Johannessen, Ph.D. 7
>
> Welcome and Opening Remarks:
>
> Mark B. McClellan, M.D., Ph.D. 8
>
> Overview of the FDA Food Security Program:
>
> Joseph A. Levitt, Esq. 27
>
> Threat/Vulnerability Assessments:
>
> Robert Brackett, Ph.D. 67
>
> Food Security Research Needs, Priorities,
>
> Resources and Challenges:
>
> Robert L. Buchanan, Ph.D. 89
>
> Prevention Research:
>
> David J. Armstrong, Ph.D. 126
>
> Food Security Research at the National Center
>
> for Toxicological Research:
>
> Daniel A. Casciano, Ph.D. 147
>
> Open Public Comment 196
>
> Animal Feed Safety System (AFSS), BSE and
>
> Food Security Research at the Center for
>
> Veterinary Medicine: Linda Youngman, M.S., Ph.D. 196
>
> Food Emergency Response Network:
>
> Carl Sciacchitano 232
>
> Facilitating Biologics Product Development
>
> to Address Threats to Food Security:
>
> Kathryn Carbone, M.D. 253
>
> Medical Countermeasures:
>
> Dianne Murphy, M.D. 273
>
> Questions and Discussion with the Board/
>
> Presenters 300
>
> Closing Remarks\--Recommendations 306
>
> P R O C E E D I N G S
>
> **Call to Order**
>
> DR. DOYLE: Good morning and welcome to our Fall meeting of the Science
> Board. It looks to be a full but exciting agenda. We are going to hear
> about food security and what the agency is doing in addressing
> food-security issues.
>
> But, before we get into that, I think we should first introduce
> ourselves and who is at the table. I am Mike Doyle. I am Chair of the
> Science Board and I am a food microbiologist at the University of
> Georgia.
>
> Dr. Laurencin?
>
> DR. LAURENCIN: I am Dr. Cato Laurencin from the University of
> Virginia, orthopedic surgery, chemical engineering and biomedical
> engineering.
>
> DR. THOMAS: John Thomas, Vice President, Retired, Professor Emeritus,
> University of Texas, San Antonio, pharmacology, toxicology.
>
> DR. SWANSON: I am Katie Swanson with General Mills. I am a food
> microbiologist.
>
> DR. PRINCIPE: I am Jose Principe. I am Professor of Electrical and
> Biomedical Engineering at the University of Florida.
>
> DR. PICKETT: I am Cecil Pickett. I am President of Research and
> Development for the Schering-Plough Corporation, also a biochemist.
>
> DR. RIVIERE: Jim Riviere. I am a Professor of Pharmacology and
> Toxicology at North Carolina State.
>
> DR. NEREM: I am Bob Nerem from Georgia Tech. I am a bioengineer.
>
> DR. ROSENBERG: I am Marty Rosenberg. I am also retired from
> GlaxoSmithKline, infectious-disease bacteriologist and teach at the
> University of Wisconsin.
>
> DR. JOHANNESSEN: Jan Johannessen. I am the Executive Secretary of the
> FDA Science Board.
>
> DR. ALDERSON: I am Norris Alderson, Associate Commissioner for Science
> at FDA.
>
> MS. GLAVIN: I am Margaret Glavin. I am the new Assistant Commissioner
> for Counterterrorism Policy at FDA.
>
> DR. BUCHANAN: Good morning. Bob Buchanan, CFSAN, Senior Science
> Advisor.
>
> DR. CASCIANO: Dan Casciano, Director for National Center for
> Toxicological Research.
>
> DR. CARBONE: Kathy Carbone, Associate Director for Research, Acting,
> at CBER.
>
> DR. YOUNGMAN: Linda Youngman. I am the Director of the Office of
> Research in the Center for Veterinary Medicine.
>
> DR. MALGHAN: I am Subhas Mulghan, representing Dr. Feigal who is on
> travel. I am from the Center for Devices and Radiological Health.
>
> MS. KIRCHNER: I am Anne Kirchner. I am Regulatory Counsel in the
> Office of the Associate Commissioner for Regulatory Affairs.
>
> DR. DOYLE: Thank you, one and all, for being here today. Just a few
> housekeeping things before we get into the meat of the matter. In
> order to talk, push the button. When you are done talking, push it
> off. There is too much clutter in the background.
>
> Next, Jan has some waiver information he would like to share with us.
>
> **Conflict of Interest Statement**
>
> DR. JOHANNESSEN: Good morning. The following announcement addresses
> the issue of conflict of interest with respect to this meeting and is
> made part of the public record to preclude even the appearance of such
> at the meeting. The Food and Drug Administration has prepared
> general-matter waivers for Drs. Doyle, Nerem, Rosenberg, Riviere,
> Laurencin, Swanson, Principe, Pickett and Thomas. A copy of the waiver
> statements may be obtained by submitting a written request to our
> Freedom of Information Office. The waivers permit them to participate
> in the meeting\'s discussion of the FDA\'s Food Security Program and
> food security research efforts.
>
> The topics of today\'s meeting are of broad applicability and, unlike
> issues before a committee in which a particular product is discussed,
> issues of broader applicability involve many industrial sponsors and
> academic institutions.
>
> The participating committee members have been screened for their
> financial interests as they may apply to these general topics at hand.
> Because general topics impact so many institutions, it is not prudent
> to recite all the potential conflicts of interest as they apply to
> each participant. The FDA acknowledges that there may be potential
> conflicts of interest but, because of the general nature of the
> discussion before the committee, these potential conflicts are
> mitigated.
>
> We have open public comment scheduled for 1 o\'clock. I would just
> remind everyone to turn your microphones on when you speak so that the
> transcriber can pick everything up.
>
> DR. DOYLE: Very good.
>
> Next, we are going to hear from the Commissioner of FDA, Dr. Mark
> McClellan.
>
> The podium is yours.
>
> **Welcome and Opening Remarks**
>
> DR. McCLELLAN: Good morning. I would like to thank Dr. Doyle not only
> for introducing me just a second ago but for his service to this
> advisory committee. Over the past four years, Mike, you have done an
> outstanding job counseling FDA on complex scientific issues, on
> emerging trends, on helping how we can best shape our responses to the
> new and challenging public-health threats facing this country, and new
> opportunities for improving public health. So we very much appreciate
> your service, most recently as Chairman of this committee.
>
> I would also like to thank the other departing members of the Science
> Board. We have a set of plaques to present you with. We begin with Dr.
> Doyle, if you don\'t mind coming up here. We don\'t give out a whole
> lot of good FDA souvenirs but this is one of them.
>
> This, like the other plaques that we will be giving out, is a memento
> for the work that these advisory board members have done. Dr. Doyle,
> research recognizes you for your distinguished service as Chairman of
> the Science Board for the Office of the Commissioner at FDA.
>
> Mike, thank you very much for your service.
>
> DR. DOYLE: Thank you very much. I appreciate it.
>
> DR. McCLELLAN: If Bob Nerem could come up, please. Bob has been
> serving with us for some time as well and has long been an advisor to
> FDA and our scientists. Bob, thank you very much for your service. It
> has been a pleasure working with you.
>
> DR. NEREM: My pleasure.
>
> DR. McCLELLAN: Dr. Martin Rosenberg, as well, has given years of
> service to this committee and years more and work on scientific issues
> related to FDA\'s major concerns. Martin, we really appreciate your
> service as well. Thank you so much.
>
> DR. NEREM: I was just getting started.
>
> DR. McCLELLAN: Dr. Harold Davis is also rotating off the committee. He
> has been a valuable contributor to FDA\'s efforts as well.
>
> This is also a good time to recognize Dr. Doyle and Jim Riviere for
> their introductions into the Institute of Medicine. Just a couple of
> weeks ago, it was announced that not only they were elected but my
> Deputy Commissioner, Dr. Lester Crawford. And I also made it in
> somehow. So this was very, very good year for FDA at the Institute of
> Medicine. I think that is just a sign of how important the work that
> we are doing here and the work that our scientific advisors are doing
> to improve the public health of the nation. Four people closely
> connected with the agency has got to be some kind of record for a
> federal agency in one year and I think it is a real testament to the
> work that you all and Les are doing to help improve the health of this
> country.
>
> At this point, I would also like to introduce a new staff member at
> the FDA who is working very closely with me. She is not a new face
> when it comes to food safety in this country, but her contributions
> now on our overall counter-terrorism strategy at the FDA are bringing
> her career to a new level of achievement in helping to improve the
> public health.
>
> Maggie Glavin is our newly appointed Assistant Commissioner for
> Counter-Terrorism. She is, as many of you know, a nationally
> recognized food-safety expert. She was with USDA for more than thirty
> years, I think, altogether\--you certainly don\'t look it\--where she
> held a number of key positions there, Acting Administrator of the Food
> Safety and Inspection Service included among them. That is a
> 10,000-person regulatory agency responsible for public health when it
> comes to the safety of the U.S. meat and poultry supply. So we are
> delighted to have Maggie here.
>
> I remember when I was talking with her earlier this year, she had just
> moved out of government service, thought she would have a little bit
> of relaxing time in a think-tank for a couple of years. But we managed
> to drag her back in. I am very glad we did. This is a critical time
> for food security and for developing better medical treatments for the
> agents of terrorism and we really need the leadership from someone
> like Maggie right now.
>
> As I said, it is very good to have her aboard. In the aftermath of
> September 11th, as we are more aware than ever of the serious
> challenges to our public safety and national security today, not just
> from what can go wrong in terms of illnesses and other threats to
> public health but what people might deliberately do to harm Americans.
> This is something that we need to think hard about every day.
>
> Maggie, with her experience in safety issues is an ideal person for
> thinking about how we can continue our traditional mission of
> protecting food safety while expanding it to encompass major food
> security concerns as well. It is that kind of comprehensive scientific
> thinking that I hope will continue to be a hallmark of FDA\'s efforts
> to address new challenges like the challenge of counter-terrorism.
>
> This is important because these terrorist challenges not only harm
> public health and safety, they can also have serious adverse
> consequences for the American economy and the global economy. Someone
> with Maggie\'s experience can help us think about all that very
> effectively.
>
> As I said, our mission today, when it comes to food safety, is also
> about food security. In response to the threats of terrorism, we are
> implementing new steps in food security that amount to the most
> fundamental enhancements of our food safety activities in more than
> thirty years. You all spent some time hearing about the steps that we
> are taking, particularly in our research programs yesterday.
>
> There are some truly new and important areas of research development
> where we have not focused in the past and no one else has either but
> that are very important for addressing when it comes to finding ways
> to make our foods not only safer but more secure.
>
> We are also taking steps, not only in developing better science and
> better knowledge to protect the food supply but also in implementing
> new programs to protect our food safety and security.
>
> We announced two regulations, final regulations, just a month ago that
> are critical as part of this effort. They reflect our efforts to come
> up with 21st Century solutions to 21st Century security problems. In
> the first regulation, we are going to be taking new steps to implement
> prior notice for foods coming into this country so that we will know
> ahead of time about all the shipments coming in. This is a reflection
> of legislation passed by Congress last year that gave us new
> authorities to obtain and analyze this information as well as new
> resources to help protect the security of our food supply.
>
> In implementing this regulation, we had to balance and consider two
> different kinds of concerns. One is the need for having a
> comprehensive system for being aware of the foods coming into this
> country ahead of time so that we can target our limited resources more
> effectively to identify and prevent safety threats from potentially
> risky foods coming into the country.
>
> The other is to make sure that we do not have any unnecessary adverse
> impacts on the large and growing food trade coming into the United
> States. More than 20 percent of all imports into this country are
> foods of one kind or another that would be affected by this regulation
> and the growing diversity and richness of our food supply is creating
> many opportunities for Americans to live better lives, get more
> diverse products at lower costs and higher quality. So trade is
> extremely important to us.
>
> So, in implementing the regulation, we took new steps. We formed new
> partnerships with the U.S. Bureau of Customs and Border Protection to
> make sure that we are integrating our resources efficiently at the
> border. We took new steps to adopt modern information systems for
> managing the information on products coming in to this country.
>
> As a result of these steps, we are going to be able to implement these
> regulations with only a minimum amount of disruption in products
> coming into this country. For example, we only need notice of foods
> being trucked in, which is a large part of the food supply coming into
> this country, only two hours ahead of time and we can completely do
> our job of screening these shipments for their potential threat,
> taking a closer look by our experts at FDA because they are going to
> be integrated into this national information system along with the
> Bureau of Customs and Border Protection, and then taking action, if
> appropriate.
>
> The second regulation involves giving us the ability to know who all
> is involved in the food distribution system in the United States. For
> the first time ever, we are requiring registration of everyone
> involved from between production on the farms and when foods get to
> their final users or restaurants or grocery stores and the like,
> everybody between those two points, so if there is a foodborne
> outbreak, we will know who to notify and how to get hold of them
> quickly if it affects a product that they have been involved with. So
> this gives us a much better ability to contain a foodborne outbreak if
> it occurs and also to contact people in the private sector who are
> involved with the production and distribution of food that may need to
> know about potential threats or safety concerns.
>
> This registration rule is also being implemented using 21st Century
> technologies. It just takes a matter of minutes to register with us
> over the Internet. That can be done 24-7 from anywhere in the world.
>
> We are conducting the implementation of these regulations with a major
> outreach effort as well, internationally, so that everyone knows what
> is expected of them. We are going phase-in the full enforcement of
> these regulations over time to make sure that everyone has a chance in
> a reasonable time period to come into full compliance.
>
> Altogether, these regulations will enable us to provide much better
> protection for the security of America\'s food supply but they will
> also help us respond much more effectively and prevent much more
> effectively naturally occurring foodborne-illness outbreaks as well.
>
> So these are a true milestone for our food-security efforts and, along
> with the food-security research programs that you heard about
> yesterday, we were working hard to get a comprehensive food-security
> plan in place, a plan that addresses everything from vulnerability and
> threat assessments to detection and outbreak prevention to emergency
> preparedness and response. You are going to hear much more about that
> strategy this morning.
>
> It reflects a science-based life-cycle approach that we are trying to
> take at FDA to assure the safety of food products. This is all based
> on a core FDA principle of efficient risk management. The idea is to
> use our limited resources to provide the greatest protection for the
> public health with the least additional cost for Americans and for our
> trading partners.
>
> So, with a strong plan and strong leadership and strong support from
> our partners and industry and governments and our partners from around
> the world, we are well on our way to giving Americans much better
> protection against the treats of terrorism through their food supply.
>
> I would also like to thank the Science Board for your support in
> helping the FDA to carry out these important activities. As you know,
> the Science Board has a critical role, an increasingly important role,
> at the FDA. We need your help to make sure that we are infusing the
> right, the best and the latest science and necessary technical
> insights into FDA\'s programs across the board and that nowhere is
> that more important than in our Food Security Program where we need to
> rely on the best and latest science to make it a success as you have
> seen in the regulations that I have just described.
>
> We have been very grateful for the Science Board\'s efforts in helping
> to supply this kind of scientific expertise to other key FDA
> initiatives. In just my limited time here, we have benefitted greatly
> from your contributions to such critical areas as pharmacogenomics and
> more efficient mechanisms for developing new drugs and demonstrating
> that new products, new medical products, are safe and effective at a
> lower cost and more predictably and in less time to quality systems
> for our own review procedures as we, like other people in the
> public-health system and in the healthcare industry, are working to
> identify best practices and spread them throughout our organization to
> efforts in critical path research in finding better ways to turn good
> scientific ideas into safe and effective products that people can
> count on.
>
> So we thank you very much for all your support and all your
> contributions to these efforts. We are going to take another step in
> this process today. The entire purpose of today\'s meeting, the
> primary purpose of today\'s meeting, is to share our progress with you
> and to obtain your input on how to direct our food-security efforts.
>
> You are going to hear from a number of different people, experts
> inside the agency and others. We are going to give you a number of
> challenging issues to consider and questions to help us address as we
> continue these food-security efforts.
>
> There is a broad agenda today to accomplish this goal and I hope that
> you will keep in mind, as we go through it, a few key questions, among
> others. First is the approach that FDA and our Center for Foods is
> taking balanced and appropriate. Are there any gaps in the program
> that we have outlined here and, if so, what are they and how can we
> best address them?
>
> Third, are we devoting adequate resources appropriately in the various
> food-security-initiative areas? Are there any areas in which you would
> recommend a reallocation of our limited human resources or our
> financial resources?
>
> Fourth, are the time tables that we outlined reasonable? If not, why
> not? Where might we better concentrate our efforts? How can we amend
> our priorities accordingly?
>
> I am sure these are not the only questions that are going to come up
> as we review our food-security activities but I am also sure that your
> insight on these and other questions is important because food
> security, itself, is not critical to our overall strategic plan, our
> overall strategic initiatives at FDA.
>
> It relates to our commitments to consumer safety. It relates to our
> commitments to national security and domestic defense. It calls for
> efficient risk management. It calls for a strong and effective FDA.
> These are all, as you have heard before, key elements of our strategic
> action plan. In all of this, we also depend on better informed
> consumers and agency partners. So this is an integral program for our
> overall strategic initiatives at the FDA.
>
> I would like to talk just a minute more about one key element in our
> strategic plan and that is better-informed consumers. I would like to
> thank those of you who are in the audience today who got up early in
> the rain to come out here to Rockville to hear and contribute to what
> we are doing today. We will appreciate your perspective as well. As
> you heard, there is a public comment period later on in the meeting
> today.
>
> We think we have been doing a good job so far in working together with
> our various partners in carrying out this critical part of our
> mission, with industry, with academic experts, with our sister
> agencies, with foreign governments and with the American public. But
> there is always room for improvement and we need to be challenging
> ourselves constantly to make sure we are keeping up and we are using
> our limited resources as effectively as possible.
>
> In light of the complex food and health challenges that we are now
> facing, we really must be on guard to use the latest and best ideas
> about how we can accomplish our mission as efficiently as possible.
> That is why meetings like this one that we are holding today are
> absolutely critical for the future of the agency.
>
> So I want to finish up by thanking you and, again, ask you for your
> best ideas and your help with the many urgent and difficult
> food-safety and security issues that we are facing today. As I have
> said before, as I discussed with you last night, I think the
> public-health challenges that we are facing today are great. They are
> unprecedented. But also unprecedented are, as a result of scientific
> progress, the opportunities to make a positive difference for the
> health of the public, both in public-health protection and in
> advancing and improving the health of the public. These opportunities
> have never been greater as well and we need your help in matching up
> the opportunities and the challenges.
>
> I am confident\--I have been here almost a year now and I am confident
> that, by working together and using the talents and dedication of the
> staff of this agency, the willingness on the part of the many
> well-trained professionals at the FDA to always take a fresh look at
> what they are doing and always make sure we are adapting and adopting
> the most effective approaches\--I am confident that we can, together,
> rise to the challenge of making sure that Americans continue to enjoy
> the best public-health protections in the world when it comes to food
> safety and food security, food products that are not just diverse and
> fairly priced, but safe and secure.
>
> I think you will also hear a little bit today about our steps to help
> make sure that foods are not only safe and secure, but also are
> developing and improving in ways that can help Americans promote their
> own health. We know more from nutrition science today and studies of
> obesity and healthy weights, about steps that people can take to
> improve their health, to avoid chronic illnesses, to live longer and
> better lives and we need help with that part of our food safety and
> security and health-promotion mission as well. Again, it is protection
> and advancement of the health of the public that we are most concerned
> about today.
>
> So, in advance of today\'s discussion, I want to thank you. I look
> forward, after you have heard the presentations today, to our wrap-up
> discussions later on in the afternoon. Again, I really appreciate the
> time and effort that you all are devoting to these critical
> public-health challenges with us.
>
> Thank you very much. Do you want me to take any questions?
>
> DR. DOYLE: Certainly. Thank you, Dr. McClellan. It\'s time for
> questions. Any questions from the Board? I guess you have awed us all
> so much that we don\'t have any questions.
>
> DR. McCLELLAN: Let\'s get right to it. I think they are ready to get
> into the substance. Thank you very much.
>
> DR. DOYLE: Thank you.
>
> Next we are going to hear from Joe Levitt who is the Director of the
> Center for Food Safety and Applied Nutrition. Joe is going to give us
> an overview of the FDA\'s Food Security Program.
>
> **Overview of the FDA Food Security Program**
>
> MR. LEVITT: Good morning. It is a pleasure to be here. Apologies. I am
> glad I got here in time for my presentation. I apologize to the
> Chairman and to the Commissioner. It is a pleasure to be here.
>
> We have, I think, a very interesting and exciting day. I want to thank
> Michael Doyle and the whole Science Board for your interest in this
> area. I thought we had a wonderful session yesterday afternoon to
> preview with some of the staff scientists some of the research that is
> going on.
>
> I certainly want to thank the Commissioner who has brought such vigor
> and energy and vision to our program, not to mention a strong advocacy
> for our resources. I think it is fair to say that the \$5 million that
> OMB allocated this past summer for research for food security would
> not have happened were it not for the personal intervention of our
> Commissioner. So we all thank you for that and for so much more.
>
> My job today is to\--I have the easy part. I am going to give you an
> overview to set the context so that the remaining speakers of the day
> will hopefully fit into the big picture.
>
> We have basically three main messages. Number one, in the area of food
> security, there is no doubt; we need to be prepared. This is a
> possibility. We all know that food can be a vehicle for contaminants
> that could make people sick or worse, that it could be used in a
> terrorist setting and it is our job to do the very best we can to be
> prepared.
>
> Number two is that it has now been two years since 9-11. We are much
> better prepared than we were two years ago. While that is so, we still
> have a very long way to go. It is a kind of issue that the more you
> see and the more you understand, the more you see how much there is to
> do and what the scope of the challenges are.
>
> But the good news is that we have not only made progress; part of that
> progress, and a very significant part of that progress, is setting out
> a blueprint on how to get there. So we feel we have that and we are
> ready and eager and moving forward.
>
> This past summer, we sent a progress report to Secretary Tommy
> Thompson on food security. What I am going to do is outline what that
> is and that will, again, lay the background for the remaining speakers
> of the day.
>
> We started with four main principles. Number one, that food security
> and food safety are integrated goals. We talked a fair amount about
> this yesterday. We need to be building on the existing food-safety
> public-health infrastructure to fight the terrorism threat as well. We
> cannot afford to have what I think of as an \"east is east and west is
> west\" approach, safety is here, security is there.
>
> We have strong systems. We have science. We have emergency-response
> systems. We have inspectors. We have scientists. We have research
> programs. We need to apply those with a new lens to look at food
> security in addition to food safety but also see them as interrelated.
> For many of these things, there are dual benefits as well and we need
> to maximize the synergy as much as we possibly can.
>
> Number two, just like in food safety, the food safety and security
> system needs to be comprehensive. When we are talking about food
> safety, we used to talk about farm to table, the whole scope of the
> food chain. We have to think about that here, too, but we also have to
> think about it more analytically in terms of how do you prevent, how
> do you protect, how do you do the full range of assessments and
> actions and preventions in a response. So this is a full soup-to-nuts
> program that we must have to be successful.
>
> Number three, while the federal government clearly plays a critical
> role, we are not the only ones in this story here. This needs to be
> built on a solid foundation of truly national partnerships. All
> federal agencies, state and local agencies, private-industry
> consumers; this is a task that it so important and so big that it will
> require all of us working together in order to achieve our goals.
>
> Finally, and this is I always feel important in almost every important
> thing we do; we have got to think of it from a consumer standpoint. We
> have to be sure that Americans have confidence in the government. A
> lot of times, I feel when we stop and analyze issues, we tend to see
> all the complexities and all the steps and the potential barriers and
> funding and all that kind of stuff.
>
> If you look at it from a consumer point of view, it is really quite
> simple; be prepared and take care of us and be honest and tell us what
> we need to do if something bad happens and, when you see it from that
> vantage point, what it really takes to provide confidence to American
> consumers. To me, that helps bring clarity of the other points. We
> have got to integrate food safety and security, build on our past
> successes.
>
> We need to have a comprehensive system and we need to make that a
> truly national partnership and make this a truly successful program.
>
> We then took that and tried to put it into thematic steps, thematic
> order. These steps are actually the main steps in the government\'s
> National Response Plan. So this is not something that the FDA brought
> up. This is our part of integrating within the broader federal
> framework.
>
> The broader federal framework has five steps; awareness, prevention,
> preparedness, response and recovery. First, awareness; you need to
> know what is going on. You need to not just provide information and
> raise consciousness but you have to get your information connections
> in there right. I am often quoted as saying, correctly, that when I
> first took this job six years ago, I never thought I would say, as
> Director of CFSAN, \"We need a closer working relationship with the
> CIA.\" I couldn\'t have imagined saying such a thing.
>
> But the fact is, it is an imperative now. And the fact is, we do, now,
> have a closer working relationship with the CIA and with the FBI and
> the whole law enforcement and intelligence community. So we have to
> get the awareness up. We have to know as much as anybody knows what is
> going on. There is now a large number of people in FDA that have
> security clearances at different levels and we have people at FDA that
> get regular intelligence briefings.
>
> Number two, as with all public-health matters, prevention is always
> the best. Whatever we can do to prevent the problem, to get out there
> in front of it and to catch something before it occurs, that is always
> preferable. The biggest advance FDA has made to date on this is at our
> borders. As I will get to in a moment, when 9-11 hit, everybody
> realized\--I remember Secretary Thompson, particularly, resonated in a
> worrisome way, \"What does it mean, we look at less than 1 percent of
> imports? What does it mean, we only had a few border around? How can
> that be? Does that look like a vulnerability?\" And Congress did pass
> appropriations which has resulted in significant numbers of added
> people both at more ports and more people at existing ports. I will go
> through some of the results from that already as well as new
> legislation including better notice of imports coming in before they
> come in, so we can have a better prevention program.
>
> Overall, three, preparedness. This gets into more the underlying
> infrastructure you need to have and develop an effective program. A
> lot of today\'s discussions are really going to be devoted to that
> element of preparedness. What is the underlying expertise we need at
> FDA to make a good, strong FDA? What are the laboratory networks that
> we need. You will be hearing a presentation on that.
>
> What is the research program and the research agenda to get the right
> scientific knowledge. We will only be successful\--as with all of our
> important programs at FDA, our success is closely linked or tied to
> the science. We have got to start with the science to know what is
> going on, how we can be effective and how we can reach objectives that
> we need to. So preparedness, in a way, is the underpinning to
> everything else here.
>
> Fourth, we know, no matter how aware we are, how much we try to
> prevent, whatever our underlying infrastructure of preparedness is,
> part of that is knowing, if something happens, we need to respond
> rapidly and clearly. So response is an absolute critical element. Is
> this something that FDA has a lot of experience with in general in
> terms of emergency response to foodborne-illness outbreaks?
>
> But we also know that, in the case of a terrorist event, it is going
> to raise the ante several levels up. There will be enormous media
> scrutiny. There will be enormous need to be able to respond almost
> instantly and that we will need to be out there with risk
> communication statements and information to consumers before we have
> all the information.
>
> We like standing up there with the answer. We know there is a
> contamination in this food product. It is Lot So and So. If you have
> that lot in your home cabinet, take it out. It is being recalled. That
> is routine stuff. That is what makes us feel comfortable.
>
> What do you do when you know there is a big problem and you don\'t
> know what the cause is and you don\'t really know exactly what is safe
> and what isn\'t. We experienced that with the anthrax-in-the-mail
> episode, by now almost two years ago. It is a scary time. But,
> nevertheless, again, think of it from a consumer point of view. They
> don\'t want us to stand up here and say, \"This is a scary time.\"
>
> They want us to stand up there and say, \"This is what we know. This
> is what we don\'t know. This is the best advice we can give you and we
> are going to keep updating you and giving you more information as soon
> as we possibly have it.\" So response is going to be not just the
> follow-up investigation but the public-communication aspect of that.
>
> Finally, something that is, I think, all too often forgotten and it is
> the last thing on the list is recovery. As much as we try to be ready
> for response, we hope it doesn\'t happen, and so the follow-through.
> We have got to be sure, again, part of a comprehensive program. If
> there is something that happens somewhere, well, you don\'t want to
> shut down that sector of the world from time forward forever.
>
> We need to have a recovery plan. How do you disinfect? Again, think of
> anthrax and the Hart Building downtown. EPA went in and had a
> disinfection program. It took a while but people are now back there
> working and it is a functional building. So recovery is a critical
> part of all this.
>
> Now, to address these five strategic categories, we put together a
> ten-point program that is more in what we think of as operational
> steps because so many of the things we do cut across these different
> categories. We found it easier just to think about it ourselves than
> to explain to others, to think of it in operational terms.
>
> So we have ten operational categories. Number one starts with a
> stronger FDA. I already mentioned quickly that, with the supplemental
> appropriations following 9-11, FDA hired over about 800 people, 650
> some-odd went to our field and the vast majority of those went to the
> border, both people at the border as well as people in laboratories
> supporting work at the border.
>
> We have already seen results. First is in terms of taking a strategic
> approach on imports. Step 1 was what I call narrow the gap, try to
> start plugging the hole and not have what appears to be a large
> vulnerability out there. So FDA has increased our presence from 40
> ports to 90 ports and we are now at virtually every major port that
> imports food that we regulate.
>
> We have increased the number of physical examinations at the border
> really at a staggering rate. Two years ago, we inspected, at the
> border, 12,000 food entries. You don\'t really know how many 12,000
> is. But, two years later, this year, our number\--we just got the
> numbers in is about 80,000.  So that is a six-fold increase in what we
> were doing before.
>
> It is still a very tiny proportion of the overall but, nevertheless,
> Step 1 established a presence, \"Don\'t let this be the weak link.\"
> We are making good progress but we know we have to do much more. We
> know the imports has to be a broader strategic approach\--part of that
> will be helped with the new Prior Notice Regulation which I will talk
> again more about in a minute\--because it is really going to come down
> to effective targeting.
>
> Our job will be, no matter how many tens of thousands we can look at,
> there are millions coming in. The way I think of it is, with better
> targeting, we have to shift it from looking for a needle in the
> haystack to either having a magnet that pulls it out or at least be
> able to say which part of the haystack we have to look more intensely
> in. That is the goal we have to get to and we are working on that
> through all of our FDA-regulated products.
>
> Number three is the new Bioterrorism Act Regulations. Again, in
> addition to the new money that was appropriated by Congress, Congress
> passed a major Bioterrorism Law. There were four major provisions in
> it concerning FDA that required regulations.
>
> There are many more provisions that relate to a broader spectrum of
> activity, but the key ones are, number one, every firm needs to be
> registered with the FDA so that we have a full inventory of who is out
> there doing what. Number two, all importers into the country, those
> five, six, main entries, they all have to tell us in advance what is
> coming in so we can put it through our computer triaging system and we
> can effectively target. That has got to be an absolutely critical part
> of our overall strategy.
>
> Those two final regulations we just published on time the last couple
> of weeks. We were on kind of a breakneck speed time frame in that the
> law was passed and signed in June of 2002. We issued proposed
> regulations in the winter and spring of 2003, final regulations for
> the first two in October of 2003 to be implemented by statutory time
> frame on December 12.
