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What's the NDI (New Dietary Ingredient) Notification Process Really Like?
With so much talk over FDA’s new dietary ingredient (NDI) draft guidance, I’ve wondered: What does a successful notification take? I decided to ask a company firsthand.
In May, FDA accepted with no objections a NDI notification for Aker BioMarine’s (Aker; Oslo, Norway) Superba krill oil, which has been marketed in the United States as a dietary ingredient in supplements since 2009. I asked Melody Harwood, director of regulatory affairs, how she would describe the experience. Her response? “Very positive.”
To start, the company enlisted expert help-specifically, Madhu Soni, PhD, of Soni & Associates-in compiling the “extensive” data. Luckily, Aker already had much of the information on hand, thanks to preparations made when acquiring Novel Foods approval in Europe. The NDI information Aker submitted follows that outlined in the new draft guidance, including data on composition, stability, manufacturing, and intended use. For safety evidence, it supplied data demonstrating that all krill oil components are naturally present in the diet; an overview of the “metabolic fate” of those components; published human and animal studies showing no adverse effects; as well as safety evidence on specific krill components EPA, DHA, and astaxanthin.
Aker also consulted legal firm Hyman, Phelps & McNamara on whether a NDI notification would be necessary at all. “The opinion [was] that although krill oil would be considered a NDI due to the fact that substantiation of marketing in the United States prior to 1994 could not be established, sufficient data were available to support the presence of krill oil in the food supply in a form in which the food has not been chemically altered from its composition as a dietary ingredient-thus negating the requirement to file a NDI notification with FDA.” Nevertheless, Aker filed the notification for added assurance for customers.
I asked whether Aker felt at the time (before the new guidance was released) FDA had provided enough direction through the NDI process. Harwood’s answer? It depends.
“Unless a company was already familiar with the NDI notification process and the reasons for the varied responses (both positive and negative) of FDA to notifications that had been submitted, it would be difficult to feel confident in the adequacy of evidence required as part of the notification. The limited guidance that had been available to industry since the passing of the Dietary Supplement Health and Education Act of 1994 was not definitive enough in terms of providing an outline of data required to be included in a successful notification...[and] whether a NDI notification was required to be submitted was not always straightforward.” She notes that the new guidance is “more of a roadmap than available prior” and that consulting FDA itself during filing was “invaluable in facilitating a positive outcome to what can be a challenging process.”
I also asked about FDA’s estimation that compiling notification data will take, on average, 20 hours. In July, the Council for Responsible Nutrition sent draft guidance comments to FDA on this, stating that the agency underestimates the time and suggesting, more realistically, 100 to 350 hours. Also, although FDA posits that no capital costs are needed, firms-like Aker did-end up investing heavily in consultants, journal articles, and legal reviews, etc.
Harwood: “Unless a company had already compiled a master file of data for a similar submission in another jurisdiction, the time frame of 20 hours suggested by the FDA would definitely be much shorter than the time that would actually be required to prepare a successful NDI notification.” She says that based on her 10 years of experience with notifications as a scientific/regulatory consultant prior to joining Aker, “the time spent from start to finish in preparing the data sufficient for a successful notification well exceeds 20 hours and more realistically approaches at least 50 hours for a straightforward notification, to more than 100 hours for a NDI that may have complex properties/study results that merit significant detail and explanation in its NDI notification.” This also doesn’t count the time for other studies needed (e.g., stability, preclinical, or clinical).
By the way, Harwood does describe FDA as “timely” in its 75-day review process. Aker submitted its original notification to the agency in late February. FDA requested additional information on analytical methods and recommended conditions of use, which Aker submitted on May 9 and 11. FDA sent its final response on May 16.