U.S. Food and Drug Administration 
Science Board

Meeting

	November 17, 2000
	9:00 a.m.

FDA Building
CDER Conference Room-1066
5630 Fishers Lane
Rockville, Maryland

Members of the Board in attendance:
		Robert S. Langer, Sc.D., Chair
		Charles A. Sanders, M.D. 
		Rita Colwell, Ph.D., S.Sc. (Hon.)
		Marion Nestle, Ph.D., M.P.H.
		Owen Fennema, Ph.D. 
		Martin Rosenberg, Ph.D. 
		Edward M. Scolnick, M.D. 
		Robert M. Nerem, Ph.D. 
		Harold Davis, D.V.M., Ph.D. 
		Marion W. Anders, D.V.M., Ph.D. 
		Michael P. Doyle, Ph.D. 
Invited Guest:
		Jane E. Henney, M.D., Commissioner
FDA participants:
		Elizabeth D. Jacobson, Ph.D., Senior Advisor for Science, FDA
		Bernard A. Schwetz, D.V.M., Ph.D., Deputy Commissioner of FDA (Acting)
		Susan K. Meadows, M.S., Executive Secretary, FDA Science Board

Agenda
Introductory Remarks
	Jane E. Henney, M.D., Commissioner	8
	Emerging Science Issues at FDA 
Introduction
	Bernard Schwetz, D.V.M. Ph.D. 	17
Challenges and Overview of Issues
	Elizabeth D. Jacobson, Ph.D. 	20
Discussion of Center Priorities
	FDA Center Directors	
		CDER - J Woodcock-44 
		NCTR - D Casciano-53 
		ORA - D Baker-59 
		CVM - S Sundlof-65 
		CBER - K Zoon-87
Open Public Comment
	Doris Haire	173
Programmatic Peer Review:  CDER
	David W. Feigal, Jr., M.D., M.P.H.	186
Hiring Update to support the Science Base of the
	CFSAN Food Ingredient Safety Program
		Alan M. Rulis, Ph.D., Director,
			Office of Premarket Approval	242
		Dennis Keefe, Ph.D., Asst to the Director
			of Premarket Approval, CFSAN	244
Action items from April meeting	276
Closing Remarks	287
Adjournment	306

	- - -

	P R O C E E D I N G S 
		DR. LANGER:  I'd like to call the meeting to order.  My name is Bob Langer, and I'm Chair of the Science Board, and I thought maybe as a first step we'll go around the table and ask everyone to introduce themselves, just briefly.  So we'll start with Harold.
		DR. DAVIS:  Good morning.  I'm Harold Davis from Amgen, a biotech company located in Thousand Oaks, California. 
		DR. NESTLE:  I'm Marion Nestle, I'm Professor and Chair of the Department of Nutrition and Food Studies at New York University.
		DR. DOYLE:  I'm Mike Doyle, I'm a Professor of Food Microbiology and Director of the Center for Food Safety at the University of Georgia.
		DR. SCOLNICK:  Ed Scolnick, I'm President of Research at Merck.
		DR. ROSENBERG:  I'm Marty Rosenberg, I head infectious disease research at SmithKline Beecham.
		DR. FENNEMA:  Owen Fennema, Emeritus Professor of Food Chemistry, University of Wisconsin-Madison.
		DR. ANDERS:  Dreg Anders, Professor and Chair, Department of Pharmacology and Physiology, University of Rochester.
		DR. NEREM:  Bob Nerem, Professor and Director of the Institute for Bioengineering and Bioscience at Georgia Institute of Technology.
		DR. COLWELL:  Rita Colwell, Director of the National Science Foundation and representing interagency cooperation.
		DR. HENNEY:  Jane Henney, Commissioner of FDA.
		DR. LANGER:  Bob Langer, Professor of Chemical and Biomedical Engineering at M.I.T. 
		DR. JACOBSON:  Liz Jacobson, Acting Senior Adviser for Science at FDA.
		DR. SCHWETZ: Bern Schwetz, Acting Deputy Commissioner of the FDA.
		MS. BOND:  Susan Bond, Office of Science, FDA, and Executive Secretary of the Board.
		MS. FOREMAN:  Christy Foreman, Office of Science, Executive Secretary for the Board.
		DR. FEIGAL:  David Feigal, Director, Center for Devices and Radiological Health.
		DR. BUCHANAN:  I am not Joe Levitt.  I'm Bob Buchanan, Senior Science Advisor for the Center for Food Safety and Applied Nutrition.
		DR. ZOON:  Kathy Zoon, I'm the Director of the Center for Biologics.
		DR. SUNDLOF:  Steve Sundlof, I'm the Director of the Center for Veterinary Medicine.
		DR. BAKER:  I'm Dennis Baker, the Associate Commissioner for Regulatory Affairs.
		DR. CASCIANO:  Dan Casciano, Director of the National Center for Toxicological Research.
		DR. LANGER:  Thank you very much.
		We're going to have Dr. Henney make a few comments, but before doing so, I just wanted Christie Foreman to make a few housekeeping announcements.
		MS. FOREMAN:  There are telephones located by the guard, in case anybody needs to use the telephones.  The restrooms are located right outside the door.  
		We are transcribing, so if you could please talk into the microphone -- and hopefully we won't have feedback like that.  To turn them on, you can touch them, and if they don't seem to be working, you can actually pick them up and bring them to you.
		We do have two scheduled breaks today; one at 10:45 and one at 3:00.  We will break for lunch from 12 to 1 and we do have our NCTR group on the Polycom, so they may be joining us shortly.  
		DR. LANGER:  Thank you.  
		Jane?
	Introductory Remarks
		DR. HENNEY:  Good morning and welcome.  I'm just delighted to be here.  As you all know, I was unable to come last year so I'm more than thrilled to be well enough to be here this year for this meeting. 
		I would like to underscore how much we need you.  We need to benefit from your advice because it is I think absolutely critical in the pace that's going on in science and technology.  This agency needs your help now more than ever.
		I think there are three things that I would bring to your consideration in terms of our need for strong science at the FDA.
		First and foremost, consumers have had confidence in this agency because of the scientific strength of our decision-making.  
		The recent Pew study done this spring and the results released, it was done of all of the regulatory agencies of government.  An overwhelming percentage, 75 to 85 percent of those surveys said they trusted FDA to make the right decision, and 74 to 87 percent believed FDA used good science in their decision-making.
		So I think a linkage between trust and using science, objective members to ground our decision and policy making is really underscored by that. 
		This wasn't exactly a just-man-on-the-street kind of interview situation.  Either it was four groups that were surveyed, clearly medical and health professionals, members of the patient advocacy groups, consumers, and then regulatory officers of much of the regulated industry who interact with us. 
		And the results across the board were quite consistent.
		So in terms of keeping that important element of consumer confidence, consumer trust in those products that we do regulate, it's absolutely essential that we have the kind of staff on board and the capabilities to reach out to gather the kind of science we need to make good decisions.
		I think the other thing that I would raise is something that you know and know well, the increasing investment that this country is making in research and development.
		And clearly the end result of all of that investment, hopefully, will be new products coming to market, and we are really the interface with that review process. 
		So having the scientific capability and the regulatory presence to make those decisions means that science at this agency must be strong.
		The third thing that has really upticked, if you will, in the last decade is something we also all know; and that is increasingly aggressive trade police as a national policy, and to really affect in a reasonable way new treaties that are taking place with other countries, with other governments, we need to have the scientific presence and the scientific skill to make sure that the standards set in those negotiations are a high standard. 
		We need to have a presence when disputes arise to make sure that we can be scientifically present and at the table making our case in terms of any disputes that do arise;
		And we need an ongoing presence of those scientific issues that are coming about through all of really increased impact of globalization.
		I would say that we have an over abundance of scientific issues that face the agency at any one time.  I think just within the last month I would tell you sort of what has been sort of our minds. 	
		Some of these have been on our minds but they have reached a different level of urgency or a different level of compelling need, clearly antibiotic resistance.  
		Things like the information that is rolling out of the human genome project, the genomics and the proteomics areas, all of the issues around bioengineered foods.  
		Clearly, the issues around transgenic fish, not only as a food product but its impact on the environment as well.  
		Decisions that we're making about products that come to market, products that must be removed from the market.  
		I would also bring to your attention some scientific policy matters, if you will, that we're also at a point of real discussion this past month; things that have been worked on for some time, but our participation in the Internet -- ICH or the chromotization efforts.
		This has been a decade-long effort between the regulatory bodies and the industries of the U.S., the EU and Japan.
		And just last week, I think, we had a session where we have come to the point of harmonizing between all of these countries and regulatory bodies on many elements, what is to be provided to the regulatory bodies by industry, resulting in a common technical document, a common dictionary to be used, reporting different events, and reporting on products that are being used.
		This was no small undertaking, and people had to work very intensely on this effort.  There's still much work to be done.  But, again, we have to from this Agency's standpoint, have strong science to participate and hold our own in those kind of discussions. 
		I would just leave my welcoming comments with that to give you a flavor of some of the kinds of things that we deal with.  
		I also wanted to bring to your attention some things that are going on in my own office in terms of either personnel or organization.  
		Clearly, after you met last year, I asked Dr. Schwetz if he would give up at least for a time one of the hats that he was wearing and become the full-time acting deputy commissioner, and he said he would.  
		But it also gave us an opportunity to ask Dr. Elizabeth Jacobson to take on the task of acting as the senior science advisor for science in my office.
		For those of you don't know Liz, she's an extraordinary person and scientist.  She was early winner of the Fleming Award, as I recall.  She's worked for many years in the research and the science policy area, in the Center and Devices, and has been really a wonderful addition to our staff.
		We have created a new office in the Office of the Commissioner, also the Office for Clinical Science.  We now have a person, Dr. David Lepai, who had been working in the Center of Drugs, detailed to that office while we're recruiting a person to head up that responsibility, largely looking at many issues in clinical science across the agency but particularly on those matters that deal with human subjects protection.  
		We also have a new function in the Office of the Commissioner, and that person is coordinating all of the different Centers and field efforts in the whole effort of bioterrorism preparedness.  
		Ellen Morrison from the field came in and pulled together a team in terms of making recommendations on how FDA should proceed in these initiatives.  And Dr. Gary Tchikami is now on detail to help develop a strategic plan in that area.
		Both of these positions are being advertised, both the ones for clinical science as well as the one for bioterrorism.  As you might know of candidates who might fill these positions on a full-time basis, we would welcome your input on that.  
		We also have, I think, another thing to recognize on the staff.  I would like to recognize the fact that Bern just recently received a very high honor and award from the Academy of Toxicology and just was out there and giving a major address. 
		And our Center on Drugs has just been told in terms of their training programs, they will be the recipient of one of the Deming awards.  So we're very proud of those accomplishments.  
		In terms of other recruitments, again, asking you to put on your thinking cap and networking cap in the National Center for Toxicological Research, Dan is searching for his deputy director for research.  
		And over in CFSAN we are looking for a person to take on the role of food safety.  
Susan Alpert, who had been in that position, just left the Agency a month or so ago.
		So those are another two key spots I think where we need people with strong scientific and research credentials in those particular positions.
		I will close my remarks with that. 
		I also know that you have a very busy day planned for you by the Office of Science, and so I will turn it back over to you, Mr. Chairman.
		DR. LANGER:  Thank you very much.
		Bern, I'll turn it to you to make some introductory comments. 
	Introductory Comments
		DR. SCHWETZ:  We wanted to use this morning to talk about emerging science issues that the Agency needs to be prepared for as we look in these next few years, and specifically from the standpoint that new science drivers, new products, new products drive, new questions, new issues, and the issues have significant implications for the resources that we need, the types of expertise we need to deal with those issues, the facilities that we need to do laboratory work and other work that's related to these issues.
		So over the past year we've been pulling together information from throughout the Agency, from the Centers, from the field group that relates to what we collectively think are the emerging issues and have begun to look at them from the standpoint of priorities and the implications for the types of people we need to have in the future to deal with the issues that these new products will represent.
		We feel that the right of change of new science, new products, new technology coming to us is going to be faster than it has before, and we don't want to be in the spot of watching what happened today to try to decide what kinds of expertise we need.  
		So we're trying to anticipate how do we match up the recruitment and the molding of the Agency scientist profile so that we're staying up with what we anticipate to be the emerging science needs over these next years.
		So Liz Jacobson and the Center Directors and Dennis Baker are going to be talking about the bigger picture, in the case of Liz, and the people from the Centers talking about some specific examples of emerging issues from within their Centers.
		We want to talk with you about these and your reaction to these issues, your thoughts about the relative priority of them, the implications that these issues have for the expertise profile that we need to have in the future and how we'll get at those people to recruit them.
		From within this bigger picture and the examples that will be laid out, we also want you to think about specific pieces of this picture and the examples that you would like to have brought back to the board for more in-depth discussion in the future, because there are some of these that are going to be much more difficult to deal with just because of their novel nature than some of the others.
		And we would really like to pick your brain on how to find the experts to help in this, what do you think is the real priority of some of these things, or do you disagree with our opinion of the likelihood that these will come to be issues?
		So that's the kind of presentation and discussion we'd like to have this morning.  So I won't say any more except to turn it over to Liz.
	Challenges and Overview of Issues
		DR. JACOBSON:  Trying to get a handle on this topic really wasn't very easy.  We have certainly a plethora of challenges, as Jane said.
		The plan for the morning is to talk about the challenges that FDA faces in terms of emerging issues or in some cases in terms of issues that are already here.
		(Slide.)
 		The intention was to have a general discussion, and then in subsequent meetings of the Science Board to discuss in-depth perhaps some specific issues that you particularly are interested in. 
		The point is that when it comes to the challenges that we face, we'd like to be able to ride the wave of innovation in science and technology like the school surfer that you see and not get overturned like the Andrea Gale. 
		Next one.  (Slide.)
 		I'm going to discuss some of the challenges and do an overview of emerging issues, and then each of the Center Directors and Dennis Baker will spend a couple of minutes on specific issues that they're contending with, and then we'll have some discussion, both on the issues, per se, how do they strike you and what do you want to talk about more in-depth next time.
		And we'll also talk about the strategies that FDA should be using to meet those issues.
		Next one.  (Slide.)
 		So what is the challenge?  Well, to try to sum it up in one slide, we really feel that our ability to make quality and timely decisions is strained, and the reason is because science and technology are booming, which is a good thing, but it's not easy to keep up with that.
		Government and industry are making very big front-end investments in research and development, but we don't really have any indexing of that research and development investment to FDA to match what's going on, and not surprisingly, the number of submissions is increasing, and the kinds of submissions that we get are also becoming more complex.  
		(Slide.)
 		This slide just illustrates part of the investments.  It doesn't even give all of the government investments in R&D.  You can see both industry and NIH, the big bars in the back, and then FDA investments are the small bars, the relative investment and regulatory science is much smaller.  
		Next one.  (Slide.)
 		PhRMA found that, not surprisingly, this wonder investment in research and development is really paying off in biotechnology products, for example.
		PhRMA did a survey this year, and they found some 369 products in the pipeline in a survey that they did.  Now you can argue the numbers in terms of well, is it really 369; what is it? 
		But I think you can't argue the trend that increases in research lead to product payoffs.
		(Slide.)
 		In spite of the sort of divergence and support that I talked about, expectations of FDA by the public are really very high.  We have a long history of public health protection at FDA, and Americans have really come to depend on it.  
		They want the products that are resulting from the science and technology revolution.  
		They expect to get those products as soon as they're reasonably available, and at the same time they really trust that the system is going to alert them to any problems, and they recognize that FDA plays a part on that alert mechanism.
		Next slide.  (Slide.)
 		This slide shows a different survey, actually, from the one that Dr. Henney mentioned.  This is a survey done by Research America.  And it showed that 70 percent of the general public surveyed knew who FDA was and what we did.  In general terms, but they were familiar.  
		Compared to some 4 percent of people who knew what NIH was and what they did.  So we really have a lot of public recognition, and we need to continue the best safety net possible for the public.
		(Slide.)
 		I guess the point I'm trying to make here is that our output may look a lot different from that of NIH or CDC or NSF or other scientific agencies because we're regulators.  But our impact on public health is every bit as dependent on our being masters of the current science as theirs is.
		And most importantly, we have the potential as the gatekeepers of new technology to have a very powerful impact on the flow of that technology to people who need it.  We're very aware of that possibility. 
		It doesn't matter whether you're talking about drugs and devices or genetically modified plants and animals or gene therapies, we still have a very important role to play. 
		Dr. Henney has said on several occasions that we stand in judgment, really, of the best efforts that industry and academia are putting forth so it's very important that we also have very high quality.  
		(Slide.)
 		In trying to do an overview of emerging issues, we decided to group them in a number of categories.  You can see them here and also there's a copy of my handouts in your package. 
		 A lot of these categories contain a mix of issues that are emerging and those that are here now, and also it really does seem to be a truism for us at FDA that many issues never go away and old ones come back, or they recycle and they come back in a slightly different form.
		Next overhead.  (Slide.)
 		Under New Science and Technologies, we have things like genomics and proteomics.
		Pharmaceutical houses are already anticipating huge changes in how drugs are developed, and today's highly inefficient approaches are envisioned to be replaced by elegant bioinformatics driven drug discovery.
		In terms of tissue engineer products, we're already seeing hybrid bioengineered products are biology is meeting engineering and where new biomaterials are being used in very exciting ways.
		This poses interesting scientific questions and also interesting regulatory questions in terms of which center has jurisdiction.  
		In robotics and nanotechnology, Bill Joy of Sun Micro Systems listed genetics, robotics, and nanotechnology as the three most powerful 21st century technologies.  
		He worries that these three carry hidden risks of huge dimensions because they're self-replicating and they'll be able to be used by many individuals and small groups.
		We don't claim to be as envisionary as that or to be worried about that aspect of things, but robotic applications and medicine are here today and we need to be able to assure their safe and effective use.
		In July, we approved a robotics surgical device, for example, that allows surgeons to perform surgery while seated at a computer console that's remote from the patient. 
		And the surgeons say that although the computer controls the instruments, it feels as though their fingers are grasping the tip.
		So it's fun to imagine doing surgery on a patient in a remote setting, somebody in Antarctica being operating on by their surgeon at Mass General, but first we really need to raise the complicated questions that are raised by robotics and engineering, software safety, and human factors design, and a number of other disciplines.
		Nanotechnology is also no longer science fiction.  In April NASA and NCI announced a Memo of Understanding to develop nano explorers, their term, for the human body in the form of injectable nano robots or nano bots that will roam the body to detect, diagnose and treat disease.  
		And that kind of leads into the next category, biosensors.  These little nano bots would be biosensors, and probably drug use delivery systems as well.  
		But there are other applications of biosensors that we're already seeing.  '
		Our scientists in-house developed a chemical sensor to identify deteriorating seafood in the package.  
		We are also evaluating a hand-held advance nucleic acid analyzer that was developed by Lawrence Livermore to identify infectious agents, and we really see this as a type of instrumentation that would have incredibly wonderful applicability to the needs we have in our field operations.
		Transgenics, of course, is in the news a lot, in all kinds of applications, including gene therapies and starlink (ph) corn.  
		I think in an application you may be less familiar with, Atlantic salmon can be genetically modified with growth hormone, and they reach their full size and therefore their market ability point many days before unmodified salmon, so there's lots of applications of this technology, and our job is to assure that there aren't any adverse health consequences to these kinds of modifications.  
		The next one.  (Slide.)
 		The next general area is information management.  I've already mentioned bioinformatics as it relates to the products of genomics and proteomics, but we also have many applications in-house and some medical devices already approved, as a matter of fact, that employ artificial intelligence so this is obviously quite a step up from the computer-driven instrumentation that we think about.  
		We within FDA have just begun a strategic planning effort in the area of knowledge management.  Like the rest of the world, we own a tremendous amount of information, and we're getting volumes more pouring in every day, and we basically need to figure out how to know what we know and how to make that corporate knowledge base available and accessible to our staff who have knowledge needs.
		And, of course, there's a lot of interest in using computational approaches for predicting biological activity and toxicological properties of chemicals.
		In one sense, the next category is called public health questions, and officers in one way all of these things are public health questions.
		But here I'm really referring to specific problems that may be new or recurrent, and I'll just mention three of them.
		One that's been around for a while is antimicrobial resistance.  It cuts across all of our centers.  Each one plays a role in some aspect of dealing with resistance bugs, from approving the drugs that go into animal feeds and evaluating devices that have growth-inhibiting coatings.
		We also have a role to play in antiterrorism efforts.  People don't usually think of us in terms of anti-bioterrorism, for example, but many of the drugs that have been proposed for treating bioterrorism agents haven't been evaluated or labeled for those indications, so there's really quite a role that we need to play there. 
		Next one.  (Slide.)
 		The next category: Better tools and methods, also a rather broad category.  We need to keep up with quantitative risk assessment and modelling.  We play a critical role in the science of clinical trial design and analysis. 
		We need better predictive tests for things like alternatives to animal testing and better biomarkers. 
		How, for example, can we better predict hepatotoxicity.  
		And we also need better methods, more rapid, more field rugged.  
		Earlier I mentioned the hand-held nucleic acid analyzer. 
		We also need better tests for other things, like food-borne and waterborne parasites or viruses.  
		We don't have regulatory methods for natural toxins and seafood and algae that are found in dietary supplements.  The methodology for detecting allergens, such as peanut allergens, in unlabeled products is not well established. 
		We need rapid methods for microbiology that are validated, that are able to work in various matrices.
		And we need to look at food processing steps to see if we can intervene and reduce the incidence of food-borne illness.
		I think the Center directors each will have a long list of methods that they need that are particular to their Center.  
		The point I'm trying to make here is that the public thinks we can test for everything, and we can't. 
		Next one.  (Slide.)
		Well, this brings us to the people related part of our issues, and the first one I wanted to touch on was the flexibility of our workforce.  
		We have a lot of issues here.  You talked about some of them at your last meeting, training and retraining, recruiting high caliber people.
		You're going to hear an update this afternoon about the recruitment effort that CFSAN has going on, our Center for Food Safety and Applied Nutrition.  
		You'll get some feedback as to how that recruitment effort is going.
		Retention of the staff that we have is also important.  The Agency‑wide attrition rate from '95 to '99 has actually gone down slightly.  Our overall attrition rate has gone from 7.2 in '95 to about 5.8 in '99.
		If you look at scientific categories, specifically, the attrition rate for 5 of 9 scientific categories has gone up very slightly.  They're all under 9 percent, but the trend in several of those -- biologists, pharmacologists, math stats, computer scientists, and microbiologists -- have gone up a little.
		Interestingly enough, the rates for chemists and engineers, the attrition rate has gone down slightly.  So this is an area we're not quite sure what to do with those numbers, but obviously we really need to pay careful attention there.
		We also need to look at what kind of alternatives we have to permanent hiring. 
		Except for our user-fee programs, we've been continually losing people or not replacing staff when they leave so that we'll have money to put into our programs.  
		So if we can't do hires, what kind of other alternatives do we have, and that's one of the topics that we want to get into some further discussion with you. 
		Next one. (Slide.)
 		The other human issue here that I wanted to talk about is patient rights and consumer needs.  The first bullet there, human subjects protection, has been in the news a lot lately.  That's something that we are, as Dr. Henney mentioned, put Dr. Dave Lapei in place to pull together our efforts in that area.
		But consumers also want freedom of choice, and they want to exercise their right to know.  This place is a very big responsibility on us to be good communicators.  So not only to do good risk management, which is clearly important, but also to do good risk communication of that risk management.
		If we don't communicate clearly to the public, if we aren't transparent and open to questions, then we're ultimately going to fail because they won't believe what we say.
		We also need to be sure that we understand human behavior, because it really plays a role in everything, from what information you put on a label and how you display it to how you arrange the knobs on anesthesia equipment.
		Next one.  (Slide.)
 		So we have to plan for a lot.  
		We have to plan for a rapidly-changing technology, for a tremendous volume of information, for rapid response to public health questions, for a flexible workforce, and for patient and consumer needs.  
		Next slide.  (Slide.)
 		We'd like to discuss two aspects of this this morning.  First, we'll have the Center directors go around and talk to you more in detail about some of the issues that we just went over.
		And then we'd like to get your reaction to the issues and to talk a little bit about which of them you'd like to do more in-depth.  I know that Dr. Nerem has already asked for a future discussion at some date on tissue-engineered products.
		And the second question that we wanted to talk about were strategies that we need to employ to be able to address these issues.  
		Next one.  (Slide.)
 		How can we attract the necessary expertise?  And Dr. Schwetz mentioned this in his remarks as well.  
		I've just listed some possibilities here that we can come back to later on things that -- everything from the current paradigm, hire somebody if you need this particular expertise, to sort of ‑‑ that's a business as usual approach ‑‑ to getting very creative with collaborations and leveraging type initiatives.
		Next one.  (Slide.)
 		Some of the additional questions that we wanted to wrestle with a little bit today are what types of expertise do you think it's going to be particularly hard for us to get and how can we successfully compete for these people?  
		How do we stay flexible in terms of being able to meet new types of scientific questions as they come along;
		And how do we keep our infrastructure developed so that we can put these people to work in the most appropriate way?
		Last slide.  (Slide.)
 		I think one thing that is clear, and I've just got a couple of quotes here on the importance of science, is that we can't do this in a vacuum.  We have to work with our stakeholders in new ways if we want to be successful in staying scientifically strong, and that's the reason we've sort of orchestrated the session here today is to have some really good discussion on some of these questions.
		I think that's the end of my remarks.
		I don't know, Bob, if you want to go right into discussions with the Center directors?
		DR. LANGER:  Yes.  I was going to see if there were any questions right now. 
		Basically what we thought we'd do is have Liz give the talk as she did, then have the Center directors go over some of their specific issues relative to their Centers.  And then we have from 11:00 to 12:00 reserved for more general discussion.
		But there may be some more specific questions now or comments, and if there are it would be great to hear them.