>
> So we came through and met that. We feel very pleased about that. In
> addition, there are two remaining regulations, one dealing with record
> keeping. So food companies will need to keep records of both who they
> bought it from and who they sell it to, what is called \"one up, one
> down,\" so that if there is an outbreak, we can more rapidly trace
> what happened to the food, either forward or backward through the
> chain,
>
> Finally, there is a fourth regulation that is called administrative
> detention. So, if we do find a contaminated lot, we can actually hold
> it right there, pending the more complicated federal court action we
> are required to take. What has happened in the past is we would have
> to go to a state authority and ask them to embargo it while we go and
> do our federal court procedures. This gives the FDA the ability to do
> that.
>
> As I said, let me go through the first two quickly that just became
> published. On food registration, what it will do is it will facilitate
> timely notification and response in the event of a food-safety threat.
> We will know where everybody is, who is the business and we will know
> what business they were in. So, if there is a problem with cheese, we
> can push the button and say, all right, we need to notify these people
> that make cheese.
>
> If it is canned fish, we can do that. Whatever it is, we can find out
> where you are. We have published an Interim Final Rule on October 10
> with an effective date of December 12. It applies to most domestic and
> foreign facilities. There are exemptions. It doesn\'t cover farms. It
> doesn\'t cover grocery stores and restaurants.
>
> The registration system is now operational. You can register\--a
> company can register on line in about ten minutes. We have gone around
> and done demonstrations. I say that is probably the single biggest
> thing that has helped us, credibility with the industry, because a
> vast industry is a nightmare; oh my gosh, what is going to happen, how
> much paperwork are we doing do, how long is it going to take, what are
> the hassles when they lose it.
>
> I have tried and I just get stuck. So we have an on-line system that
> went on-line on October 16. As of last count and last week, we already
> had 20,000 firms register. So it is moving. It is operational. There
> are a few glitches along the way, as you will have, but they have been
> able to get them rapidly fixed and continuing.
>
> It is a one-time registration, not an annual, although companies are
> required to provide updates if they change the nature of the products,
> the business they are in, if they open a new facility somewhere and
> there is no fee associated with it.
>
> We have a health line available that is 24 hours, seven days a week,
> and can be accessed worldwide. There is a part in our regulations that
> help you on how to identify food-product categories.
>
> Prior notice of food imports. This one has been actually much more
> controversial. I think the registration system, once people
> understood, \"I can do this in ten minutes? All right, I will do it.\"
> The prior notice has been much more worrisome because of the fear that
> essentially the FDA would shut down commerce. That these five, six
> main entries that come in\--that is 25,000 a day\--a lot of them come
> in over truck from Canada or Mexico. The fear, oh, my gosh, before we
> know it, the line will go from the Rio Grande all the way down to the
> Panama Canal, and what happens then.
>
> So there has been a lot of work here to work in a fully integrated way
> with what had been called the U.S. Customs Service, now is the Customs
> and Border Protection Unit within the Department of Homeland Security.
>
> So, number one, companies can submit their prior notice electronically
> in a one-stop-shopping method. They can send it through the existing
> customs electronic interface that they are used to working with
> anyway. That has been modified so that it includes all the provisions
> that we need to have included. So that was kind of breather number one
>
> Breather number two was that FDA had proposed notice noon the day
> before. Well, I guess we got people\'s attention with that. Then,
> afterward, the notion of, oh, my gosh; if they need that much time,
> they are not going to be able to work in real time. We didn\'t really
> know what the right amount was so we put that out so they have
> something to react to. We certainly got a reaction.
>
> But that has been modified again very substantially. I joke because it
> is a way to help me remember it. I am from New England and always grew
> up with Paul Revere, \"One of by land and two if by sea.\" This is
> actually two if by land and eight if by sea, but it goes to a
> two-hour, four-hour, eight-hour, depending on the mode of transport.
> It is two hours if it comes in by land, four hours if it comes in by
> rail and eight hours if it comes in by boat.
>
> I haven\'t heard such a collective sigh of relief since almost\--you
> know, after the hurricane passes, whew, we survived that one. But,
> again, that resulted not only from listening to industry but working
> with customs on what really can happen.
>
> We are also using new authority under the law to what is called
> commission customs employees to essentially be cofunctional with FDA
> as another way of expanding our work force and getting them to do a
> lot of the help at the border. We are also going to be housing more of
> our people in customs facilities to be sure these computerized
> networks hook up. Again, we have got a single consolidated system.
>
> These notices are required to be submitted electronically. There is no
> other way to do it. As I said, they have to come through the customs
> place. There are some exclusions for personal use; home-made goods,
> product regulated exclusively by USDA. They have their own system that
> takes care of that. This is not intended to do that. But these two
> regulations are the first main linchpins to do legislative authority
> helping us fight terrorism.
>
> After we get that, I am going to run down rapidly because you are
> going to hear most of the stuff in more detail later in the day.
>
> The fourth area to highlight is industry guidance for preventive
> measures. One of the very first things we did was companies come to us
> and say, \"What can we do? What should we do? What do you want us to
> do? Don\'t make us, as an industry, thousands of companies, reinvent
> the wheel and pay the same consultants over and over again for exactly
> the same information back.\"
>
> So we have put together guidance and issued that in January, so it
> must have been January 2002, which was finalized the following year
> which laid out what I think of as a menu or a smorgasbord of
> activities that companies could consider in the area of physical
> security, in the area of personnel, in the area of control over
> products, management recalls, and so forth. That has been very well
> received.
>
> We were asked to do additional specific ones, one for the retail
> industry on the principle that, if you think of it, if you are a food
> company, one of your goals is to keep strangers out. If you are a
> grocery store or restaurant, one of your jobs is to invite strangers
> in. It doesn\'t do any good to not let people in your business. So it
> presents a different dynamic, and so we have tailored a new one
> specifically for retail and a new one for cosmetics so we have the
> full gamut. Then we are starting to look at specific areas and we
> issued guidance on fluid milk last June.
>
> Vulnerability assessments; Bob Brackett is going to do a much more
> extensive presentation but I think one of the most significant things
> we have been able to do\--again, going back to where is the strength.
> The strength is in the science. Where is the importance? The
> importance is in the strategy. You start with the science. You build a
> strategy. So we started with vulnerability assessments based on
> scientific principles\--Bob will go through these\--adding in what
> information we know about threats from intelligence sources and it has
> helped us very significantly winnow down where are the areas we ought
> to be applying our attention to with the most vigor.
>
> That applies to how we focus our research agenda, how we triage
> methods needs in the laboratory, how we triage guidance to the
> industry. Everything flows from that. If you know your priorities, you
> know your strategy, you can roll. If everything is, oh, my gosh, what
> about this, what about that, you just kind of go in circles. So
> vulnerability assessments is really, the, I think, key starting for a
> government program.
>
> We also have to realize that there are going to be some times when we
> are at a heightened state of alert. We are all now familiar with a
> color-code system of red alert and orange alert and yellow and so on
> and so forth. One thing every agency in government has been asked to
> do and, I think, appropriately, is what happens, what do you do
> automatically when it goes up.
>
> Some things you will see, like I know in the Parklawn Building or, I
> guess we are next to the Parklawn Building here, if we go up to orange
> alert, I can tell you, there are more security guards out there and
> they are checking more vigorously than they would if they are at
> yellow alert. That is an example of just something that automatically
> triggers in.
>
> What triggers in with us, in addition to the things around our
> buildings, is increased scrutiny for certain kinds of products, again
> based on our vulnerability assessments. We implemented that the first
> time during Operation Liberty Shield which was coincident in time by
> design, obviously, with the beginning of the war in Iraq. So we were
> able to ramp that up. That was both a learning experience but also an
> operational experience and we felt we learned a lot about that.
>
> Again, our import program got sharpened up to these products, these
> areas of the world, and afterwards, you kind of go back down a little
> bit but try to learn, what do we learn from that. Again, you obviously
> are retooling and refining your priority-setting system.
>
> Emergency preparedness and response; again, clearly a key critical
> area. Again, FDA has a lot of experience here but we are
> continuously\--I don\'t think refining is the right word\--we are
> continuously building and strengthening that through many exercises at
> many levels.
>
> We have had an exercise just within CFSAN senior management. We have
> had exercises within FDA, within the department, with us and USDA at
> our level, with HHS and USDA at the Deputy Secretary level. We have
> had a governmentwide exercise called TOPOFF-2 that I am sure you are
> familiar with and have read about it in the papers. So we are doing
> this intensely at every level.
>
> I can tell you two things; number one, they are really sobering
> experiences because what happens is it goes through in very rapid
> fire. So you kind of live three weeks of hell in six hours. The three
> weeks have been bad enough. Six hours, you clearly realize how rapidly
> things can spin out of control if you are not on top of it.
>
> So it is both sobering but it teaches you a lot. It also forges the
> connections between the agencies vertically as well as horizontally so
> that if there is an event, we are poised, we are ready. And we have
> some sense of what we would actually do in that situation.
>
> The next two are areas you are going to hear just a lot, lot more
> about today. The first is laboratory enhancements. I think one of the
> real, if you will, light-bulbs going off over the last couple of years
> has been just the critical role that the laboratory is going to play,
> not just in research but in response.
>
> Following the anthrax episode, across the country, over the next month
> or so, there were over 100,000\--well, like 150,000\--samples taken
> across the country testing white powder to see if it was anthrax. Only
> a tiny fraction of that was in any of the states that actually even
> had a case. But you don\'t know how far it was spread. You had no way
> to track it and the labs were flooded.
>
> We know, in our own building, and those of you who heard my last
> presentation, I won\'t go through the whole recitation, but we
> experienced that in our own building when we were down at FDA. We got
> our first lab result on a Sunday night that it was presumptively
> positive. But it was all the way until the following Saturday before
> we got a confirmatory negative. That was a week of pure hell.
>
> We can\'t have that. We can\'t have a laboratory system that is so
> overloaded that you can\'t do the work. Again, think from a consumer
> perspective. Consumers want to get it done. They don\'t want to hear
> excuses. They want action. And I don\'t blame them. I am a citizen and
> I want action, too.
>
> So the importance of the laboratory, both in a cohesive and
> coordinated way but in a way that is trained for these kinds of
> agents. With biological, you start getting into BL-3-level
> laboratories and those kinds of needs, chemical agents provide their
> own challenges on how to do it. But, again, the laboratory is a
> critical foundational element for us to be successful in this effort,
> not only in response but also in surveillance. If we are going to
> start doing more surveillance here, which we will need to do.
>
> Again, based on our threat assessment and priority scheme, we need to
> have labs capable of doing the work. The FDA lab systems are simply
> not set up to work on that order of magnitude. So working with all of
> our sister agencies and with a wide number of state health and
> agriculture department laboratories as well. You will hear a lot more
> about that this afternoon.
>
> Research; most of today is going to spent on research so I think all I
> will really say here is, again, the two light bulbs that were not
> obvious were one, how important the labs are. Usually, you think of
> FDA, you think of the inspectors or you think of premarket approval
> for new products and the laboratory is kind of like a background
> thing. The laboratory has got to be central here, but the research
> agenda\--there is so much here that we need to know that we don\'t
> know.
>
> There is a fair amount we know. But, as you look at it, these are
> agents that haven\'t thought about foods, a lot of them. We don\'t
> necessarily know what interacts with them, what kills them, what dose
> responses. We don\'t necessarily know the methods for the laboratory,
> what prevention technology could be effective.
>
> So there is a whole scientific agenda that needs to be addressed. The
> initial money that will be provided, and this past summer is a good
> start. We hope it is a downpayment on what we hope in the future will
> become a dedicated research program in food security. Bob Buchanan and
> others will be going through this in great detail.
>
> Finally, you have heard me say this and refer to this throughout;
> interagency and international communications. We actually have
> exercises now involving Canada, involving Mexico and this will
> continue to expand. But, again, everybody is part of this network and
> there are intra-agency working groups on all these subjects. We have
> working groups on incident command and response, on laboratory
> preparedness, on protection steps, what we call shields, and there is,
> I think, an unparalleled level of collaboration going on across all of
> those.
>
> We tried to take a step back and kind of say, you know, where are we?
> What are the needs? What we did here is, to explain the chart, we took
> the three middle areas of those five themes, prevention, preparedness
> and response, and listed some of the specific things that fall into
> each of those categories.
>
> Then we looked at where were we in 2001. If 9-11 had been an attack on
> the food supply, how prepared would we have been? Two years later,
> where are we and where do we feel we can get to in 2007 which was four
> or five years out. Again, using the color-coded alert levels, red is
> bad. Red means we are at very high risk and very vulnerable. Green
> here is the lowest.
>
> Basically, what this chart shows, if you look in the first column, if
> 9-11 had been an attack on the food supply, we would not have been
> ready for it. Essentially, you see red in every category except for
> emergency response, given that FDA has had traditional
> emergency-response systems but, again, not geared to the pace and
> intensity that we need.
>
> Two years later, you see all of a sudden some of these are turning to
> orange. Our inspections are up. Our intelligence-gathering is up. We
> have come out with new regulations on registration and prior notice.
> We have improved our physical security.
>
> But there is just so much more to do. Again, what our blueprint is
> designed to do is to get us from this interim step to really realizing
> what the magnitude of a comprehensive program is, how to make that
> again coincident with food safety and security together but a
> comprehensive program based on a national foundation that meets and
> responds to consumer needs.
>
> Let me then just give a short preview of what the rest of your day
> will look like. The next three speakers are from my center, from
> CFSAN. Bob Brackett will talk about our threat vulnerability
> assessments. Bob Buchanan will give an overview of our research
> program. I will say, and we joke about this\--there is a joke in
> CFSAN; if you want the big picture, talk to Joe Levitt but if you want
> the real substance, talk to someone named Bob. You have two of the
> finest here today.
>
> In addition, we are happy to welcome David Armstrong who is from our
> Chicago research facility to talk about prevention research. We have a
> collaborative program out in Chicago at the Illinois Institute for
> Technology, what is often referred as the Moffitt Center. We have
> there a pilot plant, a very unique laboratory facility. We are
> building a BL-3 laboratory there and we are counting on that program
> to do a lot for us in the future in the area of prevention
> technologies.
>
> But then you are going to see this is not just a CFSAN program. This
> is an FDA-wide program. Dan Casciano will be talking about the
> important work that is going on down at NCTR in Jefferson, Arkansas.
> Dr. Linda Youngman from the Center for Veterinary Medicine will be
> going through issues relating to veterinary-medicine areas.
>
> Carl Sciacchitano from Office of Regulatory Affairs will be talking
> about the whole laboratory network, what we are calling FERN, Food
> Emergency Response Network, and the progress that is being made there,
> to cover kind of the direct food but it is also, again, a broader FDA
> program.
>
> Jesse Goodman, who is my counterpart in Center for Biologics, will be
> talking about the important work that the Center for Biologics is
> doing, particularly in the area of vaccines. Diane Murphy, from the
> Center for Drugs, will be talking about important medical
> countermeasures. Again, when you think response, it is not just going
> and finding what happened. If you have got people who are sick, how do
> you treat them? That needs to be a critical and integrated part.
>
> I think, too often, again we think food is here and drug is here. But
> it is all part, not only of the Food and Drug Administration, but it
> is all part of an integrated, comprehensive program.
>
> So I think you have got an exciting day ahead of you. I will simply
> end where I began. Number one, we need to be prepared. That is our
> job. Number two, while we are much better prepared than we were two
> years ago\--and that is clear; we are much better prepared than we
> were two years ago\--nevertheless, we have a very long way to go to do
> this right.
>
> We are not satisfied to be in the orange category. We need to be in
> the yellow and green category or we need to get there as smartly, as
> systematically and as efficiently as we possibly can. At this point,
> we are fortunate that we have developed and do have a blueprint on how
> to get there and we are ready to go, not only ready to go, but we are
> off and running.
>
> We welcome any and all input, feedback, that you have. These are new
> areas for everyone, a lot of them. And it is challenging to the mind,
> invigorating, but we also know we don\'t have a monopoly on good
> ideas. That is one reason we invite you and we hope why you are
> willing to dedicate a substantial part of your professional lives to
> helping us.
>
> So we thank you for involvement and your advice and I will take a
> couple of questions if there are any.
>
> DR. DOYLE: Joe, that was an outstanding overview to set the stage for
> today. I really do appreciate it.
>
> Do we have any questions or comments? Yes; Dr. Pickett?
>
> DR. PICKETT: Just a quick question. I was surprised to see on your
> chart, in terms of time lines, that in-line detection technologies
> would still be orange by 2007. It seems to me that, as one thinks
> about being prepared, that that is a very important component, rapid
> detection and obviously having the lab capacity to do that. So I am
> curious whether or not that area is appropriately resourced to make
> certain that, perhaps, the time lines could be shortened.
>
> MR. LEVITT: Excellent question. When Bob Buchanan is up here, you will
> see an overview of what the research priorities are. The reason it was
> listed that way is the belief, based on what we have seen so far on
> these biosensors and so forth, it is very difficult to get them
> effective in a food matrix. So that is the expectation that we have
> got, a several-year research program. It needs to be started now, but
> it is going to be longer before we get to where we are going to be
> compared to some things like laboratory methods that can be developed
> much more quickly.
>
> So it is not a reflection of what we think is the importance. It is a
> reflection of what we think is the time line to get that done and, as
> you will see, in any world, there are finite dollars and where can you
> get the most bang for each dollar that you put in. But that is simply
> why.
>
> DR. DOYLE: That is an excellent point.
>
> Dr. Riviere?
>
> DR. RIVIERE: One very quick question. What happens on the prior notice
> on shipments if you don\'t follow prior notice and come to the Board?
> In other words, what is the teeth to this regulation?
>
> MR. LEVITT: This is the way it works. Under the law, if they don\'t
> provide the prior notice, they don\'t get in, period. There is a lot
> of fear and understandable fear that\--you have got so many thousands
> and thousands of importers. How is everybody going to get the message?
>
> So what we are doing is we are putting in a transition policy so that,
> for the first four months, if they come in without it, they will get a
> feedback letter that says, \"You didn\'t do what you were supposed to
> do. We are letting you in this time. But this is what you have to do
> in the future.\" That will get ratcheted up, actually, over, first, a
> four- and then an eight-month period.
>
> That is consistent with what we would normally do with new
> regulations. When we came out, for example, with the new seafood HACCP
> regulations, the first year of inspections, we don\'t take them to
> court right away. We give them a feedback letter; \"This is a new
> regulation. This is why you need to do to comply. Next time in here,
> we are going to expect you to do it.\"
>
> So there is a phase-in, so that there is a reality base to it. To us,
> December 12 is clear. But there is a big world out there. Not
> withstanding the fact that we are doing meetings literally around the
> globe\--we had an international video conference\--nevertheless, there
> are just so many. Again, working with customs, it naturally takes time
> for the word to get all the way through. So we are trying to phase it
> in that way.
>
> DR. DOYLE: Dr. Swanson?
>
> DR. SWANSON: First of all, I would like to compliment the agency on
> the prior notice and the registry process, listening to the comments
> that were made from the proposed rule to what came out, because it is
> more efficient and workable than the original one was and we are
> working through the system.
>
> One of the things to look out for, and I think we need a creative
> solution, is we are trying to figure out how to deal with R&D-type
> samples that do come in across borders. It is one of those that really
> wouldn\'t have a huge impact on security issues because it is going
> from one research center that may be outside the country and in. We
> are registering our research facilities even though we don\'t need to
> because of this. We need to be thinking about how to creatively do
> that because we have got as many as ten or more a month that will be
> coming in and they shouldn\'t be tying up resources unnecessarily.
>
> MR. LEVITT: Okay. Good. Thank you. That is good feedback.
>
> DR. DOYLE: Dr. Thomas?
>
> DR. THOMAS: What sort of coordination might there be with USDA with
> regard to bringing in meat and other types of produce with respect to
> the new legislation?
>
> MR. LEVITT: There is a lot of collaboration with USDA. You will see
> that they are a full partner in the laboratory network. As I
> mentioned, there is a lot of activity in emergency response. The
> actual system for meat is a little different and has its own system.
> The number of meat imports is a tiny fraction compared to what we deal
> with. So what we have made sure is we are not getting in each other\'s
> way. We are not duplicating anything. But that system was working fine
> so we are trying to do fine, also.
>
> DR. DOYLE: All right. I guess that is all, Mr. Levitt. Thank you very
> much.
>
> We are going to take a short break and reconvene at 9:30. I think it
> is important that we try to do that, be on time, because we have got a
> jam-packed schedule. So, 9:30.
>
> \[Break.\[
>
> DR. DOYLE: We are now going to hear from Bob Brackett on CFSAN\'s
> activities in the area of threat and vulnerability assessments.
>
> Dr. Brackett?
>
> **Threat/Vulnerability Assessments**
>
> DR. BRACKETT: Thanks, Mike, and good morning to everyone as well.
> Thanks to Joe for giving such a good, complete overview. I think that
> is very helpful and I think it helps put into context what myself and
> the rest of the speakers will be talking about.
>
> What I usually do when I start these presentations, especially in the
> last few years, talking about food security, is start off with this
> particular slide which also lists our food-safety mission within FDA
> and that is reduce foodborne hazards to the greatest extent possible.
> It doesn\'t really matter whether it is an intentional agent or
> whether it is an accidental contamination. The goal is still the same
> and that is to protect the American public.
>
> To do that, the other question I get asked frequently, and this has
> been alluded to several times yesterday and today, is how do you sort
> of balance food safety and security and what is the difference in many
> people\'s minds.
>
> So I have put together a sort of a schematic to sort of show what at
> least is my perception of our philosophy is and how this all fits
> together. At the core of everything we do, and this has been
> mentioned, again, too, is a reliance\--and this is a necessity\--a
> reliance on sound science. This relies not only on the traditional
> laboratory sciences such as microbiology, chemistry and toxicology but
> more recent sciences that also play an important role such as risk
> assessment. All of these sort of guide the direction that we do for
> protecting the public.
>
> On that core of sound science, we layer another series of programs. We
> take advantage of the science to apply programs to protecting the food
> supply. These are the usual sort of food-safety things we look, like
> good manufacturing practice, HACCP and the surveillance programs that
> we have or that we share with our sister agency at CDC.
>
> Then, upon that, we have a third layer now which is the food security.
> These are things that we really never thought about before, such
> things as the physical security of the environment, of the production
> facility or of the transportation system, and the personnel who work
> in those systems.
>
> We have always worried about in the past, or were concerned about,
> things like sanitation, easy accessibility to equipment so that it is
> cleanable, so that it can become disinfected, so we don\'t have
> accidental contaminants.
>
> Now we are starting to say, is it too accessible? Does it make it easy
> for someone to get in there? So we have to balance, again, those sorts
> of issues with our traditional food-safety issues.
>
> Joe already put this up. This is sort of the guiding framework that we
> are using now for all of the critical infrastructures in this country
> of which food is one, and I will get to that in a moment. But the
> point I am going to focus here again on is awareness because when you
> talk about threat and vulnerability assessments, that is kind of where
> this starts.
>
> What I am going to do in this presentation is sort of give you the
> historical background, to put it all in perspective, so you know what
> we did, why we did it and when we did it.
>
> If you look back in 2001, Joe showed the middle three of those items
> where we had all orange on the chart. With awareness, it was sort of
> the same. In 2001, we had very little awareness of the vulnerability
> of the U.S. food industry to terrorism. We knew about intentional
> contaminations and tampering but not of a thinking enemy actually
> trying to harm large numbers of people through the food supply.
>
> We also had little awareness of the agents of greatest concern. We
> were worried, and we still are, about Salmonella, E. coli-157,
> Listeria, the usual foodborne pathogens, but now we had a whole other
> range of both biological agents and chemical agents and radiological
> agents that we had to consider. These are things that we really
> didn\'t think about much before that.
>
> We also had little awareness of the methods that we needed to detect
> agents in food. This has been mentioned before as well. Finally, as
> has been mentioned already, we had very little awareness of the
> characteristics and behavior of these agents in foods; that is, were
> they able to survive if they are biological agents? Were they able to
> infect a human being who would consume them. These are sort of things,
> questions, that we really had no idea at that time.
>
> So the awareness part became very, very important in 2001 and it
> became our highest priority to develop what is known as situational
> awareness; that is, we needed to know everything and we needed to know
> it fast. Of course, that was very confusing at that time because the
> problem was so big it almost seemed overwhelming.
>
> We needed to know, first of all, are foods really that important in
> protection, or as an infrastructure. If they are, what are the most
> important foods? What are the things we really need to be concerned
> about and with which agents? Finally, what are we going to do about
> it? Ultimately, our goal is to protect the food supply. So that was
> another part of the awareness component that we were trying to attain.
>
> To go to the first question about the importance of the food supply in
> this country, just a couple of different documents that have been
> released in the last few years. In 2001, the Department of Defense
> released a document, The Threat and Response Report, that, for the
> first time identified a tax on the U.S. food supply that could impact
> or affect the economic stability of the country and, in their
> interest, erode military readiness.
>
> So, in fact, they, at that time, identified foods in agriculture as a
> critical infrastructure. Then, most recently, just this past February,
> the White House, in the National Strategy for Physical Protection of
> Critical Infrastructures and Key Assets, designated officially foods
> as a part of the critical infrastructure. So it is important and it is
> recognized through the highest levels of the government.
>
> So the question also comes now, at this point, since we have to
> know\--we know that food is an important item. Why end up doing
> vulnerability at this time? As I mentioned, first of all, we want to
> identify the vulnerability to the food supply as a whole. Where are
> they likely to occur? Where can we put our resources?
>
> Then, also, important to us, is to prioritize our efforts. As was
> mentioned, there is not enough money to do everything so we have to
> focus on those things where we are going to get the biggest bang for
> the buck. This includes guidance and outreach to the industry. How are
> we going to identify to the industry, to the regulated industry and to
> the public, what things they need to be concerned about; our
> inspectional capability, so we can be more strategic in that level,
> and, as will be discussed more, the research.
>
> Again, this includes methods, the characteristics of the organisms,
> whether they are even toxic in foods. There are some debates with some
> of these agents whether they are. On the one hand, they could be
> catastrophic. On the other hand, they may do nothing. But we have to
> know about that and then, again, countermeasures that we can use to
> protect the public.
>
> When we started under the process of doing vulnerability studies for
> foods, there were a number of different ground rules or sort of
> philosophies that we included in the vulnerability assessments. First
> of all, we were interested in evaluating the public-health
> consequences of these agents and of the foods because, after all, we
> are a public-health agency, recognizing that there are other factors
> as well.
>
> To do this, we wanted to be able to facilitate decision-making about
> resource allocation. Where are we going to spend our money that is
> going to allow the greatest prevention and protection and response
> that we can minimize the risk to the public as much as possible?
> Again, the thing that we were concerned about when we originally
> started this way back in 2001, and, as I will get into actually before
> that, was morbidity and mortality\--that is, illness and death. They
> were the primary outcomes that we were considered with at that time.
>
> We did not, at that time, consider other very, very important
> consequences like economic disruption, public alarm, public panic,
> loss of confidence in the food supply and the food industry. In some
> cases, these could be much more catastrophic to the nation than the
> illnesses and death could by themselves. So these, at that time, were
> not considered. Again, we focused on the public-health implications.
>
> To get to actually where we did. Actually, prior to September 11th, we
> had originally been thinking about this but not with the same degree
> of vigor that we did after September 11th. We actually had a contract
> with the Battelle Memorial Institute to do a vulnerability assessment
> with specific foods and agents. What they provided to us was a
> decision-making tool so that, in the event that there was ever an
> outbreak, we had a way, a logical way, to trace back to try to figure
> out what the most likely candidates were that were causing it.
>
> After that, we took a much broader view. We did an internal
> vulnerability assessment within FDA and within CFSAN using a technique
> known as operational risk management which is a systematic tool for
> evaluating protective measures.
>
> Just to give you a little bit of background about ORM, it is a logical
> six-step sequence that increases effectiveness by anticipating hazards
> and reducing loss. That sounds sort of formal and I will drop down,
> actually, to the bottom point. The origin of ORM was actually with the
> military which is why these are stated the way they are. They were
> meant to protect airplanes on flight lines, to protect assets in the
> military.
>
> We had an individual who was actually with the State of California
> Public Health who came to the Air Force at that time and adapted this
> Air Force tool for foods and it worked quite well. The purpose is to
> minimize risk to acceptable levels. It doesn\'t eliminate them. It
> just shows you where you should focus your resources to protect the
> resources as best as possible.
>
> Of course, the benefits and the things that we were looking for was
> that it allowed us to prioritize our resources, our very limited
> resources.
>
> These are the six steps that were used in that particular
> vulnerability assessment with the operational risk management. Step 1
> was to identify the hazards that we were concerned with, and it is
> very food-agent-combination-specific, assess what the risks are, and I
> will get to that in a moment, look at what risk-control measures we
> might employ, make decisions to actually do those things and then
> implement the controls. Of course, it is meant to be a circular logic;
> that is, you have to go back and look at what you have done and see if
> it matters and then revise if necessary.
>
> When assessing the risk, it involved two components. One was the
> severity of an attack. It could range anywhere from negligible, minor
> disruption, all the way up to catastrophic. This means human
> illnesses. This means complete business failures. And there have been
> cases where this has occurred with natural contaminants as well. So
> the industry was aware of what this meant.
>
> Then there are several levels in between, critical and moderate, each
> of which may or may not have catastrophic effects but still could have
> a catastrophic effect on the national economy if it was done in a
> large way.
>
> Together, we compared these with the probability, and these are sort
> of subjective probabilities, that this product could be contaminated
> with that agent. It could range anywhere from unlikely\--and sometimes
> if you sit around at night and you think of all the different things
> that could happen, your imagination can start running wild and you can
> come up with some real theoretical sorts of things that could happen
> if you really stretched it. But, when it comes right down to
> practicality, you know that it is so unlikely that it is almost not
> worth paying attention to, all the way to frequent where we know that
> we have agents that have occurred in foods that has caused illness and
> death in foods and it could be added to foods again.
>
> So, when you pair those together, you end up calculating a risk by
> combining the two. As I mentioned, you do a separate calculation for
> each agent and each food or activity. This allows us to separate the
> food, the agent and the activity into scenarios such as high, medium
> and low. So it is a coarse tool, but it is one that gave us a place to
> start.
>
> There are a number of agent considerations that we had to include with
> this, one of which was accessibility of the agents. Some of the agents
> that could be used to intentionally contaminate food are easily
> accessible, either from laboratories or in the environment in many
> cases. Some are common household chemicals that could be used.
>
> We also had to consider the public-health impact; as I said, morbidity
> or mortality. Is it going to be catastrophic or is it going to be more
> of a disruption. We also considered the toxicity if were a chemical
> agent or the pathogenicity\--that is, if we knew, or if we could
> estimate as best as possible, what is the dose that would be required
> to cause a catastrophic outcome\--and then compatibility.
>
> Here is where the food technology and food science comes in together
> with the food microbiology or food chemistry. It is one thing to have
> an agent, and you could put it into a food. But, in many cases, we
> knew that it would not be able to survive the processing conditions
> that would normally be applied to that food.
>
> So we had to look at the ability to withstand processing. Or you could
> add it to a food and it would make it so foul tasting or smelling, no
> one was going to eat it anyway. So these are considerations that we
> applied.
>
> When you do that, it puts it on a matrix that is shown here which, if
> you look at the severity, at the catastrophic, on the left and the
> top, and then the frequency, you would end up ranking that a 1. As you
> go matching the probability with the severity, you end up getting
> lower and lower ranks. So you have the red being the high risks, the
> green and the blue being sort of medium risks, and the white being low
> risks.
