FDA’s draft guidance published last week on NAC (N-acetyl-L-cysteine) products labeled as dietary supplements still leaves unanswered the question of whether the world’s biggest e-commerce platform—Amazon—will resume sales of the ingredient.

Amazon in 2021 confirmed plans to remove NAC products from its e-commerce platform after FDA asserted in previous warning letters that the ingredient was excluded from the definition of a dietary supplement since it was first approved as a drug in 1963. In an April 22 Federal Register notice publishing the draft guidance, FDA said the document, when finalized, would explain its “intent to exercise enforcement discretion” regarding the distribution and sale of NAC-containing products labeled as dietary supplements.

“The enforcement discretion policy would apply to products that would be lawfully marketed dietary supplements if NAC were not excluded from the definition of 'dietary supplement' and that are not otherwise in violation of the FD&C [Federal Food, Drug & Cosmetic] Act,” FDA stated in the draft guidance.

Industry stakeholders reached out to Amazon to convey the draft guidance has been published and learn if the company intends to resume sales of NAC products.

Dan Fabricant, president and CEO of the Natural Products Association (NPA), suggested the draft guidance was a victory, but only “round one” in a larger fight with FDA, which is still facing a lawsuit from NPA regarding NAC.

Related:Amazon confirms plans on removing NAC supplements

“We’ve got to work through the ‘Amazon problem,’” he noted in an interview.

Fabricant said he reached out to Amazon following FDA’s release of the draft guidance. As of last week, he had not heard back regarding its position.

“With any large organization like that, there’s probably some internal strife,” Fabricant said. “It’s purely speculative but I would guess that’s the issue. What can be done to address that? If this [draft guidance] isn’t enough, is a conversation with FDA going to get that hurdle cleared?”

Amazon has not responded to requests from Natural Products Insider regarding FDA’s draft guidance or its previous responses to NAC-related citizen petitions filed by NPA and the Council for Responsible Nutrition (CRN). In the responses, FDA reaffirmed its position that NAC is excluded from the definition of a dietary supplement.

Payment processing platforms, including PayPal, also enacted policies against the sale of NAC products labeled as supplements after FDA issued its 2020 warning letters to companies illegally making “hangover” claims, according to industry stakeholders.

Related:FDA releases draft guidance on NAC supplements

In a Jan. 11 statement to Natural Products Insider, a PayPal spokesperson said the company “has always maintained a policy that requires merchants to sell pharmaceuticals online in accordance with the law.”

“Our policy prohibits the sale of N-acetyl-L-cysteine,” the spokesperson added.

PayPal had no comment on FDA’s draft guidance when contacted for this article.

CRN President and CEO Steve Mister said his organization has reached out to Amazon and payment platforms about the FDA draft guidance but has not received word yet regarding their plans.

“We’ve also pointed out to Amazon that they are selling [NAC] in Whole Foods and that was never removed from the shelves,” he said in an interview.

Robert Durkin is a former FDA official who is of counsel in the FDA and health care practices of the law firm Arnall Golden Gregory LLP. He opined the “draft guidance in and of itself should provide enough comfort to retailers to start marketing NAC-containing dietary supplements now.”

Although the guidance is in draft form, it “could give downstream parties greater confidence” in resuming sales of NAC products or continuing to carry them, said Will Woodlee, a partner with the law firm Kleinfeld, Kaplan & Becker LLP.

Marc Ullman, of counsel to the law firm Rivkin Radler LLP, described the draft guidance as "a win for industry" that "should cause Amazon to rescind its ban" on NAC-containing products. 

"And given Amazon’s dominance in the online market, that’s hugely significant," he said in an interview.

The likes of Amazon or PayPal may be waiting for FDA to issue final guidance, or perhaps over the longer term, a notice-and-comment regulation making NAC lawful in supplements, which FDA is considering.

“FDA has said there’s no safety issue and it’s not going to take enforcement action," Ullman said, when asked whether Amazon is perhaps waiting for a final FDA guidance. "I think it would be an incredible overabundance of caution for any retailer to say, ‘We shouldn’t get NAC back into commerce.’”

On the other hand, even if FDA exercises enforcement discretion, retailers marketing NAC—including Amazon—could still face class action lawsuits from plaintiffs' attorneys alleging false labeling or other wrongdoing. In 2019, a growing number of putative class action lawsuits were filed in California against marketers of CBD products—including two of the largest companies in the sector based on sales—after FDA reiterated its years-old stance in warning letters and a news release that the compound cannot be lawfully sold in dietary supplements.

FDA is still saying NAC is technically “illegal” in supplements, but it’s “not going to enforce against it,” Mister reflected.

“That still leaves some exposure for the industry for a state [attorney general] to say, ‘Well if it’s technically illegal under the federal law,’ we don’t care that FDA’s not enforcing it. We could do it,” he said. “It also leaves you potentially exposed [to] a plaintiff’s attorney.”

A rulemaking would remove such exposure, clarifying NAC is lawful in dietary supplements.

In the meantime, an enforcement discretion policy from FDA increases the likelihood that a judge in the U.S. Court of Appeals for the Ninth Circuit, for example, would dismiss or stay an action based on a legal doctrine known as “primary jurisdiction,” Woodlee observed.

Under this doctrine, the judiciary can stay litigation while an administrative agency like FDA is considering a matter within its expertise.

Woodlee said he is not aware of any pending class actions lawsuits against marketers of NAC products. However, he noted that doesn’t mean sellers of NAC haven’t received demand letters from plaintiffs’ attorneys. Such letters, and any out-of-court settlements, are typically not publicly disclosed.

A final regulation making NAC lawful in supplements, Woodlee agreed, “would resolve all doubt on a going-forward basis.” But whether FDA’s draft guidance in the interim gives Amazon—and its legion of attorneys and regulatory advisors—sufficient comfort to resume sales of NAC remains to be seen.