		DR. ANDERS:  I have one specific addition to your list.  We have genomics and proteomics.  There's a new area called metabanomics, which is just starting to emerge.  Now metabanomics is the multi-parametric analysis of the metabolic products of the proteol.  
		And coupled with high field enimaranalysis and bioamphormetic strategies, you can rather remarkable things in analyzing biofluids.  The big pharmaceutical corporations, I believe, have formed the metabanomics consortium.  They've recognize the advantage of it.  
		I think it plays into a lot of things that the Agency does and we might want to hear about that from some experts in the field at some future date.
		DR. JACOBSON:  Sounds good. 
		DR. LANGER:  Bob, do you want to comment?
		DR. NEREM:  Yes.  Maybe when the Center directors make their comments they could help someone like me understand how research fits into a Center and the interface between research that might be part of the Center and the regulatory activity, because it seems to me that that bridge between science and regulation is what we have to try to understand if we're to be of help to you.
		DR. JACOBSON:  That sounds good. 
		I didn't try to dissect that out specifically because we were trying to focus this on issues and, really, research plays a piece in each of those issues, even when you get to the human -- 
		DR. NEREM:  It may be future discussion, but I think your research budget is something maybe on the order of $150 million a year.  I have no idea how that translates into how it gets done in the organization. 
		DR. JACOBSON:  Okay.  Good. 
		DR. LANGER:  Other?  
		Yes, Rita.
		DR. COLWELL:  I could probably just amplify in the more general discussion, but I'm fascinated by the fact that the initiative from the National Science Foundation are, in fact, basic research, nanotechnolgy, information technology, mathematics initiative to deal with improving quantitative risk assessment in modelling, prediction modelling, as well as education and training, which is of course one of the topics you've raised.
		And we're planning a major initiative in FY 2003 of the social behavioral sciences which the topics -- the subtopics that you list of human behavior, labeling, and even where you put the knobs on the anesthesia machine, it seems to me that there's some very nice parallel directions for the two agencies and that we ought to find some ways to collaborate and leverage for you the basic research that we do that can be put into practice in a very quick way here at the FDA.  
		So this is something you might want to cover later in the discussion. 
		DR. JACOBSON:  Sounds great.  I mean, that is the kind of synergy that we were hoping would come out of this kind of a discussion. 
		DR. HENNEY:  Liz, you might mention some of the things that we do with other federal agencies like NIH, where we have the MOUs with the Dental Institute and that kind of thing.  
		DR. JACOBSON:  Yes.  Actually, I'll mention a couple of them.  
		Dr. Colwell, we've had several interactions with members of your staff in terms of doing some forecasting of what the future technologies are going to be looking like in 5 to 10 years.  That's been a very interesting exercise, and it's resulted in several workshops.  
		We also have a Memorandum of Understanding with the National Institute for Dental and Craniofacial Research where they asked us to come and talk to their grantees so that their grantees get an idea of what are the regulatory questions that they're going to be facing when they bring their ultimate research idea that's turned into a product to FDA for review.
		And so we get a wonderful heads up on what the early developments are in that particular area of science.  And they get, the grantees get, a heads up in terms of what kinds of questions they're going to be expected to answer so they can design their experiments in a way that will lead to less problems at the end and swifter movement of those ideas from idea to product to consumer or to patient. 
		DR. LANGER:  Other questions or comments before we go on?
		(No response.) 
		DR. LANGER:  Do you want to turn it over?
		DR. JACOBSON:  Yes.  Center directors, do you have any preference or should we start at one end and go down or?  Start at the other end.  
		(Laughter) 
		DR. JACOBSON:  Janet, for reasons I know you'll understand, I'm going to do what David says.
		(Laughter) 
	Center for Drug Evaluation and Research
		DR. WOODCOCK:  I'm Janet Woodcock.  I'm the head of the Center for Drugs at FDA. 
		Can everybody in the room hear me?  No.
		Can the people hear me now?  In the back, can you hear me?  Okay, good.  I'll try to make this audible. 
		I was asked just to cover a couple of our science priorities.  We have a very long list at Center for Drugs, and so I can by no means discuss all of them.
		Liz has covered a number, the range of issues that we face.  
		First, we were asked to comment on the research effort and how that fits in to our regulatory programs.  
		Center for Drugs is really not funded in a way that we can conduct a robust research program, period.  We have tremendous needs, both in the analytical area, drug analysis, in the toxicology and biomarkers area. 
		I would like to have a program and a clinical trial design and analysis because that is a scientific discipline where there are very few foci in the academic realm of how to do that, and yet it is something that we are called to judge on and contribute to every day as far as the design of clinical trials and analysis of clinical trials for registration or pre-enrolled pharmaceuticals.  
		In addition, we need more research on things like behavioral science.  We're constantly asked, you know, do doctors follow the labels, what is the effect of direct consumer advertising on consumer behavior.  
		We do not have any research dollars that can be put against those.
		And, in addition, our whole drug safety area, we have tremendous research needs.  There's a large amount of data out there in the world about the impact of the outcomes of drugs, the use of drugs from link databases that are held by managed care and payers and other sources, and we don't have funding to link to those sources.  
		So in general we don't have a robust research program to discuss because we lack funding to do that.  
		As far as our priorities, I would say our No. 1 priority is a somewhat global one, and that relates to during safety.  
		I think the last four decades in the realm of pharmaceuticals has been devoted to determining whether drugs work or not, and there's been a long effort in clinical trial design and statistics and so forth, but we all have that down pretty well.
		I think it is rare to nonexistent where FDA would approve a drug, and people say the drug actually doesn't work if you think about that. 
		And we've figured out -- and that wasn't the way 40 years ago, 30 years ago.  There was often substantial doubt about whether drugs that were on the market worked or not, and that time is over. 
		But the safety of drugs and predicting how the toxicity and how the drugs are going to behave once they're used in the market is something I think is going to be the endeavor of the next decade or so for us.  
		And that has a lot of dimensions.  We need to be able to predict the adverse event profile, and that has to do with the toxicology, with clinical trial design, but also understanding how products are going to be used out in the marketplace, and something of a behavioral science aspect that we have paid not enough attention to over the years.  
		And also ascertaining signals and analyzing those signals.  And let me go into that a little bit more.
		In prediction, everyone agrees so this is no big news, that we need better, more predictive, preclinical models and more predictive biomarkers for toxicity, and the recent experience over the past save years, say in liver toxicity, after a drug is marketed, has shown us that we still cannot predict accurately -- and we're still going through this with drugs that are before us now -- we can't predict accurately which drugs are going to result in fatal liver failure once they're on the market.
		And this is a science issue.  These drugs have all gone through animal testing and they've gone through human testing, and we still cannot say which ones are going to have the rare, fatal, hepatic necrosis associated with them.
		We're getting better, but we aren't there yet.  
		And there are other types of toxicity we're still in the dark about.  The QT prolongation for the electrocardiogram and what that's going to be mean.  There are a lot of drugs that cause this.  What is the actual effect?  What is the actual outcome out in the real world?  
		So that's preclinical.  I know people are going to talk a lot here about genomics, but understanding genomic diversity and its effect on toxicity and on drug-drug interactions is an extremely important part of predicting toxicity because toxicity may be a direct result of genetic diversity, of course.  
		And for the FDA it isn't just a matter of having scientific understanding of this.  It's a matter of trying to figure out how can we make sure that the people who are going to use these drugs out in the real world have enough understanding of this that they can use the drug safely? 
		In my mind, it's all well and good to talk about genomics and so forth, but if you can't get a real world understanding of the clinical community and alter their behavior to take into account the scientific knowledge it's generated, you're still going to have the same safety problems.
		So the challenge of identifying the genetic alterations or phenotypic alterations is just the start, at least from a regulatory point of view.  
		Clinical testing methods for prediction. We look at the animal and the clinical testing as a sort of continuum.  It has the same degree of challenges as far as trying to determine from the clinical results and predict the toxicity out in the real world.  We still are not there yet.
		As i said, capturing and disseminating this knowledge in a way that just isn't out there but is actually effective in making sure that behavior is modified appropriately based on the knowledge.
		Right now, in clinical medicine, we know much more than is effectively translated into clinical practice, and the lack of transfer of that knowledge impacts very severely as the recent IOM report on medical errors brought out.  It impacts very severely on safety in a negative way.
		Now, as far as ascertainment and risk assessment, in the post-marketing area, we have a tremendous need for better ways to not only detect signals of toxicity, which is what we do now with our spontaneous reporting system, we get hints of toxicity that's occurring out in the real world. 
		And we get about 250,000 reports yearly of adverse reactions to drugs that are spontaneously submitted to either the manufacturers or us.  But then we have to have better ways of analyzing these data, and we can't just look at the spontaneous reports.  
		They're inadequate.  They lack a denominator.  
		They don't tell us about incidents or causality, for that matter, and we're having tremendous debates about this in very public quorums.
		The withdrawal of phenylpropanolamine, potential withdrawal from the market, that was recently in all of the papers, it's an over-the-counter medication that's been on the market for decades, but we feel is associated with a higher probability of hemorrhagic stroke in young women who take it. 
		It took us 15 years, at least, to develop an appreciation of the causal link well enough to make this recommendation to the public, and we've got to do better than that in the future. 
		My second point, and I don't want to take too much time, another issue that I think is really a key for Center for Drugs, and we've put a tremendous amount of effort into this, and it really is becoming a scientific discipline, is knowledge management.  
		We are basically, in the Center for Drugs, information or knowledge workers.  We get tremendous volumes of knowledge and information and we process and analyze that information, and we have information outputs, and we must develop better medical informatics. 		And I have a list here of the types of things we're working on.  We are putting a lot of effort and work into this but we need to bring it to a much higher level to be effective in the future especially as all of this informatic information is going to start to pour into us from all the scientific efforts that are going on.
		So those I see are two of our highest priority science issues that we'll be dealing with.
	National Center for Toxicological Research
		DR. CASCIANO:  I'm going to go to the podium.  
		We at the NCTR do not have a direct regulatory mandate, but we do provide regulatory scientific background for the agency.  
		Could I have the next slide, please.
		(Slide.)
 		The issue that I decided to discuss is the issue of better predictive tests, and we at the NCTR feel that our mission is to develop, modify, characterize and validate better predictive toxicological tests.  
		We are working in these various specific areas, and I'm going to tell you a little bit about the DNA and protein-based technologies.
		Greg, we just hired a new division director of chemistry who's very interested in metabanomics.  We're in the process of developing programs in that specific area. 
		I'll tell you a little bit more about that in my subsequent slides. 
		We've developed transgenics, both transgenic mutational-based systems as well as carcinogenesis‑based system that we're in the process of validating.  
		And, of course, we're interested in understanding the toxicology response that occurs in the human and not in our rodent surrogates, and so we are constantly looking for rodent homologues for biomarkers.
		An alternative, the animals, we have a program in developing human tissues, primary human cell cultures to help us understand and predict the human response and, of course, computational science underpins everything that we do.  
		Next slide, please.  (Slide.)
 		And this is a slide that you've seen many times, and I'm going to tell you two projects we have undergoing in the DNA area.  The proteonomic area we're just beginning to develop.
		The two projects that we have ongoing are placed on this slide.  
		Human genotyping and use of gene expression profiles to predict outcome.
		Next slide, please.  (Slide.)
 		The gene expression profiling direction is based on utilizing primary rat cells from a variety of different organizations and exposing rat cells to known carcinogens or mutagens, and evaluating gene expression profiles.
		And then utilizing the same technology to investigate exposure of the particular organ to which that toxicant is directed; 
		And utilize then primary cells, human cells in culture, and be able to predict human responses.  
		So we have a relatively large program developed in that specific area.
		Next.  (Slide.)
 		Dr. Fred Kalibur at the NCTR is developing a risk chip -- he calls it a risk chip.  It's a single nucleotype polymorphism chip that the polymorphs are constituted in xenobiotic metabolism enzymes and the p450s and in the Phase 2, two enzymes, and he's also developing DNA repair polymorphs on this chip.
		He is collaborating with and leveraging with genometrics in Houston, and they're just validated a mini-chip to indicate that the process by which they are developed has potential merit.
		Next slide, please.  (Slide.)
 		Many of us in the various toxicological disciplines have been doing proteonomics for years, we just didn't call it proteonomics.  Now we're beginning to gel that apparatus to apply it to our surrogate systems as well as the humans, and protocols are beginning to be developed in these specific areas, and we're going to be moving in this direction at a high level in the future.
		Next slide, please.  (Slide.)
 		What are our problems?  The problems we've attempted to identify within the Agency is whether or not we should develop our own chips, or should we be utilizing commercially-developed chips?
		And, of course, we have the problems that everyone has, is how do we staff the bioinformatic requirement is associated with all of the new technology that I just discussed, and how do we supplement our staffs in that particular area, is a very difficult problem, especially if you're located in the middle of Arkansas.  
		So any help you can give us, people who are looking for the natural environment, who are hunters or fishermen, we would be very appreciative.
		I think this is the last slide.
		(Slide.)
 		We are attempting to utilize creative equipment other than traditional recruitment procedures, and if you have any suggestions or ideas on how we can enhance that, I'd be very interested in hearing them.
		Of course, leveraging and collaboration, this was mentioned by Liz in her discussion, and we have also the ability to purchase academicians for short periods of time.  
		This is through a methodology of interpersonal act, and we can buy academicians who are interested in spending more than just a single year as a sabbatical with us, and that's one mechanism that we are using to supplement our deficit in the bioinformatics area. 
		So if anyone has any questions, I'd be pleased to respond.  
		DR. LANGER:  Questions or comments at this point? 
		(No response.) 
		DR. LANGER:  Okay.
	Office of Regulatory Affairs
		MR. BAKER:  The Office of Regulatory Affairs, of course, is the field organization for the agency, and many of the issues that Liz brought up this morning are direct issues for our office.
		We are basically the sensory system for FDA, with our employees moving across the nation and across the world.
		Our employees have to have the ability to cover all areas for the Centers.  They've got to be steeped in science to be able to understand and identify new issues and determine if concerns warrant the attention of the agency. 
		They also have to understand how decisions of other government agencies directly impact what we do.  
		And I guess the last thing they have to do is they have to educate, and so we've got a broad-based group of people to do these things. 
		We operate out of five regions, 20 districts, and 13 laboratories doing the regulatory work.  
		And we've had, unlike some areas of the agency, we have had a tremendous turnover in staff.  In the last couple of years you have had a new ACRA (ph).  That's me.  A new deputy.  
		We've had three or four headquarter office directors come into ORA, four of four deputy office directors, five of ten headquarters division directors, four of five of our regional Food and Drug directors, 18 of our 20 district directors, and 9 of our 13 laboratory directors. 
		You're talking about a tremendous training need that we have to get at our new #cmpls, both management and our basic line employees.
		With that in mind, we've been developing a virtual university for the training of our staff into to get more rapid training to the individuals and also to reduce training costs, trying to bring them into specific locations.  It takes time and money.
		We've been working with the Office of Science to deliver training in conjunction with industry to get into new emerging science and technology issues so that our people understand what they're seeing out there.
		At the same time, we have to have them  sufficiently grounded in science so that they understand processes.  
		For example, they may be in Merck one day with a very sophisticated production technology.  The next month they may be in a place in India or China where you're working at 1930s level technology, where they're still using old balances and whatnot to weigh out ingredients. 
		So they have to be able to transition between technologies.  
		We're also having to balance between our domestic and foreign regulatory responsibilities, trying to make sure that we're covering both equally so that consumers are getting the best product possible. 
		We're having to deal with a tremendous influx or importation of goods now, and that means we have to do a better job of rapid methods, screening of products, so that we can get the best picture we can of products being entered into the country.  We have tremendous rapid methods needs.
		At the same time, we are on track with our laboratory consolidation as we move to consolidate functions and have better, more improved, more modern laboratories with better equipment.
		We've added five pulse-field Gelve electrophoresis units over the last year so that we are capable of doing some fairly high tech analytical work. 
		We are moving towards laboratory accreditation, and we are moving rapidly to get all of our laboratories accredited.  
		We have been doing a check sample program.  We did 13 during FY 2000, and this was also included as a pilot study participation in the AOAC proficiency program.
		We've been doing antibiotics sensitivity screening for Salmonella in order to generate data on the extent of antibiotic resistance, Salmonella in our food supply.
		We've worked with CFSAN on this particular project and will continue to work in this arena.
		We were instrumental in planning an implementation of the program in our Denver program.  During FY 2000, we found quite a few, actually about 250,000 isolates, found several antibiotic resistant strains.
		We've been putting on new workshops for our new laboratory directors in order to enhance communications, both amongst themselves and with our Centers.  We put one together that was the first one that was designed as an interactive workshop with discussions focusing specifically on improvement of communication amongst labs, our various customers, and development of processes to improve customer service.
		We've been working, of course, on the dioxin strategy.  As most of you know, we have dioxin as an issue.  We've worked with our Arkansas Regional Laboratory to ramp up about 500 percent our analytical capability in the area of dioxins.
		We've been active in the transgenic area and specifically recently in the transgenic corn issue.
		Finally, we've brought our public affairs specialist into a forum to deliver a message on a national basis for FDA and we essentially will choose a specific message we want them to carry.
		They do a number of things in dealing with the public at all levels, but we hadn't had a coordinated function in the past of trying to get specific messages out on behalf of the agency on a national basis. 
		We have ramped that up and that program is working well at this point in time.  
		And with that, I'll -- I've hit some very broad areas in a hurry, but I think I gave you a flavor for what's going on in ORA at this point in time.  
		DR. LANGER:  Thank you.
		Any comments or questions?
		(No response.) 
		DR. LANGER:  Steven.
	Center for Veterinary Medicine
		DR. SUNDLOF:  Well, thank you.
		The Center for Veterinary Medicine is responsible for all animal drugs and animal feeds that are used in the United States, and that includes things like pet food and feed for food animals. 
		I could give you an entire presentation that would last a day just on the issues that have come up through animal feeds, the most notable being the mad cow disease, the BSE issue.  But there are all kinds of things that can get into animal feeds that are potentially hazardous to the public. 
		But I'm not going to talk about animal feeds today, I'm going to talk about some other topics.  
		The topics I want to highlight are the ones that I spend most of my time on.
		(Slide.)
 		Antimicrobial resistance.  Quantitative risk assessment, which is an area that we're moving into, and although it is an exciting area, trying to get the regulations to catch up with the new kinds of sciences is always an issue.  And animal biotechnology.  
		The issue I spend probably most of my time dealing with is the area of antimicrobial resistance, and you've already heard some of the speakers talk about that.  
		(Slide.)
 		And our goal here is to ensure that significant human antimicrobial therapies are not compromised or lost due to the use of antimicrobials in animals, and this is a tough problem since antimicrobial drugs are very useful in animals, especially when they're needed to treat infectious diseases.
		So we have a real balancing act before us in trying to get a handle on where is the right balance between the needs of the animals and the needs of the public.  
		So we're looking at radically changing the way that we've approached it from a regulatory standpoint.
		(Slide.)
 		First of all, we need a new framework to regulate these products based on their ability to produce resistance and pathogens that are important to humans.  
		We need an improved monitoring system.
		We need to know what's going on out there in terms of the emerging resistance. 
		We talk about judicious use by veterinarians.  Veterinarians have to use these drugs more responsibly to preserve them for animals and for humans.
		(Slide.)
 		We're looking for alternatives to antimicrobials.  
		And we're investing in research in this area.
		In terms of regulatory changes -- this sounds fairly bureaucratic -- Guidance for Industry, No. 78.  I'm sure you've all read that.  It was published in 1998, and basically it was an announcement to the United States that we intend to take a more aggressive approach towards the regulation of antimicrobials in food animals especially, and that we were going to start evaluating these products based on the rate and extent of resistance development and changes in the animal enteric bacteria that are known to be pathogens to humans.  
		(Slide.)
 		So that was our first wake-up call to the public that we were really going to get serious about this. 
		(Slide.)
 		Monitoring is the next area.  Before we could regulate, we felt we needed a surveillance system out there.  It was no good trying to regulate in the absence of having good information coming back at you.  
		So we developed, in conjunction with the CDC and the USDA, what is now referred to as National Antimicrobial Resistance Monitoring System.  It's a national surveillance program.  It looks at human and animal isolates of bacteria that are pathogens to humans, and monitors over time the development of resistance.  
		Next.  (Slide.)
 		This is kind of just a schematic of how it works, the Foodnet System, CDC's Foodnet System, in order to get samples from actual patients, and there are 8 to 10 catchment areas in the United States.  
		So you get a very good representative sample of humans that have been subject to food poisoning.  They isolate the bacteria.  They send them down to CDC in Atlanta.  They run sensitivity screens on these various isolates.
		And the little Petrie dishes down there at the bottom, the gray is Salmonella, the red is Campylobacter; green is enterococcus, and yellow is shigella.  So that's how I remember those.
		And those are the organisms that we're currently screening for.  And looking at sensitivity to 17 different classes of antimicrobials.  We're using the exact same system for looking at animals.
		And mainly we're looking at animals, carcasses of animals at slaughter. 
		Collecting the same kinds of organisms from them, and looking at resistance development to those same 17 antimicrobials, and by doing it in this way, we can see the relationship of the animals developing resistance to the incidence of human disease, which is resistant to antibiotics.
		So this is extremely important.  This is the core of our regulatory system.
		Next.  (Slide.)
 		So just a recap: NARMS is to provide descriptive data on the extent, temporal trends of resistance and enteric organisms from humans and animal populations.  
		Next.  (Slide.)
 		Judicious use is another area, and it's a program that has been adopted in the human medical profession, that there's a lot of attention now on education being directed towards physicians to use drugs in a responsible manner, such that they won't produce resistance.  
		We are doing the same thing for animals, and we're working with the American Veterinary Medical Association, actually funding some of their educational programs, and having each of the species specialty so the cattlemen and the swine producers and the chicken producers and the turkey producers all are developing their own judicious use guidelines and they're doing it specifically on a disease-by-disease basis so they have very specific guidelines that they're using now in order to preserve these compounds. 
		We're also looking at alternatives to antimicrobials, and the one that seems to have most promise right now are competitive exclusion products.  Mike Doyle knows much more about this than anybody else in this room, I'm sure. 
		But what these are are cultures of microorganisms, bacteria, primarily, that are administered to the animals by various routes.  But they eventually colonize the intestinal tract of these animals, and they compete with pathogens like Salmonella, Campylobacter, and E. coli, so that the animal's intestinal tract is not colonized by those pathogens.  
		And these have a lot of promise.  From a regulatory standpoint, they have some problems that we're trying to work our way through.  We already have one of these products on the market and we hope to see a lot more in the future.  
		Research.  In order to run these programs and have sound scientific regulatory decisions, we need to have good research, and we're funding intramural research and extramural research, and you can see some of the things that we're funding there.
		We're also working with NCTR and making sure that everybody knows what everybody else is doing.  	
		But this is really important.  When you look at the issues involved here, we just don't know how these microorganisms move through the environment, what animals are causing the predominance of infection.  Some very basic issues, basic scientific issues, that we just don't have good answers for right now.  So research is very important to us.
		(Slide.)
 		The next area that I want to talk about is quantitative risk assessment.  
		We actually conducted our first and finished our first quantitative risk assessment.  And I'm a true believer now.  Where it can be done is a wonderful tool.  You have such a clearer idea of where the risks actually lie and where you need new data.  It's just a wonderful tool.  
		They're hard.  They're very difficult to conduct, and I'm glad to see that National Science Foundation is investing in some research, because I think this is a really productive area. 
		We did our quantitative risk assessment on Campylobacter and resistance to fluoroquinolones. So doing microbial risk assessments, and CFSAN is also doing these, it's harder, I think, than the general toxicology chemical type risk assessments.
		But I think they will really pay off well in the future.  
		One of the problems that we have, though, is in the communication.  Communicating to the public, when we go from a "your food is safe" standard, to "your food has a probability, some certain probability of risk."
		It doesn't really fit into our regulatory standards as they are written right now, and so as we make this transition from the safe to the 'some certain probability of risk,' it's going to be challenging and it's going to be challenging to get the message communicated to the public.
		But I feel fairly certain that that's where we're going to go.  When you look at our international trade agreements, you look at the codex alimentarious, it's all based now on risk assessment.  
		World Trade Organization.  World Trade Organization under the sanitary, Phyto-sanitary agreements, calls for, in the case of trade disputes for risk assessments.  So we're going to be seeing a lot more of these. 
		Next.  (Slide.)
		The one that we've done recently is to assess the human health impact of fluoroquinolone restraint Campylobacter infections associated with chicken consumption.  And we used a data that came out of our NARM system plus case control studies, plus a lot of other information.  And all that is available.
		Next.  (Slide.)
 		Is available on our web site.  We just published the final version last month, and it's a very interesting document if you are interested in risk assessment.  
		Next.  (Slide.)
 		We're in the process of conducting our second microbial risk assessment, and that's to look at vamyacin and causing resistance to Synercid, which is a new drug.  It's the drug of last resort after the drug of last resort.  Vancomycin is no longer effective in treating patients with enterococcal infections in the hospital.  
		This drug just came out about a year ago.  The analog of that drug in animals is vancomycin has been on the market for approximately 25 years and was passed over as a human medication.  But because of the increasing resistance seen in vancomycin the drug companies went back and found this drug to be effective.  
		Now we have a problem, potentially, with the continued use in animals.  
		Next  (Slide.)
 		The next area I want to briefly discuss is regulating products of animal biotechnology, and there are basically two forms.  
		Biopharm animals; those animals that are being raised, for instance, goats, to produce pharmaceutically-active substances in their milk, which then get purified and are used as drugs or vaccines. 
		That's one of the areas. 
		The other area is agricultural biotechnology.  And that's producing animals that grow faster or disease resistant or have other characteristics that generally serve an economic benefit to the agricultural sector. 
		CVM is dealing with both of those issues.
		(Slide.)