>
> If you are dealing with a number of different foods, this allowed us
> to set up a priority ranking of where we were going to focus our
> efforts.
>
> The results that we had gotten from the original internal assessment
> were very striking. They were so striking that we believed, and also
> our upper management in HHS believed, you know, this is worthy of a
> second look to be validated. So what we did is we commissioned a team
> put together by the Institutions of Food Technologists which included
> food microbiologists, food chemists, toxicologists, forensics experts,
> both from the industry, from the government and from universities who
> had expertise and expect knowledge of foods including food processing.
>
> So they knew things that we didn\'t because they knew where all the
> hidden skeletons in their plants were, to go through using the same
> foods, the same agent, the same process and they came up with
> virtually the same rankings that we did which was reassuring to us at
> the same time. But they also, since they had a little bit of extra
> knowledge that we didn\'t, identified some other vulnerabilities that
> we didn\'t. So that was very, very helpful and again solidified our
> ability to rank these hazards and then do additional consideration of
> them.
>
> As I mentioned, the assumptions in these early assessments were
> limiting, that they only considered morbidity and mortality. And this
> was pointed out to use over and over again, but, from limitations of
> our resources, we didn\'t consider the economic consequences, public
> alarm, loss of confidence in the food supply or interruption of the
> food stream\--that is, enough food\--which, in some foods of limited
> quantity, that may be important.
>
> So we were asked to put together some other tools that would look at
> these other consequences and integrate them in with the public-health
> concerns as well. That brought us up to our most recent type of
> vulnerability study which is known as CARVER + Shock. I will get to
> what that means. It is another acronym here in Washington.
>
> This was commissioned actually by the Homeland Security Council at the
> White House and was put together with what we have as an interagency
> food working group which combined members of the Food Safety and
> Inspection Service together with FDA-CFSAN food experts to go and
> employ this CARVER + Shock analysis to the high-risk foods that we had
> identified with the ORM procedure.
>
> It was a little bit different than the ORM. Where the ORM was sort of
> a protective, almost HACCP-like in the way it was intended to work,
> this was something that the Homeland Security Council gave to us in
> that it was meant to allow us to look for vulnerabilities in the food
> supply. It was an offensive target-prioritization tool.
>
> The goal here was to identify what are known as critical nodes that
> would be the most likely targets for a terrorist attack and then,
> again, to design shields. We wanted to protect the public, to reduce
> these.
>
> So what we had to do is gather a group of experts for each of the
> foods and look at a very, very detailed schematic of the
> food-processing scheme including very minor points which might seem
> minor to the average person or even to us but, in fact, may be very
> critical in terms of introducing an agent into the food stream.
>
> The results, again, were very similar to what we had with ORM but
> provided much, much more detail as to where in the processing or
> distribution of that food we needed to focus our efforts.
>
> The agency assessments that we had done within FDA and the ones that
> had done with Battelle were augmented because the process allowed us
> to identify not only the public-health significance but also the
> economic, psychological and political implications throughout the
> entire food-distribution system from, as Joe had mentioned, farm to
> table or to human, actually.
>
> Just to give you a little background of what CARVER really is, it is a
> process that rates independently seven factors that affect the
> desirability of a target. The C is Criticality, the public health or
> economic impact; that is, if a person was able to introduce an agent
> into a food, what would the impact be? Would they be able to actually
> do something critical with that?
>
> The second is Accessibility; that is, can they actually have access to
> a target. It is nice to be able to get it into the target, but do they
> realistically have a way to get it into the food. Recuperability is
> one that fits in with the part at the end of the five framework; can
> we recover. It addresses is this system, if it goes down, able to come
> back up or is that the end of that food company or the end of that
> whole system in the country.
>
> Vulnerability is how easy it is to attack. The example I used is a
> bank vault. A bank vault is very accessible. We are allowed to walk in
> and out if you have the right key. It is not terribly vulnerable. The
> Effect is how much the direct loss would be to the company. For
> instance, if a lot of food was contaminated but it was stopped so that
> it didn\'t make anybody sick, what would the loss be to the company
> just because they had to discard that food.
>
> Recognizability is an important part. Would a would-be aggressor be
> able to even recognize what the target is? In some cases, it is easy
> and, in some cases, it is not so easy. And then the intangible part
> that was so important to this was the Shock part of it. This was a
> scored measure of the physical, health, psychological and economic
> impacts of an attack. Sometimes, that overweighted the public-health
> part of it, as I mentioned.
>
> From this, we were able to get some very detailed analyses of specific
> foods and specific agents and it allowed us to then use that to drive
> other things that we are doing. If you look at the evolution of our
> Food Security Program throughout the last three years, you could see
> that in 2001, we started the threat assessments. We wanted awareness,
> looking at the foods and agents and then, from those, we have been
> going to building laboratory capacity and doing training and obtaining
> supplies and methods that we need to.
>
> Then, through 2003, we were trying to find intervention methods to
> prevent the public from being harmed in case this would ever happen,
> or the so-called protective shields. Much of what I will talk about
> will be followed upon by the speakers actually that follow me. So this
> sort of sets the stage for them.
>
> So I guess what I will do now is just summarize by saying that the
> vulnerability and threat assessments that we have used and continue to
> use have allowed us to prioritize efforts. And that was a very
> important first step. They have been very, very valuable. We have
> acquired a very important vulnerability information which we have also
> shared with the intelligence community and law-enforcement community
> to put what they call the threat information; that is, what does the
> intelligence community think about our idea, what threats to do they
> know from the other side and how does that match up. So we are
> combining the two.
>
> Both the food safety and food security programs are being directly
> influenced and, in some cases, driven by the assessments. They have
> been successful enough that we will continue to conduct and adapt
> these vulnerability assessments for all of the FDA regulatory products
> of concern.
>
> With that, I will stop. I don\'t know if there are questions now are
> later.
>
> DR. DOYLE: If there is a burning question or a comment from the Board.
> I guess not. Thank you, Dr. Brackett.
>
> Next we are going to hear from Dr. Robert Buchanan who is Director of
> the Office of Science at the Center for Food Safety and Applied
> Nutrition. Dr. Buchanan is going to talk about food-security research
> needs, priorities, resources and challenges.
>
> **Food Security Research Needs, Priorities**
>
> **Resources and Challenges**
>
> DR. BUCHANAN: As you might tell from my opening slide, actually, as I
> was starting to put this talk together, I was watching a Formula One
> race. So it sort of stuck in my mind. I thought it was very apropos
> because we have, during the last two years and when Joe mentioned it
> was two years almost to the day that we really scaled up to go to full
> time on this. It would be preceding that. It was actually September
> 12, but really things started to fall in place.
>
> It is hard to believe that it has only been two years. We have covered
> a lot of ground but certainly the race is not won yet. So I would like
> to follow up the same themes that Joe and Bob did, that we have come a
> long way but the race is not done.
>
> So we would like to follow that up. I just want to reiterate, and also
> I just want to thank you from the scientists at CFSAN for coming over
> and visiting yesterday. Everyone thought it was a great visit and we
> appreciate you taking the time off and yesterday\'s afternoon to visit
> our new building.
>
> I want to just reemphasize the fact that this is an area that builds
> on our past experiences but for which is one that we have had to have
> a new of thinking because it really does take a different mind set
> when you start to think about the intentional contamination of food.
>
> When we have had those experiences with tamperings and that is not
> unusual when you start thinking of things on a huge scale; that is, if
> you literally had an enemy that was purposely targeting your food
> supply, it really does take a different mind set. Certainly, a lot of
> our initial progress, we really sat down with a core group of people
> that were very familiar with the agents, with the industry, and
> literally sat around thinking about what would I do if I was going to
> contaminate the food supply.
>
> We spent a great deal of time learning about that and looking at the
> consideration of new routes of entry, new agents that we might have to
> deal with and just developing that mind set for understanding. That is
> really the basis, Bob\'s discussion about the threat assessments and
> the vulnerability assessments and the priorities that were established
> as a result of that is something that I am not going to talk about a
> great deal, but it underlies all of the decision-making that you are
> going to be seeing as I discuss our research program.
>
> I just, again, want to emphasize the fact that one of the reasons we
> were able to respond quickly is that we do have a good core of sound
> scientists and we do have a good strong research program that we can
> draw on. We have a lot of experience that is built up around that on
> our Food Safety Programs and then, taking this and enhancing it so
> that we are able to respond to a wider arena of threats.
>
> I am going to start off by sort of going to the end and coming forward
> again. As we have looked at our vulnerabilities, as we looked at where
> we were in our state of knowledge, there are basically four priority
> areas that we have been dealing with and trying to address during the
> last two years.
>
> I would like to go through those first so that you have an idea of
> what we are talking about and how we have responded to them. The first
> is knowledge of the agents. It basically falls into two categories.
> There is a great deal of knowledge of some of the agents. If it was a
> traditional food agent, we have a lot of knowledge of those.
>
> But when we started to deal with a wider arena of potential agents
> that could be intentionally put into a food, we started finding that,
> while there is a great deal of knowledge about some of these agents in
> certain contexts, there is actually very little known about them when
> you start dealing with foods.
>
> This is even down to the basic oral pathogenicity and toxigenicity.
> Most of the agents that have been traditionally looked at for
> bioterrorism or chemical terrorism have been agents that have been
> examined in a different setting and in different routes of entry. So,
> for example, most of the information we have about the pathogenicity
> of a number of organisms is inhalational or cutaneous.
>
> There is very little knowledge, in some cases, about what the oral
> doses are. Likewise, we have very little knowledge of what would be
> the matrix effects. We know from our own work with sort of more
> traditional pathogens that what food you put an organism in can have a
> tremendous impact in terms of what is the dose that is needed to cause
> disease.
>
> We have a great deal of experience in, for example, Salmonella knowing
> that if you put Salmonella in, for example, water, it behave
> differently than if you put it into a vegetable. It\'s different than
> if you put into a variety of other foods.
>
> We also had an amazingly little information about some of these agents
> and their behavior in foods. So one of the questions as we went
> through, for example, earlier in our vulnerability assessments is what
> is the behavior of small pox in food and what is the behavior of a
> variety of protozoan agents, of a variety of viral agents. We really
> had very little information about those that we had to glean. We had
> to make some really quick decisions about where to focus our research
> but we still have questions because those are also\--the behavior of
> those agents in foods is going to determine how we develop protections
> in the food supply in order to be able to either inactivate the
> organisms, prevent their entry, et cetera or, in some cases, not worry
> about them because they just don\'t last.
>
> The second primary area is then finding what is, in the jargon here in
> town, shields; that is finding ways of inactivating or neutralizing
> the agents in foods, in developing new technologies for putting an
> additional barrier up so that you protect them. It is also some
> security technologies, innovations in packaging. There are a number of
> innovations in packaging and inventory systems and forward and
> trace-back systems that are coming out that are very important in
> terms of how we would protect the product, some really innovative
> things like a hologram on the package that no longer is visible when
> you break the package in any way.
>
> A variety of these are important research areas, also. I might note,
> these are some areas that are nontraditional research areas for us but
> it certainly came to the fore.
>
> Then what I wanted to just highlight here is in-line sensors. There
> has been a lot of talk about these. You did see a prediction about how
> long it would take. For those of you who are not familiar with in-line
> sensors, they work really well in air. They work pretty good in water
> but when you start putting them in a liquid food, they tend to get
> really clogged up really fast.
>
> If you are looking at big chunks go by, they don\'t work hardly at
> all. So it is a great basic technology and we are really looking for
> advances in that, but the reality is right now, if we have a hundred
> different agents we are concerned about, we don\'t have a biosensor
> that you can put in line that could detect it and last more than about
> 30 seconds. So we are looking for this as an important area.
>
> Response and recovery; we are closely tying research here with our
> laboratory activities. Obviously, laboratory support is a critical
> element and something that we have been doing a lot of in terms of
> working with our field laboratories in the FERN in order to get this
> up and running.
>
> Rapid response research teams; what is a rapid response research team?
> I think the best example of a rapid response research team and the
> need for one is the fact that it is not just detecting the organism.
> Often, if it is a new agent, you have to solve a problem in a hurry. I
> guess the best example of being prepared is the recent SARS outbreak
> because that was critical not only identifying the epidemiology but
> identifying key laboratories that were able to do all of the basic
> research work in a matter of weeks and be able to solve an emerging
> health problem before it got out of hand.
>
> Another response and recovery; this is one that we really didn\'t
> think about until we were in for a while and said, okay; we are sort
> of getting ready. Now, what happens if it actually happened? What
> would we do? What do you do with a food company after it has had an
> incident?
>
> We had a lot of information\--we were gathering information about
> detection methods, et cetera, but we didn\'t have some of the basics
> like how do you clean up a plant afterwards. It is one thing\--sort of
> the old adage is be safe or throw it out when you start dealing with
> food.
>
> But you can\'t do that with a multimillion dollar food-processing
> plant. So one of the other areas we have been looking at is what do
> you do to assure people afterwards when you have had an incident that
> you have actually cleaned it up. Certain this, as Joe indicated, was a
> lesson we learned. We watched them try to clean up the office building
> next to us while we were still downtown and listened to the news and
> watched them try this and watched them try that until they finally got
> it. It took about six months.
>
> Then, finally, and I have held this off to the end because this is the
> area that everyone thinks about immediately is detection methods and
> detection technologies. Actually, this is broken up into several
> different components. I have subdivided them so you can see the
> different areas really when we talk about methods. We are looking for
> deployable rapid field test. It is critical, when you start dealing
> with literally hundreds of thousands of samples, you have to have a
> way of triaging samples so that you are able to get these looked at
> quickly, make tough decisions about which ones should go to the front
> of the lines, which ones shouldn\'t.
>
> We found that, even there, you have to have some real capability of
> doing a higher level of analysis in the lab again for triaging, doing
> the screening samples, so that you eliminate or put to the back end of
> the line the 90 percent of the samples that are negative and really
> focus in on getting those that you need to look at first.
>
> Laboratory-based confirmation tests; we need those\--as we start
> dealing with a wider and wider range of materials, we are looking for
> multianalyte analyses both on the chemical and microbiological side.
>
> We have learned a lot from the Bacillus anthracis case, the need to be
> able to go back and look at agents for attribution. So we have spent a
> great deal of time looking at microbiological forensics and chemical
> forensics so we can also say and help work with the FBI and other
> law-enforcement agencies to determine who did it. Really, that is part
> of the overall response.
>
> Technology transfer always is a challenge. It certainly is a challenge
> as we are starting to work with large networks out into the field
> where we are dealing with networks of 100, 150 laboratories. How do we
> transfer the technology out? How do we deal with issues about not all
> labs have the same equipment?
>
> We have transferring the technology when you are trying to keep
> certain aspects of your methods of analysis not widely distributed
> because the first lesson you learn is that if you tell someone exactly
> what you did in your method, that is the easiest way to give them a
> head start on figuring out how to get around it. I know, again, that
> is part of the thinking process that has changed.
>
> And then, finally, methods validation as we have developed these new
> methods, having a true comfort that when you put these out in the
> field that everyone will get the same result is something that we
> absolutely have to have. We also need to have a real understanding of
> the strength and weaknesses of all the methods and some idea of how
> they will perform.
>
> We work real hard in getting the false negatives associated with these
> method down to as close to zero as we can. There are often tradeoffs
> in terms of speed versus false positives. Certainly, when you are
> dealing with complex matrices like food, the number of false positives
> that you get tend to be fairly large. The problem here is that every
> time you get a false positive, it overwhelms the system. So a high
> percentage of false positives means that everyone of those has to be
> confirmed and you can just tie up the lab for weeks. So we are trying
> to get that false-positive rate down.
>
> So where are we and where are we trying to go? I am going to make a
> little pitch here for the unique aspects that we do in terms of FDA
> research is that there is a great deal when we talk about
> counter-terrorism or biological research or chemical research\--there
> is a great deal of basic research that is out there.
>
> There is a wealth of information coming out of a variety of agencies,
> academic centers, et cetera. But it is our job to take that and get
> across the gulf that exists to safe products, sound policies, and
> guidance. To do that, we focus here within FDA on what we refer to as
> FDA translational research. That is that bridge that takes us from
> really good sound ideas and getting it out to where it is actually
> useful.
>
> I just want to note this is a bridge. Under each bridge, you have a
> foundation that holds the bridge up. And, for us in CFSAN, it is an
> integrated research program that actually consists of three parts; our
> intramural program, which is a strong program that we can change on a
> dime if we have to; and extramural research program; and then a
> Centers of Excellence program. I am going to introduce each of these a
> little bit more as we go along.
>
> But, really, the bridge that we need to get to meet our mission is
> being able to take the good sound science that a lot of people are
> developing and translating it into something that is useful for the
> American consumer.
>
> I might note, we have had some help along the way. I want to thank the
> Commissioner and all those that have been involved in getting us the
> \$5 million supplemental this past year. It has certainly been
> something that has helped us get through the next lap. But I might
> note that \$5 million is only a small part of the assets that we have
> brought to bear.
>
> What really you need to consider and what we have done in the past few
> years is look at the fact that basically most of the resources we have
> brought to bear on this problem have been a redirection of existing
> resources. Within weeks of 9-11, we got all our scientists together,
> went through our initial thinking and, basically, redirected 30
> percent of our intramural research program and almost all of our
> extramural research program into this area as a critical need.
>
> Having that capability and having the willingness of our scientists to
> do it really said a lot, to me, about the quality of our research
> program.
>
> I might note that it was also the message that the Science Board gave
> us a few years earlier, this ability to respond quickly. I hope you
> see that, in this process, we listen to you.
>
> I also am up here introducing the Foods Research Program. While my
> primary focus is going to be on CFSAN\'s internal programs for the
> rest of talk, I do want to indicate, and I will introduce briefly, the
> fact that it is a multicomponent research program that involves
> multiple centers and multiple activities.
>
> These are the four major players in what we would consider the
> traditional Foods Program, though you will be hearing more about
> medical interventions, et cetera, later on. So, in addition to the
> research we are doing, the Center for Veterinary Medicine, and there
> will be a presentation later by them; the Office of Regulatory
> Affairs, and they are going to be giving a presentation on the Food
> Emergency Response Network; and also Dan Casciano will be presenting
> the activities for the National Center for Toxicological Research.
>
> Within the Center for Food Safety and Applied Nutrition, we do pretty
> much all four of those different activities, priority areas, I have
> outlined; methods development, agent characterization, intervention
> technologies and toxicity, pathogenicity, either directly or through
> our intramural-extramural activities.
>
> The basic line that I want to reinforce over and over again is that
> we, wherever possible, attempted to get an addition not only to our
> Food Security Program but an addition to our Food Safety Program.
>
> We have also tried, as much as possible, to leverage our activities
> and have been in contact with a variety of other research agencies,
> academic settings. We have worked closely with the academic community
> and our sister agencies that support research are probably tired of
> seeing us be we have been very successful in working with groups like
> NIH, CDC, USDA research agencies and also DOD.
>
> So let\'s, real quickly, just go through some of these activities
> again. I don\'t have time to go into individual projects and would be
> happy to give you details of any of those.
>
> I did want to talk and start off by indicating the response that we
> had has also been very positive in terms of when you consider some of
> the barriers that we had to overcome, particularly in the
> microbiological side, and on the chemical side also. The first thing
> we had to do is really go back and sort of go to school because, while
> we were aware of many of these agents, I can\'t say that many of us
> had worked with them in great detail during that time.
>
> So we had to learn to work with some of the nontraditional agents. We
> had to go through\--and we were under a mandate to upgrade our
> laboratory security. So, for example, not long after 9-11, if you were
> out to our Laurel, Maryland facility, it went from having a six-foot
> fence to having a fourteen-foot barbed-wire fence. Then we had to
> explain to the neighbors why there was now a fourteen-foot
> barbed-wired fence. Those are the little things you don\'t think about
> until you actually have to start doing them.
>
> We had to upgrade some critical instrumentation and we did get a lot
> of support in doing this in terms of upgrading both in our research
> labs and our field labs so that we had comparable instrumentation.
> That is how I learned how many different mass specs people want. They
> come in all kinds of flavors now and so I learned more about mass
> specs than I ever knew in a very short amount of time.
>
> Renovation of laboratories to perform at a BL-3 level. I have had
> experience with these. They are expensive. They are time consuming in
> getting up and running. This was, then, reinforced with the recent
> changes in the select agent registration. I might note that all of our
> laboratories that work with these agents are in the process of being
> registered. In fact, most of our labs have been approved for this work
> now.
>
> For those of you that are in that process, you know the millstone that
> you have to take to get that done. Our people have been really good
> about embracing these, understanding the critical nature of getting
> these approvals.
>
> I did want to just point out\--this is a picture of our Laurel,
> Maryland facility. This is where a lot of the microbiology work has
> been targeted. It was the first FDA lab to join the Laboratory
> Response Network. We have done a lot of work in terms of getting
> initial methods on the books, disseminating them through the LRN. We
> have done a lot of training of both the LRN and FERN members in
> analyzing for some of these agents and we have done a lot of work out
> there in evaluating some of the methods that are currently available.
>
> Probably they are really tired of hearing it from me, but, really, the
> mantra that we have had to keep it all in perspective is the word
> \"what can you do if it is tomorrow?\" That has really driven us, so
> we have taken a great deal of time trying to prioritize things so that
> we have something in place.
>
> It may not be the most elegant method. It may not be the most elegant
> technology. But we had to first get something in place for each of the
> critical areas that we had. I am feeling much more comfortable now
> because I can say that, based on our threat assessment, we are
> 99 percent of the way there in terms of we could do something. Now we
> are really focusing on doing it better, faster, cheaper, more of it
> per day, et cetera.
>
> One of the first things we did is not to rediscover the wheel. So the
> first thing we did is we got in touch with the military. We talked
> with the industry. We examined a variety of different sampling
> techniques, commercial facilities, to see what they had available and
> whether it would work in food.
>
> Where that didn\'t work, we started developing our own. We have had
> some real ground-breaking work based on some of our past strengths in
> molecular biology and microbial genetics to be able to develop some
> really enhanced forensic work. We have been cooperating and, as Joe
> said, all of a sudden, we have a whole bunch of new partners out
> there.
>
> We have been working very closely with the FBI, the CIA, DHS, DTRA,
> working with research partners that we have never worked with before.
> You did see a demonstration of some of the approaches that we are
> doing and being able to go back. We are not particularly focusing on
> anthrax on this. This is actually being done by another center that
> FBI is working with, but we are, in the area of enterics, really
> focusing on getting some really good forensics if we had to do
> attribution.
>
> We have talked about biosensors. This is one of the biosensors that
> our people are working in collaboration with Cornell on. The question
> about, do they work. This works really well in water. When you start
> putting milk through it, and you have a lot of bacteria in it, you get
> enough nonselective binding that it tends to foul after a while. But
> these are all things that are solvable. They just take some time.
>
> So one of reasons that, in 2007, we are still in the orange. We think
> that getting this to work for a variety of foods is going to be a
> pretty tough developmental problem.
>
> We have also been working with CDC and the LRN to try and do enough
> validation work in order to be able to make some recommendations on
> how we change our analyses. For any of you that are familiar with
> Clostridium botulinum toxin, the current standard for doing this is a
> mouse assay. That basically involves using thirty mice at a time to do
> an analysis.
>
> At 100,000 samples per day, there are not enough mice in this country
> in order to do the analyses that would have to be done. Second, I
> don\'t know if even NCTR couldn\'t handle\--you have enough? Okay. Is
> that a promise? So we have been working very closely with CDC to come
> up with an alternate algorithm on how to approach bot.
>
> This is one that we have been working with them. It is actually going
> through internal approval at the LRN. We feel now, with an ELISA that
> was developed one of the ORA researchers, that we are in a shape now
> that we could, for a terrorism event, actually go through and do most
> of the screening on an ELISA and then actually go into a mouse assay
> only for confirmation. This would drastically cut down the number of
> mice that we need so that certainly NCTR could handle it then.
>
> We have a similar level of activity on chemical methods. I might note
> that the basic testing strategy is again we don\'t know exactly what
> is in the agent. We can maybe reduce it down a bit based on the
> symptoms, but we are looking at two-stage, a nonlaboratory rapid
> screening that we can do and we have seen a lot of\--we have evaluated
> a number of ELISA techniques, lateral-flow devices, certain paper
> chromatography techniques that show a great deal of promise for
> triaging the samples.
>
> Then, ultimately, you do need to have a system of confirming them.
> These are laboratory-based and we now have a system that we are quite
> impressed with where we can look at about 300 toxic chemicals at a
> shot. The ultimate goal is to be able to screen for about 3,000 in a
> single pass.
>
> Now, it is not the most rapid way of doing things but it is one that
> we have a great deal of confidence in. But we are looking for
> improvements.
>
> Now, I might note, this is an extremely good interaction between the
> research scientists in CFSAN and our scientists in ORA in our forensic
> chemistry lab that have a lot of practical experience in actually
> investigating criminal activities. Between the two, we are working
> closely together to then get these methods out to our field
> laboratories and to members of the Food Emergency Response Network.
>
> We also, within our mission, are considering radionuclides and what
> would happen if they were introduced into a food. We do have a small
> research program in that that we are able to fund. This is taking
> place up at our Winchester Engineering and Analytical lab up in
> Massachusetts. This is one of the projects that we were able to fund
> with the \$5 million supplemental that we got.
>
> You will be hearing from CVM about their Animal Feed Safety Program. I
> am just mentioning this briefly as an introduction. I might note that
> they have an extremely good facility on food safety. Basically, they
> can manufacture, I gather, any feed that they want in small scale. So
> they have a really great facility out there to take a look at that.
> You will be hearing more about that shortly.
>
> You will be hearing more from Carl Sciacchitano on the laboratory
> response network and the food emergency response network, our ability
> to respond in terms of an emergency and some of the activities that
> need to take place in getting that ready, particularly in the area of
> methods validation.
>
> I did want to take a moment to talk and introduce the Centers of
> Excellence concept that we work on. This is basically where we have
> attempted to set up research initiatives between industry, academia
> and FDA. CFSAN currently has three of them, one with our National
> Center for Food Safety and Technology at Summit, Illinois, in
> conjunction with the Illinois Institute of Technology; our JIFSAN
> consortium which is here at the University of Maryland and then the
> National Center for Natural Products Research which is in Oxford,
> Mississippi.
>
> Each of those are a very active research component and this has been a
> model that we like where we house FDA scientists on a university
> campus and have them work on joint research programs of mutual
> interest.
>
> In terms of our CT activity, most of this activity has been out at our
> National Center for Food Safety and Technology. This center
> specializes in food processing and food engineering and food safety in
> conjunction with that and they have some unique facilities Dave
> Armstrong will talk about.
>
> Certainly, we have focused a lot of our work on finding mitigation
> strategies at the processing level there and he will talking about
> some of these projects. Also, we will be telling you about the new
> BL-3-level pilot plant that we are building out there, a very unique
> facility. It is basically that you could run a food factory with a
> BL-3 environment.
>
> Our extramural research program is a small but active component of our
> activities. It just reflects the fact, and we fully are cognizant of
> it, is the problems that we are facing in this research area are just
> too big and too important to try and do alone. We have used our
> extramural research program to get unique capabilities, unique
> expertise and unique facilities.
>
> We have been able to fund some very specific ones. These are five of
> the ones that came out of the \$5 million supplemental augmentation of
> our own internal funding and funding from ORA on extramural programs.
> You can see from the title some of the key areas that we are looking
> at. This one was specifically targeted on detection methodologies.
>
> We have also worked, as I said, strongly with several of our sister
> agencies. We have been working closely with NIH in looking for means
> for neutralizing certain pathogenic microorganisms and biologically
> derived toxins. We have worked with DOD trying to set up some research
> programs looking at dose response relationships for nontraditional
> agents. We have worked with several research institutes on, for
> example, enrichment techniques for some of the more nontraditional
> organisms.
>
> We have been able to leverage quite well and work closely with our
> research partners in a variety of agencies again with partners that,
> if you would have asked us two years ago, we weren\'t even sure that
> they existed. Now we work very closely with them.
>
> So what is the future? At least for CFSAN, it is to continue to
> address in a systematic manner the priority agent commodity
> combinations that have been derived from our vulnerability
> assessments. We will continue to focus on those first working our way
> down them until we basically get everything in the green.
>
> We will continue to be looking at these four areas as our four primary
> research needs, addressing each of them and we will continue to seek
> additional resources to accelerate this process, overcoming\--looking
> for new opportunities to get the work done faster and more
> efficiently.
>
> But the big key here, and I had to end with my race-car theme, is that
> we are looking to keep focused on the goal to make sure that we do
> cross the finish line in our goal to protect the consumer from
> terrorism via the food supply by keeping ourselves focused on the key
> translational research that FDA is most uniquely set up to do and has
> to do because, in many cases, no one else will, to assure that the
> nation\'s food supply is not only safe from accidental contamination
> but also safe from intentional harm.
>
> With that, thank you, and if I can answer any questions on specifics.
>
> DR. DOYLE: Okay. We can take a few minutes if anyone has any questions
> or comments. Yes; Dr. Nerem.
>
> DR. NEREM: Bob, you indicated earlier in your talk that, within a few
> weeks, not only was there a redirection of your intramural program but
> most of your extramural research program. I am just curious. My
> experience with extramural research programs is they are at least
> funded for a year or whatever. How did you so rapidly redirect that
> effort?
>
> DR. BUCHANAN: We didn\'t just throw everyone that we had a research
> agreement with out the window. But what we did, and, in part, we got
> lucky on the timing because it was early in our extramural-project
> cycle that we were basically able to say, here is what our priorities
> were last year. Here is what our priorities would have been if there
> hadn\'t been a change. Throw those out the window. Here are our new
> priorities. The timing was great because it was right in the early
> phase of us writing up the next RFA.
>
> So we threw those out, started over, went through a quick evaluation
> of what our internal capability was, looked where we had some gaps and
> then really focused on those areas where the extramural\--you can do
> this if this is a way of life where you have a lot of emergencies, you
> can stagger your extramural program so that you are always turning a
> certain number over. You can do it, like, twice a year.
>
> That gets to be a little tough administratively. But, in many ways, we
> have a lot of flexibility with our extramural program because we can
> change it from year to year. Even though, once we have made a
> commitment, we usually make a commitment for three years. We don\'t
> have everything and starting at the same time so it is always
> overlapping.
>
> Does that help?
>
> DR. NEREM: Yes. I guess coming from a university perspective, many
> times these extramural programs may have students doing thesis
> research on them.
>
> DR. BUCHANAN: When I say \"turn it over,\" we redirect the new money
> or the money that has not always committed. We are very realistic
> about you can\'t go back into a program and just cancel it partway
> through because it is a poor investment that way.
>
> DR. DOYLE: Dr. Laurencin?
>
> DR. LAURENCIN: Very nice talk. I have questions about your
> organization\'s priorities in terms of packaging, both in terms of,
> one, for instance, certain polymer-based packages may secrete
> catalysts or other materials into the food. Is there any analysis that
> is done in terms of the packaging that is used?
>
> The second is just in terms of protection from tampering or changes in
> the packages from the time it goes out from the supplier to market and
> how do you detect changes either by purposeful or nonpurposeful
> changes that take place in the packages?
