Public Comments to FDA
on Proposed Good Manufacturing Practices
for the Dietary Supplement Industry
Submitted by Durk Pearson & Sandy Shaw
31 March 1997
"Background. On Nov. 20, 1995, representatives of the dietary supplement industry submitted to FDA a suggested outline for the development of CGMP regulations for dietary supplements."
COMMENT: The organization that submitted the suggested outline for CGMP regulations for dietary supplements, the Natural Nutritional Foods Association, represents only their members, a small part of the dietary supplement industry. We, therefore, appreciate this opportunity to provide our comments on the NNFA's proposed CGMP regulations.
"Based on the submission and the comments that the agency receives in response to this notice, FDA will consider whether to develop a proposed rule that is designed to establish CGMP that will ensure that dietary supplements are produced under conditions that will result in a safe and properly labeled product but that does not impose any unnecessary burden on the industry."
COMMENT: We believe that any CGMP standards should be developed by the industry itself and be voluntary. Good manufacturing practices do not necessarily have to be the same for every company, as the level of quality assurance will inevitably reach a point of diminishing returns as more and more money, personnel, and technology are invested in it. Larger firms may wish to invest larger amounts of money for the ever diminishing amounts of additional safety and quality, while smaller firms may not. A reasonable standard would include a range of practices, rather than a single set of procedures that all must follow.
"The objectives of the CGMP, as stated by the industry representatives [NNFA], are to ensure that consumers are provided with dietary supplement products that : (1) Are safe and not adulterated or misbranded; (2) have the identity and provide the quantity of dietary ingredients declared in labeling; and (3) meet the quality specifications that the supplement is represented to meet. The industry [NNFA] submission was patterned after the CGMP for food regulation contained in part 110, but also contained requirements beyond those in part 110 that the industry representatives [NNFA] stated that they 'consider essential to the manufacture of safe and properly labeled dietary supplements.'"
COMMENT: Any CGMP for dietary supplements should be no stricter than for foods in common form, since the record shows that foods in common form are actually far more hazardous than dietary supplements. For example, in 1989, the worst public health problem resulting from the use of dietary supplements, eosinophilia-myalgia syndrome resulting from contaminated tryptophan, took place. About 38 people died and some 1,500 people became seriously ill. Yet, despite the unfortunate results of this tragedy, it was more risky for the consumers of soft cheese to eat soft cheese that year or any year than it was for the consumers of tryptophan to take tryptophan that year. About 9,000 people die each year from contaminated foods. The record for safety for dietary supplements is more favorable than that for foods in common form and, hence, the standards for CGMP for dietary supplements should not be stricter than for foods in common form.
"Personnel (c). Education and training. Each person engaged in the manufacture of a dietary product should have the proper education, training, and experience (or any combination thereof) needed to perform the assigned functions. Training should be in the particular operation(s) that the employee performs as they relate to the employee's functions. Appropriate documentation of training shall be retained by the manufacturer."
COMMENT: It is remarkable to believe it necessary to inform a manufacturer of the need for a employee to have education, training, and experience so as to be able to perform his/her function. A person running a shoeshine shop or a hot dog concession would know this, let alone a dietary supplement manufacturing operation. The requirement for "appropriate documentation of training" is potentially burdensome, since many persons may have training that was obtained through supervised work experience, for which there may be no specific "documentation."
"Sanitation of Buildings and Facilities. (b)(1) Cleaning and sanitizing agents used in cleaning and sanitizing procedures shall be free from undesirable microorganisms and shall be safe and adequate under conditions of use. Compliance with this requirement may be verified by any effective means including purchase of these substances under a supplier's guarantee or certification, or examination of these substances for contamination."
COMMENT: The FDA has approved a wide variety of cleaning and sanitizing compounds for the food industry. Why not just publish the list and make it available to the dietary supplement industry? That would certainly simplify matters.
"Production and Process Controls. (2)(ii). An accurate statement of the weight or measure of each raw material used in the manufacture of a dietary product. Each batch shall be formulated with the intent to provide not less than 100 percent of each claimed dietary ingredient."
COMMENT: FDA well knows that, though one may adjust one's production equipment to provide 100% of each claimed dietary ingredient, there will be a statistical range of fills around a mean value. One would have to way overfill to have, say, a 95% statistical probability of having all fills at least at 100% of the claimed dietary ingredient.
"Warehousing, Distribution and Post-Distribution Procedures. (4)(g)(3). The manufacturer, distributor, and holder of a dietary product shall at all times utilize quality control operations that reduce natural or unavoidable defects to the lowest level currently feasible." (emphasis added)
COMMENT: This is entirely unnecessary and a burden to small operations. The urgency to reduce natural or unavoidable defects depends upon the risks posed by these defects. The reduction of no risk or low risk defects to the "lowest level currently feasible" will require expensive equipment that will not increase public safety, but may drive small manufacturing operations out of business that cannot afford this equipment. One has to wonder why the NNFA has proposed such a stringent, expensive, and unnecessary rule which is reasonable for a pharmaceutical drug, but not for dietary supplements.
