At long last, 13 years after the Dietary Supplement Health and Education Act (“DSHEA”) of 1994 authorized their creation, and four years after publication of the proposed rule, FDA issued its final current Good Manufacturing Practice (cGMPs) regulations for dietary supplements on June 25, 2007. FDA’s press release announcing the new regulations is available here.
The highly anticipated final rule establishes the minimum level of GMPs for the manufacturing, packaging, labeling and holding of dietary supplements. The regulations aim at ensuring the identity, purity, strength, and composition of a dietary supplement and at guaranteeing that a “dietary supplement is manufactured, packaged, held, and labeled in a consistent and reproducible manner.”Requirements address identity testing for incoming dietary ingredients, quality control, design and construction of manufacturing plants, personnel qualifications, use of written procedures, record keeping, returned dietary supplements, and consumer complaints.
In response to the more than 400 comments FDA received in response to the March 2003 proposed rule, the Agency revised and reorganized the various regulatory provisions.New 21 C.F.R. Part 111 now consists of 16 subparts rather than the original eight subparts.The preamble to the final rule includes a chart of the reorganization and renumbering of various sections facilitating a comparison of the final and proposed rules.
The most important and obvious change is that the final rule does not apply to dietary ingredient suppliers and manufacturers.The burden of compliance with cGMPs fully lies with the dietary supplement’s manufacturer and requires dietary supplement manufacturers to test 100% of the incoming dietary ingredients.
Concurrent with the final rule, however, FDA published an interim final rule providing an alternative to the 100% identity testing requirement.In the interim rule, FDA recognizes that under some circumstances “a system of less than 100 percent identity testing would [not] material[ly diminish the] assurance of the identity of the dietary ingredient.” Thus, the interim rule provides a petitioning process for exemptions to the100% testing requirement.FDA requests comments on what type of information would satisfy the exemption. Comments are due by September 24, 2007.
Other notable differences between the proposed and final rules include:
- Increased requirements for written procedures for, among other things, manufacturing operations, quality control operations, training of personnel, laboratory operations, holding and distributing operations, and for the handling of returned dietary supplements.
- Reduced requirements for testing finished batches.The final rule allows testing of a “subset of finished dietary supplement batches [identified] through a sound statistical sampling plan” rather than testing of all finished batches.
- Because validated testing methods for the identity of dietary ingredients often may not be available, the final rule allows use of a “scientifically valid method” instead of a “validated testing method.”
- The final rule replaces the proposed requirement for a “quality control unit” with “a requirement for quality control operations performed by quality control personnel.”Quality control personnel must have “distinct and separate responsibilities related to performing [their] operation” and non-quality control activities by these designated individuals are not restricted.Quality control personnel must supervise and monitor the testing and evaluate the results and need not perform the actual testing and examination.
- Increased flexibility regarding qualification of employees and design of manufacturing facilities.For example, the final rule (unlike the proposed rule) does not exclude employees who are a potential source of microbial contamination from the premises, but excludes such individuals only from areas where contamination of the dietary supplement may occur.
Both the final GMP regulations and the interim final rule take effect on August 24, 2007, with a three-year phase-in process to limit disruption of businesses. Companies with more than 500 employees must comply by June 2008; those with 20-500 employees by June 2009; and those with less than 20 employees by June 2010.FDA will review petitions for an exemption from the 100% identity testing requirement only once the compliance date for a particular manufacturer has passed.