On July 1, 2011, four days ahead of the July 5th deadline imposed by the Food Safety Modernization Act of 2010, the Food and Drug Administration (FDA) published its “Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues” in the Federal Register.[1] It was hoped that the new draft guidance would retain the intent of the “Dietary Supplement Health and Education Act of 1994” (DSHEA) while clarifying the technical issues industry has been wrestling with for the past 17 years.[2] Instead of simple clarification, however, early evaluation of the draft document indicates significant reinterpretation of DSHEA that will, if approved, directly affect the number of notifications industry will be expected to prepare and file. To understand the magnitude of the changes and their implications on industry, we begin with DSHEA.
Principally authored by Senators Tom Harkin, D-Iowa, and Orrin Hatch, R-Utah, DSHEA was enacted by Congress on October 14, 1994. The statute was revolutionary in that it (1) identified dietary ingredients and the supplements that contain dietary ingredients as food, (2) differentiated dietary ingredients and dietary supplements from food additives and drugs, (3) provided a line of demarcation[3] between NDIs and old dietary ingredients (ODIs; use of which, with appropriate documentation of having been marketed in the United States prior to October 15, 1994, would be “grandfathered”), and (4) initiated the requirement of a 75-day premarket notification for NDIs or products containing NDIs to demonstrate that use of these substances in accordance with label instructions would “reasonably be expected to be safe.” [Section 413(a) & (c) of the FDC Act; 21 USC §350(b)]. Several observations regarding DSHEA are particularly pertinent:
Although identified as food, DSHEA differentiated dietary ingredients and dietary supplements from food additives.
DSHEA specified premarket notification for NDI, not premarket approval.
ODIs are exempt from notification.
Dietary ingredients and dietary supplements are required to meet the safety standard of a “reasonable expectation of safety”, an intentionally lower standard than that required of food ingredients. (The safety standard required of food ingredients, including food additive petitions and Generally Recognized as Safe, is “a reasonable certainty of safety”.)
DSHEA did not require that all NDIs be notified. Those NDIs which were “present in the food supply as an article used for food in a form in which the food has not been chemically altered”, for example, are exempt [FDC Act §413(a)(1)]. For those “not exempt” NDIs that require premarket notification, DSHEA permitted the notification to be filed by the manufacturer for the ingredient alone or by the distributor for the finished dietary supplement (retail product):
“There is a history of use or other evidence of safety establishing that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe and, at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides the Secretary [of Health and Human Services] with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe.” [FDC Act §413(a)(2); DSHEA §8]
Three years post-DSHEA the premarket notification process for NDIs was formally established in Federal Register Final Rule 62 FR 49886 “Premarket Notification for a New Dietary Ingredient” dated September 23, 1997. Since the final rule was initiated, it has been the responsibility of industry – the manufacturer or distributor – to file premarket notifications demonstrating safety for “not exempt” NDIs. The 1997 Final Rule was FDA’s first published interpretation of DSHEA and reveals the agency’s thoughts at that time. The year DSHEA was passed by Congress, approximately 4,000 supplement products were on the commercial market.[4] Three years later when FDA addressed the anticipated cost-benefit of the premarket notification process in the 1997 Final Rule, the agency estimated the number of notifications from “new ingredients to be 0 to 12 per year….” Costs were estimated on this basis[5] and no mention was made of the then-current number of finished products.
