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 will do that--but we're hoping to get a different mix of people so they didn't have to fly east.

My watch, it says that it is 12: 20, so we will begin--try to begin promptly at 1: 20 back in this room.

I thank you very much. Thank you to the speakers. And, Tracy, thank you especially for coming back twice in a month.

[Luncheon recess.]

MR. LEVITT: It being 1: 20, we are able to get going. I actually looked around and said, "Oh, we can't start yet, the next panel isn't up there. "I just hadn't invited them up yet.

So, again, for those that were not here this morning, my name is Joe Levitt. I'm Director of the Center for Food Safety and Applied Nutrition, and we are part way through out open public meeting on looking at an overall framework for the regulation of dietary supplements.

I have a couple of announcement's that I'll either repeat or make for the first time, while we have everybody back and attention.

Number one, at the end of the day--at the end of the day, we will provide some time for members of the public who did not have an opportunity to schedule time in advance--if you want to speak, we ask you to sign up outside at the registration desk. We do have a couple of people that have signed up. We would try to limit these presentations to about three minutes each, as the hour will be late by then but we do want to give you an opportunity, if you've traveled specifically because you wanted to make a presentation. So you sign up for that outside the door at the registration table. And we will come back to that later.

Second, I just want to repeat that for those that are interested in having information about the meeting in California on July 20th, again it's a repeat meeting. We're asking the same speakers not return and make the same statements again, but the Federal Register notice does provide a contact in California. Her name is Janet McDonal. She's actually here--or was here a second ago--right up here in the back. The Federal Register has her phone and FAX number. In addition, her e-mail address--because the others have been so difficult in getting through--is JMcDonal--it's like JMcDonald without the D at the end. If you include the "D" you're going to have trouble--@ORA. FDA. gov--and the ORA is because our field offices are under the Office of Regulatory Affairs at the FDA.

I also need to make an announcement for one person that we're not sure we can find in the audience, from our Chief Counsel's Office. Alexis Barnett, if you're here, you have a conference call at 1: 30.

[Laughter.]

Sorry to have an embarrassment if that occurred, but I was handed a note, so I thought maybe I should read it.

With that, let me welcome everybody to the afternoon session. For those who were not here this morning, we are engaging in a public dialogue on, really, how to stake a step back, four years after DSHEA and say "How are we going to develop a long-term blueprint to make this law work and fully implement it? "

We've talked about a lot of issues so far. We have divided the day up into several panels. There is an agenda that is orange that all of you have out here, and I think, without further ado, we will invite the next panel up.

We have three people on this. The first is a representative from the National Woman's Health Network, Adrian Fugh-Berman. Second is Citizens for Health, James Turner. And the third is Center for Science in the Public Interest, Ilene Heller. If the three would please come up and join us at the table, we will go through and ask each speaker to make a five minute presentation in the order that I've just described. It looks a little different when you're up here, but we have a young lady sitting in the front row who will give you a one-minute warning and a final time. And we do ask you if would adhere to that. We had terrific compliance this morning with that, and it's very helpful in moving along.

We will then go through and each member of the FDA panel will ask one question, and at the end of which I'll ask one final question, which I have telegraphed in advance, which is: A year from now, if there was one thing that you would like to see occur, it would be--blank.

And, with that, let me invite Dr. Adrian Fugh-Berman--if I have pronounced your name correctly. If not, please correct it for me--from the National Woman's Health Network.

DR. FUGH-BERMAN: Good afternoon. Pleasure to be here.

My name is Adrian Fugh-Berman, and I'm Chair of the National Woman's Health Network, which is a national consumer advocacy group that takes no money from drug companies, medical device manufacturers or dietary supplement companies for that matter. I also integrate herbal medicine into my practice, and am a consultant to the Federal Trade Commission on dietary supplement issues, and a member of the ad hoc panel on botanicals for the U. S. Pharmacopoeia. And I teach about botanicals all over the country.

It's a women's health issue because more women than men use alternative therapies. And there is a plethora of dietary supplements that are specifically marketed to women. They're very popular with consumers. They're also very popular with physicians. I've just come from Columbia's Botanical Conference last week, where it's a whole week-long course--CME course--where we teach physicians about botanicals.

The current available of unregulated products that are widely divergent in quality, safety and evidence of efficacy really raises a number of public health concerns. Consumers have no tools or guidelines with which to assess a product's quality. Labeling is very vague; contraindications aren't' listed; drug interactions aren't listed. And there are some dietary supplements that should just not be on the market at all. I have--comfrey contains pyralizidine alkaloids with proven hepatotoxicity. There is no reason for this herb to be on the market. DHEA and melatonin are very potent hormones that are not part of any sort of traditional medicine. They shouldn't be considered dietary supplements. They shouldn't be on the market.

I would disagree with the speaker this morning who would put together herbs or botanical medicines with these hormones. They're very different things. And the National Woman's Health Network would definitely support having an advisory committee on dietary supplements. I would emphasize, however, that it would be very important to have at least half of those members be conversant with botanical medicine. Herbs are quite different from other sorts of dietary supplements, and really need to be regulated differently. They span the whole spectrum, from foods to drugs, and it's really important to integrate people who are familiar with these.

I've forgotten to say that this testimony was prepared by myself and Dr. Varro Tyler, who is one of the most eminent pharmacognicists in the country. And it's one of the expertise--it's--FDA needs to integrate pharmacognicists into this discussion. There are very few pharmacognicists working in the FDA, and those that are there are mainly sort of banished to the laboratories, and they really need to be incorporated into all levels of these.

Even--science supports the use of many alternative--of many dietary supplements: St. John's wort to treat depression; garlic to lower cholesterol; folic acid to reduce the risk of neural tube defects, but even in these cases, labeling these to reflect caution. Garlic can inhibit platelets and can cause bleeding; folic acid shouldn't be used with certain drugs; St. John's wort can cause photosensitivity. It shouldn't be combined with certain anti-depressants. So it's really very important that labels be accurate, be understandable and have adequate warnings on them.

It's really important not to ignore work that's already been done. There's quite a lot of research on botanicals. There's quite a lot of research on chemical characterization of botanicals; on quality-setting for botanicals. Much of this has been done in other countries, but there's no need for us to reinvent the wheel. And I think one of the systems that we could use as a model is the Commission E, which is the body in Germany, an independent panel, that assessed more than 300 botanicals and determined whether there was evidence of efficacy and safety. Those monographs have recently been published in English.

So FDA's first priority should be safety, quality and efficacy of dietary supplements. Unsafe dietary supplements should be removed from the market. And, really, the quality issue is the most important one besides--the next most important thing besides safety. The limitations of structure and function claims have been extremely confusing to consumers. It's caused manufacturers of both worthy and unworthy products to really resort to subliminal messages and word games. There's no reason that people should not be able to make a claim when there is adequate evidence, but there is a lot of misleading labels out there, and we feel it's really important for FDA to go after labels that are already out there on the drug store shelf.

This is "Brain Gum," which "improves name and face recognition; helps in recalling telephone numbers, and improves recalling the locations of misplaced objects. "

[Laughter.]

There is a number of these "breast health" formulas; this is "Women's Breast Health," "Everywoman's Breast Basics. "These do everything except make a specific claim for preventing breast cancer. This, for instance, has a picture of a pink ribbon on it, and says "A portion of these proceeds goes to support cancer research. "--"Breast health is the number one concern of women. This formula contains the patented compound glucurate which has been shown to enhance the major cleansing pathways in the body, helps the body rid itself of pollutants and foreign elements not conducive to breast health. "

This company gives money to the "Breast Health Project" --

[Laughter.]

--and says that "Our herbal extracts are potency assured"--trademark. Potency is one of the many terms that really needs to be regulated--that these terms on these labels really need to be regulated. "Standardized" can be used for anything; "potency" can be used for anything.

I'm out of time, but I just wanted to say that you do have a lot of power on the labeling right now, and there's a lot to do on products that are currently marketed. We want to get unsafe products off the market and products with misleading claims should also be off the market. Thank you.

MR. LEVITT: Thank you very much.

Mr. Turner?

MR. TURNER: My name is James Turner, and I'm Chair of the Board of Citizens for Health.

Citizens for Health was very much involved in t\passage of DSHEA; generated a significant number of the million signatures that were sent to Congress, and has been one of the contributing plaintiffs in the Pearson case; and also generated 175,000 comments to FDA on its structure/function proposal.

We felt very strongly that changing the definition of disease was not contemplated by DSHEA, and we also feel very strongly that that regulation should be withdrawn, and suggest that any difference between the definition of disease prior to the passage of DSHEA and now would consider to be something worthy of further legal action.

Citizens for Health is committed to the four basic rights of consumers that were announced by President Kennedy in 1962: safety, choice, information and participation or access. We believe that the construct of the issue for dietary supplements is that choice and safety are in tension, and information is the primary tool that can help us balance those in an effective way.

And so in virtually all instances where Citizens for Health has participated in a public debate, it has been about enhancing the information available on a product--in this case, the product category of dietary supplements. So we believe that the number one thing to do is to work vigorously on information issues.

I've been involved in FDA issues since 1968. I've been involved with the Food Safety Council, which was a group of consumer and industry people, to work on food safety questions in the NANDA dietary supplement area, and I was involved with the nutrition dialogue that was set up between industry and consumers onnutrition labeling. We believe strongly that that kind of a process would be extremely useful here--again, focused on information--to help us work our way through the choice-safety dichotomy, or the choice-safety tension.

Specifically, we are extremely concerned that FDA--we would like FDA to refrain from arguing that it does not have authority over regulating dietary supplements. It has a lot of authority that has not yet been used. We are strongly in support of working on good manufacturing practices regulation. We believe that's very important. We think that the adverse reaction report on dietary supplements needs to be greatly improved. And we would like very much to see a process like the ones I've mentioned be used to do that. There is a major role for all of the stakeholders to be involved on an ongoing basis in working out what we believe are the crucial issues here: information strategies.

Specifically, we feel--and urge--that the FDA not appeal the Pearson case. We don't see any need to do that. We believe that you could move forward and do the definition of "significant scientific agreement"--again, in the kind of process I'm suggesting, and develop a caveat program; something that will say the kinds of comments about the use of information that is not definitive, as the court suggested. We think it's an important aspect of working out how information can be used in this field.

In the 30 years or so that I've been working on these issues, I've heard repeatedly, from day one, the concept that everything is not black and white; that FDA, or anyone else, can't draw a line and say "all the things on this side are good for everybody, all the time, and all the things on this side are bad for everybody all the time. It can't be done. "There's an area where some things fall--they're always good for everyone. And there's an area where some things fall, and all things are bad for everyone. But there's this large area in the middle.

In my experience and observation, both in studying the history of FDA, and being involved with it specifically since 1968, there has been a tendency on the FDA in dealing with dietary supplements to group all questions that are in the gray area--and to treat all questions that are in the gray area as if they were in the black area. That is the source of almost all of the difficulty that has gone on, actually, since at least 1962, and perhaps before, in the FDA's activities. It's been a--it's an enormous, costly, unpleasant social battle that's been under way.

And I'm going to take--I'm going to answer your last question right now and say what I think I would like to see as the outcome of the year's worth of work. And that is that the contentious battle that has been going on between a segment of the public and the FDA be moved away from the courts, and away from the Congress, and into processes where all of the balancing of choice and safety can be worked through, and a process that will allow all the stakeholders--consumers, producers, health groups, individuals--to be involved in shaping how we are going to talk about this category. And as Dr. Fugh-Berman has said, the category contains all kinds of things in it. So we may have to do a lot of different kinds of modulating and so forth.

But we believe very strongly that an information strategy that preserves choice and preserves safety is the goal that we should work toward. And the courts and the Congress are refined enough to make those kinds of subtle choices without the help of the kind of process that I'm talking about with the participants I've mentioned.

Thank you very much.

MR. LEVITT: Thank you.

Irene Heller, from CSPI.

MS. HELLER: The Center for Science in the Public Interest appreciates this opportunity to present our views on developing an overall strategy for achieving effective regulation of dietary supplements under DSHEA.

CSPI is a non-profit consumer organization supported by more than one million members, that has worked since 1971 to improve national health policies. My presentation will highlight recommendations which are explained in more detail in our written statement.

First, the FDA should ask Congress to establish a research program at the National Institutes of Health to evaluate the safety and efficacy of dietary supplement ingredients.

Second, the results of the research should be used as the basis for FDA determinations that particular supplements are safe or pose a significant or unreasonable risk, and specify appropriate and inappropriate labeling claims.

Third, the research program should be funded by an industry user-fee.

We also urge the FDA to take enforcement action to ensure that foods or drugs are not being marketed as dietary supplements to avoid regulatory controls that apply to those products.

The recent flurry of consumer warnings on dietary supplement ingredients, such as GBL, and herbal Fed-phen, and the proposed rule on ephedra, underscore the need for FDA to have solid safety and efficacy data prior to the time a dietary supplement ingredient is marketed. We there urge the FDA to request that Congress mandate a research program, paid for by the industry, that would systematically review the safety and efficacy of dietary supplement ingredients. Vitamins and minerals known to be generally recognized as safety and effective, and whose role in maintaining health is not the subject of controversy within the scientific community could be exempted from such review.

The results of the review will alert both the FDA and manufacturers to dietary supplements that should not be marketed, or that should only be marketed subject to certain regulatory controls. The results of the review could also be used to support health claim petitions under the NLEA. The review could be modeled on elements of the over-the-counter drug review, which determined whether particular ingredients within a given class of drugs are generally recognized as safety and efficacy, or the GRAS review of food additives. While those reviews were slow and far from perfect, they nevertheless demonstrated that comprehensive reviews of entire product categories are feasible.

The NIH would be the best entity to conduct and supervise this research. It is the premiere research institution in the United States dedicated to helping prevent, detect, diagnose and treat disease and disability. It both conducts research in the laboratories of its 24 separate entities, and supports research of non-Federal scientists in universities, medical schools, hospitals and research institutions.

The specific NIH institute that has expertise relating to a particular dietary supplement ingredient should either test or supervise the testing of that substance. For example, the National Institute on Aging is currently working on a research project on the effect of ginkgo on memory. The National Institute of Arthritis and Musculoskeletal and Skin Diseases would be the appropriate agency to test dietary supplement ingredients designed to promote healthy bones.

The Office of Dietary Supplements, which was established DSHEA, should be given sufficient funding to coordinate dietary supplement research; at least the five million that Congress authorized, but which has never been appropriated. Under DSHEA, ODS has been designated as the principal advisor to FDA on dietary supplement issues, including safety and claims. Congress specifically directed ODS to compile a data base of scientific research on dietary supplements and individual nutrients, and to coordinate NIH funding concerning dietary supplement research.

The research program itself would be funded through fees assessed on dietary supplement manufacturers. These fees would be based on an appropriate criterion, such as market share or annual sales, and waivers and fee reductions would be available for small businesses. The funds collected would be distributed in the form of research grants.

This is an exciting time in the dietary supplement and food industries, as new discoveries offer the promise of significant health benefits. But consumers need scientifically sound information about supplement ingredients if they are to make informed purchasing decisions. We therefore recommend the creation of an NIH research program that will study the safety and efficacy of dietary supplement ingredients and issue findings on which the government, industry and the consumer can rely.

Thank you.

MR. LEVITT: Thank you very much.

I wonder if I could pick up on--Irene, your comment, and ask the other two if they have additional or different ideas on how we could get the research that's needed on a lot of these products done and evaluated so the results can be available to consumers.