 		We decided on the Food and Feed Safety.  So all of these animals that are being used for biotechnology purposes, even the ag -- or even the biopharm animals, have to go someplace when they are no longer useful.  And we have to make the decision whether or not those animals can be used for human food or for animal feed.
		Generally, at this point, we have not allowed either of those things to occur, but in the future as there are more and more of these animals out there, we're going to have to make some decisions on the safety of those animals in the food supply.
		Animals of biomedical research are generally not considered safe for use in feed.
		And the other issue that we're going to be dealing with and are dealing with are the environmental issues.  
		What about the vectors that were used to create these transgenic animals?  What about the potential for escape?  
		And we regulate these on a product basis not by process, unlike the European community, which has a general concern over biotechnology rather than looking at the individual products.  We try and look at the individual products and determine whether they're safe, regardless of the method by which they were produced.
		FDA believes regulatory authority for products of genetically-engineered animals may already be in place.  
		Under our laws, under the Food, Drug and Cosmetic Act, it says: "Articles other than food intended to affect the structure or function of the body of animals is an animal drug," and if you insert genes into these animals, then you obviously change the structure of those animals, and the genes are generally inserted to produce some altered function in the animal.  So you've met both of those criteria.
		So animals that are transgenically modified, then, are regulated as animal drugs, and supposedly should be going through CVM for review.
		I noticed that NCTR is creating transgenic mice, and I've asked Dennis to initiate a seizure action immediately.  
		(Laughter) 
		But we're going to have to be dealing with these issues in the future.
		(Slide.)
 		Here's kind of the poster child.  And you've heard about it already, and that's the transgenic salmon.  These salmons are siblings.  They're the same age, except one was genetically modified, and that's the top one. 
		And you can see that the -- this is an almost irresistible technology.  Once you have the ability to do something like that, how do you stop something like that. 
		So we're trying to be very careful.  We do have this particular salmon under review as a new animal drug right now.  We have numerous challenges, many of which are, what happens if this animal escapes into the wild?  How does it compete with wild species?  
		Because of the genes it may have survival characteristics that exceed the range of wild-caught salmon.  
		So there are lots of issues that we're dealing with in the area of animal biotechnology, and we're just at the very early phase of that, and we think there's going to be an explosion in this area.
		We have other animals now that are under review, but looking at knockouts, clones, all of these new technologies are going to be issues that we'll be dealing with in the future.
		I think I'll stop there and ask for any questions. 
		DR. LANGER:  Questions?
		DR. SCOLNICK:  I have one just because you're into this subject.  
		Has anyone tried to make a cow without endogenous cow (inaudible).  
		DR. LANGER:  Could you maybe repeat the question for everyone?  
		DR. SUNDLOF:  Yes.  Has anyone tried to create a, I guess it would be a knock-out, pryon cow.  Not that I'm aware of.  Maybe somebody else has better information on that.  
		DR. SCOLNICK:  My understanding of the science is if you don't have the endogenous pryon you can't be effective.  That's what it seems to me.  I don't really understand why no one tried to do that or why an agency is not trying to foster that to get rid of the whole problem.
		DR. SUNDLOF:  That's a great thought.
		Greg. 
		DR. ANDERS:  Steve, I don't know if it's possible by conventional breeding techniques to create a mega-salmon.  But if you did, would you regulate it?
		DR. SUNDLOF:  No.  Right now, we're trying to parse out where it is we actually want to regulate our regulatory authority.  I really don't want to regulate your transgenic mice.  
		(Laughter) 
		I'm probably not that interested in ornamental fish.  There are activities going on. 
		And I'm not really interested in conventional breeding that leads to these kinds of increased productivity.  
		And then we get to another area such as what about clones?  Should we be interested in animals that are cloned because that's the new technology that's going on now. 
		They're selecting the best genetic stocks of animals, cloning those animals and using those as parental and grandparental stock for raising animals, and we know this is actually happening.
		And should we be worried about that?  So that's another area. 
		What happens with the no-takes or the partial takes?  What do we do with those animals?  Lots of interesting questions.  
		DR. NEREM:  Just to follow-up.  So conventional genetic modification through the breeding is not regulated.  At what point do you step across the line? 
		DR. SUNDLOF:  That's the question.  At what point in all of the manipulation that can go on does FDA step in?  We're actually going to be working with the National Academy of Sciences to help us and give us guidance on where is the public protection needed and where should FDA be regulating.
		DR. NEREM:  When is a GMO a GMO.
		DR. SUNDLOF:  Yes.  When is a GMO a GMO.
		DR. LANGER:  Mike.  
		DR. DOYLE:  Steve, it seems that the environmental issue is one of the biggest issues regarding the fish anyway, so how does FDA get into that?  Would that be more of an EPA issue?
		DR. SUNDLOF:  Yes.  That's a question that we hear quite a lot.  Why is it FDA that's regulating the environmental aspect?  Actually, FDA regulates under the National Environmental Police Act, NEPA.  We have authority to regulate, and we do for drugs.  For the animal drugs that we approve, we require an environmental impact assessment.
		Some of those things are huge.  When we approved another one of our controversial products, BST, we even looked at methane production as it might cause greenhouse effects.  
		We looked at needle disposal and everything else. 
		So we have experience and we have staff that is trained in this area, but we are working closely with National Marine Fishery Services and Department of Interior, and the EPA, and this is actually going on at the White House level, to make sure that we're asking the right questions and getting the right answers back on this.  So it's a multi-agency problem. 
		DR. LANGER:  Bob.
		DR. NEREM:  I have to pass this on.  Greg just made a comment to me.  
		Apparently genetic modification by trial and error, we don't regulate, but when we know what we're doing then we will regulate it.
		(Laughter) 
		DR. DAVIS:  That's been one of the issues, the concern for -- concern about genetically-modified food.  Farmers have been modifying food for hundreds of years and we haven't been regulating that.  So why is laboratory-modified food uniquely different than PhARMA-modified food?
		And if you take that analogy, we have the same thing with breeding salmon to look like them and they're getting out versus genetically modifying salmon and having them get out.
		DR. SUNDLOF:  And, in fact, there's a tremendous amount of environmental pressure, just from raising domesticated salmon, getting out and competing with the wild stocks.  That alone is a huge problem. 
		DR. LANGER:  Others?  Yes?
		DR. FENNEMA:  A comment about this quantitative risk assessment and your concern that the public might not accept this.  
		Would not a good model, which is a precedent in my mind be the 12-D concept that's been used for years and years and years for sterilization of canned food?
		DR. SUNDLOF:  I'm not familiar with that.
		DR. FENNEMA:  Well, it is a probability approach to sterilization from that, which is you've got all kinds of physical evidence of billions and billions and billions of canned foods where this has worked.  So it might be something for you to look at because it may be a useful tool in convincing the public that this works.
		DR. SUNDLOF:  Thank you.  
		DR. LANGER:  Probably we should go on.
		Kathy. 
	Center for Biologics, Evaluation and Research
		DR. ZOON:  Thank you.  It's a pleasure.  Now that Steve got everybody all charged up it's a good time to come up here.
		CBER has had a very active interest in a regulatory research paradigm since our origins, and in fact, for those of you who may not know we started back in the NIH and it wasn't until 1972 that we moved into the FDA. 
		So we have very strong ties to the NIH.  We're located on the NIH campus and our research labs, as well as very strong ties to the CDC, because many of the products we regulate have public health importance beyond just what FDA does.
		So it really needs to be a very integrated program with the National Institutes of Health, the Centers for Disease Control, and the FDA.
		So many of the issues that I'm going to describe, which are scientific priorities, have actually been focused on our regulatory mission in regard to the effects of these important issues on CBER's research program.
		Now in saying this, CBER uses both for lab and non-lab a research-reviewer model to address the question of how do we integrate the science into the regulatory paradigm?  
		Well, the same people who are doing bench work also do the reviews or the same people doing new statistical modelling are the same people who review application, and we believe this is a very effective way at integrating science into your programmatic and regulatory responsibilities.
		Recognizing the resource limitations we've had over the past several years, it's been a real challenge to maintain this program, and we have supplemented our program in a number of ways through various leveraging activities.
		One is working with the NIH on interagency agreements.  
		Another way has been working with DARPA and DoD, extensions of various grants on these areas.  CRADAs with a number of companies to deal with some of the scientific issues.  The National Vaccine Program has been another. 
		Actually, our scientists apply for research grants.  
		So with that introduction, I'd like to now go into the research priorities.
		Vaccine safety is a major research priority for the Center for Biologics, and this way it encompasses both existing vaccines that we have today on the market as well as looking for the opportunity to facilitate the approval of new vaccines as well as improvements in vaccines.
		In particular, those areas right now are focusing on several points. 
		One is adventitious agents, which is key.  We don't want anybody to get infected with something they don't think that's in the product that shouldn't be in the product.
		And to do this, we have started establishing a microarray program looking at developing microarray chips for adventitious agents, and screening vaccines.
		This is in its infancy, and we've just recently been awarded a DARPA grant to facilitate this program as well.
		The other area is looking at new cell substrates for production of vaccines.  Using continuous cell lines has always been a controversy in vaccine production, and this is an area that we would like to see move forward and we think good science behind looking at this will facilitate the production of vaccines in this area.
		We also have the new areas of vaccine production looking at new types of vaccines for herpes, human papilloma viruses, et cetera.  
		And understanding the pathogenesis of these diseases so we can have good biomarkers for efficacy is very important and to integrate these programs and the understanding of our scientists that review these vaccines are critical to doing a good job.  
		In looking at blood safety, this is another very important area for us.  Clearly, the safety of the blood supply is paramount.  Looking for new and approved methods of assuring safe blood and blood products is critical.
		This is also expanding into the tissue area, and one that we are currently engaged in setting up new programs in. 
		So what are the areas that we want to focus on here?  And much of it involves nucleic acid testing.  This is extremely important in looking at increased sensitivity, specificity, and reliability, of tests for adventitious agents.
		Again, not only are we looking for things such as HIV, HCV, HBV, but also looking at for more nuisance agents like parvovirus B19.  We're also on the lookout for new agents that may infect the blood supply, and we have a collaborative effort with the CDC as sentinel.
		If there are new agents coming into detection, that we have a joint group that works on that and then works on developing the tests that might be needed to roll-out to apply to the blood supply.  
		But I think these are areas of high specificity and specificity and sensitivity.  
		Steve pointed out, and a couple of you also mentioned the issue of TSEs.  And this is, again, a very big area for both the vaccine and bloody area.  
		TSE agents, BSE, has clearly been in the minds of a number of policies in this area, but we are working very hard in our laboratories to develop new methodologies for validation for removal of TSE, detection methods for TSE.  
		We're hoping to use both microarray and proteonomics to help facilitate those studies, as well as new diagnostics. 
		So this is an area, not only have we been working with in a national level, we have also been very much engaged in these issues with the WHO and I think have had a lot of productive, collaborative efforts in that area as well.  
		The next overhead points out, or third area, which is dealing with therapeutic product safety.  This has become increasing important to our Center with the advent of new technologies, whether we're making products from transgenic plants.
		Steve mentioned already the issue of sourcing material from transgenic animals.  If they're biological products, we would regulate those as biological products, subsequent to their introduction of producing either these products in their milk or in various other body components.
		So this is something we're looking at very closely.  I think the ability to set up new policies and new guidance needs to be based on sound science and understanding of the critical issues.  
		Again, adventitious agents.  You're going to hear that in almost every product line we have because that's a key issue for us to maintain public confidence and public health factors.
		So that's another area.  
		Xenotransplantation is another area, looking at potential sourcing of animal organs or tissues to help supply critical tissues and organs in the absence of human organs and tissues is critical.  Again, adventitious agent testing is key.  
		We've had a case with porcine endogenous retrovirus recently where CBER has actually developed the tests that are now being used to analyze those particular agents in various porcine products. 
		So these are areas.  Again, some of our challenges both now and in the future are going to be stem cells; using stem cells to create new tissues, as well as the appropriate standards and controls.  
		We need expertise in developmental biology for such things as areas in assisted reproductive technologies, as well as understanding cellular differentiation factors.
		So we're in the process of trying to recruit a couple of people in this area to have at least a core that we can then leverage with the scientific community.  We're also working very hard in that area with the National Institutes of Health to establish those types of criteria. 
		In addition, gene therapy is continuously on the horizon.  We have an advisory committee on right now looking at what are the types of science that needs to be done to assure vector safety as well as improving preclinical animal models for assessing vector safety.  
		Again, we work very closely with the NIH and the RAC in order to elicit these and have a very robust program with respect to this area.
		The next area that I would like to focus on briefly is counter- and bioterrorism.  We've had a very active engagement with both the Department of Defense for vaccines for such agents as anthrax.
		We're also concerned about issues of having appropriate vaccines for plague and various other viral agents such as smallpox and equine encephalitis viruses.  Also things such as toxins -- Botox and other types of toxins and other bacteria as well.
		We have had some limited resources that have been given to us in this area.  There's a lot more work to be general.  Clearly, there's a public health need, and both a military need for these types of agents as well as immunoglobulin products that we also regulate at the Center. 
		Last as a priority is new approaches to clinical trials and adverse event evaluation. 
		(Slide.)
		This is an area where we think a lot of emphasis needs to be placed, whether we're looking  at new designs for vaccine trials, looking at new ways to detect low frequency adverse events, whether we're looking for new ways to do product approvals with respect to examining superiority or inferiority type of trials.
		Looking at new methodologies, especially with respect to statistical approaches.  All of our scientists are engaged in these types of processes to see that if we could find the very best models to look at, getting the most out of data, new issues with respect to data mining, for looking at vaccine safety and adverse events, as well as looking at new areas for improving health-related quality of life indexes, particularly in cancer patients and applying those to clinical trial designs.
		So this is just a very quick snapshot of our priorities.
		At the end, what do we hope to get out of this research?  What's the bottom line? 
		And the bottom line for our research and the hopeful outcomes of our research will be decreased adventitious agents and these products are elimination all together. 
		Decreased adverse events that are experienced by people taking biological products.
		Increased product quality.  
		And an increase in our guidance to industry so that product development could move forward, especially in new technology areas and improve methods and standards. 
		Thank you.
		DR. LANGER:  Thank you.
		Any specific questions?
		(No response.) 
		DR. LANGER:  Bob.  
	Center for Food Safety and Nutrition
		DR. BUCHANAN:  Thank you.  I think I'll sit here. 
		First, I'd like to pass on a message from Joe who extends his regrets for not being able to be here today.  And hopefully I'll do as good a job as he would normally do. 
		I'd also like to indicate that one of the innovations that Joe put into place not long after joining CFSAN was our annual priority document that we put out on the web and we send to all of our stakeholders that we update yearly that lays out the list of items that we put on our "A" list.
		These are the things that we intend to put out each year and accomplish, and then we have a report card at the end of the year that reflects back on how much we've actually achieved during that past year.  
		The new Priorities document is just about to come out so we'll make sure you all get a copy of it when it becomes available.  
		Likewise, at that same time, we'll publish our report card for this past year.  
		Also accompanying that is we have through the Office of Science within CFSAN, we publish a regulatory research needs document.  Now that did come out in July.  It's been circulated to most of the professional organizations.  
		It's been circulated to all of the federal funding agencies and to anybody else we can think of that has money or researchers.  This has proven to be a very successful means of leveraging. 
		Our estimate right now is that just simply was one funding agency.  We've been able to secure approximately $13.5 million on FDA regulatory research needs just by providing what our priority needs are. 
		So in light of the limited time, I do want to just pick up a couple of items and discuss them briefly that I thought you would be interested in from our Priorities document, and probably the most important that's going to be impacting us directly this upcoming year is that we're moving.  And this is going to be taking a substantial amount of our time.
		With possibly the exception of our Gulf Coast seafood laboratory in Dolphin Island, Alabama, pretty much everyone else is moving at some point this year.  We'll be moving from downtown out to the College Park facility.
		In large part at the recommendations coming out of our peer review that the Science Board oversaw, we have had a major reorganization at our Mod I laboratory.  We now have the establishment of our Office of Applied Research and Safety Assessment.  
		And in addition to that, we'll be undergoing a major renovation at that fact to strengthen both our nutrition program and to strengthen our toxicology program.
		I might note here in something that you can help us with in the upcoming year is we will be as part of that reorganization recruiting a new director for that office and a lead scientist for toxicology.  Both of these are scheduled to be SBRS level positions.  So we're going to be looking for some really senior people to help us strengthen and bring into fruition some of your recommendations.
		I'd also like to mention that this is the third year of the Presidential Food Safety Initiative Program.  This has been a very highly successful program in terms of both regulatory and science issues, and that would be expected since our research program is intimately integrated into our regulatory program. 
		In that regard, we have a great deal of work to accomplish this year in a number of important areas.  Just to identify a few of them, we continue to work for implementation of HASUP both in terms of implementing our seafood program and getting our juice acid rate in a final form.
		We have initiatives in the area of egg safety, proto safety, sprout safety.  Each of these are both major regulatory initiatives and scientific issues as we support those activities.
		We were called upon by the President this past summer to accelerate our activities in the area of listeria monocytogenes, and this is both a very strong research and regulatory initiative.
		We have continuing activities in the area of antimicrobial resistance.  Many of them are in close coordination with what's going on at CVM.
		We have also had an ongoing activity in the establishment of good agricultural practices for reducing food safety concerns.  
		We've also had a number of issues that Joe talked a bit about when he met with you the last time you were together.  
		We have ongoing activities in the area of dietary supplements, and we are very pleased to see that we have been provided additional funds in this year's budget to establish a collaborative program with the University of Mississippi's Center for Natural Products Research, and that will be initiated in the upcoming year.  Certainly it is a very high priority area. 
 		We've seen, as Liz said, the recycling of a number of issues, too, that we're going to be taking a substantial amount of our time in the upcoming year will be methyl mercury and dioxin, two that have surfaced once again after lying dormant for a year or two so we'll be devoting quite a bit of effort there.
		And also one that has obviously been in the papers a lot is GMO Foods and how do we assess the safety of these products and appropriately handle them in the marketplace.  
		A second area I'd like to bring to your attention is to reinforce some of the comments that Steve made in the area of risk assessment.  
		Risk assessment, while we've been doing it in the chemical area, microbiological risk assessments have come to the forefront.  We have increasing activities in trying to integrate those two together because many of our risk assessment resources that we use for microbiology are tied up with our chemical risk assessment activities.
		So we have now a very scarce resource that we now have to be able to set priorities on in terms of where are we going to take our scientists and devote their time and energies.
		This is also -- this is where success has generated its own problem.  Certainly in the area of both food chemical, risk assessments and in food safety microbiological risk assessments, FDA has acquired an international reputation as being the leaders in this science.  
		We are called upon to assist on an international basis supporting both WHO and FAO in international risk assessments through JCFA (ph) or the newly formed ad hoc consultations on microbiological risk assessment. 
		So we're trying to balance our international commitments with our own limited resources.
		Just to give you an idea of how heavily we are involved in these international activities, Steve did mention codex alimentarious.  
		But based on my last count, 14 of the 18 codex alimentarious committees are headed, the heads of delegations, are FDA.  So it's taking on an increasingly important role.  
		We have, as one of our priorities, restructured our Advisory Committees within CFSAN, expanding them substantially.  This will be a challenge for us to get the best that we can to serve on these advisory committees, and I know that you have all been tapped here.  So any of your recommendations of who can help us in our areas of both our General Advisory Committee, Biotechnology Subcommittee, Contaminant Subcommittee, GMO Food Subcommittee, and Dietary Supplements, we're very much looking for the best and the brightest to serve on these, to help us through some very difficult scientific issues. 
		I might note, also, as a developing area that's going to take some priority considerations is in the budget language.  There has been some changes in the National Advisory Committee for microbiological criteria for food.
		This is an interdepartmental committee that we relied on heavily to bring our microbiological issues forward.  
		There is going to be a restructuring of that committee, and in the meantime we are probably going to have to expand our own Advisory Committee to deal with many of the pressing microbiological issues.  
		So, again, we are going to be looking for your help.  
		A couple of other areas that reinforcing the comments of the Center directors, assessing safety, continues to be a major thrust for us.  Two of the areas now that we're spending a lot of time on is how to effectively assess the safety of allergens, particularly in conjunction with GMO Foods, and also improving our adverse event reporting.
		Another issue that was mentioned earlier but is taking increasing importance is the validation of methodology.  
		We have the need to have methods that have been validated to the appropriate extent.  On the other hand, very often as we respond to either regulatory or public health concerns, we have the need to rapidly validate methods as we have to deal with the thousands of different food matrices that can be involved. 
		So this is going to be very much of an issue.  
		And then the final one that I'd like to mention as a priority area is the areas of tracebacks and investigations.  One that we work very closely with, ORA with.  
		Again, this is one where success brings its own problems or new challenges.  During the past years we've worked closely with CDC to get things like Foodnet and Pulsenet on line and accepted around the country.
		In the past, it used to be that food-borne disease, we'd say that about 60 percent of food-borne disease was untraceable.  Well, during the last couple of years because of things like Pulsenet, many of those small outbreaks that were scattered around the country, we now know that they are outbreaks and we could begin to trace them back.
		And that's increased tremendously the burden on our people that are involved in public health outbreak investigations.  
		And, again, we're looking for new ways of how to handle tracebacks, new ways of how to take the information that we're getting as a result of these tremendous improvements in surveillance.
		All those, informatics, and proteonomics and genomics, all that is bringing us to the point where now we're learning the answers to questions that we've never been able to ask before, and we have to find new ways of being able to investigate those and find out the sources of the problem.
		So I hope I've given you an impression that we're going to need your help.  We have a tremendously large menu to select from this upcoming year, and we're looking forward to working with you to find ways of dealing in new ways with the ongoing problems we have. 
		DR. LANGER:  Any specific comments or questions?
		Yes. 
		DR. DOYLE:  Bob, the standard methods that the Agency's been using for years has traditionally been cultural procedures.  With PCR and all these more advanced and available to us, will the Agency soon be adopting those methods routinely for the industry to use as markers, if you will? 
		DR. BUCHANAN:  Mike, if you go back and look at damage, every so often it's updated.  In the latest edition we have an increased number of methods that are what we'll call the classic rapid methods. 
		Certainly the validation of those and the ongoing validation as manufacturers, commercial kits, modify their protocols as a challenge to us.
		But I would say that many of the standard methods that we currently use in our programs, both within CFSAN and in the field are increasingly relying on things like PCR technology or immune technology.  
		So, for example, our ability to conduct an international survey for Shigella for the first time, because we always knew that Shigella was in foods, we just didn't have a cultural method that was effective, for this past year we've been able to include a survey of produce because we had a PCR method that now has become sort of the standard for the Agency.
		So, yes, we use the best as we can, understanding that these methods do have to be validated to the point that we can use them for regulatory concerns. 
		DR. LANGER:  One last presentation, David, and then we'll take a break.  
		DR. FEIGAL:  Thank you.  I actually have your ears for a little bit longer this afternoon so I'll keep my remarks focused on some of the hot topics.
		Actually, I decided to select them in an arbitrary and capricious manner.  I picked the topics that we asked Congress for money for -- 
		(Laughter) 
		-- and that they actually gave us money for, and not every year do they give us money for specific topics.  
		Last year, for example, the funds were all earmarked for faster product review, but this year they actually earmarked money for genetic testing, the reuse of single-use devices, development of standards, and then we received some money as part of larger agency efforts in the area of bioterrorism and antimicrobial resistance, and I won't say very much in those latter two areas.
		But I think that the first three actually illustrates some of the challenges and how the science intertwines with regulation.  
		The genetic revolution has already been talked about by many people here, and the issues for the Center for Devices range from topics dealing with developing the diagnostics that will be used with pharmacogenomics;
		The very rapidly expanding area of genetic testing of humans for genetic traits, and,
		Then there are many nonhuman genomic examples.  In fact, you were just asking about one of them which is the applications of genetics in the microbiology rapid diagnostics. 
		If you take a look at the way the genetic tests developed and what the challenges are, you'll see how this interplays with the regulations.
		Historically, genetic conditions in humans were found typically by looking at the biochemical markers that the disease created so tests for cystic fibrosis, tests for Tay-Sach's disease existed before we had any way of directly tapping the genes; in fact, probably before we knew exactly where those genes are.
		Those kinds of tests, historically, have been produced as kits.  They've been regulated as in vitro diagnostics, approved by the FDA and used broadly. 
		What's happened with genetic testing that's based on actually tapping the human genome is there's been an explosion from a few hundred tests a few years ago to now, over a thousand that are listed as available in the NIH's database of human genetic tests. 
		The interesting thing about these thousand genetic tests is that not even 10 of them are traditionally developed in vitro diagnostics.  These are all offered as services by individual laboratories.  
		In fact, the majority of them by university laboratories.  
		The methodology, the test itself, does not travel in interstate commerce, if you will.  The blood travels to the laboratory, and the information is returned as a service.
		And the complexity of the issues around genetic testing and the question of why should something as important as the information from genetic testing, which unfortunately is bad news.  There aren't that many genes that you can tape into that tell you something that you really wanted to know that was good.  
		The issues of informed consent, the issues of population screening, the issues of discrimination, have led the Secretary, 
Dr. Shalala, to form a Secretary's Advisory Committee on genetic testing to explore these issues, and one of the strong recommendations of that group is that these tests actually require oversight, and the ability of the regulatory process to assure that these have the same consumer protections that we do for other in vitro diagnostics.
		But the thing that we have to say as a starter is that we can't do business as usual.  Normally, in a typical year, we might have a dozen or so novel tests that are regulated with premarket approvals, and to actually look at a thousand novel tests and look at the volume of applications and the kind of evidence that's required and the challenges with some of the conditions which are rare.
		We've been looking with other agencies and in the public forum to actually develop a paradigm to phase in the regulation of these tests that's based both on the science of how they're conducted and also the public health needs.
		But then of course when we look at these tests we realize that other technologies, such trip (ph) technologies and snips (ph) and many of these things may make some of these technologies rapidly irrelevant, and it's going to be a real challenge for us to keep up.
