FIM Rationale And Proposed Guidelines For The Nutraceutical Research & Education Act – NREA

by Stephen L. DeFelice, M.D.

Presented at FIM’s 10th Nutraceutical Conference
November 10-11, 2002
The Waldorf-Astoria, New York City

Nutraceuticals & Pharmaceuticals Taken Together: A New Health Sector
Plus: A New FIM Congressional Proposal: The Nutraceutical Research & Education Act – NREA

(Please note that the NREA that was introduced in Congress by Representative Frank Pallone (D-NJ) on November 1, 1999, which is on our website, is somewhat different than this proposal. The rationale, however, is still the same. Apart from structure issues, the principal differences are: (1) the extension of the exclusivity period for claims from 7 to 10 years, and (2) the absence of the grants program).

FIM RATIONALE AND PROPOSED GUIDELINES FOR THE NUTRACEUTICAL RESEARCH & EDUCATION ACT – NREA

“Nutraceuticals” is a comprehensive term which includes foods, dietary supplements (as defined in DSHEA) and medical foods that have a health-medical benefit including the prevention and/or treatment of disease. FIM coined and defined the term in order to give this new U.S. health sector a basis and identity from which the Federal government could enact reasoned laws which would encourage nutraceutical clinical research.

FIM, under this proposal, sees no need to separate the categories of foods, medical foods and dietary supplements. The actual or potential patient can receive the same benefit of vitamin E or folic acid if in a pill or a cereal. FIM views pills and foods as dosage formulations to deliver health-medical nutraceutical benefits. FIM also believes that there is little difference between a health or medical claim. Health is primarily the absence of disease. To remain healthy means to prevent or treat disease. These are the primary objectives of medicine. Regulatory attempts to legally separate the two have created mass confusion in the health sector by discouraging clinical research, negatively impacting public well-being.

FIM is aware that the words “prevention” and “treatment” generally are applied to drugs or pharmaceuticals and not to nutraceuticals. This mentality is one example which represents the prevalent epistemologic chaos that must be resolved in order to have rational laws and regulations that will encourage research. After all, people take cranberry juice in order to “prevent” urinary tract infections and Gingko biloba to “treat” memory loss. DSHEA’s attempts to separate structure function, mechanism of action, well-being and deficiency claims from “treatment” or “prevention” of disease claims is a specific example of the epistemologic chaos that is not only having a negative impact on research but also obstructing the delivery of the truthful information to both the healthy and sick regarding the results of clinical studies. Succinctly put, if a company sponsors a clinical study with Gingko biloba which clearly demonstrates that this botanical nutraceutical decreases depression and improves cognitive function in patients with Alzheimer’s disease, the company can not make these claims. In other words, the truth could not be claimed. Who benefits from this unfortunate regulatory reality? Certainly not the patient!

Under this FIM proposal the distinctions are eliminated.

The proposed Nutraceutical Research & Education Act or NREA is based on what the people, healthy or sick, want. FIM sponsored a Gallup survey regarding this issue. The findings were based on telephone interviews with a national sample of 1,013 adults, 18 years of age and older. The general conclusions of the survey are:

1. To avoid having disease – prevention; if disease is present to diminish its intensity or get rid of it – treatment.

2. To have access to proper information regarding the efficacy and safety of the product, be it pharmaceutical or nutraceutical, that they take.

3. To have access to the product.

THE KEY TO ACHIEVING THE ABOVE IS TO DRAMATICALLY INCREASE CLINICAL RESEARCH REGARDING NUTRACEUTICALS IN ORDER TO DETERMINE WHETHER THEY ARE EFFECTIVE AND SAFE. IT IS, THEREFORE, NECESSARY FOR THE FEDERAL GOVERNMENT TO ESTABLISH THE ENVIRONMENT IN WHICH A VIGOROUS NUTRACEUTICAL CLINICAL RESEARCH-BASED INDUSTRY CAN THRIVE.

For this reason, FIM proposes the following:

1. The enactment of the Nutraceutical Research & Education Act or NREA.

2. This includes:

a. The creation of a Nutraceutical Commission (NUCOM) specifically for the review and approval of nutraceuticals.
b. The creation of a nutraceutical research grants program specifically for clinical research.