DR. FUGH-BERMAN: Well, I think the first thing is to be aware of how much research has already been done. There is a huge amount of research that's already been done on botanicals, for instance. And people have already noted that vitamins and minerals, there's also been a huge amount of research done. So, it's really important to have--to evaluate, to have access to and to evaluate that data. You have to know what's out there before you can identify gaps.

MR. LEVITT: Mr. Turner?

MR. TURNER: I think that an approach such as been suggested makes a lot of sense. I think there are some things to think about carefully. Both the examples that were cited dealt with generally recognized as safe--generally recognized as safe standard. That standard is a clear, defined standard to build a program around. It would be very important if there was going to be a review in the NIH, that a standard of a similar nature, and what, would argue, would spell out "significant scientific agreement" as a standard, and do something of that kind of review might make sense.

The problem is, however, more than just the research. The context of how the research is evaluated is equally important. So that--you know, we've strongly argued that "significant scientific agreement" should be made concrete so that everyone understands what it means.

If that were done, and there were such a program, the second problem is that the outcome of that program should not be, in my opinion--and part of our argument--should not be a yes-no program; "if you don't have enough science, you don't get on the market. "That isn't an appropriate way to do it. The appropriate way to do it is to evaluate the relationship between the science that exists, create the risk-benefit ratio dynamic that we're talking about in all of these issues, and then decide how you want to proceed.

Again, that means--wefeel strongly, from Citizens for Health, that those things which pose a serious problem should be the most severely restricted, and those things which don't pose a serious problems should be the least seriously restricted--even if we don't have firm, clear evidence of efficacy.

MR. LEVITT: Thank you.

Margaret?

MS. PORTER: Yes. Dr. Fugh-Berman, you, in addressing the structure/function rule--if I understood you correctly, I understood you to suggest that the least the lines that the Agency attempted to draw, and the proposal--you were concerned that they were not workable and would lead to subterfuge, I think was your word.

I'd be interested in the comments of any one of the panelists on sort of alternative ways of addressing the variety of claims if the Agency's structure/function proposal has the concerns that you had identified.

DR. FUGH-BERMAN: Well, I think for products for which there actually is evidence of efficacy, that there should be an independent expert panel that determines what level of evidence there is, but that there--you should be allowed to make a claim if there really is good evidence for it. But you can't extricate that from determining the quality of products; that right now, you know, if you put "ginseng" on the product label, you don't know if it's ginseng root, ginseng leaf; often Latin names aren't on it, let alone any other sort of information. And I think there's a real role for the Agency in spot checking products that are on the market; that other countries that regulate botanical medicines, particularly, do check products. IT's very important to see, you know, what the level of active ingredients are in them.

But--I've had a patient, for example, who was taking St. John's wort every day, and I asked her why she was taking it--it's indicated for depression. She wasn't depressed, but because the label claim says "Supports emotionalwell-being,"[laughs]she just thought it was a good, sort of general tonic. So it can be very confusing to consumers.

MS. HELLER: I'd like to follow up on some comments that were made this morning, as well as now. And I think there's a real need for consumer perception study to determine how consumers view these claims; whether the consumer really can distinguish between a structure/function claim or a health claim, because there are different consequences and regulatory requirements for each of those. And if a consumer thinks that the amount of scrutiny that a product that undergoes a health claim procedure is the same as something that's a structure/function claim, the consumer is greatly misled. And I think we really need to do this survey. I think it would also help in light of the Pearson decision, if that sticks, because to the extent FDA can document that disclaimers don't work; that consumers are very confused, then FDA will have more authority, I think, to just regulate things so that consumers can understand them. And that's the point of what FDA should be doing.

MR. TURNER: The problem of drawing the line between structure/function claims and health claims is a problem of categorization. And I'm not sure that it helps actually solve any of the regulatory problems that we're facing--that distinction. It happens to be where the law settled out in the last round.

But what's happening is, in a general societal way, we're going from very broad, clearly understood categories--basically, originally, food and drug, and moving systematically through a differentiation. So that things that were clearly one or the other of those concepts, are now confused, or partake of both of those. Some things are both foods and drugs. And the distinction that first was used to distinguish those was the claim made. So lots of energy was brought in on what are the claims.

But it seems to me that we're going to go through a series of categorizations, and I think that the disclaimer piece is one of the tools that's available. That's why Citizens for Health supports it. If something is not harmful, and there is some evidence supporting its efficacy, we are arguing that there should be a disclaimer that says, "FDA has not yet established that this is effective"--it would be safe, but "this is effective for the claim. However, preliminary data suggests that it might be. "And that's the three-tier label that we've petitioned for, and we've argued for in Pearson and so on.

The idea is that in the societal moving of things, things are breaking out into sub-categories. Once we get into the dietary supplement category, really, it makes relatively little difference about a hormone, whether it's making a structure/function claim, or a health claim. It poses the same safety problem. So that that distinction doesn't help us a whole lot.

MR. HUBBARD: I'd like to keep going with this. Dr. Fugh-Berman has suggested that these products, while they may have efficacy, also have safety issues. And I assume you're not saying that those safety issues rise to the level of being a significant or unreasonable risk that would require FDA to ban them, but rather --

DR. FUGH-BERMAN: Some of them absolutely do. Comfrey should be banned; herbs containing pyralizadine alkaloids should be banned.

MR. HUBBARD: And do you think we at FDA--there's enough evidence out there that comfrey should be banned?

DR.FUGH-BERMAN:[Nodding affirmative].

MR. HUBBARD: But you did--I think you said that St. John's wort and others have some use. And so are you suggesting that they, in fact, be regulated as drugs, with a risk-benefit analysis?

DR. FUGH-BERMAN: No. Botanicals need to have their--they need to have a separate kind of regulation. They span the spectrum from food to drugs, and--well, just to use an example, for instance--soybeans have endocrinological effects. There are many soy-based foods. Then there are soy foods that are enriched with genestein, which is an isoflavone that's derived from soy. Then you can also go into a health food store now and buy genestein 100 milligram capsules. We have no long-term safety data on taking purified, isolated isoflavones over long periods of time.

We do have pretty--we have indirect, but pretty substantial indirect safety data on eating soy food. So they should be in different categories. Tofu should be in a different category than purified genestein capsules.

With botanical products, they have to be regulated as botanicals and, you know, I think that we should take some lessons from other countries that have a lot of experience doing this. But they're their own animal--or their own plant, and they really have to be regulated differently. Because some of themare drugs. You can isolate drugs from plants. Some of them are ground up plants. And there's a whole spectrum in between. And right now there's no regulation of even what the terms are. So that when a manufacturer puts "standardized" on a product, it can mean "We say there are 50 capsules in the bottle, and there are 50 capsules in the bottle. "It doesn't really mean anything.

MR. HUBBARD: Well, let me ask Mr. Turner, then--if some of these products, in fact, have some health use, and structure/function or other sorts of health use, but are not universally safe, how does FDA go about--is that a labeling issue?

MR. TURNER: The issue--when you say--there's a serious problem about things which are essential for some people and unsafe for others. And it's not a problem that is only in dietary supplements, it's in a lot of areas.

Our argument is, first of all--first of all, from Citizens for Health's point of view, we think FDA should put substantial amounts of its resources in this area on figuring out the categories. I think I agree with what Dr. Fugh-Berman has said: that there's a series of--there's a whole bunch of things in this category that are different, and require a different way of being looked at. And I think that that's an important step that we need to go through.

The first step that I think FDA researches are useful for is safety questions. I think those are the most important single questions that need to be dealt with. So that if we look at safety questions, and we find things where there are safety problems--and they could be small safety problems to large safety problems, FDA needs to look at that and figure out, for example, where there is enough evidence to create an opportunity to take something off the market that shouldn't be there. That is more important as a first step in working this all out than figuring out the efficacy piece.

The labeling part of it is: for those things which are not in the category that say we can show that these things are unsafe--in that category--those things--I don't think FDA has the authority to take them off the market. But I do think it has ample authority to guide people toward the proper use of these substances, again if words that are there are given some kind of a meaning that everybody can share as being the meaning of what those words are. And I agree with the statement, for example, about "standardized. " Those kinds of words need to be useful to help people work their way through a set of categories that have--that are safe but we don't know how effective they are.

The policy problem is that if you say anything that doesn't have a full scientific evidence of efficacy that meets the FDA definition as it currently stands; if you say anything that doesn't meet that category is going to be regulated more strictly by either being kept off the market, or being confined to what it can say, the result is that many things are dumped into the same category which have all kinds of different meanings. So that you end up with people not being able to work their way through the market. And I'm arguing--we are arguing--that FDA has the ability to help shape that--taking out those things which are unsafe--it has the ability to shape the way consumers balance safety and choice around whatever issue that they particularly are looking at.

MS. HELLER: I'd just like to add one more thing. I think in the discussion of safety and efficacy we've forgotten that there are some safety issues under the rubric of "efficacy. "For example, if someone's taking a dietary supplement to prevent breast cancer and they actually have breast cancer and should be seeing someone for that, and they're not seeing someone because they're relying on this dietary supplement, that's really a safety issue, because it's preventing people from going to get the treatment that they need, and it's causing them to make unsafe decisions.

So perhaps that, in considering efficacy issues, there should be a categorization as to products which are used for very serious diseases--let's say cancer or heart disease--and products which, if they have no effect, it's not going to hurt anybody; you know, they're designed to make you're fingernails grow longer.

So I think there needs to be a distinction there.

MR. LEVITT: Dr. Yetley?

DR. YETLEY: You've all discussed safety as one of your priorities that you think the Agency should focus on. Given the range of tools and approaches and resources that the Agency has available to it, how should the AGency proceed in terms of dealing with safety issues? We can do it by regulation. You can do guidance. You can do other means. Do you have some particular advice for us on how to approach safety issues?

DR. FUGH-BERMAN: Well, I think--well, yes, it has to be--the Agency has to be familiar with the literature so that it knows what to go after. I think that its--one of its roles should be to set quality guidelines. I don't know whether those should be regulations or guidelines--but to set standards of quality for various dietary supplements. It's really important, especially in the botanical area. And there's quite a lot of research in that area.

But the main thing is going out into the stores, buying products and analyzing them, and publicizing the results. I don't think it should just be up to Consumer Reports, and CSPI, and some of the other groups that have done independent analyses to determine that a number of ginseng products on the market contain no active ingredient, or some of them actually contain ephedra instead of ginseng--that sort of thing. There's a lot of misidentification of plants; there's a lot of contamination. There's a big problem with mixing drugs in with herbs, particularly in preparations that are imported from Asia.

There's a lot of different issues out here, and there are safety issues in products that are on the shelves now.

MR. TURNER: In addition to going out to the market, the FDA--it seems to me, again, following the basic point that we are pushing from Citizens for Health, which is a dialogue process, there is a lot of information available in the dietary supplement community which people, if they had confidence in FDA would be willing and happy to share. It's very difficult, however, if the agency is looked upon as an agency which is constantly going to after whatever it can put in jail, or some comparable thing. It would be much better if we could have an open flow of information. It's not only products that have ginseng that has ephedra, but there's ephedra that has amphetamines. I mean that's another issue.

It would be useful for the FDA to organize an ongoing communication system. Two things would help develop that possibility, I think, very strongly. One would be the development of good manufacturing practices, and I think those could be expanded to some extent to include some of the standard ideas that Dr. Fugh-Berman has been mentioning. You could create potency and name of source and so forth as part of that.

And then, secondly, it is very important that the Agency seriously look at the adverse reporting system, because it's coming in now in a way that is very undifferentiated, very unclear; it's being used by competitors to fight out marketplace battles. And it's really, frankly--to be very honest with you--it's an embarrassment. And it would be useful if--and we, of course, and I'm sure these groups and the ones that were here this morning, would be more than happy to participate in a dialogue about how to make a system like that work. So, for example, if we got the adverse reporting system working effectively, and everyone had confidence in it, we, and I believe others, would encourage all of the people,e that we are involved with, in terms of practitioners and sellers and other people in the community, to participate in that, and to make information available. The way it's coming in now, however, it's undermining confidence rather than building confidence.

MS. HELLER: I think it might be useful to publish a Federal Register notice that lists the dietary supplement ingredients with which FDA has concerns, and to allow the public to comment on those particular substances, and FDA can then evaluate the evidence. And it would be helpful if down the road FDA could publish a book that would be available in health food stores so at the point of sale, consumers could see what type of rating a product had; you know, if it's safe but possibly effective; safe but definitely effective; unsafe.

MR. LEVITT: Thank you.

Dr. Bowen.

DR. BOWEN: Dr. Fugh-Berman, you mentioned in the context of botanicals that Commission E could be used as a model. Would you further elaborate on that comment?

DR. FUGH-BERMAN: Do you want me to explain what Commission E is, or --

DR. BOWEN: No. I know what Commission E is, but you could explain it briefly, and then tell us how you think that could be used as a model.

DR. FUGH-BERMAN: This was an independent group that was set up by part of the German federal health agency that was composed of physicians, pharmacologists, pharmacists, members of the industry and consumers to evaluate information on herbs, about--more than 300 herbs and herbal mixtures were evaluated and monographs were written which were used as product labels in Germany.

They have--they're sort of like consensus-conference kinds of documents. They're not referenced, but they are based on a huge amount of clinical and scientific data. And I'm not saying that we should adopt them wholesale, but it's a useful model, putting together a group that is familiar with botanical research, etcetera, to evaluate information; they come up with either positive or negative assessments based on the benefits--known benefits and known risks of botanicals, and to publish those. I think it's something that we could, if not exactly duplicate, but do in a more scientifically referenced way with a group that's familiar with the research. And I think it could be really useful.

Because there's a lot of benefits in dietary supplements, and there is quite a lot of studies showing benefits for some of these. But right now there are so many products on the market that are entirely ineffective because we have no regulation as to quality. So I really think it's--you know, there's a dual issue around safety and around quality, and we need to address it in a pretty comprehensive way.

MR. LEVITT: Okay. Thank you.

On my one question of "a year from now," I think some of this has already been answered, but I'll et everybody go down one more time and amplify, or say you've already said it.

Ms. HELLER: Okay. Basically, repeating what I said before, we need to have a systematic review of the safety and efficacy of the various dietary supplements.

MR. TURNER: I think that a substantial amount of progress could be--you know, I've already said about moving it out of--moving it into a dialogue and out of a confrontational forum--but a very substantial amount of progress could be made if the agency put energy into working through the quality questions. A lot of the issues would become much clearer if that were to be done.

DR. FUGH-BERMAN: Clear, accurate, comprehensive labeling of every dietary supplement on the market, and periodic analyses by FDA.

MR. LEVITT: Thank you. What would we do in the second year?

[Laughter.]

MR. LEVITT: Okay. Thank you all very much.

As we're moving between panels, we have--the next panel we have Dr. Gary Huber of ANA. We have Dr. Steven Dentali of Rexall Sundown. And we have Antonio Martinez of Neutraceutical Initiative.

On your agenda you have an additional name of Paul Simmons. My notes tell me that his views were--he is not appearing--that he's not here today. Is that right? --but that some of his views were covered this morning.

Thank you. Well, an efficient group. Let's go right to Dr. Huber.

DR. HUBER: Thank you for the opportunity to be here today on behalf of the American Nutraceutical Association, whose members are health care professionals and consumers.

The American Nutraceutical Association is a non-profit alliance of individuals with a shared interest in the science, technology, marketing and production of nutraceutical products. The ANA was established to develop and provide educational materials and continuing education programs on nutraceuticals for health care professionals and for consumers.

