The bare minimum current good manufacturing practice for preparation of dietary supplements for human consumption consists of 16 subparts with 84 unique requirements. Key requirement below
- Manufacturers required to implement a system of production and process controls for all stages of the manufacturing, packaging, labeling, quality control, record-keeping, storing, and distributing of DS to ensure the quality and proper identification of those supplements.
- Manufacturers required to establish their own specifications and conduct appropriate in-process and end-product tests and examinations to verify that all quality specifications for identity, purity, strength, and composition are met.
- However, 21 CFR 111 provides flexibility for the manufacturer to test either every batch of finished products or a subset of finished batches to determine that all quality specifications are met, or document why testing of dietary ingredients (DI) and monitoring of manufacturing processes will ensure that these specifications are met. This requirement also pertains to non-DI components.
- Specifications are also required for in-process production, labels and packaging components, and finished products.
- Testing subsets of finished batches would have to be based on a statistical sampling plan with a justifiable rationale for why such a plan ensures the products’ quality.
- DI suppliers are not required to conform to the rule. Therefore, the responsibility to determine DI quality rests with the manufacturer of the finished DS product (or Own Label Distributor).
- DS manufacturers must ensure the proper identity of any DI (and non-DI) components used in their products. The identity specification of any DI can only be verified by actual testing or examination, unless FDA grants an exemption from testing 100% of the time. To determine whether DI specifications are met, below are steps
- identity tests must be carried out on components prior to use;
- in-process points, steps, or stages where control is necessary to ensure the quality of the DS finished product must be monitored; and
- subset of finished batches must be tested for one or more of the established specifications for identity, purity, strength, composition, and contamination limits, using “appropriate, scientifically valid methods.”
- Manufacturers could confirm identity by conducting at least one appropriate scientifically valid test or examination (e.g., gross organoleptic analysis [analysis based on taste, smell, color, morphology, etc.]; macroscopic analysis; microscopic analysis; chemical analysis; or other scientifically valid methods).
- Identity of other (non-DI) components may also be confirmed by conducting appropriate tests or examinations or by relying on a Certificate of Analysis (C of A) from the supplier, provided that certain conditions are met.
- The C of A will be sufficient only if it includes information on test methods, limits, and actual results; if the manufacturer establishes the reliability of the supplier’s C of A through confirmation of the supplier’s tests; if the manufacturer documents how the supplier was qualified as reliable and verifies that this qualification was reviewed and approved by the manufacturer’s quality assurance personnel; and if the manufacturer periodically reconfirms the C of A.
- The rule does not provide specific guidelines or requirements for the tests that a company would need to conduct to verify the identity, purity, strength, and composition of ingredients and finished products. The tests or analyses that a manufacturer chooses to employ, however, must be “scientifically valid,” as previously described.
- The rule also does not require the use of any specific quality or grade designation, e.g., DI for which standards have been established by the United States Pharmacopeia (USP). It is entirely up to the manufacturer to establish its own specifications for the identity, purity, strength and composition of components, as well as contamination limits specifications.
- Manufacturers will also have to establish and follow written procedures for their operations and facilities, which are specified in the rule.
- They will need to keep written product records for 1 year past the expiration date (if the company chooses to affix an expiration date on its products) or 2 years beyond the date of distribution of the last batch of supplements associated with those records, and these records must be available to the FDA upon request.