>
> DR. BUCHANAN: Let me start off first by saying that the approval of a
> new packaging material\--packaging materials are considered food
> additives, anything that would leach out of them. There is a whole
> part of our agency that deals with it through our premarket approval.
> They are referred to, I guess, as indirect food additives.
>
> If we need more detail on that, I would be happy to get you in contact
> with those that would give you the specific details of what are the
> premarket requirements before something is approved.
>
> In terms of our counter-terrorism research and the importance of
> packaging, there we are primarily focused now not so much on the
> package being the vehicle for the agent, while it theoretically could,
> because the amount that diffuses into the food is so small. It is not
> likely that you could get a high enough concentration of a chemical
> toxin into the food to really cause much damage.
>
> Potentially, it could be used for microbiological means. But the way
> most of these films are manufactured and used in the plant, that is
> not one of those real likely scenarios.
>
> What would be more important here is having active packaging that
> allows you to detect when the package has been tampered with or the
> product has been counterfeited. It is the same kind of thing, is there
> something that you can put on the package like there is on the new
> twenty-dollar bill that lets you know that that was a product that
> actually came from the manufacturer and not somebody else that had
> taken it, did something with it and then repackaged it. So that is a
> very active area and that is where most of our interest is in research
> is these new package security systems.
>
> DR. DOYLE: Answer your question? Okay.
>
> Dr. Thomas?
>
> DR. THOMAS: I had a question with respect to your methods detection
> and development. You referred to on-line or in-line sensors. Are some
> of these compounds then programmed to go into a high-throughput type
> of assay? Is there going to be a continuity there or haven\'t you
> reached that point yet?
>
> DR. BUCHANAN: We are looking at a couple of different systems. There
> are some systems that are set up that periodically take a discrete
> sample, and take a look at them. In some ways, those are easier
> because you can actually put a wash step in to clean the sensor off.
>
> The ideal one is to have a high throughput where the sensor actually
> is inserted in the product line. This is particularly amenable to
> liquid products, milk or juices, et cetera, where you would actually
> be detecting on a continuing basis the analysis. The problem here is
> that those, because you don\'t have a clean step, they tend to
> accumulate food or nonspecific bacteria or other agents. The useful
> life of those has been a problem.
>
> So ideally what you would have is a sensor that stuck in that could
> detect a thousand different agents on a real-time basis and identify
> those. Certainly, one of the areas that we have been looking at is
> some of the IR technologies to at least tell you something has changed
> even if you don\'t know what the agent is.
>
> DR. DOYLE: We will take one more question and then we are going to
> have time at the end of all the morning presentations to have a
> general discussion.
>
> Dr. Rosenberg?
>
> DR. ROSENBERG: You mentioned industrial collaborations. Could you just
> kind of comment and expand a little further about how you go about
> identifying those, how do you put them place. What are the mechanisms
> that you guys use for setting up industrial interactions?
>
> DR. BUCHANAN: We have several, some of them as simple as putting
> contracts out in terms of research contractors. Martin, can I hold you
> off because I think when David gets up and talks about the Moffitt
> Consortium, that would be probably the best way of doing it because
> that was a Center of Excellence that was specifically set up to do
> that. I think he can articulate some of the lessons that have been
> learned on that.
>
> DR. DOYLE: That is a good lead-in then to our next speaker who is Dr.
> David Armstrong. Dr. Armstrong is the Associate Research Director at
> the National Center for Food Safety and Technology at Summit Argo
> which is part of the CFSAN program. Dr. Armstrong is going to share
> with us some of the research that is being done to prevent food
> contamination, intentional food contamination.
>
> **Prevention Research**
>
> DR. ARMSTRONG: Thank you, Mike. I just want to thank the Board for
> having the opportunity to talk about our research program out in
> Chicago. We don\'t often get a chance to get this kind of a public
> viewing and airing. So I appreciate the opportunity.
>
> Maybe I can start out by saying that we have a collaborative center
> that addresses food processing and packaging. If I can go back a
> minute and answer a previous question on packaging, we do have some
> non-CT projects that address in-line sensing on packaging. One of our
> projects, I can go into this in more detail with you a little later,
> is on ultrasonic detection.
>
> Another one we are just looking at now is looking at imaging to detect
> pinholes in packaging. One of the problems with these on-line sensing
> capabilities is that they are too slow. Line speeds in industry run so
> fast that you can barely see the can or whatever it is go by. So these
> things just operate to slowly many times. If you can route them off at
> certain times and use your detection method, then they work fine. So
> this is one of the issues that we are working with.
>
> I just want to go back. I feel like the entire speakers this morning
> have been preparing for me so I thank you all very much. Look at the
> strategies for critical infrastructures and we fit into, actually, the
> preparedness bullet that Mr. Levitt showed a little earlier. I don\'t
> know if you noticed or not but there were a couple of red bars there,
> so I think this scenario we need to work on.
>
> Also, in FDA\'s overall food-security strategy, we are really looking
> at the bullet, and I think we are unique here, in developing the
> effective protection strategies to shield the food supply. This, to
> me, is an incredibly important area, an area that needs a lot of
> attention.
>
> As Dr. Buchanan said, we are one of the Centers of Excellence for FDA.
> We are the Center of Excellence where the rubber meets the road, so to
> speak. We are not so basic out in Chicago but, boy, when it gets down
> to the nitty-gritty, we are right there. So we are one of these
> bridges and I would like to think we are one of the bridges to the
> real world and reality.
>
> The food-security research needs; we really need to know how these new
> or unusual agents behave in foods. There are a number of
> characteristics of foods and things that are done to foods that can
> determine their survivability. We really need to look at this in terms
> of these new CT agents.
>
> We are looking at specifically, at the National Center, inactivation
> and neutralization technologies. We are really interested in what is
> the effect of the food process on these new or added agents. Can we
> expect to get some protection? Actually dealing with microorganisms
> and toxins in foods is not new for this industry. We inactivate toxins
> and deal with pathogens all the time in this industry.
>
> True, these are new ones that might be introduced but this is not a
> new subject and certainly we have been working on food security for
> the history of the food industry, basically.
>
> Again, in our ten-point program for food security, with our interface
> with the industry, we are in a good position to suggest kinds of
> prevention measures that might be effective. So we have a unique
> position here.
>
> Let me talk a minute about these collaborative centers that Bob is
> talking about. The National Center is actually a consortium of
> government, academia and industry. We were initially focused on food
> safety. Now we are food safety and security. We have a research
> facility there for cooperative research in new processing and
> packaging technologies, modification of traditional technologies.
>
> We have had a long history and a lot of involvement in HACCP controls.
> We always have been looking at interventions in terms of what we can
> do to make the foods safer. At the National Center, we have been
> looking at new technologies, specifically, that might improve the
> safety of the foods. So we are in a good position to start working on
> CT types of research.
>
> We are also a source of training, education and information and
> programs on food safety and security. We provide a neutral forum.
> Sometimes, you can discuss issues in a research setting that you
> couldn\'t discuss with industry so easily or with other elements so
> easily in another setting. So we are a forum where food safety and
> security issues can be discussed.
>
> Why did we need a cooperative food-security consortium? In particular,
> FDA needs access to a pilot plan. We need to now about food
> processing. Our mission is unique in some ways in this way. We need to
> have access to specialized laboratories. We need a specialized
> laboratory for pathogen and packaging research, a BSL-3 laboratory.
>
> We need to have access to expertise that only research in this area
> can generate. In the case of public-health emergencies, we need to be
> able to provide facilities and equipment. And we also serve as a
> training facility for FDA states and other in the public-health arena.
>
> Our objective are to be able to address key public-health issues,
> establish scientific competencies, keep dialogues going with industry
> and academia, transfer our technology to others in the consumer-safety
> area and provide research support during emergencies. So we intend to
> foster a scientific exchange with the scientific community and we have
> done that pretty successfully, I think, for the past fifteen years.
>
> Our current collaborative research program deals with high-priority
> food safety and security research. We arrive at this program
> collectively with FDA, industry and academic input. We focus on
> intervention and prevention strategies. Now we are focusing on CT and
> BSL-3 pilot-plant research and looking at new technologies in the
> process and packaging arena.
>
> Since many of you probably will never get a chance to visit our
> facility, I took the liberty of including a few pictures here just to
> show you what our pilot plants look like, a lot of equipment that
> wouldn\'t fit into a traditional laboratory setting very well. We have
> the capability of manufacturing, on a very small scale, many kinds of
> food products there. Indeed, we do some prototype food products and
> specialized technologies.
>
> High-pressure technology has been one of the areas that we have been
> conducting a lot of research in. This is very high-pressure
> technology, by the way, going up to 100,000 psi to inactivate
> microorganisms. Our programs really directly affect FDA programs. We
> can start with the food-safety issue, have workshops or symposia,
> generate research, get industry interaction going. This eventually
> evolves into a knowledge base which may go on to provide for policy
> guidance regulations.
>
> These should be two-way arrows; in other words, we can also go
> backwards on this chart and go from guidance back into a research-type
> situation where more knowledge is needed.
>
> The participants in our consortium are FDA, the Illinois Institute of
> Technology, University of Illinois. We now have a partner in the State
> of Illinois and we are unique in that we have industry memberships.
> How we go about getting these industry memberships is through joint
> interests, joint interests where we perceive we have a need and they
> have a need. We try to get a dialogue going and generate a mutual
> interest which goes along with a mutual program.
>
> So I hope that is not too short an answer, but we have a process of
> selecting research which focuses on trying to fish out what industry
> and academia are interested in as well. We use this as a basis for
> establishing a dialogue. It is a pretty effective basis, I might say,
> because we seem to be on cutting-edge issues out there at our center
> all the time.
>
> Now I am going to talk about our shift to preventative research at the
> National Center. We were, as Bob mentioned, in a good position to
> change some of our research focus to address some of these new agents
> that might be introduced to our foods.
>
> I wanted to talk a little bit about the ongoing research that we have
> there first.
>
> We have three ongoing projects. One is on the survival and growth of
> nontraditional pathogens in foods. As we mentioned before, there is
> really not much of a knowledge base on some of these pathogens and
> their behavior in foods. There are a lot of things that are going on
> in foods that may inactivate or neutralize these things. We need to
> know about these.
>
> The second project is on the thermal resistance of microbial agents
> that might be associated with bioterrorism. There we not only have the
> technical capability but the practical capability of checking the
> thermal resistance in common food-processing techniques such as
> pasteurization or extrusion of some of the other unit processes that
> might be used in the food environment or food setting.
>
> We really need to know how some of our traditional food processing
> would affect these agents. This is going to help us greatly in our
> ability to assess what might be the impact of introduction of these.
>
> Thirdly, we have a project on the evaluation of ELISA assays to detect
> botulinal toxins in foods, C. bot toxin in foods. It is not too
> difficult to make an ELISA kit commercially but how these kits react
> with foods is another story and what the meaning of the results is is
> also of interest. Just because you may get a reaction, you may not
> have activity. So we need to determine if ELISA-kit activity
> translates to biological activity.
>
> We need to know what the impact of the food and the impact of the
> process is on this assay. So it is a much more complex situation than
> one might think at the outset.
>
> Just to into a few details on some of our projects. On the survival
> and growth of nontraditional pathogens in foods, we have been working
> with agents that do not require a license. Until we can get a select
> agent license for some of these things, we need to work with agents or
> organisms which are surrogates. Our objective is to determine if the
> agent that might be introduced will survive, grow or maybe die off in
> the event that they are added.
>
> We have very little data, really, on how some of these agents might
> behave in foods. The benefits would be that we could probably help
> answer the where and when in a case investigation. We really need this
> information to make risk-management types of decisions within the
> agency.
>
> We are finding that some of these agents might, indeed, be poor
> growers in nutrient-limited foods and we are also finding what is good
> news that some of the virulence agents that might contain virulence
> genes die off much more quickly. So that is about all I can tell you
> about our results until they are declassified, I guess I should say.
>
> We plan on continuing this work and eventually going into more select
> agents in this area; that is, agents where we can get appropriate
> license. We are going to look at other shelf-stable foods, things like
> infant formula, juices, sports drinks, et cetera.
>
> The second project we are looking at is the thermal resistance of
> nontraditional microbial agents such as C. bot toxin\--this certainly
> won\'t be the only thing we look at but this is one that we can talk
> about\--and look at, perhaps, a combination of the effects of heat
> versus pH salt and a number of other parameters in the foods.
>
> Again, we have very little data on how, say, something like C. bot
> toxin might behave and react as it goes through food-processing kinds
> of operations. This, again, would be used in risk-management
> decisions.
>
> A third area, actually, this was a natural because we actually had
> started this as a collaborative project before the CT era hit. So we
> are looking at these ELISA assays and can they detect botulinotoxin in
> foods. We have investigated food additives that might interfere with
> ELISA performance and we are also going to be a part of the Liberty
> Shield operation that goes on.
>
> In terms of new research, we are just starting. We want to look at the
> effect of thermal and shear food process that might inactivate protein
> toxins and also, then, sort of then jointly with this project, looking
> at the decontamination of food-processing facilities and equipment. As
> Bob said, if there is an incident, it is not likely that you are going
> to bury the food plant along with the food. The food plant is going to
> continue to sit there. We may sterilize the food and landfill it, but
> we are certainly going to have to do something with that equipment.
>
> Looking at the first project, effective thermal or shear in food
> processing, we know that many proteins can be denatured by mechanical
> action. As an example, I would use egg white, whipping of eggs to make
> a foam. Food processes such as extrusion, foaming, homogenization
> where you have very high shear conditions, may inactivate or at least
> partially inactivate these toxins. We are going to look at
> combinations of processes.
>
> Toxins such as C. bot toxin, ricin or fungal toxins or others might be
> investigated depending on where our risk analysis takes us. In all
> cases, we are going to attempt to correlate our biochemical assays
> whatever they are with actual loss of biological activity. We realize,
> from our past food knowledge, that, particularly on our projects with
> allergens, we have to look at the behavior of these ELISA test kits
> and how valid they are in terms of allergenicity and actual biological
> activity.
>
> We are not going to lose sight of this in our processing studies. We
> know, for example, that if you take C. bot toxin as an example, the
> toxin is still there after you process it. You have just inactivated
> it if you thermally treat it. So we are aware of this and we want to
> make sure that we are actually following biological activity. That is
> for the biochemists in the crowd.
>
> The second project I want to talk just briefly about is the
> decontamination of food-processing facilities and equipment. This
> would aid a rapid recovery after a bioterrorism incident. We know the
> food would be discarded, but the facilities and equipment would not be
> and something would have to be done with them.
>
> We need to know if the currently used food-sanitation techniques are
> effective. Again, sanitation is not anything new in the food industry.
> We battle pathogens every day but some of these are new kids on the
> block. We need to know how currently used sanitizers would work in
> this arena.
>
> This project will be coordinated with our previous project. While we
> are investigating the effects of our processing on these agents, we
> can also look at decontamination of the equipment.
>
> I wanted to talk a little bit about the build-out of our BSL-3 pilot
> plant and laboratory. In order to conduct pilot-plant-related research
> on these agents, we are going to have to have some unique
> capabilities; that is, we are going to have a BSL-3 pilot plant and we
> are going to have to meet the select agent requirements of the Patriot
> Act.
>
> There are BSL-3 laboratories around the country but I don\'t know of
> too many BSL-3 pilot plants and I don\'t know of any that are BSL-3
> and meet Patriot Act requirements. So we have got our work cut out for
> us. We would like to be able to readily transfer select agents between
> the pilot plant and laboratory that we have and we realize that we are
> going to have much more stringent personal protection measures than we
> have been used to.
>
> As Bob showed, this is a schematic of a pilot-plant and laboratory
> design that we have been working on. One of the things that we have
> evolved from sort of our design research that we have been doing on
> the pilot plant is that we need to have an equipment decontamination
> chamber or possibly we could move equipment in and out of the pilot
> plant without fully decontaminating the pilot plan.
>
> A full decontamination of any facility is really a chore and requires
> a lot of verification and validation. If we could move in enough
> equipment, that would aid our research a great deal. Also, we need
> pretty effective personnel decontamination means and we need to
> accomplish all of the safety and security requirements that go along
> with a facility like this.
>
> As I said, this BSL-3 pilot plant will have restrictions particularly
> in handling select agents. So we have to meet all the requirements of
> the Select Agent Act.
>
> This shows some of our old I will call it BSL-2, BSL-3, pilot-plant
> activity that we have done in the past. Here we are making cheese that
> is inoculated with a pathogen. The personal-protection measures that
> we will have to accomplish with this new facility are even greater
> than this. We will probably have to go to bubble suits that are
> self-contained, so this is going to be a challenge.
>
> The kind of equipment we might be using in our pilot plant is shown
> here. This laboratory food extruder on wheels we may be able to wheel
> in and wheel out and investigate food processes.
>
> Some of the other equipment potentially put in our pilot-plant
> facility.
>
> I just want to end with some of the hurdles that we are facing with CT
> research. We know we have to do, and we are involved in doing, a lot
> of security upgrades, as Bob mentioned. We have a lot of laboratory
> upgrades we need to do. We have more requirements in terms of select
> agents. We are getting a number of security audits from other agencies
> now. Here we are, FDA being inspected by other agencies.
>
> We have personal background checks that we have to deal with. Finally,
> in terms of collaboration, we are getting a mixed industry response.
> Some of our industry is just not that interested, apparently, in the
> kinds of CT work that we are doing. So I think we will continue to try
> to convince them that what we are doing is going to apply to food
> safety ultimately as well, and we are trying to bridge between food
> safety and food security such that we can apply the things that we
> learn in food security to food safety. So I don\'t see it as an
> isolated effort.
>
> So, with that I will stop and ask if there are questions.
>
> DR. DOYLE: Very good. Thank you. Do we have a pressing question or
> comment? Dr. Nerem?
>
> DR. NEREM: Just curious. You talked earlier in terms of participants,
> industry members. And then, at the end, you talk about industry
> collaborations. Is there formal industry membership in the Center?
>
> DR. ARMSTRONG: Yes.
>
> DR. NEREM: Do they pay annual dues?
>
> DR. ARMSTRONG: Yes; they do.
>
> DR. NEREM: What is the nature of the relationship?
>
> DR. ARMSTRONG: Yes; there is industry membership and they do pay what
> we call membership dues. We have several levels depending on\--I
> don\'t want to go into our sales program but we have several levels of
> industry membership depending on their interest.
>
> DR. NEREM: In addition to the membership fee, do they provide other
> financial support for research?
>
> DR. ARMSTRONG: Yes.
>
> DR. NEREM: Or is it in-kind?
>
> DR. ARMSTRONG: Yes, yes. For example, we have a high-pressure unit
> there. I think to buy one would be in the neighborhood of \$1 million.
> That was donated so that we could conduct\--in fact much of the
> equipment that you see out there has been donated. So, yes; this is a
> very natural place to do industry collaboration. Industry is
> interested in where the rubber meets the road as well and they are
> interested in the process aspects.
>
> DR. NEREM: Do they get any intellectual property rights?
>
> DR. ARMSTRONG: It depends on how the project is structured. I can be
> structured such that they can do\--with IIT, not with FDA, even
> proprietary work. But they can sign agreements amongst themselves and
> do multiclient non-FDA-involved research. So yes; there are a number
> of avenues whereby they can investigate things there as well.
>
> It makes a lot of sense to share the costs of bioplants. They are very
> expensive things to own and operate.
>
> DR. DOYLE: Good enough. Thank you, Dr. Armstrong.
>
> Next, we are going to hear from Dr. Daniel Casciano who is the
> Director of the National Center for Toxicological Research at the FDA
> facility in Arkansas. Dr. Casciano is going to address food-security
> research at the Center.
>
> **Food Security Research**
>
> **at the National Center for Toxicological Research**
>
> DR. CASCIANO: Thanks very much. I would like to thank Joe and Bob for
> inviting me to participate today in this great discussion on
> food-security efforts at the FDA.
>
> I thought, though, that prior to directing my attention to the
> food-security research at the NCTR, I would present you with a little
> bit of information who we are. The last time that I addressed the
> Science Board it was during the Kessler administration so it has been
> about five or six years. So I thought I would just put in a couple of
> commercial slides for the NCTR here.
>
> This is an aerial photograph of the NCTR. I was hoping that John
> Taylor would be here so that he could see the new addition to our
> campus. This is the Arkansas Regional Laboratory here. This was
> dedicated a couple of years ago and it is collocated with us at the
> ORA, the Office of Regulatory Affairs. The Southwest Region has their
> chemists and microbiologists in this particular group. We have started
> collaborating with them to a high degree.
>
> This campus is now called the Jefferson Labs of Arkansas. That
> includes both the ORA and the NCTR.
>
> Our mission here is described on this slide. It is to conduct
> peer-reviewed scientific research that supports and anticipates the
> FDA\'s current and future regulatory needs. So we have the luxury, we
> feel, at our institute, to do some long-term thinking that our
> colleagues in the regulatory centers don\'t have that particular
> luxury. So we feel quite gratified that we are able to interact with
> our regulatory scientist colleagues and participate in development of
> both translational needs and applied needs of the agency.
>
> This slide gives you some idea of our organization and the various
> \"ology\" groups that we have. We have a biochemical toxicology. We
> have a very good statistical group, biometry and risk assessment, that
> also houses our toxicoinformatic group. Chemistry is state of the art.
> This group houses our new proteomic and metabonomic activities.
>
> As mentioned earlier, we do a lot of rodent research and testing so we
> need an excellent veterinary-science group which we do have. We have
> an internationally recognized molecular epidemiology group and a
> well-established neurotox group. Our microbiology group has two
> functions. They have a diagnostic and surveillance function as well as
> a research function.
>
> It is the microbiology group and the chemistry group that are
> participating in our food-security research directed to agency needs.
> Our last division is genetic and reproductive tox. This group houses
> our core microarray facility.
>
> Two years ago, we instituted several Centers of Excellence which
> include our Functional Genomics Center which is our core DNA
> microarray group that supports all of the hypothesis testing at the
> NCTR that utilizes these tools. And we have a Structural Genomics
> Center that is associated with our molecular epidemiology group that
> is interested in polynucleotide, single nucleotide polymorphisms in
> the human population and they are directing their efforts toward
> understanding susceptibility of the population to various cancers.
>
> Our ToxicoInformatics Center houses our bioinformatics group. We have
> a strong bioinformatics group that supports the genomics, the
> proteomics and the metabonomics efforts. We were quite fortunate in
> recruiting several highly skilled and practiced individuals in the
> specific area. This is the glue that allows us to interpret the reams
> of information and data that are developed though these processes.
>
> This group recently developed a database, data-mining tool, that is
> available to all of the FDA. It is called the Array Track. If anybody
> is interested in obtaining that for their microarray analysis, they
> can contact me and I will make sure they get it.
>
> As a response to adverse events, we have developed an Hepatotoxicity
> Center. Several years ago, we developed the Phototox Center in
> collaboration with the NIEHS through the National Toxicology Program.
> This group supports needs, primarily needs of CFSAN in their cosmetic
> efforts and NIH compounds that have been developed through the
> National Toxicity Program. We are utilizing that system to a variety
> of dietary-supplement work as well in collaboration with CFSAN.
>
> So the outline of my talk is I am going to give you a brief
> description of our BSL-3 laboratory. As all of you know, after 9-11,
> there was a paucity of BSL-3 facilities that were available to help in
> terms of catastrophic events. So the NCTR was provided funds to
> renovate a laboratory to maintain that kind of action.
>
> I will tell you about the work that has been going on for several
> years. In the Microbiology Division, we view the counter-terrorism
> effort as the flip side of the Food Safety Initiative efforts that
> have been ongoing for several years at the NCTR and tell you some of
> their DNA-based tools that they have been developing for detection
> methodology.
>
> Recently, we have decided to direct some of our activities to develop
> proteomic tools which will allow us to speciate bacteria and also
> support other activities at the NCTR. This effort is located in the
> Division of Chemistry.
>
> So the BSL-3 lab, the update on this facility, the contract has been
> awarded and we expect a completion date of summer of 2004. We are
> renovating a laboratory that was a BSL-3 lab about fifteen years ago
> and it was not maintained. We are renovating that space to now include
> seven suites for research and testing of a variety of select agents.
> It is in this specific area that we collaborate with our on-sight
> colleagues in the Arkansas Regional Lab that are associated with ORA.
> Hopefully, we are interdigitating with them. They are participating in
> not only the testing part of our activities but also in helping us
> develop research methodologies.
>
> Another occurrence that we have utilized, the supplemental dollars
> that we received through the counter-terrorism effort, we purchased
> individual ventilated cages to house rodent-model systems. These are
> very useful adjuncts to our efforts. We can utilize these systems in
> BSL-2 laboratories as well as in BSL-3 and these systems will house
> rats and mice, and we are now beginning an effort with Cryptosporidium
> parvum that is a collaboration with the EPA and our first experiments
> using these cages.
>
> So now I am going to switch to the Microbiology Division and then I
> will tell you something about the efforts that are going on in the
> Chemistry Division. Our microbiology group has been quite active in
> the food-security and counter-terrorism effort for the last five or
> six years.
>
> The next two slides are titles of projects that are ongoing in their
> group at the NCTR. The first one is the development of a microarray
> chip for the detection of multiple antibiotic-resistance markers. This
> activity was derived early on in a collaboration with the Center for
> Veterinary Medicine.
>
> We and they were concerned about antimicrobial research in poultry
> populations. Northwest Arkansas, I think, is a capital for production
> of poultry. That is where Tysons is located. We have been allowed to
> go to certain of the farms up there to obtain excreta from the
> poultry, both chicken and turkey, to attempt to isolate bacteria that
> are resistance to the antibiotics that they are given.
>
> A second protocol that is being developed are novel molecular
> approaches for detection and analysis of the most populous bacteria
> species in the human gastrointestinal tract. Carl Cerniglia, who is
> the Division Director in microbiology has been interested in human
> gastrointestinal microflora for many years. He and his group has
> developed an in vitro system where they can identify the bacterial
> population in that in vitro culture system as well as understand
> perturbations as a function of exposure to either antibiotics or
> dietary supplements or whatever.
>
> CVM has had a great interest and we have got a collaboration with them
> on the study of mechanisms of fluoroquinolone resistance in Salmonella
> species that have occurred both in animal feeds as well as in excreta.
>
> There has been a recent use of competitive-exclusion products and
> probiotic products. We have developed systems that will help us
> understand the nature of those products and the relationship that the
> products would have with the host. We have developed in vitro models
> and in vivo models.
>
> There has been a real concern about vancomycin resistance in these
> poultry samples. We have developed molecular-screening methods for
> determining that resistance and in vitro assays for perturbation of
> colonization resistance by antibiotic residues, et cetera.
>
> We have a large study going on this, studies for fluoroquinolone
> resistance in Campylobacter species, especially those isolated from
> turkey. Evidently, there are those species that are associated with
> turkey that are not very well characterized and the group in
> microbiology are expending quite a bit of effort in doing that. They
> also have a collaboration with the Chemistry Division which I will get
> into later on in the talk.
>
> As I mentioned earlier, the division has two responsibilities, one of
> making sure that the animals that we raise and use for GLP tests are
> pathogen free. So they have tremendous expertise and experience in
> diagnostics of a variety of animal pathogens. So we utilize several
> techniques that are depicted on this slide and they range from
> biochemical techniques to molecular biological techniques.
>
> The relevance of this group to safety and security issues are depicted
> on this slide. They have a tremendous amount of experience and
> expertise in diagnostic, in microbiology and microbial identification
> and experience and expertise in the use of automated systems for
> identification of these species. They have expertise and experience in
> BSL-3 laboratory functions and operations which is very important for
> when our dedicated facilities come on line.
>
> The reason why I included this slide is that these individuals who are
> not at presented dedicated to the counter-terrorism efforts are
> available in case a catastrophe occurs and we can redirect these
> individuals who have expertise to provide us with the necessary
> support.
>
> Some of the research methods that are used in the Microbiology
> Division are depicted on this slide. They range from somewhat simple
> tests like disk diffusion and somewhat now considered traditional
> molecular technology like pulse-field gel electrophoresis and PCR to
> DNA sequencing and to DNA microarray. I will tell you a little bit
> about the efforts that are going on in some of these technologies.
>
> One of our investigators had isolated a Salmonella typhimurium
> antibiotic-resistant culture and was interested in determining the
> virulence markers that were associated with this
> antimicrobial-resistant bacteria as well as antimicrobial-resistant
> markers. So he developed this microarray assessment so that he could
> then identify more than 25 genes that were associated with this
> multi-antibiotic-resistant strain.
>
> So this technique is a much more rapid technique in comparison to the
> PCR techniques that they were using previously where they would
> evaluate one gene, a single gene, at a time.
>
> As well, as I mentioned earlier, we were interested in characterizing
> fluoroquinolone-resistant strains of Campylobacter that are isolated
> from turkeys. This is a slide projecting pulse-field gel
> electrophoresis fragments where one can identify and characterize the
> various strains using these specific restriction enzymes.
>
> Then, again, they have developed multiplex PCR techniques which can
> also discriminate various marker associated with specific strains.
>
> I mentioned earlier that there was an in vitro intestinal model that
> was developed. This is a function of coculturing a variety of bacteria
> populations with an intestinal mammalian cell in culture. The
> investigators are using this to test the efficacy of competitive
> exclusion products in evaluating the antimicrobial drug-resistance
> transfer and detecting pathogen effects on intestinal ecology and they
> are attempting to study innate immune responses to intestinal
> bacteria.
>
> Secondly, the have an in vivo model, a germ-free mouse model, where
> they are testing the efficacy again of probiotic products and
> evaluating the antimicrobial drug-transfer immune responses and
> pathogen effects. So they are comparing the in vitro model with the in
> vivo models that are available at the NCTR.
>
> As I mentioned also, there is a large interest in the artificial human
> gastrointestinal tract. This slide depicts the most representative
> bacterial species isolated from the health adult human
> gastrointestinal tract. We have probes for all of these and you can
> see, on this particular DNA microarray\--we can identify 40 of the
> predominant human intestinal bacteria.
>
> We use this technique to look at perturbation of the populations. The
> populations are very complex. However, they are very stable so we can
> determine whether or not specific antibiotics or dietary supplements
> or chemicals affect the ability of those populations to thrive.
>
> Here is the basic problem. It is not unexpected. Here is a microarray
> depiction of 11 normal human fecal samples. You can see that there is
> quite a bit of heterogeneity. So this is where we need to integrate
> our informatic tools and our statistical tools to help us normalize
> the data from one human to another.
>
> The future research depicted on the next two slides is the continued
> application of microarray chip in detecting antimicrobial-resistant
> markers and foodborne pathogens in bioterrorism agents. We have a need
> to understand the role of the various genes in resistance development
> and development of microarray methods for detecting Salmonella species
> and Vibrio species in seafood, studying the intracellular signalling
> mechanisms in mammalia cells by foodborne pathogens, especially the
> ones that are mentioned here.
>
> We are developing baseline data that may provide information on
> development of quinolone-resistance in chicken and turkey intestinal
> microflora, continue to monitor using pulse-field gel electrophoresis
> profiles and the relatedness of bacterial DNA isolated from poultry
> and human sources, evaluating the contribution of probiotics towards
> resistance of foodborne pathogens\--we think this is a real
> problem\--and continuing to collaborate with our investigators in the
> Division of Chemistry whose activities I am going to transit to now.
