U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
June 8, 1999

MR. HUBBARD: Good morning. I'm Bill Hubbard from the Commissioner's Office at FDA. We're running a little late because Joe Levitt, who is going to chair this, is caught in traffic. He should be here momentarily. We might be able to do some initial housekeeping things, however, that we were going to do anyway, to prepare for him.

So, with that, let me first introduce Margaret Porter, our General Counsel, and Beth Yetley, the head of our dietary supplements office--

DR. YETLEY: Office of Special Nutritionals.

MR. HUBBARD: Excuse me.

[Laughter.]

MR. HUBBARD: And Dr. Debra Bowen, from our Center of Drug Evaluation and Research.

Perhaps the first thing to do is to give you a brief run-through of what we're going to do today and how we're going to organize the meeting.

Beth, could you do that?

DR. YETLEY: Joe Levitt does have some opening remarks, so when he gets here we'll let him go ahead and do that, although I think that would probably between Panels I and II.

What we have done is try to organize this by panels that appeared to have somewhat common interests. We have six panels scheduled, and then at the end of the day we will have some concluding remarks.

The first panel is primarily trade associations, then we have nutrition professionals. A third panel will be consumer groups; fourth panel nutraceuticals. A fifth panel is consumer groups, and the six panel is, again, industry and industry representatives.

We will ask the entire panel to come up as a group. We will ask each member of that panel to give their remarks. We've asked them to keep this to five minutes or less. And then once the entire group has given their remarks, we will try to have a dialogue between those of us on the FDA side, and the members of the panel. This is as much information gathering, from our prospective, as we can make it. And so we wanted to have as much dialogue as we could.

The first panel, we have APHA, Lucinda Maine--I'll have you start up and wind yourself around the table--CHPA, Bill Soller; NFPA, Regina Hildwine; CRN, Annette Dickinson; RDIA, Maureen Mackey, and we also asked NNFA, Michael Ford to join this panel.

If they could come forward?

[Pause.]

MR. HUBBARD: Could I speak to Lynn Larsen to a minute?

DR. YETLEY: Lynn, we're looking for the timer. I understand we have a timer so people stay on schedule.

Okay, Ellen, down here, is going to--what? --hold up cards. Yellow means caution, I presume, and red means' you're time is up.

Okay. We have a very full schedule, so we are going to be a little bit hard-nosed about sticking with the schedule.

APHA--Lucinda Maine.

MR. HUBBARD: Lucinda, let me interrupt you. Joe Devitt is walking in now. Perhaps it would be best to go back to the original schedule.

Joe, you need to come around. Sorry about that.

[Laughter.]

MR. LEVITT: Good morning, everyone. Let's see if this microphone is working. It sounds like it is.

I apologize to everyone, including the panelists up here, for my late arrival. You know what they say: the best laid plans. If you need to get here quickly, you will find the traffic jam in Washington--at least is what I've found.

At least I can tell you that it is cooler in here than it is out there. As the day goes on, we hope the air conditioning holds. If it does not, I would encourage people to freely--whether you're up here on the panel or not, to take off your jackets, or whatever is needed, so that we have a comfortable day.

What I would like to do--if we can get the slide projector going--is to set the stage for the speakers that we have today. And Lynn is telling me--I'm just going to use the mike here, because I don't think I could get there. The only question is will it at all affect how I move the slight. Pardon me. I just couldn't quite figure out how to get from here to there.

[Pause.]

We'll start off again with a welcome. We'll welcome the members of the FDA panel; the folks from the industry; consumers; health professionals; and everybody that is here in the audience.

I hope this will be a useful day. We would like to try and do three things. I've got to remember my rules here.

Number one is--most importantly--we want to share views. We at the FDA want to hear what all the stakeholders have to say about dietary supplement strategy.

Number two, really, is a goal. Sometime in this area it feels like a dream. But to the extent that we can build consensus, obviously that is good. In order to do that--and I said this at an earlier meeting--I really ask all the speakers--I make you this deal. I'll listen to each of you, as will my colleagues, if you'll listen to each other. Because we will hear, I have no doubt, differing points of view on this subject. And it's important that everybody understand the different points of view if we have a chance and a hope of building consensus. And even without consensus, we need to prioritize the work we have to do. There's a lot of important work to be done in this area. We recognize and are becoming more, if you will, humbled by the scope and depth and breadth of what we need to do. And so one absolute goal I have out of this process is to prioritize.

Now, in terms of background, this meeting really has its origins in a meeting in this room just about year ago, when we had a general stakeholders meeting of CFSAN. We had a number of oral and written presentations, and we really focused on the central question: where do we do the most good for consumers?

That developed into the CFSAN program priorities document for 1999--what I finally referred to as the "Yellow Book. "And one of the main features under dietary supplements there was to say: we need to take a step back. We need to recognize that we've had four years of experience since DSHEA, but we need to take a step back and really develop an overall strategy for how we're going to implement this law. And, as you see, there are a long list of things that are listed, and all those are relevant.

Now, Dr. Henney, when she testified before Congress earlier this spring, I think made a number of key statements that will help frame our discussions for today.

Number one, she said FDA is aware that Americans place great faith in dietary supplements to help maintain and improve their health, and that the scientific evidence documenting the benefits of a number of supplements is increasing. So there's value here. We need to recognize that.

But, number two, the challenge to FDA is to strike the right balance between preserving consumers' access to both products and information, while assuring the safety and proper labeling of all these products. So we have access on the one hand; we have safety, proper labeling on the other hand, and we need to achieve both.

Now, we've also made a considerable set of progress to date. Attached to Dr. Henney's testimony was a list of the Federal Register documents that have been published since DSHEA on dietary supplements. We took a short little poll in FDA. Nobody outside of the Office of Special Nutritionals thought there were more than ten. But as we counted them all up, indeed there were 25 Federal Register documents already, which shows there has been a lot of work but, also, we realize a lot more to be done.

In addition to the Federal Register, you see we receive large numbers of 30-day notifications, as well as a number of scientific-based new dietary supplement ingredient notifications that we have dealt with.

Dr. Henney then continued, therefore, "It is clear, with the benefit of hindsight, that we still have a way to go, both in achieving full compliance with DSHEA, and in developing a workable regulatory framework. "I really hope that today is the day that starts us vigorously along that path.

Now, we also--this is part of a broader outreach effort--again, I talked about the meeting a year ago. We had a meeting in January dealing with international scheduling. Dr. Henney had an agency-wide stakeholder meeting in April. We held one here in the Center, on health claims on dietary supplements--and I see some of the same speakers on the first panel that I was able to hear then. We have today's meeting on overall strategy, and we are repeating this same meeting on the West Coast on July 20th.

Now, we put out a Federal Register notice, which you all, no doubt, got, or you wouldn't be here today. Again, reinforcing the statements I already read, FDA's objective in developing this strategy is to ensure consumer access to safe dietary supplements that are truthfully and misleadingly labeled, following a process of openness, flexibility, efficiency and commitment to public health.

We propose four criteria in setting priorities: number one, consumer safety; number two, health-related labeling; number three, efficiencies in the process; and number four, closure on unresolved issues. And those familiar with my general priority-setting process will see a clear similarity there.

We posed seven questions in the Federal Register notice, and I will run through those briefly, that we hope people will be addressing.

Number one: in addition to ensuring consumer access to safe dietary supplements that are truthfully and not misleadingly labeled, are there other objectives that an overall strategy should include?

Number two: are the criteria that I just went over--are the criteria for prioritizing the tasks within the supplement strategy appropriate? What specific tasks should FDA undertake first?

Number three: what factors should FDA consider in determining how best to implement the tasks; i. e. , the use of regulations, guidance, etcetera--what approach should we take?

Number four: what specific tasks should be included under the various dietary supplement program elements in the CFSAN priorities document--and I went through those earlier--claims, boundaries, CNPs, GMPs, etcetera.

Number five: are there current safety labeling or other marketplace issues that we should address quickly? We sometimes talk about the difference between something that is important and something that is urgent. And some things are both, but some things are more urgent than others, and some things are important over the long haul, but not necessarily something that has to be done first, or right away. So are there things that FDA should address quickly through enforcement actions to ensure, for example, that consumers have confidence that the products on the market are safe and truthfully and not misleadingly labeled.

Number six: what type or area of research on dietary supplements should FDA allocate its resources; so, focusing on research.

And, finally, how we can leverage. Given FDA's limited resources, what mechanisms are available or should be developed to leverage FDA's resources to meet effectively the objective of the strategy.

Now, I'll share with you our current thinking as we've been talking and meeting as we've led up to this meeting, too, and I would take those earlier long lists and really put them under three broad headings.

Number one: what are the boundaries? If we're going to have a set of rules for regulating dietary supplements, I think the first step is, what is a dietary supplement? What falls within those rules, and what falls within other sets of rules; whether it's food additive, drug, conventional food, or whatever.

Number two is safety, and I would put this in both acute safety issues, such as adverse even reporting, as well as longer term things that will help promote safety, like GMPs.

And third is the whole area of labeling and claims.

Now, meeting logistics--I think this has been gone over, but just to reiterate briefly--we have a series of panels. The first one is sitting up here already nicely. We will ask each speaker in the panel to go over and give their presentation. I would ask you not to follow my lead--you've already been here before me. We do have to focus on timeliness if we're going to allow everybody a chance to speak. We have asked everybody to try and limit your remarks to five minutes, and we will accept any additional comments, written, for the record.

We will then go through out side quickly and pose questions from FDA, and then will proceed from one panel to the next with some limited breaks and so on and so forth.

Let me just see if--there were some notes that I wanted to be sure we got to. Did you do the logistics, such as where the restrooms are and those sorts of this?

MR. HUBBARD: No, we didn't do that.

MR. LEVITT: Well, let me do--If you'll allow me one more minute, we'll get to the really important stuff.

The rest rooms are on the left and right of the main corridor. When you go out, turn right when you leave the auditorium to get to the main corridor.

Number two: food. Some people will get hungry today. There is an express cart with coffee and snacks that is located right out there. I saw it just when I ran in. That will be available until noon. Just before noon we'll talk about luncheon arrangements.

Number three: panelists for the morning should be seated in the reserve section in the front of the podium over there. So, hopefully, the other people sitting over there are the people who are going to speaking later this morning. In the afternoon, the same way. That will help us as we try to get up and down. And, as you see, the logistics for just getting up and down are challenging in and of themselves.

As I said, we'll allow five minutes per speaker. We do have somebody who's going to help us in timing. Ellen? Show us where Ellen is, thank you. We will have a one-minute warning, and a still friendly orange time, which is a nice way of saying time is done. And we would ask you to respect that. I know I was giving a speech yesterday,and all of a sudden--it was a 25 minute speech, and the 5-minute sign went up, and said, "Holy smokes," and I had to adjust myself a little bit, but was able to finish. So we all need to live with that.

As I said, we do have a full agenda, and we need to deal with that.

I'll talk about luncheon later.

Finally, a couple of concluding remarks. And, again, if this was covered before, I apologize. We made a mistake in the Federal Register notice on the closing date for comments. We meant to say August 20th for the date for comments due, instead of the earlier date. That was clearly as mistake.