Because of the many new economic and regulatory problems and opportunities presented by the Nutraceutical Revolution and the emergence of a worldwide nutraceutical industry, the NREA or some Congressional Act containing the same principles must be enacted by Congress. Its key elements should include a mechanism to create the exclusive rights to claims necessary for private investment in research and development, and the creation of appropriate channels for the review, approval and regulation of new products and claims. With regard to exclusivity, it is well established by practical experience that the availability of research-based proprietary claims leads to a research-based industry, stimulates the development and availability of technological advances, and provides a basis for regulations that facilitate and insure accurate and approved information from companies. From a purely economic standpoint, companies desire to make health-medical claims for food and nutritional products because they increase sales. Since the claims at present are not proprietary, however, the vast percentage of industry spending for such products is allocated to promotion instead of research and development. On the other hand, in the traditional pharmaceutical industry, where exclusive claims are usually created by the patent protection available to new molecular entities, investment in research and development is robust and the total research budgets exceed that of the National Institutes of Health.

Perhaps the best evidence that exclusive claims will create a research-based industry is the Orphan Drug Act, designed to facilitate the commercial development and availability of drugs for rare diseases. Under the Orphan Drug system, testing requirements may be reduced and exclusive claimscan be made based on company-sponsored research for a period of seven years after FDA approval – regardless of patent protection. Since the Act was approved in 1983, as of December 31, 1997, there have been 849 designated orphan drugs, 163 of which have been approved for sale in the United States. Thus there is no question that the Orphan Drug Act has been successful in creating a new research-driven health industry.

Regarding reliable information to the physician and consumer, clinical studies conducted for orphan drugs are presented at scientific forums and published in peer-reviewed medical journals, and thus become part of the system where data are reviewed and scrutinized within the medical scientific community. This, in addition to a formal approval structure for health-medical claims by companies, has resulted in a medical and consumer media milieu that strives for accuracy.

Using the Orphan Drug Act as a model for providing proprietary claims for nutraceuticals, companies which make the necessary investment in research and development should be granted seven years exclusivity for health-medical claims based on approved proprietary research. At the same time, the NREA would create a system that determines the appropriate level of research requirements for individual nutraceuticals, allows accurate promotional claims and provides the methodology for the review and approval of product innovations. The NREA would also increase the safety of nutraceuticals by insuring adequate assessment of risk potential and appropriate quality standards, providing post-marketing surveillance when indicated, and facilitating accurate and sufficient information on their proper use.

Has the NLEA, DSHEA and the Medical Food category substantially increased nutraceutical clinical research? It is now obvious that NLEA has not generated much clinical research. FIM predicted that this would occur because of the lack of exclusivity of the FDA approved food claim. Under NLEA, if a company applies to the FDA for a claim approval and the FDA approves such claim, then all other companies have a right to that claim. In other words, the claim is not exclusive, the result of which drives corporate money toward promotion and not research. It is too early to determine the nature of the impact of DSHEA and Medical Foods on clinical research. To be sure, some companies have begun to invest to demonstrate the clinical efficacy and safety of their nutraceutical products. It has yet to be quantified. The latter is understandable because DSHEA was passed in late 1994. It took some time for companies to absorb the message of the Act. On the average, it takes approximately four years to conceive of a product, conduct clinical research on it and have the study published in a reputable medical journal. Also, most companies were unaware of the Medical Food category until the passage of the DSHEA. Clinical research on medical foods, therefore, is following the same time-course as dietary supplements.

It is conceivable that many clinical studies will be published on nutraceutical products that demonstrate health-medical benefits within the next two years. But, at this point in time, we simply don’t know.

