FDA faces new lawsuit from NPA over anti-aging ingredient NMN

A Washington, D.C.-based trade association representing retailers and manufacturers of dietary supplement products has sued the U.S. Food and Drug Administration for the second time since late 2021 — this time over an anti-aging ingredient that’s been investigated as a new drug. 

On Wednesday, August 28, the Natural Products Association (NPA) filed a complaint in the U.S. District Court for the District of Columbia against FDA, the U.S. Department of Health and Human Services (HHS) and the leaders of both agencies. 

NPA requested a declaratory judgment, finding that β-nicotinamide mononucleotide (NMN) should not be excluded from the definition of a dietary supplement. The lawsuit is consequential not just for ingredient suppliers and finished product brands selling NMN, because it also affects the interests of a pharmaceutical company that has been conducting clinical trials of NMN using its proprietary ingredient called MIB-626. 

Metro International Biotech LLC was co-founded by David Sinclair, Ph.D., a world-renowned scientist on the aging process and ways to slow its effects. Sinclair was the subject of an in-depth Wall Street Journal article published on April 27 and featuring the headline, “Star Scientist’s Claim of ‘Reverse Aging’ Draws Hail of Criticism.” 

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An investigational new drug application (IND) filed with FDA — and the clinical trials involving Metro’s MIB-626 that have been instituted and made public — have shaped FDA’s conclusion that NMN cannot be marketed in dietary supplement products. 

The government’s determination, which Natural Products Insider first reported in November 2022, blindsided and incensed the industry because FDA previously had been aware of efforts to market NMN in supplements and even acknowledged without objection a so-called new dietary ingredient notification (NDIN) for NMN.  

FDA received and filed the premarket ingredient notification from SyncoZymes (Shanghai) Co. Ltd. on March 21, 2022.  

The date is relevant because under FDA’s interpretation of the law, if NMN was “lawfully” marketed as a dietary supplement before it was authorized for investigation as a new drug, it can continue to be marketed in supplements. FDA, however, ultimately concluded NMN was excluded from the definition of a dietary supplement, “based on new information that came to light,” while it was reviewing another ingredient notification. 

In a Nov. 4, 2022, letter to a representative of another NMN ingredient supplier, FDA wrote, “After carefully reviewing the information provided in your amended notification and other relevant sources, including our own records, we also concluded 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.” 

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Since then, the NMN market has suffered business setbacks in the U.S. Amazon announced in 2023 it would no longer allow brands to sell NMN supplements, PayPal and Shopify payment processors stopped processing sales for the ingredient, and an internet compliance company called LegitScript designated “NMN as a pseudo-pharmaceutical based on FDA’s public statements that NMN is excluded from the definition of a dietary supplement,” according to NPA’s 47-page lawsuit. 

NPA disclosed at least three of its members have suffered harm as a result of FDA’s conclusion regarding NMN, including iHerb LLC, Cellmark USA LLC and Galaxy Nutrition LLC. iHerb is a global seller of natural products and Cellmark is the U.S. distributor of NMN manufactured by the only company (SyncoZymes) that received an acknowledgment or so-called good day letter for NMN in response to its NDIN. FDA in November 2022 effectively rescinded the letter after determining NMN was excluded from the definition of a dietary supplement. 

‘Drug preclusion clause’ in DSHEA 

A substantive ruling in the lawsuit could not only determine the fate of NMN in dietary supplement products but also influence innovation in both the pharmaceutical and natural product industries. The case implicates what NPA characterized as the “drug exclusion clause” of the Dietary Supplement Health and Education Act of 1994 (DSHEA). 

This clause bars an 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. 

NPA and others in the industry have bickered with FDA over the meaning of words in the drug exclusion clause, including “substantial,” and when the clause is triggered or the date of the race to market between the drug and supplement industries. These issues are described in detail in NPA’s lawsuit. 

The federal court won’t have to interpret DSHEA if it determines that NPA lacks standing or that other procedural requirements haven’t been met before a lawsuit can be filed against FDA. The complaint, however, seeks to combat potential arguments by the government that the lawsuit is premature, that NPA has not “exhausted” its administrative remedies and that its members have not suffered any harm. 

For instance, NPA cites a “notice of FDA action” issued to an NPA member on Aug. 13 regarding a shipment of NMN (5 kilograms) imported into the U.S. and detained. In a partially redacted version of the document obtained by Natural Products Insider, FDA stated, “The article is subject to refusal of admission pursuant to section 801(a)(3) in that it appears to be a new drug within the meaning of Section 201(p) without an approved New Drug Application (NDA).” 