"Warehousing, Distribution and Post-Distribution Procedures. (4)(g)(4). The mixing of a dietary ingredient or dietary supplement containing defects above the current defect action level with another lot of dietary ingredient or dietary supplement is not permitted and renders the final product adulterated within the meaning of the act, regardless of the defect level of the final product. (emphasis added)
COMMENT: Again, the need for such a rule would be reasonable for a pharmaceutical drug which contains small amounts of powerful active ingredients, but is not reasonable for most dietary supplements. For example, suppose a lot of a powdered multi-vitamin had too little vitamin C. One could mix it with another lot of powdered multi-vitamin with extra vitamin C so that the entire mixed lot had the correct level of vitamin C. This is in no way an "adulteration" of anything. If the final lot is below the action level for the product, it should be as acceptable as a lot that "just happened" to end up with that way.
Actually, the mixing of dietary ingredients takes place during manufacturing, not warehousing, distribution, and post-distribution. All the warehouse needs to do is follow the product label instructions for storage and shelf life.
"The agency asks for comments on whether there should be new CGMP regulations, whether the regulations should be mandatory or voluntary, and, if mandatory, how long it would take establishments to come into compliance."
COMMENT: As we noted above, we do not think there should be mandatory CGMP regulations for the reasons stated before. Such regulations tend to freeze manufacturing practices into concrete, discouraging the institution of new, more cost-effective techniques. The added burden of keeping records for the government and for dealing with pop inspections (eg., warrantless searches of dubious constitutionality) is particularly great for smaller companies. Larger companies may see detailed and voluminous recordkeeping requirements as a way to get rid of smaller competitors, which is unlikely to be in the public interest.
"IV. Summary and Request for Comments, 1. Is there a need to develop specific defect action levels (DAL's) for dietary ingredients?"
COMMENT: There are thousands of dietary ingredients. To develop a specific defect action level for each of these ingredients would be an exceedingly expensive, time-consuming, and thankless project for FDA. Yet, ingredients are different and it wouldn't be possible to just lump them together. Furthermore, in most cases one could not say that at this defect action level everything is OK, but slightly beyond this point, it isn't OK. The defect action levels for most dietary supplements involve manufacturing defects far less serious than, say, bacterial contamination. In a powdered dietary supplement, for example, the usual effect of excess moisture is a clumping and hardening of the product, undesirable of course but unlikely to be hazardous. In a food, under certain conditions, moisture will foster the growth of bacteria. Dietary supplement manufacturers, guided by consumer acceptance, will know what the limits of moisture content should be.
"IV. Summary and Request for Comments, 4. 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."
COMMENT: As we noted above, the safety record for dietary supplements has been better than that for foods in common form. Therefore, there is no appropriate basis for including stricter recordkeeping by manufacturers of dietary supplements and such adoption would be arbitrary, capricious, without rational basis, in violation of statute law and in violation of the APA.
"IV. Summary and Request for Comments, 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."
COMMENT: There is no requirement that food manufacturers have reports of injuries or illnesses evaluated by competent medical authorities to determine whether followup action is necessary to protect the public health. Hence, there should be no such requirement for the manufacturers of dietary supplements. Such a requirement would not only prove to have no measurable effect on the public health, but it would be a very expensive burden for small companies, which would have to have medical followup for every instance of ordinary falls or catching a cold.
"IV. Summary and Request for Comments, 5. The presence of pharmacologically active substances in these products distinguishes them from most other foods."
COMMENT: That may be the way dietary supplements and foods were viewed decades ago, but it is not how scientists view them today. Dietary supplements that are derived from foods contain pharmacologically active substances found in the foods. The reason people eat foods at all is because of the pharmacological effects they experience as a result of eating them, which include a complex variety of physiological and psychobiochemical changes. For example, the polyphenols found in chocolate, tea, coffee, and fruits and vegetables, have a diverse array of effects including psychopharmacological effects.
"IV. Summary and Request for Comments, 5. 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 (eg., 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."
COMMENT: Many of the ingredients in dietary supplements have been evaluated for quality and safety and health effects by the large manufacturers that offer them for sale. One of the assurances that a dietary supplement manufacturer has for the quality of the ingredients he uses is the manufacturer for those ingredients. There is no reason that a dietary supplement manufacturer should be required to duplicate an evaluation already performed by a much larger company with far more resources. Including requirements for the evaluation of all pharmacologically active substances creates an unnecessary burden. There are many thousands of substances contained naturally in a fruit or a vegetable or an extract of these. Most of the pharmacologically active substances have not even been identified yet. The potencies will depend upon the quantity, concentration, and interactions with many other substances, as well as upon the particular physiology of each individual consumer. A simple mixture of vitamins and minerals would require a very expensive analysis in order to attempt the impossible, to determine all possible interactions. Yet, where is the safety concern that requires the spending of such large sums? Drug manufacturers must control closely such matters as the exact quantities of pharmacologically active ingredients, as well as interactions with other drugs or foods and of possible contaminants. This is a reasonable expectation for drug manufacturers, but not for dietary supplement or food manufacturers. Nutrient supplements are foods, not drugs.
© Copyright 1999 by Durk Pearson & Sandy Shaw
NOTICE: The "Durk Pearson & Sandy Shaw Life Extension News" is for informational purposes only. Its contents are not intended as advice for the diagnosis, treatment, or cure of any medical condition. Pearson & Shaw are scientists, not doctors. If you have a medical condition, see a physician. Durk Pearson & Sandy Shaw® do not own any part of any dietary supplement company. They license their formulations and receive royalties on sales. The formulations they design and use are those which contain their names on the label.