		As Dr. Woodcock mentioned, one of the real fundamental questions for us is how do we obtain and manage expertise and what's our role and what's the role of other groups. 
		In this area, we've tried to leverage our own expertise by working with many of the societies that deal with molecular clinical pathology, that deal with genetic testing, and patient groups that are advocates for this year.
		We switched to the re-use area.  Genetic testing is a high-tech area.  Re-use must be a very low-tech area.  You're essentially talking about washing off and cleaning things and using them over again. 
		But, in fact, re-use is actually every intertwined with all of the high-tech developments in device development because the types of products that there's the most economic incentive to re-use are the expensive, difficult to manufacture. 
		Often, things that have used miniaturization and have used complex material such as new plastics or new coatings.  
		And the ability to be sure that these products will perform after a hospital has cleaned them is a key area.  
		We began to get concerned about this area a couple of years ago as we saw more and more products that looked like they'd be very difficult to re-use, and our own laboratories began a collaborative project with Walter Reed Hospital to look at devices which had been used and what were their characteristics and how have they changed, and in what ways were they not -- what types of things were likely to be unsuitable as a starting material to remanufacture a device.
		We've had to put forward a paradigm of how we would deal with this problem.  It has some parallels in terms of the regulatory challenges, just as the home brew of the University laboratories doing their own genetic testing gives us five or six thousand new manufacturers we've never had to deal with before, if we look at all of the high complexity, clinical laboratories capable of doing this. 
		Re-use gives us the challenge of dealing with the hospitals and surgery centers.  Again, another five to ten thousand institutions that perform these practices, and how do we make sure that the devices that are used in these centers are of high quality?
		We think that our role, actually, in the laboratory stimulated much of the work which has now been picked up by industry, which has been picked up by some of the third-party reprocessors, and by some of the original equipment manufacturers that want to demonstrate why their products are appropriately labeled as single-use medical devices, and this is an area, in fact, if we did not have the ability to identify what the scientific issues were, it would sound more like arguing over technicalities about whether something is labeled a certain way, does it have to be used a certain way, and what are the legal requirements and liabilities. 
		The third area that I would like to just touch on very briefly is the whole area of standards and standards development, and interestingly this was even labeled on the budget as science development.  
		The Center has had a very strong commitment to working with standard-setting organizations.
		We have members on the Board of Directors of ANSI, NCCLS, ASTM, and we participate in many of the ISO committees, including the committees that are looking at the revision of ISO 9000 and the series that are sort of the underpinning for the requirements you need to get a CE Mark for approvals in Europe.
		So we take this very seriously.  And as part of the changes that occurred in the Center's re-engineering program, some of it codified in the modernization act, we have incorporated the standard's process into the regulatory process.
		You know that FDA's motto historically has been "In God We Trust, Everyone Else Sends in Data."  In the Center for Devices, you also can substitute conformance with the standard where a standard has been recognized for sending in the data that showed you are accomplishing the same thing that the standard has been accepted for.
		And we've had a process of identifying and recognizing standards to assist not just in the application for new products but also it's used in the third party program, the third party review program; in programs such as mutual recognition efforts which are slowly coming along and in many of the international harmonization efforts.
		So the standards movement has had a very important role.  
		Often we're in the position of evaluating the standards and the basis for the standards that's worked with the others.  In fact, that's the majority of the cases. 
		But there also are times where, in fact, our laboratories provide the data that are used by the standard organizations in order to set the standards.  
		And, obviously, we tend to pick the things that either strongly affect medical devices or affect the radiological health.  
		So this is kind of a -- just as this morning has been kind of a potpourri of issues, we could actually go on about a dozen others, but I thought I would at least begin the discussion with three areas that Congress has funded. 
		We have all the same issues that the other Centers do, which is how do we deal with managing expertise.  
		How do we attract it, how do we maintain core competencies.  How do we teach people that their job is to find the expertise they need to make a science-based regulatory decision.
		That may be within the Center.  That may be tapping resources within the Agency.  That may be extending out more broadly as other Centers do to the NIH, to the Center for Disease Control.
		That may be using our academic collaborations and other efforts. 
		The culture that we want to build in the Center is a culture that recognizes that this is a science-based endeavor, that this is science-based and evidence-based regulatory decision-making, and it's the scientist's job to bring the best science to bear on the issue.  
		Sometimes that will be from their own core, expertise and competencies, but other times there will be a contractor of knowledge, if you will.  It will be their job to make sure that we have the information and background to make the decisions.  
		So I'll be coming back to some of these themes this afternoon, so let me stop now.  If there are questions, I'll be happy to take them.
		DR. LANGER:  I think what we'll do is we'll take a 15-minute break, and then we'll come back and we can discuss specific points and then of a more general discussion we'll put on a slide to help focus that. 
		Why don't we take a 15-minute break.
		(Recess.)
		DR. LANGER:  One comment before we get started, and I wanted to put that slide up.  If everyone could activity their microphones before they speak, that would be good.  
		I was just checking to see that I had done my job.  
		So why don't we get started. 
		I wanted to put a discussion slide up. 
		Before we start on that, were they comments, specifically, or questions on David's talk?
		DR. SCOLNICK:  I wondered, given the huge volume of genes that are being sequenced, identified with disease, and the kind of logarithmic pace of that, what is it that you actually propose to regulate, specifically?
		I see this as a rather formidable problem, and I wondered, since your comments were general, what is it that you're actually suggesting that you're going to regulate?  
		DR. FEIGAL:  I think it depends on what the claim for the genetic test is.  If it's detecting the gene, then it's comparable to other kinds of diagnostics where you're dealing with the accuracy of the -- the analytic accuracy of the test.
		If you claim that you can predict development of breast cancer because you've detected the gene, it's not just enough to say that you've accurately detected the gene. 
		So those are probably the two extremes.  There's some genes where the information that it conveys is very straightforward, and in fact how to  even work with that information in the community is very straightforward.  
		Like, for example, sickle cell.  That's something that if the technology for detecting that gene changes and improves, that's a relatively low standard.  But at the other end, we're probably looking at needing to have clinical follow-up information, and then there's everything in between.
		DR. SCOLNICK:  If a university lab today tests a patient for Huntington's disease gene-related information with the complexity of what that means with regard to the length of the glutamine repeat, what is it that you would regulate, given what a university lab would be able to say to a patient, having done a precise molecular experiment?  
		DR. FEIGAL:  Well, there's been an attempt to sort the tests by the characteristics that makes them either at -- the information at high risk or puts it into a lower-risk category.
		One of the other factors is the rarity of the condition, whether or not we're dealing with rare diseases, and the ability to make the diagnosis with other kinds of information that supplement the particular test.  
		So, in fact, the Secretary's Advisory Committee has actually been struggling with an algorithm to divide the tests between those which would rely mostly on analytic accuracy versus those which would require clinical information and clinical follow-up.
		The situation where it's a rare gene that's a familial gene, not seen very often, is obviously one extreme. 
		We're using a gene for population screening or newborn screening or for making a reproductive decision, then that puts it in a different category.
		But the issues you raise in terms of the volume of information and the amount, just starts when you look at the thousand universities that have genetic tests.  
		When you think about the paradigm of evaluating a gene chip, which might have a thousand tests on the gene chip, and you think of the normal way that you evaluate even analytic specificity, you have a set of reference samples for a specific piece of information.  
		And now if you have a chip that wants to simultaneously assess 10,000 pieces of information, we won't be able to address that in the same way.  We're not going to be able to say that you've got to go point by point, and those are the issues that we need to discuss.
		This is still a work in progress, and in fact we have an advisory panel on genetic testing that will meet with us to publicly discuss these issues and get feedback.  And the Secretary's Advisory Committee has been a public committee that's discussing this. 
		DR. SCOLNICK:  I guess you know what I'm getting at.  If I'm a physician and I have a patient with Huntington's and they want some test done or it's appropriate to do some test to try to assess the risk in another family member or an unborn human, potential human, and I find that there are 38 repeats or 42 repeats, are you going to try to write regulations which are going to govern the words I use to describe the implications of that data to that family?
		And are you going to try to do that now for all of the genetic markers that are going to exist for all of the diseases that are going to have genetic predispositions as the genome information rolls out?
		I see that as an impossible task.
		DR. FEIGAL:  Well, there are some common elements, and this actually comes back to where we leverage off of other groups.
		If you look at the setting of the issue of informed consent for familial conditions, there's some common threads that come across that. 
		For example, if you're looking for a carrier state and you detect it in a child and the issue has actually been brought up for Huntington's, what do you do in a situation where a Father who has it on his side of the family doesn't want to know if he's going to develop Huntington's, but the wife wants to know which of the children are at risk? 
		But if any of the children are found to have Huntington's, you have just unmasked him.
		So the whole issues of how to do that are things so that where we see the role and where we see the partnerships with the genetics groups is for them to develop prototypes for common clinical scenarios with genetic information for how to deal with these situations, for how to deal with what should be the standards for genetic testing.
		At the other end of the spectrum, the CLIA regulations, the Clinical Laboratories Improvement Act, requires that if information is going to be used clinically, it be done in a high complexity laboratory. 
		That's probably not even the case now for all genetic tests.  There are probably some of these that are being done in research laboratories that do not meet the requirements of that act.
		There also have been situations where laboratories have had to recall and try to contact thousands of patients who have been screened because they found that the test didn't have the sensitivity that they thought they did, and they informed patients that they were not carriers for a condition, and then were notified the fact that they were when they had a child with the condition they were trying to avoid.
		So there are a whole series of complex layers.  I think what works in our favor is, although, there are thousands of genes in genetic informations, there are some common themes and some common threads, and rather than treat these all individually which would swamp us and would slow and make us the roadblock for all of us, we need to look at the way we solve problems, a chunk of information, have the right regulatory tool for the problem we're trying to deal with.
		Right now, for example, many laboratories don't appear to have a way of tracking the errors that are reported back to them in their testing.  And that's just one of the standard things that's expected of a regulated in vitro diagnostic, whether it's approved by CLIA, the State of New York, or by us.
		So it'll be a process where we'll need to phase these in, but the issue of the multiplicity information is one we've thought a lot about.  It's a real challenge.  
		We're not going to be able to do it the way we've always done it, and we need to find the ways that -- we introduce this in a way -- I think part of the challenge is to introduce it in a way that we don't lose the public's trust.  
		They're very skittish about information, about who's going to use this, who's going to have this, particularly when many employers are self-employed so your employer carries your health insurance and you order a diagnostic test and it goes back to your employer, many of those types of issues.
		So there will be a continuing process in this area of having ongoing public meetings to discuss these issues, to get feedback, to hear from groups, to see what's needed in these areas.
		Many of these issues, there's things we've learned in the past, the confidentiality issues are reminiscent of the discrimination issues with HIV testing and screening.  And so what we need to do is leverage off the things we've learned in the past, how to do these things. 
		DR. LANGER:  Yes.  
		DR. DAVIS:  It seems to me -- a totally different subject -- that Dr. Jacobson listed a daunting list of issues, and what came across as I listened to the Center directors, each seemed to have picked out one or two issues, primarily more fundamentally science-based to talk about, what seems to be lacking to me, and maybe that wasn't the intent of the presentations, there are some issues that seem to go across all the Centers, and there didn't seem to be a tie together. 
		For instance, people sort of spoke, one or two mentioned bioterrorism.  There's the whole issue of informatics, microbial resistance, et cetera.
		Is that at your level going to be some programs that stretch across these Centers that will tie issues together?  Otherwise, you're going to get into redundancies and you'll get people approaching the same problem in different ways, so you won't have a cohesive program.  Is that an issue or not?  
		DR. JACOBSON:  Yes.  There are actually a number of answers to your question.
		It wasn't the intent today to try to tie everything together.  We were trying to give sort of an overview of all of the various issues and let people see the different sides that those issues might take. 
		For issues that cross the Agency, for example, bioterrorism; as Dr. Henney said this morning, we've just instituted an office in the Commissioner's office that is going to do that kind of coordination across the Agency so we have a coordinated effort there. 
		In some of the other areas, wherever we have issues that touch every Center, we are trying to do some coordination there.  Sometimes it's not as straightforward as it might seem because different Centers operate under different legislative authorities, and so they may have to do things one way as opposed to the way another Center would do it. 
		But the intent, certainly, is not to have the right hand not knowing what the left hand is doing.
		One of the things we wanted to talk about today was which of these issues do you want to hear more about in the future?  Because we'd like to pick off a few of them each Board meeting and talk about them, and if you wanted to start, for example, with some of the crosscutting ones, that might be a nice way to proceed.
		DR. LANGER:  We may want to continue.  We will want to continue this discussion, obviously, but along those lines in the 4:00 discussion one of the goals is to figure out what will be in other meetings. 
		So, actually, that will be very useful to get some thoughts on that.  
		Yes?  
		DR. NEREM:  Yes, I sort of wanted to pyramid on his comment.  When we talk about research, I realize it's very small compared to the program.  In the outside world, disciplinary research is the name of the game. 
		When you think about FDA where you're going to have all kinds of products, therapies, that will be a combination of a device, a biologic device, a drug system; is there actual inter-center research taking place or is each Center doing its own thing?  
		And that may relate to how do we attract the people?  
		DR. LANGER:  I think this is a good way to get into -- that's a good question -- sort of a good way to get into the slide up there.  
		It looks like there's several people from FDA that want to comment.  
		So, yes, if you want to start, and then Bern wanted to comment, too.
		DR. JACOBSON:  I think that's exactly one of the issues that we want to talk about and to start dealing with, is this whole interdisciplinary.  I mentioned it in the discussion that it raises interesting science questions and interesting regulatory questions.
		In terms of ongoing research, right now, I guess, I have to look at the Center Directors; I would say most of it is probably Center driven, but we do have a number of projects, especially in areas that have multiple -- 
		DR. NEREM:  Research projects are more or less coordination of activity.
		DR. JACOBSON:  Well, for example, we have just started a project, a coordination in the microarray area, where we're getting the people together across the Agency who are working in the area to see what should our research program look like in that area; what should we be doing as an Agency rather than having everybody go off and do individual.  
		DR. DAVIS:  Let's just do a fundamental question.  I am very familiar with Dan and the group at NCTR, but part of my dilemma is what percent of the Centers you would say are research based.  
		DR. JACOBSON:  It's different for every Center.
		DR. DAVIS:  That's right.  And so I'm trying to get a sense of what percent of the FDA presently would be labeled researchers.  It might be different for every Agency, every Center, but there's got to be some FDA; you've got X number of people and a certain percentage of those people where researchers -- 
		DR. JACOBSON:  Yes.  I don't have that number.  
		DR. DAVIS:  -- in the more stricter sense of this. 
		DR. JACOBSON:  I mean, we could go down the row and we could have each of the Centers tell you what percentage it is, but we can also get you that kind of information.  
		DR. ANDERS:  Can I hop in on this?  Because I think Harold and I see some of the Agency sort of a prism of NCTR where we've both served.
		DR. JACOBSON:  Yes.
		DR. ANDERS:  And one thing I know I was impressed with over the years, that the Agency appeared to lack an orderly means of setting priorities for research that would cut across the Centers and to which the -- frankly impressive resources at the NCTR could contribute.
		So I understand there's bits of research, there's pieces of research going on in all the Centers.
		There's one Center devoted fully to research and not regulation.  How do the priorities get set for the Agency?  
 		DR. JACOBSON:  Well, I mean -- does anybody want to take a crack at that?
		Right now, it's pretty much Center-driven.  For example, NCTR, as you said, is essentially 100 percent research.
		DR. CASCIANO:  About 35 percent of our research are directly related to chemicals that are nominated by the various Centers for cancer bioassay and risk assessment.  So there's quite a bit of coordination between the Centers regarding cancer bioassay.
		There's a lot of discussion investigator-to-investigator between the various Centers.
		So there's some understanding regarding the kinds of activities that are going on in each of the Centers, and it needs to be better, that's for sure. 
		But there's a concerted effort now I think where the Center Directors are communicating to a much higher degree in the last year because of constraints on funding and the desire to not duplicate what's going on in various Centers.
		I think we're moving in the direction to approach.  
		DR. JACOBSON:  I just also want to give you another number, though, and Janet it is probably even lower than this.  But CDRH research capability of about a thousand people, there are, what, fewer than a hundred that are actually at the bench?  
		DR. FEIGAL:  I think it's about 150 assigned to that group.  About a third of their time is not for research (no mic -- inaudible).
		DR. JACOBSON:  So that's a big difference.
		DR. DAVIS:  The nature of my question was if you're trying to attract talent, one of the questions, how do we attract people.  
		You take CBER with Kathy; are we talking about attracting bench-level scientists who do work to go into a group of 20 percent staff, researchers, or are we talking about attracting a single person to come in who understands the scientific arena and be a scientific force but not necessarily do work?  
		So without knowing percentages, I don't have any idea what kind of people we're talking about attracting. 
		DR. LANGER:  Kathy.
		DR. ZOON:  Just to address your question, it actually involves several levels in the Center for Biologics.
		We have full-time reviewers, and then we have research reviewers.  And I would put the research reviewers in the class of both lab-based and non-laboratory-based research reviewers.
		If you look at the level of effort in our Center, we have about 820 FTEs, and probably between -- we have between -- probably it varies from time to time, but probably between 150 to 200 FTEs on research-related regulatory activities.  And that would include product testing.  That's lab-based activities.  
		I would be more encompassing and say those are lab-based activities.  
		So that kind of gives you a feel.  When we have research reviewers, they do research and review.  The amount of time that a research reviewer will spend on research, used to be in the order of, I would say, 60, 70 percent.  That's now in the order of probably more like 40 to 50 percent.  
		There's more review responsibilities than there have been in the past so that number will fluctuate based on the regulatory workload of the Center.  But their fundamental work in their area of discipline, we use the Staff Fellowship Program, which is -- and the ERDA Program, which are training programs, to bring in new young people into the organization.  
		The staff Fellows will do research and review.  We just modified the ERDA program to allow ERDAs which are post-docs, intramural training program, to do some part of their time of doing review work. 
		In the past, ERDAs weren't allowed to do any review work.  They were only allowed to work in the lab.  
		So what we're looking at is an opportunity to bring young people in, the best of those young people we'll retain.  Those people will turn over and then we'll bring new people in to train.  So we use this as sort of a way to look at enhance new science in the organization by bringing people in from new disciplines that we think they're needed in, and then we try to retain the best.
		Now getting more senior people into the organization, which is the other issue is far more challenging.  I think it's much more difficult to recruit people into the Agency at a senior level.  We've met with challenges in that area and that's a lot more difficult that I think to get really top-notch people from the outside of the Agency, to come in take over these research and review responsibilities.
		So I think that's where we need the most help.
		DR. LANGER:  Bern wanted to make a comment.
		DR. SCHWETZ:  In response to your question about the number of people, let me give you some ball park estimates of the numbers and some different kinds of jobs.
		As we've looked to define how many researchers do we have, how many laboratory workers do we have, how many scientists do we have in the Agency, we have concluded that it's very difficult to use the personnel classification system to give you information.  
		Because it doesn't accurately reflect, necessarily, what a person is doing today, because a person might have been hired as a chemist 15 years ago and they're working as a chemist today, but they're still classified as a chemist.  So the numbers are not accurate. 
		But as we've gone through and have tried to reconstruct what we look like, out of our 9,400 people, we estate that between 6,500 and 7,000 is what you would call scientists, scientists being clinicians, engineers, epidemiologists, and the more traditional scientists that you would consider.
		So about 6,500, 7,000 of the 9,400 employees that we have. 
		We estimate that between 2,000 and 2,500 are involved in laboratory work.  That's not all research because a lot of that is support work for the field work, support work within NCTR, within CBER, within CDER.  
		So these are not people who are doing practical-driven, investigator-initiated research, these are laboratory workers doing routine analytical work, so that's about 2,000 to 2,500 of the 9,400.
		Then if you the ask the question, well, how many of these are really doing research of the type that you would say are investigator-initiated, mission-oriented applied research or fundamental or basic, however you want to do it, it's quite a bit less than half of those 2,000, so it's probably closer to a third of those 2,000 people that are actually involved in that kind of research.
		But I would also say that we have very, very few people whose job it is to come in and write protocols and do the best science you can.  You can count those people on one or two hands.
		For the most part, they're brought in to work on a very specific question, so the research may be investigator-initiated, but it's mission-oriented to a problem that Kathy has with a vaccine or a problem that Dennis has with the method or whatever it is.  Does that help?  
		DR. DAVIS:  Um-hum.  
		DR. SCOLNICK:  I guess a related question I have really relates to instrumentation  Let me just give you some booked.  
		If you look at the budget slide that one of you put on, increase in (inaudible) at NIH and industry versus the funding at FDA, it's a rather telling slide, which I'm sure you're all aware of.
		You're well aware that everybody says it's kind of a new revolution going on in biology, which is true.  The last time we went through a real technological C change in biology was in the late '70s when cloning technology came in, molecular cloning technology came into biology, it really revolutionized biology for the next 10 or 15 years.
		That technology was relatively cheap.  It was easy to do.  Kind of traditional comment that somebody make is you could teach a high school student to do it and they could do it in their garage, if they really wanted to do it after a week's training. 
		Things that are happening today related to genome sequencing and array technologies which are developing proteonomic technologies which are in their infancy in technology, the high technology machines that are being used, MSMS, LCMS, MS, those are very expensive, hard-to-learn technologies.
		And then you add on to that the IT technologies that are needed in order to interpret the data or to begin to interpret the data, and the dearth of people who exist, who can help you develop the algorithms, how in the world, or what is the FDA plan, for trying to get whether you can really do this in house with that kind of budget or whether you're going to have to develop a completely different kind of paradigm to be able to have the expertise to judge the information that's going to be coming in, maybe not in the next couple years, but certainly over the next 10 to 50 years.
		I think that's the most formidable challenge you face. What's your plan for dealing with that?  
		DR. LANGER:  Kathy.
		DR. ZOON:  Well, I don't have the whole solution -- 
		(Laughter) -- 
		DR. ZOON:  -- but I have a tiny piece of it and one that's worth exploring. 
		I think one of the things I think -- and Dan Casciano and I had this talk a number of 
times -- to think that FDA will have an entire bioinformatics system that's going to be able to do this all by ourselves and maintain this is out of the question.  
		So the question is how do you deal and integrate into what's going on at the moment.  	There's several things that have possibilities.  
		One is NIH and particularly the NCI has set up this huge bioinformatics program.  They're using a contractor, actually, to do it.  And so one way, we've met the contractor and we may be able to facilitate our interaction into this, put data into the system, be able to leverage the data, the whole system by feeding into this particular type of contract operation.
		And that's not all encompassing but rather than developing our own which would be enormously expensive and probably out of the question, if you can get into a piece of what's already going on and just pay your share of what it is but have access to the whole database, then that's a much more practical application of this.
		So those are the kind of opportunities I think we need to look at in the different areas where there's information, and there may be different bioinformatic systems for different types of problems. 
		DR. LANGER:  Yes.  
		DR. COLWELL:  I think it's an opportune time for a lot more interagency cooperation and address the point that you raise.  
		It seems to me that we need to find a way for perhaps the Center directors or representatives to sit in on panels for some of the areas of funding that we do so that you could see what is coming up and actually be able to be informed and to be able to discuss with those investigators who do get funded, or perhaps if those investigators, one or two, don't get funding, funded, than what would be appropriate for you to pick it up.
		So I think this interaction can be very very productive, and I think there are a number of ways we can go about it. 
		Also, it would seem to me that we could develop workshops that we could co-fund that would address perhaps the microarray chip question.  What would be the appropriate way for FDA would limit the resources to be able to move appropriately and effectively in this direction. 
		I don't think it in any way would deflect from the basic research mission of the NSF.  It would simply be a very nice way to partner.  
		We do have a program in bioengineering with the Veteran Administration.  There we look at esthetic devices and looking at neurological research that our investigators and theirs can collaborate on.
		Clearly, no single agency is going to have enough money to do anything completely. 
		Obviously, at least to me, collaborations are critical.  
		You're gong to have a heck of a time getting information technology expertise.  Every agency has been reading about it in the newspapers.  We don't pay competitively, but there's some attempt to try to step out of the box on that, and it may happen.  But in the meantime, it seems to me that again we ought to be able to team up in a way that we could provide perhaps expertise that we jointly contract out or work on obtaining.
		We don't try to maintain our in-house computer systems.  We do that by contract.  But there may be some way of being able to carry that out.
		In any case, I think there's some very good opportunities to enhance the research capability of the FDA by this kind of partnership and a more effective, maybe a tripartite partnership with the NIH in the basic research areas that are keen interest and great importance for the FDA.  
		DR. SCHWETZ:  Rita, we would very much like to engage in those discussions with you to figure out how we can bring these two parallel organizations together with bridges.  
		DR. COLWELL:  Let's do that.  We'll follow-up on that.  
		DR. SCHWETZ:  We'd like to do that.
		DR. COLWELL:  Yes.
		DR. LANGER:  Yes?
		DR. ROSENBERG:  In terms of tapping expertise as you have on the slide, that would also help solve that problem because I think one of the places you could very nicely attract from is the NIH, and I don't think you partner well with them at all.  I don't think they know you exist.
		In fact, the industry knows you exist far more than the NIH knows that you exist, and yet given the structure and how you do business the NIH scientist would want to move to this kind of a field and this kind of analysis, this would be a much more attractive switch for the NIH-type scientist.  And I think you're missing out on that opportunity by not doing more of this as well.
		DR. LANGER:  Mike.
		DR. DOYLE:  Following up on what Rita said, I think she's right on, but there are bigger opportunities than just NSF and NIH.  I mean, DoD is also considering getting into the microarray area and tremendous amounts of dollars will probably be invested into that in terms of infectious diseases and all, and I could just see an excellent partnership there with FDA and USDA and those interested in food safety.
		DR. DAVIS:  Further goes to my question about the organization of programs and processes across the agencies.  And it speaks of even outside of the Agency, because these are going to be such daunting issues that the costs and the amount of material to be regulated or controlled is just tremendous.  
