CRN presses FDA again on NAC ingredient’s legal status in newly filed comments

In comments submitted to FDA on January 25, CRN says the agency continues to fail to address the key question the association asked in a citizen petition last year—whether NAC can be banned as a supplement ingredient under the FD&C Act’s drug preclusion clause—and is now demanding the agency respond within 30 days.

The Council for Responsible Nutrition (CRN; Washington, DC) yesterday filed new comments with FDA over whether the agency can continue to try to lawfully ban the ingredient N-acetyl-L-cysteine (NAC) from use in dietary supplements. These comments follow a letter CRN sent to FDA on January 4, 2022, as well as a citizen petition CRN sent FDA in June 2021. CRN says FDA continues to fail to address the key question the association has asked the agency to answer: whether NAC can be legally banned as a dietary supplement ingredient under the Federal Food, Drug, and Cosmetic Act’s (FD&C Act) drug preclusion clause.

Dietary supplement associations, including CRN, the Natural Products Association (NPA; Washington, DC), and the American Herbal Products Association (AHPA; Silver Spring, MD), either filed citizen petitions or comments with FDA last year over NAC. This came after, in July 2020, FDA unexpectedly sent warning letters to some companies selling NAC dietary supplements, telling them that NAC is not legally allowed in dietary supplements. Despite the agency’s own previous position allowing NAC as a supplement ingredient, including in its favorable review of prior NAC structure-function claims notifications for supplements, the FDA warning letters sent in July 2020 stated that NAC is now illegal for use in supplements under the FD&C Act’s “drug exclusion provision” (Section 201(ff)(3)(B)(i)) because it had been approved as a new drug in 1963. In response to this turn of opinion by FDA, several supplement sellers, including Amazon.com, subsequently began preemptively removing NAC supplements from retail.

CRN’s citizen petition in June 2021, another citizen petition NPA filed separately in August 2021, plus comments on these petitions filed by the American Herbal Products Association (AHPA; Silver Spring, MD) here and here pointed out key reasons why the drug exclusion clause cannot be applied to disallow NAC as a supplement ingredient. Those reasons include the fact that there is evidence that NAC was sold as a supplement before NAC was approved as a drug, and that the NAC drug’s approval date isn’t adequately proven. For more background on those arguments, click here.

But the top argument industry leaders are making to FDA is that the FD&C Act’s drug preclusion clause cannot be applied retroactively to delegitimize dietary supplement ingredients that were already on the market before the drug preclusion provision became law.

CRN says this is the key question FDA needs to answer and that the agency has repeatedly failed to answer. Instead, in response to CRN’s citizen petition, in November 2021 FDA sent CRN a “tentative response,” not addressing CRN’s questions about FDA’s legal reasons for trying to apply the drug exclusion clause to NAC retroactively but rather asking for more evidence to show that NAC supplements were on the market before NAC became a drug. CRN says this evidence was already provided to the agency, and, moreover, that it’s extraneous because the heart of the issue is whether FDA can apply the drug exclusion clause to NAC at all.

Following the “tentative response” FDA sent to CRN in November, the association sent another letter to the agency on January 4, 2022, again asking the agency to answer its legal question. Failing adequate response from FDA, on January 25, 2022, CRN filed official comments with the agency demanding a response.

CRN’s new comments strongly ask the agency to “provide a substantive response addressing CRN’s legal concerns within 30 days,” meaning by February 24, 2022.

In addition, as it did in its January 4, 2022, letter to FDA, CRN asked the agency not to review the citizen petitions filed by CRN and NPA together. CRN states that while it is asking solely for FDA to reverse its position on NAC due to the agency’s wrongful application of the drug exclusion clause, NPA asks for that but also requests, as an alternative, that FDA use its rulemaking authority to allow NAC to remain a legal dietary ingredient.

CRN’s newly filed comments state: “CRN reiterates that it is inappropriate for FDA to review the two citizen petitions concurrently, as they request different actions from the Agency. Further, by introducing concurrent review, FDA appears to be disregarding the legal challenges to the NAC position raised by CRN, and intimating that it has declined CRN’s request for legal review without the Agency actually formally stating this.”

CRN’s newly filed comments are the latest development in the industry’s fight with FDA over NAC. In December, following its citizen petition, NPA additionally sued FDA over NAC.