IV. Summary and Request for Comments FDA asks for comments on the regulatory framework presented in the industry submission in section II. of this document and the economic issues discussed above. In addition, the agency requests comments on the following issues:

1. Is there a need to develop specific defect action levels (DAL's) for dietary ingredients? While FDA has established DAL's for many food ingredients, including botanical food ingredients, these DAL's reflect their use for specific purposes, for example, the use of many botanicals as spices, flavorings, or other trace ingredients in foods. The DAL's are designed to provide reasonable assurance of the safety and wholesomeness of the ingredient when it is present in the food supply in small quantities. However, the use of a botanical in a dietary supplement may result in a much greater exposure to the botanical ingredient for consumers because the dietary supplement will be consumed in greater amounts than if the ingredient was in a food as a spice or flavoring agent. Therefore, FDA tentatively concludes that it would not be appropriate to apply the current DAL's to dietary supplements, and the agency requests comments that would assist in developing DAL's for dietary supplements.

2. FDA requests comments on appropriate testing requirements to provide positive identification of dietary ingredients, particularly plant materials, used in dietary supplements. The misidentification of dietary ingredients, particularly plant materials, used in dietary supplements may present a significant public health and economic concern. However, the analytical methodology available for identifying many dietary ingredients is limited. Furthermore, section 402(g)(2) of the act states that CGMP regulations may not impose standards for which there is no current and generally available analytical methodology. FDA is asking for comments on the technical and scientific feasibility for the identification of different types of dietary ingredients. The agency also solicits information on what constitutes ``adequate testing'' for identity of different types of ingredients, and, in the absence of testing, what types of practices would be effective alternatives to testing to ensure the identity of different types of dietary ingredients.

3. FDA requests comments on standards that should be met in certifying that a dietary ingredient or dietary supplement is not contaminated with filth; that it is free of harmful contaminants, pesticide residues, or other impurities; that it is microbiologically safe; and that it meets specified quality and identity standards. For food (Sec. 110.80), it is CGMP for a manufacturer to accept certification from a supplier that products do not contain microorganisms or filth or other foreign material that would adulterate the product in lieu of direct testing or evaluation of the raw materials or final product. However, many ingredients used in dietary supplements do not have a history of food use in the United Page 5708 States, and thus the potential for contamination with microorganisms or filth is unknown. The agency does not have information that provides a basis for it to determine whether certification by a supplier provides adequate assurance that a dietary ingredient is what it purports to be and is not adulterated. Therefore, the agency asks for comments on whether a certification will provide assurance that dietary ingredients are not contaminated, or whether specific testing requirements are necessary and would effectively ensure the safety and wholesomeness of these products.

4. CGMP is intended to ensure that a firm follows quality control and other procedures necessary to ensure that a food is safe for its intended use. It is possible that a firm will develop adequate standard operating procedures and other mechanisms to achieve this end, but that such procedures will not be followed. The agency asks for comments on whether there is a need for CGMP to include requirements for manufacturers to establish procedures to document that the procedures prescribed for the manufacture of a dietary supplement are followed on a continuing or day-to-day basis. FDA is aware that no provision of part 110 deals with the establishment of documentation that a manufacturer is following established procedures prescribed for the manufacture of a dietary supplement, and that section 402(g) of the act states that any CGMP regulations for dietary supplements are to be modeled after the CGMP regulations for food. However, FDA's tentative judgment is that section 402(g) of the act does not preclude FDA from adopting CGMP regulations for dietary supplements that have no counterpart in part 110 if there is an appropriate basis for so doing. FDA requests comments on this issue.

5. The agency asks for comments on whether dietary supplement CGMP should require that reports of injuries or illnesses to a firm be evaluated by competent medical authorities to determine whether followup action is necessary to protect the public health. Many dietary supplements contain pharmacologically active substances, and some may contain potential allergens that result in adverse events in certain consumers. The presence of pharmacologically active substances in these products distinguishes them from most other foods. Because of the potential for serious injury or illness in some persons from the consumption of such substances, it may be necessary that trained medical professionals, rather than quality control or nonmedical scientific/regulatory personnel, evaluate all reported adverse events associated with the use of a specific substance and advise responsible management of their findings. FDA also asks for comments on whether CGMP for dietary supplements should contain a requirement that a firm establish procedures for determining whether a reported injury constitutes a serious problem, and what actions are to be taken when serious problems are identified. FDA is aware that no provision of part 110 deals with followup to reports of illness or injury, and that section 402(g) of the act states that any CGMP regulations for dietary supplements are to be modeled after the CGMP regulations for food. However, as stated above, FDA's tentative judgment is that section 402(g) of the act does not preclude FDA from adopting CGMP regulations for dietary supplements that have no counterpart in part 110 if there is an appropriate basis for so doing.

6. FDA asks for comments on whether CGMP for dietary supplements should require that manufacturers establish procedures to identify, evaluate, and respond to potential safety concerns with dietary ingredients. As discussed above, many dietary ingredients have little history of use in food in the United States or of use in the amounts that would be used in a dietary supplement. Moreover, dietary ingredients are excepted from the definition of ``food additive'' in section 201(s)(6) of the act (21 U.S.C. 321(s)(6)). In these circumstances, it may be appropriate to provide that CGMP requires that a manufacturer critically evaluate the available scientific information on the safety of the dietary ingredients that it intends to use in its products to assure itself that those products will be safe. FDA asks for comments on whether such an evaluation is necessary, and, if so, what elements need to be included in such an evaluation and their relative importance (e.g., the presence and potency of pharmacologically active substances, the presence of different microorganisms, the presence of different contaminants and impurities). In addition, the agency asks for comments on whether it should require that such an evaluation be documented in a firm's records, and, if so, what type of records would be adequate to document that such an evaluation had occurred.

7. The agency asks for comments on whether specific controls are necessary for computer controlled or assisted operations. Many modern manufacturing operations rely on computers to ensure that proper procedures are followed in the handling and processing of ingredients and the manufacture of food products. If such equipment is used in the production of dietary supplements, FDA requests comment on how best to ensure that the software programs and equipment used to direct and monitor the manufacturing process are properly designed, tested, validated, and monitored.

8. The agency asks for comments on whether certain, or all, of the requirements for manufacturing and handling dietary ingredients and dietary supplements may be more effectively addressed by a regulation based on the principles of Hazard Analysis and Critical Control Points (HACCP), rather than the system outlined in the industry submission. FDA has issued regulations based on HACCP to ensure the safety of other foods (i.e., seafood) (Ref. 3) and has issued an advance notice of proposed rulemaking on the appropriateness of extending the HACCP concept to other segments of the food industry (Ref. 4). HACCP-based requirements enable manufacturers to develop and implement processes and controls that are tailored to their specific products and manufacturing operations. Because of the wide variety of dietary ingredients and dietary supplements and because of the heterogenous composition of the dietary supplement industry, CGMP based on the principles of HACCP may provide a more flexible and less burdensome regulatory framework for manufacturers and distributors than the approach set out in the industry submission.

9. The dietary supplement industry includes a broad spectrum of firms that conduct one or more distinct operations, such as the manufacture or distribution of raw dietary ingredients, the manufacture of finished products, or solely the distribution and sale of finished products (manufactured by a separate firm) at the wholesale or retail level. Consequently, the dietary supplement CGMP regulations may need to address the distinctive requirements of each of these segments of the industry in order to effectively ensure that dietary supplements are what they are represented to be and are safe for their intended use. The agency asks for comments on whether broad CGMP regulations will be adequate, or whether it will be necessary to address the operations of particular segments of the dietary supplement industry.

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