By Mike Montemarano, Associate Editor11.15.22
FDA declared that beta nicotinamide-mononucleotide (NMN) may not be sold or marketed as a dietary supplement in the U.S. because it was first authorized for investigation as a new drug.
NMN has been sold as a dietary supplement ingredient for several years, often marketed for anti-aging as an NAD+ booster (nicotinamide adenine dinucleotide).
Inner Mongolia Kingdomway Pharmaceutical Limited (Kingdomway) had filed a New Dietary Ingredient Notification (NDIN) for its NMN ingredient, which FDA rejected on the drug preclusion grounds.
“FDA has carefully reviewed the information provided […] and other relevant sources, including our own records, and has determined that NMN was not marketed as a dietary supplement, except unlawfully without an NDI notification, or as a food before FDA authorized it for investigation as a new drug,” Philip Yeager, director of the division of research and evaluation at Office of Dietary Supplement Programs (ODSP) Center for Food Safety and Applied Nutrition (CFSAN), wrote on Nov. 4. “NMN is an article for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public.”
One study Yeager pointed to was a randomized, controlled, human clinical study sponsored by Metro International Biotech, LLC, which investigated an NMN drug’s potential effects in COVID-19 patients and was published in 2021. Another study, posted in 2021, investigated the same drug in patients with Alzheimer’s disease. A third study Yeager referenced investigated the drug’s effects in Friedreich’s Ataxia, and was posted in 2021.
FDA has also cited the drug preclusion provision when it comes to cannabidiol (CBD). A CBD isolate is currently approved as a drug, branded as Epidiolex in the U.S., used to treat seizures in children with a rare disorder.
In a follow-up response to Kingdomway’s appeal, Yeager wrote that FDA is prohibited from disclosing the date on which NMN was first authorized for investigation as a new drug.
FDA’s interpretation of the drug preclusion statute is that dietary ingredients must have been widely consumed in foods prior to a New Dietary Ingredient Notification, “Because dietary supplements are generally consumed by a narrower segment of the population than conventional foods and typically have a shorter history of use,” Yeager wrote. This “typically provides less information about a substance’s safety than prior use in conventional foods. […] The legislative history of DSHEA also supports that ‘the food supply’ refers to foods other than dietary supplements.”
“Prior to the release of its October 11 and November 4 letters, the agency had acknowledged a New Dietary Ingredient Notification for β-NMN without objection. Additionally, FDA has not previously raised any concerns publicly about the ingredient being used in dietary supplements,” Mister said.
“Much of the innovation for dietary supplements comes from the introduction of new ingredients,” he continued. “But FDA’s actions demonstrate a disregard for consumers who benefit from the innovation and investments of dietary supplement companies. These decisions to broadly invoke drug preclusion to protect the profits and monopolies of drug companies do not serve a public safety objective. FDA’s reasoning and its refusal to provide a date certain when the authorization as a drug occurred just further raise concerns that it is protecting pharma’s interests over consumer welfare.”
According to Mister, the announcement “furthers FDA’s course of plucking individual ingredients out of the supplement marketplace without warning. Manufacturers, retailers, and consumers are left in limbo each time this happens.”
NMN has been sold as a dietary supplement ingredient for several years, often marketed for anti-aging as an NAD+ booster (nicotinamide adenine dinucleotide).
Inner Mongolia Kingdomway Pharmaceutical Limited (Kingdomway) had filed a New Dietary Ingredient Notification (NDIN) for its NMN ingredient, which FDA rejected on the drug preclusion grounds.
“FDA has carefully reviewed the information provided […] and other relevant sources, including our own records, and has determined that NMN was not marketed as a dietary supplement, except unlawfully without an NDI notification, or as a food before FDA authorized it for investigation as a new drug,” Philip Yeager, director of the division of research and evaluation at Office of Dietary Supplement Programs (ODSP) Center for Food Safety and Applied Nutrition (CFSAN), wrote on Nov. 4. “NMN is an article for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public.”
One study Yeager pointed to was a randomized, controlled, human clinical study sponsored by Metro International Biotech, LLC, which investigated an NMN drug’s potential effects in COVID-19 patients and was published in 2021. Another study, posted in 2021, investigated the same drug in patients with Alzheimer’s disease. A third study Yeager referenced investigated the drug’s effects in Friedreich’s Ataxia, and was posted in 2021.
A Familiar Refrain
The NMN news follows the recent saga over N-acetyl-cysteine (NAC), which FDA claims was precluded from use in dietary supplements. However, the agency said it would exercise enforcement discretion while it conducts a safety review and considers rulemaking on the matter.FDA has also cited the drug preclusion provision when it comes to cannabidiol (CBD). A CBD isolate is currently approved as a drug, branded as Epidiolex in the U.S., used to treat seizures in children with a rare disorder.
In a follow-up response to Kingdomway’s appeal, Yeager wrote that FDA is prohibited from disclosing the date on which NMN was first authorized for investigation as a new drug.
FDA’s interpretation of the drug preclusion statute is that dietary ingredients must have been widely consumed in foods prior to a New Dietary Ingredient Notification, “Because dietary supplements are generally consumed by a narrower segment of the population than conventional foods and typically have a shorter history of use,” Yeager wrote. This “typically provides less information about a substance’s safety than prior use in conventional foods. […] The legislative history of DSHEA also supports that ‘the food supply’ refers to foods other than dietary supplements.”
Uncertainty Surrounds Drug Preclusion
According to Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), the NMN case is part of an ongoing issue surrounding FDA’s lack of transparency regarding its drug preclusion interpretations.“Prior to the release of its October 11 and November 4 letters, the agency had acknowledged a New Dietary Ingredient Notification for β-NMN without objection. Additionally, FDA has not previously raised any concerns publicly about the ingredient being used in dietary supplements,” Mister said.
“Much of the innovation for dietary supplements comes from the introduction of new ingredients,” he continued. “But FDA’s actions demonstrate a disregard for consumers who benefit from the innovation and investments of dietary supplement companies. These decisions to broadly invoke drug preclusion to protect the profits and monopolies of drug companies do not serve a public safety objective. FDA’s reasoning and its refusal to provide a date certain when the authorization as a drug occurred just further raise concerns that it is protecting pharma’s interests over consumer welfare.”
According to Mister, the announcement “furthers FDA’s course of plucking individual ingredients out of the supplement marketplace without warning. Manufacturers, retailers, and consumers are left in limbo each time this happens.”