		As Ed was mentioning, the kind of thing, the data that we're going to be generating with microarrays and who's going to have the resources to generate all that, I firmly believe if the FDA thinks they have trouble now with clinical data and all that stuff that's just sitting there, that it would be wonderful if somebody could go through it and make heads or tails out of it.
		It's going to get even worse with the amount of data that we're going to be generating in the future.  
		FEMALE VOICE:  Yes, I agree.
		DR. DAVIS:  You won't have a place to store it all. 
		And so I think it's imperative that there be some cross-center, cross-agency initiative, and I wouldn't leave industry out, especially for those of us who are regulating.  I think perhaps trying to get in early to help drive where we're going and how we're going to be regulated and getting some agreement on what processes ought to say and what data we ought to submit, how that data ought to come in, et cetera.  
		So you might be able to get some partnership there with resources and expertise.
		DR. LANGER:  Bob and then Rita.
		DR. NEREM:  Yes.  Two comments, first picking up on Rita's comment.  
		NSF has engineering research centers, has science and technology centers.  Some of those centers are operated in areas very pertinent to FDA so that's another place to partner. 
		Beyond that, I want to ask Liz a question.
		Do you have in your new position a budget for crosscutting science initiatives or is all the research money out there in the Centers as part of their -- whatever they get from Congress?  I don't know how this works.  
		DR. JACOBSON:  I have requested a small budget for sort of seed projects, seed money, to get cross-agency things going, but no, I don't have a budget.
		DR. NEREM:  Never request a small amount.  You should always request a large amount. 
		(Laughter) 
		DR. JACOBSON:  At FDA, we only have small budgets.
		DR. LANGER:  Bob will be a special consultant.  He knows how to ask for a lot of money.  
		DR. NEREM:  And get it.  
		(Laughter) 
		DR. LANGER:  Rita. 
		DR. COLWELL:  Actually, there is an interagency initiative on information technology.  
		I want to pick up on Mike's comments about a lot of money put into it.  Indeed, there is.  And again the comment about the across the agency, even that initiative within the NSF is an agency-wide initiative because it involves every single aspect of it. 
		Building databases and research on building databases and searching databases is worth putting a lot of money into in DARPA, particularly putting a lot of money into it.  
		Now this is a political issue, but it seems to me that the FDA ought to find a way to get into the interagency information technology initiative.  Serving the FY 2001 budget is closed, but the FY 2002 is in the preparation and your appropriate political contacts.  I don't know what they are but, in any case, I think an argument can be made for new money or database building and searching and for software development that can be done collaboratively as part of the interagency initiative. 
		DR. NESTLE:  I don't know about anybody else, but I'm just enormously alarmed by this morning's discussion. 
		We've heard three things at this meeting that put together, have me in a complete panic about this.
		One is the budgetary situation.  
		The second is the Agency's budget is determined by the Agriculture Committee not by a committee that deals with health.
		And the third is the collection of demands on the agency that we've heard about this morning.  This is obviously a crisis situation and the kinds of suggestions that are being made are band-aids dealing with a situation that seems to me is overwhelmingly alarming.
		I'm a consumer representative on this Committee and, as such, I get to say outrageous things like this -- 
		(Laughter) 
		-- but I think this is a national crisis.
		That's how I see it from what I've heard this morning.
		We have a situation in which all of these new technologies and new devices and new drugs and new everything are coming on the market with absolutely no ability to determine whether they're safe or not for the public. 
		Something has to be done about this and I think it's great to talk about interagency cooperation but I think it's going to take a great deal more than that, and we ought to be talking about it if we can.
		DR. COLWELL:  Yes.  There's no question.  I don't think anybody around the table is going to argue about the budget not being sufficient for FDA, otherwise, we wouldn't be here.  But we have to face the political reality.  
		I don't think the interagency collaboration is a band-aid.  I think having been involved in various panels and committees and things for FDA over the last 15 years, it's very clear that a major infusion of money from Congress is not on the horizon.  
		It isn't on the horizon, really, for any one agency, but I think we have to find innovative ways to address just the issues that you're raising, the budget shortfalls, this burgeoning of science and technology that's occurring.  
		It's changing.  That is somehow changing the whole pharmaceutical approach to human health.  It's turning into a very much complicated kind of thing.  It's nutraceuticals, pharmaceuticals, it's preventive medicine in a different way, which means engaging the public and the consumer in a much more informed way, which means that probably the FDA is going to have to develop a really good web site for information for the consumer.  That's another step to take.  
		So there isn't any simple solution.  But we can't just wring our hands.  We've got to find ways to help out.
		DR. NESTLE:  Don't get me wrong, I'm not opposed to interagency collaboration, I just wouldn't underestimate its difficulty.
		DR. COLWELL:  Oh, I agree with you.
		DR. DAVIS:  I'd also like to say I share your alarm; however, I wouldn't want to sit here quietly and say I feel that the drugs that are coming out on the market, that we have no way of attesting to their safety, et cetera.
		As a representative of a company who provides drugs to the public, I feel very comfortable that what we do allows us to be somewhat comfortable with the drugs that we're putting on.  I think FDA does a great job in that. 
		So I am not -- I don't share your concern that we have no way of attesting for the safety of the products we're putting on the market.  
		I am alarmed that the task that is before us with incorporating science as it is developing is a daunting one, and we better do something tremendous with or dramatic to fix that problem; but I don't go to sleep at night concerned that we're putting unsafe drugs on the market.
		DR. LANGER:  Other comments?  
		It sounds like there are a few.
		Bob and then Liz.
		DR. BUCHANAN:  As you wrestle with coming up with recommendations, I do offer a note of caution, having been in an involvement the last three years in a very large interagency type of activity.  
		The reality of budgetary increases, which we all like to get, is that they tend to be small, and more often you're slated to do something which means that you have to stop something else. 
		So, really, what we're looking for often is advice on budget optimization not just relying on budgetary increases.  So one of the things that we have to wrestle with is if we're going into genomics or proteonomics or all of the other new technologies, what in our mission are we going to stop doing; for example, do we quit looking in the food field, warehouses?  That's an issue.
		How often do we get to go in and inspect a warehouse, because in most situations it's a zero sum gain.  
		If you put more money into the foods program, who are you going to take it away from?  Again, that's the issues that we've been wrestling.

		So as you think of recommendations, think also of the impact those recommendations are going to have if we don't get budgetary increases.  
		DR. LANGER:  Liz.
		DR. JACOBSON:  I just wanted to say that with respect to the things that you said, Dr. Nestle, I'd like to think of it in terms of urgency.
		The whole point of going through this kind of a description of what we're facing is to bring out and make more public, make more obvious what are the problems that FDA is facing, and I think one of the things that interagency collaborations can do for us is to help get our problems on other people's agenda.
		It's really difficult, though.  I agree with you.  And our priorities, our mission, isn't necessarily the other Agency's mission, and so it's difficult to get attention, but we kind of have to deal the hand that we're dealt, and right now we have a lot of incredibly pressing technologies and products that are coming at us.
		I also disagree with what you said, that you know we don't have any way to know that anything is safe.  I think we would all disagree with that. 
		We also have to sit and sort of try to strategically think, how are we going to change the way we're doing business because I think we are sort of in a paradigm shift.  We can't keep doing things according to the old paradigm.  That simply isn't going to work. 
		Meetings like this one, one of the things we're hoping to get is some discussion and some advice on directions that we should be moving and, frankly, ideas for ways to move out.
		DR. SCOLNICK:  I would ask you back a question, and it's a tough question.
		Do you have a strategic planning process in place within the agency to try to address the kinds of questions that the Board is asking you about this morning?  
		If you do, you know, are you in a position in some period of time to come back to the Science Board with an overview of that plan as to how the Agency is planning to spend its money and change how its doing, whatever it's doing.  Or if you don't have that process in place, what would it take to put it in place?  A really good strategic plan for the FDA in the new millennium?  
		DR. LANGER:  Do you want to answer it and then Janet has a comment. 
		DR. SCHWETZ:  Jeff Weber, the head of our Budget Management Office, may like to comment more on this, but one of the things we've been trying to turn around in the last few years is to move away from the budget determining what you do to us determining what the budget needs to be for the things we need to do.
		There's been a lot more attention paid to that in the last few years than there were in the previous years that I've been in the agency, so we're trying to get that turned around through the large number of meetings that we have to talk about priorities and needs and what can we not do if we're going to change priorities before the budget numbers are sorted out.
		So we've been going through that process pretty religiously in the last few years to get people to share ideas early on about what the priorities are to be able to integrate them between and across the Centers and the rest of the Agency.
		So there's big progress in that area.  But even when we come up with a budget and the pieces get lopped off a lot of that planning comes to no avail when the budget isn't near as big as what we thought it needed to be.
		DR. LANGER:  Jeff.  
		JEFF:  Right.  I've been here for one full budget cycle now and the tail end of the last budget cycle, and what I see in the beginning of the cycle what we are trying to do is some strategic planning, although it's short-term strategic planning as opposed to long-term strategic planning. 
		And what myself and the head of the planning office have done recently is gone around and met with each one of the Center directors and each one of the deputies to try and design an approved process for future years.  
		And one of the continuing themes that keep coming out is that we do need to do some type of long-range strategic planning, and eventually we're going to come to the leadership team and make a recommendation on a revised process based on everything that we've heard from the Center directors.
		There is long-term strategic planning in each one of the Centers now, or most of the Centers, are either have a strategic plan or on the verge of completing a strategic plan, so it's probably a good idea for the Center to get into some long-range strategic planning as well.  
		I also want to touch on the point that Dr. Schwetz made.  We can have all the strategic planning and all the budgeting up front in advance, but when we start with a budget that we submit to the Department it gets whittled down, it goes to OMB, then it goes to Congress.
		When we finally get our budget back, we're lucky to get enough resources to continue to pay the salaries of our employees, because we have not been getting our current services paid for so we have to absorb a 3.7 percent pay raise this year, plus within grades and promotions if you want to keep your good employees, awards, et cetera, otherwise, the attrition will be even greater than it is now.  And that's about $42 million.  
		So that right off the top whatever Congress gives us this year, we're spending $42 million to maintain our existing staff.  
		So there really isn't much left to try and shuffle around between priorities even if they don't give you sufficient resources.
		And I'll give you one perfect example.
		Congress decided this year that antimicrobial resistance was a very high priority for them.  We have resources requested in our budget, six or seven million dollars, but they added $3 million on top of that for CVM, well needed, we'll put it to good use.
		However, in doing that, they decided they're just going to take the $3 million away from CBER.  So CBER now has less money for blood work, less money for vaccine work, less money for tissue work, without any consultation with FDA as to how do we want to re-prioritize those resources.
		So we can prioritize all we want, but when those decisions are made without our consultation, it's very difficult.  
		We've had conversations internally, where do we want to shift resources if CBER needs help because they have to do that work as well.  
		And everybody is so strapped that there really is no other place to take the money from to providing that additional support to CBER.
		So those are the kind of issues that we're dealing with.  I mean, it sounds simple on the surface but it is very difficult to juggle the dollars when you don't really have enough to do your basic mission to begin with.
		DR. LANGER:  Janet, do you want to make a comment?
		DR. WOODCOCK:  Yes.  I just wanted to provide a couple points of clarification with respect to what Dr. Nestle said.  
		As far as drugs, we probably, right now, given the science have the greatest predictive ability ever for humans to predict drug safety post-marketing, but it isn't ideal and we're still not where we should be.  So it isn't that we can't predict drugs toxicity profile after marketing, it's just we aren't at the level.  
		Society, I think, is required, demanding a higher level of assurance and confidence than they have in the past and we need to keep pushing our ability to do that.  
		With respect to what Dr. Davis asked, CDER, I think my calculations are correct, 3 percent of our employees are engaged in laboratory research.  It's a very small number of people.  I would say they are fully-leveraged right now.
		So given our budgetary constraints, it's very difficult for us to do any more cross-collaborations than we are doing. 
		For example, with spectroscopy, we use St. Louis University and other partners that we have to give us access to advance techniques.  That's probably the only way we can do it with just a handful of people.
		So our ability, actually, to leverage further with further cross-organization collaborations is fairly limited, simply by the number of people we have.
		DR. LANGER:  Other comments?
		(No response.) 
		Why don't we take a break.  We'll get back together at 1:00 for a couple of comments. 
		(Luncheon recess.)

	A F T E R N O O N   S E S S I O N
	(1:08 p.m.)
		DR. LANGER:  We're going to start now with Public Comments, and we have Doris Haire, from the American Foundation for Maternal and Child Health would like to make some comments.  	Open Public Comment
		MS. HAIRE:  Good afternoon.  I appreciate this opportunity to share my concerns with the members of the FDA Science Board and to ask the Board to urge the FDA to create an Interdisciplinary Obstetric Advisory Board comprised of pediatricians, pediatric neurologists, behavioral scientists, midwives, obstetric nurses, and obstetricians to evaluate the safety of drugs to be administered to pregnant and parturient women.
		The FDA cannot expect a Maternal Health Drug Advisory Committee made up almost exclusively of obstetricians to be objective about the drugs they have administered to their patients.  
		Such a group does not have the training or expertise to determine the delayed, long-term effects of the drugs they administer to parturients or on the long-term development of the exposed offspring.
		I've heard obstetricians in that Committee remind the group that there would be serious repercussions for obstetricians if the Committee were to recommend that a drug previously approved by the committee to be removed from the market.  
		The fact that the makers of Pitocin, Marcaine, Sublimaze, and other drugs commonly used in obstetric care have chosen to remove their labels from the Physicians Desk Reference, only adds to our conviction that they wish to withhold ready information regarding the risk of their products not only from the public but from the doctors and other health care providers. 
		Most nurses and midwives that I have discussed this with tell me that when they have asked the hospital pharmacist for a copy of the package insert they are refused.
		I am concerned that as the number of children with learning disability, autism, dyslexia, attention deficit disorder and hyperactivity continue to mount to a frightening number, the FDA does not appear to make a strong endeavor to see if obstetric drugs contribute to these problems.
		For some reason, the scientists seem to have let the science of human parturition slip through the cracks.  As evidence of this scientific vacuum, a recent Report of the Task Force on the NIH Women's Health Research Agenda for the 21st Century failed to mention the need to improve the safety of childbirth for the woman and her baby and the potential adverse effects of obstetric drugs and interventions on the neurologic development of the offspring.
		In light of the soaring rate of autism, 500 percent in 10 years in some states, it behooves the FDA to question whether  cervical wideners, uterine stimulants and various pain-relieving drugs administered to the parturient permanently alter the brain circuitry of the fetus and newborn sufficiently to interfere with the normal dendritic arborization within the infant's brain.
		Virtually all drugs administered to the parturient cross the placenta, enter the circulatory system and brain of the fetus and newborn infant where the drugs and their metabolites may remain for days if not weeks. 
		It is ironic that women who do not wish to become pregnant are provided a package insert with their contraceptive drugs to ensure that they understand the risk of taking the drug.  Yet the woman who wishes to have a safe birth and experience for her baby as well as herself receives no package insert advising her of the known and potential risk to her and her baby.
		I urge the Science Board to recommend that the FDA require package inserts to be made available on request to all expectant mothers who wish to know about the drugs they will be offered during pregnancy, labor, delivery, and postpartum. 
		Consider the information the doctor receives regarding the risk of oxytocin.  The manufacturer of oxytocin warns the provider in the package insert:  "Maternal deaths due to hypertensive episodes, subarachnoid hemorrhage, rupture of the uterus, fetal deaths, and permanent central nervous system or brain damage of the infant due to various causes have been reported to be associated with the use of parental oxytocic drugs for induction of labor or for the augmentation in the first and second stages of labor."
		In addition to the more benign effects of uterine stimulants, the American manufacturer of Pitocin points out in the package insert that oxytocin can cause maternal hypertensive episodes, subarachnoid hemorrhage, anaphylactic reaction, postpartum hemorrhage, cardiac arrhythmias, fatal afibrinogenemia, premature ventricular contractions, pelvic hematoma, uterine hypertonicity, uterine spasm, tetanic contractions, uterine rupture, increased blood loss, convulsions, coma, and fatal oxytocin-induced water intoxication.  
		Yet, I don't hesitate to say that none of the women, or virtually none of the women in this country have any idea of the risks of oxytocin. 
		The following adverse effects of maternally administered oxytocin have been reported for the infant and the fetus -- bradycardia, premature ventricular contractions, and other arrhythmias, low one-minute and five-minute Apgar scores, neonatal jaundice, neonatal retinal hemorrhage, permanent central nervous system damage or brain damage, and fetal death.
		Uterine stimulants which foreshorten the oxygen-replenishing intervals between contractions by making the contractions too long, too strong, and perhaps even more important, too close together increase the likelihood that fetal brain cells will die. 
		All of these effects increase the possibility of neurologic insult to the fetus.  No one really knows how often these adverse effects occur because, as you know, there is no law or regulation in any country which requires the doctor to report an adverse drug reaction to the country's drug regulating agency even if the patient dies.
		I don't know how many of you saw yesterday's Los Angeles Times, but I was very pleased that they included that in the information on the front page.
		There are growing indications that oxytocin may contribute to the incidence of autism.  As I said, a 500 percent increase in 10 years in some of the states.
		But is oxytocin or is it the drug used in epidurals that then precipitates the need for oxytocin?
		Considering the following information which the U.S. Food and Drug Administration currently requires the manufacturer of bupivacaine, the drug most commonly used in epidurals.  The government-approved labeling for bupivacaine, which is produced by Marcaine, reads:
		"Local anesthetics rapidly cross the placenta and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity.  Adverse reactions in the parturient fetus and neonate involve alterations in the central nervous system, peripheral vascular tone, and cardiac function."
		But this is even more interesting:  
		"Neurological effects following epidural or caudal anesthesia may include spinal block of varying magnitude --including high or total spinal block-- hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia; paresthesia; weakness; paralysis of the lower extremities and loss of sphincter control, all of which may have slow, incomplete, or no recovery; headache; backache; septic meningitis; meningismus; slowing of labor; increased incidence of forceps delivery; and cranial nerve palsies due to traction on nerves and the loss of cerebral spinal fluid."
 		"Neurologic effects following other procedures or roots of administration may include persistent anesthesia, paresthesia, weakness, paralysis, all of which may have slow, incomplete, or no recovery."
		I'm here because I have tried to do all the proper things first, and my husband always, being a lawyer, always says, "Do the proper things first, and when that doesn't work, try something else."  So that I hope that the Science Board of the FDA will encourage the FDA to move to require package inserts for all obstetric-related drugs. 
		Rosenblatt and her fellow investigators found the bupivacaine administered to the mother during labor can have a prolonged effect on the subsequent development of the exposed offspring.  The investigators found that newborn infants, when greater exposure to bupivacaine in utero were more likely to be cyanotic and nonresponsive.  They also found that visual skills and alertness decreased significantly with increases in the cord blood concentrations of bupivacaine, particularly in the first day of life, but also throughout the next six weeks.  
		Adverse effects of bupivacaine levels on the infant's motor organization, his ability to control his own state of consciousness, and his physiologic response to stress were also observed.
		Sepkowski and Barry Braselton carried out a similar investigation after that, and they found all of their data supported the findings of Rosenblatt.
		As early as 1975, the FDA acknowledged in its General Considerations for the Clinical Evaluation of Drugs in Infants and Children that drugs trapped in the infant's brain at birth have the potential to adversely affect the rapidly developing nerve circuitry of the brain and central nervous system by altering the rate at which the nerve cells in the brain mature; the process by which the brain cells develop individual characteristics and capacity to carry out specific functions; the process by which the brain cells are guided into the proper place within the brain and central nervous system; the interconnection of the branch‑like nerve fibers as the circuitry of the brain is formed; and the forming of the insulating sheath of myelin as a fat-like substance around the nerve fibers which help to assure the nerve impulses -- the messages to and from the brain -- will travel their normal routes in their normal rate of speed. 
		Now the work of Zheng, Heintz, and Hatten reaffirm that the migration of neurons among the glial fibers within the brain can be altered by changing the normal chemistry of the rapidly‑developing brain.
		At no other time in an individual's life is his or her brain more vulnerable to alteration, trauma and permanent injury during the hours which surround that individual's life.
		And, yet, the FDA it seems has completely disregarded the potential of these drugs to affect the baby, and I hope that -- I have much more that I would like to say but I realize that my time is up -- but I hope that the Board of Science -- there doesn't seem to be any other source that we can turn to at the FDA -- but I hope that the Board of Science will see to it that the FDA begins to look at the effect of obstetric-related drugs on the well-being of the infant.  
		We all have an investment in these children, and I doubt whether there's anyone in this room that doesn't know some child who is learning disabled or autistic, and there is a good chance that we can prevent this.  
		Thank you.
		DR. LANGER:  Are there any comments?  
		(No response.) 
		Thank you very much.
		MS. HAIRE:  You're welcome.  
		DR. LANGER:  We'll make sure that this gets to the appropriate places.  
		Are there any other public comments that anyone wants to make?  
		(No response.) 
		It looks like there are not.  Why don't we continue with the agenda and have David talk about the programmatic peer review for the Center of Devices and Radiologic Health.
		DR. JACOBSON:  While David's getting set up, let me just make a comment here.  
		CDRH is the next Center at FDA that's going to undergo a peer review process, and David's going to talk to you about that.  CFSAN, CBER, and NCTR have already done a peer review process, and at the last meeting we talked about the results of the CFSAN process, and after that meeting Drs. Fennema and Schwetz put together some guidelines to be used for the peer review process, and I just wanted to tell you two things:
		(1)  The guidelines are in your notebooks so you can see what they look like; and, 
		(2)  Don't surprised that the presentation you're going to hear right now is not following all of the guidelines because CDRH was already underway as those were being put together, and we sort of see that process as a transition, and we didn't want to delay their effort by holding them up. 
		David.  
		DR. FEIGAL:  Thanks very much. 
	Programmatic Peer Review - CDRH
		DR. FEIGAL:  What I'd like to do today is present to you work that's been in progress.  When I came to the Center a year and a half ago, one of the first things I did was ask the senior leadership to begin a process of evaluating how we use science in the Center.
		I was in the Center for Biologics at the time of the external review, and I was actually eager to have our Center participate in the review and talk to Bern Schwetz about the possibility that we be up next.
		And we're in a process here where we have formulated a fairly mature proposal, but it's not cast in stone.  We can modify it, we look for your suggestions about how to make this more useful.  I think you'll see we have incorporated some of the suggestions that have come up from the time of the other reviews.
		I wanted to actually begin this by providing a little bit of background about the Center and a little bit of background about another process which has been going on at the same time, which is a strategic review.
		An appropriate place to start in talking about the Center is to talk about our mission.  It's actually a mission that's very close to the heart of the employees in the Center.  CDRH promotes and protects the health of the public by insuring the safety and effectiveness of medical devices and the safety of radiological products.
		It's a very broad mandate.  It includes thousands of types of products, both therapeutic products and consumer products in the case of radiological products.
		The consumer protection, our sort of modus operandis is similar to other therapeutic products.  One large category of consumer protections and where we apply our science is in the area of risk management.
		As in the case for drugs and biologics, there are devices that require clearance before first human use in the form of an investigational device exemption.
		We of course are concerned about the safe experimental use during product development and of the evidence needed to be sure that the risk of widespread use that occurs with market approval are warranted and in the post-marketing period we had programs that evaluate the adverse experiences.
		The other -- and I think probably the crosscutting, and I'll make this case a little bit later -- is that the really fundamental underpinning of the way that we do business is as a science based, regulatory decision body.  
		The majority of that historically has been evidence based.  But then as I mentioned this morning, increasingly, we're utilizing standards.  
		Then, finally, there's part of the operation that has to do more with the assurance of the integrity of products, the enforcement sides of dealing with fraudulent products, products which are poorly manufactured, or inappropriate and bad clinical practices.
		The Center for Devices, actually looking around the posters around the room, Center for Drugs forgot that FDA stands for the Federal Device Administration.  They left off the 1976 Device Amendments.
		(Slide.)
 		Before 1976, devices that were regulated were regulated as drugs, with new drug applications.  
		But in '76, device amendments were passed which defined devices, gave us authorities to move against violative products, established a tiered system of control based on risk, and established standards of evidence for marketing claims. 
		I think you really have to sort of understand a little bit of the background of the system to understand what the scientific task is we deal with.
		In 1976, there were probably as many as 100,000 medical devices already on the market, and these are sometimes referred to as pre-amendment marketed devices.  And there was a process of classifying them by risk, from the highest classification, Class 3, down to the Class 2 and Class 1.  
		And there was a process for bringing products onto the market by establishing that they were substantially equivalent to a previously-marketed device.
		All devices have certain types of controls.  There are general controls that include facility, registration, and product listing; 
		Premarket notification except for the majority of the Class 1 devices which are exempt;
		A requirement to follow good manufacturing practices or quality systems; and, 
		A system for reporting device failures.
		(Slide.)
 		The intermediate risk classes are the first area we actually begin requiring information that's specific to the device.  If you look at the Class 1 devices, the controls there are very broad and general controls and do not relate to the performance of the specific device.
		So the largest category of devices that are on the market and that are approved today are based on establishing that they are substantially equivalent to a predicate, to a product that was marketed before 1976, and when a product is cleared it joins that group of predicates.
		(Slide.)
 		To give you an idea of the size of this, these are the number of applications over the last 20 years.
		These are the number of premarket notifications of 510(k) applications, and if you work this out to a roughly 200-day business day, it means that day in/day out there are about 20 510(k) approvals or clearances per day by the Center.  
		This is the typical application, or about 40 hours, if you take the average number of hours, the number of FTEs working in this program, to evaluate this group of products. 
		Then in addition to these four to five thousand number of new devices that come into the market every year, there are an approximate equal number of devices which are exempt.  
		One of our basic challenges is how do we work within this framework and how do we provide consumer protection and science-based regulation for this group of products. 
