On July 5, 2011, FDA published its much-anticipated Draft Guidance for Industry; New Dietary Ingredient (NDI) Notifications and Related Issues. Industry had been urging FDA to release such Guidance for years, citing an inability to divine the standards the agency applies in its NDI reviews, an inability to predict what material FDA actually considers to be a dietary ingredient, and the agencys NDI teams frequent failure to process submissions within the 75-day period required by the Dietary Supplement Health and Education Act of 1994 (DSHEA). The guidance, however, appears to be yet another example of, be careful of what you wish for.
Initial industry response cited concerns ranging from the type of documentation FDA indicates it is willing to accept as evidence that an ingredient was marketed prior to Oct. 14, 1994 (making it an old dietary ingredient and thus exempt from the stricture of the Guidance) to the requirement that NDI submissions contain information that looks strikingly familiar to what is required in order to support a food-additive petition. In addition to this type of broad area of concern, I believe four specific areas in the guidance document should be reviewed by all ingredient companies and dietary supplement manufacturers while they consider the potential impact of on their business.
1. Dietary Supplement Notification
Section IV of the guidance document consistently refers to the need to submit notifications for every dietary supplement containing an NDI. Notification by the ingredient supplier alone will not suffice. Any company that is manufacturing or marketing a multi-ingredient dietary supplement using a NDI will be required to submit its own notification for its specific product; multiple notifications will be required if a company uses the NDI in multiple products that do not have precisely the same dietary ingredients. In other words, if a company manufactures a single ingredient astaxanthin supplement, it can rely on its suppliers NDI notification. If it manufactures an astaxanthin/vitamin A dietary supplement, it will need to submit its own NDI notification that provides all of the information outlined in the Guidance. If it also manufactures an astaxanthin/glucosamine/boswellia dietary supplement, it will have to submit yet another NDI notification. Moreover, the Guidance would appear to require each of these submissions to include manufacturing data from the original NDI Notification that is quite likely considered proprietary/trade secret information by the ingredient developer. How FDA proposes to process the mountain of paper under which it would be buried under this process is not discussed in the Guidance.
Citing only the agencys determination earlier this year that homotaurine as produced by OVOS Natural Health cannot be a dietary ingredient because it is not the kind of amino acid the agency believes Congress intended to be covered by the term amino acid in DSHEA and because it is a synthetically produced, albeit nature identical, copy of a substance found in kelpSection IV D, question 2 of the NDI Guidance declares, A synthetic copy of a constituent of a botanical was never part of the botanical and thus cannot be a constituent of the botanical that qualifies as a dietary ingredient . . .. Similarly, a synthetic version of a botanical extract is not an extract of a botanical . . . because it was not actually extracted from the botanical. Thus, in what may be the most anti-innovative part of the guidance, FDA announced any synthetic dietary ingredient that does not fit its definition of vitamin, mineral or amino acid that was not on the market the day before DSHEA passed cannot be sold. The agency takes this position without regard for whether the synthetic substance is chemically identical to and behaves in the body in exactly the same way as what is found in nature, and shows utter disregard for economic and ecological consequences of barring this type of innovation.
In two other startlingly anti-innovative parts of the guidance, FDA appears to eliminate all new probiotic strains from consideration as dietary ingredients while suggesting that the application of nanotechnology to dietary supplements may be impossible. In Section IV, C, question 3, FDA simply states, Bacteria that have never been consumed as food (before DSHEA?) are unlikely to be dietary ingredients. FDA does not have a separate regulatory category or definition for dietary ingredients consisting of live or viable microorganisms. Later, in Section VI, question 43, the Guidance states, Because there is little scientific literature discussing the safety of nanomaterials in dietary supplements, FDA recommends that notifiers contact FDA prior to submitting a NDI notification for a NDI that contains nanomaterials or otherwise involves the application of nanotechnology. This position by FDA does not appear to hold much promise for the future of nanotechnology in dietary supplements.
4. Solvents/Changes in Manufacturing Process
In yet another example of clear regulatory overreach, in Section IV B, question 4, FDA cites the use of any solvent other than water or aqueous ethanol (tincture) to make an extract as creating an NDI requiring notification to FDA. No consideration is given to whether the extraction process (or any subsequent change thereto) creates an ingredient profile that would cause a toxicologist the slightest concern. The guidance would appear to require NDI notifications even where advanced technology that leaves behind no residue or causes no change to the ingredient profile like supercritical fluid extraction (CO2) is used. Even where HPLC or other analysis revealed the absence of any peaks or residue, the draft guidance appears to require a NDI notification.
Industry Needs to Respond
Together with various other positions staked out in the draft NDI guidance, these portions of the document indicate FDA takes an incredibly narrow view of what can be considered a dietary ingredient and an incredibly overbroad view of what would require the submission of a NDI notification. The guidance is clearly anti-innovative and designed to provide FDA with a platform to severely narrow the dietary supplement category while citing industrys failure to act responsibly. Though it is difficult to imagine FDA ever being able to actually implement this guidance due to the sheer volume of paperwork it would create by virtue of the new dietary supplement notification provisions alone, it is nevertheless incumbent upon industry to place its objections to FDAs flouting of DSHEA on the record. Any company whose business would be adversely affected if FDA was to ever act on this document should submit comments on the record by Oct. 3, 2011, detailing the economic impact they would face as well as FDAs failure to honor both the letter and spirit of DSHEA.
Marc Ullman is a partner at the New York-based law firm Ullman, Shapiro & Ullman LLC .