To complicate the picture FDA is now attempting to limit the claiming language of both dietary supplements and medical foods, the outcome of which is not predictable and which may have a significant negative impact on corporations who favor investing in clinical research. (FIM’s views are expressed in the attached letter to the President’s Commission on Dietary Supplement Labels regarding DSHEA. Also included in the letter is FIM’s response to the FDA’s ANPR or Advance Notice of Proposed Rulemaking on medical foods.) (See attached letter)

If you have a regulatory system which regulates in two different ways and makes one easy and the other difficult, which is what we presently have with DSHEA, the tendency of the market will be to force things into the definitions of the simpler and not the more complicated one. Thus, DSHEA permits a company to make claims on a specific product whether or not it conducts clinical research on the product in order to determine whether the claims are justified. Because of this and what both FIM and the FDA agree upon is the disturbing degree of unsubstantiated health-medical claims that are presently being made primarily due to the passage of DSHEA. This huge promotional effort being made by corporations is undoubtedly delivering a plethora of false health messages to both the sick and the well regarding safety and efficacy. FIM believes that, despite FDA’s attempts to limit the promotion of unsubstantiated claims, this phenomenon will continue.

NUTRACEUTICAL COMMISSION (NUCOM)

Because current regulatory categories, as perceived by companies that are inclined to conduct clinical research, do not readily confer exclusivity to nutraceuticals, a new regulatory process must be created for their review and approval. At the same time, in the interest of efficiency, care should be taken to incorporate rather than duplicate the roles of established regulatory agencies.

In order to accommodate nutraceuticals within this existing regulatory framework, an inter-departmental commission – known as the Nutraceutical Commission (NUCOM) – should be created to administer the review and approval requirements of nutraceuticals as well as to work across government lines with the FDA, FTC, USDA and their respective functions. The new commission would be housed within the FDA under a Nutraceutical Commissioner, who reports to the Commissioner of the FDA and is appointed by the Secretary of Health and Human Services.

Under the new regulatory process, companies would be able to decide whether to pursue a potential new product development as a nutraceutical or pharmaceutical. If a company chooses to develop a product as a nutraceutical, an option prior to conducting studies would be to submit to NUCOM an executive summary of its proposed product development, following guidelines developed by NUCOM. Unless rejected as unreviewable by NUCOM, the proposed product development could then be moved forward.

Study requirements for a potential new nutraceutical product would be open and flexible. Given the broad role of nutraceuticals, for example, epidemiological data may frequently provide significant evidence in addition to clinical studies. Also, because nutraceuticals frequently work as consolidated substances or mixtures, the focus will be on preventive or therapeutic results, and not necessarily the often economically prohibitive task of identifying whether or not any specific product component is the active one in isolation. After all the best nutraceutical in the world is a mixture called a meal. It keeps people alive. The overriding requirement for supporting data will be that they must be appropriate and sufficient for accurate and reliable health-medical claims, and demonstrate an acceptable level of risk to public safety.

Whenever nutraceuticals are substances that are routinely consumed by the public and generally recognized as safe, there can be little or no requirement for preclinical testing. This will significantly enhance the feasibility of nutraceutical product development by eliminating much of the time and cost required for the development of traditional new drugs. Moreover, in addition to the NUCOM review, safety issues will also be assessed prior to clinical studies by an Investigational Review Board (IRB) within or outside each research institution.

After a sponsor completes its studies and submits a New Nutraceutical Application (NNA), NUCOM will then decide one of the following: (a) that it is not acceptable for review, based on format or merits, or (b) that it is acceptable for review as a nutraceutical.

If the NNA is found acceptable for review, NUCOM will send it for review by appropriate outside experts, drawn from a list of authorities in various specialties assembled by NIH through consultation with medical and other professional societies. Because regimented guidelines and subcategories are difficult to formulate in the area of nutraceuticals, submissions will be reviewed on a case-by-case basis, using the flexibility of the outside expert system.

In order to increase objectivity and provide a comprehensive and logical framework for the review of products and claims, a Nutraceutical Index would be established as an integral part of the evaluation process. Using the Nutraceutical Index, experts selected by NUCOM would evaluate a submission both in terms of the advantages and disadvantages of a product’s availability and unavailability. Each submission would then be classified as either a medical nutraceutical (promoted to physicians only), or a general nutraceutical (promoted to physicians and the public) – depending on the request of its sponsor and the subsequent evaluation.

NUCOM would be responsible for harmonizing the index and evaluations, but can override the experts’ evaluations only for compelling reasons. Once a submission is judged approvable, final labeling – including product claims – would be determined and approved by NUCOM in cooperation with the appropriate regulatory elements within the regulatory agencies. Product approval and labeling decisions through NUCOM, however, would be binding and enforced by the FDA, FTC and USDA in their established roles.