		The other group of products, and probably one that you will see more and be highlighted more in terms of the review because the more novel ones are more of a challenge to us, scientifically, are the products which require premarket applications, the Class 3 products.
		And when there's not substantial equivalence to a predicate then you must establish that the product is safe and effective.  
		This is the volume of the PMAs, and the thing to note on this is that the scale is one log smaller.  The other scale went up to about 9,000, this scale goes up to about 900.
		(Slide.)
 		The blue line at the bottom is the number of new PMAs approved per year, and it's actually about the same volume as the number of new molecular entity drugs.  It runs between 60 to about 100 per year.
		The red line are the supplements to those PMAs, and they have a structure that's very similar to a drug supplement.  If there's a new indication or some other significant modification that requires a supplemental application.  
		Then the green bar are the actual number of IDEs.  These are equivalent to INDs, if you're more familiar to the drug process, and it actually shows you the relatively small volume of products that actually are required to have FDA supervision for the clinical studies.
		In fact, one of the things that shapes the scientific challenges for the Center is that of devices that come to the market, fully 90 percent of them will not have human testing, and quite appropriately so.
		So we need to take a look at what it is that we need to evaluate these family of devices.
		When we think of the organization of the programs and of the resources, it's often phrased in terms of a premarket program and a postmarket program.  In fact, I think we used those words this morning.  
		And the consumer protections are sometimes grouped under that.  If you look at the premarket consumer protection controls, we think of the requirements for safe experimentation, premarket safety, the standards to establish effectiveness before a product is marketed, the process of inspecting research and IRBs.
		On the postmarket side, there are all of the laws, actually some of the oldest authorities that the agency has, about truthful promotion, systems for adverse event reporting, postmarket studies, and manufacturing inspections.  
		Now, as we thought a little bit about the paradigm for reviewing the science, one logical way is to, and I think there's an element in some of the past reviews, is to think of this basic system, to think of our laboratory and our research programs, and then have the science review come in and take a look at that.
		(Slide.)
 		If you look at where we've actually got our resources deployed, though, and you can take a look at primarily fiscal year '98, if you look at '95, it's similar, although you'll see a shifting of all areas into the premarket program. 
		But you'll see if we actually just showed you the programs that were strictly doing research projects and science and laboratory projects and epidemiology and some of the other areas, that we would actually only be showing you less than 10 percent of the activities of the Center.  
		As a science based and an evidence based regulatory agency, we sort of asked ourselves, is there another way to better share the vision of how we see ourselves as a science-based organization.  
		So instead of premarket/post-market, we took a step back, because these are awfully regulatory terms and an inventor doesn't say, "Gee, I'd like to have a premarket device or a premarket invention or a post-market inventions," we thought a little bit of the whole process of the life cycle of a device.  
		Device begins as a concept.  Prototypes are built.  Preclinical work, if it's needed, is done.  A clinical program is begun.  Again, this won't be needed for every type of device, but this information is compiled together to begin scale-up for full commercial manufacturing and commercial marketing.  
		There's a period of commercial use for the product, and then there's a period where the product is obsolete and it's replaced by another product.  It may gracefully fade from the market or it may be withdrawn or it may more dramatically be given the hook but that's usually not the case. 
		So, in fact, if we think about in a non-regulatory sense the entities we're dealing with we're really dealing with a product lifecycle, and it's a product lifecycle that it's intensely interconnected.
		One of the difficulties of trying to do these things separately is what you learn from the preclinical phases or from the prototype informs the way you design your clinical program or has an impact on your manufacturing experiences.  
		(Slide.)
 		Similarly, manufacturing experiences are going to feed back to the choices you may make about the way that you're going to prototype the next generation of the device so that, in fact, even this kind of an interconnected diagram of product development really reflects for devices a more complex process, which is that of a pipeline.
		One of the things that's different about devices than drugs is that the agency has no authority to grant any type of patent extension or exclusivity, not even orphan drug exclusivity.
		The one mechanism we have, Humanitarian Device Exemption, is actually much more like a treatment IND, and it does not grant any marketing exclusivity.
		The average life expectancy -- or not life expectancy -- average time on the market for many devices is about 15 to 18 months, and in fact, there's some types of devices that are replaced by another version about every six months.  If you've ever tried to versions of a PC, two copies of a PC about four months apart, it's a little disconcerting to have that brand new PC you bought no longer manufactured, but the device manufacturing world is very very much like that. 
		As we thought about this process and thought about how different that was than the drug process where if you're lucky with a drug you get it marketed early in its patent life and you'll have a prolonged period where you can do post-marketing studies.
		It's almost irrelevant in some ways to talk about post‑marketing studies for devices because the product will be off the market and replaced by the next generation before you can really launch those products.
		And so that as we began looking at this and saying to ourselves what is it about devices and device regulation that we need to make different it was that we need to think about all the connections and we need to think of them as a family of products across multiple generations.  
		Part of this actually came from a comment about in vitro diagnostics for an infectious disease screening agent where someone from the Center for Disease Control said, you know, you only get over other version of this product.  
		In Europe, they market -- every time they update it and make it a little more accurate, it goes on the market, but your regulatory cycle is too long and there isn't time to get them on the market so they actually give you every other version of that.  And that didn't strike me as something that fit well with our public health mission of promoting rapid access to product improvements and product corrections.
		Where does scientific work come from?  This is another way of sort of organizing and sort of saying, what are we trying to get ready for as we look for an external review of our science.
		Some of the work is very product specific; so, for example, if you take the applications, the protocols, the 510(k) applications, the PMAs, the meetings, the advisory panels, these are all science-based activities.  They are very interesting if we're just talking about procedural issues or those kinds of details.  
		There are a variety of things that product-class specific, and the guidances that the Center produces, the Centers that we participate or recognize, workshops, special products, cut across products.
		Then there's work that is regulatory work that deals with the interaction between the science and the regulatory process itself.
		The way we've changed the 510(k) paradigm, to change the evidence rules to incorporate standards, for example, is an example of that.  It's very much tied into the science.  You couldn't do that just based on saying well, is there some way to streamline, this is an administrative process.  We had to say, can the standards actually replace part of the application.  
		Or, similarly, with MDR reporting when we developed a system for summary reporting for common adverse effects, we did not need every single individual report, is an example of something that requires understanding the epidemiology and the science of the issues.
		And there's issues relating to manufacturer's assistance and the other things.
		The fourth category in terms of origins of scientific work is one that this group has grappled with, which is how do we develop and maintain the competency of the scientists that we have.  
		What are the research projects that we do?
		How do they relate to the rest of the work that we do?  
		How well integrated are our scientists in the professional meetings? 
		And do they do the kind of things in normal sort of scientific citizenship, help plan meetings, help participate in scientific organizations.
		This is a much broader grouping of scientific activities than just our research proposals.
		If we go back to the total product life cycle and we say well, how does industry see the Center for Devices, in fact, you can even look at the ways we put on meetings and conferences and workshops. 
		You'll often see them organized around different specific regulatory mechanisms.
		Every year, for example, we cosponsor a meeting on how to submit applications in the PMA or the 510(k) process.  
		(Slide.)
 		If you look at these, one of the interesting things when you step back and look at them is that they still really aren't the science of product development.
		What most of these things are are data holders.
		(Slide.)
 		They are things are either the industry is communicating with us, such as when they send us protocols or applications or report MDRs which are adverse experiences from devices or when they send us a post‑marketing study. 
		Or there are things we communicate to industry with such as when we provide guidance or we make a determination about product designations or issue, a safety alert, or a warning letter. 
		(Slide.)
 		If we come back to sort of say where is the underlying science in the regulatory decisions, we come back to a view that steps back a little more and say, well, if we go back to that life cycle of a product, what are the disciplines and how do they surround that life cycle.
		So at the time that you're developing the concept for a product, you're beginning to work with designs and design, think of what the design controls will be.  
		The engineering that's needed to do prototyping -- and some of these are just illustrative, they don't apply to every device -- but if you're developing an implant you need to understand biomaterials and biocompatibility. 
		You need to understand the toxicology of the coatings that you may use or of the materials that may leech out of an implant.  
		In the preclinical phase, you may be doing and setting up hazard analysis based on the mode of action. 
		You may be developing bench strength testing or failure mode analysis that allow you to better design the product. 
		At the clinical phases of developing the science, there are all the issues around study design and statistics and the review of that family that really set up the evidence that is set out in the statute as the basis for allowing the approval of a PMA. 
		Quality systems.  And actually quality systems are more -- are a broader family of concepts than where they are on this chart where they're placed down with manufacturing, but relates to all of the different kind of things that you need to do to understand how do you manufacture something consistently in a way that it will perform as expected.  
		When we get to the post‑marketing side, we have all of the sciences of epidemiology and the sciences of understanding how to evaluate adverse events or the forensic engineering that occurs when you've got a device that's failed and you've worked backwards and you've found what is the failure mode mechanism which feeds back into the redesign of the program.
		And when we do have serious problems, the kind of science in doing quantitative risk analysis and assessment to try and decide what are the appropriate actions to take.
		What we would like to do in our science review is to actually be able to present the breadth of the science in the center to you about these products.
		We intend to actually tell you quite a bit about our research programs and our laboratory programs, but I think what our vision of is our science is it's imbedded in everything we do.  And if we want your input about how well we do our job, we need to do them well in all of these domains, and we need the issue of the quality of the recruits, the understanding of the scientists that work here, the ability to keep people at the top of their game, applies to all of these standards, as well as to the things that are traditionally thought of as research.
		(Slide.)
 		So, in short, we need to prepare for the workforce of the future.  This is a product we're currently evaluating in the Center.  
		(Laughter) 
		We'd like to have it battery operated so it would work a little bit better.  There's no predicate, that's right.  And we started from the most appropriate end here to begin mechanizing.  We need a little better informatics to work from top-down on this kind of a system.
		(Slide.)
 		Well, let me tell you what we have done so far and give you a proposed outline for a report which hasn't been written yet, so it's very easy to change this outline, it's very easy for us to take direction about how to change this and about how to make this process the most useful. 
		The CDRH leadership, by which I mean by deputies and the office directors of the Center, met and convened a science working group, that's been working for about a year, to actually work on the sort of concept of our being deliberative and thoughtful about what the science needs and the organization of science in the Center.
		What we're posed to do now is to put together an internal science review group that will produce an internal review document, and we've asked this group to be able to do this in about 3-1/2 to 4 months.
		And one of the requests of this group to the Centers that are doing a review is to have a critical self-assessment, and that's the purpose of this group.
		It will be an FDA group, although we've asked one person from outside the Center to come in and at least give us a little non-CDRH perspective.
		(Slide.)
 		It's not intended to put our best foot forward.  It's intended to be self-critical and to say "What are the challenges we're facing?"  "What are the areas the we really need to have a strategy for dealing with?"  Which is why there's an arrow coming in from the side there about our strategic plan, which is very much intertwined with the science review.
		The external science review group which have been the groups that this group has heard reports from the other Centers will have the internal document.
		They are welcome to interact with any parts of the other groups, and we're anticipating that we will invite them for a three-and-a-half day process to do an in-depth evaluation, and as a starting point have the internal review document.  But identify, perhaps, some of the bigger picture issues that are at the level where this group can particularly help us.  
		And then, finally, there will be a presentation to you, the FDA, Science Board, and recommendations to us which we will value and incorporate into the way that we move forward with meeting our challenges.
		(Slide.)
 		This is the proposed Table of Contents, an Introduction and Background.  We will provide, even in more depth, a description of the device and radiological health programs and give you an idea of the workload of the size and composition of the staff, the way the Center is organized, the description of the industry and the other stakeholders that we deal with, and provide you our mission, vision, and our own conception of the role of science in the Center.
		We would like to in this internal document expand on the topic which I've just introduced this afternoon, which is how science relates to the total product life cycle.  The basic paradigm is that this is science based regulation, that if you look at what we do, almost all of it relates on us receiving a scientific, data-driven, information about an issue that's been raised about the product appropriate to where it is in its lifecycle. 
		Our guidances are often methods guidances on how to provide that evidence.
		And the materials that we receive from companies that help us evaluate whether a new biomaterial is appropriate, are in fact usually study reports analysis, and then we review those and work to make a science based decision in that. 
		So that's the paradigm that we would like to present.
		Part of what we have to think about is what are the scientific roles in this process.  There was some discussion this morning about what do we really need.  We could pick an area, for example, like pharmacogenomics as an example of an area where I don't think we have anybody in the Center who actually has a background in pharmacogenomics.
		If we step back and say, what are we going to eventually be faced with, eventually we'll be faced with a product that wants to demonstrate that when a diagnostic pharmacogenomic test is used with a drug that drug can better be targeted to patients who will really benefit from that, and that will be an evidenced-based decision.  
		So we can work backwards and say what is it that we're going to need to know to be able to evaluate that?  Our responsibility in that will be to evaluate whether or not there is a test that is reproducible and in the setting of a drug evaluation sorts patients from those who will benefit from the drug from those who won't.
		And we can come back to it and say, well, what's our role in that?  What is it that we have to understand about that?  Which of those are sort of core competencies that cut across in vitro diagnostics and which of them require specialized knowledge of pharmacogenomics?
		And it gets back to the issue of where are we with these things?  Where in the Center do we need to be able to design the experiments?  Where in the Center do we have to be able to look at the results of fairly common clinical issues even though the tools will vary and the products will vary?
		We will present to you as part of this section the scientific domains, the clinical disciplines, the engineering, the physical and the life sciences that we currently have in the Center, and take a look at whether or not these are positioned to be the kinds of domains and kinds of disciplines that we need to have represented as we look forward to what we anticipate in the next five to 10 years.  
		And then we will go through the kinds of scientific work we do and whether or not we are appropriately configured in using our resources appropriately to do these tasks. 
		One of the strategies we have picked is that since we're not going to actually spend the time going through one part of the program, like our laboratory program in detail, where we could go through those programs in that amount of time and give you detailed descriptions of that, we decided that one way we could drill down and give some depth to the science review and still talk about every part of the Center is to take a product are that could illustrate the way that science is used. 
		We're not making claims that this is representative that it will serve all purposes.  As you can see, it's only part of the proposal.
		What we chose was an area of electrical stimulators which includes families of products, probably the pacemakers are the most well known and some of the most mature products in this area. 
		What we will do is really show you in great depth this product line and how the issues around the entire Center, around the total product lifecycle, how this product is evaluated and how we use their science.
		So to supplement some of the broad views and overarching issues that we'll present for the rest of the Center, we'd propose, actually, having part of the external review panel, having expertise in this area, who can come in and be self-critical and say, "Do you really have what you need to keep up with this area."  
		We know that this is an area that historically has had market launches for these products in Europe before they were launched here for a variety of regulatory and other reasons.  
		Let's take a hard look at that and see what is that all about.  
		So this is one part of our proposal that we would appreciate some feedback, but the concept is that we'd like to illustrate the breadth of the regulatory activity in some depth.
		Then, finally, there are a list of specific issues that we would like to deal with.  And, mind you, that this is the Table of Contents for the internal science review document that we're going to present to you.  The external group will develop its own Table of Contents.
		But we will share with you our assessment of how we prioritize and peer review our projects.  
		We have a major challenge in front of us sometime in the next five to seven years.  
		In fact, this year would have had the planning money but it looks like the planning money might be the year after that.  But we're going to have to rebuild every laboratory we have at a new facility because the FDA is moving to the White Oak campus.
		So our current laboratories, which are a few hundred yards from here are all going to be closed down and moved, and we're going to have to decide what are the configuration we want?  Those laboratories which were built for historical reasons and configured the way they are for a variety of reasons, we're now in a position to start with the architects.
		We, internally, shouldn't miss this opportunity to say what is the best way to configure these laboratories for the needs of the future, not just in terms of the contents of the laboratory but how should they be imbedded in the Center?  
		Do we want the laboratories to be an integral part that interacts with all the scientists in the Center and interspersed with the different groups, close to the review groups that they work with? Or is there more economy of scale and critical mass if they're located together?
		And there are also the other issues, such as we obviously share some overlap of tissue-based products, tissue-based devices.  
		Where should we collocate, not just the laboratory sciences but the reviews sciences with other Centers such as the Center for Biologics.  Or if we're building systems that are essentially drug delivery devices, are there some operates to actually get the connections we need with the Center for Drugs?
		So even though this plan was not put together with the primary purpose of dealing with White Oak, it's an opportunity for us to really ask ourselves where do we want to be?  What do we want the Center and its science programs to look like?  And we can even answer that question and do that physically with this opportunity.
		And the timing is perfect with this review because the timing will occur just before the time we need to start talking to architects about how to do the movement.  
		I've put down the issue of recruitment.  It's actually a much broader issue than that.  It's all the human resource issues around recruiting a group of scientists and maintaining them at the top of their game.
		We will present to you in the Internal Science Review our assessment of the current situation.  We will be self-critical.  We will, of course, be proud to tell you where we think our strengths are and where we've made more contributions.
		But we will also try and be not apologetic about the fact that there are areas where we can improve.
		There are opportunities that we have now that we need to be aware of and plan to take advantage of.  And similarly there are threats.  We usually think of the budget as a threat.  
		(Laughter) 
		But there are other threats.  There are threats to just being overwhelmed by advances in science.
		There are threats to having an international C change in the way that products are regulated.
		There are many things that we need to consider, and we will share our assessment of that with you.  
		We will look at ourselves and say, where do we do well and where are we improving.  And we will identify where we have gaps and where we're falling behind.
		We will also share with you our strategic vision and our plan for ways we can address this and ask you whether or not you think these are the things we need to do.  
		Our Vision Statement is actually quite short. 
		The Mission Statement was one long statement.  The Vision Statement is also a single statement.  
		"Insuring the health of the public throughout the products' life cycle with the coda that it's "everybody's business."  It's not something we can do alone.  It's something that is a shared responsibility.  It probably most fundamentally is the manufacturer's responsibility.  We have a role, even the consumer has a role in the use of therapeutic products.  There's consumers who have a real taste for the cutting edge.
		In fact, the idea that it's not approved in this country is practically proof that it must be good.
		And then there are those that are more conservative and say, "I can't believe you're asking me to take this when it hasn't even been tested yet and there's old stuff there."
		People need to grapple with this notion that we're dealing, really, with a whole family of technologies.
		I could actually go on the rest of the afternoon about our goal areas.  We will present this in detail in the strategic plan and how we think it addresses the challenges we have to face.
		The goal areas that we've identified which we think give us the tools to tackle some of the challenges are things that relate to living the vision of the total product lifecycle.  A lot of that has to do with making the connections within the Center. 
		Many of the questions were asked this morning about are you connected as you work on bioterrorism across the agency.  
		You could have asked the same question, are you connected inside a Center when you work on some products.  And it's a real challenge for us.  We need to do that.
		Magnet for Excellence.  We borrowed this phrase from the magnet schools.  What would we have to do to make the workplace a place that would attract scientists and other staff to come and work with us the same way that a magnet school attracts the best and the brightest in an area?  
		What do we need to do about the scientific environment and about the culture of the place and the opportunities to do that? 
		Dr. Woodcock and others talked about knowledge management.  We'd started talking about information technology, and then we realized that actually that was just a tool, and that what the real issue is to make sure that we understand what are the knowledge domains that we're having to deal with, that we understand the expertise we need, the reference systems we need, that we have the ability to trade and maintain and develop this.
		The final goal area is something we call "meaningful metrics," which is a little bit of a backwards slap at whatever we're doing now, applies that we're using non-meaningful metrics at the moment, but it was not intended entirely to mean that. 
		But we really want the things that we do to be measurable in the way that we accomplish our mission, the way that we promote and protect the public health.
		We want to be able to understand how our actions translate, what the impact is and to make our priorities based upon that. 
		We want to take a look at our statutory responsibilities and say, how do we meet those, how do we play in all of those areas and learn from the approaches taken in other disciplines, in other countries, in other regulatory agencies, to make sure that we can do this.
		So our Proposed Table of Contents that we're asking for feedback, we're proposing that this be the internal science review document that be made available sometime in March or early April, that in the meantime we use the process to select an external panel, which it's a stretch, it's a bit of a push, but I think we've designed this so it would be possible to get this done by the spring meeting so that we would be able to have the external panel come back in the spring meeting.
		As I mentioned to you before while we've been thinking about this and we have ideas about this, even the internal review is something which is very malleable and can change, and we present this today really to get feedback on how to do this.  
		Actually, I wanted to finish with a slide that quotes a book that the Commissioner bought us.  The Commissioner keeps buying books for the Center 
directors -- 
		(Laughter) 
		-- and fortunately they're all about one plane ride in length.  
		This was a nice short, you didn't even have to have a stopover for this book. 
		(Slide.)
 		This is a book, Kevin Kelly talking about the New Economy, the Rules of the New Economy.  It really resonated with me when I thought about how we had been grappling with our vision of the Center.  
		The New Economy has three distinguishing characteristics:
		It's global;
		It favors the intangible, by which he meant ideas, information, relationships; and,
		It's intensely interlinked.
		When I go back to sort of the logo of how we think about products being developed and the global nature of device manufacturing and the way that information is increasingly imbedded in the devices themselves, and the need for us to be imbedded in the whole process, both in the process of consumer protection and imbedded in the business cycle of these products to promote their availability;
		I think that this actually describes very well where we see things.
		(Slide.)
 		In short, we don't want the final picture of the campus at White Oak to look something like this.
		(Laughter) 
		We have a much rosier vision of that, and we look forward to your feedback on our proposal.  It's ambitious to get this all done by this spring, but we're enthusiastic about doing it.
		DR. LANGER:  Thank you.
		Comments?  Suggestions?  
		I thought you might, since you have just been through it.
		DR. FENNEMA:  I'd like to commend you, first of all, for a very thoughtful outline for this and most importantly for the recognition of the importance of self-evaluation in this process, because in any review process, it is the self-evaluation that turns out to be about 90 percent of the value.  
		The reviewers come in for three days or four days or whatever it is, and causally look over things that are happening and make snap judgments on what they see.  
		This is done actually much better by the review panel if there's a thorough self-evaluation in advance so that the review panel can consider these things in self-evaluation and offer their opinions on these.
		So I think this is really a very, very good first step for a very sound review process, and so I do congratulate you.
		DR. LANGER:  Bob.
		Everybody should turn their microphones on.
		DR. HENNEY:  We'll remember.  Congratulations.  So don't worry.  
		DR. NEREM:  I thought it was a well-laid plan, David, and I agree with Owens' comments about self-assessment.  I've been through university's many times, and that's really a critical part. 
		A couple comments.  
		One is:  I think it's important that you do pick something to really go in-depth, and electrical stimulation actually is an interesting one.  Because on the one hand, some may think of it as being more traditional, the kind of medical devices that you people have experience with, but in fact I know several companies that are thinking about putting electrical stimulation together with tissue-engineered products.
		So it actually represents an opportunity for that kind of broader look.
		I was intrigued by one part of your outline.
		You talked about assessing internal strengths and weaknesses and internal and external threats and opportunities.  I would hope you would also assess internal threats and opportunities. 
		(Laughter) 
		DR. FEIGAL:  Yes, we have those, too.
		DR. LANGER:  Yes.
		DR. ROSENBERG:  Do you have a particular section where you're going to actually propose recommendations, where you would actually present the set of proposals to the reviewers for response?  
		DR. FEIGAL:  Yes.  We do that as part of using the goal areas of the strategic plan, to make recommendations.
		We would identify in the situation analysis, which is near the end, where we think are things that we need to address, and we would see if we could build it into one of the theme areas.
		So, for example, if the issue had to do with recruitment, retention, development of professional skills, that would fit quite logically both in knowledge management and magnet for excellence, workplace excellence kinds of goals.  
		By the time spring has started, we will actually have some projects underway that we can point to as works in progress.  
		In fact, that was another reason that we liked the timing, sort of the convergence of forces, is because we're getting ready to organize an effort to change things in the Center, and this would be our proposal to you of some of the things we've identified in the science area and some proposals of how we might do it.  
		Then we would very much welcome other suggestions or comments on things that you might not be as productive as other things we can do.
		DR. ROSENBERG:  Yes.  It will help focus that discussion.  
		DR. FEIGAL:  Yes.
		DR. LANGER:  Bob? 
		DR. NEREM:  Is all of FDA moving to White Oak?
		DR. HENNEY:  The parts of FDA that will move to White Oak first will be the Center for Drugs, Center for Devices, next up the ORA and Office of the Commissioner and Biologics will follow in sequence.  It's really planned out as a six to seven year, although when we had the ground-breaking a few weeks ago I encouraged the Congressional committees that our 100th year anniversary of the FDA will be in 2006, and so it would be a very nice way to celebrate it if we were practically completed by that time.  So we don't know if we'll move up on their urgency list or not. 
		But those will be the components that will be consolidated in White Oak.  
		CVM and the Center on Foods are really over near to the University, more in that area, the University of Maryland kind of campus.  So we will have two major components that will be -- 
		DR. FEIGAL:  Are there any buildings designed yet?
		DR. HENNEY:  The Center on Drugs is just undergoing design.  All the rest of them will just come in sequence.  
		They have had an initial design, yes.  And, quite frankly, some of that design, while attractive, still I think we want to look at the interior again because it's still very much the silo kind of concept with each Center with their own facilities and some shared facilities in terms of the animal facilities and like that. 
		But I have really asked the Center directors along with the architects to -- we think some of the places in which we might have either better interconnectedness by the interface or a plan whereby even after a Center moves that once we would all be out there we can retool the flow.  So that's kind of where we are going with this.
		DR. FEIGAL:  I would strongly encourage you on that.  I have become a firm believer that the way you organize people in space does not have to have any relationship to the organizational structure of the institution, and that's a way to build bridges between stovepipes.
		DR. HENNEY:  Well, intra-Center, David has introduced kind of a novel idea as well within the Center on the Device Center, in that he's also having his major office directors collocate with each other at least two days a week within his own office so that he can make sure that they are talking to one another too.