We want to emphasize that we believe we currently stand at a most serious confluence of important forces coming together in the nutraceutical world. This is a critical crossroad for the consumers of nutraceuticals. What are these critical factors that we should consider?

First, unprecedented numbers of Americans are now consuming nutraceuticals and other dietary supplements. There is every reason to believe that they will continue to do this in the future. For the most part, they are doing so with a blind trust in those who manufacture and distribute these products.

Second, United States' health care delivery systems are changing. They are not stable. They remain in enormous flux as we search for a means of health care that will work and that is affordable. In this period of change, increasing numbers of Americans are searching for more control over their destiny of their own health. They also want more freedom to control their own health care. One way that Americans at all levels are fulfilling their quest of these objectives is to turn to nutraceuticals and dietary supplements. In doing so they want to achieve as much good health as possible. They want to live as long as possible, and they want to be free of the rages of chronic illness, physical disability and mental impairment for as much of their life as possible. Faced with a medical care system and a pharmaceutical industry that has focused on disease, not on prevention, they are turning to nutraceutical products and dietary supplements in their quest to fulfill these needs.

Third, those who manufacture and distribute nutraceuticals and dietary supplements can now market their products without adequate levels of external accountability for quality or safety.

Fourth--and finally--a major force adding momentum to the potential conflict resulting from the confluence of these movements is the fact that the unremitting growth of the nutraceutical industry seen over the past few years appears to be slowing and in some cases plateauing. As a consequence, the nutraceutical market is becoming, each and every day, more competitive. Without control, and without accountability for quality or safety, the opportunity to follow the first rule for those who care about the health of the people they serve--to do no harm--has a potential to be diminished and lessened under these circumstances. We need a reliable, independent and intelligent adverse event reporting system.

In the perspective of these considerations, we need therefore to ask some important questions. Can nutraceutical products be manufactured under current good manufacturing practices? Does a nutraceutical product contain a standardized extract that has been validated by scientific and clinical studies? How do the consumers know that the products they take actually contain the required dosages of ingredients required to produce the desired results as promised in marketing materials provided by the manufacturers and distributors? Most importantly, is the product safe, and does the product have integrity? Without clear and acceptable answers to these questions, the safety and integrity of the nutraceutical products and the dietary supplements will be compromised.

What can we do? The pathways of responsibility leading to a good solution must be shared. The American Nutraceutical Association recommends attention be given to the following priority issues concerning the consumer's safety.

One, quality assurance. Manufacturers and distributors of nutraceuticals and dietary supplements need guidelines for current good manufacturing practices and production standards to protect the consumer. The FDA is the logical source to develop these guidelines and with help from the manufacturers of supplements and from the trade associations who represent their interests. Ideally, the nutraceutical industry should be responsible for somehow regulating itself through a third-party validation mechanism. If the nutraceutical industry does not satisfactorily self-regulate, regulation must come from without.

Two, standardization. This is a complex challenge, but nutraceutical products must be standardized. Both the consumer and the manufacturer will benefit from products that are standardized, reliable and dependable. Nutraceutical products must have a reliable consistency.

Three, product stability. Most nutraceuticals are derived from natural sources that are prone to degradation. Once active components are standardized, their stability and shelf-life can be determined. Nutraceuticals of the future must be labeled with expiration dates and recommended storage instructions.

Four, bioavailability. What are the pharmakinetics of nutraceuticals? What are their interactions with diet and with medications?

Five, clinical validation is an essential and critical priority for nutraceuticals. Safety and clinical efficacy are definite consumer concerns.

People are going to continue to buy and consume nutraceuticals --

MR. LEVITT: Excuse me--if you could try to summarize, please?

DR. HUBER: The consumer needs to be able to trust health care professionals to whom those nutraceuticals most want to turn and with reliable knowledge about nutraceutical products.

In summary, the consumer and health care professionals need to know that nutraceuticals are safe, and that they are produced and marketed with integrity.

Thank you.

MR. LEVITT: Thank you very much.

Next would be Dr. Dentali:

DR. DENTALI: Thank you, and thank you for having this forum here today.

I guess I should say a little bit about my background; that I was trained as an herbalist, a pharmaceutical scientists and a pharmacognicist. I've served on several--a few GRAS committee efforts regarding botanicals, and I was a member of the special working group on ephedrine safety in foods.

My position at Rexall Sundown is a new one. I've been there two months. My understanding is that Rexall Sundown is the largest supplier to the mass market of dietary supplements and also botanical products.

I want to thank Dr. Fugh-Berman and Mr. Turner for making the point that botanicals are different. Because, really, when you look at dietary supplement categories, there's basically two: botanicals and all others. That's because there are special concerns that are brought up when you're dealing with botanicals, and that's really what I'm going to speak about today.

Although DSHEA will help in providing consumers of information on and access to safety and efficacy dietary supplements, it really does not adequately address many, if not most, when dietary supplements are of botanical origin, in my opinion. Indeed, the DSHEA Presidentially-appointed commission on labeling spent a considerable amount of time and effort attempting to resolve issues surrounding the labeling of dietary supplement of botanical origin.

Many assumptions regarding dietary supplements really don't fit. It is a--as they are themselves a huge mixture of components--dietary supplements span many different categories, you can draw the line pretty much anywhere. If you want to take different examples, you can make whatever case you would like as food, dietary supplement or drug.

The World Health Organization recognizes that most of the world's population relies on botanical products, or what are known as "traditional remedies" for much of the health needs of the world. In fact, recognizing this importance, they published a guideline on their assessment, and this guideline helps to ensure the safe use and manufacturing of botanical materials used as traditional remedies. So really what I'm suggesting here is the category of "traditional remedies," or something such as that.

In the green handout that was out front was a headline, "FDA is Considering a New Category. "I apologize, I don't have it up here to refer to. It's not within CFSAN, but that idea is obviously receiving more and more attention for a good reason.

While many developing and developed countries have an extensive monograph system for traditionally-used botanicals, we in the U. S. cannot, in conjunction with a product, educate consumers as to the most basic of western concepts--honorable action. Indeed, practically all the modes of action that I was taught regarding traditional uses of North American herbs cannot be used without the corresponding product being considered a drug.

Although traditional remedies are often understood to have a broad range of actions appropriate for a myriad of conditions, the present structure limits what manufacturers can share regarding what is considered common knowledge among many peoples. This traditional remedy category--this establishment--I feel falls into the long-haul category but, however, its implementation brings into focus many of the issues that you deal with, such as boundaries, safety and labeling issues--those that are of immediate concern regarding botanical preparations. In other words, this or a similar category is needed for a rational and effective regulatory foundation for dietary supplements of botanical origin.

The solution resides, I believe, in part, to a well-developed monograph system created by expert committees, the members of which are uniquely qualified to assess the botany, historical use, chemistry, pharmacology, safety and efficacy of herbal materials. The best I've seen in this regard is the American Herbal Pharmacopoeia, not to dis the USP. And, by the way, the American Herbal Pharmacopoeia is a non-governmental pharmacopoeial system, so there actually must be two.

Botanicals are a special case requiring special botanical expertise and treatment. This issue deserves expert advice input from botanical experts, both inside and outside the industry. In fact, I don't think you can do it well without it. So I think there's an area where it will continue to appear as something that deserves attention and I believe that the traditional medicines category is one way to address that.

Thank you.

MR. LEVITT: Thank you very much.

Mr. Martinez.

MR. MARTINEZ: Thank you very much, and good afternoon.

I'm happy to be here on behalf of the Nutraceutical Initiative, which is an outreach project that's collaborating with the Foundation for Innovation in Medicine in Cranford, New Jersey, which is headed by Dr. Steven DeFelice, the gentleman who actually coined the term "nutraceutical. "

I'm also here as someone who was intimately involved with the development and passage of DSHEA, and I'm happy to see my colleagues Mr. McNamara and Mr. Turner here also--individuals who were intimately involved with the formulation and the development of that legislation.

We are at a state where the confusion that exists in the marketplace really begs a question as to whether the AGency has the right kind of tools in order to address them. At its most basic level, we're really talking about safety and information questions. What we have now in the marketplace is a condition where price is driving the marketplace when it comes to dietary supplements, nutraceuticals, functional foods--whatever you want to call them--should be research-driven marketplace.

Unfortunately, there are not the kinds of incentives that promote the development of good research-driven marketplace. Also, we have a new aspect to this whole question--and I can speak to this because I represent--in addition, I was an attorney in a managed care organization that would like to cover these kinds of products, but have great difficulty due to the fact that there is not yet any mechanism that critically evaluates these kinds of products, short of going the drug route, which is not a practical matter for most of these products.

I know we don't have a lot of time, so I'm going to jump a little bit. One other point I want to get in before my five minutes is, when it comes to enforcement, we'd like to see the Agency begin some type of proportional enforcement, where if there are labeling problems with a company out there with a product with bad labeling, the Agency should take action to take care of that; act quickly to remove unsafe products.

What the Nutraceutical Initiative would like to envision as a solution to this problem is unlike what is suggested by the Center for Science in the Public Interest, which is a government-driven, research-based approach, we would like to see, very similar to an Orphan Drug Act enacted by Congress, but dealing with functional foods and dietary supplements. In fact, there is draft of that legislation that is circulating on Capitol Hill, and while we had hoped that this legislation would have been introduced this springtime, it is my belief that it should be introduced in the Congress by the summer. But it will not be introduced without consulting with the Agency, and we will be moving along those channels shortly.

But ultimately what we want to see is the company that does the research ought to get a reward, and they ought to be tell the whole story--the whole truth--about their products, and they should be able to do that exclusively for a time--set period under the law. One of the conditions in return for that would be that the manufacturer would engage, and be responsible for post-marketing surveillance of its products, and that way you would have a phenomena going on in the marketplace where you would have a tested product, with a--and with its ingredient, and its formulation, and you will be able to actually get the kind of data that will answer safety-related questions and at the same time the marketplace will change because if there is at least one approved product out there, the competitors--sort of like a generic situation--will try to come as closely and match the tested product. Thus we'll have a situation where the bad products--the junk that's out there--will not be able to withstand the market forces there, plus you'd be able now to have a situation where the mainstream health care professionals will now be able to look to something; and patients and people at risk--there are different types of sub-groups of consumers. And we need to have the right kind of public policy that accomplishes that.

So we look forward to working with the Agency; working with the public, working with industry to accomplish this. It's quite impressive to see how this whole process has matured, and we certainly expect to be in the middle and involved with this.

Thank you very much for your time. I'll take your questions.

MR. LEVITT: Thank you all very much.

Let me begin with just kind of a nomenclature question. Two of the three speakers, as well as the title we assigned is called "nutraceuticals. "I think if we all read through the act, we wouldn't find that term.

Help me understand, within the legal terms within the statute of dietary supplement, conventional food, food additive, drug--within those terms, where does nutraceuticals fit?

DR. HUBER: Unfortunately, I don't think there's an agreed-upon definition, so one gets a whole series of definitions, and that really, I think clouds the issue.

MR. LEVITT: Okay. But in your mind, when you stood up and said, "I'm here to speak about nutraceuticals," what were you referring to?

DR. HUBER: A naturally-occurring product that has some biological activity that will affect health.

MR. LEVITT: Okay.

MR. MARTINEZ: As we are looking at "nutraceutical," I'll work off of Dr. DeFelice's definition, and also what is being looked at on paper from a legislative standpoint. It would be anything that--a substance that is found in food, or food as itself, that can provide a health benefit that we have further defined as--that can be used for the prevention of disease, the reduction of risk factors associated with disease, and for the management, from a dietary standpoint, of disease.

DR. DENTALI: I'm really glad I didn't mention the word.

[Laughter.]

MR. LEVITT: And just following up to the first two speakers--not that that wasn't clear--what--give me some sense of proportion of the products you're talking about with the dietary supplements? 50 percent? 20 percent? 100 percent? 90 percent? Versus foods?

MR. MARTINEZ: I would argue that both--you could apply this definition to either.

MR. LEVITT: No, no--you're misunderstanding my question.

MR. MARTINEZ: I'm sorry.

MR. LEVITT: Of the universe of products you're talking about --

MR. MARTINEZ: Mm-hmm.

MR. LEVITT: --how many of them are dietary supplements?

MR. MARTINEZ: Oh--I would say at least more than half, to two-thirds.

MR. LEVITT: Okay.

MR. MARTINEZ: The dietary supplements have been further out there--I mean, functional foods are now just coming into play.

MR. LEVITT: Would you agree with that

DR. HUBER: Without a clear definition I don't think you can have precise numbers.

MR. LEVITT: Okay. But what--you would say a large proportion are dietary supplements?

DR.HUBER:[Simultaneous discussion].

MR. LEVITT: Yes? Okay.

Margaret.

MS. PORTER: Yes. This is a question for Dr. Dentali, but others would be welcome to address it as well.

I heard you say very clearly "botanicals are different," and that under certain circumstances botanicals could be foods, or dietary supplements, or drugs. But I think I also heard you to recommend that claims not be used as the basis for deciding whether a botanical is a drug or a dietary supplement.

If I understood you correctly, I'd be interested in what other criteria you would use to draw those kinds of distinctions?

DR. DENTALI: I don't know if claims itself can work well enough the way are using them right now, without a traditional medicines category. I think that's one solution it provides--it may allow a vehicle to make claims and set them off so the consumer understands the distinction, if indeed consumers would.

The other answer is it would have to be done on a case-by-case basis. And I'm not trying to dodge the question. I've written--I've extensively reviewed the literature and written on safety on three botanicals; on Kava, on ephedra and on ginkgo--with a popular book being on ginkgo. And they're three completely different situations.

Kava, in fact, completely defines the cultures where it is still traditionally used. So I don't know if you can say if it's food, drug or whatever, but it's--and ephedra has a discrete traditional uses and not others. Ginkgo, the product that has been the most--the research has done on, is a semi-purified extract. So looking at uses--looking at historical use--intended use is certainly part of that. But I think you have to take it on a case-by-case basis and look at the totality of the information on what it is--what the historic use is and how it's being used.

MS. PORTER: Would either one of the other panelists care to comment on that question?

Thanks.

MR. HUBBARD: Dr. Dentali, your description of the monograph system sounds very much like the way we regulate over-the-counter drugs; and, of course the President's commission a couple of years ago recommended that we consider regulating botanicals because they are somewhat different in that way. Are you saying, then, that that over-the-counter drug model is more appropriate for those products?

DR. DENTALI: It's possible, if it's modified. I think that there are--I think you have--what we don't want to do is live in a world we've got to prove everything scientifically before we can use what we know by common sense works--unless there is common sense or science that shows us that we should treat it otherwise. Comfrey's a good example; comfrey root should probably not be taken internally in products. We have enough good science there for internal use of pyralizadine alkaloids that there's a serious question for safety. However comfrey leaf, the levels are much less; comfrey externally, I've found very little that helps for bruises and contusions as a poultice of comfrey.

So, if we have an intelligent monograph system that takes into account all the variety of--all the different--the word isn't coming that I'm looking for--something of that nature, but you would have to then expand it. I think we must not try and shove botanicals into an existing framework, but design one that is designed for them.

MR. LEVITT: Dr. Yetley.

DR. YETLEY: Well, Dr. Dentali just answered the question I was going to ask, so I'll have to think of another one quickly.

