The Commission members were Professor Norman R. Farnsworth, Research Professor of Pharmacognosy and Senior University Scholar at the University of Illinois at Chicago; Robert S. McCaleb, President of the Herb Research Foundation; Annette Dickinson, Ph.D., of the Council for Responsible Nutrition; Malden Nesheim, Professor of Nutrition and former Provost at Cornell University; Shiriki K. Kumanyika, Associate Director for Epidemiology at Pennsylvania State University School of Medicine; Anthony T Podesta, an attorney and legislative expert on issues relating to food and drug law; and Margaret Gilhooley, Professor of Food and Drug Law at Seton Hall Law School in New Jersey and a former FDA attorney.
A brief overview of the report, with specific emphasis on botanicals, follows:
FORMAT OF THE REPORT
In the DSHEA, Congress mandated that the recommendations of the CDSL be published as proposed rules, which could become regulations after public comment and any necessary revisions. The Commission chose to limit the items in its reports which could be considered proposed rules, making three kinds of statements:
Findings -- Conclusions reached by the Commission;
Policy Guidance -- Advice to agencies, groups or individuals, not meant as recommended regulatory changes;
Recommendations -- Proposals to Congress or governmental agencies (usually FDA) intended to be acted upon.
SAFETY OF DIETARY SUPPLEMENTS
Dietary supplement proponents often claim that they are relatively safe, especially when compared to pharmaceutical drugs, yet one of the primary issues expressed by individuals and groups during Congressional hearings on DSHEA was concern about safety and potential misuse or abuse of dietary supplements, particularly botanicals. During the CDSL public hearings, supplement proponents charged the FDA had abused its authority by improperly classifying herbs as "unsafe food additives." Proponents of stronger regulation -- including regulators themselves -- claimed that DSHEA hampers the FDA's ability to protect the public. The Act itself states that dietary supplements "are safe within a broad range of intake, and safety problems with the supplements are relatively rare." Congress emphasized in DSHEA that the government should act quickly if a safety problem arises, but that it should not impose unreasonable barriers or restrict access to safe products. The Commission underscored b oth points, stating the following:
CONCERNING THE SAFETY OF BOTANICALS, THE REPORT STATES:
"There are relatively few reports in the scientific literature that indicate potential or actual toxicity following the use of these products. When such reports are found, they often are single-case reports involving allergenic reactions or toxicity due to improper labeling, adulteration, or an idiosyncratic reaction...."
ON ENFORCEMENT ISSUES:
"The Commission recognizes the importance of having adequate and timely enforcement procedures for products marketed as dietary supplements that are not safe or have a high potential for abuse, while maintaining a regulatory climate that preserves the availability of safe products. The apparent safety of the majority of products now marketed as dietary supplements actually increases the importance of having adequate enforcement mechanisms, because consumers may then assume that a wide margin of safety automatically applies to any product classified as a dietary supplement."
Further, in contrast to the characterization of the FDA, supplement opponents and sometimes the media, the Commission pointed out that the safety standard for dietary supplements is tougher than for food: "Under DSHEA, FDA must show affirmatively in court, that there is an unreasonable risk posed by consumption of a dietary supplement. The agency need not show that injury has occurred, only that a reasonable possibility of harm exists."
The Commission made no formal recommendations in the area of safety, but made these suggestions (Policy Guidance):
1. The supplement industry must accept the responsibility of assuring the safety of dietary supplements and take actions to meet expectations expressed in DSHEA that supplements are and will continue to be safe for use by the public.
2. The CDSL urged the FDA, industry, scientists and consumer groups to cooperate in the development of postmarketing surveillance systems so that adverse reactions can be reported and corrected quickly. The report cites examples of how other nations employ such reporting systems, including Australia, England, France, and the World Health Organization (WHO) monitoring center in Sweden.
3. The Commission urged manufacturers to include appropriate warnings on labels, as permitted by DSHEA.
4. CDSL urged the FDA to take swift enforcement action to address safety issues such as those posed by "products containing ephedrine alkaloids."