Skip to 2011 and in the recent draft guidance FDA estimates about 55,600 dietary supplement products are on the market[6] and expresses concern that only about 700 NDI notifications have been filed since DSHEA’s passage[7] (actual number, 715 as of September 14, 2011[8]). While 55,600 is a much larger number than 715, few would presume a one-to-one correspondence between “not exempt” NDIs and retail products. This seems obvious, but no one has mentioned, even in general terms, how many of these 55,600 supplements are expected to be adulterated (contain at least one unnotified NDI) v. how many are not (contain only ODIs and/or exempt NDIs and/or “not exempt” NDIs that have been notified). Depending on whether one holds to the conservative 1994-1997 interpretation of DSHEA or ventures into the views espoused by the new draft guidance, categorization would be expected to give very different answers. Since July’s publication of the draft guidance, FDA has indicated it expects to receive about 55 NDI notifications annually, based on the average number of NDI notifications filed in the years 2008 through 2010 [FDA Docket No. FDA-2011-N-0410]. Although this is a 458% increase over the 1997 estimate of “0 to 12”, 55 annual notifications seem far fewer than what FDA believes is truly appropriate based on wording of the draft guidance:
“Section 413(a)(2) of the FD&C Act (21 U.S.C. 350b(a)(2)) makes clear that any dietary supplement that contains a NDI is deemed adulterated unless the manufacturer or distributor of the dietary ingredient or the dietary supplement submits a NDI notification at least 75 days before introducing it into interstate commerce. The statute places the obligation for submitting the notification on each manufacturer or distributor. The original notifier conducted its safety evaluation based on the characteristics and intended use of the specific product under review, including the composition and labeling of the dietary supplement that the notifier was proposing to market. Any other manufacturer or distributor who wishes to market its own dietary supplement containing the same NDI should submit a NDI notification to FDA explaining its own basis for concluding that this new product containing the NDI will ‘reasonably expected to be safe’ under the conditions recommended or suggested in the new product’s labeling.”
Industry is justifiably concerned that retail products may be pulled from shelves, that company resources may have to be mobilized to submit hundreds of notifications for products that had previously been viewed as appropriate for commerce, and that revenue may be lost along with market position during this process. There is also justifiable concern that the new draft guidance shifts the notification process toward a food-additive style petition process. The stated requirement for notification of every retail product is highly suggestive of the kind of premarket approval system that DSHEA was created to protect against. If this shift in FDA position is not in disagreement with DSHEA per se, it certainly is in disagreement with the 1997 Final Rule 62 FR 49886, in which FDA disagreed with the suggestion that a “substantive, rather than a procedural regulation is necessary to respond to section 413(a)(2) of the act.” The purpose of DSHEA (in accordance with the 1997 Final Rule) was to balance consumer safety, that is, the consumer’s reasonable expectation of safety, with consumer access. The authors ensured that the act was very clear in establishing the findings of Congress on matters regarding dietary supplements and commerce [DSHEA §2(13) and §2(15)]:
“(13) although the Federal Government should take swift action against products that are unsafe or adulterated, the Federal Government should not take any actions to impose unreasonable regulatory barriers limiting or slowing the flow of safe products and accurate information to consumers; …”
“(15)(A) legislative action that protects the right of access of consumers to safe dietary supplements is necessary in order to promote wellness;….”
References
[1] The original 90-day public comment period has been extended and is currently scheduled to close December 2nd.
[2] Technical questions such as “What substances qualify as new dietary ingredients (NDIs)?” and “When must a NDI notification (NDIN) be filed?”
[3] “…the term ‘‘new dietary ingredient’’ means a dietary ingredient that was not marketed in the United States before October 15, 1994 and does not include any dietary ingredient which was marketed in the United States before October 15, 1994.” [Section 413 (c) of the federal Food, Drug and Cosmetic Act (FDC Act); 21 USC §350(b)]
[4] DSHEA §2(12)(C)
[5] A cost of $410 was estimated per notification, “for an annual cost range of $0 to $4,920 per year.”
[6] “Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues”, July 2011 (<http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/Dietary Supplements/ucm257563.htm>; site accessed August 23, 2011)
[7] Of these, 162 were acknowledged by FDA with “no objection”, 450 were rejected due primarily to inadequate information or being incomplete. FDA requested additional information from the submitting companies for the remaining notifications.
[8] Daniel Fabricant, Director of the FDA Division of Dietary Supplement Programs, in “FDA’s NDI Guidance Document and Its Impact on the Dietary Supplement Industry”, a webinar sponsored by the Council for Responsible Nutrition (CRN), Washington, D.C., and Virgo Publishing, Phoenix, AZ, September 14, 2011.