Number two: the slides I just showed are available in today's handouts and on our Web site.

Number three: if you want written requests for the meeting transcript, the meeting is being transcribed. You can ask FDA's FOI office. Give us two weeks, please, or 15 days, it actually says here. And the address of the office is on the back of the Federal Register notice. And I mentioned the similar meeting in California.

Now, somebody also handed me something here that I think I'm supposed to say, so let's see.

[Pause.]

Okay. I think these items have essentially be covered.

With that, I will take a deep breath, try and sit back and relax, and if we can figure out the lights and the logistics, we will proceed to the first panel. And my list says that Dr. Lucinda Maine, Senior Vice President Professional Affairs, APhA is our first speaker, and she is standing at the podium, ready.

Thank you. If we can turn this off, we can focus attention on you. Thank you very much.

Please, Dr. Maine.

DR. MAINE: Yes. Thank you for the opportunity to provide input to the Center on how you can best develop an overall strategy for achieving effective regulation of dietary supplements.

I do represent the American Pharmaceutical Association, the national professional society of pharmacists, with over 210,000 pharmacists, scientists, students and technicians.

I'll briefly address your key questions, first by sharing where the Association finds itself with respect to policy development on what we believe is one of the most profound examples of consumerism in health and wellness. Then, drawing on the results of recent focus groups held with pharmacists, I'll share our perspective from a key health care provider that hopefully will guide the agency as you struggle with these important questions.

We are respectful of the constrains on the agency from public pressure to keep dietary supplements in a largely unregulated environment. I personally had begun to wonder whether a contributor to this consumer opinion is the fundamental belief held by consumers that an acceptable threshold of regulation on these products currently exists. These products appear on the shelves of our nation's pharmacies where many other categories of traditionally regulated products are found. Consumer belief would be supported by the history of strong regulation by this agency for the full range of products currently and clearly in your jurisdiction.

Our association initiated policy development on these products in 1997, per the request of both our practitioner and science members. Ultimately, five suggested policies came before our house, and that related to the need for informed decision-making pharmacists and public; the need for additional sources of quality education and publication for practitioners; suggestions that manufacturers provide evidence of the use of good manufacturing practices; and the adherence to standards and quality control sufficient to ensure that only quality products are available for sale to the public.

I believe reflective of the evolution in pharmacists at the time, the house overwhelmingly adopted the policy stating that informed decision-making should be the basis what pharmacists and consumers do, and that APhA needed to provide pharmacists assistance, in terms of education and publications to facilitate their counseling of patients on proper use, indications, safety and interactions between these and other products. Deferred were the policies on what the profession should require from manufacturers and suppliers of these products in terms of standardization and assurance of quality.

TWo years later pharmacists find themselves increasingly called upon to provide consumers information regarding the use of these products. APhA's education and publications efforts have expanded during this timeframe in response to great demand from our members to provide the most credible information possible. A continuing challenge to the Association and to pharmacists is the lack of information on efficacy, safety, standard dosage, side effects and interactions with traditional therapies and conditions. This information is that which pharmacists and other health care providers have come to use and find easily available for traditionally regulated products. APhA will again be focusing on the development of meaningful policy specific to the regulation of these products over the next nine months, and we welcome input from FDA and key stakeholders as we embark on this path.

Findings from two focus groups of pharmacists recently conducted by APhA provide additional guidance to your key questions. Pharmacists are using a variety of terms to define this category, and their terms do differ from those used by consumers, in many cases. The key issue for pharmacists is determining the quality and efficacy of a supplement. Pharmacists that all types of consumers are approaching them seeking information regarding the purchase of these products. Often it appears that the consumer is seeking to establish credibility to a decision that they have reached based on advertising, consumer media and word of mouth recommendations from friends, family and others.

Pharmacists do want manufacturers to prove the quality of their products using means similar to the trusted approach for pharmaceuticals--controlled clinical trials with results disseminated and peer reviewed in reputable publications. And pharmacists want to see standards established for this category of products.

The current scientific and regulatory environment for dietary supplements is clearly insufficient. One area for research that the FDA could embark upon would be the ability of these products to actually deliver the intended substance. Recently publish research in our journal The Journal of the American Pharmaceutical Association, has indicated problems with, for example, dissolution. The product was--the publication was entitled "The Comparison of Melatonin Products against USP's Nutritional Supplement Standards," and we did find that not all products dissolved according to the USP specifications.

I will close with my recommendations, and there are four.

There is a need to establish what consumers believe is the current regulatory framework for dietary supplements. I think this speaks to your "boundaries. "

There is a need to clarify the nomenclature and criteria for classification of products.

A systematic process for aggregating and applying the most credible evidence is required.

And I believe adverse event reporting for these products should be integrated into existing systems and systematically analyzed, with that information being fed back to consumers.

Thanks again for the opportunity to participate in today's panel.

MR. LEVITT: Thank you very much.

Our next speaker is William Soller, from CHPA. And, Bill, I won't take this out of your time, but as you're standing up there and getting ready--I neglected--I saw you over there, and I just assumed you were on the list--but Michael Ford is not on the written agenda, but he's sitting up here and will be one of the speakers of this panel, and we certainly welcome you here, too.

Please, Dr. Soller.

DR. SOLLER: Good morning. I'm Dr. Bill Soller, Senior Vice President and Director of Science and Technology for the Consumer Health Care Products Association, which represents producers of quality dietary supplements and non-prescription medicines, including over 200 member companies across the manufacturing, distribution, supply and service sectors of the self-care industry.

We have detailed written comments that supplement these oral remarks and have been put into the record today.

In setting its priorities, CFSAN should place safety first; that is, enforcement, GMPs, and AERs, as well as the development of a three to five year detailed strategic plan or gaps analysis. While activity in the claims area may proceed as priority is given to safety issues, its completion should be targeted farther in the future than that for resolving the safety-related issues, and I have six points.

First, in passing DSHEA, Congress intended that consumers would use dietary supplements for health promotion, health maintenance, and disease risk reduction. Consumer confidence is essential to product use. Allegations that the dietary supplement industry is unregulated or that FDA does not have sufficient enforcement powers, which it does, acts to undermine consumer confidence. Therefore, foundational to CFSAN's overall strategy for dietary supplements is an effective enforcement policy that removes unsafe products from the marketplace and that ensures truthful, not misleading, and substantiated claims on dietary supplements. Because of the complementary jurisdiction of FDA and FTC in this area, the two agencies must coordinate closely, and a public workshop on this matter would be helpful for all stakeholders to understand the current relationship between these agencies.

Second, the dietary supplement industry has maintained that specific GMP regulations would be helpful for ensure that dietary supplements are safe and not adulterated or mis-branded; have the identify and provide the quantity of dietary supplement ingredients declared in the label; and meet the quality specs that the product is represented to meet. We recommend that FDA make the publication of proposed GMPs a top priority in 1999, and consider the additional comments that we have developed and appended to our written comments.

Third, as outlined in our remarks to the House Committee on Government Reform on May 27, we recommend that CFSAN prepare a written plan for, and adopt a systems approach for AERs similar to that recommended in FDA's May 1999 "Managing the Risks for Medical Product Use: Creating a Risk Management Framework. "We think the system should be grounded in the Agency's current safety policy and have specific refinements to CFSAN's current AER surveillance of dietary supplements, such as defined protocols for consistent handling of AERs, training and re-examining AER listing on the CFSAN Web site, etcetera.

Fourth, boundaries between different types of products--drugs, conventional foods, dietary supplements, and cosmetics--should be based on a product's claim which defines the intended use of the product. In this way, a product may have more than one intended use which should not be considered an overlapping situation, but rather one that is coexistent. Importantly, because the two major confounding issues in FDA's structure/function proposal related to the overly broad redefinition of "disease," and the intricate interrelationship between health promotion maintenance and disease prevention, we recommend that FDA re-propose its structure/function proposed rule as a focused, regulatory statement that closely incorporates the intent of DSHEA, amends FDA's proposed redefinition of "disease," as we proposed in our comments; omits the confusing and ambiguous proposed criteria; and addresses implied claims by the statutorily required disclaimer on structure/function claims.

We also recommend development of a guidance on structure/function claims for dietary supplements consistent with DSHEA, and modeled after the FTC advertising guidance to industry.

Fifth, we don't recommend--we do not recommend that CFSAN move forward at this time with the appointment of a formal dietary supplement advisory committee. CHPA considers the priorities of safety, an overall strategic plan or gaps analysis and claims policy of sufficient potential resource intensity that the appointment of another special advisory committee, in a formal sense, would detract at this time from the needed refinements in CFSAN's operations and activities. The operational mechanism of special working groups, as needed, on the Foods Advisory Committee appears to be working, given the nature and extent of the agenda fordietary supplements at this time.

And, finally, industry has an interest in helping to ensure that FDA is appropriately staffed and funded to meet its statutory obligations of promoting and protecting the public health. Only if we know and contribute to the three to five year plan or gaps analysis for CFSAN are we able to knowledgeably pursue appropriations requests to build the CFSAN infrastructure needed for dietary supplements, hence the importance of what comes our of today's meeting.

Thank you very much.

MR. LEVITT: Thank you very much.

Our next speaker is from the National Food Processors Association, Regina Hildwine, Director, Food Labeling and Standards.

MS. HILDWINE: Good morning. I'm very grateful for this opportunity to present NFPA's views.

NFPA--National Food Processors Association, is the principal scientific trade association representing the food processing industry. There are copies of my remarks out on the desk. We are going to file written comments at a later date.

Today I'm very briefly going to discuss issues related to safety and labeling claims, and I'm going to bring in some things relative to other classes of foods.

NFPA is interested in dietary supplements because they are foods. NFPA supports a regulatory policy which is consistent for all foodswith respect to safety and label claims. NFPA also believes that safety comes first. NFPA is aware that the law makes different provisions for the burden of proving safety of ingredients for dietary supplements and for other foods. While, by law, dietary ingredients of dietary supplements are no longer deemed to be food additives, NFPA believes that this does not absolve the dietary supplement industry from responsibility for safety of their products and ingredients. Dietary supplement companies should continue to assess the safety of their products and ingredients prior to market, monitor safety after market introduction, and have procedures in place in the event a recall is necessary. Dietary supplements are not exempt from voluntary recall provisions.

To assist the dietary supplement industry in assuring the safety of its products, NFPA believes that FDA should proceed promptly with the rulemaking of good manufacturing practices--that is, GMPs--for dietary supplements. We see this as a top priority. The experience of the food industry is that FMPs serve as a useful outline for those production and processing procedures which result in safe and high quality food products.

The dietary supplement industry should also be encouraged to notify FDA that key dietary ingredients of their products are generally recognized as safe--that is GRAS--especially dietary ingredients with some history of use. We see this as another objective that should be considered. Using GRAS notifications for dietary ingredients with a history of use would complement the current pre-market notification procedures for new dietary ingredients or dietary supplements. GRAS substances are not food additives by legal definition, so dietary supplement ingredients would not be excluded from consideration under GRAS provisions. Ingredients of dietary supplements should be help to the same GRAS standard as conventional food ingredients.

