Supplement GMPs Should Set Dissolution, Disintegration Requirements – USP
This article was originally published in The Tan Sheet
Executive Summary
Dissolution or disintegration requirements for dietary supplements ought to be mandated by FDA in order to confirm product quality, the U.S. Pharmacopeia says in Aug. 11 comments on the supplement good manufacturing practices proposed rule
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Dissolution or disintegration requirements for dietary supplements ought to be mandated by FDA in order to confirm product quality, the U.S. Pharmacopeia says in Aug. 11 comments on the supplement good manufacturing practices proposed rule. Though the agency has said that dissolution and disintegration requirements for dietary supplements "are premature and therefore are not included in the proposed rule," USP "disagrees [as] such requirements are important tools to establish the quality of dietary supplements." FDA "should require dissolution and disintegration testing whenever scientifically available" and state that inclusion of a disintegration or dissolution test in an official compendium like the USP-NF "shall be prima facie evidence of such availability," USP says. The group points out that the agency has "in fact adopted by regulation USP dissolution requirements for certain dietary supplements, such as folic acid and calcium." The "failure to require this testing could result in dietary supplements that are not bioavailable and may have negative health implications," USP warns. At the very least, USP suggests dissolution and disintegration requirements be adopted "for vitamins and minerals and those dietary supplements with well-characterized active ingredients." USP requires dissolution or disintegration testing for dietary supplement products that are voluntarily entered by their manufacturers into its Dietary Supplement Verification Program (1 (Also see "USP Supplement Verification Program Backed By $20 Mil. Campaign" - Pink Sheet, 14 Oct, 2002.), p. 15). USP additionally recommends that FDA follow its lead and require expiration dating for dietary supplements. "Without this, manufacturers cannot possibly assure the appropriate potency or strength of the dietary supplement for the product's 'shelf life' [which] is inconsistent with FDA's own regulation requiring 100% potency for the duration of a dietary supplement's shelf life," according to the group. Further, "without an expiration date and records to establish this dating, any investigation of a subpotent product is likely to be compromised," USP says. Addressing the use of ingredient certificates of analysis, USP suggests the agency "consider modifying the amount of testing based on the use of a certificate of analysis" and thus "adopt a statistical approach to process validation instead of testing each lot." Such a modification of the proposed rule would avoid the time and cost burden of having to test every batch, according to USP. In separate comments filed the same day, the American Herbal Products Association expresses similar views in favor of allowing certificates of analysis, asserting "any unwillingness by FDA to find a meaningful role for sound certification documents will result in duplicative testing" (2 (Also see "Certificates Of Analysis, Written GMP Procedures Urged By AHPA, CRN" - Pink Sheet, 18 Aug, 2003.), p. 7). USP also addresses the proposed rule's restriction on placing an unqualified statement on product labels that says: "Produced in compliance with dietary supplement current good manufacturing practices." FDA prohibits this statement in the reg because it "may mislead consumers into believing that the dietary supplement is superior or is safe and effective," USP notes. However, USP believes the rule also should "exclude statements such as the dietary supplement 'is produced using good laboratory practices' or 'is produced using good practices' or 'is produced in compliance with USP good manufacturing practices.'" Such statements "currently appear on dietary supplement labels and may also be misleading," the group argues. FDA should designate USP-NF compendial procedures, which include dietary supplement reference standards and monographs, as "scientifically valid" as well, USP states. "In the proposed rule, FDA did not define but instead characterized its own and AOAC procedures as scientifically valid but failed to mention [USP] compendial procedures." Comments on the GMP proposed rule, which was published in the March 13 Federal Register, were due Aug. 11. The agency will accept further views on the economic impact of the rule through Sept. 9. |