GUIDELINES FOR SUFFICIENT EVIDENCE TO MAKE NUTRACEUTICAL CLAIMS

At the 1996 FIM conference entitled, “How to Develop, Make Claims On and Market Medical Foods”, FIM recommended the following guidelines for standardizing health-medical claims for all nutraceuticals:

1. There must be sufficient clinical data to support the claim. (The studies need not be double-blind.)

2. Accepted surrogate markers or biomarkers (instead of clinical end-points) can be sufficient to support a claim. A surrogate or biomarker, for example, could be a biochemical measurement. If a nutraceutical lowered cholesterol, the implication would be that it could prevent heart disease. A clinical study, however, which demonstrates that this substance can reduce the recurrence of heart attacks is a clinical end-point.

3. Acceptable clinical data to support the product rationale or mechanism of action are desirable but not always necessary. All pertinent data must be published in respected medical-scientific journals. (This is the first step of the peer review process.)

4. Independent consensus or medical expert group opinion should be obtained. (This is the second step of the peer review process.)

5. Post-marketing surveillance. When indicated, this effort should concentrate particularly, though not exclusively, on aspects of safety.

The FIM recommendations do not quantify the amount of data needed. For example, a fortified chicken soup that, when taken for a few days, reduces the symptoms of the common cold, would require much less data and post-marketing surveillance (if any) than a new oriental botanical herb that is effective in improving cognitive function and intended for chronic administration.

To those who stubbornly cling to traditional pharmaceutical clinical research guidelines, these cannot entirely apply to nutraceuticals. For example, if one were to evaluate all the possible combinations of the nine nutraceuticals presented at one of FIM’s conferences discussing nine cardiovascular nutraceuticals in traditional pharmaceutical clinical models, the cost of such research could conceivably approach the entire annual clinical research budget of the NIH. Product quality. Good Manufacturing Practices, USP standards and other requirements could also be monitored and enforced by existing agencies under established regulations and procedures. Labeling may be modified by NUCOM, if warranted, by subsequently positive or negative data.

A policy must be developed to discourage generic substitution during the exclusivity period for nutraceutical advances, since premature generic substitution would undercut the dynamics of the research-based economic system for the development of product innovations.

CLINICAL RESEARCH NUTRACEUTICAL GRANTS PROGRAM

The basic ingredients of any innovative process are: (a) having an idea, and (b) testing it. The fewer obstacles between (a) and (b), the greater the innovative potential. For example, if Einstein or Da Vinci felt the urge to create, they could simply walk to the blackboard or the easel to express such creativity.

The innovative process in medicine, however, is vastly more difficult and costly. It usually involves a substance or technique (the idea) and the clinical evaluation of the aforementioned (testing it). Penicillin in a test tube is undiscovered unless it is clinically tested and found medically useful. Antioxidants that protect rodents from deleterious cardiovascular situations should only be recommended for rodents until they are proven clinically effective in people. Far too many claims made to the public are primarily supported only by animal or other preclinical data.

One of the great tragedies of our times is that, over the past twenty years, a pervasive and aggressive national mentality and policy have evolved which have effectively blocked the creative clinical investigator at the critical step in the discovery process – the clinical testing of an idea. To compound the problem, the current ugly face of spiraling litigation further discourages many physician innovators from testing their ideas in patients.

The phenomena of the Orphan Drug Act, AIDS group activism and revised regulatory procedures for accelerating the availability of important new therapies are powerful tacit endorsements by society of the critical importance of clinical research. The argument is compelling, therefore, to encourage clinical research on promising nutraceutical products.

Since clinical research is the key for discovery, and is particularly difficult to conduct in a highly regulated environment, it is proposed that a federal grants program be established specifically to increase nutraceutical clinical research. And, since it is the largest creative body of the federal government, it is proposed that the National Institutes of Health hold responsibility for administering such a program.

Given that the intent of laws and regulations is to serve the public interest, and it is deemed important to bring the benefits of nutraceuticals to the American public, then the encouragement of clinical research by Congress is not only one of the keystones necessary for success but an essential duty of this great institution.

