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Natural Products Association meets with FDA on anti-aging ingredient, NMN

FDA buildings 2020
In addition to meeting with FDA officials, NPA's leader also requested FDA open a docket so stakeholders can submit evidence to the agency about the presence of NMN in food and supplements. Such a docket could provide stakeholders an opportunity to establish NMN was lawfully marketed in food before the anti-aging ingredient was authorized for investigation as a new drug.

On Wednesday, Nov. 30, representatives from the Natural Products Association (NPA) met with four FDA officials in response to a recent determination by regulators that an anti-aging ingredient, β-NMN (beta-nicotinamide mononucleotide), cannot be marketed in dietary supplements due to its earlier investigation as a pharmaceutical drug.

The next day, NPA CEO and President Dan Fabricant requested FDA open a docket on NMN to allow stakeholders to submit information and comments to the agency on the presence of the ingredient in food and supplements.

Cara Welch, who oversees FDA’s Office of Dietary Supplement Programs (ODSP), advised Fabricant in an email that her agency would review and respond to NPA’s request.

In an interview last week following the meeting, Fabricant said he and NPA’s outside counsel, Kevin Bell, “made a few key points” during the 50-minute conference call with FDA officials, who included Welch and two other representatives from ODSP, as well as a lawyer from the Office of Chief Counsel, Louisa Nickerson. Several industry stakeholders also joined the conference call, including Now Health Group CEO Jim Emme, an NPA board member.

During the meeting, Fabricant recollected, he said NMN poses no safety issues, and he challenged FDA on its legal interpretation of a section in U.S. law that prohibits ingredients in dietary supplements if they have been authorized for investigation as a new drug and the subject of substantial clinical investigations that have been instituted and made public.

According to FDA, the prohibition doesn’t apply if the ingredient or “article" was lawfully marketed as a food or dietary supplement before it was authorized for investigation as a new drug.

NPA has shared documents with FDA that may have relevance to the analysis above. The materials include a few patents related to NMN in food and supplements, as well as a company’s announcement four years ago that its ingredient was self-affirmed GRAS (generally recognized as safe).

The December 2018 announcement by Nutraland USA suggested an intent to sell NMN as a food—perhaps before the ingredient was authorized for investigation as a new drug.

According to its website, Nutraland USA was incorporated in California in 2011, the company has an R&D center and manufacturing facility at its joint venture in China, and its roots date back to the 1990s when its “key team members started working in the nutraceutical industry.”

The company did not respond to two emails and a message delivered through its website for this story. Fabricant said he had not spoken with Nutraland USA, but he planned to.

What does NPA’s leader find “most troubling” about the NMN dilemma? That FDA concluded NMN is excluded from supplements without first checking if stakeholders in the natural products industry had evidence relevant to its determination, according to Fabricant, who oversaw FDA's Division of Dietary Supplement Programs from 2011 until 2014.

Industry stakeholders also have expressed frustration that FDA changed its position concerning the legality of NMN in dietary supplements.

In May, for example, FDA acknowledged without objection a new dietary ingredient notification (NDIN) for NMM, clearing a path for the ingredient to be marketed lawfully in supplements.

The agency changed its position after making the association between an article authorized for investigation as a new drug—called MIB-626—and NMN.

“When the FDA initially reviewed NDI notifications relating to NMN, NMN was not clearly identified as an article that was authorized for investigation, i.e. MIB-626,” an FDA spokesperson said in a Nov. 10 email. “Once the FDA was made aware of the connection between NMN and MIB-626, we concluded NMN is, in fact, excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(ii) of the FD&C [Food, Drug & Cosmetic] Act.”

Massachusetts-based Metro International Biotech has been studying MIB-626, or NMN, to treat such medical conditions as Alzheimer’s and Friedreich's Ataxia, a rare disease the National Institutes of Health says causes progressive nerve system damage and movement problems.

David Livingston, president and CEO of Metro International Biotech, previously declined to comment on FDA’s conclusions in letters to ingredient suppliers that NMN is excluded from the definition of a dietary supplement.

A recent FDA letter on NMN, Livingston said in a Nov. 10 email, “speaks for itself, and of course we will abide by their adjudication on this matter.”

The rational for FDA’s NMN determination, including analysis of several related legal issues, is articulated in a Nov. 4 letter to Inner Mongolia Kingdomway Pharmaceutical Limited (Kingdomway).

“Now, we have to provide all this other information when FDA didn’t look,” Fabricant said in the phone interview, where he was joined by Bell, outside counsel to NPA and a partner with Arnall Golden Gregory LLP. “Where does that come from in the statute?”

As for the materials NPA sent to FDA in advance of the meeting, FDA shared it had not closely reviewed the information and “couldn’t speak to much of it,” according to Bell.

The lawyer said he asked FDA officials if any of the information forwarded to FDA was helpful or not helpful. Bell said Welch responded it would need evidence NMN was lawfully marketed as a food or supplement prior to the date the ingredient was authorized for investigation as a new drug, which FDA does not publicly disclose.

“Unfortunately, there’s nothing very surprising that comes from these [FDA meetings] because they don’t commit to anything,” said Bell, who represented NPA in a lawsuit against FDA relating to FDA’s determination that NAC (N-acetyl-L-cysteine) is excluded from the definition of a dietary supplement due to its approval as a drug in 1963. That lawsuit was recently voluntarily dismissed after FDA issued a policy of “enforcement discretion,” providing an avenue for brands to continue to sell NAC supplements in the U.S.

FDA did not respond to specific questions for this article about the substance of the meeting last week with NPA or whether it would open a docket in response to NPA’s request. FDA also did not comment on its response to information shared with the agency, including the self-affirmed GRAS announcement in 2018.

However, the agency issued a statement in response to several questions from Natural Products Insider.

“The FDA has communicated with various groups in recent weeks regarding the conclusion that NMN is excluded from the definition of dietary supplement, as described in the November 4, 2022 letter,” an FDA spokesperson said in an email. “We are aware that industry stakeholders are interested in understanding more about the FDA’s position as well as learning what information would be relevant to revisiting this conclusion. We refer interested parties to the explanation in the November 4, 2022, letter. The FDA values the input we receive from all stakeholders and will review the information provided to us.”

NMN is still being widely sold on the internet. One brand said it believed NMN is a supplement and that such a position is shared by leading industry trade associations.

NMN “has been safely studied as a supplement since 2017, which predates its research in other areas, and we plan to continue offering it to our customers,” said the company, which spoke on condition of anonymity so it could speak freely without unwanted attention from FDA.

FDA did not reveal whether it intends to take enforcement action against brands that continue to sell NMN in dietary supplement products. The agency, however, reiterated NMN may not be marketed in or as a dietary supplement.

“If the FDA determines that a product labeled as a dietary supplement is unsafe or otherwise violates the law, the agency takes action as appropriate, based on public health priorities and available resources,” the FDA spokesperson said. “We are committed to working collaboratively with all of our stakeholders to help ensure dietary supplements are safe, produced in conformity with current good manufacturing practices and accurately labeled.”

 

 

 

 

 

 

 

 

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