Industries and regulatory agencies, like people, grow and evolve over time. The recent publication of FDA’s final rule for dietary supplement GMPs (good manufacturing practices) marks a milestone in the evolution and maturation of the supplement industry and shows an almost unprecedented willingness on FDA’s part to be responsive to meaningful public comments from key stakeholders.
The best public policy and the most meaningful regulation is a result of public/private partnerships, with government, industry and consumer groups working together. All three share a common goal: creating a diverse marketplace that serves the needs of consumers.
When it comes to GMPs, no one is better equipped than the industry to evaluate the processes and controls necessary to ensure consistent production of quality products. The industry’s understanding of both the costs involved in such practices and the benefits to be realized from gaining the long-term trust of consumers is unmatched. Recognition of the importance of quality assurance led the industry to provide FDA with comprehensive draft GMPs in 1995, only a year after the passage of the Dietary Supplement Health & Education Act (DSHEA). This draft would have required rigorous process controls and extensive written procedures, two of the most critical components of quality assurance, and FDA published it as an Advance Notice of Proposed Rulemaking in 1997. Inexplicably, FDA’s Proposed Rule in 2003 departed from recognized principles and, instead, put heavy emphasis on exhaustive testing of the finished product, as though quality could be “tested into”
the product. Industry and other stakeholders submitted extensive comments, and the Final Rule demonstrates FDA listened to those comments and responded with major improvements by, among other things, recognizing quality must be emphasized throughout the manufacturing process, not just at the end.
The evolution of the GMPs demonstrates how an advancing regulatory body and a maturing industry can work together for the common good. The result is a comprehensive rule that provides industry with some flexibility but clearly demonstrates FDA’s painstakingly thoughtful approach to creating regulation that will level the playing-field among all supplement manufacturers and help ensure consumers have access to quality products.
The final GMP rule is a truly remarkable achievement—for FDA and for the industry—and it would not have been possible without the untold hours of work lavished upon it by all concerned in an effort to get it right. There are numerous significant changes from the proposed rule to the final rule that have made the GMPs more robust and more appropriate for the industry and its consumers. DSHEA acknowledged millions of consumers believe dietary supplements may help augment daily diets and provide health benefits, and the GMP rule also recognizes the need to ensure the quality of dietary supplements in order for consumers to obtain their potential health benefits. There were several changes in the final rule, as compared to the industry draft and the 2003 proposal.
Written procedures: The industry draft submitted in 1995 put a heavy emphasis on the importance of written standard operating procedures (SOPs), which are essential to any process control system, helping to ensure uniformity of operations and permitting adequate training of personnel. FDA’s 2003 proposal included almost no requirements for SOPs. But the final GMPs require written procedures for almost all key aspects of the manufacturing process, including personnel procedure s, cleanliness of the physical plant and equipment, quality control operations, laboratory and testing procedures, packaging, labeling and product distribution.
Identity testing: The final rule requires identity testing of all incoming dietary ingredients. This provision was supported by virtually all industry comments. However, FDA has published a separate Interim Final Rule that would permit manufacturers to petition FDA for an exemption from this 100-percent identity testing requirement if the controls established by the ingredient supplier and the manufacturer’s performance record appear to justify a statistically sound sampling approach to identity testing. Comments on this Interim Final Rule are due by Sept. 24, 2007.
Quality of ingredients: All components of dietary supplements must meet specifications established by the manufacturer. Suppliers typically test ingredients and provide manufacturers with a certificate of analysis (C of A) showing test results. FDA’s 2003 proposal would not have permitted manufacturers to rely on a supplier’s C of A, but would have required retesting. The final rule permits reliance on a C of A for various specifications (other than identity, for dietary ingredients), provided the reliability of the supplier’s process controls and testing has been verified by the manufacturer.
Role of testing: The proposed rule was overly focused on end-product testing, instead of focusing on fully adequate process controls. Exhaustive testing of the finished product is inefficient and extremely costly, and quality cannot be “tested into” a product. The final rule features a more comprehensive set of requirements for process controls, ensuring product quality is built into the system from the beginning and maintained throughout—a more reliable way to guarantee quality. Comprehensive process controls can justify a reduced testing burden at the end, and the final rule permits a sound statistical approach to end-product testing.
Responsible parties: In 2003, FDA proposed to require manufacturers of dietary ingredients as well as manufacturers of finished products to comply with dietary supplement GMPs. In the final rule, FDA concludes it is finished product manufacturers, not the ingredient suppliers, who are ultimately responsible for product quality. Therefore, the new dietary supplement GMPs apply to finished product manufacturers and distributors, not to ingredient suppliers.
Ingredient suppliers will need to continue to comply with existing food GMPs. It is incumbent upon manufacturers to work with reliable ingredient suppliers to ensure ingredient specifications are met, and not to sacrifice quality for cost.
Expiration dating: Despite strong industry support for expiration dating, FDA declined to add a requirement for shelf-life dating or expi ration dating, although the agency encourages its use. FDA believes there are not generally available methods for all ingredients sufficient to determine expiration dating, especially for botanical dietary ingredients. Manufacturers that do use an expiration date must have data to support the selection of the date.
Access to records: Despite industry’s protest that FDA lacks legal authority to demand access to records, the final rule requires companies to provide records to FDA inspectors upon request.
The final dietary supplement GMPs have been many years in the making, and the industry and FDA are anxious to move forward with their implementation. FDA is actively cooperating with industry to educate companies about the new regulation. Trade associations and other groups are sponsoring numerous educational events, and FDA is generously providing personnel to participate and answer questions during Webinars, seminars and conferences. Through these efforts, industry and FDA are making every effort to explain specifics of the rule and clarify confusion, to help expedite company compliance and avoid misunderstandings regarding FDA’s expectations.
The new GMPs are not perfect but should make the dietary supplement industry stronger and give consumers more confidence in the quality of the products they choose. Now it is up to the industry to implement the GMPs and up to FDA to enforce them. Clear understanding of the requirements and consistent enforcement will be the keys to success.
Annette Dickinson, Ph.D., is a former president and current consultant for the Council for Responsible Nutrition (CRN). Andrew Shao, Ph.D., is CRN’s vice president of scientific and regulatory affairs.
Editor’s Note: CRN and Virgo Publishing hosted a Webinar on the new GMPs, which is available on demand at www.Nutrilearn.com.