Consideration under GRAS provisions should address current levels of consumption and conditions of use for dietary ingredients, including herbals and botanicals. Current uses may be very different from historical uses.

We note that some botanical ingredients have utilized the new GRAS notification process, however their notified as "flavors. "To assist the dietary supplement and, indeed, all sectors of the food industry, NFPA recommends that FDA should promptly finalize its proposed GRAS notification process. The supplement industry should then be encouraged to use this provision to ensure that the users of supplement ingredients, including herbal and botanical ingredients that there is no question of the safety of these substances.

NFPA believes that the dietary supplement industry should carry the burden of ensuring its products are safe, and FDA should provide a regulatory environment, through GMPs and GRAS, to assist the industry in its endeavors.

Regarding label claims of health benefits, conventional foods and dietary supplements enjoy similar, if not always identical, regulatory approaches--and I talk a lot about this all over town. In the area of health claims, both conventional foods and dietary supplements should be subject to the same provisions, and this includes extending FDAMA health claims provisions ultimately to supplements. NFPA also believes that the recent court decision in Pearson v. Shalala ultimately will exert equal force on claims labeling rules for both dietary supplements and conventional foods.

With respect to structure/function claims, NFPA commented last year that FDA's unfortunate proposed rule would have as much of an adverse effect on claims for conventional foods as it would on dietary supplements. The proposed redefinition of disease would adversely affect health claims and structure/function claims across the board.

NFPA has urged FDA to withdraw this proposal and we repeat our request today. We also ask FDA to take to heart the arguments we put forward with respect to nutritive value.

It's imperative that all types of claims on all foods, including dietary supplements be well substantiated or fairly carefully and explicitly qualified. We believe that FDA needs to be aggressive in its enforcement posture against any poorly substantiated, poorly qualified or otherwise misleading claims. And we also urge FDA to work in cooperation with the Federal Trade Commission.

All these reforms--safety and claims--are needed not only to ensure a level playing field between dietary supplements and conventional foods, but to prepare a positive environment for new types of foods being designed to provide health benefits beyond those of basic nutrition. Whether these novel foods or dietary supplements in the form of conventional foods, or traditional foods enhanced with properties or components associated more with dietary supplements, NFPA believes that the course to a barrier-free regulatory environment lies in correcting the flaws in current rules and a strong enforcement approach, rather than embarking on a new regulatory scheme.

Thank you very much.

MR. LEVITT: Thank you.

Next we'll hear from Dr. Annette Dickinson, Council for Responsible Nutrition.

DR. DICKINSON: The Council for Responsible Nutrition is a trade association of the dietary supplement industry, representing approximately 100 member companies, ranging from suppliers of raw ingredients to finished product manufacturers; manufacturers of national brands as well as store brands; and manufacturers of products which are marketed through all channels of distribution, including mass market, health food stores, direct sales and mail order.

We are encouraged by FDA's state commitment to an open and participatory process, but we hope--and, in fact, we have confidence--that that process will, in fact, go beyond what is possible in this meeting which was, unfortunately, announced with less than 30 days' of notice, and permits only five minutes per presentation. So we look forward to additional discussions in the future.

FDA indicates that the two primary objectives for its dietary supplement strategy are to assure consumers of safe dietary supplements, and to assure consumers that labeling is truthful and not misleading. We fully support these two objectives, but we would urge FDA to add a third overall objective to this plan, and that is to fully implement DSHEA.

FDA may currently be of the opinion that this is implicit in its strategy, but we believe it needs to be made explicit and, in fact, we believe the most critical issue facing FDA and the industry today is the perceived failure to implement DSHEA, which leads to the inappropriate conclusion that FDA lacks authority to regulate these products when, in fact, the issue--as has been mentioned already--is more enforcement and implementation.

We believe that all of the elements of the overall strategy can be encompassed in three headings: one for safety, which actually is not a current heading in the proposed outline--one for safety and one for GMPs. Under the issue of safety, FDA needs to address--continue to address--the issue of new ingredients of dietary supplements and also adverse event reporting. We fully support FDA's continued review and action on new dietary ingredients notifications, and have supported FDA action that has been taken earlier this year. However, we have been disappointed that in one case involving GBL FDA's action was based on a new drug--unapproved new drug theory, rather than relying on the provisions of DSHEA directly as the basis for enforcement action.

We also support the need for prompt and effective adverse event reporting, and the current system needs improvement, because it is not prompt and it puts companies at a risk of having a product falsely associated with an adverse event.

We have suggested a number of specific modifications to the adverse event reporting system in our written statement provided today, and we will expand on that in our final statements before this is over. This include involving companies directly in evaluating adverse events; evaluation reports with regard to the strength of association; correcting errors that may have appeared in public reports; and carefully considering whether there is, in fact, a role for specific identification of companies and products. In looking at some previous FDA adverse event reporting systems on food additives and other ingredients, in general, specific company and product name is not included in the overall report.

On the issue of claims, FDA has a number of issues facing it, including statements of nutritional support, NLEA health claims, and FDAMA health claims. We encourage FDA to rely specifically on DSHEA for the definition of statements of nutritional support and to recognize that the only dividing line provided by DSHEA between statements of nutritional support and disease statements is the specific mention of a disease condition. We would urge the agency to withdraw the proposal that was published last year, and to implement--simply proceed with implementing DSHEA on this point.

On NLEA health claims, we would encourage FDA's review and approval of four new petitions that have been filed or will be filed in the next week or so, and to implement the requirements of the Pearson decision, if necessary, in evaluating those petitions.

We also encourage FDA to fully implement the FDAMA health claims provisions, using the criteria that are specified in the Act, and without adding new requirements which are not included in the law itself.

On the issue of GMPs, we join the previous speakers in urging that FDA make the completion of the GMP process a very high priority. We and our members who prepared and submitted the drafts on which the current proposal is based stand ready to provide any additional assistance that we can provide in moving that process forward.

My final two points regarding leveraging of resources and stakeholder involvement: FDA needs to leverage its resources, and we believe that one of the ways to do that is to appoint a dietary supplement advisory committee to help review important issues relating to this product category. In the meantime, FDA needs to continue to rely on working groups to supplement the existing Food Advisory Committee, which does not have the expertise in our product category. At this time, we call on FDA specifically to appoint dietary supplement industry liaison members to the existing Food Advisory Committee, and also to any dietary supplement advisory committee that may ultimately be established.

The industry wishes to be involved with FDA as a major stakeholder in regulating this product category. We believe in the importance of private-public partnerships, and we are prepared to work with FDA to improve mutual communication and action. Often, when serious issues arise, we learn about it only hours before a public announcement is made. We want to be a more meaningful partner with you in resolving solutions to those problems, whenever possible.

Thank you.

MR. LEVITT: Thank you very much.

Next, we have Dr. Maureen Mackey from RDIA.

DR. MACKEY: Thank you for the opportunity to speak today on behalf of the Research-based Dietary Ingredient Association, which is an association of companies including Cargill, Galogen, Monsanto and Novartis, committed to championing the role of science in the development of functional food ingredients and related products.

Our comments today are directed towards the agency's request for input on its objectives to ensure consumer access to safe dietary supplements that are truthfully and not misleadingly labeled. We also will address the agency's request for guidance in developing implementation strategies that leverage its limited resources.

RDIA urges FDA to develop a regulatory framework for foods and dietary supplements that, first, has consistent and transparent standards for safety and claims substantiation; has timely and predictable processes for regulatory acceptance; and, thirdly, rewards investment in research. I'll first talk about standards for safety.

As we would all agree, consumers have the right to know that the foods and dietary supplements they consume are safe. These products should meet a common safety standard that their consumption will not pose a significant or unreasonable to health when used as intended. Meeting this standard may require a scientific process that includes original research. For example, if the safety assessment of a new dietary ingredients in a dietary supplement indicates that the safety standard articulated above cannot be met through experience based on common use and published literature, then safety research will be required. We believe there is a need for uniformity of understanding in the industry as to what the safety standard means, and what information is required to be assured the standard is met. While DSHEA does not prescribe the specific safety-assessment process, neither does it excuse any company from determining that its products are safe for the target population at the specified level of ingestion. We urge FDA to work with industry to help assure uniformity in understanding what information and science are required to meet the safety standard as indicated under the law.

Second, standard for claim substantiation. RDIA believes that foods and dietary supplements whose benefits to health have been demonstrated via sound scientific research to a reasonable certainty should be able to describe these benefits on labeling, whether a structure/function claim, NLEA health claims or FDAMA health claims. The nature of the science needed to support a claim likely will vary, depending on the type of claim made, but the same standard of reasonable certainty that the claim is truthful and not misleading should be required. We encourage FDA to apply this standard evenly to all types of claims on both foods and dietary supplements.

One of the obstacles to developing responsible claims for products is the lack of clarity regarding the nature and extent of evidence constituting adequate substantiation. We realize it is not feasible or even desirable to prescribe a set of studies needed to substantiate every claim. However, we believe it is appropriate to establish a process for gathering, evaluating and weighing the evidence that may substantiate a claim, and to require that this process be applied consistently. We would bring your attention to the Functional Foods Technical Committee of the International Life Sciences Institute, which is developing a proposal for such a process, and is seeking scientific input and acceptance. RDIA supports this effort and believes it will help assure that claims are evaluated according to a consistent, scientifically sound process.

Third, I'll talk about timely and predictable processes for regulatory acceptance. RDIA believes there should be mechanisms in place to assure that claims made on foods and dietary supplements do, in fact, meet a standard of reasonable certainty, and that they can be used by manufacturers within a timely manner after their data evaluation is complete. RDIA believes it makes sense for industry to participate actively in its own monitoring. For example, industry could develop guidelines that would help its members perform appropriate and adequate studies to assure reasonable certainty. In addition, an independent expert review process could be established to verify that claims are substantiated. This option would take much of the burden of data evaluation off the FDA. These measures, however, are not meant to replace FDA's role and authority in taking action against claims. Rather, they would limit the number of situations in which FDA would need to act.

And, lastly, incentives for investing in research. RDIA believes the regulatory system should be designed and implemented in a way that encourages research and development of products that benefit people. For example, suppose a manufacturer of a dietary supplement invests significantly in well-conducted clinical studies to demonstrate its product reduces blood cholesterol consistently in subjects with moderately elevated cholesterol, when taken as part of an overall dietary plan. The current petition and approval process forhealth claims under NLEA is too uncertain and time-consuming, and the provisions that data supporting a health claim be publicly available, and that any company can use an approved claim, are strong deterrents to research investment. Instead, the manufacturer should be rewarded for its investment by having the freedom to make a labeling claim, such as "When taken as part of an overall dietary plan, this product can help lower moderately elevated cholesterol levels. "Such a claim should be allowed, because that is what the data truthfully and not misleadingly showed. We realize some of our proposed objectives require legislative change. In the meantime, RDIA urges the FDA to step back from its current view on claims and generate discussion within the scientific and public health communities and industry on how the results of scientific studies about products should be presented appropriately to consumers.

Thank you.

MR. LEVITT: Thank you very much.

And, again, our final speak on this panel is Michael Ford from NNFA. Again, I apologize for not having your name on the written agenda.

