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FDA, marketers of NAC may have motives to seek rulemaking

FDA buildings 2020
FDA said in recently published draft guidance it’s still considering commencing a rulemaking to authorize the use of NAC as a dietary supplement.

A first-of-its-kind FDA rulemaking legalizing NAC (N-acetyl-L-cysteine) in dietary supplements could provide a “proof of concept that this authority works and that the agency can use it appropriately and effectively,” according to Will Woodlee, a Washington, D.C.-based lawyer who advises firms on FDA regulatory matters.

Woodlee is among a group of industry experts who believe FDA has an incentive to use its authority for the first time in nearly 30 years to make an ingredient lawful in dietary supplements through a notice-and-comment rulemaking, despite its determination that the “article” was first approved or researched as a drug.

A rulemaking on NAC would make FDA’s future exercise of its authority “more predictable” and “more efficient,” said Woodlee, a partner with the law firm Kleinfeld, Kaplan & Becker LLP, in an interview.

Recently, FDA published a draft guidance document on NAC, signaling its plans to exercise enforcement discretion regarding products containing the ingredient and labeled as dietary supplements. The document, an FDA spokesperson said, “is the first draft guidance regarding an enforcement discretion policy related to the sale and distribution of certain products that are labeled as dietary supplements but are excluded from the definition of ‘dietary supplement’ under section 201(ff)(3)(B)(i) of the Federal Food, Drug and Cosmetic Act (FD&C Act).”

“For clarification, the draft guidance does not describe a policy of enforcement discretion with respect to the definition of ‘dietary supplement,’” the FDA spokesperson added. Instead, “the draft describes a policy of enforcement discretion with respect to other provisions of the FD&C Act in certain circumstances (as described in the draft guidance), such as sections 301(d) and 505(a) regarding the sale and distribution of unapproved new drugs.”

FDA said in the guidance it’s still considering commencing a rulemaking to authorize the use of NAC as a dietary supplement. The agency suggested it’s more prone to do so if it does not identify any safety-related concerns, which it hasn’t recognized to date.

Meanwhile, at least some industry representatives want FDA to publish a final guidance—and sooner rather than later.

“We’re hoping and we’re going to continue our efforts to push that this [guidance] is on a fast track to be finalized,” said Dan Fabricant, president and CEO of the Natural Products Association (NPA), which has a lawsuit still pending in U.S. District Court against FDA pertaining to NAC.

A final guidance could help “stabilize the market,” Fabricant said in an interview. FDA, he acknowledged, could backtrack on its plans to exercise enforcement discretion, though he said that’s “highly unlikely.”

“The agency has said in typical qualified government terms that they don’t think there are safety concerns with respect to NAC dietary supplements, and I think based on my understanding of the record, there aren’t any such concerns,” Woodlee said.

The circumstances surrounding NAC offer “the perfect test case for the agency to move forward with at least a proposed rule,” the lawyer added.

The FD&C Act, as amended by the Dietary Supplement Health and Education Act of 1994 (DSHEA), gives FDA authority (through the secretary of the U.S. Department of Health and Human Services) to make NAC lawful in supplements through a regulation.

The law does not “give any factors whatsoever for FDA to account for when making decisions whether to or not proceed with use of this authority,” Woodlee observed. “Like it or not, safety seems to be the primary driver in the agency’s thinking about whether or not to proceed with rulemaking.”

Former FDA official Robert Durkin said he was concerned FDA was tying a safety analysis to a rulemaking. Safety is addressed in another section of the FD&C Act, said Durkin, who is of counsel in the FDA and health care practices of the law firm Arnall Golden Gregory LLP (AGG).

“FDA should support the secretary promulgating a regulation for both NAC and CBD and then use the authorities they already have under the Act to ensure products on the market are safe, or to remove unsafe products from the market,” he said in an interview.

CBD is another ingredient that FDA has determined is excluded from the definition of a dietary supplement since it was first authorized for investigation as a new drug and the subject of substantial clinical investigations made public.

Durkin, who previously held top positions in FDA’s Office of Dietary Supplement Programs (ODSP), said he suspected FDA has already concluded NAC is safe.

FDA officials "know the effect of a draft guidance is similar to the effect of a final guidance just because they stay in draft for so long,” Durkin said. “With that in mind, I’m very sure that FDA has completed their safety determination … for NAC, and they know it’s safe.”

Durkin said he is skeptical FDA will finalize a guidance or issue a regulation. “I’d be surprised but then again I could be wrong.”

Attorney Marc Ullman, who advises dietary supplement companies on compliance with FDA regulations, expressed some concerns that FDA may never promulgate a regulation for NAC. He observed the agency is not bound by any timeline to do so. 

"This kind of thing is like citizen petitions, which can sit for 10 years, and then the submitter will get a letter. ‘Are you still interested in this because we’d like to take it off our docket, not that we want to respond to it,'" Ullman, who's of counsel to the law firm Rivkin Radler LLP, said in an interview.

He added, “The agency, by its very nature, I believe, will want to do the minimum it has to do to resolve the situation without making any other significant legal decisions.”

Despite FDA’s plans to exercise enforcement discretion, the dietary supplement industry could benefit from a rulemaking on NAC because it would reduce its exposure to enforcement actions from a state attorney general or the plaintiffs’ bar, according to Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN).

“When you have enforcement discretion, FDA has not condoned the behavior,” he said in an interview, adding NAC—based on FDA’s interpretation of the law—still technically remains illegal in supplements.

A rulemaking on NAC would be one of “first impression,” Mister said. “There’s going to be a lot of comment on it if they move forward. What are the factors that FDA should be considering? All the statute says is they use their discretion for notice-and-comment rulemaking if the secretary believes the ingredient would be lawful. What does that mean?”

Some industry stakeholders, including Mister, believe FDA has an incentive to figure all that out, since an NAC rulemaking could set forth a pathway for other ingredients that FDA determines were first studied or approved as a drug before being marketed in supplements. But whether FDA will actually move forward with a regulation that could take several months or years to complete remains to be seen.

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