FDA has declined a request from the Natural Products Association (NPA) to open a docket on anti-aging ingredient β-NMN (beta-nicotinamide mononucleotide), concluding interested parties already have the chance to submit relevant information to the agency.
Cara Welch, who oversees FDA’s Office of Dietary Supplement Programs (ODSP), described the opening of a public docket, which is frequently accompanied by a Federal Register notice, as a “discretionary act,” excluding when a statute or regulation requires such an act, and she said a Federal Register notice is not warranted.
“FDA has communicated its conclusion that NMN is excluded from the definition of a dietary supplement by letter to all the notifiers who have a new dietary ingredient (NDI) notification on file pertaining to NMN,” Welch wrote in the Jan. 20 letter to NPA President and CEO Dan Fabricant. “In these letters, we have invited each notifier to provide any additional evidence they may have regarding the earliest marketing of NMN as a food or dietary supplement.”
Welch also reiterated NMN is excluded from the definition of a dietary supplement and that its position has not changed even after receiving additional materials from interested parties seeking to change FDA’s determination.
Welch also said in the letter to Fabricant that her agency “will continue to review any relevant evidence submitted to us.”
In the fall of 2022, FDA concluded in letters to ingredient suppliers that NMN is excluded from the definition of a dietary supplement due to being first authorized for investigation as a new drug and the subject of substantial clinical investigations that have been instituted and made public.
The news came as a surprise—and was perceived by some industry stakeholders as unfair—since FDA did not raise the drug preclusion issue in its responses to five NDI notifications between the summer of 2020 and the spring of 2022. One of the ingredient notifications (filed by SyncoZymes [Shanghai] Co. Ltd.) was even acknowledged by FDA without any objections, receiving a so-called acknowledgement or AKL letter.
In her letter to Fabricant, Welch acknowledged receiving materials from interested parties regarding NMN, including a Dec. 21, 2018, announcement by Nutraland USA (shared by NPA with FDA) that its ingredient was generally recognized as safe (GRAS) by an independent review panel.
“GRAS evaluations concern safety, not marketing, and the date of a GRAS evaluation is not evidence of when an ingredient was first marketed as food,” Welch wrote.
Other documents received by FDA also have not changed its determination that NMN is excluded from the definition of a dietary supplement.
“Although we have decided not to open a docket at this time, we will continue to review any relevant evidence submitted to us,” Welch concluded. “Should you or your member companies have additional information to submit to FDA pertaining to the earliest marketing of NMN as a food or dietary supplement, please send it to [email protected] and reference ‘NMN marketing’ in the subject line.”
NPA response to FDA NMN letter
Fabricant, who oversaw FDA’s Division of Dietary Supplement Programs during part of the Obama administration, questioned in what way his former employer is protecting the public health through its determinations that certain ingredients—including cannabidiol (CBD), NMN and N-acetyl cysteine (NAC)—are excluded from the definition of a dietary supplement.
“When it comes to dietary supplements and foods, FDA is dug in on an adversarial strategy, whereas with pharmaceuticals the agency clearly sees them as a customer and behaves with trusting and cooperative postures,” he maintained in an emailed statement to Natural Products Insider.
Instead of focusing its limited resources on firms who are intentionally adulterating or misbranding products, FDA is making “matters difficult” for rule followers who have submitted an NDI notification or conducted a self-GRAS evaluation, Fabricant said.
He also disagreed with FDA’s interpretation that Nutraland USA’s press release on its self-GRAS announcement doesn’t constitute evidence of marketing of NMN as a food prior to the ingredient being authorized for investigation as a new drug.
“That coupled with FDA’s reversal on an NDI AKL letter, which isn’t authorized in either the statute or the regulations, without a rendering of a product being adulterated or misbranded, should get everyone’s attention,” Fabricant added. “If they [FDA officials] can pull an AKL once without foundation, what’s to stop it from happening again and again? It would seem the agency has returned to their pre-DSHEA [Dietary Supplement Health and Education Act] view that their job is to limit the entry of novel ingredients to the food and dietary supplement marketplace. As we did on NAC, we will leave no stone unturned in finding a solution to ensure a safe and vibrant marketplace. Americans who want access to and want to develop innovative health and wellness products shouldn’t be treated like a second-class citizen by the FDA.”
FDA, on the other hand, has maintained it is simply applying applicable provisions of federal law, and once the agency made the connection between a drug under investigation called MIB-626 and NMN, it determined the ingredient was excluded from the definition of a dietary supplement.
“While review of whether a particular ingredient is excluded from the definition of dietary supplement is not required as part of a new dietary ingredient notification review, the FDA makes an effort to conduct a thorough review of the NDI that is the subject of an NDI notification, including the identity and safety information provided, as well as other regulatory issues that are applicable, during the review period,” an FDA spokesperson said in an emailed statement in November. “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. 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 Act. The reasons for our conclusion are explained in the FDA’s supplemental response letter to NDIN 1259.”