MR. FORD: Okay. Well, thank you very much for accommodating me. I do appreciate it, and we appreciate this series of hearings.

We agree with the three identified themes of maintaining a credible FDA program, and maintaining a science-based program with highly qualified scientists, and maintaining FDA's importance to consumers in the regulated agency, but we want you to act. We need you to get off of the thematic and on to the schematic, so to speak.

With the issues that you have identified, with respect to claims, we would agree with you. While maybe you haven't stated this publicly, but we believe there's a great deal of fraud in the claims in the marketplace. And the only answer that there is for dealing with that fraud is enforcement of DSHEA. It is your only course.

We believe that structure/function statements, as described in the law, are quite broad in scope and there is not a need to make medical-style claims. We believe that the structure/function statements afford the industry ample opportunity to expand their markets. But you must enforce--you must see the substantiation for these claims, because if you don't, then the fraud will continue. And DSHEA gives you the tools that you need to take care of business.

As far as defining the boundaries--all the -ceuticals that are out there: the neutriceuticals, the cosmeceuticals--you have a lot on the table to deal with. And we suggest that you consider the appointment of expert advisory group--not necessarily, perhaps, through the Advisory Committee Act, but more of an ad hoc but standing group that could combine the best from academia, consumer groups, industry, congress and, of course, the FDA, to help you through some of these issues where I think that you do need assistance.

I agree with what's been stated today that GMPs are extremely important. We believe the ANPR that came out was a little more drug-like than perhaps intended, even though it came substantially from the industry. I believe the industry has moved along, the technology has moved along. We are moving along, also. And yesterday NNFA completed its first inspection of a member company. As I've said here before, we now have mandatory GMP compliance--GMPs that we have put together--for continuing membership in the Association. And we hope to have the opportunity to sit down with you and talk with you more about that, and even invite you on some of the inspections and see the process that we are using.

With the adverse event reports, obviously there's a lot of improvement needed. I want to stress here today that NNFA has not supported any of the arbitrary efforts budgetarily or legislatively to undermine the AER safety issues. We want to work with you to get the AER program the way it needs to be but, let's face it, when we're talking AERs--we're talking ephedra--you truly need to move, again, on your regulation. We believe that perhaps you didn't go the right way with your regulation. We have suggested a guidance. But if you feel strongly that you went the right way, based on your AERs, then go ahead and finalize it. If the industry believes that you've not met your burden of proof, then I guess it will be worked out in court. But I think that would be a reasonable move at this point, rather than continuing with what kind of tends to be a rope-a-dope strategy, that the fraud in the industry, and the injuries in the industry are just going to do the industry in ultimately if you stand by. Don't stand by. Act.

I think that the responsible part of this industry wants rules, and they just want to know what they are. They want to play by them if they know what they are.

As far as the research needs, I think the FDA has mighty research needs. We support a science-base for claims and for regulations. Hopefully, there's room for collaboration with the Office of Dietary Supplements and the Center for Complementary and Alternative Medicine when it comes to the products in our area.

My main message--well, I do want to get to resource needs. We think the industry is trying to help you out with some meaningful self-regulation but obviously you need more dough to serve the public well on the safety issues, and to enforce against the outliers. And that's what I suggest that you do to use your money wisely is stop trying to get most of the mainstream companies that are in the sort of a gray area, go after the outliers--I think we all know who they are; they're making outrageous claims--you could use your resources better. If we knew what an adequate budget would be for you to enforce DSHEA adequately, we would probably advocate for that on the Hill for you, which would be an unusual situation but something we would jump right into.

Please use your authority--base your decisions on law and science. You will find that you do have industry support.

MR. LEVITT: Thank you very much.

What we'll now do--and this will be our first try at this, so we thank you for being the test--the focus group for us. What we're going to try to do is, I think, as each of the FDA panelists to ask one question, and then we'll see where we are on time. But we'll probably then be moving to the next panel.

So, I'll go first and the others can be sitting here thinking of what your question is.

My question relates to the general issue of how we get outside advice into the process. CRN has been very forceful and consistent in advocating a separate advisory committee, and has recently submitted a written proposal on that subject. CHPA thought that that was not the right approach, and has an alternative. Over here we had yet a third alternative. There was a fourth idea for leveraging outside help. How do we make sense of this? You've all each other. You talk to each other. Just kind of quick thoughts down--or is this just something--FDA should hear all the views, make a decision and move on, kind of based on your last point?

MR. FORD: Well, we've been talking--

MR. LEVITT: You need to speak into the mike, and we can pass the mikes down the table, as needed.

MR. FORD: Okay. We've been thinking about this advisory committee issue for a long time, and we're probably more in agreement with CRN than with other groups, that there needs to be a group you can turn to. But our thinking has progressed somewhat, and wonder if the bureaucracy and expenditures that would be associated with appointing a committee through the Advisory Committee Act is necessary, in terms of getting the expertise that you need. I think that's what you really need is the expert advice, more than something--a body to make regulatory decisions for you. So we're looking at the idea of a voluntary group that would have some substance, from a variety of sectors, that could help you through a lot of the bumpy roads ahead.

DR. MACKEY: We like the GRAS notification process quite a bit; the assembling of private experts to evaluate your data product by product. We also think that a similar process could be developed for claim; if you wanted an extra measure of credibility behind your claim, that an independent body--we've suggested something like the Life Sciences Research office--could be commissioned to undertake this kind of thing. It would be voluntary, but you could distinguish your claim somehow on labeling.

DR. DICKINSON: We think the priority is for FDA to have access to the right experts as it goes about making these decisions. As you say, we have supported a formal dietary supplement advisory committee. In the process of developing that--and we understand that it can sometimes take a year or more to develop--in the process of developing that, or even if you decide not to develop that, we think that the immediate priority is to get that kind of expertise available to you through the Food Advisory Committee, which you are already using to refer many of these questions to, by outside working groups such as those you have already convened, but possibly by additional ones of those, and by incorporating into that committee representatives of the affected industry and other interests who are involved in the dietary supplement business. I think that's the immediate priority for purposes of dealing with issues that are on the table right now today as you move forward in considering the value of a separate committee.

MR. LEVITT: Okay. Thank you.

Regina?

MS. HILDWINE: Well, we didn't talk about this in our prepared remarks. Certainly, NFPA believes that any point at which FDA interacts with outside organizations has to be publicly transparent. And we believe that that is the protection afforded by the Advisory Committee Act. The exact mechanism that you use--I think you're going to have to figure out what works best, but I believe that the APA is going to give protections relative to transparency and public process, and that's very much needed in this area.

MR. LEVITT: Bill?

DR. SOLLER: Yes, just a quick comment.

Our thought here really is on the operant word "at this time. "And we look at this in regards to priorities that you have, and as we've kind of looked at this landscape, we see enforcement GMPs and AERs as being the top priority issues, and then over a longer term, probably the claims situation playing out. So, you know, the operant word being "at this time. "

MR. LEVITT: Excuse me, Bill. Does that mean that you see the proposal for an advisory committee as relating primarily to claims, and not to GMPs, AERs, etcetera?

DR. SOLLER: I was just getting into that.

What I was saying is that as we look at this and think about the sort of building the infrastructure within Special Nutritionals and CFSAN, versus some sort of claims review--and let me just return to that in a moment.

The infrastructure on AERs and GMPs, just given my experience with advisory committees, both on the RX and the OTC side, is that you're not necessarily going to get the expertise out of academia that has dealt with GMPs and AERs in a particular product category. And that's building the basic infrastructure. So the kind of working group approach that's been used with the Food Advisory Committee, that has very heavy industry input when you look at it, compared to other types of working groups, is more along the lines of what Michael Ford was saying as something other than a formal advisory committee.

Now, as you get into the claims area, and you think about botanical drugs and the sorts of things that are going to come out of NIH, and potentially go for either an RX, and RX to OTC switch, or and OTC drug type of claim--and that is a possibility--we have, of course, the Nonprescription Drug Advisory Committee that, under its purview, does have botanical drugs--senna, cascara, sagrada, and psyllium and so on--so it's not foreign to that area. But you made need special botanical expertise as you explore that in the initial period.

I think, as you get into DSHEA type claims and structure/function claims, that could be a morass, in terms of a formal advisory committee, and could be less productive than going after the outliers, as was suggested by Michael Ford earlier. And I think that is how, in looking at an advisory committee, you have to think about where your priorities are, and then what type of groups do you really need in to give you advice. And on AERs I would ask: would not CDER be a very important, and perhaps the primary focus that you want to work with, particularly with respect to Jane Henney's May '99 publication, which is a very, very important document for you to look at in the AER sector. And I would say maybe you don't need that much input from outside groups on some of these issues.

MR. LEVITT: Do you have anything to add?

DR. MAINE: Just very quickly--we don't have a formal position on an advisory committee. I think what you'd needed to do, though, is set as efficiently as you can, a table that brings together the broadest community of interest, with the credible scientists, the provider community, the industry and consumer interests reflected, so that the dialogue that needs to occur can occur, but again in a way that doesn't hamper the agency from moving forward on its priorities.

MR. LEVITT: Okay. Let me turn to Margaret Porter.

MS. PORTER: The question I have relates to safety and ADRs, and I know a number of the panel has indicated the importance of an adequate ADR system in assuring the safety of dietary supplements. And I now that several of you have said you're going to submit additional comments for the record on this. But I'd be interested just in this context, if any of you would address sort of what you see as the relative responsibilities and abilities of various stakeholders in the system, whether it's consumers, manufacturers, retailers, health professionals, the Agency, in terms of identifying information on adverse events, reporting that information and monitoring it?

DR. MAINE: I would just start with identifying the fact that I think we have no good model for adverse event reporting in the full range of products that I would classify as pharmacotherapies, and I include these in that.

I am respectful--tomorrow there's an excellent meeting, for instance, that's being held on this topic specifically. And I think that the reporting mechanisms have to be evolved so that simple reporting, but meaningful reporting, is available from everyone: consumers, providers, and all other stakeholders, but that it has to go into an intelligent system that will analyze that information so that it is not spurious, it's not misleading, and that it can really be fed back, particularly, from our perspective, to the provider community that needs to use it in the course of constructing meaningful plans for patient health and well-being in the course of integrating both traditional and non-traditional approaches to care.

MR. LEVITT: Margaret, just a point on definition. If we can call it AER, and not ADR, then we're ; in the right realm here. If that's fair enough.

I think the sources that we have, in terms of spontaneous reporting--the medical literature, the medication error system of USP tests, the toxic exposure surveillance system of the American Association of Poison Controls Centers, NICE out of CPSC--and I may have missed one or two others.

As we look at that, and our experience in consumer products, that the sources are there and they are available in terms of bringing in signals. And we've picked up, you know, on a handful of reports on anaphylaxis and a voluntary program for a warning on neosporin, by way of example, and it was only a handful of reports over a fairly long period of time, and therefore very rare reaction. You can get those kinds of signals out of what we currently get, and our experience is that those are--we don't need to look for other sources.