CONCLUSION

The NREA proposed by the Foundation for Innovation in Medicine would establish the mechanism for exclusivity that is essential for the creation of a responsible, industry-funded, primarily clinical research-based industry. It would establish for the first time an appropriate channel for the submission, review and regulation of new products and claims in this increasingly important new category. It would streamline and facilitate their appropriate research and development. It would enhance their safe and proper use, and provide public access to accurate and sufficient product information. And it would broaden the dispersal of federal grants to include the clinical testing as well as the initial identification of potential nutraceutical advances.

The adoption of these economic and regulatory reforms would result in major advancements in the health of the American public, the continuing global competitiveness of the U.S. food and drug industries, and a positive response to the demonstrated public interest in government regulations that support, rather than block, the development and availability of nutraceutical products that can have a major impact on the prevention and/or treatment of disease.

FIM’s RESPONSE TO THE FDA ANPR ON MEDICAL FOODS

Kenneth D. Fisher, Ph.D.
Executive Director
Commission on Dietary Supplement Labels
Office of Disease Prevention and Health Promotion
Room 738G
Hubert H. Humphrey Building
200 Independence Avenue, S.W.
Washington, DC 20201

Dear Dr. Fisher:

I am responding to the draft document of the Commission on Dietary Supplement Labels regarding dietary supplements (DSHEA). Comments will also be made regarding conventional foods (NLEA) and medical foods (Orphan Drug Act). Though NLEA, DSHEA and the medical foods regulations under the Orphan Drug Act are distinct legal and regulatory entities, they are inextricably intertwined in the government’s attempt to significantly improve the health of the American people.

With the above in mind, let’s turn to the second charge of the Commission which is to… “evaluate how best to provide truthful, scientifically valid, and not misleading information to consumers so that such consumers may make informed and appropriate healthcare choices for themselves and their families.”

It naturally follows that in order to address this charge, two fundamental questions should be asked. They are:

1. How do we obtain truthful, scientifically valid and not misleading information?

– and –

2. How do we inform consumers of such information so that reasonable choices can be made?

Regarding the generation of truthful and valid information, the best way to bring this about is to conduct research, particularly clinical research, on the products of which the consumer will be informed.

Regarding the transmission of such information to consumers (the healthy and the sick), the conclusions of the data obtained by clinical research should be both truthfully and effectively transmitted.

At this point, DSHEA does not seem to be the answer to the first question and certainly does not provide an answer to the second one. In fact, DSHEA encourages the dissemination of confusing and semitruthful instead of truthful information.

Recently, the Foundation for Innovation in Medicine (FIM) responded to the FDA’s Advance Notice for Proposed Rulemaking (ANPR) on medical foods. FIM’s response to the ANPR is included at this point in order to present a view broader than DSHEA and its impact on research and dissemination of truthful information.

THE FOUNDATION FOR INNOVATION IN MEDICINE’S (FIM) RESPONSE TO THE FDA ANPR ON MEDICAL FOODS

– An Overview of the Nutraceutical Revolution –

April 10, 1997

Dockets Management Branch (HFA-305)
U.S. Food and Drug Administration
Department of Health & Human Services
Room 1-23
12420 Parklawn Drive
Rockville, MD 20857

Re: Docket No. 96N-0364
Comments Re: “Regulation of Medical Foods”

To The Food and Drug Administration:

The Foundation for Innovation in Medicine (FIM) congratulates the FDA for its Advance Notice of Proposed Rulemaking (ANPR) dealing with the regulation of medical foods. FIM is particularly supportive of FDA’s comments regarding the importance of producing quality products and encouraging clinical research. Unfortunately, there is a single item in this proposal that, if implemented, will nullify the general good of the ANPR for it will have a major negative impact on the health of the American people. The proposal which deals with the dramatic constriction of the definition of a medical food will significantly discourage U.S. corporate investment in the clinical research that is essential to demonstrate reasonable efficacy and safety of individual medical food products. We must ask ourselves, “Do we want this?”

