Cicadas follow a 17-year life cycle, lying hidden in the soil only to emerge in a startling cacophony of noise and an intense flurry of activity. So it is too with the issue of New Dietary Ingredients, lying mostly concealed within the language the industry's foundation regulation for the past 17 years only to rear its head now with the recent release of FDA's draft guidance on the subject.
An attempt was made on July 26 and 27 in Salt Lake City to bring some order to the noise at an NDI Guidance Seminar hosted by the United Natural Products Association. An impressive list of speakers, headlined by Daniel Fabricant, Ph.D., director of FDA’s Division of Dietary Supplement Programs and including UNPA executive director Loren Israelsen, Michael McGuffin, president of the American Herbal Products Association (AHPA) and Mark Blumenthal, executive director of the American Botanical Council (ABC) dissected and debated the language of the guidance and the relevant portions of the Dietary Supplement Health and Education (DSHEA).
"I can’t say this enough. This is guidance. The authorities here, the authorities to regulate NDIs, were established in DSHEA," Fabricant said. It is the only area in which FDA can exercise "preventive control" of the dietary supplement market, he said.
The key sticking point of the guidance that emerged from the presentations and discussions is this: Is the NDI process based on the ingredient, or is a filing required for a finished product that includes a NDI regardless for the most part of whether the ingredient supplier had already filed a notification on that ingredient? The language of the guidance, re-emphasized by Fabricant in his remarks, unequivocally comes down on the side of the latter.
To use a hypothetical example, the guidance as elucidated by Fabricant would require a notification on a new finished product that combined an ingredient whose safety was already vetted via a NDI filing with a commonly accepted grandfathered ingredient such as vitamin C. "That would be more of an administrative filing than anything else," Fabricant said, "and that is the expectation here." The presumption is that changing the formulation, even in a presumably benign fashion as above, requires the safety of the product to be analyzed anew.
As he has on other occasions, Fabricant noted the disparity of the 700 NDI filings received to date (actually 547 according AHPA’s NDI database) and the 55,000-plus products now on the market. It was noted during the sessions that FDA has 10 staffers dedicated to receiving and responding to NDI filings, to which the agency, by statute, must respond within 75 days. When questioned on how the agency planned to deal with the potentially huge workload, Fabricant responded that the statute said 75 days, and FDA would meet that deadline.
Agreeing to disagree
This adherence to the finished product side of this question by the agency is one area in which FDA and industry may ultimately agree to disagree, Israelsen said. To bolster his view, one that was shared by most of the conference attendees, Israelsen produced a rough draft of the relevant portion of DSHEA that he had helped edit during the final hours of the crafting of DSHEA when he was a staffer for Sen. Orrin Hatch, R. Utah, who contributed video commentary to the seminar.
The word "supplements" was crossed out in the heading of the section and replaced with "ingredients." The text of the section, though, was completed in a hurry without much back and forth, and became law in a less precise and explicit fashion than it might have. It does contain both the words "ingredient" and “dietary supplement.” Hence the current debate, and the issuance of a 39-page guidance that expands upon the following six paragraph-long section of DSHEA:
Chapter IV of the Federal Food, Drug, and Cosmetic Act is amended by adding at the end the following:
"NEW DIETARY INGREDIENTS
- "SEC. 413. (a) IN GENERAL.- A dietary supplement which contains a new dietary ingredient shall be deemed adulterated under section 402(f) unless it meets one of the following requirements:The Secretary shall keep confidential any information provided under paragraph (2) for 90 days following its receipt. After the expiration of such 90 days, the Secretary shall place such information on public display, except matters in the information which are trade secrets or otherwise confidential, commercial information.
- "(1) The dietary supplement contains only dietary ingredients which have been present in the food supply as an article used for food in a form in which the food has not been chemically altered.
- "(2) 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 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.
- "(b) PETITION. - Any person may file with the Secretary a petition proposing the issuance of an order prescribing the conditions under which a new dietary ingredient under its intended conditions of use will reasonably be expected to be safe. The Secretary shall make a decision on such petition within 180 days of the date the petition is filed with the Secretary. For purposes of chapter 7 of title 5, United States Code, the decision of the Secretary shall be considered final agency action.
- "(c) DEFINITION. - For purposes of this section, 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.".
McGuffin, for his part, was unequivocal in his view that the intent of DSHEA was to focus the NDI process on new ingredients, not new finished products. "Let's be clear: The law doesn’t say that," he said.
Another speaker, Patricia Knight, who was also on Hatch's staff at the time, voiced her unease that the "preventive control" mentioned by Fabricant was tantamount to premarket approval, something the crafters of DSHEA sought specifically to avoid. “It is a notification, and we were very explicit about that,” she said.
As mentioned earlier, no true consensus was reached on the best strategy for industry going forward. But Israelsen, McGuffin and Fabricant all urged companies to submit comments.
"If these things aren't clear in the guidance, tell us in the docket," Fabricant said.
Continuing coverage on NewHope360 will focus on other aspects of the seminar, including the issues of documenting Old Dietary Ingredient status, toxicological concerns and the GRAS process as it relates to the NDI guidance.