Although some provisions of the final rule may be controversial (such as FDA's claim to records access authority), the major dietary supplement trade associations have long encouraged FDA's development of dietary supplement cGMP regulations and have expressed support for the final rule. Thus, it is not expected that there will be any major challenges to the new provisions.
The remainder of this article (1) provides background on the development of the cGMP regulations, (2) highlights the final rule's basic provisions, (3) summarizes the changes from the 2003 proposal, and (4) evaluates the potential impact on component/ingredient suppliers. Please let us know if you have any questions or would like more detailed information about any of these points.
The final rule establishes industry-wide standards that specify requirements for the following areas: (1) personnel; (2) physical plants and grounds; (3) equipment and utensils; (4) production and process controls; (5) quality control; (6) components; (7) manufacturing; (8) laboratory operations; (9) packaging and labeling; (10) holding and distribution; (11) returned dietary supplements; (12) handling product complaints; and (13) record-keeping. The new regulations are the result of a process that began with the passage of the Dietary Supplement Health and Education Act (DSHEA), 1 which amended the Federal Food, Drug, and Cosmetic Act (FDC Act) to establish a framework for regulating dietary supplements. Among other provisions, the Secretary of Health and Human Services (through delegation to FDA) was given the authority to promulgate regulations establishing cGMPs for dietary supplements. These requirements were to be "modeled after" CGMPs for food2 and could not impose requirements for which there were no generally available analytical methods.3FDA published an Advanced Notice of Proposed Rulemaking (ANPR) in 1997,4 followed by numerous public meetings to gather input from affected parties. This process led to the publication of the 2003 proposal. After reviewing nearly 400 comments on the proposal, the Agency reorganized and modified numerous provisions as reflected in the final rule.
FDA goes to great lengths to describe how the final rule has been "modeled" after the food GMPs. Nevertheless, it is likely that there will continue to be controversy over the scope of certain of the final rule's requirements (and especially FDA's assertion of its authority to access the records required to be compiled and maintained).
II.Highlights of the Final Rule
In summary, the final rule does the following:
Interestingly, although DSHEA specifically authorized FDA to establish expiration dating requirements for dietary supplements, the Agency did not include such provisions in the 2003 proposal and has not incorporated them into the final rule.5
III.Significant Changes from 2003 Proposal
Based on the comments received on the 2003 proposal, FDA modified the final rule in several respects. As noted above, the most significant change is that the final rule applies only to producers of finished dietary supplements; producers of "dietary ingredients"6 are not subject to the final rule. Other changes from the 2003 proposal include the following points:
IV.Impact on Suppliers of Components
As noted above, manufacturers of dietary ingredients and other components16 used in the manufacture of dietary supplements (e.g., binders, fillers, flow aids, solvents, etc.) are not subject to the requirements of the new rule. However, FDA states that dietary ingredient manufacturers are still subject to the existing "general" food GMP regulations found in 21 C.F.R. Part 110. 17 In addition, the Agency appears to endorse the idea that dietary supplement manufacturers may wish to impose certain of the final rule's provisions on their suppliers:
Because the final rule gives manufacturers an incentive to qualify suppliers of dietary ingredients, persons who manufacture, package, label, or hold dietary ingredients may wish to familiarize themselves with these dietary supplement CGMP requirements and use them in manufacturing, packing, labeling, or holding operations for dietary ingredients.18
Apart from this potential "upstream push" of the cGMP requirements, there are provisions of the final rule that will affect suppliers. For example, while a dietary supplement producer can rely on a CofA from a supplier (except to establish the identity of a dietary ingredient), the CofA must include the following information:19
(1) a description of the test or examination method(s) used by the supplier; (2) limits of the test or examinations; and
(3) actual results of the tests or examinations.
As a result, suppliers of all components used in dietary supplements (not just dietary ingredients) may need to provide more detailed information to their dietary supplement customers than they have in the past. In addition, for component ingredients that are the subject of a compendial monograph (such as the U.S. Pharmacopeia (USP) or National Formulary (NF)), it will no longer be sufficient to simply note that the ingredient "meets" or "passes" the compendial specification; the actual test results will need to be provided.
Along with the use of the CofA, component suppliers may be subject to greater quality scrutiny by their customers. Dietary supplement manufacturers are also required to initially qualify their suppliers by establishing the reliability of the supplier's CofA through confirming the supplier's reported analytical results. Subsequently, the customer is required to periodically re-confirm the reliability of the CofA and maintain documentation of how this process was carried out.20 Thus, ingredient suppliers may be subject to greater quality scrutiny by their customers (possibly including conducting quality audits of supplier's manufacturing operations).
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Overall, the dietary supplement cGMPs are expected to be viewed as a positive development for the industry, leading to greater consumer confidence in the quality of the products available in the marketplace.
For further information about this issue or FDA's regulation of dietary supplements generally, please contact Frederick A. Stearns at 202-434-4288 or via e-mail at email@example.com.
1Pub. L. No. 103-417 (1994).
2FDA's "umbrella" food GMPs are found in 21 C.F.R. Part 110. More specific quality requirements have been established for infant formula (21 C.F.R. Part 106); thermally processed low-acid foods (21 C.F.R. Part 113); acidified foods (21 C.F.R. Part 114); and bottled drinking water (21 C.F.R. Part 129).
3FDC Act § 402(g)(2).
4 62 Fed. Reg. 5700 (February 6, 1997).
572 Fed. Reg. at 34852 (col. 3) ("[W]e decline to require expiration dating because there may not be adequate methods available for assessing the strength of a dietary ingredient.").
6Dietary ingredients include: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary substance for use by humans to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any these ingredients. FDC Act § 201(ff).
7The "Dietary Supplement and Nonprescription Drug Consumer Protection Act" (Pub. L. No. 109-462) (signed into law on December 22, 2006).
872 Fed. Reg. at 34800 (FDA response to Comment 51) (col. 2).
9Id. at 34801 (FDA response to Comment 53) (col. 1-2).
1072 Fed. Reg. at 34835 (FDA response to Comment 145) (col. 1).
11Id. (col. 1-3).
12The interim final rule can be found at 72 Fed. Reg. 34959 (June 25, 2007).
1372 Fed. Reg. at 34835 (FDA response to Comment 145) (col. 3).
14Id. at 34862 (FDA response to Comment 214) (col. 2-3).
15Id. at 34875 (FDA response to Comment 237) (col. 3).
16For purposes of the final rule, a "component" means "any substance intended for use in the manufacture of a dietary supplement, including those that may not appear in the finished batch of the dietary supplement." New 21 C.F.R. § 111.3; 72 Fed. Reg. at 34944. This term includes dietary ingredients and other ingredients intended to be present in the finished dietary supplement. FDA did not intend for the term "component" to include things like packaging materials, although the Agency recognized that the term may be confusing, noting that "[t]here may be differences in how components are referred to by certain manufacturers and how we refer to it in this final rule." 72 Fed. Reg. at 34795 (FDA response to Comment 39) (col. 3).
1772 Fed. Reg. at 34792 (FDA response to Comment 29) (col. 2).
19New 21 C.F.R. § 111.75(a)(2)(ii)(B); 72 Fed. Reg. at 34949.
20New 21 C.F.R. § 111.75(a)(2); 72 Fed. Reg. at 34949.