		So I think that we share your advocacy for looking for unique ways in which we can make sure that the interdisciplinary nature of what we do we can greatly facilitate that.
		DR. FEIGAL:  When I first came to FDA was with a group that had a rule that no two people from the same discipline could have adjacent offices.  And it really --
		DR. NEREM:  That's the way my Institute's organized.
		DR. FEIGAL:  -- it really created a sense of teamwork that wouldn't have worked as well had people been grouped in their little departments and been fighting each other for space at the borders and all the rest of that. 
		DR. NEREM:  So the extreme of that is that no two people from the same Center can have adjacent offices.
		(Laughter) 
		DR. FEIGAL:  It's one of those map puzzles, you know.  How many holes do you need to make a unique map?
		DR. LANGER:  Other comments?  
		Is there any other feedback that you'd like?
		DR. FEIGAL:  Well, I guess one of the most critical logistics questions from those that have done one of the reviews is is this too short of a time frame or do you think we can get this done?  
		DR. NEREM:  I didn't understand the time frame because you talked about the internal document being done by March, at worst early April.  
		DR. FEIGAL:  Yes.  
		DR. NEREM:  Our next meeting is April 13.
		DR. FEIGAL:  Yes, you're right.  May I was thinking February, March.  
		DR. NEREM:  I don't think there's any way you could bring in -- 
		DR. FEIGAL:  No, we had worked backwards to give about -- we had thought that it would push an external group to have about six weeks to prepare for this meeting, so that was what we were working back from.
		And so one question is whether that's enough time. 
		DR. NEREM:  I think you can do the internal by then and it would be interesting for this group to see the internal document at that time and then do the external thing after the April meeting.
		DR. FEIGAL:  How much time would the external group need to prepare for a report back to this group?
		DR. LANGER:  Owen?
		DR. FENNEMA:  Well, if we look at the guidelines -- 
		DR. LANGER:  Do you have your machine on?  I mean your microphone.
		DR. FENNEMA:  If we look at the guidelines, which a proposed for you in your book, there's supposed to be a six-month lag after -- which could start, actually, before your internal review is over.
		DR. FEIGAL:  Yes.
		DR. FENNEMA:  That's a possibility.  But there's supposed to be that six-month, and I think that's desirable because just to make sure there's no misunderstandings on the part of either party.
		But once that's done, then I think if the Review Committee has simply, you know, six weeks, eight weeks to look at this internal report and to lay out the procedures for the actual meeting itself, review meeting itself, that would be sufficient.  
		And then, which is not in the guidelines, it's my feeling that there ought to be a requirement in there that a written report from the Review Committee is prepared within four months or less. 
		And if all this were done properly, you could have that written report finalized and ready for this group in November again next year.  That would, I think, be completely doable.  
		DR. FEIGAL:  So one sequence could be that we could begin convening the group -- it sounds like that you would consider an invitation for us to come back and present our internal review to the entire Board in the spring and then have an external review that would have until the fall to get back to you, even though they might do their work before summer? 
		DR. LANGER:  Okay.  Any other suggestions or comments?  
		DR. SCHWETZ:  A couple of other things that need to happen that David hasn't listed.  One of them is to select a chair for the Committee, and we have preferred to have a chair be from the Science Board.
		Then David will also, with people in his Center, prepare a list of people to consider as review team members, but I haven't had the Center make the phone calls and ask people -- in fact, what I use is their list of people and begin to make phone calls and ask those people who they would recommend to be on this review panel. 
		And the chair could help with that process because that makes it go a lot quicker, and with someone of the stature of Dr. Fennema he was able to get people to answer the phone more quickly because they recognized his name, than for me to make cold calls to people I don't know.
		So it's good if I can work with the chair to begin to develop a list of people who could serve as the review team and then make the final cut on that. 
		The point is this is not the decision of the Center director to make the final cut on the panel.  We would work with Dr. Henney for that. 
		So those are a couple of other things that can begin to happen now.
		DR. FEIGAL:  Yes.  We've taken it as our role to find people to nominate for you to consider, but it's not our place to pick a Committee.  
		DR. SCHWETZ:  Sure.  
		DR. LANGER:  Other comments?
		Yes, Bob. 
		DR. NEREM:  Did you say that the external committee would come in for three-and-a-half days?
		DR. FEIGAL:  That was the proposal.
		DR. NEREM:  Is that realistic, Owen? You've chaired one of these things. 
		DR. FENNEMA:  Well, I think this depends -- and I can't speak with any authority about this in terms of the answer -- but it depends on the complexity, the size and complexity of the organization, how many subgroups, distinct subgroups you have in it, because you want at least two members on the Review Committee to be able to look at each major subgroup in their organization.  
		So that kind of dictates the size of the Committee you're going to have.  
		And then you want all of these subgroups to report and have ample time for discussion during the meeting, and so you put that all together and it kind of determines how long the meeting has to be, so I don't know how many subgroups you've got, but -- 
		DR. FEIGAL:  Yes.
		DR. NEREM:  They are picking one area of technology for in-depth assessment.
		But some of the other groups would be looking at issues Center-wide in some of those processes so it's kind of more of a hybrid.  
		DR. NEREM:  I'm just worried about getting the kind of people you would want for that.  
		DR. FEIGAL:  We realize.  In the Center of Biologics, they had a five-day review, and we felt that was unlikely to -- it would be hard to find people that would be able to do five days.
		DR. NEREM:  If you did it in Hawaii you might be able to.  
		DR. HENNEY:  White Oak is not in Hawaii.
		DR. NEREM:  There must be a White Oak in Hawaii.
		DR. FEIGAL:  That's right.  Black Oak.
		(Laughter) 
		DR. FEIGAL:  I think we can work on some of those details and some of the planning.  We can begin to design the review with some of the logistic reality so that we don't get a Committee that feels it's taken too superficial a look or that it hasn't used its time wisely.
		DR. CASCIANO:  If Hawaii is not available, Arkansas is available.  
		DR. LANGER:  They're close.  
		(Laughter) 
		DR. LANGER:  Any other comments, suggestions?
		DR. SCOLNICK:  Would there be voting machines also?
		DR. FEIGAL:  There were definitely human factors problems with that butterfly.  We can talk to you about human factors.  
		DR. LANGER:  That sounds good.  
		(Laughter) 

		DR. HENNEY:  It's not been classified as a medical device yet.  
		DR. LANGER:  Thank you very much.  We'll look forward to that next time.
		I guess the next topic is the hiring update to support the science base of the CFSAN Food Ingredient Safety Program.  
	Hiring Update
		DR. JACOBSON:  Yes.  If I could just add a couple of words here.
		Last time you met you heard CFSAN's plans for hiring 50 or so new people into their food ingredient safety program, and you were very interested in how that recruitment process was being put together and what was going to result from it, and we thought you'd appreciate an update today on how it has been working.  That's what we're going to do.
		I think Dennis Keefe is going to be giving the presentation.  Is it Dennis or Alan?  		MR. RULIS:  Yes, I'll start. 
		Can I be heard?  Is the microphone going?  It's going red here.  
		Good afternoon.  I'm Alan Rulis, the Director of the Office of Premarket Approval in FDA's Center for Food Safety and Applied Nutrition.
		With me this afternoon is Dr. Dennis Keefe of the same office.  Dennis has been charged to create a hiring committee within our office and procure new hires as a result of having received -- the Center having received new appropriated funds as of Fiscal Year 2000.
		That gave us an opportunity to bring on board about 50 new employees, and we're currently in the midst of that process.   
		As you recall, in April of this year we met with you to describe the program that we had in mind, and at that time, of course, we were pretty much at a dead stop.  We had not hired in a long time.  We had not hired nearly that many people in a long time in our office.
		We had to relearn how to do that and do that well.  The biggest fear I had at the time was where are we going to find highly-qualified candidates who, in the year 2000, want to come to work for the government, who are highly qualified and who are highly diverse.
		Today we are going to give you a little bit of a report on this is sort of a mid-course report on our progress, and Dennis from my office will hopefully provide you some of the answers to those questions.
		DR. KEEFE:  I'm not from Devices, so I need some help.
		(Laughter) 
		The first slide.  (Slide.)
 		Just to restate.  The mission of the OPA recruiting team -- this is the Office of Premarket Recruiting Team -- is to recruit highly qualified --
		DR. JACOBSON:  Maybe you could pull your microphone up a little because it's hard to hear you.  Thanks.  
		DR. KEEFE:  Our mission is to recruit highly-qualified scientists.  That's our ultimate mission here, the focusing on the science of what we're doing. 
		As Allen mentioned, when we spoke to you last April, we were just beginning this process, and we had a lot to learn not only in the office, but we also had 
to -- I think our personnel office had to relearn how to do recruiting and hiring.  That's something we haven't done for a while.  
		We take this very serious.  The number of FTEs that we're talking about is going to have a dramatic effect on the functioning of our office, of the Center and of the Agency not only for the next few years but in the future.
		Personally, for me, this is important because these are the probably the people I'm going to have to work with for the next few years and I want to make sure they're good. 
		So if I can have the next slide.
		(Slide.)
 		Just to give you a summary of our recruiting team:  Again, it's composed of the regulatory scientists in the office and also with participation from the Center's personnel specialists.  
		We've defined our hiring goals as we have numbers of chemists we want to get, toxicologists, environmental scientists and consumer safety officers we want to bring on board. 
		We've also identified specific scientific areas of expertise that we want to recruit for in those broader categories.  And these include data mining and especially genetic toxicology.  
		Part of the funding for this program is part of the premarket notification program for food contact materials, and these are areas of expertise that we will need to meet our legislative mandates.  
		So if I could have the next slide, please.  (Slide.)
 		So about the time we met last year or last April -- I'm sorry, it hasn't been a year; I'm sorry, it seems like it's been a long time -- we had to go through a lot of mundane, sort of personnel efforts.
		That is, updating our position descriptions;
		We had to develop procedures, SOPs, if you will, for screening the paper applications, developing guidance for people to interview and candidates, and setting up procedures for the interviewing. 
		We also set up a procedure for how the office would make recommendations to the director to make decisions on potential candidates, and what we've done is to -- in bringing in candidates for interviews, we've had them meet not only people in their area of expertise but also people in the other disciplines in the office.
		So not only does a candidate get a broad breadth view of what the office does and the science involved in the office, but our toxicologists can have input on the decision on whether to hire a particular chemist and vice verse so this has worked very well for us.
		Again, we've included FDA personnel specialists in this to help us make the process as efficient as possible.  
		So if I could have the next slide.
		This is a snapshot of all of the hiring under the appropriations, and this includes -- this is about 50 FTEs.  About 10 of those are outside of our particular office, and if you look at the graph, if you look at it back in April, we were down to about five, and most of these hires were outside of the office.
		We hadn't made any hires when we last met, and you see the filled circles are committed FTEs, people who are either on board now, physically, in our offices, or will be coming on board soon.
		The open circles is just a linear extrapolation from the curve on what we expect in the next few months as far as bringing new people on board.
		So, again, this represents the full 51, 52 FTEs that we have appropriations for. 
		If I could have the next slide.
		(Slide.)
 		We've broken the numbers down for the specific recruiting in the office, which is what our recruiting team is focusing on.  
		In the first column you have the different disciplines, if you will -- review chemists, review toxicologists, consumer safety officers, et cetera.
		In the next column you see the staffing levels in these areas, in April in the office, you see a total of about 90 FTEs dedicated to the review function of the office.
		Our targeted goals, initially, were to bring on 6 review chemists, 17 review toxicologists, consumer safety officers, et cetera, for a total of 42 FTEs.
		And in the final column, you see where we are now.  If you look, we're halfway there.  We're about halfway there.  
		I think when we talked to you in April of last year our goal was to try to reach the halfway point by the end of this fiscal year or, or the past fiscal year.  We almost made it.
		I think in your package you have the results of a survey that we provided to he recruits that we have on board that provides information on their undergraduate institutions, the graduate institutions, their dissertation topics, any of their postgraduate experiences.
		I think if you look at that information, I think you would agree that we've recruited highly qualified individuals from across the nation, and amongst these 20, I think 7 of them are under-represented minorities, so we've been pretty successful there.  This has been quite a happy result.
		DR. DAVIS:  (Off microphone.) Should we ask questions now?
		DR. KEEFE:  Sure, please. 
		DR. DAVIS:  (Off microphone.)  You have a goal of 17 toxicologists but you've only hired 7?  
		DR. KEEFE:  Yes.  
		DR. DAVIS:  (Off microphone.)  Could you comment on that?  And the fact that you had a goal of 9 clerical people and you haven't hired any.  I assume clerical people would be a group you might easily find locally and be able to find those people without a lot of problems.
		DR. KEEFE:  Right.  Our initial targets with the recruiting was to try to get the review scientists on board as soon as possible so that we could alleviate some of the back -- I don't want to say -- the workload in the office, so we could then more specifically target our specific needs like the data mining expert, a genetic toxicologist.
		So we were focusing on the major scientific disciplines.  If you look at the numbers, amongst the top three, we're pretty equal there on the number we've brought forward. 
		Clearly, we need to focus on bringing in more toxicologists and we need to bring in the administrative clerical support, and that's our next steps.
		DR. SCOLNICK:  Looking at the table that you've provided us with, I don't know whether you can show that to the panel or not, it says: Number of candidates interviewed, number of pending offers, target, numbers of on board, et cetera.  
		The number of candidates, is the striking of feature of the table, but there's a potential column that's missing.  
		For chemists you have six candidates interviewed and five on board who accepted the offer.
		DR. KEEFE:  Yes.
		DR. SCOLNICK:  How many applied?
		DR. KEEFE:  That becomes a difficult number to get to because of the way the vacancy announcements are constructed for the agency, there's one open, continuous vacancy announcement agency wide. 
		So what we've had to do is go out and screen the paper applications and identify potential candidates and then decide whether to interview them or not.
		So there isn't a direct application process.  So I really can't answer that. 
		DR. SCOLNICK:  For toxicologists there were 16 interviewed and 5 accepted out of the 16.  So what would be helpful to me at least is to know even though it looks like you've been successful is among the toxicologists you offered it to, what was your rank versus the number that -- how did you rank them and who you preferred would accept versus the people who accepted you?
		And say the chemists, where there are six offers and five acceptances, how many qualified applicants did you look at to decide to interview six?
		Because one of the things, at most institutions, they have many more applicants for their jobs or their slots in schools than they end up accepting, and it various in what institutional situation.
		Some places it's 10 to 1, 20 to 1, 2 to 1, 3 to 1, and I think whatever metrics you can bring to bear on your hiring process, like how many applicants you're really getting, what is your rank list for the ones that you put up the offers for, who accepts, who doesn't on that ranking; some additional metrics would help at least me see the quality of what you're hiring.
		DR. DAVIS:  (Off microphone.) The one in which we look at is are you an employer of choice?  So, for instance, if you interview 16 toxicologists and you only hire 7, out of that 16 were 13 of them candidates you would have liked to have had and only 7 accepted?  
		Or did the 16 that you brought in, they looked good on paper,but when you got them in you wouldn't have made offers to but eight of them?  
		DR. KEEFE:  Right.  
		DR. DAVIS:  (Off microphone.) So you offered 8 and you got 7, which looks pretty good.  But if you offered 16 and got 7 that's a whole different story.
		DR. SCOLNICK:  And if among the top 16 you wanted the top 8 and you only got the bottom 7, then you know you still have a problem.  And it just allows you to constantly improve your hiring process and the quality of what you're getting to measure yourself. 
		DR. HENNEY:  Alan, did you have a comment to add to that?  
		DR. RULIS:  No, I don't have the numbers exactly in my mind, but as I think through the process I would guess that we had quite a few more than -- you know, the numbers up here represent a subset of obviously a small subset of the people who expressed interest, but I think of the people who we interviewed, there were a number that we decided we would not proceed further with.
		And I don't exactly know the factor, but perhaps this represents maybe a third or so -- or maybe a half or a third of the candidates available.  But we could get those numbers and I think the next time we talk with you we'll expand the table out and try to give you a better feeling for that.  
		DR. KEEFE:  We certainly can produce those, but we just haven't been thinking in those terms.  But that would be helpful.  
		DR. DAVIS:  (Off microphone.)  It's important that you think in those terms than show us the numbers.  
		DR. KEEFE:  That would be helpful.  No, I mean, we can do that.  We have the database of the candidates that we've identified as strong candidates.
		DR. DAVIS: (Off microphone.)  So it's really key that you know whether or not you're getting the people you want, or are you just filling the slots because you've got open head count.
		And the other question I have is with this table, does the government have temporary workers?  You know, as I look at this, to me, aside from the fact I know you need toxicologists, but I would think you need administrative support, too.
		So my question is here you have hired nobody and you've got nine slots.  It would seem to me that you have people wanting the jobs.  
		So if you couldn't bring people in full time, could you hire temporaries?  Get them in, see how they worked out?  I mean, you can switch them over.  Therefore, you'd be able to get that work done while you're looking for the right candidates or something.
		If this has taken eight months, six months, you know, and you haven't filled any of those slots, I would think administrative workers can be quite critical as well.  
		DR. HENNEY:  Alan?
		DR. RULIS:  Yes, just to put this into a little bit of context.
		I think your point is well taken.  I think that, you know, we do need to concentrate on that cadre of folks.  Dennis' point here is that we have purposefully focused on the scientists we need to do the job. 
		We do have currently a cadre of clerical people and program support people throughout the office.  This is an expansion of that, considerable expansion of that.  But in the course of this hiring, we have gone out and hired temps.  
		We've hired all sorts of part-time workers to carry on while we bring on full-time folks.  We've just focused really on the full-time hires.  We've focused on the scientists first.  
		I fully expect that by the next time we get together we will have our cadre of support people.  They're a whole lot easier to find, you're right.  And there's no problem, particularly, with doing that.  But in the context of what exists in the office now, we have a base of those kinds of workers who are supplying us what we need.
		DR. KEEFE:  Any other questions?
		DR. LANGER:  Marion?
		DR. NESTLE:  Yes.  I was curious about this FDA Outreach list.  Is that yours or is that somebody else's?  It must not be yours if you don't recognize it.
		DR. KEEFE:  Is this part of the -- there is also in our package of information a strategic plan that I was going to mention later.
		DR. JACOBSON:  Yes, that's something different. 
		DR. KEEFE:  That's something different?
		DR. JACOBSON:  They may very well have outreached some of these groups in this hiring effort, but this is Agency-wide.  
		DR. NESTLE:  Yes.  I was very curious about this list, which is the list of places where it looks like recruiting was done, and I was curious to know whether you're doing this and whether other places are involved.  
		DR. KEEFE:  I can tell you I'm not doing it.
		DR. NESTLE:  Okay.  How are you recruiting?
		DR. KEEFE:  If I could have the next slide.
		(Laughter) 
		DR. NESTLE:  I set you up.
		DR. KEEFE:  Thank you.
		(Slide.)
 		I just want to briefly talk about some of the things we've learned, lessons learned.  
		With regard to getting the word out, advertising in professional scientific journals is great.
		Utilizing the web.
		Attending scientific professional meetings in person.  
		Having our scientists go out and not just sending somebody from the personnel office to talk about the science of it what we're doing, to identify candidates and encourage them to apply.  
		And, surprisingly, using emails to send to department heads as opposed to letters or phone calls, they're much more responsive.  
		Letters, we go very little response to. 
		Phone calls, not much either.  But the emails really worked.  
		DR. NEREM:  Emails are the easiest to pass on.
		DR. KEEFE:  Yes, exactly.  Exactly.  
		DR. ANDERS:  Do you code your applicants?  Do you know which of these strategies is most efficacious?
		DR. KEEFE:  No.  
		DR. ANDERS:  Where do you most of your applicants come from? 
		DR. KEEFE:  Well, actually, most of our applications, we -- for example, the chemists.  Most of the chemists were identified at scientific meetings and were encouraged to apply, and we worked with them to prepare their packages, to meet the OPM guidelines so that they didn't get lost in the process.  	That was our best way.
		And also with the toxicologists, that's worked very well.  In fact, I would say across the board where we've really found people is face-to-face at professional meetings.  
		DR. ROSENBERG:  Are any of your people you've brought on senior people or do they all tend to be senior start-up people?  
		DR. KEEFE:  Most of the people we've brought on are newly hatched PhDs or PhDs with a couple years of post-doc.  We have a few more senior people, especially I think we have a couple of toxicologists that we're bringing on board that they're a little higher, more experienced level.  
		But, again, our initial emphasis was to focus on getting scientists in, qualified scientists in, and try to refine it, focus these other targeted areas later.
		DR. SCOLNICK:  This opens up potential bias can of worms.  We always look at the kinds of letters you get and people usually say, well, this people is among the best 10 percent post docs I've ever had.  Five percent are graduates, 1 percent, 20 percent. 
		Do you look for that kind of information in your recruiting?
		DR. KEEFE:  We do a very rigorous screening of the paper presentation that the candidate presents to us and with the personal interactions at the meetings. 
		We look closely at the references for any identification for weaknesses and in the application.
		We focus again on the science and their writing skills because writing skills are critical to us.
		And 95 percent of the candidates we brought in for seminars, so we look at their verbal skills, we look at their ability to organize presentations in a logical manner.  
		DR. LANGER:  I don't know if your question was answered.  
		DR. SCOLNICK:  No, it wasn't answered.  But I'm just trying to raise the awareness level as high as possible.  
		DR. LANGER:  I got it.  I got it.  Okay.  Because I think that's exactly what I look for.  
		(Laughter) 
		DR. NEREM:  Two things, following up on that, number one: There is an old adage that anybody can get good letters, it's only a question of whom they can get them from.
		The second thing is you talked about carefully reading the reference letters, but do you talk to these people on the phone?  Because frequently they'll say things that they won't put in writing for obvious reasons.
		DR. LANGER:  That's all the tricks.  That's exactly right.  
		DR. SCOLNICK:  That's why I asked the question.  I realized I was getting into a complicated area. 
		DR. KEEFE:  If we have questions about the candidate and especially if there's questions that are deriving from the references, we will call them, and we have called them, and we have actually identified some candidates that looked very strong on paper, but after following up with the references, we decided not to make offers to them.
		DR. NEREM:  Probably people use a lot of different language, but if someone at the end of the letters says, "If you have any further questions, please contact me," that's sort of saying maybe you ought to contact me. 
		(Laughter) 
		DR. KEEFE:  No, we take this very seriously.  This is -- 
		DR. NEREM:  I'm sure you do.
		DR. KEEFE:  -- these are people we have to work with.  We have a mission to do in our office, and we're not just bringing in warm bodies.
		DR. NEREM:  No, I just want to make sure you're using all the tricks.  
		DR. KEEFE:  No, I appreciate that.  I appreciate that.  
		DR. SCOLNICK:  It's especially important when you're starting a new recruitment process like this for a larger group of people, because if you do it well it will be autocatalytic, whatever.  Those people will attract  the next wave and you just raise the whole level.  It's really critical.  
		DR. LANGER:  Bob, you had a question?
		DR. BUCHANAN:  More a comment than a question.
		I also wanted to point out that we're very sensitive to the issue of there's a tendency among scientists to go to the same group of friends or acquaintances to look for new post-docs or whatever, and this winds up, we deal with a very small pool of candidates this way.  
		So we make a very concerted effort to blind this process in a way and go out to make sure we're getting the sampling of diversity that's out there and set up the criteria for looking in that manner. 
		So if it seems like we go to some great deal of extra steps, we are doing it specifically for that reason.
		DR. NESTLE:  I was just going to comment that I don't know who Greg Diachenko (ph) is, but he must be a great resource in your office, according to these comments?
		DR. KEEFE:  If you remember we were talking about the chemists, he's head of our chemistry review group.
		DR. NESTLE:  And so he just goes out and talks and?  
		DR. KEEFE:  Well, he's attended some of the Job Fairs, ACS meetings, et cetera.  
 		DR. NESTLE:  Well, have him do more of that.  It seems to be working.  
		DR. KEEFE:  Yes.  
		If I could have the next slide, then.
		(Slide.)
 		So other lessons learned, interacting with the candidates:  As I mentioned before, have the candidate interact with the across-the-board scientists in the offices is very good for not only giving the candidate an idea of what we're doing but also for evaluating the candidate.
		When we're interacting with them, we're talking about the science of what we're doing, what the job is like, what the challenges are.  
		As far as procedurally, once we've identified a candidate that we want to make an offer to, following up with the candidate, being persistent with the candidate, keeping them informed of where they are in the process is very important. 
		It's very important for the people in the office to learn the hiring rules within FDA and OPM.  The FDA personnel office has been very helpful with that, not only at Parklawn but at the Center.
		Again, monitoring all aspects of the process when we're trying to get offers to them and making sure things don't get lost, it's very important.  
		If I could have the next slide.
		(Slide.)
 		Again, in selecting the candidates, we're focusing on the science and their scientific ability relative to the mission of the office and how they will fit into what the office has to do in the future.
		If I could have the next slide. 
		(Slide.)
		So the next steps we envision:  
		Obviously, we're going to redouble our efforts with the toxicologists.  
		We are going to be recruiting for candidates for the bridge positions.  These are the non-clerical support people.  These would be people that have information technology background, help maybe project officers, helping with contracting work, these sorts of positions.  
		We also are going to use the CFSAN strategic plan for recruiting which is in your package. 
		This was prepared by a new hire that was part of one of our FTEs in the Center, and she's developed a recruitment plan that has identified resources that we can tap into to continue this work.
		We are also exploring ways we can interact or develop a relationship with universities.  
		Just this morning I met with somebody from Duke University about setting up a relationship in the future, perhaps an internship program, or somehow we could work together to improve our process here, not only for recruiting but also for getting the word out about what sciences we do in the Center. 
		I think that's at. 
		If there's any questions, I would be happy to answer them.  
		DR. DAVIS:  (Off microphone.)  I see in the book that you have a listing of universities for diversity outreach sources, and you mentioned having people go to the university.  I don't know if you have any African-Americans in CFSAN who have positions of importance for sending people like that out with you to help recruit.