>
> In our Division of Chemistry, the main goal there is developing
> detection methods. We are directing most of our activity towards rapid
> bacterial characterization by mass spectrometry. You see here the
> tools that we are using. We are using pyrolysis mass spec and MALDI
> Tof mass spec in conjunction with pattern recognition.
>
> These pattern recognition algorithms are those that are available
> commercially as well as those that are being developed within the
> Division of Chemistry. You can see the strategy of each of these
> tools. In the pyrolysis method, to heat bacteria and then distinguish
> bacteria by patterns of ions from all biochemical constituents while
> the MALDI Tof uses a laser to ionize the proteins and distinguish the
> bacteria by patterns of protein masses and, perhaps also, by the
> quantity of protein that each of the bacteria produce.
>
> This is a slide of the two tools. You can see here that the pyrolysis
> mass spec has a much smaller footprint which makes, in the words of my
> colleagues who are doing this work, it somewhat portable where you can
> see the MALDI is certainly a laboratory-based instrument that is not
> at all portable at the present time. It also gives some information
> regarding the development of reproducible spectra, the number of cells
> that are needed to produce each spectrum and the amount of time it
> takes to obtain a spectrum. So it is fairly rapid identification of
> protein spectra.
>
> At the present time, our current major issues and questions are
> comparing the pyrolysis mass spec to the MALDI mass spec. We are
> evaluating the time of time it takes per sample, the specificity, the
> reliability and the practicality and, of course, the unit cost per
> analysis.
>
> We are using as the standard the typical microbiological standards.
> That includes the PFGE and serotyping and antibiotic resistance
> profiles. The organisms that we are working with presently are shown
> on this slide. In addition to the hardware analytical development, we
> have two patent-pending discoveries that are associated with the
> pattern-recognition algorithms.
>
> This is a dendogram that shows the pulse-field gel electrophoresis
> profile of various species and serotypes of Salmonella. As you can
> see, they are pretty similar in nature. If you look at the color
> spectrum, I am going to show you the mass spec principle component
> now\--I hope you can see this. Is that legible? Using the mass spec,
> one can then discriminate those various strains and, by
> principle-component analysis, they were able to separate these strains
> and they are able to separate two of the strains that were not able to
> be separated by pulse-field gel electrophoresis.
>
> This slide shows a raw spectrum of a Vibrio that was associated with a
> Gulf outbreak in 1998. We collaborated with our colleagues from the
> ORA and we published a paper on distinguishing various species of
> Vibrio. This is what the raw data looks like. I don\'t pretend to
> understand much of this, but I can at least tell you what my
> colleagues told me.
>
> By applying their pattern-recognition tools with a single positively
> charged ion, with the same biomarkers, they are able to smooth out the
> spectrum and make better evaluations regarding the validity and
> usefulness of each of the specific biomarkers that are associated with
> this strain.
>
> Once again, they were able to determine that not only by using the +1
> charge transformation but by doubly charged and triply charged that
> those charged ions enhance the ability to discriminate the protein
> spectra which allows them to have much more confidence in the
> evaluation and interpretation.
>
> So, at the present time, this is what this slide indicates are
> preliminary comparisons between the two types of analytical tools, the
> pyrolysis mass spec and the MALDI Tof mass spec. Right now, it seems
> to be cheaper to do MALDI. The capital investment is much lower here
> than it is in the MALDI. The cost per analysis is better with the
> MALDI Tof. However, the taxonomic power, the stability of the spectra
> and the database, the practicality and use for chemical agents seems
> to be tilting towards the pyrolysis mass spec.
>
> So, in summary, what I have tried to do is give you an update of what
> is happening at the NCTR regarding renovation of the facility into a
> BSL-3 laboratory. I have provided you with some information regarding
> our DNA-based tools that we are developing to assess counter-terrorism
> agents and our proteomic tools.
>
> I have to acknowledge my colleagues who helped me put this together.
> John Wilkes was the mass spectroscopist and Carl Cerniglia is the
> microbiologist.
>
> I will take questions.
>
> DR. DOYLE: Do we have any specific questions for Dr. Casciano? Have a
> seat, Dan. We are going to have some questions for you. Dr. McClellan,
> in his introductory comments, gave us four questions that he would
> like the Board to respond to relative to the Food Security Program of
> the agency. First of all, is the approach the FDA is taking for food
> security balanced and appropriate? Secondly, are there any gaps and,
> if so, what are they? Thirdly, is the agency devoting adequate
> resources to appropriate areas of food security? Fourth, are the time
> tables that we have seen reasonable?
>
> So, with those four questions in mind, I would like to see what each
> of you think. Perhaps, I could start out with a few of my own
> questions. With regard to the CFSAN extramural research program, which
> seems to me that there are an awful lot of critical needs that have
> been identified that the agency, itself, cannot address completely
> with the resources that it has internally.
>
> One good example; I know the National Center for Food Safety and
> Technology in Illinois is doing a lot of work to strengthen the
> prevention and preparedness program. But there seems to be a lot more
> that needs to be done than can be done by just this one facility.
>
> So I guess I see this as kind of a major gap where there needs to be
> more extramural funding by CFSAN specifically in this critical area;
> that is the area of preparedness and prevention. I know my experience
> has been that a lot of money comes to NIH for food-security research
> that is in the food-safety arena but much of that, if not all of it,
> is dedicated more towards basic research and medical issues, clinical
> issues, and not specifically toward some of the practical issues of
> food processing and what can we do to control or eliminate intentional
> contaminates.
>
> Dr. Thomas?
>
> DR. THOMAS: Let me ask\--maybe it was mentioned during the course of
> yesterday and, perhaps, today, but there didn\'t seem to be a lot of
> emphasis on neurotoxins in terms of method development and some of the
> marine toxins. Are the marine-toxin detection methods being developed
> at Dolphin Island, for example? Where is this piece of the puzzle fit
> in?
>
> DR. DOYLE: Dr. Buchanan?
>
> DR. BUCHANAN: I can help you with some of this. We have two
> laboratories on marine toxins. One of the laboratories is the Dolphin
> Island laboratory and that is devoted to basically two research areas.
> One is Vibrio species and that accounts for about 50 percent of their
> activity. The other is marine toxins.
>
> We also have a second group at our Mercourt Campus that is a
> marine-toxin group headed up by Sherwood Hall. They primarily focus on
> some of the select agent marine toxins, saxitoxin, tetrodotoxin. So it
> is an active component of what we are doing.
>
> A lot of it is oriented towards detection in the environment, to a
> lesser degree on how we would get rid of it out of those products. But
> it primarily detection oriented.
>
> DR. THOMAS: Have you been able to leverage off of, say, for example,
> DOD or even EPA with respect to, say, the organophosphates?
>
> DR. BUCHANAN: In terms of the organophosphates?
>
> DR. THOMAS: Yes.
>
> DR. BUCHANAN: To a degree. Most of our activities in this has been
> focused, again, on the detection technologies and how to get them out
> of a food. It is pretty easy when you are dealing with water. It is a
> lot tougher when you are dealing with a complex matrix. Actually, that
> research has been quite successful and so we are really quite pleased
> with the way that is going.
>
> DR. DOYLE: Dr. Casciano?
>
> DR. CASCIANO: There has been some work at the NCTR in collaboration
> with Jan with demoic acid efforts, too. So the toxic endpoints are
> available. We have directed our activity towards the biological
> efforts but we have small-molecule chemists that are expert in these
> specific areas there too.
>
> DR. BUCHANAN: The other thing, John, that you need to consider, when
> you say neurotoxins, that is a really large group. So that includes
> all of our work in Clostridium botulinum which is a neurotoxin. It
> includes our original threat evaluation of nerve gasses, et cetera,
> which the key there was finding out what their characteristics are in
> food. They tend to be so reactive that they are not nearly as much of
> a concern unless you got into some pretty strange scenarios.
>
> So we do look at a whole variety of them. So that is a really
> broad-based question you asked.
>
> DR. DOYLE: All right. We will go with Dr. Nerem. We have got a lot of
> questions now. Dr. Riviere, Dr. Pickett and Dr. Laurencin.
>
> DR. NEREM: In spite of the excellent presentations, I still came away
> with absolutely no idea\--maybe I just missed it\--as to the size of
> the effort, what number of people, research staff, involved in
> Illinois, the number of research staff involved in what Dan talked
> about. So can I get a little help on that?
>
> DR. CASCIANO: At the NCTR, we have approximately eight people directly
> working on counter-terrorism efforts and about 15 to 17 that are
> working on the Food Safety Initiative efforts. So there is some
> overlap between the two studies.
>
> DR. BUCHANAN: In terms of our program, working with a rough estimate
> of 200 research scientists, we approximately have, when you look at
> dual-use projects that are food security and food safety, we account
> for about 40 percent of our program is associated with that. So you
> are talking probably in the range of 80 scientists.
>
> DR. NEREM: That includes the people in Illinois?
>
> DR. BUCHANAN: That would include everyone. Now, the one thing that you
> don\'t have in that calculation is in Illinois we are also leveraging
> IIT, some of the industry scientists. So typically what you would have
> in those activities is take the number of scientists we have out at
> Illinois which is\--Dave can give you a better estimate, but I am
> going to say there are maybe 20 scientists all together I would say
> that 60 percent of them are involved in those kinds of activities so
> we have twelve. Then you double it, at least, for the leveraging that
> we get from the other groups.
>
> DR. DOYLE: Mr. Levitt?
>
> MR. LEVITT: Just to help further answer the question, I was going to
> ask Dr. Buchanan to give the size of the extramural funding, also.
>
> DR. BUCHANAN: The extramural funding is \$2.83 million currently.
>
> DR. DOYLE: Dr. Riviere?
>
> DR. RIVIERE: I would like to, first of all, get on the record to show
> an excellent development of CFSAN research programs in these areas. I
> was on some previous committees that evaluated this. It was sporadic,
> spastic, not connected, not integrated with anyone within the agency
> or other agencies. It looks like a very different program now.
>
> I think the extramural program is always a concern and we are
> suffering because of \$2.83 million. That is a concern and that
> probably is the answer to the question I have. Every time I have come
> to these, people are always lacking data on, like, oral pathogenicity.
> You have come up to risk assessments and you can determine where it is
> and you can detect it at the other end. But that critical link, really
> the dose response and the pathogenicity, is just not there.
>
> So now you are dealing with all these exotic agents. There is not good
> data with the regular food-safety pathogens and that doesn\'t seem to
> be addressed in at least what I can see in the research programs
> coming up. If I had to come with a gap, I would say that is a gap.
>
> DR. BUCHANAN: We would agree. Now, the one thing that we didn\'t make
> a presentation on was that we have been trying to work with DOD to
> find some additional funds there. There is, through their TISWIK
> program\--we are attempting to negotiate some oral feeding studies
> with Bacillus anthracis. We have, out of our old food-safety program,
> funded dose-response studies, for example with the University of
> Georgia on Listeria. Those are just being completed.
>
> But these are extremely expensive studies. They are very hard to get
> the funds for. They are, particularly if you are using nonhuman
> primates, politically very sensitive. So that is a real tough area to
> do research and it is an area that, particularly if you get beyond
> rodents, it is not one that we would do. We would, in part, turn to
> NCTR to help in that area or, in this case, with DOD.
>
> DR. DOYLE: Dr. Pickett?
>
> DR. PICKETT: It would seem to me that the mission that you currently
> have underway is really pretty significant and the amount of resources
> that you have talked about applying to the mission seems to be
> significantly underfunded. So I just would like to, first of all, put
> that sort of on the record.
>
> One of the things that is unclear to me, and what has caught my eye
> through all the presentations, is Dr. Levitt\'s chart on time lines
> because what is unclear to me, based upon the chart and the risk
> level, has to do with what criteria is being used to define what is,
> in fact, low risk or acceptable risk. For example, in terms of in-line
> detection technologies, what criteria is being applied to decide, in
> fact, that you will be at low risk?
>
> DR. DOYLE: Dr. Buchanan?
>
> DR. BUCHANAN: In terms of in-line detectors, and please understand
> that at some point we can\'t get down to\--I would love to be able to
> give you numbers in some cases. Low risk for us would be to have, for
> the priority foods and agents that we have developed as a result of
> our vulnerability assessment, to have\--a green would be that we would
> have a sensor that could detect all of them in most, 90 percent, of
> the industries where such technologies were applicable. There is a big
> technology transfer component into that one.
>
> The orange would be\--at the other end of the extreme is that we have
> some viable candidates that looks like we might actually get to
> technology-transfer points. The red is basically\--it is a nice idea.
> We don\'t have any direct applications on the horizon. So we are
> moving there.
>
> DR. PICKETT: I thought that is how you would quantify it. So my
> question would be have you mapped, as an organization, the resources
> that you would need to actually get to these various stages?
>
> DR. BUCHANAN: We have attempted to. It is a very large number.
>
> DR. PICKETT: What is the delta between your current staff and where
> you feel you need to be as an organization?
>
> DR. BUCHANAN: I will let Joe answer that one.
>
> MR. LEVITT: It is obviously an excellent on-point question. As you
> know, the government, as a whole, funding in all agencies is a
> difficult issue. We have budget processes to address them. I think
> everybody looks at counter-terrorism, whether it is very specifically
> like in food or very globally like any of the various commissions that
> come out, show there are very substantial gaps.
>
> So you have both a question of size of the gap and time to get there
> and how you phase it in. But we are working within the administration
> to identify not only what the size of those gaps are but what is the
> most efficient way to phase those in that get the most benefit the
> most quickly.
>
> The kinds of things that you are hearing today, the need for the
> laboratories, the need for the research agenda, the need to be sure
> there is a connection between the science and the inspections, this is
> what is coming to the top of the agenda that we are defining.
>
> DR. NEREM: Can I just ask quickly, Joe, I didn\'t feel like you really
> answered the question.
>
> MR. LEVITT: The rules of engagement don\'t let me.
>
> DR. DOYLE: I guess that is far as we go with that one. Dr. Laurencin?
>
> DR. LAURENCIN: My concerns in looking at these different criteria,
> balances, gaps, resources and time tables is that, again it doesn\'t
> appear that there is defined road map to success. Again, just talking
> about going with Dr. Pickett\'s comments, I saw 2003, I saw 2007. I
> didn\'t see 2004, 5 and 5 to get there. I would think that that would
> be a part of any sort of presentation in terms of where you are and
> where you going, so milestones, goals, et cetera, and how to achieve
> them.
>
> Second, again, in terms of the issue about funding, I sit on an
> advisory board for NIAMS, the NIH Musculoskeletal Advisory Board. We
> talk about issues that come up in terms of if you have funding, what
> would the funding be. They can define what their funding needs are.
> Their response is that we can\'t achieve this funding because all the
> money is going for security and bioterrorism and all the money goes
> for that, so there is no way we will get there.
>
> But, if we were working in bioterrorism, man, there would be no
> problem. We should be able to get our funding. So I would ask you to
> sort of think about what the needs are sort of define what those needs
> are because if you are not defining those needs to us, I am sure that
> it may be more difficult to be able to gain the finding that is
> needed. The rest of the scientific community I guess is actually
> feeling the pinch, at least they think that they are feeling the
> pinch, because funding is actually being more diverted to issues of
> security and bioterrorism rather than these other primary areas that
> have been in the past.
>
> In terms of the intramural and extramural affairs, I also have
> questions about where that is going. A lot of organizations and
> institutes, they actually decide what their division of intramural
> funding and extramural funding is. We had our briefing yesterday where
> it was discussed that money has come in for this, money has come in
> for this, we are happy, we are using it.
>
> But a lot of other organizations, they decided where their intramural
> and extramural funding comes from, what their budget is going to be
> and what their plan is. Also, I didn\'t see an evaluation of\--I saw
> the presentation, which was nice in terms of extramural affairs, but I
> didn\'t see an evaluation of how successful it is and, in terms of
> what the goals have been in terms of the different projects. As a
> jumping-off point for where you should be going with the extramural
> program in terms of funding.
>
> So in terms of resources, in terms of time tables, these are the
> questions that I think are needed to be able to gain a focus about
> what should happen in the future.
>
> DR. DOYLE: Very good. Thank you.
>
> DR. LAURENCIN: Is there any response to that at all?
>
> MR. LEVITT: I think they are all valid issues. They give you a little
> sense of funding history. The FDA received, in the supplemental
> appropriation following 9-11, an appropriation of \$153 million. The
> agency at the time, overall, would have been about \$1.5, \$1.6
> billion. So that would be about an 8- to 10-percent increase.
>
> Out of that \$153 million, 97 went to food. Of that 97, 90 went to the
> field with the primary focus being at the border and in the labs
> focused on the border. That was viewed as a first big gaping hole. As
> I described, a lot of progress has been made there. That left only
> \$7 million out of that 97 to be devoted to scientific support that my
> center provides.
>
> What we have seen, what we have clearly realized, is the picture needs
> to be much more balanced. That is what we are trying to achieve. That
> is kind of Point 1.
>
> Therefore, second, most of the gains we have achieved to date that
> have been described have been achieved out of redirection of existing
> resources. We are very proud we have been able to do that, but you can
> only get so far in doing that. What we are trying to articulate, and
> we welcome any help you can provide us or point us or things we can
> improve on, is how to articulate the need. What are the things that we
> feel, and maybe we are too close to it, hamstrung by is so much of
> what is driving our need is what is contained is classified documents.
>
> So, once you get past that, it becomes a much more generalized
> presentation such as you have seen today. A disadvantage of our
> private discussions within the government is they are private but they
> do allow us to go into that information in much more detail. So we are
> pursuing that.
>
> Finally, there is never enough money to go around. It doesn\'t matter
> who you are; there will be nobody who thinks they have more than they
> need. Over at NIH, while the NIH, I believe, did reach their goal of
> doubling over whatever four-, five-year period it was. In the
> beginning, all those were to go to not bioterrorism because it wasn\'t
> viewed as a major issue five years ago, and the last increase that
> went to Institute for Infectious Diseases was \$1.75 billion in a base
> increase which is the same size as the entire FDA.
>
> But, nevertheless, from an NIH point of view, that is money that would
> have gone to other things. So I think what we have to do is to
> continue to identify, as best we can, exactly as you say, where are
> the highest-priority needs. What has not yet come through in a visible
> enough way is what we see are compelling needs specifically dealing
> with food products and threats from terrorism is this focussed sector
> and how to get sufficient resources to deal with both basic and
> applied research needs, the translational work that FDA does.
>
> But this is also, over the long time, early in the game. I think it
> will be making progress. The fact that OMB did allocate the \$5
> million over the summer, that is a signal that at least they are
> starting to hear that message. We will continue to push vigorously and
> we appreciate, certainly, the comments today that a number of you seem
> to feel that that is a not only viable but an important goal to try
> and achieve.
>
> DR. DOYLE: Dr. Swanson.
>
> DR. SWANSON: I think that funding or lack thereof is a reoccurring
> theme that exists here, anywhere, in the community these days. But I
> do think, with regard to whether or not the program is balanced,
> combining the ORM approach with the CARVER model I think was a major
> step forward in making sure that the limited resources that you had
> are directed in those activities that are going to have the biggest
> benefit.
>
> When it was just ORM, it wasn\'t quite targeted appropriately. So I do
> think that that was a step forward.
>
> One of the things, another reoccurring theme that exists with foods,
> is always that sample matrix problem that exists when you are trying
> to discuss in-line sampling, trying to get that hazard out of the food
> in some way. I am just wondering if there has been any effort to look
> at not necessarily the hazard of concern but the different types of
> food matrices that you deal with in a holistic approach and say, what
> is it about a high-fat food, or a liquid food, or a very proteinaceous
> food, that you can identify some common themes so that when an event
> occurs, or a food is implicated, there are certain protocols or
> strategies that could be applied that would help get the food out, or
> the hazard out.
>
> DR. BUCHANAN: That is exactly the approach that we are taking. We
> divide foods up into certain categories, some based on their physical
> characteristics, some based on their compositional characteristics. We
> try to direct our program so that we, particularly on the methodology,
> are really focussing in on that or, in some cases, some simple
> techniques for bypassing some of those problems.
>
> For example, if you are dealing with a food system that is multiphasic
> and you are dealing with a microorganism\--you are almost always
> dealing with a microorganism in the liquid phase. Some of our most
> successful approaches on taking some existing technologies and making
> them useful has been simply to centrifuge the sample and separate the
> two phases and look in the lower one that tends to eliminate some of
> the interference problems.
>
> So, yes; we are looking at those in terms of categories. I would like
> to focus a little bit on the biosensors, the in-line sensors. That
> seems to be an area that really captures people\'s imagination. They
> are looking for a magic bullet that they are able to use in that
> light. We think it is an important area but we can\'t put all our eggs
> in that basket.
>
> It absolutely would be irresponsible to take all of our research
> dollars and devote it to in-line sensors. We can get as much bang for
> the buck in coming up with being able to pasteurize a product
> appropriately or look at the packaging technology. So this is really
> one where we have to look at the specific food, the specific agent we
> are concerned about and then look for the specific attributes that we
> can take advantage of. There really is \"no one size fits all\" here.
>
> MR. LEVITT: Could I just amplify on that a bit. I think your question
> really hits an important point which is that, in the products we
> regulate, we have an enormous breadth and variety. If you just take,
> say, under whatever assessment, the top ten or fifteen foods out of
> hundreds and the top twenty or thirty agents, already, ten, twenty
> foods, twenty, thirty agents, multiply it out. You are talking lots of
> different combinations.
>
> So, number one, we have to narrow it down somehow and we are. But,
> number two, we have to look at common themes and not feel like every
> single one needs to be reinvented. So we are constantly looking at how
> to get two for, three for, four for, out of any particular research
> project, how to get cross-cutting themes, common platforms, different
> things that can be done to try and get more cost effectiveness out of
> whatever amount of research dollars and capability we have to put into
> it.
>
> But that is recognizing that the challenge here is incredibly vast and
> so we have to keep attention on where can we do the most good the
> fastest while also keeping some room for long-term goals. And that is
> kind of the balance between the laboratory methods and the in-line
> sensors.
>
> DR. DOYLE: Could I just follow up on this in-line sensor question.
> Part of the issue is time line, could we reduce the time line. Mr.
> Levitt made an excellent comment about there are so many issues out
> there, there are so many foods, there are so many agents.
>
> But could you approach this from another perspective and get the
> private sector more involved because if there is money to be made, you
> can often entice the private sector to invest its own resources to go
> this direction. But I think the private sector needs guidance as to
> what are the areas, the types of foods, the types of agents, that they
> should be focused on.
>
> I know there are programs with security and all, but that is a thought
> anyway in terms of reducing the time line and, perhaps, coming up with
> an effective approach.
>
> Dr. Rosenberg?
>
> DR. ROSENBERG: Actually, my comment expands on what you just stated. I
> get the sense in the years that I have been watching the funding
> situation here is that it is clear that the agency that you are within
> doesn\'t recognize your agency as a research-based agency. They give
> you money to protect our borders. They don\'t give you money to do
> much research. They give all the money to do research to NIH. You
> stated it another way, but that is the reality.
>
> It seems to me you have a couple of choices here. You either have to
> somehow convince Congress or Homeland Security or whoever it is that
> hands out money that more of that research dollar should be divided
> and come to FDA over other agencies that it is given, or something
> that I don\'t think you do very well because I don\'t think you do it
> well historically, maybe because, again, of the role you play,
> somewhat insular and having to protect the nation against everything
> that is out there.
>
> But, in this case, I am wondering if you are properly leveraging
> interactions with the industry, meaning, I guess the food industry or
> the diagnostic and tools industries who will make products. If they
> can see some advantage of those products being used to do this testing
> and there is money to be made, they will make anything you want to.
> They follow green stuff around.
>
> All you have got to do is make sure that those needs are such that
> they want to work on them. You don\'t have to develop all these tools
> yourself, I think, if you can leverage them. I began to hear that
> today. I think this thing you have done in Chicago sounds pretty
> interesting. It is the first attempt at that. Maybe you could be doing
> a lot more and maybe even leveraging not just with industry but maybe
> even some more leveraging with NIH, itself.
>
> I am wondering if your interactions with NIH are strong enough to try
> to leverage what they are going to spend in microbial disease and what
> their endpoints are, whether, again, there aren\'t ways you can gain
> from that in that a lot of those detection tools and the tools that
> they are going spend money on can also solve problems that you are
> trying to also solve.
>
> DR. DOYLE: Dr. Buchanan.
>
> DR. BUCHANAN: Let me respond in part. I don\'t want to appear
> defensive on this one but I would like to go back to our estimation
> that, in 2007, we would still be in the orange in terms of in-line
> sensors. This is a good scenario. In-line sensors have been a dream
> and active research area for foodborne pathogens for about a decade.
> Would you agree with that, Mike? It is about a decade of use.
>
> When we came up with our estimate of what we would be able to achieve,
> we had no thought at all that we were going to achieve this all
> in-house. What we were looking at was that, by strategic investment on
> our part, leveraging with the industry, leveraging with the people
> that are actively doing this type of detection-sensor research, which
> has been, to a large part, some of our national laboratories, not us.
>
> But it has been out in academia. It has been out with some of the
> other groups. Under the best-case scenario, and unless someone got
> really lucky to have a broad array of biosensors and get the problems
> that we are hearing about from industry solved\--at this point, it is
> primarily a development. So, yes; somebody might be get lucky. But to
> get these solved and then the technology transferred within a
> five-year period is a pretty optimistic viewpoint on a technology that
> has had ten years of problems making the leap from basic science\--it
> works really well in the laboratory\--to it works really good in a
> processing plant or dealing with the wide variety of foods.
>
> I turn to the people that are on the panel and ask do you know other
> ways of dealing with this that you would come up with a better
> estimate. We don\'t have a lot of money to invest; it is leveraging.
> We would rely on the fact that industry is interested in the product.
> Two, there are a bunch of researchers out there that are interested in
> making that jump. What we haven\'t seen is that bridge.
>
> There are some really great ideas. We haven\'t seen the translational
> research that have taken those great ideas that work really well in
> air sensors and then making that transition to will it work in the
> milk stream, will it work in a truckload of produce, will it work well
> in a stream of ground beef which represents some really tough
> application areas.
>
> In part, if you people have a better way of estimating how long it is
> going to take, we are trying to be realistic so that we don\'t
> overpromise something too often. In this kind of research, we hear a
> lot of promises. We don\'t see a lot of, here is what actually going
> to happen.
>
> DR. DOYLE: Dr. Thomas?
>
> DR. THOMAS: I have a couple of comments. First of all, I would like to
> see some priority setting in those outlying years, 2004, 2005, sort of
> make a jump there. Certainly some of that is predicate upon what you
> have accomplished this year so you might not be able to fill in all
> the blanks, but I think some sort of priority setting might be to your
> advantage.
>
> The other thing, and it is just a generic observation, your regulatory
> agency. As soon as you start talking about research, you have got to
> go head on with the NIH. So I would forget about using the term
> research. I would talk about methods development because that is
> really what you are doing.
>
> These methods development are extremely important to your mission.
> Now, I realize we are maybe arguing semantics but I think you have a
> better chance of selling your programs if you say, yes; we are in food
> security but we need the methods development, and just avoid the word
> \"research,\" that very simplistic approach. But maybe that is naive
> remark on my part, but, otherwise, you just get painted with the broad
> brush of a regulatory agency. \"That is not your mission.\" Well,
> methods development is your mission.
>
> DR. DOYLE: I think we are getting hungry. So why don\'t we take a
> 45-minute break and reconvene at 1 o\'clock. I know there are more
> questions. We have more time at the end of the day to ask more
> questions. So save your questions and let\'s reconvene at 1 o\'clock.
>
> \[Whereupon, at 12:15 p.m., the proceedings were recessed to be
> resumed at 1:00 p.m.\]
>
> A F T E R N O O N P R O C E E D I N G S
>
> \[1:10 p.m.\]
>
> DR. DOYLE: This brings us to the open public comment part of the
> program.
>
> **Open Public Hearing**
>
> DR. DOYLE: Do we have anyone from the public who would like to make a
> comment? Seeing none, I guess we will move on with our agenda
>
> Do we have any other discussion that we cut off at lunch that we want
> to continue before we get into the next speaker? We can pick up on the
> discussion later.
>
> That, then, brings us to Linda Youngman who is the Director of the
> Office of Research at the Center for Veterinary Medicine. Linda is
> going to address the issue of Animal Feed Safety System, BSE and
> food-security research at the Center for Veterinary Medicine.
>
> Dr. Youngman.
>
> **Animal Feed Safety System, BSE and Food Security**
>
> **Research at the Center for Veterinary Medicine.**
>
> DR. YOUNGMAN: Thank you. I am speaking on behalf to day of Dr. Stephen
> Sundloff, our Center Director. I am going to be talking about our
> Animal Feed Safety System, what we have been doing to protect this
> country from the possible emergency of BSE and also some of the
> food-security research we have been conducting at the Office of
> Research.
>
> Our mission is to conduct research to insure public health, the safety
> an animal-health products and also the safety of animal feed in this
> country. I want to show this slide. I always try and get it into my
> talks if I can because I am so very proud of our scientists with their
> unique training and our unique facilities.
>
> This is an overhead view of our Nierkirk Road Campus. Some of you
> visited us about a year ago to see how we prioritize our research
> programs. This little building here is about three floors of offices
> and labs. That is where we have our laboratories. We have about 165
> acres total, about 70 staff. What is unique about our facility is we
> have large animal research buildings and surgery suites with a
> pneumonic table that you can do horse surgery on.
>
> Specialized laboratories, I have already mentioned. An aquaculture
> facility that is just there. Pastures, a feed-mixing facility which
> Bob Buchanan showed you a picture of that. And we also have a
> quarantine facility just off here. So we have very unique facilities
> to support large-animal research and also counter-terrorism research.
>
> So CVM has four broad approaches to our counter-terrorism efforts. We
> first consult with different government agencies and different centers
> within our own agency. We participate in numerous emergency-response
> networks. We also spend a lot of time focusing on animal-feed safety
> programs and research. Finally, we have dedicated research programs on
> BSE and other matters that are important to the Center for Veterinary
> Medicine.
>
> Under consultative, CVM veterinarians provided assistance to and
> consulted with the U.K. Department of Health during their 2001
> outbreak and foot-and-mouth disease. Then, some months later, these
> same veterinarians attended foot-and-mouth disease training exercises
> in the U.K. and helped to compile a rather thick document of lessons
> learned from the U.K. incident so that we have procedures in place.
> So, if something like that happens in this country, we have thought
> through and learned from the U.K. experience to try and figure out
> what we need to do here to solve the problem quicker.
>
> So that was a very important piece of work because if I were a
> terrorist, this would be a very easy way to attack U.S. agriculture.
> Foot-and-mouth disease is highly communicable and we want to protect
> this country from it.
>
> We also consult with CDER on procedures for providing animal drugs for
> human use should the human drug supply be tampered with. So these are
> some of the consulting work that we do.
>
> We also participate in the National Response Plan with integrates
> procedures for how federal agencies should work together to respond
> during an emergency. We also participate on a working group, on agents
> of bioterrorism for the NCCLS group, which stands for National
> Committee for Clinical Laboratory Standards.
