FDA requests more information on NAC supplements

FDA on Wednesday announced a request for additional information for past use on NAC (N-acetyl-L-cysteine) in products marketed as dietary supplements.

Perhaps more encouraging to NAC brands, FDA also signaled it is open to the idea of a rulemaking to make the ingredient lawful in dietary supplements. FDA and industry have been at odds over the agency’s assertions in 2020 warning letters that the law prohibits NAC’s use in supplements because the ingredient was first approved as a drug in 1963.

In tentative responses to citizen petitions filed by the Council for Responsible Nutrition (CRN) and Natural Products Association (NPA), FDA requested additional information from the petitioners and interested parties, according to a constituent update.

FDA explained it “needs additional time to carefully and thoroughly review the complex questions posed in these petitions.”

FDA is seeking information on the first date NAC was marketed as a dietary supplement or as a food, the safe use of the ingredient in products marketed as a supplement, and any safety concerns. The agency requested interested parties submit such information by Jan. 25, 2022, while it continues to evaluate both citizen petitions.

“If applicable, the FDA will use the information submitted to the public docket and other applicable information to determine if rulemaking to make NAC lawful as a dietary supplement is appropriate,” FDA stated in the constituent update.

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FDA added it will use the information submitted for its analysis and provide a final response to both petitioners directly once its review was completed. The agency is reviewing the CRN and NPA petitions at the same time due to the overlapping issues.

To help FDA assess NPA’s request to commence a rulemaking, FDA asked in its tentative responses to the petitions that interested parties submit information to the NPA docket (FDA-2021-P-0938). Among other things, FDA expressed interest in receiving information related to product formulations and conditions of use, sales and marketing data, and data regarding adverse events associated with use of NAC products.

NAC helps the body replenish its stores of glutathione, an antioxidant, and features several other health benefits, according to WebMD. A 2019 article in the journal Antioxidants described NAC as “a precursor to the amino acid L-cysteine and consequently the antioxidant glutathione” that is found in onion.

FDA’s constituent update could foreshadow a first-of-its-kind rulemaking to make an ingredient lawful in dietary supplements when a substance or “article” was first approved or studied as a drug. FDA has never exercised such authority since passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA), though it has been asked to do so for some ingredients, including CBD—an FDA-approved drug to treat certain types of epilepsy.

Industry stakeholders have maintained NAC has been safely sold in dietary supplements for over a quarter century. That could perhaps make NAC a better candidate for a rulemaking than hemp-based CBD, which FDA said poses certain safety concerns and requires additional data to assess its risks to public health.

Reaction from trade associations

FDA’s responses were met with criticism from both petitioners. 

DSHEA’s provisions “may not be interpreted retroactively to remove ingredients that were lawfully marketed in 1994 and have enjoyed a long history of safe use since then,” said Steve Mister, president and CEO of CRN, in a statement. "The delay in clearing up the status of NAC by asking for more data and refusing to admit its error disregards the law and disserves consumers who use NAC."

Dan Fabricant, president and CEO of NPA, said FDA should have either commenced a rulemaking immediately or denied his organization's request, instead of asking for more information about an ingredient that's been sold in dietary supplements for decades.

"Give us a clear path forward," he said in an interview. "Is our path through the courts or is our path through rulemaking?"