I think all three of you are suggesting that you want to find a way for many of these products to be marketed so that they are either useful in disease treatment or management of diseases. Do you see this as being under DSHEA? Do you see this as having to need another category, and why aren't you interested in existing categories? I'm thinking explicitly of Dr. Martinez's example of wanting something similar to orphan drug law. Why do you see that orphan drug law as it exists now would not work?

MR. MARTINEZ: Just simply because it's almost like if you look at the products that are on the market, they tell half a story. They don't tell the whole story. And manufacturers--it's a big semantical game with the Agency. I can tell you that as a private attorney, when I work with supplement companies, we're all--it's all about semantics, and coming up with a way that tries to stay within the boundaries which were set within the law when, really, I know what the--if a company acts, has done the research and know that its product can have a benefit for a particular disease risk factor, let's say hypothetically, they would like to have a functional way to communicate that information to the public. And that's what's missing. And we need to have something in place that would give an incentive for the companies to do that knowing that, hey, if I spend the money to do the kind of research, then my competitors aren't coming to come out the next day working off of my research, and come out with the same kind of product. There would be some kind of protection.

In exchange for that for a period of time there would be, you know, the kind of post-marketing surveillance and other things. I think this is something that we will sit down and further discuss with the Agency. I know there's interest on this in Congress about this, because I think we all want to resolve the controversies with dietary supplements, because they promise so much. You know, we've just got to come up with the right framework for that. And certainly the Orphan Drug Act is an example where incentives work; 5,000 orphan drug conditions. Before the Orphan Drug Act there were very orphan drugs. Since the passage now, over 15 years, we have over--almost 200 now, new orphan drugs to help people with orphan diseases. So that system does work.

MR. LEVITT: Excuse me. Just to clarify, if I may--and I know I'm violating my own rule. There's got to be some advantage to being the chair--is the Orphan Drug Act analogy, I clearly understood the idea of if you put the money and do the testing, you ought to get some exclusivity in marketing. That part I got. The Orphan Drug Act, of course, also works within a system of pre-market review for that. Do you envision that as part of the system you're thinking of?

MR. MARTINEZ: Well, in the draft that is out there there will be an actual--there will be an actual commission set up--established--that's overseen by FDA, but established out of the NIH. This commission would set up--working off of similar stuff that's been FDAMA--to basically, if a company does the clinical research, it puts together its best evidence, presents it to this body, the body will make ajudgment on it, and that judgment would be reviewed by the agency and the agency can add things to it--additional information, etcetera--conditions for the claim, and that claim would be exclusive to that holder for a time certain. And we believe that this will actually start shifting resources to research, which ultimately is what we need to resolve the controversies with dietary supplements and functional foods.

MR. LEVITT: Okay. Thank you.

Dr. Bowen.

DR. DENTALI: Could I follow up on that first?

MR. LEVITT: Please. Because we've got lot's of time.

DR. DENTALI: I want to say that I think we need to use all the existing categories, to whatever extent that they are useful and that they'll serve the purpose. And I still think outside of that we may still find--indeed, I believe we will find cases where it doesn't work. And I think we need to balance the strength of the substantiation on the claim that's being made. If someone wants to sell a product that they're saying cures migraines, and that product is feverfew, I expect no less than drugs out there that have that same claim for that to be sold.

However, if there's a substantial body of traditional information--of which there is--to say that "many people report using feverfew helps prevent their migraines," and this is how it's used--and that happens to be true--that may be useful information for a consumer, if there's no safety issues, you know, of any type being involved.

So, you know, we have to balance the consumer information with the risk of using the product. Now, feverfew is a good example because it's the only product in North America that's used as a raw botanical for a drug indication--and that's in Canada. Dried feverfew leaf, 90 percent leaf material of a certain percentage perthenolide is approved for treating migraines. And it's under a traditional medicines category--excuse me, it's not. But Canada is another example of also traditional medicines category which has good and bad parts to it.

The unfortunate situation is that you need to look at what is--if you're going to use those clinicals in Canada for that indication, then what you're selling needs to be closely comparable to what was used in the clinical trials. So that's Canada's situation for that drug identification.

We may have a third situation here where maybe those--we don't think those trials are good enough to establish it as a drug here; indeed, we may not have that type of mechanism. But for consumers to be aware that maybe we want to just allow the Internet--but do manufacturers play a part in that? Does the FDA play a part in that? Is there a risk involved? Should this be useful information for consumers that people have traditionally reported this as effective, and let people try it.

We may find that a traditional category could be a good vehicle for providing information to consumers to increase access to safe, effective remedies.

So that's pretty much--it's the claims that's important that we balance that. I had another point, but I don't remember what it was.

[Laughter.]

MR. LEVITT: Okay.

Dr. Bowen.

DR. BOWEN: Well, I think the whole discussion here in the last little bit has raised a lot of questions for us, and I guess what I had heard was that you're thinking of some of the existing systems that we have to manage some of the issues around botanical drugs--drugs, food, dietary supplement, whatever part of that continuum they're on--and that potentially raises the question of is a separate system needed for that? And then, if so, would some of the review be pre-market for certain claims? Would some of the review for those products that are already used in traditional medicine--wherever--and then what those products were for those claims. And it's very interesting, and I don't think I have a question here, but it's interesting. It raises a lot of those issues.

MR. LEVITT: Does anybody want a further comment?

MR. MARTINEZ: I just think there's going to be sort of an amalgam of what you're outlining, where hopefully we'll have policy in place that will allow this kind of basic information to apply in general, much like what Dr. Dentali suggests. But for companies go the--you know, the extra distance here, that they would be--and that's going to be ultimately to the whole marketplace's benefit. Because once we have products out there that have been tested, and have been critically and scientifically evaluated, you will see the marketplace will change, because you cannot--if you know that you have something that works, the junk that's going to be out there will not stay out there, and you will then see an embracing and a utilization of this by the mainstream medical community. I mean, the bottom line is, the public is far ahead of the Agency, of the--you know, the marketplace is ahead of the regulators here, and we need to kind of bring this now into some kind of coordinated fashion from a public policy standpoint.

And there was some--there are tools in place, but of course we've seen the limitations, I think, of--for example, with DSHEA, with structure/function claims, and this--obviously we would need to go now to what the next step is. I mean, bottom line is people want to be able to tell the story about their products, but the whole truth. And we would look forward to working with the Agency in that regard.

MR. LEVITT: Very good. You folks are stimulating thinking.

Margaret Porter has one follow-up question. I have one follow-up, and then we'll do the run-down of "one item. "This is following up on Dr. Dentali's point that, yes, we still have some time.

[Laughter.]

You were courageous enough to stick your neck out and suggest that the traditional medicine system in Canada has--I think you said both good and bad parts to it. And since, obviously, you're suggesting that we look at those kinds of alternative systems to try to see whether there's something that we could learn from them.

I'd be curious as to what you would venture to say you think are the good parts, and what you think are the bad parts.

DR. DENTALI: Well, I think the good part is that it allows, basically, the familiarity that an herbalist has with traditionally used materials to be shared with the public, and to make those available.

One of the bad parts, and this--again, it goes back to how you're implementing things. If someone has a serious heart condition, they probably shouldn't be running off to take hawthorn. Now, there's very good--well, you know, we can talk about what's very good, and what research is available to show that hawthorn has discrete effects on improving cardiac function over a long period of time. It's effects are more, indeed, dietary supplement/nutritional in nature. Many of the compounds now that are falling under "the active compounds" of dietary supplements fall into very broad categories--sub-categories of flavanoids. So that hawthorn cannot be recommended for heart conditions maybe prevents the population from including it as part of their diet, which would possibly prevent a lot more heart disease from arising.

So, you know, whatever system we come up with, or philosophy we come up with--whether it be of medicines or regulations--there's always going to be outliers. So the more points of view we can have on a topic, the more likely we are to come to an enlightened regulations on it.

This comes to, also, with the issue of standardization--we tend to assume that standardization is a simple thing and beyond that awe tend to assume that it's measuring the amount of constituents. It is not. And the examples in the industry are a good way of how you can completely miss the point.

Standardization is the complete body of information and controls that guarantee a consistent product. And in many cases, not only do we not know what to measure, we don't even know how to measure it. What you guarantee is that you had the correct plant, it was grown properly, it was harvested properly, it was dried properly--which is the single most important part in determining the quality of the crude botanical material--and it was manufactured and processed properly. And again, indeed, these are the issues that the industry is grappling with in coming up with definitions.

Use of the word "potency," is one that's been raised before, and deserves proper attention.

So--but gaining the basic familiarity that's, I think, the benefit of a Commission E-type approach, that these things--these assumptions that we have of how to regulate and apply to botanicals oftentimes don't hold true when the details start being raised. What are we exactly talking about when we try to imply a pharmaceutical on to it that it doesn't fit. Not always, but a lot of the time.

So, again, wherever what we have works, we need to use it. But if there's areas where it doesn't work, we need to be open for creative endeavors on how to deal with that.

MR. LEVITT: I thank you--oh, you want to --

MR. MARTINEZ: Yes, one thing--just as a historical footnote, I find it kind of fascinating and sort of we've come full circle here is one of the factors that actually led to DSHEA was the fact that when the botanical industry requested establishing a botanical ingredients review panel, the Agency refused to do that. And that was one of the factors that led to the development and passage of DSHEA. Here we are now--here can see that the Agency is actually contemplating here, now what are we going to do have a handle with botanicals. So it's good that we've--there's sort of a listening now to that. So--just--it was a comment.

MR. LEVITT: Thank you. And I congratulate Dr. Dentali for not only answering Margaret's question but mine at the same time.

Why don't we then go through our last rapid-fire wrap-up. Again, looking a year from now, if I could ask people to try to focus in narrowly on one thing that could be accomplished a year from now, what would that be?

DR. DENTALI: The establishment of a category, and the expertise to provide us and the populace with a greater familiarity of botanicals so that we can use them in all appropriate ways.

MR. LEVITT: Mr. Martinez.

MR. MARTINEZ: A year from now I'd like to see a Nutraceutical Act being debated and under full consideration by the U. S. Congress.

MR. LEVITT: I guess that means there's nothing we have to do in the next year.

DR. HUBER: And what's been said all day long--safety, safety and safety.

MR. LEVITT: Yes--Bill Hubbard wants to make one quick comment.

MR. HUBBARD: I'd just like to say that your comments sound very much like these--you're not talking about these things as foods. I mean, DSHEA is for foods. You know comments very much lead one into the--trying to find a category that's appropriate for these products, that they have medicinal properties, they have some risks, they need to be properly used, potency needs to be established. And I guess I go back to my earlier discussion with you, Dr. Dentali, about OTC. Maybe the OTC model's not perfect or not, but somehow, you know, your comments don't lead me in the direction of saying these are food products that should be treated that way. These are a particular kind of product that should have some regulation, but also have benefits and usefulness and need their niche. And I think that--that's what's you're saying, right?

DR. DENTALI: No.

MR. HUBBARD: Okay.

DR. DENTALI: Only because there are perfect examples where they clearly are foods. Chickweed is an excellent example. I used to--as an undergraduate student I made salads pretty much where chickweed was half of it on a regular basis. So clearly that's a food. It's recognized as a food, it's used as a food. I don't know about claims for it's being used in weight-loss. Certainly any claims along that nature, they'd have to be evaluated. Dandelion greens--food. The list goes on and on. If we want to look at that category, there's a huge amount.

So it is a continuum, completely, where we could find examples and win an argument on either end of the story, and every place in between.

MR. LEVITT: Okay. Well, listen, I thank this panel very much again. Before you go down, let me just make a couple of announcements. We are going to take a 15 minute break and reconvene at three o'clock.

Before everybody runs out to do that, I have a message--or there is a message for Mrs. Joy Joseph. If you're in the audience, if you could Naomi Kulicob in the back of the auditorium--she's standing with her hand like this--she'll be happy to give you that message.

And, finally, if there are people who want to make a statement at the end of the meeting, please register outside and then afterwards I'll have the next speakers come to the front of the room over here.

Thank you very much. We'll see you at three o'clock.

[Recess.]

MR. LEVITT: Well, if I could ask for people's attention. If people could take their seats.

We are in danger of being on time.

[Pause.]

MR. LEVITT: We're ready to start the final segment of the day; what we'd like to call the homestretch.

We have two panels, and a small number of individuals who also have asked to speak. I believe that on our Consumer panel, unless somebody has just walked into the room in the last couple of moments, that one of the listed people, Phil Howry, is not here at the moment. If he's able to get here later in the afternoon we will definitely fit him in, because I know he's traveling from some distance.

But let me welcome up to the podium Fred Bingham and Richard Johnson, and we'll be happy to hear your presentations.

10: 25 As they come up--we'll continue, as we've done before, with each speaker making a five-minute presentation. AGain, once you're up here I can focus your attention in the front row, and you'll see a little sign that will come up with "one minute left," and a little sign that will come up when your time has expired.

We'll then subject you to hopefully friendly and constructive questioning.

[Laughter.]

And as this group is smaller, I hope it does not look like an unequal distribution of energy. But I'm sure you have very interesting things to contribute. And please step right up to the podium.

MR. BINGHAM: I'd like to thank you for allowing me to be here today. I'm delighted that this process is proceeding.

My name is Fred Bingham. I'm the Executive Directive of DAAIR. We're the largest HIV-AIDS Virus club in the United States. We supply low-cost and sometimes no-cost nutritional supplements to people with HIV and AIDS and other chronic illnesses. We have about 5,000 members.

This statement has also been co-authored by Michael Onstott, who is Executive Director of the National AIDS Nutrient Bank, based on the West Coast. And he'll be giving testimony out there on July 20th, I believe.

All right. All consumers of dietary supplements, including people with HIV and AIDS, have a right to expect that the products we use are pure and safe, and that they contain the substances claimed on the label in the amounts specified. Guaranteeing the safety of supplements and the accuracy of labels with regard to contents is the responsibility of the manufacturers and Food and Drug Administration.

Consumers also have a right to accurate, clear and non-misleading information about dietary supplements. Currently, however, there are only a handful of informative claims with which the FDA agrees. Totally unsubstantiated health-related claims are essentially undifferentiated with those that are backed by specific, well-designed clinical studies. The practice of following virtually all manufacturer-driven label claims with FDA's statement that these claims have not been evaluated by FDA does not provide enough information for most consumers--definitely not. FDA's disclaimer may, in fact, mislead people to believe that all claims not evaluated by the FDA are more or less equivalent.

With all the above factors in mind, we would like to address five interrelated areas of concern regarding the regulation of dietary supplements.

Labeling information. As indicated below, dietary supplements should contain sections, or boxes, that provide the following information: supplement facts; active ingredients, etcetera; health claims and FDA disclaimers to health claims; a safety profile--safety and purity; and GMP--good manufacturing practices.

Safety profile--and I've gone into some of this--this statement will be substantially elaborated on by the 20th of July. The system for reporting adverse events associated with dietary supplements should be enhanced and made consumer friendly. Outreach and education to those who use supplements must become a high priority. Product safety should be evaluated using standardized and objective criteria to determine if adverse effects are likely to occur, or if they have occurred. If adverse events have been identified, then it should be further determined if they rise beyond an objective threshold past which FDA action is required. Once verified, the current mechanisms for FDA response are adequate.

Dietary supplement labels should indicate if a product may be associated with historically known or reported adverse effects and contraindications. This information should be--would be contained in the "safety profile" section of the label. Labels for formulas containing new biochemical ingredients would also indicate that the product was associated with a very limited history of use.