>
> We have recently initiated contact with the Laboratory Research
> Network which is coordinated by CDC. We also recently became involved
> with FERN, which you are going to hear about next. We have also
> participated in COOP, or Continuity of Operations Exercises. We have
> participated in other exercises as well but we can\'t name them.
>
> Under animal-feed safety, CVM has developed a system. It is a
> proactive, preventive system to prevent accidental or deliberate
> contamination of animal feed. We are working with feed manufacturers
> in this and I will tell you more about that in a bit.
>
> We also actively conduct animal-feed safety research. These are, right
> now anyway, surveys of foodborne pathogens to establish baselines. You
> need the baselines to know what are the naturally occurring levels of
> foodborne pathogens in feed. So if there is, perhaps, a subtle
> outbreak or some contamination, you have a quantitative comparison
> level.
>
> Under research, I am going to talk about BSE and our development of
> methods to detect prohibited proteins from prohibited species in
> animal feed. This is a really very important issue for CVM. This is to
> help enforce the FDA\'s feed ban.
>
> We also are doing a lot of surveillance programs. I will mention
> several of them. One is NARMS which stands for National Antimicrobial
> Resistance Monitoring System. Again, it is to establish baseline
> levels of naturally occurring foodborne pathogens in retail foods.
>
> Pulsenet, which is an extension of NARMS, which is DNA fingerprinting
> of foodborne pathogens, to try and detect are there some that have
> been genetically altered, for example. Also microbiology source
> tracking to identify the animal origin of foodborne pathogens.
> Finally, I will finish off by talking about rapid-test methods, both
> microbiological and we want to possibly extend that to possible
> chemical contaminates in animal feed. These studies represent only a
> part of CVM\'s ongoing research.
>
> I want to talk a little bit more about the foot-and-mouth disease. I
> said that CVM veterinarians went to the U.K. during the outbreak, and
> they came back. Some of the key lessons learned\--you will see a
> common theme here; assess the human health risks resulting from
> disposal of the animal carcasses; plan ahead, know what you are doing,
> be prepared; have systems in place so when something happens, you are
> ready to go; identify public-health laboratories with adequate
> biosafety-level standards to test human samples; and conduct training
> exercises for public-health workers at national, regional and local
> levels.
>
> Again, these are just some of the key lessons learned but the
> take-home message here is be prepared. We have a document about that
> thick that came out of these training exercises. So we know how we are
> going to respond if something like that happened in this country.
>
> Now, I want to shift gears to the Animal Feed Safety System. The
> Animal Feed Safety System is a comprehensive risk-based feed-safety
> system. It is coordinated by FDA and by state and animal feed-control
> officials, or AFCO, which stands for Association of American Feed
> Control Officials.
>
> It involves both complete feed and ingredient producers. The areas of
> greatest regulatory concern are being identified using risk analysis
> and working with feed manufacturers who can help us understand better
> and we can help work with them to identify the greatest hazards and
> then try to work out ways to mitigate those.
>
> So the Animal Feed Safety System describes how animal feeds should be
> manufactured and distributed, thereby insuring the safety of the
> animals consuming the feed and also the safety of people consuming
> food products from the animals.
>
> So the concept is to develop an umbrella risk-based preventive system,
> a proactive system, to improve industry\'s knowledge of how to
> identify and minimize problems, particularly those that might be
> related to bioterrorism.
>
> Just to let you know that I think we are the right track, feed
> manufacturers supported this approach at a recent, about a
> month-and-a-half-ago, meeting of people involved in the Animal Feed
> Safety System.
>
> Under animal-feed safety research, our main objective initially is to
> establish a network to support nationwide surveys that examine the
> prevalence and antibiotic-susceptibility profiles of human foodborne
> pathogens in feed commodities. Later, armed with that information, we
> want to conduct research and develop intervention strategies.
>
> Why is it important. Again, I keep coming back to this; to establish
> baseline levels that give you a point of comparisons so if there is a
> subtle assault on the feed supply, we can pick it up, and it is
> collaboration between CVM, CDC, NARMS, which I will mention more about
> later, and the Office of Regulatory Affairs field laboratories.
>
> In 2002, we did a survey of rendered animal protein products. That
> work is completed and I will show you a little bit of the data from
> that 2002 survey in a minute. In 2003, we have been doing a survey of
> plant protein sources. That work is in progress. In 2004, we plan to
> survey complete feeds and expand our surveying by involving others in
> helping us to collect samples.
>
> These are some data from the 2002 survey where Salmonella and E. coli
> were measured in various feed commodities. Admittedly, the sample
> number, the total sample number, is quite small. But what you will
> note, if you just focus on these last two columns, is that the percent
> positivity in these animal feeds for Salmonella was about 34 percent.
> For E. coli, it was about 40 percent.
>
> Our plans for the future, again, are to expand our feed surveys
> utilizing the NARMS infrastructure and ORA district laboratories and
> offices to help us collect feed nationwide to try and make our surveys
> more representative of the nation as a whole. We also want to compare
> the reliability of new rapid-testing methods to existing cultural
> microbiological methods in animal feed.
>
> We then want to expand to include tests for suspected chemical
> contaminates in animal-feed samples. As long as we have collected the
> samples, let\'s see if we can get methods up and running for
> chemicals, also. Also, because we have a feed-mixing facility, which
> you saw a picture of when Bob Buchanan spoke, we want to investigate
> the utility of industrial processes in decontamination and pathogen
> reduction in animal feeds.
>
> Now, I would like to talk about BSE, which is of critical importance
> for CVM. We want to prevent the accidental or deliberate introduction
> and spread of BSE in the U.S. To do that, FDA prohibits the feeding of
> mammalian protein to cattle.
>
> What CVM has done thus far is we have conducted over 25,000 feed-mill
> inspections to date. Those inspections show right now about a 99.6
> percent compliance rate which is pretty darned good. But I will admit
> to you that this compliance rate is based on inspections of feed-mill
> records only. The assumption is that if SOPs are in place to ensure
> feeds remain free from prohibited proteins, then the feed mill is
> called compliant. But we would like to do a better job than that. We
> want to measure feed samples. We want to do random sampling with the
> BSE method.
>
> Just to let you know why this is important, CVM did some estimates
> about the first year BSE-related costs in this country. These are
> conservative estimates but we think it might be in the ballpark of
> about \$64 billion because the industry is so much larger in this
> country than it is in the U.K. because are a much bigger country.
>
> BSE regulation was like \$53 million. There is a big difference
> between the two. There is one thing that I wanted to go back to what
> Bob Brackett was talking about. I was glad he brought it up. It is not
> just the monetary cost we are talking about here. There is also an
> emotional cost to the public and their perception of the safety of
> food supplies in this country and also their confidence in their
> government.
>
> I wanted to say about that, I lived in the U.K. for ten years while
> BSE was emerging in that country. I know that the public did lose
> confidence in their government, largely over BSE because the
> government kept saying, it\'s not a problem, it\'s not a problem. And
> then people started to die. So there is that element of it that we
> have to be aware of, also.
>
> So how do you prevent BSE? It depends on changing feeding practices,
> not feeding potentially infected tissues to ruminants. Specifically,
> the FDA feed ban is a mammal-to-ruminant feeding prohibition. It
> involves prohibited species and prohibited tissues. The prohibited
> species are cow, deer, elk, sheep and goat whereas horse and pig are
> exempt or permitted in animal feed.
>
> It also involves prohibited tissues, meat and bone meal, bovine meat
> and bone meal, are prohibited but blood meal, milk gelatin and plate
> waste are exempt.
>
> Now to talk about our methods. CVM has optimized and validated a
> PCR-based method for detection of bovine-derived material in complete
> feed and feed ingredients. We are currently transferring this
> PCR-based method to FDA\'s Office of Regulatory Affairs for use as a
> regulatory method.
>
> CVM\'s PCR method is viewed by ORA as easier and quicker to perform,
> the reason being, right now they are using feed microscopy which means
> you have to examine the feed for hair and bone remnants. That takes a
> lot of time. So, CVM\'s PCR method permits more effective enforcement
> of FDA\'s feed ban since it permits higher sample throughput.
>
> Here are the details of the method. Again, I said the prohibited
> species were cow, deer, elk, sheep and goat. Permitted species were
> horse and pig. We use a universal primer. You can see it has DNA here
> from both the prohibited species and the permitted ones. By using
> enzymatic digestion, in this case here, to separate out the pig, in
> this case here to separate out horse, we can distinguish between the
> prohibited and permitted species.
>
> We are currently validating a DNA forensic kit including use of this
> universal primer. This, again, will greatly increase sample throughput
> in the number of samples that can be tested by ORA.
>
> The final piece of this, the tissue designation, the only way to
> distinguish meat and bone meal from blood, gelatin and milk is with
> antibodies. The gelatin needs to be removed prior to detection. It was
> shown in the U.K. to increase the incidence of false positives.
>
> So CVM has identified four unique heat-stable proteins that are
> present only in bovine meat and bone meal. We have developed a novel
> approach to eliminate this gelatin by using 2D gel electrophoresis
> based on pH and size. And then we use column separation.
>
> So our next steps are to do an ELISA. We want to produce monoclonal
> antibodies and polyclonal antibodies and then establish a capture
> ELISA so we can distinguish the tissues also.
>
> This is what we are proposing for a regulatory testing scheme. We use
> the universal primer to determine presence or absence of prohibited
> species. If it is a negative result, no more testing. But if it is
> positive, we do a second PCR with enzyme cutting so we can separate
> out horse and pig. Then, at the end, we use an antibody-based test for
> prohibited bovine-derived proteins. That is the future that we expect
> we will be able to do that in the next few months or so. Our expert is
> here.
>
> I will next shift gears to NARMS which I said stood for the National
> Antimicrobial Resistance Monitoring System. CVM participates in a
> number of surveillance systems in NARMS FoodNet and PulseNet. These
> are all surveillance systems of retain meat and human foodborne
> illnesses with the aim of, hopefully, using that information to reduce
> human illness.
>
> It establishes baseline data on pathogens and provides an alert system
> should animal feeds or retail foods become threatened.
>
> Here is some data from 2002 where we have been surveilling retail
> meats; in this case, chicken, ground beef, ground turkey and pork. You
> can see the numbers that we sampled were pretty large. Some of the
> states are doing all four pathogens that we are looking at,
> Campylobacter, Salmonella, E. coli and Enterococcus, and some are only
> doing Campylobacter and Salmonella. That is why they are bigger
> numbers, because some of the states are only doing the two.
>
> Most species of E. coli and Enterococci are not generally considered
> to be human foodborne pathogens because, right away, if you look for
> the four types of meat that we looked at, the levels of E. coli and
> Enterococci are pretty high. So, because they are not human foodborne
> pathogens, however, let\'s focus on Campylobacter because
> Campylobacter and Salmonella are the most common causes of human
> foodborne illness of bacterial etiology.
>
> Right here, you can see a problem with chicken. This is a concern. It
> is over 50 percent. Even the Salmonella in chicken, and in ground
> turkey, is higher than we would like it to be. So our surveys are
> giving us information on these foodborne pathogens and the prevalence
> in different types of meat. But the next question is what are the
> antimicrobial susceptibility profiles.
>
> These are data from the Iowa Retail Meat Survey which was the pilot
> for NARMS. We do have the resistant phenotypes for that study so I am
> going to show you that. Here we have data for ground turkey, ground
> beef and chicken breast. Admittedly, the number for this pilot is very
> small. I also don\'t have the breakdown of numbers of isolates from
> the different meats.
>
> But you can see that some of the\--in particular, ground turkey, for
> some of the drugs that we tested, the percent resistance bacteria was
> fairly high. But this may be based on very small numbers. You have to
> keep that in mind because the whole thing only has 153 isolates total.
> But these are the kinds of surveys we need to do to try and identify
> where the problems are and how can we intervene.
>
> The isolates, after they pass through for antimicrobial susceptibility
> testing, go to PulseNet. Pulsenet is the national network for DNA
> fingerprinting of foodborne pathogens. It is a collaboration between
> FDA, CDC, USDA, state, regional public-health laboratories. The
> objective is to reduce the burden of foodborne illnesses and assist
> during outbreaks leading to faster intervention.
>
> CVM\'s role in this is to determine prevalence of these four pathogens
> that I talked about earlier, these four bacteria\--sorry\--and also,
> the antibiotic resistance among these pathogens. Then PulseNet\'s role
> in this is to develop DNA fingerprintings by doing dendograms to
> determine genetic relatedness and to submit these to the PulseNet
> database so comparisons can be made between the fingerprints from the
> animal isolates, the retail meat isolates, and any human isolates that
> are presented to the CDC to see if there is an association between
> people eating contaminated meat and them getting ill with resistant
> bacteria.
>
> Next the isolates are passed to our microbial source tracking research
> team. The ultimate aim of this is to try and identify\--again going
> back to a risk-based system, let\'s find where our greatest risks are
> and then try to deal with those first.
>
> So we want to identify the animal source causing the greatest number
> of human foodborne bacterial illnesses and then intervene to reduce
> disease. So we want to find out is the biggest problem coming from
> poultry, pork, cattle? Where is it coming from?
>
> We use various phenotypical methods, genotypic methods. And then we do
> data mining on all of that information combined to try and see is the
> biggest problem coming from poultry, pork or where. Then we want to
> intervene to reduce that risk with that information.
>
> Are we having an effect? This is just showing you relative rates from
> 1996 to 2001\--I am sorry the data are not more up to date\--of
> laboratory-diagnosed infections per 100,000 people. This is for
> Campylobacter, Salmonella and Shigella. The good news is what you see
> is a gentle downward trend for human foodborne illnesses over this
> time frame.
>
> So, hopefully, CVM\'s surveillance programs may be helping to reduce
> that incidence of human foodborne illness. We certainly hope we are
> having an impact. That is the aim of our survival.
>
> I mentioned that we would be comparing some of the existing culture
> microbiological methods to rapid-test methods. These are just a few of
> the microbiological rapid-test methods that we are thinking we will be
> comparing against.
>
> We also have spent a lot of time developing multi-residue methods for
> drugs in meat, eggs and fish. Now, these are drug methods for
> chemicals but we think this strategy is applicable to chemical
> contaminates. To be able to look at multiresidues in one analytical
> run, we use a two-phase extraction and we extract and then measure
> both aqueous and lipid-soluble chemicals in one analytical run. So we
> do the water solubles, lipid solubles, combine them, one run.
>
> Here is the data for drugs. You can see here we can detect 18
> different veterinary drugs in a single analysis, one run instead of
> 18. So I know it is not a field rapid-test method but it is a
> laboratory rapid-test method that, in an emergency, we could possibly
> use the same kind of strategy for chemical contaminants.
>
> Just to summarize what I have been talking about, we have done a lot
> of work on foot-and-mouth disease with the U.K. Department of Health.
> We are also working with CDER to inventory animal drugs for human use
> in case of emergency. We also participate in numerous
> counter-terrorism working groups and emergency-response networks.
>
> We have also developed a risk-based proactive animal-feed safety
> system working with manufacturers to try and identify the greatest
> risks and then intervene to reduce those risks. We also have done a
> lot of surveys to determine baseline prevalence and resistance of
> pathogens in animal feed and we are planning to expand that utilizing
> NARMS and ORA district offices.
>
> We are also actively conducting research, particularly in methods to
> detect and prevent BSE from emerging in this country, developing
> methods for bovine DNA and prohibited proteins in animal feed for
> enforcement of the BSE regulation.
>
> We also conduct surveys of retail meats for pathogens, antimicrobial
> resistance, DNA fingerprinting and to identify the animal origin, the
> animal species, causing the biggest problem in terms of human
> foodborne illness. We are also working to develop and evaluate
> microbiological and possibly chemical rapid tests.
>
> I would like to acknowledge the PIs and the various people who helped
> me put this talk together. Some of them are sitting here to help
> answer questions if you have any. I am most appreciative of their
> help.
>
> If you want more information, this is our website. And I am happy to
> answer any questions I can.
>
> DR. DOYLE: Any questions? Dr. Thomas.
>
> DR. THOMAS: Yes, please. The nomenclature for compliance rates with
> respect to feed or grinding facilities, that is kind of a misleading
> term.
>
> DR. YOUNGMAN: Yes.
>
> DR. THOMAS: If your whole thrust is safety, this is really a
> record-keeping activity, isn\'t it?
>
> DR. YOUNGMAN: At the moment.
>
> DR. THOMAS: You could call it regulatory appliance, because that is
> probably the law. But if the major thrust of your program is safety,
> and I realize you need to develop a BSE. You certainly couldn\'t test
> for 25,000\--well, maybe you could. But it would seem to me that the
> nomenclature for compliance\--
>
> DR. YOUNGMAN: You think we should choose a different word; yes.
>
> DR. THOMAS: I think it is misleading. That\'s all. If your main thrust
> is to protect the public from BSE, if someone reads that the feed
> company is in compliance, that, to me, would mean, well, it must be
> free of BSE. But all it means is that they are keeping their records.
> Is that right? Is that a right interpretation?
>
> DR. YOUNGMAN: That is a good point. We probably should change the
> term. But that is why I wanted to explain fully what that meant
> because it does seem\--we want to do a better job. We just haven\'t
> had the method ready yet.
>
> DR. THOMAS: No; I understand that. But, in the meantime, you could
> call it record keeping or regulatory compliance because, as it is, it
> is generic and one could make the assumption that it is safety
> compliance when, in fact, it is not.
>
> DR. YOUNGMAN: Right.
>
> DR. THOMAS: The other thing is, and this is a question for my
> edification, do you do any testing for CW? I notice you had elk and
> deer on one of those for chronic wasting disease or is that the
> Department of Interior?
>
> DR. YOUNGMAN: We don\'t do that; no. That seems to be driven
> differently state by state. It is also a touchy issue in this
> department.
>
> DR. THOMAS: Okay. I was just curious. Thank you.
>
> MR. LEVITT: Could we just take a minute? Actually, for whatever quirk
> of history, deer and elk and CWD is the responsibility of the Center
> for Food Safety and Applied Nutrition, not either the Food Safety
> Inspection Service which handles poultry instead of the Veterinary
> Medicine which handles veterinary medicine. A quirk of life, but Dr.
> Brackett is very up on that. He can give you, I think, a two-minute
> update on that.
>
> DR. BRACKETT: Two minutes or less, I guess. We have been working with
> APHIS on the ranch-raised deer and elk. They have an eradication plan
> that they are putting together and we have worked closely with them in
> designing their eradication plan such that any of the food products
> that come from them, or any of the FDA-regulated products\--that would
> be foods, dietary supplements, or cosmetics, if that were the
> case\--would be addressed by that.
>
> When it comes to hunter-killed or wild animals, that is the domain of
> the states.
>
> DR. THOMAS: Suppose there is a commercial meat market that
> coincidentally sells venison. It could theoretically be a mom-and-pop
> operation, but you don\'t have any inspection responsibility for that?
>
> DR. BRACKETT: That part would be, if it was the venison. But we
> normally wouldn\'t be into a meat market because that would be USDA\'s
> jurisdiction. But our guidance or our direction towards that is to
> lead the commercial industries into producing products in sort of a
> HACCP-like manner so that one could do a trace-back and show that meat
> or the ingredients actually came from a CWD-free heard.
>
> DR. THOMAS: Thank you.
>
> DR. DOYLE: Dr. Laurencin.
>
> DR. LAURENCIN: Just a couple of questions. I saw the data where you
> had looked at turkey and these other types of poultry and found 80
> percent levels of E. coli in terms of present in the samples there.
> But what percentage were of the real disease-causing E. coli? Are you
> correlating the ones that were antibiotic-resistant with the ones that
> were disease causing?
>
> DR. YOUNGMAN: That is some work we are doing right now. That is why I
> showed you data from a pilot that led to NARMS. So we are doing the
> same kind of work on those isolates looking at their resistance
> profiles to a whole panel of drugs.
>
> DR. LAURENCIN: Those that are resistant are the ones that are
> disease-causing, would be disease-causing?
>
> DR. YOUNGMAN: You are talking about E. coli 0157 and things like that?
>
> DR. LAURENCIN: Right.
>
> DR. YOUNGMAN: Yes; we are going to be looking at that as well. I
> don\'t have the answer for that right now.
>
> DR. LAURENCIN: Now, in terms of the feed inspections that are being
> done, what percentage of the feeds does this constitute and what
> percentage are you finding in terms of being positive, in terms of\--
>
> DR. YOUNGMAN: I showed data on Salmonella and E. coli. For Salmonella,
> the feeds that we have looked at so far were 34 percent positive.
>
> DR. LAURENCIN: I am just saying containing bone meal and things like
> that, in terms of violations, in terms of containing bone meal from
> cows and things of that sort, the BSE\--
>
> DR. YOUNGMAN: We haven\'t done that kind of an inspection of the feed
> to look for bone remnants or hair. ORA field laboratories are doing
> that.
>
> DR. LAURENCIN: Okay.
>
> DR. YOUNGMAN: Hopefully, as soon as we finish development of our
> method, that is going to be chaired out with the ORA laboratories so
> that they can run the method that we have been developing.
>
> DR. DOYLE: Dr. Riviere?
>
> DR. RIVIERE: I guess we are here to offer suggestions. That would seem
> to be more of a priority area because, I mean, again, you look at
> these and 80 percent of the feed has E. coli in it. Do you follow up
> on all those samples because I think we have had this discussion in
> other venues before. Why bother.
>
> DR. YOUNGMAN: If they are not foodborne pathogens.
>
> DR. RIVIERE: Yes; if 80, 90 percent of the feed is going to be
> positive for E. coli, why monitor E. coli?
>
> DR. YOUNGMAN: The retail meats, you mean?
>
> DR. RIVIERE: Yes, unless you actually follow through on what type of
> E. coli is it and to start looking at the incidence of a pathogenic E.
> coli.
>
> DR. YOUNGMAN: But we are following up on that by looking at the
> resistance profiles on those same isolates.
>
> DR. RIVIERE: So you do that on all the samples that are isolated?
>
> DR. YOUNGMAN: In NARMS; yes. NARMS, if you remember the total numbers
> for 2002, it was two-and-a-half thousand meats that were surveyed for
> Campylobacter and Salmonella and about one-and-a-half thousand for E.
> coli and Enterococci.
>
> DR. RIVIERE: So when you do these samples and you detect E. coli\--
>
> DR. YOUNGMAN: At some point, we are going to have to make a choice. I
> see where you are going with this
>
> DR. RIVIERE: Where I am going is, you know, an 80 percent positive
> rate, you are not getting any information at all out of it. You are
> not intervening to reduce that rate, so why put resources into
> monitoring that if you aren\'t going to get something out of it.
>
> DR. YOUNGMAN: Obviously, our resources are better placed at looking at
> Campylobacter and Salmonella which we know are causing the greatest
> number of human foodborne illnesses which is what we are after, which
> is what we are trying to effect.
>
> We are going to have to make that choice because we do have limited
> resources. We all know we have less money this year so we have to
> make\--
>
> DR. RIVIERE: What are your resources on this program? How many people
> are\--
>
> DR. YOUNGMAN: On which program?
>
> DR. RIVIERE: On what you presented today for the biosecurity.
>
> DR. YOUNGMAN: On counter-terrorism?
>
> DR. RIVIERE: On counter-terrorism.
>
> DR. YOUNGMAN: And the Animal Feed Safety System and the BSE
> development work and our surveys, CVM has about 330 employees total.
> We are, by far, the smallest center. If I had to hazard a guess for
> putting together for the BSE work, the surveillance work, the Feed
> Survey work, my guess would be about\--and the people who are working
> on the Animal Feed Safety System, maybe about 30 total out of 330. Is
> that about ballpark?
>
> DR. NEREM: 30 scientists or 30 total including support staff.
>
> DR. YOUNGMAN: 30 total FTEs, full-time equivalents.
>
> DR. RIVIERE: I guess I would echo very similar to what we discussed
> earlier with CFSAN. This is an obviously major issue and you are going
> in looking at feed records that you know that if somebody did
> accidently get bone meal in it, they are not going to market them. So,
> again, the effort, so, looking at this without really diving into more
> detail, I know this is tied into other food safety programs\--for
> instance, PulseNet, and all that\--to try to find out patterns of
> resistance.
>
> DR. YOUNGMAN: If I can just clarify. Out of our about 330 people in
> our center, the vast majority of these people are devoted to review
> functions.
>
> DR. RIVIERE: I know, but I guess there is a hole here. I would be
> concerned that BSE\--
>
> DR. YOUNGMAN: I guess the next order of business for us is
> surveillance and compliance and research is kind of way down there on
> the totem pole. So 30 people actually\--I mention we have about 70
> people total at our Office of Research Facility. We have got a large
> number of them devoted to\--
>
> DR. RIVIERE: Oh, I understand. We are here to try to help you. But I
> guess the point to make a statement of is that that is a very small
> group looking on a potentially\--
>
> DR. YOUNGMAN: Some really important issues.
>
> DR. RIVIERE: \--catastrophic issue. Look what happened in Canada with
> one cow and what that did to a regional beef industry.
>
> DR. YOUNGMAN: And we were involved with that. People in our office in
> Surveillance and Compliance helped with that cleanup after that
> incident.
>
> DR. RIVIERE: So I guess I would feel more comfortable seeing the 90
> percent E. coli, I realize, is history to E. coli but some of those
> resources to be implementing your animal-protein detection in feed and
> going on the premises looking for it.
>
> DR. YOUNGMAN: Although another thing I will say about that is we need
> to do a survey to know where we are.
>
> DR. RIVIERE: Oh, yes.
>
> DR. YOUNGMAN: 2002 is the first year we really did a large enough
> survey that we could have some confidence in the results. The Iowa
> Retail Meat Survey, which was the pilot for that study, only had 153
> and you can\'t really draw conclusions from a study that small.
>
> DR. RIVIERE: Then the question would be then why do the study if you
> can\'t draw conclusions from the study.
>
> DR. YOUNGMAN: Well, I think we can draw conclusions from the study. We
> certainly saw that there was a problem with the Campylobacter in
> chicken, for example. And Salmonella in turkey and chicken. It points
> us to where we need to go and it also pointed us to where, okay, maybe
> we don\'t need to do so much more work anymore and put our resources
> in another arena.
>
> DR. RIVIERE: So you are drawing conclusions.
>
> DR. YOUNGMAN: Right. I knew that was where you were going.
>
> DR. DOYLE: To clarify, you are concerned about both the BSE Research
> and Compliance Program, or just the Compliance Program?
>
> DR. RIVIERE: I think that the BSE Research Program has come up with
> what looks like a test that you have validated. So now it is basically
> translational, if you just get it out to the Compliance Program and
> focus efforts on that.
>
> DR. DOYLE: Thank you.
>
> Dr. Laurencin?
>
> DR. LAURENCIN: I just want to underscore that, in terms of if you look
> at cost benefit, in terms of you have given that \$52 million versus
> \$52 billion ratio in terms of cost benefit, and so I want to
> underscore, I think efforts really should be on the BSE end. I know
> there is a burden of disease that happens with E. coli, but, if you
> measure the numbers between E. coli, the project involving E. coli
> versus the project involving BSE detection, I think it probably pales
> in comparison in terms of the two.
>
> So I think one of the things I am saying is you have limited resources
> to go one way or the other, and in terms of national strategy, in
> terms of this area, I think the issue about BSE is probably a greater
> and more pressing issue and will have the biggest payoff for you in
> terms of prevention.
>
> DR. YOUNGMAN: Thank you for your comments.
>
> DR. DOYLE: Thank you very much, Dr. Young.
>
> Next we are going to hear from Carl Sciacchitano who is a Senior
> Microbiologist in the Division of Field Programs in the Office of
> Regulatory Affairs. He is going to address what we had heard over and
> over again, the FERN Program, which is the Food Emergency Response
> Network.
>
> **Food Emergency Response Network (FERN)**
>
> MR. SCIACCHITANO: Thank you very much and thank you for inviting me,
> thank you to the FDA advisory committee, inviting me to give this
> presentation on FERN today. I appreciate it.
>
> A couple of things to consider or to put things into context to begin
> with the FERN presentation. One, this is a joint initiative with USDA,
> particularly Pat McCaskey\'s group. Secondly, I want to coin a phrase
> with Joe Levitt this morning of a national partnership with FERN. It
> is very important to understand what that really means because, as we
> go through this talk and you see the types of food laboratories
> involved in this process, it really is a national effort. I really
> want to highlight that.
>
> I recognize, during the course of the presentation, the number of
> different agencies and types of labs that are involved in FERN and the
> associated complexities with a number of these issues as we move
> towards protecting the consumer from a terrorist attack on the food
> supply. So just a couple of things.
>
> The mission of FERN, just to be simplistic here, is to integrate the
> nation\'s food-testing laboratories for detection of threat agents in
> food at all levels of government. FERN looks at identifying not only
> biological but the chemical and radiological agents that might harm
> our food supply.
>
> You saw this theme this morning with Joe Levitt and Bob Brackett and
> Bob Buchanan; prevention, preparedness, response and recovery. These
> are the primary objectives of FERN. For prevention, looking at the
> federal and state surveillance sampling programs to monitor the food
> supply. This includes domestic and import.
>
> Preparedness; we need to strengthen the federal, state, local
> capacities and capabilities. When we talk about response, looking at
> surge capacity to handle a terrorist attack or attacks, or a national
> emergency involving the food supply. Recovery; we can\'t forget
> recovery. It is very important with this initiative to support recall,
> seizure and disposal of contaminated goods and also, and most
> important, to provide assurance to the consumer as a whole.
>
> Just a little history before I get into this slide. Prior to 9-11, in
> the past five years, since about 1998, we have been actively
> collaborating with federal, state and local partners really to build
> better bridges in such areas as accreditation, method validation and
> data sharing. These initiatives have been ongoing and it has really
> opened the doors for a lot of activities and communication that we
> really needed approval on before that, all in a goal to enhance
> consumer protection.
>
> But, as Dr. Brackett mentioned this morning, in February of 2003,
> Homeland Security Council assembled the Interagency Food Working
> Group. Really, that was to establish an interagency effort to protect
> the food supply and minimize food as a target. Three working groups
> were established; the Interagency Incident and Management Working
> Group; what Bob talked about this morning, the Vulnerability Shield
> Working Group; and the Laboratory Working Group which I will discuss.
>
> Out of the Laboratory Working Group and, in conjunction with our past
> success dealing with the federal and state and local levels, FERN was
> given specific directives. But, before we got into establishing more
> of the dynamics and the development of FERN and the logistics that are
> behind FERN, one would have to realize the number of different types
> of food-testing laboratories out there. I like this slide because, of
> all these activities from routine surveillance to outbreak
> investigation, and I will just go across, method validation,
> compliance issues, CT surveillance, you have also the training
> component, and proficiency that goes along with that.
>
> These are the many activities that are cutting across most of these
> food-testing laboratories. If you look at the types, that include
> environmental, veterinary diagnostic, agriculture, clinical and the
> federal laboratories.
>
> That is a large cumbersome feat. It is complicated. So we set up the
> following components of FERN. I will briefly go over this for you.
>
> One component, and a large component, is the FERN Steering Committee.
> The other major component is the FERN National Operations Center which
> includes the FERN support programs. Then we have what is called the
> regional coordination centers, ideally, and this is the ideal state,
> five regional coordination centers. I am going to go into each one
> briefly.