5. Federal and state agencies are responsible for enforcement actions and may need to be given additional resources to develop the evidence, "in the context of their overall health priorities."
NLEA HEALTH CLAIMS IN DIETARY SUPPLEMENT LABELING
The predecessor of DSHEA was the Nutrition Labeling and Education Act of 1990 (NLEA), a law allowing FDA to approve "health claims" for both conventional foods and dietary supplements. Health claims are statements that characterize the relationship between a nutrient and a disease or health-related condition. These health claims for conventional foods were to be approved only when "significant scientific agreement" exists; Congress left to the FDA's discretion what level of evidence would be required to make health claims for dietary supplements. Supplement proponents argued that a standard of "significant scientific evidence" was more appropriate, as it is often difficult to get scientists to agree on fine points in science, especially for the fast-breaking area of nutritional research.
In order to maintain "a level playing field" FDA chose the same significant scientific agreement standard for supplements as for foods. The supplement industry feared that many supplements might not pass such a standard, and that the FDA was not maintaining a level playing field, by requiring more "agreement" for supplements than for foods. DSHEA's sponsor, Sen. Orrin Hatch, maintained that nothing is wrong with the standard, but with the FDA's interpretation of that standard. The Commission recommended that:
1. "The process of approval of health claims as defined by NLEA should be the same for dietary supplements and conventional foods.
2. "The standard of significant scientific agreement is appropriate and serves the public interest." However, CDSL added a statement that this standard "should not be so strictly interpreted as to require unanimous or near-unanimous support." This seems to echo Sen. Hatch's concern about overinterpretation of the phrase.
3. "The FDA should ensure that broad input is obtained to ascertain the degree of scientific agreement for a claim." The CDSL encouraged using panels of qualified scientists outside the agency and giving considerable weight to the views of other government agencies. This is significant, since other government agencies supported the claim for folic acid against birth defects long before the FDA thought there was "agreement." The Commission is recommending (not just a suggestion) that the FDA stop being so insular in its decision-making.
DSHEA STATEMENTS OF NUTRITIONAL SUPPORT
One of the major changes DSHEA made in food and drug law is that it allows dietary supplements to bear "statements of nutritional support" including "structure and function" claims, which allow some health-related information to be conveyed on product labels. Such claims must be truthful and not misleading and must be based on scientific evidence in the possession of the manufacturer at the time the claim is made. The standards of evidence for such claims are not as strict as those for health claims under NLEA, and they may be made without the FDA's concurrence or permission.
The CDSL report offers the following policy guidelines (not regulatory proposals or "recommendations") in developing and evaluating these statements/claims:
1. "Statements of nutritional support should provide useful information to consumers about the intended use of a product."
2. "Statements of nutritional support should be supported by scientifically valid evidence substantiating that the statements are truthful and not misleading."
3. "Statements indicating the role of a nutrient or dietary ingredient in affecting the structure or function of humans may be made when the statements do not suggest disease prevention or treatment."
4. The terms "stimulate," "maintain;" "support," "regulate," or "promote" "can be appropriate when the statements do not suggest disease prevention or treatment or use for a serious health condition."
5. "Statements should not be made for products to `restore' normal or `correct' abnormal function when abnormality implies the presence of disease." The report cites a claim to "restore" normal blood pressure as an example, if the abnormality implies hypertension.
6. These statements should be distinct from NLEA health claims and should not "state or imply a link between a supplement and prevention of a specific disease or health-related condition."
7. These statements are not drug claims and should not refer to specific diseases, disorders, or classes of diseases and should not use the terms "diagnose," "treat," "prevent," "cure," or "mitigate" -- words that are listed in the Food, Drug and Cosmetic Act as part of the definition of "drug."
The Commission recommends that to the extent that financial and human resources are available, FDA should continue to give guidance to manufacturers by responding to letters of notification (i.e., those from the manufacturer notifying FDA of the intent to market a product with a specific claim) when FDA deems a proposed statement to be inappropriate.