All dietary supplement labels should be required to devote a small but prominent section to inform consumers if a product is manufactured under a credible standard of GMP. This standard, as proposed by various manufacturers' associations, should be higher than the standard for food, but not as onerous as that which is required for pharmaceutical drugs. The FDA would supervise verification of a manufacturer's compliance with GMP for a selected product. The Agency would also periodically check for contaminants in a variety of dietary supplements to assure their purity.

Health claims. If a manufacturer or distributor of a dietary supplement makes a health or disease related claim, that claim must be evaluated under an objective standard to determine the degree to which the claim is valid. Once evaluated, claims would be rated on a scale of 1 to 4. The lowest rating, level 1, would be associated with the absence or extreme paucity of scientific evidence, while the highest rating, level 4, would indicate that there "significant scientific agreement" and that FDA agrees with the claim. Levels 2 and 3 claims would require varying degrees of scientific proof and/or verification of long-term history of use, and would be accompanied by an FDA disclaimer. Appropriately, level 2 would require a higher standard of proof than level 2, while level 3 would represent a considerable body of scientific studies and other specific evidence that clearly placed it above level 2.

Consumer outreach and education. The goal in implementing the proposed label additions and changes is to benefit consumers and assist us in making informed choices. This requires extensive consumer outreach, media campaigns, as well as educational seminars and public meetings. A collaborative effort that includes input form a broad range of consumer groups, scientists, FDA officials and representatives from the dietary supplement industry must be mounted in order for labeling information to become genuinely useful for those who use supplements.

Assisted by others in the collaboration, consumers should take the lead in determining how best to approach the goal of comprehensive, user-friendly labels to avoid consumer deception and fraud.

And funding and resource allocation--I'd just like to say that we propose that Congress authorize the allocation of some additional funds to assure that the FDA can monitor the safety and content of dietary supplements, but we also further propose that funding for necessary improvements in labeling and evaluation of label claims, as well a portion of the consumer outreach efforts be substantially obtained through a nominal surcharge on each unit of dietary supplement sold in the United States.

Thank you.

MR. LEVITT: Thank you very much.

Mr. Johnson, please.

MR. JOHNSON: Good afternoon. My name is Richard Johnson, and I am the AARP Delaware State President.

AARP is interested in the regulation of dietary supplement because lots of our members and other older persons use supplement products. In recent years, we have commented on FDA proposals regarding the regulation of supplements and claims made on product labels.

At the outset, we'd like to commend FDA's work in standardizing the label supplements. Clear, readable supplement product labels regarding nutrient content and ingredients, with uniform standards for claims are essential to providing consumers the information they need to make wise choices. Ironically, consumers are not getting adequate assurance that the products they choose are safe. Without proof of product safety, the supplements that people take to improve their health may actually cause harm.

We believe that the Agency's number one priority in the area of supplement regulation should be to ensure the safety of these products. We understand that the Dietary Supplement Health and Education Act significantly hampers FDA's ability to remove dangerous supplements from the market. We also recognize that the Agency has limited resources to dedicate to this issue. However, we urge the Agency to think creatively about what it can do to address supplement safety. A major obstacle to supplement safety is a lack of scientifically sound research. There has been some research on vitamins and minerals, however research is needed on many other dietary ingredients.

Without a requirement for FDA review and approval before marketing products, manufacturers have no research incentive. The inability of manufacturers to patent many of their products and recoup safety research costs is another disincentive to research.

Given FDA's limited research funds, it should consider alternative funding avenues. One possible source could be a user-fee program. Every supplement manufacturer could be assessed an annual fee based on some appropriate criterion. The monies collected would be distributed as research grants. Under such a program the Agency could establish an advisory council to develop research priorities. One issue of concern to our members is the possibility of serious interaction between certain supplement products and prescriptive medicines.

Implementing a user-fee research program may be challenging, however. Some interests may believe it more appropriate to implement such research through the National Institutes of Health--the NIH. AARP urges the FDA to work with other Federal agencies like the NIH, and with Congress, the supplement industry, and interested consumer groups like AARP to establish a supplement safety research program.

A second issue of concern to us is the problem of product classification. A product labeling standards and safety requirements depend on whether it is classified as a drug, a food or a dietary supplement. But classifications are not always clear, and are less clear when products can cross the lines of definition. For example, Benecol and Take Charge are two margarine products that contain an added substance which lowers cholesterol. Calling these products something other than drugs or foods--functional foods, or nutraceuticals--is confusing. We urge that product classifications be structured such that manufacturers cannot use them to skirt appropriate regulations. FDA must ensure that the products are appropriately classified and conform to proper standards.

Finally, we'd like to mention our concern about the efficacy of supplement products. If sufficient funds were available, we would like both the safety and efficacy of supplement products to be researched. Some of the research is already being done. For example, the Office of Complementary and Alternative Medicine at NIH is currently funding research in conjunction with the National Institute on Aging, on the effects of ginkgo on memory. Clearly, more of this type of research is needed.

At the same time, we believe that the agency could be doing a better job of reviewing the adequacy of scientific support for the claims on product labels. AARP members are especially concerned about the claims on products marketed to older persons, such as those that claim to improve memory, promote prostate health, and reverse the aging process. Our concern is not just that these products may be worthless, but also that they may not be harmless. Such claims may lead a person to forego proven treatments, and select alternative remedies that are based on unsubstantiated promises.

AARP appreciates the opportunity to present our views on an FDA approach to supplement regulations. We would welcome and opportunity to participate in the development of a sound regulatory system that protects consumer health and safety in this rapidly expanding area of health promotion products.

Thank you.

MR. LEVITT: Thank you very much.

Again, what we'll do is we'll go right down the row here, and try to do one question each, and then at the end, I'll ask you to just summarize: if there was one thing that you could have a year from now, what would that be?

My question relates to safety. Both of you have emphasized that as an important area. The law talks about what's called "unreasonable or significant risk. "Without dwelling too much, from a lawyer's point of view but just from a consumer's point of view, for this category of products, what--how should we go about deciding what's a reasonable risk and what's not a reasonable risk? You know, what benchmarks, or from a consumer point of view--you know, would you want to be assured of?

MR. BRIGHAM: I think that anything that might affect your health that you unknowingly might take because it's not specified or not proven to be safe is unreasonable.

MR. LEVITT: Okay. Thank you.

Would you like to--

MR. JOHNSON: Well, no--that's really a tough question. I don't know. All I know is that you need to establish some kind of objective criteria for--

MR. LEVITT: Mm-hmm.

MR. JOHNSON: --for establishing this definition, and that there really hasn't been up to this point. I don't know if it--it would involve industry and obviously health care professionals and consumers perhaps--

MR. LEVITT: Mm-hmm.

MR. JOHNSON: --and some kind of working group or panel. I mean, I--there are so many dietary supplements sold that in some way can be dangerous. I mean our catalog is littered with warnings on the things that we sell. We do quite a lot of research on them. But--and I think that safety is the number one priority here, for sure.

But also I think that the health benefits that are gained from these supplements is significant and needs to be recognized and regulated appropriately.

MR. LEVITT: Thank you.

Margaret?

MS. PORTER: My question is about consumer research. The second panel this morning, I think, really stimulated us to look at issues about doing more research, or having more research done on how consumers actually use supplements, what they really understand or don't understand from the labels that are there; whether they follow the dosage restrictions, etcetera, etcetera. And as representatives of major consumer organizations, I'd be interested in your perspective on whether that kind of research is appropriate; whether your organizations ever do that kind of research into the behavior and attitudes and preferences of your consumers, or how you think the agency would go about getting such research done.

MR. BRIGHAM: I think that it's a very necessary thing. I would strongly encourage you to formalize that and proceed in some way.

DAAIR is a relatively small organization, with limited funding, and we really haven't taken an objective look at--I mean, intuitively--because I know so much about my organization, I can kind of answer that on an intuitive level, but on an objective, measured level, I can't. And I'm sure AARP might be able to do a little bit better with some sort of funding.

But I think that that may be one of the first steps that might be taken in order to structure the label. I mean, these different--well, we're proposing these different boxes on the label, to see just exactly how they are being used, and what are the limitations and understandings, and limitations of understanding. I think that would be one of the first things I would do.

MR. JOHNSON: AARP is, as you know, a large organization, and in addition to having 33 million members, there are probably about 600,000 volunteers within that structure, plus the staff members that give guidance. All of the feeling is that this is very important, to have consumer education. And in many of the fields, the major activity of these volunteers with AARP is information and education. And we have various things that are very important to AARP, such as Social Security and Medicare solvency and that type thing. And I'm sure that, as a function of that, we would really advocate the information and education as to what is necessary to make consumers more informed about these items, and what is the proper of these things, and such as that.

Consumers, left to themselves, I think would tend to go in the direction of if one pill is good, two may be better. And so there needs to be some information to be disseminated that would help to counter that.

MR. LEVITT: Bill Hubbard?

MR. HUBBARD: Do you believe that your constituencies are more vulnerable to unsafe dietary supplements than the general population, and do you have any objective data of injuries or adverse events from supplements in your various members?

MR. JOHNSON: What was your first part of your--

MR. HUBBARD: Do you believe that your members, or your constituencies, are more vulnerable to unsafe dietary supplements than the general population?

MR. JOHNSON: Speaking for AARP, we represent, generally, the older people in our society, and I think that they are probably more vulnerable because they are the ones that are taking a lot of prescriptive drugs. And the problems arise where some of these supplements may actually interfere or cause difficulty if you're taking a prescriptive drug.

I was surprised, in reading some of the literature in preparation for this, that garlic is a blood thinner--

MR. HUBBARD: Mm-hmm. Right.

MR. JOHNSON: --and yet there's a lot of advertising of garlic to be used. And if you're on, such as I am, a medication which already thins your blood--and many adults, or many seniors may be in that category--that would be an area of a severe problem. So I think--yes, the AARP members are probably more prone to have this difficulty than others.

MR. BRIGHAM: Interestingly enough, my answer is very similar. I mean, people with HIV and AIDS are also on a great deal of pharmaceutical drugs. I mean, speaking personally for myself, with kava kava, I used it at a--about a year ago, and then re-challenged myself with it. I actually ended up in the emergency room. I was on hamilor and nortriptyline--a tricyclic anti-depressant. And trying to manage some anxiety before I went on to a prescription drug, I took kava kava. And then I re-challenged--the first time, I was admitted to the emergency room. The second time, I just went to the emergency room because I was taking a lower dose, and I just wanted to see if it really did it. But I nearly passed out. I mean, I went through waves of passing out.

And, you know, and then there's--the historical use of kava kava can't extend past three months anyway. You develop quite a substantial rash--skin rash--and dermatitis, it's known, if it's used consecutively. And we have warnings throughout our catalog on blood thinning agents--many of the coumarins and stuff, and different herbs and botanicals.

MR. LEVITT: Bill, if I could just follow up with you briefly on that--so, in your mind, the remedy for that problem is labeling on products? I mean, everybody--

MR. BRIGHAM: Yes.

MR. LEVITT: --doesn't necessarily have the catalog that you're referring to.

MR. BRIGHAM: Right. No. I think there needs to be some labeling on--definitely there needs to be some labeling, some safety--you know. And even if it means a label which opens up. You know--I mean, I know we're getting into OTC and things like that--I mean, that goes into these contraindications. You know--and, I mean, they certainly do exist. And to ignore them--it's really, really needed.

MR. JOHNSON: And expanding a little bit on what the gentleman said, as we talked of these needs for information on labels, I could envision a label that would stretch across the table on a small bottle. But I think it's necessary, and if it can't be done on a label, it has to be done somehow, that the people are aware. I've heard garlic advertised many times over television and radio, without ever hearing any of the adverse or possible adverse effects. And, again, it surprised me to find that that was a side effect.

MR. LEVITT: Okay. Thank you.

Dr. Yetley?

DR. YETLEY: You both indicated that you would like to see FDA get more input from consumers, particularly your consumer constituencies in designing label information.

What mechanisms do you suggest that would facilitate that process?

MR. BRIGHAM: Well, the establishment of maybe a bi-coastal group--working group or panels or something--to meet on a regular basis to establish a framework of what to achieve, and goals to achieve. I mean, and actually having some, you know, regular timely meetings with consumers throughout a process, you know, that establishes a process and objective goals within a period of time, I mean, and on a regular basis, and is more formalized.

DR. YETLEY: Would you see this as separate from an advisory committee that was discussed earlier, or would you see that this could be incorporated into that process?

MR. BRIGHAM: I wasn't here for the advisory committee, but I think I might see it separate.

MR. JOHNSON: If we're talking about getting input from consumers, it might be possible with some of the AARP publications. We have a publication called The Bulletin which goes to all AARP members, and the Modern Maturity magazine. And I'm not sure if this could be accomplished in a very quick fashion, but if there were such a thing as a questionnaire that would ask what are your inputs that you might have as to the needs on labeling for the various consumer issues, that might be something that could be done through the publications that we have.

The other question that you had as to should this be in addition to an advisory council, I'd say yes, they should be separate entities; one being from an advisory council, and then any other input you can get from consumers directly.

MR. LEVITT: Thank you.

Dr. Bowen?

DR. BOWEN: My question is do you have any data from your groups of consumers who use these drug products, are they using it in concert with what is actually listed on the label, or are they using it differently. And, in specific, could you talk about the disclaimer--the FDA disclaimer--about the information. What purpose do you think that serves, or if that helps?

MR. JOHNSON: I don't have any information that we have knowledge of specific instances. Now, the disclaimer you're mentioning is the one that says the FDA does not recommend--I think that's very valuable, and I think--and, again, some of these things I wasn't aware of until I read this literature on this subject, but in reading that, it seemed that that would at least give people pause if they would read something that was making some claims, and then they would see that this was not something that FDA would sanction on the basis of the words in that disclaimer.

I think it's very valuable.

MR. BRIGHAM: I actually--I think the opposite. I think that there is--it's a wild, wild west show out there right now, as far as I'm concerned. I mean, I can't believe I'm sounding as conservative as I am--

[Laughter.]

--but--since FDA knows which side of the fence--I've been before you before on a number of occasions, in Congress and whatever. But it is--it's a wild, wild west show out there, and I think that the statement is becoming essentially meaningless at this point. It's just, you know--and there is a substantial amount of deception and fraud going on. I'm not--you're kind of focusing on health and safety issues, which are certainly there--certainly not as much as OTC drugs or pharmaceutical drugs. But with the health--related to health claims and health benefits, I think that it's pretty--it's a disaster.

So--and there needs to be some more formalized standard of objectivity and--I mean, I know FDA is going through the process of redefining, or defining what scientific agreement is or is not or whatever. But, I mean, even aside from that, just trying to at least tier these health claims a little bit to try and more inform the consumer, you know. And then it's amazing how small they put that disclaimer--the FDA. I have to look for it, and it's like--when I'm looking at one of the ads, or whatever. It's really--you should at least require it to be in 10 point type.

[Laughter.]

MR. BRIGHAM: But, again, someone who has been involved with this for a long time may find that it's something that you overlook. But for a novice, or someone that's not that involved in these use of dietary supplements, I think it would cause me pause at least.

MR. LEVITT: Okay.

Margaret, did you say you have a quick follow-up?

MS. PORTER: Yes--I really did understand you not to think that the disclaimer was very helpful, Mr. Bingham.

I'm interested in your suggestion--and I know you said your written comments are going to more fully elaborate this--

MR. BRIGHAM: Right.