I would encourage that you look at our comments--the detailed comments on page 4--as well as what we did last month which the Burton hearings on dietary supplements to get an idea as to where we are coming from, and a broader perspective on AER reporting. And I would also encourage looking at the May '99 report, because it goes to what Lucinda was saying earlier that what needs to happen on the CDER side, as well as the CFSAN side--remember, we're going to have new dietary supplement ingredients come out; we're going to have new drugs that will come out and will be used in a much broader population of people. And the potential for rare interactions in that regard, although they would be rare, and at probably at a low exposure setting, if you will, still need to be tracked. And so we need that integration. And what is outlined in that May '99 report to CDER on medical products I think is the foundational setting for CFSAN to move forward.

What we are working on right now is a much more detailed type of plan on AER reporting, in terms of the specifics as to when do you share things, who do you share them with, how are they reported on the Web site? A table of contents as it appears is simply not something that is very helpful and, in fact, potentially misleading, and there may be another way of thinking out of the box on that one to meet the need of being FOI-able, but also meeting the need of being complete, valid and so on. And that's what we're struggling with right now, to get the right kind of thing before August and into the system through our comments.

MS. HILDWINE: Again, this is one that we didn't cover in our prepared remarks, but I think it was a year ago--a little more than that--we did present to the Food Advisory Committee relative to safety of dietary supplements on the subject of surveillance.

Dietary supplements are foods. We believe the models that have been in place for a long time for foods are very useful here, and those models essentially put the burden for surveillance--the first line of reporting--on the industry, because it is, after all, the industry that's providing products that go into the mouths of consumers. And there is a long history on the food side of FDA-industry cooperation relative to adverse events; a long history of voluntary compliance with the industry; a long history of voluntary recall preparation, which NFPA has been a longstanding part of. We would encourage FDA, keeping in mind that dietary supplements are legally classified as foods, to look to the food models for adverse event reporting and safety surveillance issues in the marketplace, because I think that that's going to be very helpful as you go forward with this process.

DR. DICKINSON: We would support this call to look to the food models. We do think the adverse event reporting system has been demonstrably effective in pointing out--signalling--errors, problems that need to be corrected. I think some of the problems that we've had in the ephedra area which is the one, of course, that we're all struggling with most greatly at this moment, comes from trying to over interpret the adverse reaction reports and to draw from that the kinds of information that FDA's own preamble to the adverse reaction list indicates cannot be done: that is, identifying a particular dose that is safe or unsafe; identifying what the denominator is or even, in some cases, what the numerator is. I think the system as it's currently operated has the capacity to work if we apply intelligent analysis to it, as Lucinda was suggesting. And what we're going to be struggling with in our further comments is ways of doing that more effectively.

But then you--you know, as in Dr. Levitt's--Mr. Levitt's iceberg that he shows as an example that AERs are really just a signal--just the tip of the iceberg--you really need to go to the underlying science and to other issues, probably, for defining what is a safe dose, and what kind of regulatory action needs to be taken once that signal is sent up.

DR. MACKEY: I would simply second Regina's comments. There are certainly examples--published articles in the literature--documenting how adverse events for food additives has been conducted. And, you know, there's some experience there to look into.

MR. FORD: I would agree substantially with Dr. Dickinson's comments. I think you need, when looking at dietary supplement, and particularly botanicals, you need a little bit of different criteria as to determine which of these reports make it into your final report as you look through--and as Annette says, you know, this always comes back with--AER seems to come back to ephedra. The reports in there are just all over the place. We have no idea, many times, what the recent history--medical history--of the person is, what else they may have taken, what pre-existing conditions they may have, and that's, I think, important information with botanicals, and I don't know exactly how you always get at that information. I do understand, though, we're talking about a list that has a--as I've said here before--complaint about SlimFast that it had an off taste. Well, you know, so does Drano but I think it would probably produce a much greater adverse event.

So there needs to be some criteria about how these reports get in. There was conversation awhile ago among the trade associations and FDA about a consistent 800 number of some kind on the label. That would probably get you more reports, but I'm not sure it would necessarily improve the quality.

MR. LEVITT: Thank you very much.

Mr. Hubbard?

MR. HUBBARD: I actually was going to ask about AERs as well.

As you know, with the drug and device model, we rely principally on physicians--the so-called "learned interveners"--and manufacturers for information.

Dr. Dickinson, you suggested we could rely more on the manufacturers. Were you thinking of more the drug model, where manufacturers have an obligation to seek out data and report to FDA?

DR. DICKINSON: No, I was thinking of a food-based model, but in which the reports, once FDA receives them, would be referred to the manufacturer so that the manufacturer can be involved, both in determining that the actual--the product has been correctly identified; the manufacturer's been correctly identified; provide some additional information to you regarding the ingredients and the nature of the product; and be actively involved in determining the likely association between that report and the product.

MR. LEVITT: Bill?

DR. SOLLER: Yes, I don't think that a mandatory AER system would necessary be the way to go here, given the overall safety and what we know from the sources of AER reporting. I think we're really talking about refinements to the system.

It's true that manufacturers are going to have the sincere motivation of making sure that that AER is as accurate as possible. One of the things that's difficult here is that FDA may not release the name of the voluntary reporter, under MedWatch. And you can understand, it would probably undermine the system. But part of some of the discussions that we've had focus on whether FDA is able to encourage the voluntary reporter to also notify the company, particularly of the serious AERs, because that's what we're really interested in. And I think as you look at the AER system, focus in on the serious ones, recognizing that the broad perspective of all these products is that they're very safe. And if there can be some kind of linkage there, then I think you're able to--linkage between FDA, the voluntary reporter, and then the voluntary reporter also telling the company on the serious AERs--then you're helping to partner, in your follow-up process, by having the company also work in terms of identifying what is a valid report, what may have changed in the report, etcetera.

MR. LEVITT: Dr. Yetley?

DR. YETLEY: Thank you.

Some of you have mentioned the high priority for GMP regulations for dietary supplements. If you were to describe the overarching philosophy that FDA should follow in dealing with GMP regulations, what would it be? And what should it not be--for dietary supplements?

MR. FORD: We have approached out GMPs--we believe in the old rising tide lifting all boats. And we have a very inclusive and consultative type of approach. We don't want to intimidate companies. We think that most of them, with a little ratcheting, will do just fine with GMPs. So I think they need to be realistic. But just to cut to the chase, to me the most important elements of our GMPs is that raw material needs to be tested for safety and identity on the loading dock when it's received, and finished product, lots and batches need to be tested for safety and identity as far as label integrity is concerned. And everything else in the middle is important, but that's the heart and soul. Because I think that's the question that keeps getting raised when I pick up the newspaper, is about the safety and identity of the products, and that's what the GMPs, in my view, should be there to guarantee.

MR. LEVITT: Let's go down to Annette, and then Bill.

DR. DICKINSON: I would agree that the overarching principle for GMPs is to assure that products have the identity and quality that there are represented to have so that consumers have confidence that what they see on the label is what they actually get in the product. And I think that's the direction that the GMP working groups have been going toward as they work through the Food Advisory Committee to refine the proposal that has been discussed.

I think one of the things that they are not--at least in our view--is that they are not HACCP; that the nature of this product category is such that GMPs are really the answer to regularizing the products in this category, and that they don't, by and large, represent the kind of microbial or other challenges that have made HACCP FDA's choice in some other product areas.

MR. LEVITT: Bill?

DR. SOLLER: Yes--generally in agreement. And moving beyond the identity-quality-potency and purity types of goals of GMPs, our experience in GMPs has been that as an overarching philosophy--now, setting that aside from objectives of identity, potency, purity and so on--is that GMPs are best when they specify the goal, and don't over-engineer how to get there. And that is probably the most important overarching philosophy for any product GMP that would fall within FDA's bailiwick.

Now, there will be specifics within GMPs, and I don't mean to say that you are totally devoid of those. But it's quite clear that you need to build in the kind of flexibility into GMPs that allow technology advancements, and basically specify: this is your expectation for what identity, quality, potency and purity would be, allowing the flexibility for companies to get there.

The second is--and just a brief point--if you had to think about the one area in GMPs that is most sensitive for this industry--and that's the supplier side of this--and ensuring that what comes into the manufacturer, distributor, re-packager and so on is of high quality and known element is extremely important.

DR. MAINE: The only other new thought that I would add to that is that they have to be enforceable. That's what the people who are in the distribution channels are--

DR. SOLLERHere, here.

DR. MAINE: --interested in seeing.

MR. LEVITT: Thank you.

Just before I move on to Dr. Bowen, I think after we deal with Dr. Bowen's question, I'm going to ask one final one. I'm going to tell you what it is now, so you can also be thinking of it--which is just to go down the panel, rapid fire--looking ahead a year from now--and I'll be asking all the panel this--looking a year ahead from now, if FDA could accomplish one thing in this area, what would it be? So you can be thinking of that as Dr. Bowen asks her question. I don't mean to distract from that, but I didn't want to hit you with that cold.

DR. BOWEN: Okay. I think this will be an easier one for you, compared to what you have already been asked, and it's about, again, the safety issue, and the adverse event reporting.

I heard that what you want is a prompt and complete notification system, and clearly we also want that; and that want you want is an intelligent system, once we have those AERs reported, in terms of feeding back what we receive. What I'm interested in knowing from you is: does industry, since you prefer a voluntary kind of system--does industry have general SOPs in place that facilitate picking up adverse event reports and would include something like literature reports and screening and surveillance of not only your direct reports but anything else that you could find out?

MR. LEVITT: Who would like to start? Dr. Soller?

DR. SOLLER: I'm not going to represent that the industry is necessarily consistent across all sectors, but at least my experience is that the larger companies--obviously, those with the resources for the infrastructure--follow AERs as a matter of survival in a litigative world. That's a very clear driving force. And if you then say what about, perhaps, smaller companies, or companies that are starting up and so on, our experience on the OTC side has been as we have had to compile AERs for your Non-Prescription Drug Advisory Committee over these many years, is that we generally can account for the very large exposure of the American public to a particular product. And if you're looking at the inherent toxicity of a particular ingredient, that's what you really need to drive for, as you think about whether it's voluntary or mandatory; that you can really use a system that is able to derive from the large exposure base, but not the entire exposure base necessarily.

I'm not sure whether that helps in some of the thinking on where you were going with this--

DR. BOWEN: I think that helps somewhat from the OTC drug perspective, and some of the people that are now moving into dietary supplements on that side. But maybe from the food side--the three in the middle--the four, I guess.

MS. HILDWINE: The food industry certainly has SOPs in place--most companies do. NFPA helps them--helps set them up. We help educate staff as to what to be looking for. And I would say that operations staff in food company, as well as staff further down the chain, are very vigilant in monitoring problems. A lot of food companies, as you know, have consumer response centers, where they receive all kinds of responses from consumers, including, in some instances, complaints and adverse event reports--at which point science kicks in. Because like all other foods, the adverse events associated with dietary supplements may be somewhat distal to ingestion. And so, at that point, it's very much necessary to determine that the suspect is, in fact, associated with the adverse event. Science does this. NFPA has been doing this for decades to determine that, in fact, an adverse event is associated with the suspect product, at which point companies then--assuming a positive finding--companies then kick into their process to withdraw the product from the market, or engage in a recall, and then if the Agency isn't already involved, involve the Agency.

