Dietary Supplement GMPs Finally Released, Journey to Compliance Begins

WASHINGTONIn mid-June, FDA released a final rule on current Good Manufacturing Practices (cGMPs) for dietary supplements, establishing requirements to ensure products are made in a consistent, quality manner and are accurately labeled and free from impurities. This much-anticipated ruling applies to companies that manufacture, package or store dietary supplements; FDA management explained, for the most part, retailers are not included in this rule, while health care practitioners will be considered on a case-by-case basis. The final rule is effective Aug. 24, 2007, but there is a 36-month phase-in period for companies to comply, depending on size.

 The final rule will help ensure that dietary supplements are manufactured with controls that result in a consistent product free of contamination, with accurate labeling, said Robert E. Brackett, Ph.D., director of FDAs Center for Food Safety and Applied Nutrition (CFSAN).

Among the rules 800-plus pages of requirements, manufacturers will be compelled to evaluate the identity, purity, strength and composition of their dietary supplements. This helps to ensure finished products contain actual labeled contents, but not adulterants such as pesticides, bacteria or heavy metals. If dietary supplements contain contaminants or do not contain the dietary ingredient they are represented to contain, FDA would consider those products adulterated or misbranded.

The rule further contains requirements for establishing quality control procedures, designing and constructing manufacturing plants, and testing ingredients and the finished product, as well as provisions for handling consumer product complaints and for recordkeepingincluding standard operating procedures (SOPs).

While the final rule specifically mandates 100-percent testing of ingredients, Brackett said those requirements are flexible to allow for ongoing improvements in scientific methods used for verifying identity, purity, strength and composition of dietary supplements. He further noted the agency published an interim final rule on how manufacturers could petition FDA for an exemption to the cGMP requirement for 100-percent identity testing of specific ingredients used in the processing of dietary supplements. However, he conceded FDA has no firm sense of what information or documentation will be adequate to qualify for reduced testing.

There is an economic analysis section in the lengthy regulation, outlining the estimated costs companies of various sizes might incur in achieving compliance with the GMP rule. It is based partly on a survey of industry companies and comments submitted to the proposed rule. While set-up costs for very small (under $1 million annual revenues), small ($5 million to $10 million) and large companies ($10 million to $50 million) range from $20K to $31K, small companies (20 to 499 employees) are expected to have significantly higher annual costs of compliance of $184Kdouble the estimated annual costs of $46K for very small and $69K for large companies. FDA estimated 140 very small and 32 small dietary supplement manufacturers will be at risk of going out of business.

In announcing the publication of the final rule, FDA leaders reported they intend to conduct outreach programs to educate consumers and industry members, as well as FDA staff. The agency also stated enforcement of compliance with these GMPs will fall under the agencys normal program of facilities inspections and rule enforcement.

The release of the final rule on supplement GMPs quickly spawned new programs from third-party companies offering help for manufacturers and other companies on complying with the new regulations. NSF Internationals Global Lifescience Solutions (GLS), a contract research and consulting company, and Pharmaceutical Consulting Services, a full service compliance consulting company, each announced programs to audit and advise on compliance issues.

Industry critic ConsumerLab.com also announced two initiatives related to the final GMPs, which the company heavily bashed. The historically secretive company said it would now offer free online access to its testing methods and standards covering the top categories of supplements. It also launched a new testing program designed to help companies more economically meet new GMP testing requirements while applying ConsumerLabs rigorous methods and standards.

Tod Cooperman, M.D., president of ConsumerLab.com, said: Unfortunately, it is possible for a company to manufacture a bad supplement under the new good manufacturing practices. The GMPs require manufacturers to test all ingredients going into supplements, but fail to specify the methods and standards by which ingredients are to be judged.

Reaction to ConsumerLabs statement was harsh. Steven Mister, president and CEO of the Council for Responsible Nutrition (CRN), said ConsumerLabs move was not surprising. Its comments about the GMPs are self-serving and disingenuous, he remarked, adding the GMPs will tremendously advance quality in this industry, whether manufacturers choose to participate in the ConsumerLab programs or not. We are pleased, however, to see [ConsumerLab] says it is finally making public without a fee its testing methods and standardsboth of which have previously been unavailable for public scrutiny. He advised a robust discussion of whether the ConsumerLab methods are the most appropriate for analyzing particular ingredients or contaminants in the matrix of the finished product.

In addition to emerging consulting programs, the GMPs prompted industry meetings with expert commentary and analysis of the lengthy GMP publication. CRN (CRNusa.org) paired with Virgo Publishing to present a Webinar, CRNs Overview of the Dietary Supplement GMPs, featuring commentary from Bill H. Frankos, Ph.D., director of Division of Dietary Supplement Programs (DDSP), FDA; Annette Dickinson, Ph.D., CRN past president and consultant; Eugene Lambert, senior counsel, food and drug practice, Covington & Burling; Paul Bolar, CRN board member and Regulatory Affairs Committee co-chairperson, vice president of Pharmavite; Joy Joseph, industry consultant; Kevin Boot, regulatory counsel, Embria Health Sciences; Michael Bradley, director nutritional scientific affairs, Perrigo; and David R. Schoneker, director of global regulatory affairs, Colorcon. The American Herbal Products Association (AHPA.org) also held a teleconference to review important aspects of the regulations, with Frankos, attorney Marc Ullman of Ullman, Shapiro & Ullman; and AHPAs president, Michael McGuffin.

The prevailing sentiment is that a great deal of industry input on the proposed rule is reflected in the final rule, which was modeled on existing food GMPs, drug GMPs, third-party supplement GMPs and industry practices. Industry members are uring companies to submit comments on the rule for possible exemptions from 100-percent testing of ingredients. Manufacturers were similarly urged to carefully select and qualify ingredient suppliers, documenting the quality procedures and operations of each supplier.

A replay of the Virgo/CRN Webinar which broke down the GMP rule into its specific requirements on personnel, equipment, facilities, documentation, testing, record keeping and quality control designis available on-demand at www.NaturalProductsInsider.com.