MS. PORTER: --or your comments on the West Coast next month, but I understand you to be advocating a several- tier system that evaluates various levels of evidence with respect to the varying degrees of efficacy of particular claims. And, as you know, the more levels one has, the more--shall we say--complex a system can become. And I'd be curious as to whether you are going to be advocating whether we would go to a--some sort of a monograph system, or whether you've got some models that you would have us examine if we were to try to look at that kind of a system?

MR. BRIGHAM: I think I need to think about that a little bit further.

MS. PORTER: Sure.

MR. BRIGHAM: But, I mean, I don't know about going to a monograph system. That may ultimately be necessary. But I thinkthat this--I mean, if the public can understand the food pyramid I think they can understand a four-tiered health claim system. And--

[Laughter.]

--I mean, and other things, including safety profile and GMP.

MR. LEVITT: Thank you.

Dr. Yetley, you have a quick follow-up?

DR. YETLEY: Yes, I was just going--I think your comment--I was going to ask you about how well you thought consumers would understand a tiered system, in terms of the shades of qualification. I think there are questions as to how well consumers understand the food pyramid, so I don't know about the analogy--

[Laughter.]

--but if either one of you had any comments, in terms of how consumers understand various shades of qualification to a message?

MR. BRIGHAM: Well, I think it's really a matter of outreach and education, and you should be given the funds for this, either through congress, or through some kind of tax--or, well, let's not use that nasty word--user-fee on dietary supplements--per unit of dietary supplements. And we obviously want you to dramatically increase your role and expand it in this area. And it's going to take substantial funding, and it's going to take a lot of consumer outreach and education. But I think it can be done. And I think getting together this working group, or bi-coastal working group of consumers is a good way to start as well, you know, in addition to industry and other groups.

MR. LEVITT: Mr. Johnson, do you care to comment how you think your constituents would respond to a four-tiered--

MR. JOHNSON: I don't have any idea.

MR. LEVITT: Okay. Thank you.

With that, then, we'll give you one last opportunity to look ahead a year from now and say to us, FDA, if I could see one clear accomplishment a year from now, that would be--

MR. JOHNSON: Safety. And, again, as I said, if we had two that we could talk about: safety and efficacy. But safety is the primary concern.

MR. LEVITT: Thank you.

Mr. Bingham?

MR. BRIGHAM: Make some stop-gap--I hate to use that work, because I know the process is going to be long and tedious to work through this enormously complicated issue of dietary supplements and the functional foods and--but some stop-gap safety assessment of various nutraceuticals, vitamins, supplements and herbs that might pose a potential risk to the public health that are out there. And have them placed in some way that--on the bottle, in a box, or whatever. I mean, I don't know, but, you know--I mean, I can list, you know, about 15 of them off the top of my head, just, you know, right now.

You know, and getting at least that.

MR. LEVITT: Okay. Thank you. And if in your written comments you would identify those 15 or so, we'd be happy to know specifically which ones you thought needed attention.

MR. BRIGHAM: Right.

MR. LEVITT: Listen--I thank both of you very much.

That concludes this panel. We have one final panel, four lawyers.

[Laughter.]

And we have Claudia Lewis-Eng, we have Jim Prochnow, Steve McNamara, Steve Allis. If you could kind of figure out how to sit in that order, it makes it a little easier. From either end.

[Pause.]

Okay. Again--although I think you all have been watching the proceedings--what we'll do is each speaker will have five minutes. It looks a little different when you're up here. Right down here we have the one-minute warning, and the "time as expired" sign. If we could try to adhere to that. People have been very good--I want to compliment all the speakers, who have been very good about trying to stick within that. And then we'll go down and ask some questions.

Please, first speaker, identify yourself and where you're from. And in the case of the lawyers, please, if you could talk about who you are representing here today.

MS. LEWIS-ENG: Certainly.

Good afternoon. I'm Claudia Lewis-Eng, and I'm an Associate with Emord and Associates. And today I'm here on behalf of our clients Pure Encapsulations, American Preventive Medical Association, Dr. Julian Whitaker, Mycology Research, andWeider Nutrition International.

I would like to thank the FDA for hosting this public meeting and providing us with an opportunity to have this oral presentation.

In announcing the meeting, CFSAN made references to its 1999 priorities document for regulating dietary supplements. While I agree with many of the Agency's priorities, I must say there was a glaring omission. On January 15th of this year, the U. S. Court of Appeals for the D. C. Circuit made a decision in Pearson v. Shalala. And that decision stands for the general proposition that the government may not suppress outright commercial speech that is only potentially misleading, as opposed to inherently misleading.

In that case, the petitioners submitted four health claim petitions to the FDA, together with the scientific information, and the FDA rejected all four health claims. Those health claims were: omega-3 fatty acids in reduction of heart disease; anti-oxidant vitamins in reduction in the risk of certain kinds of cancer; consumption of fiber in reduction in the risk of colorectal cancer; and 8 milligrams of folic acid in dietary supplement is more effective in reducing neural tube defects than in common food form.

In the Pearson case, the U. S. Court of Appeals stated that the fact that FDA found the scientific evidence submitted by the petitioners inconclusive was not good enough to reject the claims and, instead, that the FDA should impose the use of disclaimers to balance the potentially misleading speech. And that's what I am here today to urge the FDA to make as its number one priority: to authorize those four health claims submitted by the petitioners, and include the use of disclaimers to balance the potentially misleading speech if the disclaimers are necessary.

I also urge the Agency to employ the use of disclaimers in the case of other health claim petitions presented to the Agency, as opposed to the outright suppression of speech. In fact, our firm just recently submitted three health-claims petitions to the Agency.

The first health-claim petition was merely seeking a clarification from a rule that we already feel applies to dietary supplements, and that is psyllium husk seeds in the reduction of coronary heart disease. But the second two we think that the Agency should really take a good look at the science that we submitted and, if necessary, attach disclaimers to balance any potentially misleading speech the Agency might find. And those are folic acid, B-6 and B-12, and the reduction of cardiovascular disease; and Saw Palmetto and the reduction of BPH--benign hyperplasia. The firm at this time also intends to submit one more health-claims petition, and that would be vitamin E and the reduction of heart disease.

And so I would urge the Agency, upon looking at those petitions to really look closely and try to develop some disclaimers that could be used, as opposed to rejecting the health claims, finding that the scientific information is inconclusive.

And just a gentle reminder to the Agency: we strongly believe that the Pearson case governs every instance in which the FDA would choose to regulate health claims. The case and its Constitutional impact should really be a priority with the Agency, and we look forward to seeing the use of disclaimers, as opposed to the rejection of the health claims.

And since I still have some time, I would like--have one other point that I would like to touch on briefly, and that is the AER system. Currently, FDA has a system of collecting adverse event reports. And it doesn't seem that there's much organization or a systematic method of collecting that data. For example, there are some instances where people don't really inform the Agency of the products they were using, how much they were using, what other types of medications they were taking, what other things that might have gone into causing the adverse event--yet the Agency relies on this information for promulgating proposed rules. And that was the case in ephedrine.

So we think that the FDA should take time to restructure its AR system and perhaps have a separate system for dietary supplements as opposed to combining with the food information. So we also want the FDA to take time to confirm that the information put on the Web is accurate, and do as much background checking as the Agency can in order to make sure that information that's posted on the Web does not adversely affect innocent companies.

Thank you very much.

MR. LEVITT: Thank you.

Next speaker--from Patton Boggs, Jim Prochnow. Help me with the name, because I'm not sure--

[Pause.]

MR. PROCHNOW: Jim Prochnow, from the wild, wild west--from Denver, Colorado.

Our law firm is based in Washington, D. C. , but I am the chairman of the Denver segment of the office, that deals with dietary supplements, both from the standpoint of FDA, Federal Trade Commission, state regulators, product liability suits, and all the other forces that help to regulate dietary supplements in the marketplace.

And, basically, we represent a variety of manufacturers, distributors--whether by mail order catalog, by multi-level marketing, by health food stores, mass merchandisers, things like this. And in preparation for this meeting, what we did was we sent out an e-mail to virtually all of our clients asking for their input about the questions that were raised in the Federal Register about the importance of dietary supplement regulation in the future.

We've gotten, to date, about a third of those responses back, but we will tabulate them by the time that the comments are over. And, actually, quite a few of them are going to--at lengths to describe what they think are--their opinion of how dietary supplements and dietary supplement companies should be regulated in the future, and we'll be making a very intricate matrix of that information and passing it along to the FDA, and make it available to others who are interested in that information.

Today, with the very restricted time element here, I'm going to make only three points. One is this: in our judgment, DSHEA, which was passed--that magic date in October of 1994--we think already is a very comprehensive framework for governing the dietary supplement industry. If there's going to be any tinkering with DSHEA, it should be with the expansion of benefits to consumers and the industry, and not with any restriction of DSHEA by regulation or otherwise. That's the first point.

Secondly is this: we think that the way that the FDA can best give input from the American public is actually keying off something that one of the last panelist members said, and that's "go to the people more. "It's okay to have these types of meetings, and it's okay to deal with the major trade associations, who have a very important role to play. But like the FDA has done in the area of medical devices, our clients believe, and I believe that what they should do is hold a series of meetings in Colorado, where there's a lot of dietary supplement companies of every nature; in Utah, perhaps the hotbed of dietary supplement companies; in California, New Mexico, and places like that--have one representative from the FDA in Washington, if they have the resources, otherwise have the local district office; invite the folks in for a three-hour meeting, and sit down and talk with them. And then you can really find out, on a local basis what's going on. It's the best way to get the most information in a cost-effective way.

The other comment that I wanted to make today--and my biggest comment--is this: the FDA has good folks that are sitting here, but they probably aren't going to get much funding than they have now to carry out their duties. So I hear all of these people saying a lot of good things about what these good folks should do, but the fact of the matter is they're going to be able to do very little more than they're doing now without a lot of increased Federal funding, and that's unlikely to happen in today's political atmosphere--and in the atmosphere of the dietary supplement industry.

So what I'm proposing today is that everybody here should think about something that actually was raised by one of the last people to speak, but I'm going to raise a more specific thing, and that's this: and that's an industry-funded check-off program. For those of you that know what check-off programs are all about, basically it's where the industry itself has Federal legislation that enables monies--not a tax--but monies to be collected on a per-unit basis, whether it's a half-cent per bottle, or whatever's agreed upon--the money is not spent by the Federal government. The money is--it's a check-off program that's spent by the industry. The industry itself elects members to a council. It's a very intricate thing. It's been done very successfully in the cotton industry, in the beef industry, in the propane industry, now the heating oil industry. It's a very effective thing. People can disagree with different aspects of it. But the important thing is, it would be industry-controlled as opposed to the FDA controlled.

When DSHEA was passed, I remember the fighting that went on beforehand, and the fight was to have less FDA regulation, not more. And the reason for that is this: it was thought that historically the FDA was at odds with the industry and with the American public over health. I think that attitude is shifting somewhat. Still, the regulators are never going to know as much about your industry as you know about the industry. And unless you want more regulation, the industry itself, either through a check-off program, or through some other mechanism, is going to have to develop an effective means to regulate itself.

Personally, I'm not in favor of any more regulation. The marketplace is a powerful regulator itself. Product liability suits, claims, insurance--things like that. But if there's going to be more regulation, let's let the industry do it, and not the FDA and the government.

Thank you.

MR. LEVITT: Thank you very much.

Next is Steve McNamara:

MR. McNAMARA: Good afternoon. I'm Steve McNamara. I'm with a law firm that generally limits its practice to matters of food, drug, medical device and cosmetic regulation. And I'm here today specifically on behalf of one of our clients--Starlight International, headquartered in the lovely location of Monterrey, California, where some of us would like to be more often. Starlight is a manufacturer and distributor of dietary supplement products.

I've been asked to address today and issue that, interestingly, does not appear to have been raised at all at this meeting up until now. It's an issue that goes to the heart of FDA's authority in certain respects; for example, I heard Mr. Levitt earlier ask one of the prior speakers, "Would you recommend that we use regulations or guidelines or what? "It's also an issue that could save FDA a lot of resources if approached appropriately, I believe.

And basically, this is the point. And I should say here, we have a detailed paper that discusses the citations and quotes the supporting authority for all of this. I'm just going to try and hit the high points in an oral summary.

The basic point is this: I've spent about 50 hours going through the legislative history of the Dietary Supplement Health and Education Act over the last two weeks, at the request of the client, to look at this particular issue. It brought back a lot of memories. As some of the FDAers will recollect, I testified both in the House and the Senate for the coalition of Utah companies that asked Senator Hatch to introduce and sponsor the Dietary Supplement Health and Education Act. So I've been rather thoroughly involved with this for the past five years.

Having refreshed my memory, and having looked at the facts, it seems to me that--it would be pretty clear that because of certain unique provisions in the Dietary Supplement Health and Education Act--provisions that were specifically considered during the legislative process--and because of provisions that do not apply to any other parts of the Food, Drug and Cosmetic Act, it appears to us to be the case that FDA does not have the authority to issue a regulation that has binding effect with respect to the adulteration or safety provisions of the law that have been discussed earlier today.

Let me just, for purposes of oral summary, and recognizing that many of you are not lawyers, go to the essence of some of the key points.

First of all, on the face of the law itself, Section 402(f)(1) of the Food, Drug and Cosmetic Act, as amended by the Dietary Supplement Health and Education Act, there are a series of provisions to the effect that a dietary supplement will be deemed to be adulterated"if"--and these have been referred to by FDA representatives today, including Mr. Levitt, and summarized at one point accurately as, a dietary supplement's adulterated if it presents a "significant or unreasonable risk of illness or injury" etcetera.

At the close of this section, however, after all of these adulteration provisions are provided, there is the following unusual provision: "In any proceeding under this subparagraph, the United States shall bear the burden of proof on each element to show that a dietary supplement is adulterated. The Court shall decide any issue--" any issue--"--under this paragraph on a de novo basis--" i. e. , all over again, from scratch, not relying on a conclusion that has already been reached in the past by the FDA.

I believe on the face of the law that says that if FDA goes to all of the work to publish a regulation, and then marches into court with a regulation that says a particular section--particular dietary supplement is adulterated because it contains a certain amount, for example, of ephedra that exceeds the level that the regulation allows, and that therefore the supplement is adulterated, the Agency will not be able to rely on the regulation but will instead need to prove its case from scratch that that particular supplement is adulterated under the statutory standard, and that the company would be free to offer data to show that its product, as evaluated by it, with its own marketing history is, in fact, safe for use and not adulterated. And the regulation would not establish the outcome.

I am reassured in my conclusion about this by looking at the legislative proceedings. It happens that this very section of the law originally had a provision in it for FDA to issue regulations, but that that provision--that authorization for regulations--was explicitly deleted before the final section of the law was passed. Furthermore, the earlier provision did not have the section that said that a court shall decide any issue on a de novo basis. And, in fact, that was added when this section was put in and when the explicitly provision for a regulation was deleted.

There's more in the legislative history. It's discussed in some detailed in the paper. We will welcome other dietary supplement companies focusing on this issue in taking a good hard look at it, because we believe it establishes a point that many in the industry will have a common point of view about: that FDA itself, when it moves to articulate what it believes the law requires with respect to safety or efficacy under Section 402(f)(1) should be relying on guidelines, not regulations. And if it spends all the money--time, money and effortthat are necessary to issue a regulation, the regulation won't have any more effect in court than a guideline anyway. So why not creatively shift to guidelines, rely upon guidelines, and the agency can get a lot more guideline work done in a shorter amount of time and with less resources than would be taken by regulation.