This is--it's very clearly drawn out at NFPA. We have a publication that helps companies set this up, and certainly we'd be happy to make that available to the Agency. I think you probably already have it, as a matter of fact.

DR. DICKINSON: If I understood your question to go somewhat beyond, perhaps, what the individual companies may do in the way of SOPs and follow-up, I don't believe there is, on a larger, industry-wide basis, or even on an association basis, the kind of tracking, perhaps, that I'm just hearing that NFPA has in place. And I think this is something we could learn from NFPA's model to do that better.

DR. MACKEY: Certainly NutraSweet had an active adverse event reporting process back in the '80s that involved reaction to consumer call-ins. We had physicians on staff to evaluate the claims, get back to the callers personally. This is how some of our studies were--on, for example, whether aspertame caused headaches--this is how some of our studies were initiated; people who claimed that they had an adverse headache after consumer our product.

Other companies certainly would do this for fat substitutes as well. We have what we call adverse event reporting. We also have post-marketing surveillance as to how much exposure are getting from our product; is that within the safety that we've established for the product? I think that's another aspect that, in some instances, it makes sense to undertake: just how much are people actually eating, versus what do the data say is the safe level.

MR. LEVITT: Thank you.

Michael?

MR. FORD: Well, I'm not sure I have a lot to add at the end here, but I would agree with the assertion of inconsistency, at least, across the industry. There is sort of an informal system out there that when the distributors come to the health food store every week or two, and if product has been brought back with a complaint, that complaint usually will be voiced by the health food store retailer to the distributor. It gets back to the company, and I think the companies do respond when they see a problem with a product out there; they'll pull the product, or it might affect the way the use directions show up on the label.

But it's very inconsistent, and it's quite informal.

MR. LEVITT: Okay. Thank you.

Well, in the spirit of us all trying to learn something from the meeting today, I hope you'll take back the--certainly--feeling that--the example in the food industry, there is quite systematic approach that maybe could be looked at by members from industry, too.

Okay. My last pop-quiz question: one thing a year from now. Rapid-fire, please.

DR. MAINE: Id have to say that it is the--whatever would--it will take to translate credible science related to these products into accessible and meaningful labeling for consumers and health care providers.

DR. SOLLER: When I was growing up my dad always asked me "What do you want for your birthday? " and I always said, "Can I have two things? "

But number one--drawing from that--and you wouldn't dis my dad, I hope--drawing from that, I would say an enforcement policy that removes unsafe products from the market place and ensures truthful, not misleading, and substantiated claims on dietary supplements. And, secondly, because it will set up what you're going to do for the next three to five years, a strategic plan, or a gaps analysis, that really defines your resource needs.

MR. LEVITT: Thank you.

Regina?

MS. HILDWINE: A lot of what I mentioned had implications for conventional foods, so I'm going to rule all that out, and I'm going to say that a year from now I would really like to see that we've reached the close of a comment period on a proposed role on good manufacturing practices for dietary supplements.

MR. LEVITT: Thank you.

Annette?

DR. DICKINSON: I would endorse the GMP as one of those but, like Bill, I'm going to take the opportunity to have a second one, and the second one is a visible FDA presence, in terms of implementation and enforcement, so that we deal with the outliers, and so that the impression is not given that there's a vacuum.

MR. LEVITT: Thank you.

Maureen?

DR. MACKEY: Yes, I would say that there were consistently applied standards; guidance from the Agency as to how to do that; how to affirm the safety of your product and to substantiate it's claims.

MR. LEVITT: Michael?

MR. FORD: I want to read in the Washington Post: "Year-long FDA Moratorium on DSHEA Regulation Promulgation Works. "The bill--"'The Act is a good one when we enforce it,' Levitt says. "

[Laughter.]

MR. LEVITT: Okay. Very good.

Listen, I want to thank this panel very much. And if we can, I guess, in an orderly way--I wasn't here when you--I don't know what you had to do to get up here--

[Laughter.]

--but if we could exit that way and allow you to get off before the next group tries to come up. But our next group is composed of Paul Thomas, Tracy Fox, Mary Ellen Camire, Joseph Valentino.

[Pause.]

MR. LEVITT: Okay. While we are on logistics--I mean, while we're moving back and forth, let me do a couple of logistical things. I will repeat this just before lunch, but in case anybody wants to leave before I get to say this--attendees who are not government employees, which, looking around the room, is most of the people in the audience, who did not get visitor's passes when you went to the building, if you want to get back in after lunch you need to pick up a pass from the staff on your way out from lunch. There are going to be only just the correct number of passes for the non-government folks who signed in with the guards. So if you want to get back in, you need to get your guest pass so when you come back in it's an easier process. I will repeat that later. But it certainly did serve a purpose, and allow our next group of speakers to be seated. So I'll get a two-fer out of that.

Thank you. I suspect most of you were here at the beginning but, if not, we'll ask to go five minutes per speaker. We have somebody sitting right up here that will give you a one-minute warning and final, friendly "Time is up; " and ask speakers to adhere to that as much as possible.

Then we'll go down the list. Each of us will ask one question, and then afterwards I give you a chance--the "year from now" question, or what do you want from your birthday a year from now, to use the Sollerism.

Okay. With that, our first speaker is Paul Thomas, Secretary of SNE.

DR. THOMAS: Okay. Well, thank you and good morning.

The 1,400 members of SNE acknowledge the growing role that supplements play in American life. We also recognize the need for more authoritative information about them so consumers can make more informed, sensible decisions about supplement use. But we think that making such decisions can be hard in today's environment. It's only natural that so many people are confused about supplements, given the large number of products available and the plethora of information from advertising, product promotions, media reporting of single studies, and word-of-mouth from sellers. It's hard even for experts to separate from the pseudo-science without a good bit of digging.

SNE recommends that FDA consider adding a strong consumer research and information component to its overall strategy on regulating supplements, and we have three specific suggestions.

Number one, FDA should take the lead in conducting and encouraging others to conduct high quality consumer research on supplement use. Last year, FDA asked its Food Advisory Committee to help identify questions to ask consumers about supplements in future surveys and focus groups. FDA's Alan Levy stated that while half the population takes supplements, very little is known about consumer understanding and use of product labeling. He added that FDA's current research on supplements focuses on who uses them, how many are used and reasons for use, in a relatively simple kind of way: "What do you take? What are you using it for? ""I take echinacea for colds. ""Thank you. "Dr. Levy acknowledged that more research is needed where consumers are asked their thoughts about supplements.

Now, we agree. Clearly more research is needed on how the labeling, advertising and various promotions of supplements shapes consumer perceptions of them and their willingness to try such products. We need detailed studies, both qualitative and quantitative, and theory-based, that explore how consumers come to decision about whether or not to supplement, and details of the decision-making process itself. Do consumers make meaningful distinctions between health claims and nutritional support claims? Do they evaluate advertising copy and label information in the same way or differently? What do consumers recommend that FDA do to regulate supplements? The research needs to move beyond simple surveys and a few focus groups.

FDA might use its Food Advisory Committee to help define the questions that need to be asked, and do what it can to stimulate the needed research. FDA might also develop a workshop or conference to get advice from the scientific community on developing a more consumer-focused research agenda on supplements, and we can, of course, provide you the names of some Society for Nutrition Education members who might want to participate.

Now, suggestion two. At present, supplement manufacturers do not have to provide FDA with substantiation of their claims of nutritional support for their products, even though DSHEA says the manufacturer must have that substantiation that the claims are truthful and not misleading. We believe that FDA should require that the evidence on which the manufacturer is relying be provided to the agency and be made publicly available. Then more claims of nutritional support might be investigated by scientists, journalists and perhaps even FDA itself. The results, we think, would help consumers become more savvy users of supplements.

Suggestion three. Consumers and health care professionals need easily accessible and authoritative information about supplements without having to search too many diverse sources, or to conduct their own literature reviews. The Office of Dietary Supplements, for example, is preparing fact sheets on some supplements. U. S. Pharmacopoeia has produced short monographs on various botanicals. And recently, the American Society of Anesthesiologists issued a warning about using certain herbs before surgery. Authoritative information such as this should be accessible from a single source that is very frequently updated. The FDA or ODS Web site might be the right source. But irrespective of placement, FDA could do more to encourage the development of a central source of authoritative statements regarding supplements, and then promoting it.

And, again, on behalf of the Society for Nutrition Education, I want to thank you for the opportunity to comment on FDA's efforts to develop an overall strategy for regulating supplements. Consumers need easy access to good, authoritative information to make sensible decisions about these products and more consumer research is needed to develop better policies and regulations that will allow the dietary supplements industry to thrive, but not at the expense of consumer misunderstanding and confusing about the benefits and limitations of its products.

Thank you.

MR. LEVITT: Thank you very much.

Our next speaker is Tracy Fox, American Dietetic Association.

MS. FOX: Good morning. My name is Tracy Fox. I'm a registered dietician and a senior Federal regulatory manager with the Government Affairs Office of the American Dietetic Association.

With over 70,000 members, ADA's mission is to serve the public through the promotion of optimal nutrition health and well-being. ADA supports the need for consumers to have access to dietary supplements as long as their opportunity to choose is made in the context of a fully informed choice and assured public safety measures. To this end, we continue to stand behind the need for stricter regulation and oversight of the dietary supplements, and applaud the efforts of FDA.

We congratulate FDA for holding this open meeting and soliciting input from various organizations on the complex issues surrounding the regulation of dietary supplements. We also urge FDA to look closely at the recommendations made by the Presidential Commission on Dietary Supplement Labels in November of 1997 to ensure that these recommendations are incorporated effectively into FDA's overall strategy.

In my oral testimony today, I'll highlight some of the key issues that ADA urges FDA to consider as you proceed through developing a strategy. My written comments provide much more detail in a number of areas, including adverse event reporting, good manufacturing practices, and significant scientific agreement. Copies of the testimony are out front as well.

FDA has asked whether there are other objectives in addition to ensuring consumer's access to safe dietary supplements that are truthful and not misleadingly labeled that should be addressed in an overall dietary supplement strategy. Frankly, if FDA accomplishes this and this alone, given the relative limited authority it has under DSHEA, then the strategy should be considered an enormous success. However, ADA recommends that that statement--"ensuring consumer access to safe dietary supplements that are truthful and not misleadingly labeled"--should be the overarching goal of FDA's supplement strategy. This goal would then drive the development of more specific and measurable objectives to coincide with elements of the Center for Food Safety and Applied Nutrition--the elements that they have already identified in the 1999 program priorities document--as well as the recommendations that were made by the Presidential Commission on Dietary Supplement Labels. We also urge FDA to consider establishing an advisory committee on dietary supplement comprised of multi-disciplinary, well-respected experts to provide on-going counsel and guidance.

ADA agrees with the need to define boundaries between the various categories of products in order to provide industry with a more structured approach to marketing and labeling, and to provide consumers with accurate information. The proliferation of claims on a variety of products has created an environment of confusion and distrust among health professionals and consumers.

