FDA should focus the 75-day premarket notification process specifically on ingredients, not finished products, industry stakeholders asserted at the agency's public meeting on new dietary ingredient (NDI) submissions Nov. 15.

The agency currently evaluates all NDI applications, including those that are submitted for supplement products as a whole, rather than individual ingredients.

"FDA should not be concerned with how an ingredient was used or how it is labeled," National Nutritional Foods Association Executive Director David Seckman said at the meeting. "This information does not go to the safety of the dietary ingredient, and should not alter the review process as to whether a specific dietary ingredient is safe for use."

The meeting featured presentations from industry trade groups, company representatives and regulatory consultants. No presentations or comments were made by FDA.

The FDA panel included Center for Food Safety & Applied Nutrition Deputy Director of Regulatory Affairs Michael Landa; CFSAN Office of Nutritional Products, Labeling & Dietary Supplements Director Barbara Schneeman, PhD; Division of Dietary Supplement Programs (DDSP) Director Susan Walker, MD; DDSP Special Assistant to Division Director Vasilios Frankos, PhD; and DDSP Consumer Safety Officer Kelly Randolph.

Presentations at the meeting centered on the scope of NDI filing requirements.

FDA previously has found fault with submissions that do not detail other ingredients in the product, American Herbal Products Association President Michael McGuffin noted.

"I really strongly argue against any requirement that [makes it so] the only way I can get my new dietary ingredient approved is [to] disclose every other ingredient that it may ever be marketed with," he said.

"That puts an unfair burden on every product that has a single new dietary ingredient versus the whole world of products that have only old dietary ingredients."

Council for Responsible Nutrition President Annette Dickinson, PhD, said that FDA's request for certain information on supplement products is "appropriate." However, FDA should not expect labeling information as part of a 75-day premarket notification, she argued.

"We would simply note that in many cases the dietary ingredient notification is filed by the ingredient supplier, or by a manufacturer during a pre-launch phase of development of the product," said Dickinson. "The label simply may not be available at that point. So we do not believe the submission of label should be a critical part of that process."

Meeting participants also addressed the grandfathering of ingredients marketed prior to October 1994 and what crieria could deem "old" ingredients "new," and therefore require an NDI.

"We have discovered...that we don't necessarily have agreement within our association about the breadth of what might be grandfathered and whether there are conditions under which an old ingredient might become a new ingredient," Dickinson noted.

Both NNFA and AHPA have compiled lists of products that are believed to have been available before 1994.

Ingredients not listed on documents that have achieved "authoritative status" can still be grandfathered if adequate evidence is available to support a case for pre-1994 sale, Seckman maintained.

Human clinical trials, product ads, catalogues, order forms and invoices are evidence of pre-DSHEA product marketing, Seckman said.

In recent warning letters, FDA has said that some ingredients were not grandfathered because they were not "legally" marketed before 1994, Dickinson explained.

"The term 'legally marketed' does not appear in DSHEA and we do not believe that necessarily legal marketing is criteria for what is grandfathered," she asserted.

Dickinson pointed out that amino acids were at one time considered illegal substances under FDA food additive regulations, but nonetheless were marketed in supplements and now occupy their own subcategory in the definition of supplement products.

On a related issue, FDA sought comment on which changes to an ingredient's chemical composition might necessitate an NDI submission for that ingredient, even if it was marketed prior to 1994.

Ingredients should be considered chemically unaltered "as long as the resulting dietary ingredient is found in nature," Seckman said. "If it can be shown that an ingredient, either as a single entity or complex, can be found in our diets and there is no evidence of ill effects, that ingredient should be allowed for sale."

"Moreover, FDA should not assume that changes in processing or formulation always result in a change in the chemical structure that would require an NDI filing," Seckman added.

Still, companies should "err on the side of caution" when determining which ingredients are considered "new," Pharmavite VP-Regulatory & Legal Affairs Paul Bolar recommended.

Bolar cited modifications that result in new salt forms, new esters, chelates or complexes as examples of ingredients that should require a new submission.

Additionally, botanical ingredients taken from plants and used in supplements before 1994 - but obtained from parts of the plant not previously comprised in a product - should be considered new dietary ingredients, Bolar argued.

Dickinson recommended a Generally Recognized as Safe (GRAS) model like the one used for OTC drugs as a way of evaluating expectations of safety for supplements.

"We believe the GRAS self-determination process is an example of a highly effective and flexible process which allows manufacturers to make a determination of safety relying heavily on the insight of experts, or committees of experts, to help them make that determination and to help respond to any questions FDA may have," she said.

A program implemented by the Environmental Protection Agency for determining safe chemicals could serve as another example for assessing supplement safety, according to Dickinson.

The EPA new chemicals program involves structure/activity analysis to calculate possible interactions based on those of similarly structured chemicals.

Dietary Supplement Reps Ask FDA For Clarity Across The Board On NDIs

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