Hopefully, the following points will convince FDA of the importance of FIM’s aforementioned point of view:

I. The Nutraceutical Revolution

“Nutraceuticals” is a comprehensive term which includes foods, dietary supplement (as defined in DSHEA), medical foods, etc. that have a health-medical benefit including the prevention and/or treatment of disease. I coined and defined the term in order to give this new U.S. health sector a basis from which the

Federal government could enact rational laws which would encourage nutraceutical research, and particularly clinical trials.

The revolution began in 1983 when the NIH consensus group recommended calcium for the prevention of post-menopausal osteoporosis. Within a very short period of time, the vast majority of Americans knew about this recommendation.

Historically in the United States, the health food industry was a consumer business largely based on traditional home and other remedies. Then in the early 1980’s, the potential medical benefits of products such as calcium and fiber rose to prominence – with university-based clinical data to support claims for their benefits. Sparked by mass and medical media coverage, for the first time in modern U.S. medicine, physicians joined consumers in their broad belief that nutrients have medical value. This marked the entry of nutraceuticals into the mainstream of clinical practice and scientific medical research. It gave rise to an increasingly urgent need to rationalize the scientific and medical development and commercial availability of these products, and factual communications about them, to a new audience of physicians and consumers. Clinical data stole center stage and continue to drive the nutraceutical revolution as exemplified by such products as folic acid and vitamin E.

II. The Federal Government Response – NLEA and DSHEA

Because of increasing consumer belief and media interest in the enormous benefits of nutraceuticals coupled with a continuous flow of positive clinical data supporting these benefits, understandable pressures were brought to bear on the federal government which resulted in the enactment of two historic laws – NLEA and DSHEA. Though symbolically a major breakthrough in the psychology of permitting nutraceutical claims, the NLEA primarily discourages research because it grants the right to make a health-medical claim on a specific food or category of foods to all companies. For example, let’s assume that company A sponsors the research which demonstrates that its chicken soup reduces the morbidity (signs and symptoms) of the common cold. Let’s also assume that the clinical data are sufficiently adequate to convince the FDA to grant the company the right to make that claim. FDA, according to NLEA, must then grant the right to make such a claim to all companies and not only the one that sponsored the research. Why then should company A sponsor the research? To support its competitor? Of course not! Company A will instead spend money on promotion, not research. The NLEA, though a major step forward, is indeed a major deterrent to research oriented companies. History has convincingly supported this view. NLEA has spawned few research-oriented nutraceutical companies .

After NLEA, the Congress passed DSHEA which deals with dietary supplements. DSHEA, unlike NLEA, permits companies, without prior FDA approval, to make claims on dietary supplements regarding structure-function, mechanism of action, well-being and classic deficiencies. DSHEA, however, prohibits claims made regarding the diagnosis, treatment, mitigation, cure, and prevention of disease.

FIM originally believed this major piece of legislation would have an immediate and highly positive impact on creating an academic-corporate research-oriented nutraceutical complex such as exists in the traditional pharmaceutical and biotech industries. Unfortunately, the expected research surge is not yet evident. Companies inform FIM that the vagueness of DSHEA regarding the rules for claimsmaking profoundly discourages research initiatives. For example, if a company invested in clinical research which demonstrated that capsules containing a cranberry extract prevented the recurrence of urinary tract infections in women, it would not be able to make this claim. Instead of claiming, “Our cranberry extract prevents urinary tract infections” – which is the truth – it, under DSHEA, might be able to say, “Our cranberry extract provides dietary support for a healthy urinary tract”, which is a half-truth and can be easily misleading. The conclusion is that the more research one does, the less one can say about it, resulting not only in a corporate hesitancy to invest in research but also a deprivation of the delivery of nature’s promise to all of us. (For the record, FIM does not fully agree with the corporate opinion regarding the degree of the negative impact of DSHEA on research. In time, FIM believes that companies will become comfortable with DSHEA and invest in research. But, this is only a FIM opinion.)

III. Medical Foods

After the passage of DSHEA, companies, both large and small, turned to their legal consultants to advise them regarding the confusing rules of DSHEA concerning product claims. A significant number of them recommended that companies develop products as medical foods and not as dietary supplements. FDA prior approval is not necessary for a health claim for a medical food, and claims can be made regarding the positive nutritional properties of a product related to a disease, provided that corporations stress that the products must be given to patients under a physician’s or medical supervision. Corporations feel much more comfortable with these clear rules for claiming. As a result, though not yet quantified, companies have initiated a substantial number of clinical studies in order to demonstrate the safety and efficacy of many medical food products.

