FDA Confirms N-acetyl-L-cysteine (NAC) is Excluded From the Dietary Supplement Definition and Leaves Open Potential Rulemaking to Allow the use of NAC in Dietary Supplements
We previously reported on FDA’s November 24, 2021 tentative response denying requests in two citizens petitions (June 1, 2021 Council for Responsible Nutrition (CRN) petition and August 18, 2021 Natural Products Association (NPA) petition) to change its position that N-acetyl-L-cysteine (NAC) products are excluded from the dietary supplement definition under section 201(ff)(3)(B)(ii) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). At that time, FDA also requested information on the earliest date that NAC was marketed as a dietary supplement or as a food, in case there could be new evidence showing NAC was marketed as a dietary supplement before it was approved as a new drug. Additionally, FDA requested data, research results, and other information related to the safe use of NAC in products marketed as dietary supplements and any safety concerns.
In a March 31, 2022 Constituent Update, FDA announced it has confirmed that NAC is excluded from the definition of a dietary supplement. FDA’s response letter to CRN and NPA’s petitions outlines the legal background for its interpretation that the Dietary Supplement Health and Education Act of 1994 (DSHEA) provides only two exceptions from the exclusion from the dietary supplement definition of an article such as NAC that has been approved as a new drug, namely: (1) the article was marketed as a dietary supplement or as a food before such approval (or its authorization for investigation as a new drug, if there were substantial clinical investigations that were made public), or (2) FDA issues a regulation to allow use of the article in a dietary supplement. FDA noted that while acetylcysteine (another name for NAC) was approved as a new drug on September 14, 1963 for administration by inhalation, it is the same “article” for purposes of the exclusion clause as NAC for ingestion, which the earliest evidence FDA found of marketing as a dietary supplement or as a food is an August/September 1991 advertisement for an NAC-containing supplement.
While FDA’s response to the citizen petitions confirms that NAC is excluded from the definition of a dietary supplement, the agency has not yet reached a decision on the NPA citizen petition’s alternative request that FDA undertake rulemaking to allow the use of NAC in dietary supplements. FDA’s March 31, 2022 response letter notes it has received comments supporting NPA’s rulemaking request and providing information on the safety of NAC in dietary supplements and, thus far, has not identified safety concerns for such use. In the interim, until FDA proposes a rule, which the response letter characterizes as “likely,” the response letter states, “we think it appropriate to consider exercising enforcement discretion for products labeled as dietary supplements that contain NAC if such products would be lawfully marketed dietary supplements if NAC were not excluded from the definition of dietary supplement and are not otherwise in violation of the FD&C Act, and we intend to issue guidance on this topic.”