SUBSTANTIATION OF STATEMENTS OF NUTRITIONAL SUPPORT
The Commission reviewed over 1,000 claims submitted to FDA by manufacturers and agreed that guidelines are needed to standardize the format of the notification letters that manufacturers send to FDA within the 30-day time period from the date of first offering the new claims. Such letters should include the following: statement of purpose of the product, vendor information (address, etc.), product identification including copy of the label, ingredient statement (including, for botanicals, the common name, Latin name with botanical authority, and plant part used), and intended use, including recommended dosage and appropriate contraindications and warnings.
The Commission initially recommended that the letter include a summary of the evidence used to substantiate the safety and efficacy of the product, and a consumer version of the summary evidence. This recommendation was dropped in the final por report and replaced with "policy guidance" urging manufacturers to provide such summaries "in the notification letter or in a separate public notice."
The Commission also made specific suggestions regarding the contents of the manufacturer's substantiation files. They should include the following items: a copy of the notification letter sent to FDA, key evidence to substantiate statements of nutritional support or structure/function claims, "including an interpretive summary of the evidence by individual(s) qualified by train ing and experience," identity and quantity of ingredients that are the subject of the claim, evidence substantiating safety of the product, assurance that good manufacturing practices were followed in producing the product, and the qualifications of the person(s) who reviewed the evidence for safety and efficacy.
PUBLICATIONS USED IN CONNECTION WITH SALES (THIRD PARTY LITERATURE)
The Commission supports increased use of third party literature "to help consumers use dietary supplements appropriately." It approves the use of summaries of scientific studies that mention a particular brand of product that was used in a study. The report recognizes that "Several organizations [including the American Botanical Council and the Herb Research Foundation] are currently publishing materials specifically intended as `third party literature.' This literature can provide useful information for consumers, provided it meets all of the requirements of DSHEA, including the requirements that the information be truthful, not misleading, and balanced." The report suggests that the FDA should undertake proactive monitoring and develop regulatory guidance "if necessary."
BOTANICAL PRODUCTS
One of the most controversial and probably most misunderstood recommendations of the draft report published in June deals with the possibility of reviewing and approving therapeutic claims for some herbs as over-the-counter (OTC) drugs. Many people have incorrectly interpreted this recommendation as a move by the Commission members to remove herbs from dietary supplement status and place them back under FDA's more extensive control as drugs. Some public comments claimed that the Commission overreached its mission by dealing with the therapeutic use of botanicals. These comments claim that under DSHEA, herbs and other supplements are defined as foods, and thus any suggestions about potential regulation of herbs as drugs is clearly outside the intention of the Act and the mission of the Commission. Much of this comes from fear that such recommendations will result in herbs being classified as drugs and no longer as dietary supplements. This is not what the Commission is recommendi ng.
As many in the botanical community are aware, people use herbs and other supplements in a variety of ways, sometimes for the prevention or treatment of disease. The Commission noted that some supplement uses "are similar to" OTC drug uses. Public testimony before the Commission raised this issue repeatedly, and CDSL commented that "in some cases, current scientific evidence supports such (OTC drug) uses." The report is careful to emphasize that drug-only status for herbs is not under consideration: "the Commission recognizes that DSHEA includes botanicals under the definition of dietary supplements and does not intend to recommend any change in legislation to alter the status of these products as dietary supplements."
Based on prior testimony by ABC and others, the report makes brief mention of the regulation of herbs in foreign countries. CDSL reviewed the World Health Organization (WHO) "Guidelines of the Assessment of Herbal Medicines" as well as regulations in Australia, England, France and Germany, where herbal products are generally marketed as licensed drugs. CDSL also reviewed regulation in Japan, China and other countries; with 18 regulatory schemes reviewed, 12 of which allowed a more streamlined means of approving therapeutic claims for botanicals labeled as drugs.