The shipment of detained NMN arrived on July 11 at the port of entry in Louisville, Ky., the FDA document shows, and the importer had until Sept. 3 to respond to the notice. The FDA notice stated the firm (whose name was redacted in the document obtained by Natural Products Insider) had the right to offer testimony to FDA “regarding the admissibility of the article(s) or the manner in which the article(s) can be brought into compliance,” though the “testimony must be provided to FDA on or before the dates shown above or products are subject to refusal.”

Meanwhile, FDA has yet to substantively respond to an NMN-related citizen petition filed in March 2023 by NPA and the Alliance for Natural Health. The petition requested FDA determine NMN is not excluded from the definition of a dietary supplement or commit to exercising enforcement discretion regarding the selling of NMN as a dietary supplement. In the alternative, the petitioners requested FDA recommend that the secretary of HHS issue a regulation finding that NMN would be lawful in supplements. 

On Aug. 30, 2023, the agency advised the groups it had not reached a decision within 180 days on the petition “due to competing agency priorities.” In response to the petition, Metro International Biotech requested that FDA uphold its determination that NMN is excluded from the definition of a dietary supplement and cannot be marketed in such products. 

“FDA has shown it will seek to enforce its conclusion on NMN and improperly detain NMN while intentionally refusing to respond to NPA’s citizen’s petition,” NPA stated in the lawsuit. “This is not an issue that will resolve itself absent judicial intervention.”  

Significance of NMN lawsuit 

The law firm Arnall Golden Gregory LLP (AGG) is representing NPA in the lawsuit. Attorneys Matthew D. Zapadka, Kevin M. Bell, Andrew K. Beverina and April Meeks are listed at the end of the complaint. 

In a phone interview Wednesday, Bell explained the importance of the lawsuit against FDA. He said the agency must “start getting comfortable with the idea” that the industry will “challenge and respond” to FDA when it takes actions or inactions, such as those associated with NMN. 

“I think there is a history of this industry not challenging FDA’s positions,” said Bell, a partner with AGG and longtime outside counsel to NPA. 

The NMN lawsuit against FDA demonstrates “this is a new day,” he added. “When you do something that harms our industry that we disagree with, that we think is legally incorrect, we’re going to start challenging [FDA]. You see it on the drug side all the time. You rarely see it on the food/supplement side.”  

NPA President and CEO Dan Fabricant, Ph.D., suggested FDA is unwilling to have discussions with industry to try to resolve disagreements “in a timely and reasonable manner.”  

“It’s got to be [dragged] through the courts, which is unfortunate,” he said in an interview. 

The case is significant not only because NMN is an important ingredient for the supplement industry. FDA’s determinations on NMN have harmed the new dietary ingredient notification process, argued Fabricant, who oversaw FDA’s Division of Dietary Supplement Programs from 2011 until 2014. This notification process is a requirement in DSHEA to demonstrate the safety of an ingredient like NMN. 

“You had a properly formatted, lawfully submitted NDI [that received] a ‘good day’ letter, and then FDA pulled the good day letter,” Fabricant said. “That’s never happened before.” 

Requested relief 

Among other relief, NPA’s lawsuit requests a declaration that the drug exclusion clause in DSHEA “does not apply to the dietary ingredient NMN and that FDA’s actions are contrary to law, and arbitrary and capricious.” Should the U.S. District Court determine that FDA hasn’t taken “final agency action” and that NPA lacks standing to bring the case, the lawsuit requests alternative relief, or specifically an order requiring FDA to issue a final decision on NPA’s citizen petition within 21 days of the court’s determination that there has been no final agency action. 

This isn’t the only lawsuit filed against FDA by NPA in recent years. NPA sued FDA in December 2021 over its determination that another ingredient — N-acetyl-L-cysteine (NAC) — was excluded from the definition of a dietary supplement. NPA eventually voluntarily dismissed the case after FDA issued a final guidance or policy of “enforcement discretion” for NAC-containing products labeled as dietary supplements. AGG also represented NPA in that case. 

This summer, FDA revealed plans to publish a first-of-its-kind rule to make an ingredient (NAC) lawful in dietary supplements, despite it being first researched or approved as a drug. 

Asked for comment on the NMN lawsuit, an FDA spokesperson said the agency doesn't comment on pending litigation.

Editor's note: This article was corrected to clarify that NPA's lawsuit against FDA was filed on Wednesday, Aug. 28, not August 27.