NDI draft guidance needs extensive revision, AHPA asserts

AHPA filed its 41-page comments document on the Food and Drug Administration’s docket on Dec. 12, the final day the comment period was open. The document addressed AHPA’s concerns with the updated NDI draft guidance, which was issued in August.  AHPA said in its document that it has many of the same concerns it expressed with the first go round of the guidance, which was issued in 2011. 

Overarching concerns​

Michael McGuffin, president of AHPA, said that while the group has a number of specific concerns with FDA’s language in the updated guidance, two of these rose above the others. 

“Our most innovative suggestions may be: one, any subsequent draft or final NDI guidance should actually encourage ingredient companies that submit NDI notifications to provide very broad descriptions of the many dietary supplements that may contain the NDI. And two, FDA should create a list of FDA-recognized ODIs that does not require the kind of absolute proof that FDA has described, but should instead list all ingredient that were likely marketed in 1994, as shown by the trade association-submitted lists and ​AHPA​’s Herbs of Commerce, as well as ingredients derived from these ODIs through traditional food preparation processes,”​ McGuffin said.

 “If FDA accepts the first of these recommendations, this will move away from any expectation that many thousands of NDI notifications will need to be submitted; and if they accept the second, there will be better certainty of the identify of ingredients that are not, in fact, subject to notification requirements. Both such outcomes would allow industry and FDA to focus attention on truly novel ingredients and would align the guidance with the Congressional intent that led to the enactment of DSHEA in 1994,”​ he added.

Duplicative filings​

On McGuffin’s first point, the AHPA comments elaborate how the group believes the draft guidance should be altered to prevent duplicative NDI filings.  Whether the NDI process should be ingredient-based or focused on finished products that contain new ingredients has been a bone of contention since the first draft guidance was issued. The updated NDI draft guidance did nothing to allay these concerns; if anything, it did the contrary.  FDA’s point of view is that establishing the safety of a new ingredient via a NDI notification is only a first step;  that safety must be established anew for every product matrix that NDI appears in.  In AHPA’s view (one it shares with the industry at large) this is unnecessary from a safety point of view and runs counter to the intent of DSHEA.  

“AHPA disagrees with an approach to NDI notifications and evaluations that assumes separate NDI notifications are required for every dietary supplement that contains an NDI; such an approach is inconsistent with the statute and is wholly impractical and economically impossible. . . .The law clearly does not intend NDI notifications to require detailed information, data, and analysis for every possible combination of dietary ingredients, dosage forms, excipient profiles, etc..” ​AHPA’s comments state.

If FDA were to start to operate in the manner specified in the guidance, AHPA said it believes the system would more or less grind to a halt. It sets up a scenario that is clearly unworkable in the group’s view.

“It is not in the interest either of industry, consumers, or FDA itself for large numbers of pointless NDI notices to be filed. AHPA estimates conservatively that the current draft guidance could trigger filing of tens of thousands of notices, which will put a tremendous strain not only on industry but also on the Agency and will likely result in a severe constriction in the range of dietary ingredients available in the marketplace,”​ the group’s comments state.

As a solution, AHPA proposes that NDI submissions include a description of the kind of products the new ingredient is likely to be used in. Ingredient developers usually have a very good idea of their target markets and could be expected to develop their safety dossiers along those lines. It’s rare that ingredients end up being applied to wholly unforeseen product matrices, a situation akin to off label uses of pharmaceuticals.

How to assemble an ODI list​

Another point of disagreement has been what constitutes an Old Dietary Ingredient, i.e. one that was on the market as of Oct. 15 1994 and because of a history of use can be assumed to be safe without further ado.  In the first draft guidance FDA rejected the notion that any of the several lists of such ingredients compiled by industry stakeholders could be used as a reference for establishing an official list. In the updated draft guidance, the agency has signaled a greater willingness to work on the issue, but AHPA still has concerns with how restrictively FDA might look at what kind of ingredients might make that final list.  In AHPA’s view, the way this effort is laid out in the updated guidance, the agency is looking for such a restrictive set of data points that only a few legacy ingredients will make the final ODI cut.

FDA’s reasons for rejecting those industry ODI lists had to do with the poor characterization of the ingredients described including, in the case of botanical ingredients, not being specific about the plant part used or not including precise information about how it was extracted. AHPA said it admits those early lists were not perfect, but should not be rejected wholesale because of easily rectified shortcomings.

“AHPA recommends that FDA completely transform its view of these documents and their usefulness in creating a list of FDA-recognized ODIs. The limitations FDA has previously identified with these could be readily overcome, for example by removing from the list drug ingredients (e.g., acetaminophen), as well as herbal ingredients that are known to be highly toxic (e.g., ​Nerium oleander) or that are no longer allowed to be sold as dietary ingredients (e.g., various species of Ephedra known to contain ephedrine alkaloids),”​ the group wrote.

Similarly, AHPA said it’s own Herbs of Commerce has some of the same shortcomings but can still provide a valuable resource to help inform the creation of an official ODI list.

In other portions of its comments, AHPA addressed concerns about what kind of toxicity testing the updated draft guidance is calling for. It also includes an in-depth discussion of the concept of chemical alteration, and specifically makes the point that supercritical CO2 extracts (a technology singled out by FDA in the updated guidance) have been in the food supply in the form of various color and flavor extracts without safety concerns for many years.

Time to bury hatchet​

McGuffin said he hopes the agency will be open to working together with industry to refine the NDI process into one that is workable while still keeping safety in mind. 

“​AHPA​ believes it is time to turn the page on the decades of discord and misunderstanding between FDA and the dietary supplements industry. FDA could go a long way toward making this needed progress by exhibiting some openness to the creative suggestions ​AHPA​ has proposed, each of which would still support the shared demand that all supplements in the market are reasonably expected to be safe,”​ he said.