The Dietary Supplement Health and Education Act of 1994 (DSHEA) aimed to preserve incentives for the pharmaceutical industry by excluding researched or approved drugs from being marketed in supplements.
That is unless the “article” investigated or approved as a drug was first marketed in a dietary supplement.
FDA’s position that NAC (N-acetyl-L-cysteine) cannot be lawfully marketed in a dietary supplement—because it was first approved as a drug in 1963—has raised an important question for the supplement and drug industries, regulators, and potentially, the U.S. courts.
Does the drug exclusion clause apply to articles studied or approved before or after October 1994? The answer to that question hasn’t been directly answered by FDA or settled in the courts—at least not yet.
Industry stakeholders, meanwhile, have provided FDA evidence that NAC was marketed in dietary supplements before 1994.
-- In its pending lawsuit against FDA, the Natural Products Association (NPA) attached documents (Exhibit 1) to show evidence of NAC’s marketing in nutritional products as early as 1991.
-- NPA attached a separate FDA document (Exhibit 2 titled “Unsubstantiated Claims and Documented Health Hazards in the Dietary Supplement Marketplace”) from 1993, which cited a claim that NAC “has been found to stop the spread of AIDS cells in the body.”
-- The American Herbal Products Association (AHPA) provided FDA evidence that NAC was being marketed in supplements as early as 1991—attaching to its comments an August 1991 brochure from a company called Pharmline Inc., whose product line featured NAC. AHPA provided further evidence to show NAC was marketed in subsequent years in the 1990s prior to DSHEA’s passage.
Regulatory consultant Jim Lassiter, who started working in the natural products industry in 1976, is among those who believes Congress did not intend to retroactively apply the drug exclusion provision to DSHEA.
“The original idea was to ensure and calm FDA that drugs would not make their way into the food supply,” Lassiter said in an interview. “And that was a concession in effect by industry at the time, and it made sense. And industry’s position was, ‘No. We’re not looking to put drugs into dietary supplements, and here’s how we’ll prevent that.’ But again, how we will prevent it begins in 1994, not 1963.”
Several of Lassiter’s clients at the consulting firm he founded, REJIMUS, are finished product brands that continue to sell NAC.
NAC is “an unsettled [regulatory] matter, and there’s a decent degree of confidence among [brands] that it will be resolved favorably,” Lassiter said.
He added, “I think ‘favorable’ has shades of gray involved too. I’m not fully optimistic that a simple solution will be provided, although it is possible. There’s some really well reasoned arguments at play here.”
One potential solution is an FDA rulemaking to allow NAC in supplements, despite the 1963 drug approval. In August, several months before filing its lawsuit, NPA submitted a citizen petition to FDA, requesting the agency either determine NAC is not excluded from the definition of a dietary supplement or, in the alternative, initiate rulemaking.
Then in a constituent update in November, FDA suggested it’s open to considering a rulemaking for NAC. FDA has requested by Jan. 25 additional information on the past use of NAC, including 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.
To move forward with a rulemaking, Lassiter said industry would need to essentially provide FDA the equivalent of a new dietary ingredient notification (NDIN) to assure the agency that NAC is reasonably expected to be safe.
He feels industry can meet that burden and demonstrate NAC’s safe use before DSHEA and after its passage. But some industry stakeholders, including the Council for Responsible Nutrition (CRN), contend a rulemaking is unnecessary.
In a citizen petition and subsequent letter, CRN has prodded FDA to answer whether the drug exclusion clause has retroactive effect. CRN contends the answer is “no,” citing a presumption in case law that legislation doesn’t have retroactive effect unless Congress clearly intended otherwise.
“This is not an issue that requires fact-finding or data-gathering,” Steve Mister, president and CEO of CRN, said in a previous article published by Natural Products Insider. “This is a pure legal question.”
So far, FDA hasn’t squarely answered the question raised by CRN, NPA and others. However, its determination regarding NAC is perceived by industry as giving retroactive effect to the drug exclusion clause.
“FDA’s position on NAC was legally erroneous because, among other things, the drug provision of DSHEA was not entitled to be applied retroactively,” NPA’s outside law firm, Arnall Golden Gregory LLP (AGG), wrote in the lawsuit.
Among other forms of relief, NPA requests a declaratory judgment that the drug exclusion provision does not retroactively apply to NAC supplements. The U.S. Department of Justice likely will have no choice but to address the “retroactive” issue if NPA’s lawsuit against FDA overcomes potential procedural hurdles and moves ahead for a ruling on the merits.
Even so, civil litigation between industry and the federal government can take years to resolve in the U.S. trial and appellate courts.
“I’ve gone back and forth about this … but I think that [FDA rulemaking] is the most potentially expeditious route forward,” Lassiter concluded. “Anything else likely involves courts, and you can just throw ‘expeditious’ right out the window at that point.”