It appears, therefore, that the medical food category has led to what we all want — an increase in preclinical and particularly clinical research. This phenomenon should not be tampered with but encouraged. It naturally follows that the degree of restriction of the definition of a medical food will be followed by a proportional decrease in clinical research. Once more, “Do we want this?”

IV. Epistemologic Chaos: The Need to Understand it

After the NIH consensus group on calcium and osteoporosis, FIM predicted that future positive clinical trials of nutraceutical products would result in new Federal laws that would diminish the restrictions on making health-medical claims. Because of the complexity of the situation, FIM also predicted that these initial new laws would be substantially imperfect and would periodically be improved upon as the societal nutraceutical learning curve increased. The greatest obstacle to bringing about rational changes in new laws and regulations is the attempt by the government to distinguish a health versus a medical claim. The distinction is epistemologically false. In a vast majority of cases there is no distinction between a health and medical claim. Both primarily deal with the prevention and treatment of disease. People consume fiber to both prevent and treat heart disease, feverfew to prevent migraine, and echinacea and chicken soup to treat the common cold – all medical indications related to disease. Logical and effective legislation which encourages research cannot be brought about until the distinction between health and medical claims is abolished. The lack of a surge of clinical research after the passage of DSHEA is a powerful testimony to support this argument for the health related claims permitted in DSHEA are really medical or disease claims, yet companies are prohibited from making such medical or disease claims.

The ANPR distinguishes foods for special dietary use from medical foods. This unnecessary distinction is another example of the epistemologic chaos that creates confusion for research oriented companies. Also, any attempt to define what constitutes a “distinctive nutritional requirement” is truly a difficult one. I would strongly recommend that a group of medical and scientific experts be assembled by the FDA to attempt to clearly define this term for its definition will heavily impact on the degree of nutraceutical research.

The principles that should determine the acceptability of claims for medical foods are similar to those qualitatively similar to those governing medical-health claims for drugs – sufficient evidence for efficacy and safety regardless of its formulation or mechanism of action. At the 1996 FIM conference entitled, “How to Develop, Make Claims On and Market Medical Foods”, FIM recommended the following guidelines for standardizing health-medical claims for all nutraceuticals (foods, dietary supplements, medical foods, etc.):

1. There must be sufficient clinical data to support the claim. (The studies need not be double-blind.)

2. Acceptable surrogate markers (instead of clinical endpoints) can be sufficient to support a claim.

3. Acceptable clinical data to support the product rationale are desirable but not always necessary.

4. All pertinent data must be published in respected medical scientific journals. (This is the first step of the peer review process.)

5. Independent consensus or expert group opinion should be obtained. (This is the second step of the peer review process.)

6. Post-marketing surveillance. This effort should concentrate particularly, though not exclusively, on aspects of safety.

If our society is to enjoy the enormous benefits that ongoing medical food research would bring about, then it is imperative that the definition of the medical food remain unchanged. There is little evidence that DSHEA and the category of “foods for special dietary use” has sparked a surge of corporate preclinical and clinical research. On the other hand, it is common knowledge among industry observers that the medical food regulations have indeed sparked an abundance of research. Considering all the aforementioned points, the wise position would be for all of us to wait a few years to determine, in a quantifiable way, the impact of DSHEA and medical foods on the availability of products with demonstrated health-medical benefits that will positively impact the prevention and treatment of disease.

FDA is particularly concerned about the increasing number of insufficiently substantiated healthmedical claims being made by companies, many of which can be characterized as charlatanic. An effective way to increase such charlatanic behavior would be to constrict the definition of a medical food which, as repeatedly mentioned before, would decrease clinical research which is necessary to support truthful claims. The generation and promotion of sound clinical data supporting effective and safe products is the best way to drive out poorly documented or bad ones. I hope you agree.

Sincerely yours,
Stephen L. DeFelice, M.D.

Return to reference to this letter in the Rationale And Proposed Guidelines document.