The petition requests the FDA reverse its decision to reject NMN’s classification as a dietary ingredient and to use enforcement discretion.
The Natural Products Association (NPA) and the Alliance for Natural Health (ANH), two organizations representing the dietary supplements industry, have filed a Citizen’s Petition with the Food and Drug Administration (FDA). Their petition asks the FDA to reevaluate its position concerning the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN). As of November 2022, the FDA determined that NMN isn’t a dietary ingredient, citing that it’s under investigation as a drug. According to the FDA, the Dietary Supplement Health and Education Act (DSHEA) prevents vendors from marketing NMN as a supplement since it’s been classified as an investigational new drug (IND).
In the citizen petition, the NPA and ANH criticized the FDA’s interpretation of the DSHEA drug preclusion clause. The clause states that a molecule or compound isn’t a dietary supplement if it was “authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigation has been instituted and for which the existence of such investigation has been made public.”
The petition says that the FDA’s interpretation is troubling, because “(1) INDs are not authorized by the FDA, and (2) to Petitioners’ knowledge, there is no public access to a database or list of current articles that are subject to an IND. In fact, FDA’s regulations prevent it from publicly revealing the effective date of an IND or the source of an IND.” The petition goes on to question why Congress has set up a sort of “race-to-market” between pharmaceutical and dietary supplement companies without providing access to relevant information for determining the marketability of their products.
Concerning NMN, due to the FDA’s interpretation of DSHEA and other regulations, the FDA cannot identify the date when NMN was authorized as an IND. NMN was on the market as early as 2016 in Japan and no later than 2018 in the US, and the Agency acknowledged without objection a new dietary ingredient notification (NDIN) filed by SyncoZymes Co. Ltd. (Shanghai) in 2022. The FDA retracted its NDIN acknowledgement, citing NMN being under investigation as a drug and objected to NDINs that other companies submitted.
The petition further contends that the FDA’s interpretation of Section 201(ff)(3) of DSHEA is too narrow. According to the FDA, Section 201(ff)(3) requires manufacturers to prove that an article was marketed as a dietary supplement or food in the US prior to drug investigation or approval. The petitioners argue that there isn’t anything in the plain language of the statutes that requires marketing only in the US. “FDA is improperly trying to import a limitation into the statute that does not exist,” wrote the petitioners. “In fact, the 2016 Draft Guidance on NDINs provides (on page 68) that the data and information to substantiate a history of safe use is not limited to the United States.”
“The agency’s reversal on NMN NDIs is without statutory authority,” said Daniel Fabricant, PhD, CEO of the NPA in a press release. “The secrecy behind the IND dates, the evidence of a GRAS notice predating any IND on NMN, and NMS’s presence in the food supply all could’ve been rectified. Just like the case with NAC, the citizen’s petition gives the industry a platform to move towards a resolution concerning the ability to market NMN in or as a dietary supplement. In the case of NAC, NPA’s Citizen’s Petition was the vehicle that made possible its return to commerce on all platforms.”
The approach of submitting a petition is similar to the case of N-acetyl cysteine (NAC), which resulted in the FDA announcing enforcement discretion. “Seeing the example that NAC set, it did set a precedent, it’s one that should have been used before,” said Dr. Fabricant in a press release.
The Citizen’s Petitions asks the FDA to 1) determine that NMN isn’t excluded from being defined as a dietary supplement, 2) commit to practicing enforcement discretion on dietary supplements marketed as containing NMN, and 3) recommend the Secretary of Health and Human Services issues a regulation comment finding that NMN is lawful.