>
> From the federal FERN Steering Committee member standpoint, we have
> very good representation from not only the federal side but also the
> state side. Not too long ago, the correct date was September 9th to
> 11th, we had our first Steering Committee meeting. Letters of
> invitation were sent to all the federal agencies and we had good
> response, you can see on the screen, from the Department, from FDA,
> from ORA, CFSAN, CDC, the various parts of USDA, FSIS, APHIS, AMS and
> GIPSA.
>
> We had Customs, DOD, FBI, EPA. We had representation from APHL. We had
> representation from the ag community, public health and veterinary
> diagnostics, again, going back to what Joe Levitt said this morning, a
> national partnership.
>
> Some of the FERN Steering Committee responsibilities include FERN
> guidelines, policies and procedures. Again, bear with me, this is an
> overview of how we are going to implement many of the activities under
> FERN. It is ideal to coordinate, integrate and develop national
> resources to support FERN. They will have oversight development of the
> FERN National Operations Center and obviously provide support and
> guidance to the FERN support programs.
>
> While the management of the FERN lies within the FERN National
> Operations Center, and to go over some of the issues that this center
> will have to deal with, are the responsibilities of the day-to-day
> operations of FERN. A lot of this has been done by collateral duties
> and we recognize that full-time support needs to be included and we
> are trying to achieve that.
>
> Oversight and implementation of the policies and procedures; again, I
> want to mention that a lot of the issues and exercises will lead to
> harmonization and standardization of a lot of these processes so
> people are communicating and collaborating and we are doing the right
> things the right way.
>
> Looking over\--not over, but looking to coordinate regional
> coordination center activities, looking at what the FERN support
> programs have to offer and making sure those are implemented in the
> regional coordination centers. You can see the flow of logistics are
> coming down to provide that harmonization; communication establishment
> and looking at, obviously, the needs and capabilities of what we need
> to do. We have to direct the right resources to the right places.
>
> To do this, initially, we have set up five subcommittees; Training,
> which is being chaired by Todd Bozevich at our Division of Human
> Health Resource Development out of the Office of Regulatory Affairs;
> Proficiency Testing is chaired by Bob Buchanan; we have the Method
> Development and Validation Subcommittees. That is being chaired by
> Linda Kelly at USDA. We have a Surveillance Subcommittee chaired by
> Pat McCaskey and the Electronic Communication Subcommittee that is
> chaired by Julie Stocklin out of ORA.
>
> I would be remiss not to mention the hard work and efforts that have
> already been devoted to this process provided by leadership from
> CFSAN, from ORA, from other federal agencies like CDC, from our state
> counterparts as well to help to devise and develop not only these
> trainings that are listed here on the screen but method development as
> well. A lot of effort has gone into this to facilitate and expand our
> capabilities and our capacities.
>
> As far as the regional coordination centers, right now it consists of
> the FDA and USDA representation, the state agricultural, the state
> veterinary diagnostic, public health and any other\--well, for that
> matter, EPA. From the regional standpoint, it is open to
> participation, especially when you are looking at a voluntary basis,
> to help provide that key representation and those needs of that region
> as a regional coordination center.
>
> Right now, I have listed the possibility of virtual hubs but right now
> we are just trying to staff some with collateral duties to these
> regional coordination centers to get them up and running. Right now,
> we have two regional coordination center that are being developed.
> Once we go and show the proof of concept with these regional
> coordination centers, we will, hopefully\--and the goal is five
> regional coordination centers, when I say \"goal.\"
>
> There are a number of significant responsibilities the regional
> coordination centers have from going out, as an outreach program to
> identify the laboratories in their region, looking at the capabilities
> and needs of those laboratories, looking at what laboratories will
> have screening capabilities, what laboratories will have confirmatory
> capabilities, what laboratories will have both. These things have to
> be done.
>
> Coordinating the response during a terrorist attack on the food
> supply, looking at their surveillance sampling program, looking at
> proficiency programs, hat is all going to be run through those regions
> and coordinated.
>
> The other component, it is a mature system. I am going to talk about
> eLEXNET for a couple of slides, but the issue really involves the
> collection and storage of FERN-related data. As the slide indicates,
> we must find a way to share and store critical information like
> surveillance-sample data, proficiency data and, obviously, test data.
>
> To capture this information for FERN, the Electronic Laboratory
> Exchange Network is the vehicle to do that. I will explain what that
> means in a minute. Ideally, and this goes back three years, when we
> first implemented eLEXNET back in 2000, we were very proactive in
> looking at the needs of the laboratories. As the slide illustrates, we
> have a lot of silos vertically and horizontally within the federal
> agencies and the state agencies.
>
> We have our own let\'s call our databases that maybe communicate
> within only that database. We need a system that can communicate a lot
> of these activities from inspectional activities, the
> quality-assurance component, down to even outreach like education.
> Again, I am trying to make this simplistic but there are so many
> different activities that are going on within the umbrella of national
> laboratories, one would want to communicate that and not burden the
> laboratories to have to re-key information every time they have to
> submit or enter different data.
>
> So we are very proactive. Again, during the implementation, that was
> one of the mandates that this has to evolve with the needs of the
> consumer, and consumer are the government users for this system.
>
> Briefly, eLEXNET is an integrated secure system designed for federal,
> state and local agencies involved in food-safety activities. It is a
> critical system, a necessary infrastructure to provide an early
> warning system, identify potentially hazardous foods and possibly
> identifying or assessing risks and analyzing trends.
>
> Right now, currently, there are 101 laboratories participating eLEXNET
> representing all 50 states of which 55 states are actively submitting
> data into eLEXNET.
>
> Just a brief slide on over the 160,000 sample test records that are in
> the eLEXNET currently. We just released Version 3.2 a couple of months
> ago. That includes over 3,700 analytes where one can capture and share
> data information. Also, there are over 16,500 imported products of
> information in the eLEXNET.
>
> One of the key utilities of eLEXNET is the GIS reporting functions. As
> you can see here, you can select on particular commodities, detected,
> nondetected, and determine which regions of the country are affected
> by that product. You can have the drill-down capabilities where you
> can go the region, to your state, to your county.
>
> A future module, if you will, that will be added to eLEXNET is called
> the National Food Laboratory Directory. This will give the user the
> utility of determining what laboratories are out there that can do, or
> analyze, a particular food, what type of methods they are running for
> that particular food, in a nutshell, what is the capacity and
> capability of that food laboratory.
>
> Here, looking at a generic list, looking at Salmonella, looking
> at\--you can pick a particular matrix or specimen type, looking at any
> disease related to that incident and call on laboratories that can
> identify it. You also have the drill-down capability looking in a
> state, determining quickly what laboratories can do what. This is
> going to be very beneficial for FERN activities and we hope to see
> this released in the next several months.
>
> I mentioned something being proactive. We are also looking forward to
> working with the National Animal Health Laboratory Network, NAHLN.
> They are currently developing their own system, much similar to
> eLEXNET. Really, if you look at the center of this slide, you will see
> HL7 Data Exchange.
>
> I am not I.T. and I don\'t pretend to be, but all I can say to make
> sense out of this is that we are working towards common data elements
> so you can share information that is efficient and not burdensome to
> the laboratories. We don\'t want to have disparate systems not
> communicating.
>
> In addition to that, we are building components like I just mentioned,
> the Food Laboratory Directory, and the future methods repository which
> we are going to build that maybe these systems can share. One person
> might not own these, but we can share that information.
>
> Again, looking at broader picture, again, the future, and this is my
> opinion, the future will look at many different types of networks and
> the possibility of looking at common data elements like HL7 so we can
> rapidly share communication, whatever discipline, whatever food type,
> and looking at sharing system modules like methods repository
> laboratory directory and any other type of laboratory or common
> functions that may arise in the future.
>
> In conclusion, I would like to mention some next steps for FERN;
> obviously, resource issues to support the capabilities and capacities
> of FERN. We are currently expanding FERN\'s capability and capacity.
> You heard from Joe Levitt this morning, Bob Brackett this morning and
> Bob Buchanan how we are trying to, with current resources, expand and
> enhance the infrastructure of these food-testing laboratories.
>
> In addition, we will continue the important initiative of
> communicating and collaborating with other networks. We will continue
> to strive to achieve products from the subcommittee activities,
> developing food-surveillance sampling and proficiency-sampling
> programs, developing validated biological, chemical and radiological
> methods for food, developing and prioritizing training plans and
> obviously keep the training mode and the expansion of eLEXNET on a
> continuous basis to meet the needs of our food-testing laboratories.
>
> I thank you for your time.
>
> DR. DOYLE: Thank you.
>
> Do you have any questions? Yes, John?
>
> DR. THOMAS: Thank you. What sort of\--you certainly have a lot of
> interface with several agencies, but I am reminded of the first
> responders and FEMA. Where does that fit into the scheme of your
> earlier slide. They were conspicuously absent.
>
> MR. SCIACCHITANO: That is a great question. In initial discussions of
> looking at regions, we did note the FEMA distribution of regions. But
> we ended up looking at the five FDA regions. We do need, as we work
> through this process, not only with the Steering Committee but to
> include those types of individuals. When we are looking at emergency
> response and those activities. Those will develop as we develop our
> operating procedures.
>
> DR. THOMAS: If nothing else, they should be in a system to collateral
> it off to you once some of the issues have been identified at an early
> stage.
>
> MR. SCIACCHITANO: One further comment. We are working with Ellen
> Morrison of Emergency Operations and her group to ensure that
> continuity and we are on the same page.
>
> DR. THOMAS: The other question I had, if I may, was one of your
> bullets pertained to training. Did I understand you had about 150
> sites, or that is the goal, 150 labs, or what? Or did I get that
> wrong?
>
> MR. SCIACCHITANO: I didn\'t mention specifically number of
> laboratories.
>
> DR. THOMAS: I guess my question was more related to training and
> quality assurance and how do you know that Lab A on the West Coast is
> going to have the same capability as Lab B on the East Coast? Who is
> going to coordinate that?
>
> MR. SCIACCHITANO: Again, that is a great question. What we have done
> with the Steering Committee is identify these subcommittees. Let\'s
> pick Training, for instance; training through prioritization of
> vulnerability assessments, methods that are ready to go that have been
> validated, training problems will be put together.
>
> In conjunction with those training programs, you need to perfect your
> Proficiency Program to establish that competency and credibility of
> those laboratories. So, again, you are going out and we have to figure
> out, again, as we go along what the training vehicle is. There are a
> number of laboratories that need to have specific training, how do you
> get that outreach and to include joining that almost at the hip with
> the proficiency program to make sure those samples that are going into
> those laboratories that receive the training. That is underway.
>
> DR. THOMAS: It would seem to me that you need a template of
> technologies at a basal level. You start from there and you build on
> that so that you can get some quality assurance across the\--
>
> MR. SCIACCITANO: If you look across from the subcommittee point of
> view, from the methods development validation, which includes the
> research component, the training, proficiency to surveillance,
> sampling and then the data sharing, there is a continuum. There needs
> to be a liaison in each of those groups. As a matter of fact, there
> are some of the same subcommittees that are on other subcommittees to
> make sure.
>
> DR. DOYLE: Any other questions? Dr. Pickett?
>
> DR. PICKETT: Just a quick question. The National Operations Center is
> sort of, I guess, the nuts and bolts of all of this together from a
> project management function. What is the staff size?
>
> MR. SCIACCHITANO: I thought I would get that question. The staff
> size\--how is this for an answer\--the staff size is evolving. We are
> starting out at a figure and merging towards an appropriate number
> that can support a huge operation like our own.
>
> DR. THOMAS: Are you running for Congress?
>
> DR. PICKETT: How do you get resources?
>
> MR. LEVITT: A lot of what we are at here, in terms of time, is
> developing the framework and the plans and the blueprints and we are
> working within the administration in order to get funding for them. We
> need to get the administration to back it before we are in a position
> to go and explain that to Congress and the numbers and so forth.
>
> So this is a necessary first step in terms of understanding what it is
> that you need, how to put it together, what it takes to do it. Just
> like the research we talked about this morning, you need to have all
> that groundwork done before you can go and say, I need so much money,
> because if you just go and say, send me money, they say, why. Just
> like the question before, what are the time lines, what do you and
> what are your milestones, this is a\--it was once a project that is
> now growing into a bona fide program we hope and believe.
>
> Again, we kind of began with, oh my gosh, what if it happens tomorrow
> and what is available, how do you do it right. You are seeing now
> Phase 2 or Phase 3 which is how do you do it right. In putting that
> together, Carl and his colleagues and John Marazelli, one of Carl\'s
> supervisors, co-chairs the committee with USDA.
>
> But, when you saw the number of agencies on that screen, it is a
> success story even at the early skeleton stage to have that many
> agencies sitting around a table talking about collaboratively funding
> something like this. Again, those are first steps in terms when you
> asked the question.
>
> But we recognize that right now it has more framework and plans and
> goals and directions than it has hard resources associated with it.
>
> DR. DOYLE: Any other comments, questions? Thank you, Carl.
>
> We have a tough question next. Do we want to take a break or do we
> want to keep moving? Keep moving? All right. That is the consensus.
>
> Next we are going to hear from Dr. Kathy Carbone who is the Associate
> Director for Research with the Center for Biologics Evaluation and
> Research. She is going to talk about facilitating biologics product
> development to address threats to food security.
>
> **Facilitating Biologics Product Development**
>
> **to Address Threats to Food Security**
>
> DR. CARBONE: This is a test. I am not Jesse Goodman. He sends his
> sincere apologies. He has a very bad sprain of his back and was unable
> to come today. So you have a poor substitute but I will do my best.
>
> The talk will start with a few introductory slides about CBER, about
> CBER-CT and then we will go into some more detailed information about
> the research program and its relevance to the mission of the FDA.
>
> CBER\'s roles and the products that we regulate; our role is to
> facilitate product development. We have to be ready to assure
> emergency use and regulatory approval of best possible safety and
> effectiveness assessment with products that are needed in a hurry. We,
> therefore, have to facilitate this product availability. We have to,
> however, also ensure its integrity and perform the related research
> and regulatory activities that are required to do these things.
>
> Our role in products; we regulate our vaccines through the Office of
> Vaccines, immunoglobulins, blood and blood products through the Office
> of Blood and gene, cell and tissue therapies in that office.
>
> In the CT area, we have 133 active applications, 561 amendments to
> those and recently, through some unmet-needs projects internal funding
> mechanism, we funded 93 CT unmet needs.
>
> The approaches that we used to speed product availability and
> licensure for products that are needed for countermeasures are that we
> have, and always have had, a long tradition of early and frequent
> consultations between the sponsor, the end user and FDA. We have the
> availability for emergency use of a product under IND. We have
> available to us fast-track and accelerated-approval processes. We do
> priority reviews. We can approve a product using the Animal Rule,
> which I will discuss briefly and Dr. Murphy has in her talk as well.
>
> We pay careful attention to risk-benefit and risk-management issues
> and we provide incentives. So we try and do the best balance in a risk
> model of speed and safety.
>
> The Animal Rule, just very briefly. It is obvious in certain
> conditions there are important drugs and biologicals that reduce or
> prevent serious and life-threatening conditions in the CT arena,
> counter-terrorism arena. In the cases where human efficacy trials are
> not feasible\--i.e., there is no wild small pox\--or ethical\--for
> example, one would not challenge somebody with anthrax for an anthrax
> vaccine\--then animal efficacy data can be used.
>
> The use of animal efficacy data must be scientifically appropriate. It
> sounds fairly straightforward. However, we still need human clinical
> data for immunogenicity, pharmacokinetics. Safety must be performed in
> humans. Civilian use often includes subpoputions for biologics and the
> approval is subject to postmarketing studies when any needed
> restrictions are in use.
>
> Limitations; it is important in this rule to have a valid animal model
> of disease. That is often lacking. How we predictably bridge the
> animal data to humans is an area that is somewhat difficult to address
> and confidence in the product may still be an issue, even in a valid
> model.
>
> Availability under IND is another technique we can use to get a
> product out quickly. It allows rapid access to an unlicensed product
> if there is an emergency need. It has simplification and flexibility.
> It is obviously very applicable to counter-terrorism and
> counter-bioterrorism. It goes hand-in-hand with working towards
> licensure wherever feasible and there is a rapid turnaround and active
> assistance from the FDA in that process. Recent examples that have
> taken a lot of time and energy and with some success are smallpox,
> anthrax and botulism, biologicals used to treat those or prevent
> those.
>
> In terms of our research, we focus on the critical pathways to
> development, and I will just use the same analogy as Bob Buchanan with
> the bridge, try and bridge the basic to the product. We target unmet
> needs with regulatory implications to facilitate development of
> products. It allows us to make regulation more scientific and less
> defensive. We can benefit multiple sponsors through our activities.
>
> It maintains our staff on the cutting-edge expertise particularly with
> biotechnologies and the novel technologies that are coming down the
> pike. I will give you some examples of some vaccine development
> utilizing these novel technologies in a few slides. And it provides us
> with the scientific expertise and confidence to foster objectivity.
>
> It reduces the risk of reflexive over or under protectiveness in the
> regulatory process. If someone doesn\'t truly understand what they are
> looking at, when they regulate, the chances are they will either pass
> inappropriately because they are reflexively under protective or they
> might conceivably become conservative and simply say no. So
> understanding the science and keeping up with the science is critical
> to a science-based regulation.
>
> In terms of mission relevance of our research program, since I took
> over for Neil Goldman about a year ago, we have instituted some
> tracking within the center. One of the areas we have instituted is to
> have the investigators directly link their research projects to
> applications undergoing review. So more than 100 biological licensing
> applications and 342 new investigational drug applications are
> supported by these research programs.
>
> Over 85 principle investigators, 61 percent of their research programs
> have either counter-bioterrorism components or are relevant to
> counter-bioterrorism. For example, some investigators have actually
> moved into areas of counter-bioterrorism, relevance such as the
> investigator who has developed a high-throughput assay for smallpox
> vaccine potency measurements. Some people have moved their programs
> already based in an important area to include counter-bioterrorism
> such as neurotoxicity, test development for vaccines to include, say,
> smallpox vaccine.
>
> We also analyze the types of research at CBER. Because our researchers
> are also regulators, they spend about 25 to 75 percent of their time
> actively regulating. We tend to think of our research projects in very
> regulatorily important divisions. The most important, or most numerous
> work, we do is in the area of product safety.
>
> Product characterization; about 26 percent of our programs are
> primarily designated as a product characterization program in which
> they develop methods and assays, mechanisms of action, biological
> responses and disease pathogenesis for example.
>
> Product efficacy; the program is about 20 percent designated as
> primarily product efficacy, developing surrogate measures of efficacy.
> This can be extremely critical, for example, despite tens of thousands
> of children who have received experimental rotavirus vaccines
> including the product that was licensed, no immune surrogate was
> detected that predicted protection for disease.
>
> Having an immune surrogate takes the numbers of patients required to
> test in an efficacy system from down to the thousands from the tens of
> thousands. In order to test a product, you require disease prevention.
> A vaccine requires, often, tens of thousands of individuals to test.
> So it is a major streamlining advance in terms of research.
>
> Clinical-trial design, et cetera, is not always bench research in our
> case and we have a very active statistical and epidemiological group
> and 7 percent we will call \"other.\"
>
> The CBER research program; obviously, a research program has to be
> externally validated and productive. Otherwise, it is not a research
> program. There have been 369 publications reported from these 85
> programs in Fiscal Year 2003. An example would be molecular
> determinants of vaccine virulence published in Journal of Virology,
> work on endogenous porcine retrovirus in xenotransplantation, an assay
> method in detection published in Journal of Virology, again the rapid
> throughput smallpox vaccine potency assay published in Journal of
> Infectious Diseases and a method to assess preclinical smallpox
> vaccine neurotoxicity which is in press in Vaccine.
>
> This helps us with QCing our research program because it is an
> external validation but it also is a very important part of research
> that we perform in the FDA in CBER because actually this becomes
> public information and is useful to everybody for speeding regulation.
>
> We also collaborate with multiple outside institutions. We track
> collaborations. We have over 100 collaborations with academia and
> other government agencies, some with industry. Some of these come with
> leveraging for funds, contracts and grants and some are intellectual
> and some are for professional development.
>
> The vaccines become very useful in terms of threats of biological
> terrorist attacks because, as we all anticipate, one of the hallmarks
> of a biological terrorist attack is an event that targets food
> distributed over a wide area that could challenge the ability to
> respond.
>
> Vaccines are effective and important countermeasures for foodborne
> pathogens in specific bioterrorism and counter-terrorism applications
> but, as was brought up earlier, it is difficult to predict the utility
> of a countermeasure specifically for bioterrorism because the risk of
> it actually occurring is not completely known. However, if you can do
> double duty, in that the biologic for addressing a counter-terrorism
> or counter-bioterrorism application is also utilitarian in other
> settings, medical settings.
>
> In addition, the whole pathway, the whole mechanisms, are important
> for emerging infectious diseases and accidental outbreaks are the same
> kinds of issues we need to address with biologics along with
> deliberate. Widespread continuing threats are difficult. It is not
> really vaccines versus treatment. It is really both because sometimes
> it may be difficult to disseminate treatment and vaccines can be used
> as a preventative.
>
> Traditionally, obviously, and I will go through this quickly, there
> are traditional agents that are addressed. There are agents that can
> be used and there are also unknown agents. This is just a publication
> by one of our investigators, Dennis Kopeko, in collaboration with
> multiple organizations addressing the ability of a live Salmonella
> vector which can be used to actually insert both anthrax and Shigella
> and other genes to provide multivalent vaccines.
>
> Many people are thinking that a different vaccine for every agent is
> difficult. However, multivalent vaccines can be of great use. This is
> in your handout so I will just go through this quickly.
>
> We have, as was mentioned earlier, the issue of gastrointestinal
> anthrax and the public-health significance. For us, in biologics, a
> vaccine that would be effective against GI anthrax attack would be
> valuable. It is obviously a serious illness and has serious medical
> and economic impact. However, this is one of the areas where
> basic-science gaps make it difficult for us to regulate products in
> that the whole notion of what is gut immunity, how does it work, is
> really poorly understood.
>
> If we ever regulate a vaccine and want to test it for GI anthrax, a
> suitable model needs to be developed, whether it is us, whether it is
> another center, whether it is outside in collaboration, but from the
> vaccine point of view, CBER would have an interest in dealing with the
> immune response and the protectiveness through the immune response in
> the gut.
>
> Botulism toxins is also, obviously, a very important area for us. We
> have limited medical countermeasures and so vaccines or immunoglobulin
> therapies are very important and we have done a lot of work with
> trying to proactively deal with issues of what is a protective
> response, how do you measure the potency of an immunoglobulin product,
> et cetera.
>
> Now, I just wanted to point out very quickly for botulism and for
> cholera that the difficulty of regulating, even in a standard sense,
> in these agents is difficult but, when you look at the novel
> technologies that are being utilized for some of these vaccines, there
> is no history of regulation. This would have to be created and you
> need people who understand the science in order to do this.
>
> For example, currently under investigation\--these are all
> public\--these are from the literature so these are all public
> materials. There are recombinant neurotoxins under investigation from
> yeast. There is, obviously, a good double-duty CT vaccine that uses,
> actually, an encephalitis recombinant vaccine carrying the neurotoxin,
> DNA vaccination, inhaled vaccines with a heavy chain of recombinant
> neurotoxin and even a microsphere encapsulated vaccine with
> biodegradable polymer. This is really novel technology.
>
> We have within CBER some experts on neurotoxin who are, in addition to
> doing some work on how to neutralize the toxin, where it goes, where
> it binds, are also doing important work on assay development as well
> as the other things I mentioned earlier.
>
> To expand the box a little bit, there are agents which people don\'t
> think of. Obviously, this is not a warfare agent, but this might be an
> agent of terrorism, children 3 to 35 months can be quite susceptible.
> This is a very hearty virus, rotavirus, and we have no vaccine. So we
> have an individual at CBER who is an expert in rotavirus vaccines, and
> expert in mechanisms.
>
> Recall that the previous vaccine which is licensed was withdrawn by
> the manufacturer due to a serious but uncommon adverse event of
> intussusception. The fact is nobody knows why this vaccine seemed to
> be linked with the intussusception. Nobody knows the mechanism and how
> do we prevent that with the other vaccines. Knowing more about the
> mechanisms of virulence of these viruses is, therefore, important.
>
> Cholera vaccine, to just give a quick list of some interesting
> approaches. Live attenuated but intranasal delivery, oral-killed
> vaccine, recombinant plant-derived edible toxin, toxin conjugated to a
> retrovirus virus-like particle but delivered intranasally, and Vibrio
> cholera ghosts, essentially the nonliving bacterial envelope. The is
> devoid of cytoplasmic contents but still looks like the bacteria.
>
> Listeria has been used with DNA vaccination with the hemolysin, oral
> inoculation with the live attenuated bacteria and, interestingly, the
> attenuated bacteria has actually been used as a live vaccine vector
> for HIV. These are all very interesting and novel technologies that we
> have to deal with.
>
> Finally, to end, trying to be a little \"edge of the wedge here,\"
> SARS is obviously an important agent. In many cases, it is
> indistinguishable from an actual counter-terrorism event. It was not,
> obviously, but there are some similar features. So addressing SARS is
> like addressing CT. There is some evidence, certainly, in the
> literature of animals that this can be enterically spread.
> Coronaviruses can be enterically spread.
>
> There was some interesting reports from Amoy Gardens regarding high
> levels of diarrhea, recovery of the virus from plumbing and found in
> the stool of patients as well as animals. So the question is what is
> the risk of this novel agent in foodborne transmission. We don\'t
> really know.
>
> There was a recent interesting report that showed some viral particles
> in the intestine of SARS patients and they were able to recover virus
> RNA from the stool and some virus actually from the intestinal
> biopsies.
>
> So, in summary, facilitating vaccine development is another
> countermeasure development for foodborne illness. Food security is
> important to everyone. As you can see, multiple centers here are
> interested and participate in food security including CBER and,
> hopefully, the vaccines, anything we develop that could be used for
> other routes, like anthrax being a classic example, inhalation as well
> as foodborne.
>
> Prophylaxis vaccination for serious infectious disease; the present of
> a safe vaccine and the ability to do some prophylactic prevention with
> vaccination would be quite helpful. Antisera are important for
> mainstay treatments for botulism and we currently have\--there are
> interesting humanized forms coming out, human monoclonal antibodies
> being investigated, and these will all help reduce adverse events and
> hopefully improve efficacy.
>
> Vaccines, as I have shown you, to protect against novel foodborne
> infections are utilizing novel technological approaches. Scientific
> needs include a better understanding of intestinal immunity and
> protection and oral vaccine delivery, which is, of course, a very
> rapid, easy and non-expert way of delivering a vaccine.
>
> Finally, thank you very much in advance for your comments, suggestions
> and for your time and attention.
>
> DR. DOYLE: Thank you for that.
>
> Any comments or questions of Dr. Carbone? Well, I have one. Relative
> to some of the select agents like Yersinia pestis, I didn\'t see any
> vaccine or treatment identified up there. But there are so many
> possibilities. If we were to vaccinate everybody against all these
> select agents, that would probably be impractical. So what is the best
> approach?
>
> DR. CARBONE: Yersinia pestis, and correct me, Bob, if I am wrong, is
> not an effective foodborne pathogen because it is rapidly inactivated
> in food. So that was one of the reasons why it wasn\'t on this.
> Obviously, it is very important it CT, but, well, everything is a
> risk-based analysis. Some of the vaccines will be useful and will be
> used routinely in, say, the military where there would be a
> significant risk.
>
> Some could be, particularly if they are stable-type vaccines and
> particularly if they can be administered, for example, by nonexperts
> or nonmedical personnel, they could be disseminated and ready to go.
> In the case of, for example, the Salmonella vector, the ability to
> give one attenuated bacteria that might carry proteins or genes that
> produce proteins for multiple organisms would limit the number.
>
> Every organization has to be considered risk-based and this is the
> difficulty with CT because you don\'t really know, necessarily, ahead
> of time. Now, in the case of many vaccines, if they are properly
> studied\--the smallpox vaccine is effective post-exposure. So if we
> can do the studies either with the animal models, if we need to, or
> with a human situation to determine the vaccine works post-exposure,
> then that would be, obviously, if we had a plan to distribute it
> appropriately, very effective and not used until it was absolutely
> needed.
>
> All these things are absolutely under consideration.
>
> DR. DOYLE: Thank you.
>
> Dr. Rosenberg.
>
> DR. ROSENBERG: You had a slide that kind of surprised me. Of all the
> stuff that is in IND or in NDA effort, 61 percent of those things are
> now CT-related?
>
> DR. CARBONE: I\'m sorry; I talked fast and I flashed through fast.
> Those were, of our 85 principle investigators and their programs,
> approximately 60 percent of those programs, research programs, have a
> CT component, either applicable to CT or actually addresses CT agents.
>
> DR. ROSENBERG: Okay. Thank you.
>
> DR. DOYLE: Any other comments or questions? Thank you.
>
> DR. CARBONE: Thank you.
>
> DR. DOYLE: Next we are going to hear from Dr. Dianne Murphy who is
> Director of the Office of Counter-Terrorism and Pediatric Drug
> Development for CDER. She is going to address medical countermeasures.
>
> **Medical Countermeasures**
>
> DR. MURPHY: Since I was to be the last speaker, I brought some\--as I
> learned in UVA, if you want people to attend your conference, you have
> got to feed them. So I brought a little sugar and caffeine to hope
> that we can get through this part without my looking out and seeing
> too many people nodding off. Since I think there is an error in the
> very last slides about which you really want to hear, you have to stay
> awake to find out where the error is.
>
> I have taken a different approach to my presentation because, in
> essence, you are going to hear we haven\'t really\--we have a number
> of products that are already approved from the medical countermeasures
> for humans who may acquire these organisms via food and water. Where
> we have gaps, they are not on the A list and, as you are going to
> hear, we are still working our way through the A list. So my goal this
> afternoon was to show you the human medical counterpart of medical
> countertherapies, what we are doing and how it might be applicable to
> some of the gaps that remain in food and waterborne diseases.
>
> Our mission statement, basically, is I just stated it, which was to
> identify gaps in the current medical countermeasures. In other words,
> we are marching down the agents on the A list. I wish we had gotten to
> the B list but we are still on the A list, as I said. We are
> identifying where we have therapies that are labeled. I am sure that
> has all been reviewed, the difference between a product that may be
> used in the practice of medicine versus it having an indication in the
> label.
>
> We then, after we identify where we have needs, we then say what are
> the knowledge gaps. And then we try to identify if that knowledge
> exists. When I say knowledge gap, I mean knowledge gap that we at FDA
> have. Do we have the data submitted to us? Is it in the agency
> somewhere because sometimes, and I am sure you are aware of this,
> companies do studies and they submit them and they may not have made
> it for that indication or they actually do the study and don\'t submit
> the data, but we know that it is around, or it is not done in
> relationship to development for a product indication but we know from
> academic or scientific literature that those studies are out there.
>
> So we will attempt to find that information. So what is needed, is
> what this is saying, to get this product labeled. Who has the
> information, if it is, and can we bring it in to the agency? And then
> we construct an action plan.