Within the dietary supplement definition, we urge FDA to consider an approach that delineates those supplements that occur naturally in commonly eaten foods, and those that do not. Under this approach, vitamins and minerals for which some form of requirements or formulation standards have been established, such as by the Institute of Medicine, or United States Pharmacopoeia, and about which there is a considerable research base, would be in one category along with other known nutrients or components of body function. Botanicals, like St. John's wort, echinacea, as well as hormones, like DHEA and melatonin, of which less is known, and therefore present unknown or potentially greater risk, would be in a different category. The components in the latter category would require more scrutiny or limits. This would also help the Center in allocating resources and focusing on supplements that could present a greater risk.

ADA continues to believe that health and nutrient content claims, as well as structure and function claims on foods and dietary supplement should be based on the totality of publicly available scientific evidence, including results from well-designed studies conducted in a manner that is consistent with generally recognized scientific procedures and principles. DSHEA, as well as the 1997 Food and Drug Administration Modernization Act, did not change that overarching public health need. To this end, we urge FDA to expeditiously outline criteria on characteristics for significant scientific agreement. This will help the public, consumers, researchers and certainly the industry itself. And my written comments go into much more detail about the components of significant scientific agreement and some ideas.

ADA, like the Society for Nutrition Education, supports the need for the contents of manufacturers' substantiation files to be more readily available--to FDA as well as health professionals, researchers and consumers. How can consumers make informed choices, or health care professionals be knowledgeable about products, if the only information available is what's contained on the supplement label--equivalent in size to a 3x5 inch index card. In addition, when claims are made for supplements and the research base includes a particular formulation, then the product making the claim must use the same formulation. That's common sense.

I see my time is up. I think some of the other areas, includingcommunicating to consumers as well as research needs and the research area, we would certainly support more research into basic supplement research itself, in terms of the bioactive components and the mechanisms underlying the action of the supplement. We also support the need for additional consumer research. We need to understand their attitudes, purchase decisions, usage behaviors, and sources for dietary supplement information.

Again, thank you for the opportunity of allowing ADA to testify, and we certainly urge FDA, as they struggle with developing a strategy, to think of consumers first and foremost in implementing a strategy and, again, to take a look at the recommendations by the Presidential Commission. And we look forward to working with FDA, other government agencies, the private industry--food industry, supplement industry--in reaching the ultimate goal of providing safe supplements to consumers.

Thank you.

MR. LEVITT: Okay. Thank you very much.

Our third speaker on this panel is Dr. Mary Ellen Camire, IFT--Institute of Food Technologists.

DR. CAMIRE: I'm Mary Ellen Camire, and I'm an associate professor in the Department of Food Science and Human Nutrition at the University of Maine, and I'm speaking here on behalf of the Institute of Food Technologists, which is a non-profit scientific society with about 28,000 members working as food scientists, food technologists and in related professions, in academia, industry and government positions. We will be submitting written comments later in more detail; particularly academicians like myself like to take a little break in the summer. But we'd like to make three main points today.

We think that some clarifications that will be key to FDA's overall strategy will be making clear distinctions between foods and dietary supplements. There is a great deal of confusion I think, both for manufacturers and consumers at this time. You can walk into stores and see soups and teas that are clearly marked "Herbal Supplement" on their front package panel. They contain a supplement facts panel containing nutrition information. Is this enough information for consumers to know if it's a food or a supplement, when it looks and it appears in every other respect like a food. It's not clear. And this is what the consumer research will be very important.

Many food products, and particularly we're seeing this in snack foods and beverages, are adding botanicals and other dietary supplement ingredients to conventional foods, but maintaining that food identity, keeping the nutrition facts panel. So you may have a tea which is a very traditional way of taking botanical ingredient, but add St. John's wort or another herb, and then it's up to the manufacturer to decide are they inclined to market it as a dietary supplement or as a food. In some cases the packaging is the only distinction that the ingredients may be exactly the same. And I think that's very confusing to people, particularly small food manufacturers like we have in Maine.

In order to prevent unnecessary research and development expenditures which may be exceeding possibly millions of dollars at this point for food products that contain added dietary supplement ingredients, it would be very helpful for FDA to issue a talk paper or similar vehicle to explain to food manufacturer how these ingredients can be incorporated, and what the distinctions between foods and dietary supplements are.

The second issue we'd like to address is to urge FDA to assign priority to finishing up unfinished business; that final rules or to let people know rules will be issued on issues that have come up in the past and need to be taken care of. In particular, the advance notice of proposed rule-making for ephedra-containing supplements was issued over two years ago, and IFT strongly made comments over four years ago regarding the safety of ephedra supplements.

In addition to working on that one, which I think is important in terms of preventing any additional deaths, while maintaining access for the people who are using these supplements responsibility and do use it in the traditional fashion, we also need to make sure that there's rules coming out--forthcoming--on good manufacturing practices and though we don't totally agree maybe with some of the proposed ideas regarding structure/function claims and the definition of disease, that closure needs to be brought to that subject as well.

Finally, we'd like to recommend formation of dietary supplement advisory committee, though I'm going to amend my remarks, given the discussion we've had this morning that some form of advisory group is needed, maybe not in the traditional sense; scientists with expertise in botanicals, particular, but also other dietary supplement ingredients, could provide very important and valuable assistance to FDA in what has become a great deal of research burden for FDA scientists. The Food Advisory Committee thus far has done an excellent job working with ad hoc groups, but we think additional assistance is needed, and this may help reduce some of the workload involved with dietary supplements. And although the formation of such a committee was not outlined in the CFSAN priorities, I think perhaps it should be added.

Thanks.

MR. LEVITT: Thank you very much.

Our final speaker on this panel is from the USP, Joseph Valentino.

MR. VALENTINO: Thank you for this opportunity.

The United States Pharmacopoeia is a unique organization. We're a non-profit standard-setting body, and we publish the USP--the United States Pharmacopoeia National Formulary--and these are the only non-governmental pharmacopoeia in the world. It's because of this uniqueness that I never know where we're going to be placed on a panel. So today, I guess, either I'm a nutritional professional or a member of the food industry.

Because of time constraints, I'll address the questions posed in the Federal Register in our written, but I'll try to use my time today to focus on a specific area that we believe needs attention by the Agency.

The United States Pharmacopoeia promotes the public health by establishing and disseminating officially-recognized standards of quality for the use of medicines and other health care technologies. In 1995, based on concerns about the safety, quality and use of dietary supplements, USP members--about 400 organizations--adopted a resolution to provide standards for these products. Over the past four years USP has begun developing monographs in the National Formulary for those botanical-based dietary supplements that account for about 90 percent of U. S. retail sales. This is approximately 24 botanicals, and I have a chart in my handout which indicates the status of the progress we've made.

These monographs contain standards of identity, strength, quality and purity, and there's even a chapter on manufacturing practices for nutritional supplements. Compliance with standards in the official compendia the USP and NF would help eliminate the reported problems involving potency variations and product contaminations.

The Federal Food, Drug and Cosmetic Act indicates that dietary supplements purporting to conform to the standards of the official compendia must do so, or they will be considered misbranded. FDA should take regulatory action against those products which purport to meet USP or NF standards on their label and that fail to do so. Further, the FDA should take advantage of this provision regarding dietary supplements and the USP-NF recognition in the drug provisions of the Food and Drug Act, by recognizing USP standards and NF standards and methods of analysis in their regulations, and encourage their use by industry to ensure the potency and purity and ultimately the safety of dietary supplements. We would also welcome the participation in the development of these standards and analytical methods by FDA.

Compliance with USP or NF standards would provide for uniform designations of identity and strength on labels, and would allow consumers to make meaningful selections of products and be assured of their performance.

Now, in order that consumers not be misled, USP recommends that FDA also carefully review labeling that inaccurately implies compliance with USP or NF standards, or contains statements that are false or meaningless, or designed to mislead consumers as to the quality of the product. Included among these statements are--quote--"standardized" or "meets laboratory standards," or some that even say "meet USP dissolution standards. "The first two statements do not provide useful information to consumers. And even the third may be misleading if the product is not in the USP or NF; or, if it is, and it meets the USP dissolution standards but it fails to meet the other quality standards.

In conclusion, let me say that USP looks forward to working with the FDA to assure the quality of dietary supplements in the marketplace.

MR. LEVITT: Thank you very much.

Again, we'll go through the same process we did before. I'll start with a question and we'll proceed right down the row.

My question is on the issue of substantiation of claims. A couple of speakers addressed that to some degree, and my question is where would you put, in an overall priority, the substantiation issue on claims, compared to some of the safety issues that have gotten also a lot of comment already today--primarily the enforcement; the AERs, the GMPs and so forth. I think everybody agrees substantiation is needed, but where do you think that fits in the hierarchy, in terms of urgency?

Please?

DR. CAMIRE: Well, I think we have to maintain safety as the number one priority, but substantiation is important, particularly given the NPR survey that came out this year that said more than half of Americans surveyed didn't feel that the claims that were on dietary supplement labels were really accurate, to paraphrase them.

So I think that's important to consumers that hey have some confidence in what's on the label. But I think we don't have the framework yet to be able to make those recommendations and that may be a longer-term goal; within the next three to five years.

MR. LEVITT: Good. Thank you.

Tracy?

MS. FOX: Again, I would have to agree--we can't say safety is going to be second, and substantiation first. However, I do think that substantiation is absolutely critical. If there can be two top goals it would be safety, clearly, and substantiation. Because if FDA is going to adhere to the strategy of making sure that consumers are not misled, then that is substantiation, and that is also safety. And I think that is absolutely critical.

There are many claims out there, on many different types of products, and I think we need to rein that in and really get a feel, as health professionals, what we can be telling consumers.

MR. LEVITT: Thank you.

Anybody else want to address--it's optional.

MR. VALENTINO: I was just going to say that I'll limit my remarks to the standards aspects, and I think that the--it's important that the claims being made regarding the standards and the quality of the product be substantiated, and that FDA take a separate look at that.

DR. THOMAS: And I would just concur, as well, that safety probably first, but substantiation of claims is a very close second. And, let's face it, consumers are deciding whether or not to take particular supplements largely on the basis of hoping for some kind of effect. And what is on the label is probably--and also in advertising--is probably a major source of information for them in their decision-making process. And, unlike with foods that you might eat because they taste good, they're crunchy--you know, that sort of thing--you're taking dietary supplements for specific health-related types of effects, and here the labeling and the information that is available about them is critical.

MR. LEVITT: Okay. Thank you very much.

If I could pass the microphone over to Margaret Porter.

DR. PORTER: My question is a follow-up to something that I think I heard Tracy Fox say, which is suggesting in that as we tray--the Agency tries to figure out how to set priorities, that we may want to consider looking at the universe of dietary supplements and drawing distinctions among the categories. And I think I understood you to say that with respect to dietary supplements that might be naturally occurring in commonly eaten foods, perhaps we ought to consider giving a lower priority, or a lower attention to those products; and that with respect to botanicals and hormones, that we might apply a higher scrutiny. And I was wondering if I heard you right and, if so, if you might elaborate on the basis for that recommendation, and also what the other panelists might care to comment.