The Commission suggested that for botanical products that cannot meet FDA OTC review requirements, "more study is needed regarding the establishment of some alternative system for regulating botanicals that are used for purposes other than to supplement the diet." The study should include "the types of disclaimers that might apply and the appropriateness of such a system within the U.S. regulatory framework. Such a comprehensive study would go beyond the mandate of this Commission, which is limited to dietary supplement uses of these products." These are important words and can provide the basis for major progress for proper labeling of therapeutic claims for herbs. The Commission concluded that "a comprehensive evaluation of regulatory systems used in other countries for botanical remedies is needed."
RECOMMENDATIONS ON BOTANICALS
1. "The Commission recognizes that, under DSHEA, botanical products should continue to be marketed as dietary supplements when properly labeled."
2. "The Commission strongly recommends that FDA promptly establish an OTC botanical products panel to consider petitions from manufacturers for preventive and therapeutic uses of such products."
This should lay to rest the concerns of some who believed that the Commission was recommending a shift of herbs to the OTC drug category. The CDSL emphasized that herbs are dietary supplements and should remain as such, and pointed out what some supplement proponents may have forgotten: "Botanicals have always been included as potential candidates for OTC status. The Commission is not recommending a new category of OTC drugs, but believes that a dedicated OTC panel on botanicals would facilitate the review of OTC claims."
EXPERT EVALUATION OF SAFETY, LABEL STATEMENTS, AND CLAIMS
The Commission also suggested that the industry consider establishing an expert advisory committee on supplements "to provide scientific review of label statements and claims and to provide guidance to the industry regarding the safety, benefit, and appropriate labeling of specific products." This is an important step and echoes the proposal for a Botanical Ingredient Review expert panel initially proposed by the Herb Research Foundation and the American Herbal Products Association in 1991 in public comments on NLEA (AHPA, 1991). Unfortunately, at that time, FDA rejected the idea of an outside scientific panel to review the safety of herbs. This rejection and other related events are key issues that motivated the industry and consumer movement to support DSHEA. Now, the CDSL is suggesting a similar system, with the mission of advising industry on "safety benefits and appropriate labeling of specific products."
RESEARCH ISSUES
The report concludes that it is in the public's interest that more research be conducted that "documents the relationships between dietary supplements and maintenance of health and/or avoidance of disease." It would like to see "incentive mechanisms" developed to encourage industry to research products. The Commission strongly supports continued research by federal agencies on the benefits of dietary supplements. In addition, the Commission made this recommendation (not just a suggestion) to the Office of Dietary Supplements (ODS): "ODS should place greater emphasis on its assigned role of advising other government agencies on a broad range of issues relating to dietary supplements."
And in a recommendation to Congress:
"ODS should be funded at the level authorized by DSHEA."
CONCLUSION
The Commission finished its work making very few of the kind of "recommendations" that would be published as proposed rules. Instead, it provided background, analysis, and differing viewpoints on specific issues in the complex area of supplement regulation. It made many suggestions (called "policy guidance") which should serve as recommended, but voluntary, directions for consideration by industry, Congress and government agencies.
In summary, the report:
1. underscores the safety of supplements;
2. endorses the industry's expert panel recommendation (the Botanical Ingredient Review or BIR);
3. urges both industry and the FDA to seek expertise outside their ranks;
4. recommends further research (and research funding) as well as consideration of other regulatory options, including OTC drug approval (when appropriate and requested by industry); and
5. suggests consideration of a mechanism for approval of further therapeutic claims for products which may not meet the scientific standards required for OTC approval, such as the traditional use claims currently allowed abroad.
SOURCE:
Commission on Dietary Supplement Labels. Report to the President, the Congress, and the Secretary of Health and Human Services. November, 1997. Available on DHHS homepage heep://web.health.gov/dietsupp
REFERENCE
American Herbal Products Association. 1991. Botanical Ingredient Review Proposal to the Food and Drug Administration. May 8. In HerbalGram 25:32-37.
Article copyright American Botanical Council.
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By Rob McCaleb and Mark Blumenthal