		The same thing would be sending females to Spellman, to a woman's school.  People like to be recruited by people who look like them.  And when they say it's a great place to work they seem to be more believable.  
		DR. KEEFE:  Right.  Actually, I think the fact that we have been somewhat successful with the minority candidates, we make an effort when we do interview them, to make sure that they do meet some people like them in the interviewing process.  So I think that's helped.  
		DR. DAVIS:  Okay.
		DR. LANGER:  Yes?
		DR. FENNEMA:  Looking at this page of comments from new hires, which is in the stuff that was mailed to us earlier, and as I read over this, I found several places in here which seemed to be very good source material in your recruiting documents, if you made quotes from this, as to why they selected a position with FDA, there's some very good comments in here that I think other people considering work at FDA would be interested in hearing about.  So you ought to consider, I think, using that  
		DR. KEEFE:  Maybe I'm not clear.  You mean as a promotional?  
		VOICES:  Yes.  
		DR. LANGER:  That would be effective.  That's a good suggestion.  
		DR. KEEFE:  That's a very good idea.  That's a very good idea.  
		DR. FENNEMA:  There's some very positive statements there. 
		DR. LANGER:  Other comments or suggestions?
		(No response.) 
		Why don't we take about a 15-minute break and be back at 3:00.  We're a little ahead of ourselves.
		Yes?  
		DR. DAVIS:  (Not microphone.)  I'm going to have to leave after the break, but can you give me some guidance on the follow-up to the public comment, because I'll be gone, but how that's normally handled?
		We had a young lade come forward and make a public comment and went away, and we didn't way anything to her.  I don't know if she's gone already but do we go into Closed Session with that or get back to the Board?  I'd like to know where we stand with that. 
		DR. LANGER:  Absolutely.  
		DR. DAVIS:  I would have appreciated if you told her something, to be honest.  
		DR. LANGER:  Yes.  Do you want to go over it?
		DR. SCHWETZ:  This was an appeal to the Board to make a recommendation -- to urge the Agency to form an advisory committee and some additional steps.
		So I think it's up to you as the Science Board to discuss whether you want to just recognize that you listened and be silent on recommendation or do you want to make a specific recommendation or do you want to disagree with what was recommended?
		I think you need to decide how you want to follow-up on that.
		DR. JACOBSON:  And before you do that, let me just say that she gave us a quite lengthy written version of her remarks.  In fact, she didn't have time to give all of her total statement and she did cut it short.  So you might want us to distribute to that to you so you can read it before you make your recommendation.  
		DR. HENNEY:  I wasn't here when she made her presentation so don't know the content, but as it might be appropriate, we might want to provide something to the Board to inform you about what the Agency might be doing with respect to the issue as well so then you can come to a better conclusion as to what you might recommend.
		DR. DAVIS:  Yeah, I would like -- this was about drugs.  We'd have to have somebody from the Center of Drugs respond to the Board on the issues. 
		But I'd also like to hope that she would be told that there will be a response coming back from the Board just so she doesn't leave thinking that we totally ignored her.
		DR. LANGER:  Right.  So is the suggestion then that we'll get that information from the FDA and we'll have that on the agenda next time?  However you think.
		DR. HENNEY:  If I could leave it to Liz, since I wasn't here.  But it seems to me that if there was only one person making a particular point, we should get you the full document that she wanted to provide to you or make sure that you got.  
		We could give you more information about what the FDA may or may not be doing in that area, and then you could make a recommendation either by mail or at the next meeting.  And we certainly will follow-up with her about what your decision has been and any other further Agency action that she might want to be aware of.
		DR. ANDERS:  We'll need to know the composition of the Advisory Committee.  Because much of her complaint was that it wasn't representative. 
		DR. HENNEY:  Okay.
		DR. LANGER:  I think what we'll do, then, if it's all right with everybody, we'll get her document to everybody, we'll get some feedback from the FDA to everybody, and then we can probably do something by email, to get some type of follow-up before the next meeting.  I think that probably she would appreciate as well.
		I think maybe we can write her to tell her we're doing just that, from me or you or maybe both of us.
		DR. HENNEY:  Yes, that's good.
		DR. LANGER:  Good point.
		So we'll take the 15-minute break.  There's some energy-lifters over there. 
		(Laughter)
		(Recess) 
		DR. LANGER:  I guess we'll get started again.
		The next topic is an update on remaining action items from the April meeting, and Liz Jacobson is going to do that.
		I think that's probably something, my sense, there were a lot of comments made at the last meeting and we wanted to go over with everyone how these were follow-up on and to see if there are any other suggestions.
	Action Items
		DR. JACOBSON:  Okay, great.  And I think this is actually something we will tack onto the end of forthcoming meetings as well just to try to make sure we're addressing everything.  
		I really had three major things I wanted to update you on today.  
		The first one is the last time you met you had asked for the Office of Women's Health to further discuss their science research program, especially with regard to their peer review process.  
		We had originally planned, we had it on the agenda for today's meeting to have an update, but we ran into a scheduling conflict, and so we are postponing that with apologies until the next Board meeting. 
		But it may actually be serendipitously good because we just appointed a new director of that office, Dr. Susan Wood, who actually had run the Office of Women's Health in the department.  And she's on board and she'll be six months or so into the job so I think the timing on that may actually be better than if we had done it now.  
		The next issue was CFSAN's genetically-modified foods.  At the last meeting you had suggested that CFSAN consider a public education campaign for genetically-modified foods similar to the Fight Back campaign that they did. 
		We haven't instituted a specified campaign, although we are utilizing our web site as a tool to get out information about genetically-modified foods and our regulation of them and what that means. 
		The industry itself has initiated a public education campaign actually, and we see our role, really, as assuring safety rather than as promoting that particular technology.  So we thought that was an appropriate response.  Obviously, you'll react in a few minutes as to whether it was or not.
		And then the third issue that I wanted to touch on was human resources and recruiting, and you have a fairly large piece of your folder there, the last tab, talks about some of our human resources initiatives.
		You had a number of recommendations.  You recommended established relationships and networks with more universities, expanding outside the Beltway area, and utilizing more diverse sources such as historically black colleges and universities.  
		In the last year, FY 2000, we participated in a number of outreach activities.  We went to 46 different universities' job fairs and societies.  Eighteen of those were at places with a high minority representation.  
		We had not just recruiters and our EEO personnel going to those, but we also had our scientists going to those places to do the recruiting.  
		The list of those is included in the information package.  
		We also heard from you that we should expand our search outside the Beltway, and we provided you a list of -- in that year, 2000, we hired about 700 people, and those 700 people came from over 200 colleges and universities.  
		Obviously, not every one of those 700 people was from a college or university because some of them were support staff, et cetera.  But there were 200 places represented, and we gave you that list also.
		I think if you look at that you can see that we do have some pretty good geographical diversity.
		We probably don't lack for hiring mechanisms in terms of bringing people on.  We do have about 18 different mechanisms, personnel type mechanisms we can use.  Some of them are long and extremely laborious.  Some of them are relatively easy, and we can talk more about those in the future if you'd like to do that.
		We also established a new recruitment counsel for FDA to try to make sure that our agency recruiters are up to speed, know about changes in laws and regulations, and recruiting techniques, and they get an hour of training every month as part of their duties.
		And we have, again, EEO specialists, staffing specialists and Center recruitment personnel on that counsel.
		It meets every month and it helps to promote sharing of applications across the agency, recruitment efforts and also trying to share sort of lessons learned.
		We also have job fairs that figure out how they're going to get staffed and things like that. 
		We also are beginning to explore the use of headhunters for key personnel.  We haven't really don't that in the past, and this is an avenue that may be very promising for recruiting key individuals.
		We have a student hiring effort.  Through a conference grant, we hosted 160 Hispanic students and provided workshops to them on career opportunities -- tobacco, food safety, HIV AIDS.  These are young students.
		We had 16 Hispanic interns hired during the summer, and 9 Hispanic students were hired for the fall internship program, and we also have some part-time students from several high schools.  Obviously, they're not beyond the Beltway, or at least if they are not too far beyond. 
		And the students work part time during the week and then full time during vacations.
		As I said, in terms of technical hires, we hired just over 200 employees in a number of technical job series.  And you had specifically indicated we should target bioengineering.  
		In 2,000 we hired 10 engineers in CDRH.  Of these 10, 5 were biomedical engineers but most had a biomedical background or some related experience.  They ranged from people that had just graduated with a Bachelor's to PhD level with prior work experience.
		You also asked us for something that we struggled with a bit.  You said you wanted to see c.v.s of everyone we had hired.  Well, that would have been 700 c.v.s and we thought, well, let's just go back to them with an alternate proposal, and we can kind of negotiate a little.
		Rather than do 700, what we dud was we abstracted from these 200 scientists descriptive information, including the grade level, the degrees they had, the schools attended, prior experience, and associations and honors that they had received.  That's in your package.  We did it by specialty.  
		So you can get a feeling for what kind of chemists, for example, CDER is bringing on board, and what kind of engineers CDRH is bringing on board.
		If you really want the c.vs, we can talk about that.  We did remove the names of the candidates to protect their privacy on this list that we're giving you, but we thought that might be more helpful than just a stack of c.v.s yea big. 
		And then the other thing you had asked for was information on the publications of staff.  We are currently working on a publication database for the Agency.  It's available on our Intranet, and we are going to be making it available on our Internet so that you can dial into it.  
		When we do get that up and running on the Internet, which we hope will be early this next year, you'll be able to see publications of the FDA staff so I think we will have answered your question that way.
		DR. FENNEMA:  (Off microphone.) When you summarize some of this data, the percentage of offers you make which are accepted, that would be I think useful information.  
		DR. JACOBSON:  Okay.
		DR. FENNEMA:  Not too difficult to compile.
		DR. JACOBSON:  I don't know.  Mary?
		MARY:  It's something we can get. 
		DR. JACOBSON:  Yes, it's something we can get.  We will.  
		The last thing I wanted to mention was that if you are interested, I am proposing that next meeting we tell you a little bit our plans for an FDA corporate university.  You heard Dennis Baker talk today about the field's Virtual University.  We see that would be a component of the FDA corporate university. 
		In fact, our trainers and the people that run our staff colleges are on a retreat this week to talk about what that might look like and how we would start implementing it.  
		So we couldn't really fit it in today, but if you're interested -- 
		DR. NEREM:  What is the significance of the word "corporate"?  
		DR. JACOBSON:  It's with a small "c."  The idea is a university that spans the entire organization.
		DR. NEREM:  Okay.
		DR. JACOBSON:  So if you're interested in that, we would propose to do a brief presentation on that maybe next meeting.  We're having a lot of things piled with the next meeting agenda.
		Also, we were going to consult with Dr. Rosenberg, because he had promised to talk to us about how SmithKline Beecham approaches the similar corporate university idea in an industry.
		That's the end of my report.
		DR. LANGER:  Comments, suggestions?
		Yes.  
		DR. DOYLE:  I noticed the first page here says "FDA Outreach Activities," and job fairs and all.  I assume this is part of the recruiting process.  
		DR. JACOBSON:  Yes.
		DR. DOYLE:  But I see about a quarter of these are law schools.  Are you trying to convert lawyers into scientists? 
		(Laughter) 
		DR. JACOBSON:  You think we could?  
		DR. DOYLE:  I don't know.  I commend you.
		DR. NEREM:  The more lawyers they hire the fewer that are out there to litigate.  
		DR. LANGER:  That's right.  But they have a lot of people to hire.  It's a big job.
		(Laughter) 
		Any other comments or suggestions?
		DR. NESTLE:  Yes.  Better find a word other than "corporate."  
		DR. JACOBSON:  Okay. 
		DR. NESTLE:  Because I had exactly the same question.  What does that mean?
		DR. JACOBSON:  I'm not a trainer or educator, per se, but I think it's sort of a term of art that the training community uses which we can certainly get rid of.
		I actually empathize with your point because when I worked in CDRH our address is Corporate Boulevard, and that always used to offend me that I worked on Corporate Boulevard.
		DR. NEREM:  I do want to thank you for not giving us 700 c.v.s.
		(Laughter) 
		DR. JACOBSON:  Well, we were trying to address the spirit of what you asked for. 
		DR. NESTLE:  And the environmental impact.
 		DR. LANGER:  Any other comments that anyone wants to make on this session?
		DR. DOYLE:  I think the approach that you took with the web site is right on, to inform the public of what FDA's responsibility is and what they're doing in terms of foods genetically-modified.  Just right.
		DR. LANGER:  The last session is Science Board Discussion, Closing Remarks, and Future Direction. 
	Discussion, Closing Remarks, Future Direction
		DR. LANGER:  Let me just start this by going over the action items that I at least wrote down.
		First of all, there were a lot of comments that people made, and many of them have been taken down.
		I counted three action items, and again people may want to add to this list.  One thing that came up was the idea of partnerships between FDA and National Science Foundation, for example, but also NIH, DoD and industry.
		And that's one thing that was going to be followed up, I guess, with some discussions, at least certainly with respect to NSF, with respect to Dr. Colwell, and some of the people at the FDA. 
		I think that that will be expanded into a broader exploration of possible partnerships.
		A second action item was the Public Comment that was gone over.  The way that's going to be followed up is to send the transcript of those comments, as well as the Agency comments, on that to the Science Board to get their recommendation. 
		The third action item is the CDRH internal review, which is really to go ahead as planned, first with the internal review and then following that with an external review.  
		Those are my action items that I would put down for the record.  I would be happy to have anybody add to those or modify those and then to add any others just to get people's comments.
		Yes, sir.  
		DR. FENNEMA:  I would like to make an addition.
		DR. LANGER:  Sure.
		DR. FENNEMA:  This is my perception, and we talked a little bit about this earlier, but it seems to me the single greatest threat to FDA is an inadequate budget, which is inadequate to assure timely science-based, regulatory activities.  
		I think if nothing else that surpasses that in importance, and I would propose that we make a resolution on this and then follow this up with some activities from the Board to take care of this.  So may I read this?
		DR. LANGER:  Certainly. 
		DR. FENNEMA:  "The Science Board recognizes with concern the absence of appropriate advocacy efforts in behalf of FDA during the Congressional budgetary process."
		I look at NIH and I look at the U.S. Department of Agriculture, and they have a whole cadre of advocates in there speaking on their behalf, and FDA does not.  I don't think FDA will ever have advocacy with the other groups I've mentioned, but I think this can be done a lot better than it's being done now.
		FDA obviously can't do this.  They can't be the one to stipulate this.  But I think this Board could take some activities in this regard, if that's the sentiment of the Board to do so.
		DR. LANGER:  First, I want to get the -- I'm not sure how we pursue that.  Just structurally?
		DR. SCHWETZ:  For you to recognize that this is -- the way the situation is that there isn't a large body of support out there from constituents.  I don't think there's any problem with you recognizing that in a written form.  
		If you have recommendations that you would like to make about how to resolve it, that's fine, unless they are lobbying. 
		So if you come up with some kind of a written statement that would resemble a lobbyist statement about getting money as opposed to a statement about mechanisms by which the level of attention of the people that we support could be increased, those are two different things.
		DR. LANGER:  I think there's two points in terms of what Owen is saying.  
		One is us making a statement like that.
		But then the second thing is what we do about it.  
		DR. SCHWETZ:  Yes.  
		DR. LANGER:  Let me just open that up -- 
		DR. NESTLE:  Was there more, Owen?  Was that the end of your statement or did you have more?
		DR. FENNEMA:  That's the end of my statement in terms of the physician.  I think it would naturally follow that we would have to talk about what the Board could do in terms of helping in this respect.
		I've talked to Bern a little bit during the break about this issue, and one example that I could speak only from the area of the food field is that at the Institute of Food Technologist's annual meeting, they organize a meeting for the chief research officers of our research corporations. 
		And I think I can get on the program and make a presentation of this kind, talking about the need to do this, particularly if I had some back-up help from FDA there, Bern or a retired official of FDA, to answer questions about this. 
		So that's one course of action that could be taken.  And I think there are many other avenues and other kinds of professional organizations where this could be done.  
		DR. LANGER:  Let me just get the people's comments from the Science Board.
		DR. NESTLE:  I think if we don't do that we're useless.
		DR. LANGER:  Okay. 
		Other comments?
		DR. ANDERS:  We don't want to be useless.
		(Laughter) 
		DR. LANGER:  I don't think anybody could disagree with that. 
		Bob.  
		DR. NEREM:  Without our going out individually and doing what Owen has proposed he could with his group, our recognizing this problem is useless.
		DR. LANGER:  Right. 
		DR. FENNEMA:  No, that's right.  I agree with you.  Just to say it is not -- 
		DR. LANGER:  Right.  So I guess the point is what do we do?  I mean, I think that we can certainly make this statement, put your statement into the record, if that's okay.  And then I think we can try to do the types of things that you're suggesting.  
		DR. NEREM:  Do you want to read that again?
		DR. LANGER:  Yes, maybe that would be a good idea.
		DR. FENNEMA:  Okay.  "The Science Board recognizes with concern the absence of appropriate advocacy efforts on behalf of FDA during the Congressional budgetary process."  
		DR. LANGER:  I guess what I was trying to ask, is that statement an OK statement?  I guess to put in our record?  I don't want to put you in a difficult position.  I just don't want to have a statement that makes it sounds like we're lobbying, either. 
		DR. FENNEMA:  I know.  I wondered about this at the outset, and we don't want to do anything that's going to be embarrassing for FDA in this setting right here.
		DR. NEREM:  No, I'm not sure that's the kind of statement we ought to make.  
		DR. LANGER:  Yes.  I wonder, too.  I mean, I'm almost thinking that the statement that we might want to make is something along the lines that we recognize the FDA is certainly going to need increased funding.  
		I mean, just to pick an example, that the FDA certainly needs increased funding, and maybe we can work on this; but increased funding if they're going to be able to keep up with, I think a number of people made the point, about all of the information that's coming forward and how without getting more funding to do more science or understand more science, the FDA will be able to do its job in terms of regulating things.
		DR. ROSENBERG:  I'm even concerned about putting it in terms of science -- 
		DR. LANGER:  Yes.
		DR. ROSENBERG:  -- which always seems to get you nowhere.  
		DR. LANGER:  Yes.  
		DR. ROSENBERG:  It's really in terms of the products that are going to be made available to the public, and that product flow and the importance to the industries that require that product flow for their continued existence, and that the FDA is the group that has to work efficiently to make sure that product flow and ensure it's value to the people of the United States.
		DR. LANGER:  Right. 
		DR. ROSENBERG:  And it's to somehow connect the fact that they're not just -- they serve more than just to protect the people.  They deliver things to the people that are good for the people.  
		And if that process doesn't work efficiently, everybody suffers on both ends.  
		DR. LANGER:  Right.  
		DR. NESTLE:  Can I say something?  I have to leave and so I'd like to say something before I do.
		That is that I think a much stronger statement is needed.  I'm not the slightest bit worried about embarrassing FDA.  I think if the Board has a position it should take a position.
		I wonder if we couldn't develop a much stronger position or a much more nuanced position in which we talk about this as a public health issue, which is how I see it, a very serious public health issue, and go into some of the details and perhaps write a -- rather than a one-sentence statement write a position on it.
		And that would be something that we would develop over time, perhaps not in consultation with FDA officials but separate from FDA officials as something that the Board did on its own. 
		I don't know how other people feel about it, but that would be my suggestion.
		DR. LANGER:  What do people feel about that?  I guess my only concern is I think this is a -- the spirit of what is being said I think is very good.  I think we have to figure out, from what everybody is saying, exactly the right way to say it, whether it's one sentence or 10 pages or what exactly the thrust is.
		DR. NESTLE:  Yes.  This may not be something that we can decide this afternoon. 
		DR. LANGER:  That's actually exactly what I was going to say.  You said it for me.  But I think it's certainly something that we want to follow-up.  I don't know if I'd even put it as an action item, per se, but I think that we should try to find the time to talk about it between now and say the next meeting.
		DR. FENNEMA:  Well, I'm not married to the statement.  
		DR. LANGER:  No, I understand that. 
		DR. FENNEMA:  But the sentiment I feel strongly about.  And what I would really like to know and I think it would be useful to know is whether the group agrees with this sentiment or not.  That doesn't need to be in the official -- 
		DR. LANGER:  Yes.  Not everybody has spoken, but I think everybody that has agrees with, certainly it seems to me in part, but different people feel more strongly about certain aspects of it than others, and that's kind of what I'm hearing.  
		There are a couple of people that haven't spoken.  
		DR. DAVIS:  (Off microphone.) To me, we sit here and say we are concerned about FDA's future ability to continue to do what it's done, so we are concerned that as a Board we need to be making our concerns known.
		So I'm very much on board with us doing something.  
		I guess I agree with Marion, to just make that statement and put it in the record will accomplish very little.  I think it's time that we probably make our statement as the advisors of this Board to whomever those -- the powers that be.  
		DR. LANGER:  A couple more comments?
		DR. ANDERS:  It's the issue of efficacy.  We could make all the statements in the world.  What statement will get to the place where it will do some good, and any statement we construct has to get to that place.
		And if there's no statement we can construct that will be efficacious, then we're wasting our time.
		So how do you get a response to something you do?
		DR. LANGER:  Bob, why don't you make a comment, then Owen.  It sounds like a few.  That's okay.  Bob, you first. 
		DR. NEREM:  I wrote a slightly altered statement.  I have a feeling we probably shouldn't pass any resolution today.  We may want to put something up and then table it.  
		DR. LANGER:  Sure. 
		DR. NEREM:  But I do think we have to come at it a different way.  The statement I wrote, because I think it really expresses where I'm coming from is:
		"The Science Board recognizes that as we move into the 21st century the regulatory process will become rate-limiting in the economic development of this country and in providing the best possible health care to our citizens. 
		"The Science Board, individually, thus commits itself to a leadership role in the education of our political leaders and the public."
		DR. LANGER:  That's pretty good. 
		DR. NEREM:  I mean, I think what we have to talk about is not who we can give some statement to --
		DR. LANGER:  Right.
		DR. NEREM:  -- but what are we going to do.
		DR. LANGER:  That's a good statement. 
		VOICES:  That's a good statement.
		DR. FENNEMA:  The statement is meaningless.  The activity is what counts.
		DR. LANGER:  Right.  So the question is do we want to put a statement down or not?  Do we want to write a paper or not? 
		DR. DAVIS:  I agree, but let's not solve that today.  
		DR. LANGER:  I agree with that, too.
		I think there have been a lot of good suggestions, and we should find the time to continue this discussion.  But I think that comes closest to the spirit.  I agree with what everybody is saying.
		So why don't we table this for now but definitely come back to it.  
		DR. NESTLE:  Before the next meeting.
		DR. LANGER:  Before the next meeting, yes.
		DR. FENNEMA:  We could have a conference call.
		DR. LANGER:  Yes.  I can think of several ways to deal with it.  We'll figure out how to do that.
		DR. SCHWETZ:  Bob?
		DR. LANGER:  Yes.  
		DR. SCHWETZ:  May I provide one?
		DR. LANGER:  Yes.  Bern and then Bob.
		DR. SCHWETZ:  One additional piece of information that you can use to work from, Neil Goldman reminded me that in the Committee Report that David Korn chaired, the Committee that David Korn chaired in reviewing the Science of the Agency, a report that was accepted by the Science Board maybe three years ago, it was well defined in there that one of the difficulties that the Agency is facing is a shortage of resources.
		So if you wanted to reference something and extend it, update it to today, in the context of looking at new technology, new science, new issues, that's another.  I will provide you with the comments. 
		DR. LANGER:  Yes, it would probably be good.  I was actually on that committee.  
		DR. SCHWETZ:  So we can send it to everybody so they have it.
		DR. LANGER:  Yes.  Okay.
		DR. SCHWETZ:  That can be part of your thought process. 
		DR. LANGER:  That's a good idea.  
		Other comments on action items?  
		Bob, you did.  
		DR. BUCHANAN:  I was just reflecting on this process and we can help you with, I believe, with Liz's agreement, I don't know if we've made a concerted effort to get out to the professional societies, to the trade organizations, to the Trade Press, the role of the Science Board, how important it is to us, convincing them that when you do speak they ought to listen.
		I think that's a role that we could take on in playing up the activities of this Board so that we sort of lay the groundwork for when you do talk that somebody wants to hear you.  
		DR. LANGER:  Yes.  That's true.  Okay, that's a good suggestion. 
		Other comments on this?
		(No response.) 
		We're going to leave those three action items as they are.  
		The other topics are other discussion items, future direction?  I'll be happy to hear from anybody in this room or the Science Board or members of the FDA on this.  Any comments, suggestions on things we ought to go over or do or do differently? 
		DR. JACOBSON:  Let me just ask.  One of the issues was what topics, if any, did you want to go into in more depth. 
		I know Bob Nerem had asked actually before this meeting for a further discussion of tissue engineering, and I just wanted to ask you if you have other suggestions, other topics.  You don't have to say it here today.  You can just get to us as we plan for the April meeting.  
		Bob, I am assuming you still are interested in that? 
		DR. NEREM:  Yes.  And I'm interested in it both because of my interest in engineering, but also as an example of a technology that cuts across the Agency.
		And recognizing the political constraints, one still has to wonder about if FDA is organized the way it should be for the 21st century.  
		DR. LANGER:  Right. 
		DR. JACOBSON:  Good question.
		DR. LANGER:  Other points that anybody wants to make?
		(No response.) 
		DR. LANGER:  Okay.  Then the next meeting is the 13th of April, I believe.  
		Can I get a motion to adjourn. 
		DR. ANDERS:  So moved.  
		DR. NEREM:  So moved.  
		I hope that's not a Friday.  
		DR. LANGER:  Is that bad for you? 
		DR. NEREM:  Friday the 13th.
		DR. LANGER:  Friday the 13th.  Yes.  It will be a lucky day.  
		Thank you all very much for coming.  
		(Whereupon, at 3:35 p.m., the meeting was adjourned.)