MS. FOX: You did hear me correctly, in terms of--within the definition of dietary supplement as FDA undertakes the very difficult task of defining the boundaries, I think because we all recognize there are limited resources. We also all recognize that there are very safe products out there, and very--with a very good research base. And I think you need to draw the line somewhere. This is just a consideration. It's clearly very preliminary; it's something that as we were struggling with trying to identify, within our own minds, the boundaries and the definitions, that this is one approach that I think is worthy of further discussion; not necessarily drawing the line very clearly. I don't think that's going to happen. But I think it's at least a gradation approach, in terms of trying to identify those products that we really don't know much about but for which--are out there in the marketplace, consumers are purchasing them and taking them, and we don't have a strong research base for them.

So that is one approach that I think is worthy of consideration and further discussion.

DR. PORTER: Is there anybody else who's interested in commenting on that?

DR. CAMIRE: I'd just like to say that in regards to the research priorities, I think it ties in that this is an area we need more research, and I agree that we have a little bit more comfort level with things that are derived from foods and culinary herbs, but we're not sure how processing many of these components: when we do an alcohol extract, when we freeze-dry, when we isolate individual components. And we don't know how that effects the efficacy and the safety of those isolated materials. And that certainly could be something for CFSAN to consider as a research area.

MR. VALENTINO: I was going to say, from our perspective, we--obviously, if there's an inherent toxicology problem with a substance we'll try and set standards for it. But we say items are "safe. "They're safe if what we think they are. But if you can have something with not an inherent adverse effect but yet if it's contaminated with pesticides or some other impurity, or it's transformed somehow, that article is no longer safe. So what we have done is we've given priority to attempting to cover as many products on the market--the largest percentage on the market that the people will be taking--with this in mind.

DR. THOMAS: And I would agree with both Tracy's recommended protocol and Joe's statement, as well, that you take into account the--perhaps the naturalness, the familiarity of the different types of supplements as a set of criteria, but also, probably, as important, is the number of people that are taking particular kinds of supplement, as perhaps measured by sales volume is one measure.

MR. LEVITT: Okay. Thank you very much.

Bill Hubbard.

MR. HUBBARD: As you know, one of the provisions of DSHEA differentiated so-called structure/function claims from disease claims.

The earlier panel was fairly critical of the proposal we did on that issue recently, but yet they were also urging us to act against unsubstantiated claims.

Do you have any views on that proposal? The structure/function proposal? Are you familiar with it?

MS. FOX: Yes.

DR. THOMAS: Well, I--I'm sorry.

MS. FOX: Go ahead.

DR. THOMAS: I'm familiar with it personally, but as far as the Society for Nutrition Education goes, probably most of its members and its Board has not evaluated it, so I wouldn't be comfortable in speaking for them on that particular proposal.

MS. FOX: ADA did provide comments on the proposed structure/function claim rule, and I believe we--I think we generally support the definition that FDA proposed of disease. And, certainly, while we agree with the need for guidance in the area of structure/function claims, I think that is one of the most difficult undertakings in terms of trying to really grapple with the complex issue of what is a structure/function claim and what is a disease claim. And I frankly think that that's where the consumer research is needed, because I don't think consumers really know the difference between--or really--not that they don't know the difference between it, but I really think they can easily extrapolate from the structure/function claim to--perhaps inappropriately, to a disease claim. And I think the consumer research base is probably going to need to be there much more strongly in order to really handle that issue effectively.

Any other reactions to that?

Okay. Dr. Yetley?

DR. YETLEY: Either explicit or implicit in many of your comments was the need for research and sound science to back up a lot of the issues. You're all members of professional associations. What ways can your associations help us leverage research expertise and actual funding for research projects?

DR. CAMIRE: Well, I'll address that, since I'm incoming chair of IFT's research committee and nutrition division.

I think that IFT, in particular, because we have people working in the food industry, in the dietary supplement industry, and food scientists as well as nutritionists, we'd be happy to provide expertise and to help point out individuals who may have expertise that FDA does not have. I think it's also important for us to make sure that you have adequate funding, and I think the last panel addressed the need for FDA to tell us what you're going to need in order for us to help get funding so that you're able to adequately do your research.

MR. VALENTINO: In April of next year the USP convention will be meeting, and they will be electing an expert committee on dietary supplements. And it may be that we should explore ways on how the FDA can utilize and get opinions or decisions or whatever from this expert committee more than they do now. Right now you have an ad hoc reviewer that sits in at the meetings and learns from their deliberations, but there may be something more formal that we can do with the Agency so that you can take advantage of this expert group.

MS. FOX: I think also as FDA establishes kind of its research agenda in terms of the types of research needed, it would be beneficial to establish, or to really closely look with industry, with scientists, with researchers, to look at creative funding mechanisms as well; funding mechanisms that can take advantage of, I think, the experts and the resources in the industry arena, and tap into that to focus research, as well as develop strategies, that it can be very complementary in terms of being as objective as possible, yet still tapping into the resources and the expertise of the industry.

MR. LEVITT: Okay. Very good.

Dr. Bowen.

DR. BOWEN: Okay. This is a somewhat more directed question about research.

Three out of four of you mentioned consumer research should be an FDA priority. And I'd like for you to comment--each of you--on FDA's role, what that should be. Should it be to encourage the research? To ask for it? To actually do the research? And, in your opinion, what do we need to know from consumers?

DR. THOMAS: Well, I think I presented some of those research needs in my statement, but I certainly think that FDA needs this kind of research; at the very least, should be asking for it; certainly should be encouraging it; and, to the extent that it can, given its limited resources, actually undertaking it. And, certainly, under Alan Levy, you have made some good moves in that direction and have raised some interesting issues with the focus groups and questions that prompt additional kinds of questions and research needs.

I think we need more knowledge of consumer behavior regarding supplements in terms of the sources of information that they use; their evaluations of labeling information and advertising claims, and how that affects their decision-making process--their general sense of the potential usefulness of dietary supplements.

I also think it's probably a good idea that more effort be made, actually, to find out what consumers think FDA's role should be in the area of dietary supplements and its regulation. And probably this isn't for FDA alone, but also for consumer input related to decisions regarding policies within the Federal government as a whole, including Federal Trade Commission, for example. And I think this kind of information is really very critical for FDA and other agencies to develop effective public policies in this area that respond to perceived consumer needs, and that are likely then to be better liked and appreciated because of having had the opportunity of input rather than what is often, typically, the case, where we have a variety of, you know, industry, professional societies, etcetera--the usual group of people that generally comment in forums such as this and to proposed regulations. They need to be asked more directly.

MR. VALENTINO: I was going to say that the USP just recently conducted a study as to what is considered "useful information" for patients, relative to the patient inserts for medications. And this was done in conjunction with Duke in North Carolina. And it may be that we could develop another program which could tack onto that, and would be considered useful information relative to dietary supplements.

MS. FOX: I think also there--since the use of dietary supplements is growing so rapidly, some of the government survey instruments have also been modified, or I know there are plans for modifying some of those large-scale instruments to capture this important information from consumers. And I think efforts in that direction should be increase as well. There might be some opportunities with CDC behavior factor assessment survey. There might be some really good opportunities to, across the board, capture some very basic information, even just on usage; how consumers--what they view the label as, in terms of dosing requirements.

There was a recent article in the Journal of the American Dietetic Association that found the majority of high school students exceeding dosage on a very regular basis for supplements, of course, that were recommended by their coaches. And I think this is the kind of information that we really need, and we need more of. And I think there are some opportunities in existing survey instruments. UPS does one. ADA does a trend survey. These are really good avenues to take a look at, as well as government surveys.

DR. CAMIRE: And I'd like to echo Tracy comment that I think it's important to encourage collaboration on this issue. USDA and ODS, CDC; FTC has done some excellent work in this area--their study on how consumers responded to qualified health claims and advertising. It could very easily be reworked into looking at structure/function claims on dietary supplements.

But I think it would be also important to look at how consumers respond to that disclaimer, and to see if that is really helpful or not, because that does take up, you know, valuable space on the package label, and to find out really--my personal sense is that people disregard the disclaimer and they are, indeed, using the supplements to treat or prevent a disease. And if, in fact, that is how the public is using them, then we may need to re-think about how we provide these claims on the package labels.

DR. BOWEN: Thank you. I think those suggestions are very helpful.

MR. LEVITT: For our one last final question--you heard before--a year from now, if there was one thing that could be accomplished, that would be?

Dr. Thomas--we'll move right down the row.

DR. THOMAS: Well, again I think that we will have significantly more knowledge of consumer behavior regarding supplements, and maybe a workshop or a conference with a broad group of people to help set a research agenda.

MR. LEVITT: Mr. Valentino?

MR. VALENTINO? : I think I'd like to see a joint USP-FDA committee formed, and that they be charged with three things: one, that we develop an active working relationship in the standards area, where you comment and we develop standards, not only for the materials but for the extracts, and for the dosage forms, and the development of reference standards. That's very important in this area.

Two, I think the committee should be charged with exploring with USP cooperating with our practitioners reporting programs. We do operate practitioner reporting programs in which we make information available to the FDA and the industry now, and we may be able to work off of these programs and cooperate with you on that.

And then the last point was the one I made previously. I think that they'd be charged with exploring how the FDA could utilize the decisions of the USP advisory panels in their decision-making.

MR. LEVITT: Thank you.

Tracy?

MS. FOX: To not have to testify at any more FDA hearings--

[Laughter.]

MS. FOX: --on this issue, because it's all been resolved.

Actually, I think probably the two main areas are--I'd have to say safety first, to make sure that the system in place in this country provides assurances to health care professionals and consumers--and I think it's important to say "provides assurances," because I believe for the most part the system is safe, in terms of the manufacturing of supplements, but I think more importantly, consumers need to feel comfortable, and so do health care professionals.

And I think the next phase would be claims substantiation. I think that's a critical first step in educating consumers, and educating health care professionals on the effective, ineffective, appropriate, inappropriate uses of supplements.

MR. LEVITT: Thanks.

And Mary Ellen.

DR. CAMIRE: I'd obviously like to see final rules on the ephedrine-containing supplements, and I'd also like to see more supplement companies feeling comfortable putting contraindications on their product labels.

MR. LEVITT: Okay. Thank you very much.

Before I let you go down, let me just take a couple minutes on logistics.

First, not to scare anybody, but we're on schedule.

[Laughter.]

Before people leave, there are three quick announcements that I need to make. One is, as I said before, if you're not a government employee, and you did not get a visitor pass, on the way out, if you want to get back in easily, please get a visitor pass on your way out. That's number one.

Number two is that in your package you do have a green sheet that looks like this, that lists some convenient places for lunch that you can get to an back in an hour.

And, number three--and I'll repeat this again after lunch, but in case there's some people that are not coming back--with regard to the meeting in July in California, we had provided a contact in the Federal Register: our public affairs specialist, named Janet McDonal, and we had provided a phone number and a FAX number. Under Murphy's law, some people have had trouble getting through on the phone and/or the FAX, and I would like to provide, in addition, an e-mail contact, which is JMcDonal--without the D at the end, for some reason--so that's JMcDonal@ORA. FDA. gov. Again, that's JMcDonal@ORA. FDA. gov for interest in the California meeting. And again what we're hoping is we'll get different speakers. The goal is not to see if the same speakers can fly out to California and repeat the same presentations.

[Laughter.]

MR. LEVITT: No word that Tracy