Congress struck a careful balance between providing consumers with access to safe dietary supplements and maintaining strict safety and efficacy standards for drugs when it enacted DSHEA in 1994.

• The law includes a “drug exclusion clause” with a “first-to-market” provision. See 21 U.S.C. § 321(ff)(3).
  
• The drug exclusion clause prevents a company from marketing as a dietary supplement a product that contains an ingredient that has been approved as a drug or authorized for investigation as a potential new drug. This preserves incentives for drug development because drug manufacturers are required to invest in expensive clinical trials to show that a new drug is safe and effective without concern that the same ingredient will be marketed as a dietary supplement.
  
• At the same time, the first-to-market provision prevents a drug manufacturer from forcing off the market a dietary supplement that contains a historical and lawful supplement ingredient. This preserves the dietary supplement pathway to market for ingredients marketed as a supplement before they were investigated as a new drug.

A recent decision by FDA concerning the regulatory status of nicotinamide mononucleotide (NMN) upsets the careful balance struck by Congress in DSHEA.

• In a major shift, FDA reversed its previous position and determined that NMN can be marketed as a dietary supplement. See FDA Response to Citizen Petition, Docket No. FDA-2023-P-0872 (Sep. 9, 2025).
  
• NMN is a naturally occurring molecule that is a precursor to nicotinamide adenine dinucleotide (NAD+), an essential coenzyme crucial for hundreds of cellular processes, including energy production, DNA repair, and gene expression regulation. As NAD+ levels in the body decline with age, various age-related health issues may result.
  
• FDA previously took the position that NMN was excluded from the definition of a dietary supplement under the “drug exclusion clause” because a drug manufacturer, Metro International Biotech, LLC (Metro), was authorized to investigate NMN as a new drug before NMN was lawfully marketed in the United States as a supplement.
  
  • FDA rejected the argument that NMN’s marketing as a dietary supplement outside the United States, in Japan, before Metro was authorized to investigate NMN as a new drug, qualified under DSHEA’s “first-to-market” provision.
    
  • Likewise, FDA previously rejected the argument that NMN’s unlawful marketing as a dietary supplement in the United States without a new dietary ingredient notification (“NDIN”), before it was authorized for investigation as a new drug, qualified under the “first-to-market” provision.
    
    • Because NMN is a new dietary ingredient (i.e., was not marketed in the United States in a dietary supplement before October 15, 1994) that is not exempt from notification, it could only be lawfully marketed in the United States if its marketer first submitted an NDIN with safety information showing that it is reasonably expected to be safe.
      
    • FDA objected to NDINs for NMN submitted before Metro was authorized to investigate NMN as a new drug because, among other things, FDA determined that the safety data provided was insufficient.
      
    • FDA objected to NDINs for NMN submitted after Metro was authorized to investigate NMN as a new drug both (i) because the safety data provided was insufficient and (ii) because, under the “drug exclusion clause,” NMN had been authorized for investigation as a new drug.
      
  • FDA now has reversed its previous position and concluded that NMN is not excluded from the definition of a dietary supplement under the “drug exclusion clause” based on evidence that NMN was unlawfully marketed as a dietary supplement in the United States, without an NDIN, before it was authorized for investigation as a new drug.

Because FDA’s abrupt and inexplicable reversal appears to be contrary to law, arbitrary and capricious, inconsistent with the objectives of DSHEA, and the source of substantial confusion within the pharmaceutical and supplement industries, FDA should explain to the Congress how the Agency’s new interpretation of the “drug exclusion clause” will not harm the balance and incentives that have been in place for more than 30 years.

• How is FDA’s abrupt switch from requiring lawful marketing under the “first-to-market” clause to not requiring lawful marketing under that clause consistent with Congress’ intent in light of the “drug exclusion clause”?
  
• How does rewarding the unlawful marketing of an ingredient as a dietary supplement without an NDIN under the “first-to-market” clause protect consumers from unsafe dietary supplements?
  
• How does rewarding the unlawful marketing of an ingredient as a dietary supplement without an NDIN under the “first-to-market” clause protect competitors who abide by the law’s requirements and submit an NDIN before marketing dietary supplements that contain a new dietary ingredient?
  
  
• How does rewarding the unlawful marketing of an ingredient as a dietary supplement without an NDIN under the “first-to-market” clause preserve incentives for drug development?
  
• Why would Congress have wanted to incentivize unscrupulous dietary supplement companies to engage in conduct that Congress has made a federal crime?