>
> Our goal is to assure the availability of safe and effective drugs to
> treat victims of counter-terrorism and to make sure that people have
> access to therapies and that FDA is not seen as a pointy-headed
> bureaucratic who won\'t allow gentamicin to be used even though it has
> been around, it has been as old as dirt, I have heard someone tell me,
> so what is our program here?
>
> Well, we want to know it works so how do we go about making sure that
> it works for the indication that people are recommending it to be used
> for?
>
> This is a little background on some of the approvals that have
> occurred already that are directed mostly for the military\--the
> military uses these\--that are directed as countermeasures against
> various agents both infectious and chemical and radiologic are on
> here, as you can see. Atropine is used in connection with some of the
> antidotes to nerve agents as is pralidoxime, diazepam. Then we have
> others that have been used for cyanide. This is a skin protectant.
> This is just a combination, a new way of providing the antidotes
> against nerve agents so that the soldier or the exposed person
> doesn\'t have to do multiple injections. So it is a combination
> product.
>
> This one is particular important, pyridostigmine bromide. This was the
> first therapy actually approved under the Animal Efficacy Rule that
> you have heard mentioned by the last speaker. But these, again,
> ranging from 1973 to 2002, almost a decade, really were aimed more
> towards the military type of development program.
>
> Now, what about homeland defense approvals. Potassium iodide, you are
> all familiar with that, I\'m sure. Again, an older product to use to
> prevent longer-term complications, protect the thyroid gland after one
> has been exposed to, or there has been exposure to, radiation.
>
> Ciprofloxicin was approved for\--this stands for post-exposure
> prophylaxis. After you have been exposed to anthrax, take your cipro.
> I am going to spend a little bit of time today going through that
> because that was the precursor to the Animal Rule. It is also a good
> example of how the agency went out and found the missing\--I
> shouldn\'t say missing; that\'s wrong. The agency had the various
> groups get together and bring this in as an application so that we
> could determine whether this product, ciprofloxicin, would be useful
> to treat anthrax.
>
> At the time, the need was identified as a product that might treat an
> organism, anthrax organism, that had been engineered so it was
> resistant to penicillin or doxycycline. So that is why that was begun.
> As you can see, we did that in August, 2000. It was approved so we had
> begun the work well before that.
>
> After 9-11, I am going to go into this process about how the agency
> basically looks at material it has internally and is able to make a
> determination, itself, that something is safe and efficacious and
> actually does all the work, publishes it and tells someone to bring in
> an application instead of the usual process where we are waiting for
> someone to bring us an application and then we review it.
>
> Again, some more. This is particularly important because it makes the
> product available for children which is another thing. When you are
> developing products or countermeasures, you have to think about entire
> populations, now, not just\--on the previous side, there are mostly
> healthy young people. Now, when you are developing products for the
> homeland security, you really have to have a product to treat infants,
> children, pregnant women, elderly, people who are immune-compromised.
> All of those populations need to be considered when you are developing
> products.
>
> This was important because during\--this is sort of like telling tales
> on yourself, but I might as well, in public, anyway. Right after 9-11,
> we are trying to develop information for people on how to use various
> products but, actually, we had published information for how to use
> some of the potassium iodide tablets that were larger, how to prepare
> them for children. The instructions said something like, divide in
> half or a fourth or whatever.
>
> Finally, someone called us up and said, \"Did anybody try to do
> this?\" The answer must have been no because, when you tried to do it,
> the tablet just crumbled. So developing a more reliable preparation
> that was at least half the dose, of the adult dose, that smaller
> children could use because you got down to, like, a fourth of the
> tablet, and that this could be divided if it had to be, so trying to
> answer some of those questions or activities with which we have been
> involved.
>
> Prussian blue is an oral agent that you take to eliminate certain
> radioactive elements to which you have been exposed. It basically
> helps bind them and remove them. Again, atropine for children. Again,
> the earlier atropine was a larger quantity. Atropine is one of those
> 0.0 products you are trying to calculate based on weight. Errors are
> very common. So it was important to have atropine preparation that
> also could be used quickly for children. That was a program that was
> successfully approved.
>
> Calcium and zinc DPTA, again a finding that the agency did, and I will
> explain a little bit more about that, for a product that works\--this
> is an I.V. product that helps bind transuranic elements, radioactive
> elements, upon exposure.
>
> These activities basically were things that have been done by agency,
> these last four here. By that, I mean I will give you this one right
> here as a specific example, calcium and zinc DPTA. We knew that we
> needed more options, therapeutic options, in the realm of radioactive
> therapies for exposure to radioactive materials. We knew that the
> Department of Energy, DOE, had contractors who are responsible for
> going out and providing therapies, calcium and zinc DTPA, Prussian
> blue to people who were exposed in accidents in the various
> nuclear-reactor sites.
>
> We were able to work with DOE and Oak Ridge Laboratories which is
> where most of the contract was based to obtain all of these case
> records. It was hundreds. They literally just faxed them to us, so
> many every day, and then one of our medical officers sat down with all
> of these hundreds of case records and developed an assessment of the
> elimination of radiation and developed a metric, as you would for any
> study, who had baseline, who didn\'t, who had interim, how was the
> follow up, what was the response, what were the endpoints.
>
> He did that and then put that back together. Then, working with our
> Review Division, we were able to determine that this product does
> work. It will decrease your load of transuranics that you have been
> exposed to over time. And it is safe to use in a certain\--if used as
> directed.
>
> So these are examples of how we have tried to go out and find the data
> to help fill in the gaps that exist. These are regulatory mechanisms
> that we have used and I am going to go in a little bit more detail on
> a few of them because they are so critical to our ongoing progress and
> some of the funding mechanisms that we were able to use when we did
> receive some money from Congress to move forward in this arena.
>
> The ways that we can expedite drug development, because I, again,
> bring this up because it is a long process. How can we help facilitate
> making sure these products become available. One of the things people
> think of the agency, or at least the drug part, is as a group of
> scientists who sit there, wait for the company to back their truck up
> and unload volumes and then we look at them and tell them what they
> did right and what they did wrong and decree whether they have been
> able to pass the approval bar or not.
>
> But, really, that is not what happens, particularly for serious and
> life-threatening diseases, the agency becomes much more involved early
> on. I mention that because it gets into trial design. It gets into
> deciding what are the studies that need to be done. That is really
> what all of this is about.
>
> You particularly see this in the area of oncology. You see this in the
> area of HIV in which we actually had some new regulations in that time
> period about how to develop mandatory early consultation with the
> agency for serious and life-threatening diseases.
>
> We have worked with the sponsor on deciding what is the study design
> that is most likely to provide you the information that we are going
> to need. It may be different than if you came to us and we were at
> NIH, we had a different research goal. Our research goal is to have
> evidence sufficient to allow us to label the product.
>
> And we will work with them in deciding, yes, we agree, these are what
> the endpoints should be, whether you can use animal models or not. We
> will also work with them in fast-tracking certain products if we
> don\'t have options, it is serious and life-threatening diseases. By
> that, the agency has said, we are going to be more flexible and we
> will allow you to submit what we call a rolling NDA. In other words,
> as you get the information, submit it, not just get it, keep it all
> and submit it in one big package, and we will work with you as we get
> the information.
>
> Accelerated approval was really how ciprofloxicin was approved. The
> Animal Rule, as I told you, was pirydo. I am going to walk through
> those because I think they are interesting in how you gather
> scientific information in not the usual way and what happened here.
>
> This ended up being approved under Subpart H which allows us to
> approve a product for serious and life-threatening disease if we have
> a validated surrogate marker, a marker that we feel we have
> characterized well enough. The surrogate marker here was this
> concentration of antibiotic over the minimal inhibitory concentration
> was greater than ten times that which would kill the bug.
>
> This was our marker. Basically, what we did is we said we are going to
> agree that if you achieve this level in humans and we can link it to
> what happened in the animals, because you cannot conduct these studies
> in humans\--this is pre-Animal Rule\--that we will accept this as a
> surrogate marker that the humans are going to behave the same way as
> the animals did.
>
> In microbiology, we can do this. We have lots and lots of experience
> in trying to\--in in vitro data that others may not have, like for
> nerve agents. So this is an approach we can use.
>
> We did, however, depend on heavily what has been called Dr.
> Friedlander\'s work, his animal model where he exposed monkeys to
> inhaled anthrax spores. You will see the various antibiotics that he
> exposed them to. So we went out to DOD and said, we know you have got
> these studies. We know that you looked at ciprofloxicin and we would
> really like you to get together with the company that makes this
> product and see if we think we have sufficient information to submit
> an application.
>
> We also knew that there was human pathophysiology from the Sverdlovsk
> accident. I am sure most of you have heard about that where anthrax
> was released into the environment in Russia from one of their research
> facilities. It resulted in a number of deaths. We actually brought the
> individuals who had gone over there and done some of the pathology and
> we brought them in and had them present to us, actually got some of
> the slides.
>
> So we were able to look at the pathophysiology in humans, compare it
> to the pathophysiology that we had in the monkeys and put that
> building block of evidence in place. In addition, we had a huge safety
> database on ciprofloxicin including children which this is usually
> contraindicated for children.
>
> So this was the way the agency tried to put together filling that
> knowledge gap I that I mentioned earlier and trying to get a product
> available to the public.
>
> This Kaplan-Meier curve\--you just wish all companies had curves that
> look like this. Here is your control monkeys and they die if you
> don\'t give them anything. Here is your product. Actually, one of
> these deaths was an accident. They had to gavage the medication and
> they gavaged it into the lungs.
>
> But I wanted to point out that not only did we have that curve for
> ciprofloxicin, we also had it for vaccines, penicillin and doxycycline
> and doxy-plus-vaccine. That is what allowed us to do our Federal
> Register finding. The Federal Register finding, basically, was, as I
> said earlier, where we looked at the data we had internally on these
> products for blood levels and other safety information, plus we sought
> updates on all of these products on their safety profiles.
>
> We were able to, then, determine, using the data that Friedlander data
> again, we were able to determine that we thought that these products
> were safe and efficacious for use in post-exposure prophylaxis if you
> were exposed to anthrax spores.
>
> We published this in the Federal Register along with a guidance on how
> to submit it, along with the draft labeling and just said, \"Here it
> is. Somebody submit an application who thinks they can manufacture
> this.\" You will have to pass all of our criteria for that,
> manufacturing, but this is really\--the agency did the work.
>
> We did the same thing with Prussian blue but we actually did this
> mostly from scientific literature that we were able to combine with
> other information that we had. And, as I already explained to you, the
> calcium and zinc DTPA. Again, these are Federal Register notices of
> finding, the agency is finding, safety and efficacy.
>
> The Animal Rule, which was mentioned to you earlier, is to be applied
> when you can\'t ethically or practically, because the disease doesn\'t
> occur anymore. This is what is happening now with certain diseases,
> certainly in this country, on the A list; plague, hemorrhagic fevers,
> smallpox, how were we going to get information for these products.
>
> As was stated, these are the fundamental elements that you must
> have\--if you are going to say a product is approved under the Animal
> Rule, you have to understand the drug\'s mechanisms as much as we do
> in our current state of knowledge. I say that because ten years from
> now, we are going to understand more, certainly in the area of
> antivirals, than we do right now.
>
> You have to be able to extrapolate from the animal models to the
> response\--you should be able to extrapolate from the animals to
> humans. I am not going to really go over this in much more detail
> except clearly you have to be able to come up with a dose. You have to
> be able to figure out from the animals the dose in humans.
>
> That is important because of some of the issues we are running into
> now because animals may have different species sensibilities or
> toxicities that humans don\'t have. So, sometimes, you have to give a
> higher dose in the animal and you are not going to be able to give
> that in humans, or, other times, the animal is very sensitive. So
> there are issues here but it is not as simple as everyone thinks it
> might be. And then you still have to have the safety assessment in
> humans.
>
> The pirydostigmine was important because not only was it the first
> time that we used the Animal Rule but it is an example, again, where
> we had a large safety database because it already was approved for
> another reason. That is one of the problems we are beginning to run
> into as you get into newer molecules, is you are not having this large
> safety database. I just brought that up because that is an issue we
> are going to have to deal with in the future.
>
> The other is that the efficacy part of this\--this is very interesting
> because this is an old system. This is an acetylcholinesterase system
> that we are dealing with here. We were seeing different responses to
> the protective effect of the pirydo in different animal species. That
> would theoretically say, well, you can\'t use the Animal Rule because
> why are animals behaving differently. How do you know how humans are
> going to behave?
>
> You had to work out why the animals were behaving differently. It
> turns out that they have carboxylase systems or scavenger systems that
> the lower animals, rodents, that the high animals don\'t have, higher
> species, and that actually they had experiments in which, if you block
> that system, you can get the lower animals or the rodents to behave
> more like the higher-level animals. By that, I mean, they then would
> be protected by the pirydo.
>
> You could give the enzyme to the higher species, meaning the nonhuman
> primates, and get them to\--if you gave them an I.V. infusion, you
> could then eliminate the protective effect of the pirydo. So, by doing
> these experiments, you were able to see why, and understand the
> pathophysiology and explain the differences and then, knowing the
> human system, you were able to predict what the protective effect
> would be in humans.
>
> So I thought it was just a very interesting case where you have a new
> rule. The first time you go to apply it and you have got all these
> complications, already when you thought you passed one of the big
> barriers of having the safety database there. So it is very
> interesting.
>
> So that is what the agency has been to do on its own, working with
> sponsors, working with DOD, working with DOE, working with a
> variety\--CDC. Actually, you are going to hear a little bit more about
> the CDC coming up in some of these activities that we have proceeded
> with under funding mechanisms using grants, contracts or interagency
> agreements and, hopefully, some day, there will be bioshield out there
> so that we will have additional ways that people can move products
> forward.
>
> One of the things that I mentioned earlier is that, when you have a
> countermeasure for Homeland Security, you have to be able to apply it
> to everybody in the population. So we were very interested after the
> anthrax events\--we would get calls; what do you do with pregnant
> women? What do you do with lactating women? What do you do with
> children? These products\--cipro was counterindicated. We had enough
> studies where we were able to say that the risk-benefit\--you can use
> it.
>
> There are concerns with doxycycline, as you all know, with teeth
> staining and bone growth in neonates and stuff like that. So what
> could we do about gathering additional information? What we have been
> able to put together is a program through the Office of Women\'s
> Health where they have contracted out for programs, various programs,
> to look at the pharmacokinetics, the safety profile of these various
> drugs.
>
> Amoxicillin; you say, why amoxicillin? Amoxicillin, actually, in a
> pregnant woman, you all know that the volume and distribution is
> different but they really don\'t have the PK. So, if you are in a
> serious and life-threatening situation, you, sure as heck, want to
> know that you are giving that pregnant woman the right dose and that
> you are not underdosing her or overdosing her.
>
> So this is an area in which we are trying to obtain additional
> information. The same thing for ciprofloxicin, doxy, particularly
> looking at lactating women and elderly. These products, again, doing
> pharmacokinetics in pregnant women and fetal safety outcome of infants
> who were exposed for whatever reason to these products. Those data, we
> are collecting both the pharmacokinetics study data and the exposure
> data over time.
>
> Additional activities have been working with NIH\'s Allergy and
> Infectious Disease Institute and the Army\'s Research Institute in our
> plague studies in non-human primates because the agency actually prior
> to 9-11 had already begun to look at what data there might be
> available for gentamicin and other products that have been recommended
> by various expert groups for use against pneumonic plague and actually
> talked to the people at Hopkins where the biodefense group recommended
> this and talked to various leaders in research throughout the country.
>
> The CDC helped us by helping us collect all of the human clinical
> trials in the Southwest area because it does still occur, as you know.
> Plague still occurs in this country. So we collected all the cases
> from the Southwest part of the United States and looked at them. They
> were all confounded, multiple drugs. It wasn\'t a trial. We could not
> come to any conclusion.
>
> So we have been in the situation of trying to define how we are going
> to get some products approved for the treatment of pneumonic plague.
> The way we are going to have to about that is working with NIAID and
> the non-human-primate animal model which we have already begun\--we
> have already completed the natural-history study with the USAMRAAD and
> NIAID. We are already looking at our dosing studies and have begun to
> do the preliminary hypothesis testing of exposure of these animals to
> pneumonic plague and treatment with different doses before we go into
> the randomization.
>
> The irony of all this now is that the facilities to do this research
> and the animals have become very difficult. They have become
> source-limiting in trying to do these trials. But, again, it is
> collaboration, as you have heard all day, with many different groups
> in trying to get this done.
>
> Another thing that we are doing is looking\--when you have lived
> through this anthrax use of antibiotics for 60 days, people have
> really tremendous difficulty tolerating it. If you have read the CDC
> reports on this, they stopped taking their medications. Not a good
> thing when you have a serious life-threatening disease.
>
> So we have been trying to develop a better understanding of the
> long-term use of some of these antibiotics and looking at various
> databases that may have this information. We are also working with
> NIAID and some academic institutions in developing smaller bridging
> animal models. We are working in the field with not only plague but
> viral hemorrhagic fevers trying to see what can be developed in some
> of these areas.
>
> Now, let me see is this has got the slide with the correction. No; it
> has still got the error. If you look at this, you will see that
> Salmonella, something happened. You should not have penicillin there,
> if you would please correct that. This chloro should be back up on
> this line here so that it should read, cipro, chloro, the furoxone,
> and ampicillin for the Salmonella. And then, because you took the
> chloro off of here, because it was supposed to be up here. It is not
> approved for Listeria.
>
> So I spent all this time talking about what we are doing to try to
> develop products on the A list of agents and, when you get to the
> pathogens that would be involved in food and waterborne types of
> activities, you will see that we really actually have quite a few
> options even though one of these products is no longer marketed.
>
> We still have a number of options, except for when you get to Yersinia
> enterocolitica. These are approved in the label with specific
> indications. You can go into our labels and find\--I have a long list
> of products that have these organisms listed as you may use them, but
> for a specific indication of a foodborne disease, these are the ones
> that we have for right now.
>
> The next, for protozoa. Crypto is approved in children\--this is
> ironic\--but not in adults. So, if you are under eleven, you are
> approved to take this product. Nothing for Cyclospora. Giardia, pretty
> much the same as for the Cryptosporidium. Metronidazole for Entamoeba
> and the pyrimethamine for toxoplasmosis.
>
> These are the labeled approved. There are plenty of approved drugs in
> the practice of medicine that you will see recommended, but these are
> the ones that are labeled. For the Vibrios, I always doxy et al.
> because it is a huge number of the tetracycline class.
>
> I end with these slides just to tell you that right now, as I said in
> the beginning, we don\'t have any programs that are under development
> for the ones that have these zeros in them.
>
> I have run way over time but I was told that that was okay. So I will
> end with offering to answer any questions.
>
> DR. DOYLE: Any questions for Dr. Murphy? Comments? Dr. Rosenberg?
>
> DR. ROSENBERG: Did anybody come forward?
>
> DR. MURPHY: Come forward for what?
>
> DR. ROSENBERG: You said that you put out this thing for people to come
> forward and get it approved.
>
> DR. MURPHY: Oh, yes.
>
> DR. ROSENBERG: Is it all done now?
>
> DR. MURPHY: For the Prussian blue, we have applicants.
>
> DR. ROSENBERG: For the antibiotics?
>
> DR. MURPHY: I can\'t say too much about the rest of them. I am not
> allowed to even say. But, for the one that is public that we just
> approved, yes. For the tetracyclines, for the doxy, we were able to
> get that relabeled, yes. That did happen.
>
> DR. DOYLE: Any other questions?
>
> DR. MURPHY: Thank you very much.
>
> DR. DOYLE: Thank you, Dr. Murphy.
>
> **Questions and Discussions**
>
> DR. DOYLE: That then brings us to the question and discussion section
> for the end of the day. So if you have any questions or comments
> regarding this afternoon\'s presentations and, if not, this morning\'s
> presentations, we can address them now.
>
> I have one that I didn\'t get in this morning so let me try this one.
> Is the agency actually using new technology to enable import
> inspection?
>
> MR. LEVITT: Tell me a little more. Are you thinking laboratory things?
> Are you thinking computerized things? What do you mean when you say
> new technology?
>
> DR. DOYLE: Across the board in terms of out-of-the-box techniques to
> inspect imported foods. We are not able to test but a small percentage
> of imports. We are going to have to be creative in how we go about
> that. So are we using new technologies that are coming forward to
> inspect and, if not, are we doing research in this area to develop
> those new technologies?
>
> MR. LEVITT: I am not at the front line at the border, but I will give
> you my impression. If anybody from ORA has more specifics, you are
> welcome to. The agency, among our many large tasks, is developing and
> expanding on what I refer to briefly as the Import Strategic Plan. The
> first step in that plan was to have a greater presence at the border.
> We described that.
>
> The second phase of that is to take the new prior notice and use it
> better for targeting. That is only two in a much broader scope of
> trying to get both more efficient at the border but also a much
> broader look from origin to final use, more understanding what happens
> in final\--a lot more what happens in foreign countries before it gets
> here, again, for targeting purposes.
>
> Probably\--I am not sure it is what you meant by
> technologies\--utilizing computer targeting systems is one of the
> things that is at the top of the priority-needs area, of what is
> really going to help us here, both the ability to get the information
> in and then have the right computerized targeting to get there.
>
> I think your question had a little more to do with at the border. It
> is kind of like the border version of the in-line sensor. I don\'t
> think we are that advanced yet but I will see if Dr. Buchanan knows
> more about that.
>
> DR. BUCHANAN: Probably the best example of where we have changed some
> of or border inspections is the inspection of foods coming across the
> border for radionuclide contamination. We have gone to a lot of the
> area of radiation sensors. We have a greater percentage of the product
> that goes through that detection system. It did during our Liberty
> Shield light up several potential problems; in fact, it identified
> some material that was coming through. As it turns out, it wasn\'t
> terrorism but it was lit up that way, and we found some material that
> way.
>
> So we are trying to adapt these as we can. We do have a portfolio of
> rapid methods available if we need to start using them. So we
> continually upgrade our laboratory.
>
> MR. LEVITT: Excuse me. We have someone from ORA who has a little more
> detail. So I will let her identify herself and speak.
>
> DR. DOYLE: Thank you.
>
> DR. WEKELL: I am Marleen Wekell. I am not from ORA anymore. I am with
> CVM. But ORA\--and it is too bad there isn\'t someone here because
> they do have a lot of things they are doing. It is too bad they can\'t
> share that. But they are working more closely with Customs now and
> Customs has a database and an electronic system that we are trying to
> dovetail into.
>
> We also are in the process of developing mobile laboratories,
> microbiological and chemistry, which could be deployed at the border
> if we need them, the work together with CFSAN, the Moffitt Center on
> the rapid methods. We are trying very hard to get rapid methods that
> could be deployed at the border.
>
> And then we have a surveillance system so we can target. But there is
> very much work being done by ORA and I am just sorry no one was here
> to represent them.
>
> DR. DOYLE: The reason I asked the question is because Secretary
> Thompson, I believe it was, who made the point so strongly that we
> have concerns about food that is imported. There was a lot of press in
> this area. I think it would be helpful for the agency to let it be
> known to the public not that we have just hired more inspectors but
> what are we doing to prevent contaminated food from coming in because
> I often get asked questions from reporters, \"Well, just hiring more
> inspectors; is that going to resolve the problem of intentional
> contamination of foods?\" I don\'t have the answer. I send them to the
> FDA, but I don\'t know if you want to talk to them directly about
> that.
>
> But, somehow, I think it would be helpful to share with the public, to
> give them a better feeling that good things are being done to prevent
> contaminated food from coming into the country because we have spent
> more money on it. We hear that there are more inspections. But only
> testing 4 percent of food, to me, does not give me a good sense that
> we are fully protected.
>
> DR. DOYLE: Anyone else? Dr. Thomas?
>
> DR. THOMAS: Just one quick remark. That would suggest to me that you
> need a post-employment surveillance system to put in place when you
> come back X months from now after these 800 new hires, how many\--some
> bean counter is going to look at some of those things and see what
> they got for their money.
>
> DR. ALDERSON: We do have metrics on inspections. You can count on
> that.
>
> MR. LEVITT: I mean, this is only a partial response. I may have said
> it so quickly but, just in terms of activity, it doesn\'t tell you
> what you got out of the activity. But the additional people, we went
> from 12,000 what we call physical exams at the border to 80,000. That
> is a six-fold jump in two years.
>
> Now, that doesn\'t take the next story of how many things did you
> find, how much did it help, is it meaningful and so on and so forth,
> and your point is, I think, exactly on target. We need to do a better
> job of explaining what that really means in terms the public can
> understand.
>
> DR. DOYLE: Any other thoughts or comments?
>
> **Closing Remarks\--Recommendations**
>
> DR. DOYLE: I think we are ready to summarize, if that is all right.
> Don\'t hold me to this, Board, because if I say something wrong or
> could be said better, help me with this.
>
> First of all, I think that the Science Board has witnesses an
> impressive example of how quickly and effectively the FDA can response
> to addressing unanticipated public-health threats and issues, that
> CFSAN and NCTR, NCFST, CVM, ORA, CBER and CDER have responded
> expediently and, in Dr. McClellan\'s terms, in developing 21st Century
> solutions to 21st Century security problems.
>
> Based on our tour yesterday, well, not a tour but our meeting with
> CFSAN, I think we had a good\--not only a good overview but what, in
> Dr. Ken Shine\'s words, a \"wow\" as to what accomplishments have been
> made in this area in such a short period of time, just some impressive
> research accomplishments in a short eighteen months.
>
> Importantly, there appears to be a dual-purpose function here in that
> there is good synergy between food-security and food-safety research.
> In particular, we want to thank Joe Levitt and Bob Buchanan and the
> CFSAN team for the impressive overview that we received yesterday of
> CFSAN\'s food-security research program.
>
> In terms of gaps, and I do want to have the input of the Board here
> because I may not have captured everything and I may have said
> something wrong. The first gap I have noted is that the food-security
> mission of FDA is underfunded. I see agreement there.
>
> DR. NEREM: By an amount we don\'t know because we haven\'t been given
> any information.
>
> DR. DOYLE: You took the words out of my mouth. I was just about to get
> to that. It would be helpful to develop a road map to achieve goals
> for 2004, 2005, 2006. There needs to be some priority setting. It
> would be beneficial to map the resources needed to accomplish the
> goals as well as provide budget information.
>
> Secondly, there appears to be a need for expansion of the CFSAN
> extramural research program to address critical applied issues in food
> security and safety especially in the areas of preparedness and
> prevention.
>
> Thirdly, there appears to be a need to place more emphasis on
> determining the dose response of nontraditional foodborne select
> agents in foods.
>
> The fourth gap suggests that there needs to be more emphasis placed on
> translating methods developed from CVM\'s research activities to the
> Center\'s Compliance Program. This, in particular, has to do with the
> BSE issue. Did I say that right?
>
> The next point is FDA needs to better articulate its needs for
> addressing food-safety issues. One suggestion I heard was there is a
> need to identify the agency\'s methods-development needs as such
> rather than describing this as a research need because FDA is, in some
> circles, not considered to be a research organization. So the point
> is, rather than saying we need more research on methods, the agency
> needs to have information on methods development and not include the
> word \"research,\" as one suggestion.
>
> Do we have any other gaps or comments that you all would want to
> share?
>
> Then I can move on to my personal one and that is I want to thank all
> of my colleagues on the Science Board for their commitment to
> providing FDA guidance that will strengthen the agency\'s science
> program. In particular, I want to thank my colleagues, Bob Nerem and
> Marty Rosenberg and Harold Davis who, unfortunately, was not able to
> be with us today, but who will leaving the Board.
>
> I also want to thank Jan Johannessen for his first time out of the box
> as being the staff coordinator here and doing a super job, and Norris
> Alderson for his involvement with the Board. Finally, I want to thank
> and commend Commission McClellan for his superb efforts in
> communicating to the public the FDA\'s activities and accomplishments
> in the protection and advancement of the health of the public.
>
> So with that, does anyone have anything else to say?
>
> DR. NEREM: I just think we all owe you a vote of thanks. This is your
> last meeting and you thanked everyone else. But you did a great job
> and I can\'t imagine how you pulled that report together. So,
> congratulations.
>
> DR. DOYLE: Thank you for that. Joe, you wanted to comment?
>
> MR. LEVITT: Took the words right out of my mouth. I want to thank you
> for your role, first as a member of the Science Board and as Chair of
> the Science Board. We really appreciate the opportunity of all the
> members to present here today.
>
> Just as it looks like I am just about at the end, we will let the
> Commissioner know that we are just about closing and if he has any
> final comments.
>
> DR. McCLELLAN: There is that sense of timing again. I see that, as in
> everything else Joe does, there has been an extreme amount of
> efficiency here and you walked through quickly. I had a chance to talk
> a little bit to Dan and some of the others who have been attending
> about a number of the comments.
>
> I just want to say a couple of things generally. One is that, in
> preparing for this meeting, and in general this year, we have tried to
> think really hard about how we can use our limited resources as
> effectively as possible. One of the most important prerequisites for
> instilling public confidence and building up the agency is confidence
> about us spending the dollars effectively.
>
> I think that we have redoubled our efforts in this area and will
> continue to do so. I think your suggestions and guidance here are much
> appreciated.
>
> I just want to conclude by coming back to something that I talked
> about with you all last night which is the complexity and challenges
> in our public-health mission. I want to make sure that we are matching
> that complexity with equally creative responsiveness and technical
> capabilities. The discussion that we have had today has been extremely
> helpful in making sure that happens in the area of food security and
> counter-terrorism more generally.
>
> We are going to have you back in a few months to talk about some
> emerging scientific and public-health problems in other areas. In the
> meantime, if you are interested, we would definitely like to call on
> you for other advice and we will look forward to following up on some
> of the comments that you made here today.
>
> One of the things that I have also tried to do is take advantage of
> resources where I can find them. You can bet that if you give us some
> specific suggestions\--it is not to discourage them, but if you give
> us some specific suggestions, we will be back in touch about how we
> can get you to help us follow up on them, too.
>
> So I want to thank you all very much for your contributions today. I
> especially want to thank Joe for his leadership in the overall
> food-security program and for the Center for Food Safety and Applied
> Nutrition at what I think has been an absolutely critical time in
> which the center has risen to the challenge.
>
> We were talking earlier this month about how we have already had five
> press conferences this year with the Secretary and have pointed out
> that the year is not over yet, so there may well be more coming. It
> has been a banner year for the center from the standpoint of new
> progress on food safety, new regulations, new research programs, from
> the standpoint of applied-nutrition programs as well as we are taking
> fundamental new steps to make better health information available to
> consumers and help address the growing challenge of obesity and other
> opportunities for improving health around better nutrition.
>
> Joe\'s leadership has just been tremendous in all that. I have valued
> him as a colleague, valued the whole team. It is a great team at
> CFSAN, but it starts with good leadership and Joe has been great for
> that.
>
> Mike and the rest of you who are rotating off, we are going to miss
> you. We really appreciate the service. As I said before, we are going
> to continue to call on you, so thanks to all of you for your work on
> this meeting today and for your continued support for FDA and its
> vital public-health mission.
>
> This is perfect timing.
>
> DR. DOYLE: I think it has been a great meeting and thank you one and
> all. I guess the meeting is adjourned. Have a safe trip back.
>
> \[Whereupon, at 3:25 p.m., the meeting was adjourned.\]