Thank you, Steve.

Steven Allis--last speaker on this panel.

MR. ALLIS: Thank you.

As the last speaker, I'm sure I'm--everyone's got the same thought right now. So I'll try to just hit a few key points and then move on to the next phase.

My name is Steven Allis, and I'm an associate at the Firm of Emord and Associates. I represent a company called Biogenics, which does business as Eola International. They manufacture a variety of dietary supplements, including dietary supplements containing ephedra.

When I first saw the notice for this meeting it, to me, summarized that FDA was looking for comment on how to identify where to proceed; how to prioritize its tasks and to put those tasks into effect, or to accomplish those tasks. I'm not asking in the comments to really do much of a change. I'm not really focusing so much on that, I'm focusing more on how to go about that change; not exactly what should be changed, but the processed involved with that.

There are three points I'd like to focus on.

The first is that in the decision that the agency is going to make, it should rely on sound science, which is a very obvious statement. And I'm sure your scientific staff would agree with that, because that's their bread and butter. The sound science standard, the standards used to evaluate that have been recently affected by the Pearson decision, recently mentioned by Ms. Lewis-Eng. And in that decision, the court, as part of it, said that the FDA needs to define a scientific standard that would be applied to dietary supplements. And the language, of course, involved "significant scientific agreement. "

And what I want to point out is, as far as the procedure used for defining the scientific standard here--the point that what I want to refer to--a duality I've noticed with the agency, not only working as an attorney but as a former scientific reviewer in the Office of Device Evaluation--I have seen that when a company wants to petition the FDA, as with the recent health-claims petitions that my firm submitted, the standard, of course, there is scientific evidence that demonstrates significant scientific agreement. And in that, it's not really clear where that lies, especially after the Pearson decision.

Some science like well controlled randomized studies, of course, fall under the category of good science. Things such as anecdotal evidence are usually--are almost totally rejected, and they should be, because they're not really good science. They're little cases here--someone had this affect, and someone had this other effect. So in that situation a company is asking FDA to do something and the reaction is, well you have to reach a certain level of science. Some science is bad, some science is good--we're going to draw the line somewhere in the middle.

Now, when the opposite happens--when FDA is seeking to take action, as in the case with ephedra, these anecdotal reports all of sudden become valuable. They're used as a basis for saying, "Okay, we have something--some information, scientific or not, that is going to be used to base our regulations on--to base our regulatory decisions on. "And as in the case of ephedra, a number of adverse event reports--AERs--were used as a primary basis for prompting the regulation which is currently pending of ephedra.

The problem, of course, with AERs is that they are just cites--or one moment in time where someone had an effect from a product, and that's just kind of floating out there. There's no real reference to put that in. It's not a study where you had a certain population, or we can derive a percentage from: how many people had a bad result. And not only that, but the AERs also are flawed because they--sometimes you don't know what product they took, how much they took of it, what other conditions they had. And I just bring up these--this duality. We have a situation where FDA--where someone's asking FDA to do something and the standard is a strong scientific standard. And when FDA is trying to do something that involves an industry or a company, that standard gets kind of ignored. It's kind of made a little bit over inclusive. And I'm just asking that whatever the Agency decides, to stick with sound science in its procedures.

The second theme is to ask the agency not to overregulate. Now, that's another overstatement, but what I'm getting at with that is--again, I can use ephedra as a good example. That's a product where there are some bad actors out there. The product has been tied to a possible illicit use for some manufacturers. There's also problems that might be attributed to the labeling claims, or over--too high of a concentration of ephedra.

Now, what I would hate to see is where a few bad actors ruin it for the whole industry. And that's particularly alarming when you consider that the existing statute and regulations could allow effective regulation to get these bad actors from ruining it for the rest of the industry.

There are already regulations in place to prevent claims that aren't supported by science. There are various other tools already in place that could be used to stop these bad actors. There's no reason to put another layer of regulation to restrict ephedra, particularly when that regulation is based on, like I said before, the faulty science of the AERs.

And as a last point, I want to refer to--whatever the Agency does, to be fair. And that's another overbroad statement. Here, I have to refer to what Texas has recently done, or is trying to do with ephedra, and that would be passing regulations saying that "we're going to regulate botanical ephedra a certain way, and synthetic ephedra another way. "There's no real justification for treating the two differently if it comes from a plant source or a chemical source. There is no science that I could find out there, or that anyone I relied on could find out there, saying that there is--the body recognizes the difference between the two.

I'm just using Texas as an example of an agency that is saying, "We're going to treat these two versions of the product differently" with no apparent rationale.

So I just ask for the Agency to keep fairness in mind when they're applying any of the regulations of industry.

Thank you for your time.

MR. LEVITT: Thank you very much.

For my first question I'd like, if I may, take advantage of the fact that we have four very knowledgeable lawyers up here, and while not picking up necessarily on the particular points you made, you're all familiar with DSHEA.

One of the things that has struck me in learning more about it is there is a long litany of issues that might benefit from definition, clarification, throughout that statute. In your experience, could you each list, just in your mind, one or two legal definitional kinds of issues that would really us paying attention to, giving clarification to?

MR. PROCHNOW: This is Jim Prochnow. The question that I get asked the most frequently by clients is what does "substantiation" mean? Usually I say, the FDA has refused to define substantiation in its comments to various rules, and said it's kind of like pornography; we recognize it when see it.

But substantiation is a huge issue, because people do want to comply with the law. And, as you know, as a quid pro quo for making structure/function statements, you have to have substantiation for what you say is true. So I would say in the clarification arena, more clarification about what's "substantiation" would be helpful.

And I want to say I agree with Steve. And I say use of guidance documents is the way to get this done, as opposed to regulation. It will take too long for regulations, and you need the industry to buy in on it from a voluntary basis anyway. So I'm all in favor of substantiation, and the use of guidance documents to accomplish what the FDA needs to accomplish in this area.

MR. LEVITT: Thank you.

Who else would like to comment?

Steve?

MR. McNAMARA: Well, I do think there's a fundamental problem over the so-called "disease" definition, but that goes even broader. I mean, part of it goes to the issue that several people referred to earlier: the FDA's proposal from April of a year ago. And we all, I trust, are aware of the volume of response, and the strongly felt disagreement.

But there seems to be a belief on FDA's part, held closely and deeply, that somehow disease-related claims are not appropriate for things that are foods, and dietary supplements are a sub-category of food. In fact, the definition of "food for special dietary use," which has been in the FDA regulations since the 1940s, and which includes among the defined categories "dietary supplement products" as a type of food for special dietary use, has recognized that claims of special dietary usefulness for a food may include claims about providing usefulness with respect to physical, physiological, pathological or other conditions including, but not limited to, the conditions of disease. I've more or less got that verbatim. And that's in Part 105--I guess . 3, somewhere along that line, in the definitional section.

I would submit to you that there are perfectly appropriate dietary supplement uses with respect to disease, and to say that something is "disease-related," to use the conceptual dividing line that FDA often uses, is not an appropriate divider for deciding whether something ceases to be an appropriate food or not; and that there are very good cases to be made, which will be made--and I hope they don't need to eventually be thrashed out in litigation--to the effect that disease-related claims are indeed appropriate in certain circumstances, for certain products, for things that are dietary supplements or, indeed, foods for special dietary use.

And I think that if we are to avoid that black hostility that I believe Jim Turner talked about earlier, that this is an apt time for the Agency to reflect on some fundamental instincts about what's acceptable for a food and a supplement, and a food for special dietary use, insofar as that's an appropriate umbrella term for supplements.

And I personally believe that there's a very good legal argument, as well as a good policy argument, that there'snumber of disease-related representations that deserve to get in--appropriately, properly--and that the Agency's instinct is so resistent to that, and its proposals are so resistent to that, its courtesy letters are so resistent to that, that we find ourselves dealing with these issues always in conflict situations. It's regrettable.

I mean, one of--you asked earlier about advisory committees, whether they're advisory committees, or however they're set up. It really will be advantageous to the industry and to the FDA, I think, if you can find ways for some of these issues, which have been dealt with in contentious contexts to be dealt with in non-contentious contexts.

MR. LEVITT: Thank you.

Yes.

MS. LEWIS-ENG: I do have one comment that I would like to make.

I don't really have a clarification comment under DSHEA that I would like to ask, but I do have one under FDAMA. Since the agency is really looking at priorities at this time, I think that we should have a clear definition of what an "authoritative statement" is. I think there has been lots of upheaval in the industry--dietary supplement industry in terms of what exactly constitutes an authoritative statement, and the agencies such as NIH and the FDA and others who are approved under FDAMA don't seem to agree what an authoritative statement is. And I think that really should be clarified.

MR. LEVITT: Okay. Thank you. I think that counts.

[Laughter.]

Steve, do you have anything you'd like to add?

MR. ALLIS: Your question related to where we could establish or improve on definitions that you rely on?

MR. LEVITT: Yes.

MR. ALLIS: All I can really do is reiterate my point is that looking at this from a legal perspective, or regulatory perspective, it's easy to ignore the science side of it, which is what I was trying to stress in my talk, which is that it's pretty easy to define what's good science and what's bad science most of the time. And as far as a definition goes, just, like I said in my speech a minute ago was that if it's going to be bad science for use for someone to apply to the Agency, it should still be bad science when the Agency wants to rely on it for passing regulations.

MR. LEVITT: Okay. Thank you.

Margaret.

MS. PORTER: Well, I have several questions I'll try to discipline myself and start with one that I actually asked the earlier panel.

I was pretty stimulated by this morning's second panel really urging the Agency to find ways of doing consumer research or having others do consumer research that really looked intensively at how dietary supplements are actually used; whether consumers really follow the labeled indication, follow the dosage indicates; whether they use supplements for purposes that are not advised by the manufacturers, and whatever, on the labeling and otherwise.

And I was interested in any comments that you might want to make on behalf of your clients about the appropriateness of that kind of research; the usefulness for which it could be used. I know that in the Pearson context there is a strong suggestion that the Agency look at that in the context of disclaimers. I'm acknowledging that, but also asking some broader questions, and I'd be interested in any comments you might have.

MR. PROCHNOW: In my judgment, I think it's a very important component to the resolution of all of these issues. I mean, consumers are the ones that are to benefit from taking dietary supplements. They probably drove the enactment of DSHEA. The question always is: how do you pay for this and get it done in a reasonable period of time.

Now, although I respect what the FDA has done in the past, still it seems its efforts with respect to the ephedra rule, and structure/function rule not get too far. So I think that if there's going to be some research in this industry, again it has to somehow be--the industry has to, I think, carry the water on that issue, with input from the FDA.

I think the industry wants to do some of these things, and is looking for a mechanism of how to carry this out. I think there's got to be a partnership involved here, and I think Annette Dickinson talked about a partnership this morning. I just happen to think--I'm trying to be creative and think about our clients, or about a program that the industry can buy into to fund some of these things. Because of this requires a lot of money. And without that happening, I don't see it being done.

But we use consumer research on trademark issues in this industry all the time, and for other things. So I think it's imperative that something like that should be done.

MR. McNAMARA: I trust the assumption is that it's not being done in all cases. I mean, there are some substantial companies--I would assume, but I don't know that I have the right to make the assumption--often the larger ones, that have, I know, spent a great deal of money on appropriate research of various kinds. I think the first focus tends to be on the substantiation of the health-related structure/function statement, but there--it's not appropriate to name brand names up here, but there's a major line of products out there now with a clinically-proven representation on the front panel. I think you'll find that people who are making those kinds of claims have done a lot of work to substantiate those, at least certain of the companies that are larger companies, that I'm familiar with are, in fact, doing that.

And--so I wouldn't reach the quick and cavalier assumption that things are not being done, or at least that it's any materially different than perhaps you find with respect to other industries that FDA regulates, where there's a variety of performance. But you should also not judge companies that do comply by those that don't. And I think that there are many out there who feel that sometimes they've put in the work to defend what they've got, and then they're tarred by generalizations that are made about others.

One of the other factors that I really think is important here that no one has raised yet, and that I know that Dr. Yetley and Mr. Levitt have heard me raise in other contexts, has to do with insofar as you're worried about a definition, or insofar as you're--you know a product is a supplement or a drug, or insofar as you're worried about whether a claim is an appropriate claim or not; insofar as the Agency expresses an opinion, it ought to be willing to follow through on that opinion.

And one of the negative impacts right now that we are all living with, if we're honest, is that the Agency is issuing letters that express opinions that nobody pays attention to; or that the addressees have paid no attention to. I've mentioned one that I know--again, I'm not going to mention a brand name up here, but anyone out there in the industry's probably familiar. I mean, the Agency sent at least five letters expressing the view that a particular name and claim are illegal and inappropriate for a particular product that's quite successful. And it has been increasingly successful, notwithstanding the FDA's repeated letters. And the Agency's done nothing, and the product is just booming in the marketplace.

Now, believe me, when other companies come and consult with you about, "Well, can we make the following claim or not," and you say, "Well, you know the agency issued a letter about that point last year. "And they say, "Tell me about something other than an FDA letter. I know what happened to the letter that FDA wrote that other company. They didn't do anything to follow through on it. The people that withheld from meeting the competition lost lots of money. And I have no confidence in FDA paper. "

And whatever structure you come up with--earlier commenters this morning, I noticed, were talking about enforcement. I'm not up here to ask you to go out and have enforcement actions. I'm here to defend companies. But I believe that the wrong way to have the railroad run is for the Agency to express views that it does not follow through upon. You're wasting your money if you're sending that kind of a letter. You're not only getting no bang for the buck out of it, but you're undermining the respect for the agency in other contexts.

And a fundamental question should be going through the head of the Agency, whenever it expresses an opinion in writing, and that is: do we mean it enough that we mean it? Or are we just putting it out there, and if people ignore it, we'll do nothing. And--enough to say on that.

Others?

MS. LEWIS-ENG: Whenever it comes to scientific substantiation, the question of money always arises. And I represent a number of clients who wouldn't be afraid or unwilling to spend a substantial amount of money to submit scientific substantiation to the Agency if they had faith that the Agency would take an objective view of the scientific substantiation.

In the past, when I sort of encouraged this type of clinical trials and whatnot, to take place, the most--the response I received most often is that, "I'm not certain that the FDA is going to take this scientific evidence that I produced seriously, based on its past actions that the Agency has taken. "

So I would submit to the Agency that perhaps until the industry has more faith in the Agency, in terms of being objective and not having biases, if you will, that perhaps the Agency could team up with universities, or private contractors, if you will, to come up with some scientific information that everyone could pull from, and they get a grasp of what the Agency is actually looking for, and what will work with the Agency. And they might be willing to spend their own dollars on the scientific substantiation.

MR. LEVITT: Thank you.

Did you want to say something? Please.

MR. ALLIS: Like what I've stated before is that the companies do want--for the most part, do want to do the science. The clients that I represent with Ms. Lewis-Eng, they have an interest in having the science and putting the investment into the product. Of course, there's something you should keep in mind, which is that there's a risk not only that the other guy in the market won't have to be meeting the same burden, also, as I've seen in dealing with science and submission to the Agency, there's very little guidance sometimes, or access to people who will be reviewing the science, to find out whether a little flaw is going to be a fatal flaw later on when you come to the end of your study. That could be a huge expense, especially for the smaller companies that predominantly are found in this industry.

