CRN submitted its comments on the New Dietary Ingredients draft guidance on Dec. 12, the final day the comments docket was open. The 36-page document lays out the group’s views on what’s good and might need tweaking, and what’s plain wrong with the draft guidance as it stands. The comments focus on areas such as the definition of dietary ingredients, how an authoritative list of Old Dietary Ingredients not subject to NDI provisions might be created and whether and when manufacturing changes to those ingredients change them to the degree that they become NDIs. In addition, the group gave its views for how the safety of those legacy ingredients could be established and commented on FDA’s proposal for Master Files in NDI submissions.
Definition of dietary ingredient
On the subject of what constitutes a dietary ingredient, Steve Mister, president and CEO of CRN, said the group was concerned that FDA was laying out an overly restrictive definition. In particular, the agency has taken aim at so-called synthetic botanicals (bioidentical is a term favored by many developers of these ingredients). CRN views this as a new twist added by FDA that did not exist in the underlying legislation, the Dietary Supplement Health and Education Act (DSHEA). Synthetic ingredients, such as vitamins and others, have been on the market for a long time, for the agency to in effect say, “Only these and no more,” is not justifiable, the group asserted.
“The list referenced by FDA includes dietary ingredients generally marketed in synthetic form, such as CoQ10, and dietary ingredients that had not historically been used to supplement the diet, such as H2O2,” the comments stated.
“In short, the law requires the term “dietary substance” under Section 201(ff)(1)(E) to encompass ingredients intended to supplement the diet that do not have historical use in conventional food. It also allows a synthetic copy of a botanical constituent to be a “constituent” under Section 201(ff)(1)(F) as long as it is chemically equivalent to its nature-derived counterpart,” the group’s comments added.
“We have been consistent that synthetic versions of botanical ingredients should be considered legitimate under the law,” Mister told NutraIngredients-USA. Mister said the concern about definitional boundaries extends to the agency’s restrictive view of what a “metabolite” of a dietary ingredient means. FDA has taken the stance that you can start with a legal dietary ingredient, subject to various processing steps and end up with a legal metabolite of that ingredient as long as the processing steps mimic a metabolic pathway within the body. CRN observed that this goes beyond legislative intent and calls on data that does not exist, as many metabolic pathways have not been scientifically confirmed.
“We’re nervous about the way FDA was saying only certain kinds of metabolites were allowed and not others. It’s the same with amino acids; they like some, but not others,” Mister said.
”Congress meant for dietary ingredients to be a very encompassing category,” he said.
CRN applauded FDA’s willingness to establish a list of Old Dietary Ingredients. In the first draft guidance, FDA said the various lists that had been compiled by stakeholders were of little use and bascially left the quesiton of an ODI lsit at that. In the more recent version, the agency signaled a willingness to work with industry to compile such a list, but CRN took issue with the agency’s view of what kind of data would support placing a given ingredient on the list. In particular, CRN viewed the agency’s desire to have a 25-year history of safe use to have been plucked out of a hat, more or less. That stipulation was not supported by evidence, but rather was taken from a draft of an EU novel foods requirement that was never put into final form, CRN said.
Who gets onto the ODI list?
But exactly how such a list would be compiled is still up in the air and will best be accomplished with a collaborative effort between FDA and industry, Mister said. Among the issues such a collaboration might delve into is how to prove something was on the market in 1994. Many companies have entered the business since then, and others have exited, taking their manufacturing and sales records with them.
“We don’t have all the answers. But the hurdle to get on the list can’t be so high that nobody can clear it. Then it’s not going to be a very big list and not very useful,” Mister said.
On the subject of what kinds of changes that might kick an ODI off that list, CRN stated that safety should the be the guiding principle, not an overly broad determination of what “chemically altered” means. If it’s still the same ingredient but changed only slightly, such as extracted with CO2 instead of ethanol, that shouldn’t be a cause for concern, the group said.
“We urge FDA to interpret “chemically altered” to mean only those changes that alter an ingredient’s chemical identity or its potential for safe use in dietary supplements. This interpretation is consistent with both congressional intent and the agency’s public health goals,” CRN’s comments state.
As for ingredients that are clearly NDIs, CRN strongly urged FDA to step back from the verbiage in the draft guidance that would require a new filing on almost every new product that contains an NDI. Once the safety of an NDI has been established, CRN said new products should using that ingredient should be good to go, unless a compelling argument could be made that a new formulation might present an unusual risk.
“We continue to recommend that FDA permit ingredient manufacturers or distributors to submit NDI notifications that serve as the basis for establishing the safety of an NDI in a range of dietary supplements. Firms should self-determine whether additional notifications are needed based on an evaluation of the safety of the supplement containing the NDI,” the group’s comments state.