The future of NMN: NPA lawsuit, amended FDA petition might determine itThe future of NMN: NPA lawsuit, amended FDA petition might determine it

A trade association in Washington, D.C., has filed an amended citizen petition with the U.S. Food and Drug Administration, elaborating on arguments that β-NMN (beta-nicotinamide mononucleotide) should not be excluded from the definition of a dietary supplement.

In challenging the FDA’s position that NMN cannot be lawfully marketed in supplements, the Natural Products Association in a 17-page filing incorporates arguments made in a lawsuit against the FDA.

U.S. District Judge Paul L. Friedman in October ordered that proceedings in the lawsuit are stayed until FDA answers NPA’s citizen petition. FDA intends to answer the petition by July 31, according to a court filing.

NPA requested in the amended petition that the FDA’s commissioner determine NMN is not excluded from the definition of a dietary supplement or commit to exercising “enforcement discretion in connection with the marketing and selling of NMN in or as a dietary supplement.” Alternatively, NPA requested the FDA recommend that the secretary of HHS (U.S. Department of Health and Human Services) decide NMN is lawful in supplements through a notice-and-comment rulemaking.

The lawsuit in the nation’s capital and amended citizen petition could not only shape the future of NMN in dietary supplements but also influence future innovation of—and investment in—other new dietary ingredients. According to the latest estimate from New Hope Network’s Nutrition Business Journal, supplements generated $67.48 billion in domestic 2024 sales.

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‘Drug exclusion clause’

The dispute between NPA and the U.S. government is focused on the FDA’s interpretation of a clause in the law that excludes an “article” or ingredient from being marketed in a dietary supplement if it was first approved as a drug, or first authorized for investigation as a new drug and the subject of “substantial clinical investigations” that have been instituted and made public.

In reliance on clinical trials conducted by Metro International Biotech LLC (Metro), the FDA has concluded NMN was authorized for investigation before it was lawfully marketed in the U.S. in supplements and therefore is prohibited from being sold in natural products.

Metro, whose proprietary form of NMN is called MIB-626, has filed a motion to intervene in the lawsuit and is awaiting a decision from Judge Friedman.

NPA, in its lawsuit and amended citizen petition, challenges the FDA’s interpretation of the so-called drug exclusion clause in the Dietary Supplement Health and Education Act of 1994 (DSHEA).

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“The proper interpretation of this clause—based on canons of statutory construction—requires the investigations to be both substantial and public before the article can be excluded from the definition of a dietary supplement,” according to NPA’s amended petition. “In other words, the operative date for determining when an article is excluded from the definition of a dietary supplement should be the date that all three requirements are satisfied. But FDA’s interpretation reads ‘substantial’ and ‘public’ (and arguably ‘authorized for investigation’) out of the statute.”

What’s more, Metro’s MIB-626—the subject of patents—cannot trigger the drug exclusion clause because it is different from the naturally occurring NMN marketed in supplements, NPA argued. Citing the Patent Act, the amended petition asserts that a patent cannot be granted on a compound like NMN unless it is distinguishable from that existing in nature.

“This means that MIB-626 must be something different than the naturally occurring NMN used in dietary supplements that NPA’s members seek to market in the United States,” NPA wrote in its amended petition, which was signed by its president and CEO, Daniel Fabricant. The trade association maintained “it is scientifically wrong and procedurally improper, arbitrary and capricious for FDA to bar use of NMN as a dietary supplement by citing non-NMN clinical investigations.”

Even if Metro’s investigations of MIB-626 studied NMN, “they still would not trigger the drug exclusion clause because they are not substantial clinical investigations, nor could it, given the absence of any definition of what makes a clinical trial substantial,” according to the amended petition.

NPA cited the absence of FDA guidance on the issue, adding that the FDA “appears to read the word ‘substantial’ out of the statute by treating any clinical investigation as substantial.” The first clinical study of MIB-626 cited by FDA consisted of seven participants, while a second trial lasted for just 14 days and involved 42 participants, NPA said. Both trials purportedly began in 2021.

In addition to seeking to intervene in NPA’s lawsuit, Metro International Biotech previously requested in an administrative filing that the FDA uphold its determination that NMN is excluded from the definition of a dietary supplement. The clinical-stage pharmaceutical company made the request in response to NPA’s original petition.

“The FDA should not permit NMN products to be sold as a dietary supplement, which would be in violation of the drug exclusion clause and without sufficient demonstration of safety, adequate directions for use, or compliance with good manufacturing practices,” Metro concluded in its Nov. 20, 2023, letter to FDA.

This piece originally appeared on SupplySide Supplement Journal, a New Hope Network sister website. Visit the site for information on the nutrition industry—from supplements and functional foods to sports nutrition and manufacturing.