Another thing I would want to bring up is that the health-claims petitions that we filed recently--adopting health claims such as that might alleviate the need for some of the dietary supplement claims that are being generated by individual manufacturers, if they could rely, or fall back on a health-claims petition--or, I'm sorry, an approved health-claims petition. Maybe that statement might forego the need to come up with, maybe, some more extravagant claims or objectionable claims.

MR. LEVITT: Thank you.

Before we move on to Dr. Yetley, let me note that Mr. Hubbard needed to leave. And I'm sure, Margaret, Bill would want to have yielded his time to you. And so, when we finish, if you'd like to have another couple of questions, I'm sure this group is eager to answer them.

Beth.

DR. YETLEY: Some of the previous panels had urged the FDA to take stronger action relative to safety and substantiation of claims.

How would you recommend that the FDA deal with the recommendations that hey were making to us?

MS. LEWIS-ENG: Well, I wasn't here this morning. But, of course, safety is of the utmost concern. As a consumer myself, I wouldn't advise the Agency to just put products on the market because there was some inclusive scientific evidence that wasn't really--didn't substantiate the claim at all.

What I'm looking for is that very rarely in the scientific is there a total agreement, and I'm just looking for some balance that the Agency can put on the health claims and substantiation requirement so that the small actors, as well as the large actors in the industry, can compete effectively in the market--with safety, of course, being the number one concern.

MR. PROCHNOW: In my judgment, the biggest thing that you could do for safety right now, I think, is to either adopt the GMPs that have been proposed by the industry in a guidance document, or issue a regulation for them. It will send a signal to the industry that this GMP process, and other processes, can have an end to them, and that the FDA can bring to finality certain things.

It's important, not only for the substance of them, but for the fact that they are actually issued, in the form of a guidance document or regulation. Because right now, whether it's in the context of just manufacturers and distributors wanting to be able to have safe products, but people will conform to a--whether it's a quasi-regulatory document like a guidance document or a regulation--but I believe there's got tobe some finality to the GMP process, and that's the single biggest thing at the present time.

The second thing, I think, is selective--maybe sending out more warning letters and then, as Mr. McNamara suggested, taking some action with respect to some of the warning letters, because that makes a difference and an impact in the industry as well.

MR. LEVITT: Okay.

DR. BOWEN: I'm tempted to yield my question, but I guess I'm very curious, so I'm going to ask it.

Mr. Prochnow, you mentioned that you thought that FDA could get a lot of mileage out of holding meetings across the country in areas where consumers use dietary supplements pretty extensively. If that were possible, how would you envision those meetings to happen? The forum of those meetings?

MR. PROCHNOW: How do I envision them to happen in what? I'm sorry.

DR. BOWEN: Sort of the format, the forum of these--

MR. PROCHNOW: Yes. I think basically what it would be is this--is that you would send out a notice--let's just pick Colorado Springs--that there will be a meeting in Colorado Springs, and the people that will be there will be the District Director of Colorado and somebody--let's say Bob Moore--from the Washington, D. C. office. There will be a topic presented--let's say it's quality control and good manufacturing practices in thedietary supplement industry. I think there should be a short, like, overview, and maybe that topic divided into five segments. And then the meeting should be split up with, let's say, 10 people--let's say you have 40 people there--10 people in a session that considers one of the issues, reports back and makes recommendations to the group as a whole.

I think that process, you know, can take a half day or take a day, but it worked really effectively in the meetings I went with the medical device community, and it's been just--the people I've talked to have come away feeling that they finally had the FDA listening to things. And it's just so often that there's so little chance for a mass of people to be participating in meetings like this that you'll really find out what the multi-level marketing distributor sees as the problems it confronts, or the contract manufacturer says "Here's where I really need some help," or where we could use some more working with or regulation with the FDA.

It's that kind of format that I think would be very effective.

MR. LEVITT: Thank you.

I'll give the phone back to Margaret.

MS. PORTER: This is--actually, Dr. Bowen actually asked one of my next questions. So let me just do a little bit of follow up, because I think that your comments, when you focused on sort of taking the Agency to the--going to the people and really engaging in a grass-roots way, I think the Agency also found the Denver meetings with the medical device industry quite productive, in terms of really having a way of listening to concerns and responding to them.

There are several different kinds of people that I think the Agency's interested in trying to reach out to at a grass-roots level. Certainly one kind of stakeholder is the industry itself, and you suggested, I think, the forum under which the Agency might do that.

Do you have some suggestions for reaching consumers directly? We've obviously heard from a number of national or regional consumer organizations today, but I'd be interested if you've got some suggestions for grass-roots consumer outreach as well.

MR. PROCHNOW: I'll let others speak to it. But one thing I do want to say is I think the gentleman who represented AARP had a really good suggestion. I'm now an AARP member, for all of you that were wondering.

[Laughter.]

But their magazines--I mean, I read Modern Maturity. I'm 55 years old now and all of that, and it's the people who are in that age category--this is important things, and they respond to it. And you're talking about a huge segment of the American population. So I think the use of some mass media opportunities like that is the best way that I can think of. But others probably have other ideas about that.

MR. McNAMARA: It strikes me there are lots of interesting and important segments of consumers. A significant segment of dietary supplement users, it appears to me, based on things that have just happened to come up in our practice of the law, include younger people in college and high school. There's a group of people who are highly interested in issues relating to diet and health and in supplements, and in alternatives, and I assume there are ways to reach college-age people as well. And one--again, we're lawyers, not marketing folks, but one certainly can get advice about reaching the various segments.

But it seems to me the important issue is to try and reach a lot of them. Sitting here as another--I hate to say how many years'--member of the AARP, but those--my children never read those magazines. Let's put it that way.

MR. LEVITT: Okay. Thank you very much.

Before we let you walk back down, we get the one final question: looking ahead a year from now, if FDA could do one thing it would be?

MR. ALLIS: Umm--

MR. LEVITT: One thing.

MR. ALLIS: One thing.

[Laughter.]

MR. ALLIS: Better access through guidance and interaction with your review staff so we can hit these targets that seem to be moving targets some times; the definitions and such.

MR. LEVITT: Okay.

Steve McNamara.

MR. McNAMARA: Well, I'm here for a particular client, so focusing on that particular's interest I'd like to see FDA withdraw the pending proposal on ephedra; have informal meetings that could then be held with the ephedra dietary supplement industry, focusing upon things that FDA may want, including long-term follow-up and issues that like, and have a guideline, or at least an indefinite interim guideline issued about the Agency's views about labeling composition and what a responsible company should be doing, including--insofar as you feel that's important--follow-up monitoring and reporting to the agency about events.

MR. LEVITT: Okay. Thank you.

Jim.

MR. PROCHNOW: I think I'm going to be able to do one--and-a-half here, because I agree with everything that Steve had to say about the ephedra rule: guidance document only.

Beyond that, I think that, seriously, all of the people here have raised this issue about maybe not more regulation but the need for the FDA to be actively involved in the process with the industry. And so therefore, at the end of this year I would hope that we have completed a round of intimate industry meetings in a lot of different districts throughout the United States, so we're in a better position to move forward with a master strategy plan after next year.

MR. LEVITT: Okay. Thank you.

Claudia.

MS. LEWIS-ENG: And to be totally predictable--

[Laughter.]

--I would like to say I would like to see a faithful implementation by the Agency of Pearson v. Shalala. And I also would like to say that I want to rally behind Jim and Steve's request that the FDA withdraw the proposal on ephedra.

MR. LEVITT: Okay. I thank this panel very much. As you're getting ready to get up and walk back down, there are two additional people that have asked to speak. I'd ask them to come up together, and we'll have a mini-panel here.

One is Anne Fonfa, and one is Mary Silverman. And then that will conclude our day.

Thank you very much, the four of you. And thank you for traveling--and the many other people that traveled, too.

[Pause.]

MS. FONFA: I'm just going to start.

MR. LEVITT: Thank you. If you'll just let the gentleman behind you sit down. And again, while you're up here, we'll give you the same five minutes everybody else had--

MS. FONFA: Thank you.

MR. LEVITT: --and we've got the timer right down here in the front way. If you can identify who you are, and where you're from, and who you're representing. Thank you.

MS. FONFA: My name is Anne Fonfa, and I'm a cancer patient. I represent a group called the Annie Appleseed Project, and what we do is speak and for cancer patients who are using alternative and complementary therapies which, as you probably know, is a majority of cancer patients. I also speak to health professionals and other people about this issue.

So--patients are using complementary therapies and alternatives, which include dietary supplements and every single thing we heard mentioned here today. I echo the safety concerns of everyone else, but I have to say, for cancer patients, proof of efficacy has become the critical thing. People are doing things right now. They're not waiting for safety, and they're certainly apparently not waiting for efficacy. So, from my perspective we can solve two birds with one stone if we focus on efficacy, I think we'll find that that will resolve the safety questions pretty clearly.

Standards for drug development that we're currently using for cancer have been toxicity, terrible effects that are called "side effects" but aren't. So we're not as concerned as others might be about the safety in the same way. We don't mean it in the same way that everyone else does.

I also agree with many of the speakers that research exists and can be looked at, and I think it needs to be brought together in a way that will make it clear to cancer patients, and others, what it is that we can use appropriately.

I don't think we should limit anything to a single element. That's been a problem in both drug development and with supplements. We know that people use things in combination, and that needs to be studied directly.

We need to send a message to pharmaceutical companies that supplements can be used with their products, and that they need to be concerned about their--the dangers of their products. I don't think it's specifically the herbs and other things that are so dangerous, but the way they interact with pharmaceuticals. And I think if garlic is a blood thinner, that's not necessarily bad. It may indicate that we could consider use of garlic as a way to reduce our use of pharmaceuticals, because every pharmaceutical product as unwanted effects.

We want health care professionals to be involved. No one was here today. That's a concern of mine. I think they should be part of this process.

The final thing is I think--I wrote something here that I can't even interpret. Oh, yes--patients start a regiment of supplements, and then they become scared because they are looking at the statement that says it hasn't been evaluated by FDA. And that's a concern, because they start something and they stop it. They may desperately need something. They may have been already finished with conventional treatment, which is the way most people use alternative or complementary therapies; or they're looking for them to reduce side effects. And since they're not sure how it works, its efficacy, they lose faith in it, and they stop at a point at which they might be gaining something from it. Because we're used to pharmaceuticals, we want an instant reaction, and we know that herbals and dietary supplement may take time--at least I know that, and you all know that. But many of the cancer patients are without direct information.

So I truly think that going toward efficacy immediately, and having statements of efficacy would be extremely useful to our population. We're doing it now. Our lives are at stake. Our time is limited and our money's limited.

Thank you.

MR. LEVITT: Thank you.

Please--you may sit right there if you like.

MR. SILVERMAN: Okay. Thank you.

My name is Maury Silverman, from Silver Spring, Maryland, and I wanted to share some personal impressions.

Several people here asked your panel about completing the ephedra regulation question. And I have some impressions and thoughts I'd like to share with you, and ask your comments.

I've watched that issue through the years. I was personally somebody who worked for passage of the DSHEA law. I think it's a good law, and a good structure; and that industry and consumers and the FDA need to join ranks and work effectively and objectively to implement it and get it down to the details beyond what might be in the actual language that went through late that night at the end of that session.

I wonder if the ephedra issue is kind of a bad red herring for all of us ; all people concerned. I remember attending the two-day Food Advisory Subcommittee meeting on ephedra--it's, oh, many years ago now. And I remember well one of your best experts at the table was Varro Tyler. And he flat-out stated on the second day, "Regulate the chemical ephedrine as a drug, as it is. Regulate the botanical ephedra alkaloids under DSHEA. "And he gave labeling recommendations; label contraindications, label a maximum daily dose and per serving dose, that's objective for the benefits of ephedra.

I want to ask you two questions. I remember seeing the effects literature that was brought to that meeting, and it was clearly all effects of chemical ephedrine. And I want to ask a basic question before you decide on a final rule, or whether to accept it, toss it out, revise it, just go back to a guidance procedure--whatever.

Has FDA distinguished where the serious side effects came from? Chemical ephedrine, or botanical ephedra--also known as mah-wong; it's also known as Mormon's tea, for a good reason.

I think that's an important question to be answered, and it might clear up what some of the confusion has been, because Varro Tyler's remarks that day several years ago echo in my mind with this.

I'd also like to ask if FDA has ever determined if dietary supplements have been spiked with chemical ephedrine, and is that a possibility where some of what are called the "serious side effects" are coming from?

I also attended the Government Reform and Oversight Committee Hearing a few Thursdays ago, and a lot of that testimony was illuminating. There was a gentleman who gave a very good historical and scientific narrative about the thermogenesis properties of ephedra. And I think that's why one of the common names for ephedra, or the botanical source is Mormon tea. It's what helped those people go west in the middle of a winter and predominantly make it there.

And I think these are important questions to be asked and answered. And like one of the previous people that were up here at this table said, please don't let the bad actors throw the good people and well-meaning people out. Please don't throw the baby out with the bath water.

One example was the testimony the other Thursday that the proposed dosages of ephedra are lower than the effective doses for thermogenesis in weight loss. And, as you know, there have been a lot of problems with some of the pharmaceutical drugs that are put in the marketplace for weight loss problems. And I think this should be done objectively and in a reasoned manner.

Some of it kind of reminds me of all the brouhaha over tryptophan which, my understanding was a problem with a Japanese manufacturer, Shawa Denka, that they took some of the activated charcoal steps out of their process and their might have been a bioengineered organism involved there was a problem with. And there was a later Mayo clinic study that identified a contaminant. And that the lots of the those contaminated batches correlated with where the incidence of the eosinea myalgia syndrome came up--explained a lot. I heard testimony that there was virtually none of these cases in Canada, because none of those lots reached Canadian markets. And I feel sad that if issues like that are used by the people who would like to gut the DSHEA law, when we really need to implement it right.

An example, I think, would be the good manufacturing processes provisions in DSHEA could have solved the tryptophan problem before it really became a problem with eosinea myalgia syndrome. And I think these are some things that need to be thought about, taken to heart, and part of the learning process in developing this law, and implementing it properly for the public safety and in all people's interest. I think that's in all our interests, and that we should do this in a calm, reasoned manner, and look at the history of this, and do it right.

Thank you.

MR. LEVITT: Thank you very much for that presentation.

I'm not sure if you were here in the morning when we began, but one of the things I tried to explain is, today is really for us to kind of take in information and to listen, and to elicit more, and not get into a back and forth. You know, I presume, from everything you've said that we did issue a proposed rule on ephedra a couple of years ago that did have a lot of information in there: what the agency based in on. We're now looking at all of that in trying to make the determination where to go. But, beyond that, we really--this is not the forum--

MR. SILVERMAN: No. All we realize--is we ask you to take all these comments home with you--

MR. LEVITT: Right.

MR. SILVERMAN: --and take them to heart. Thank you.

MR. LEVITT: Okay. Thank you very much. Let me thank both of you.

[Pause.]

That concludes our meeting today. We started a few minutes late, but we've finished a few minutes early. That's because, I think, number one, people came very prepared; people were very gracious and adhered to the rules of procedure that were laid out.

Let me again thank everybody who came today; people who presented. We will be taking all this information in, together with written comments at a meeting we're having on the West Coast in July, and really trying to develop--as I said at the beginning--an overall framework. Clearly our goal is to implement DSHEA in a responsible way and to get consumers, as one of the speakers reinforced, access to products that are safe and properly labeled.

Let me thank everybody for their attention. Thank the panelists. And that will bring this meeting to a close.

[Whereupon, at 4: 42 p.m. , the meeting was adjourned.]

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