The American Herbal Products Association (AHPA) provided FDA evidence that NAC (N-acetyl-L-cysteine) was marketed in supplements in the early 1990s before enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA).
The ingredient isn’t barred from being marketed in dietary supplements because a “prior drug exclusion provision” in the law doesn’t apply to already-approved drug ingredients at the time of DSHEA’s enactment, according to recent comments AHPA filed with FDA.
AHPA also provided FDA examples of ingredients including vitamin C that were approved as drugs decades before passage of DSHEA, yet remain widely available in supplements.
“Congress could not have reasonably expected that, upon DSHEA’s enactment, all Vitamin C and D dietary supplements would be removed from the market absent evidence that they were marketed prior to the 1940s (or 1970s/1980s),” AHPA wrote to FDA.
Even if FDA disagrees with AHPA’s conclusion that the prior drug exclusion provision doesn’t apply to NAC, the trade group urged the agency to issue a regulation—finding NAC is a lawful dietary supplement. FDA, through authority granted to the secretary of the U.S. Department of Health and Human Services (HHS), could issue such a regulation, though it has never done so in the nearly three-decade history of DSHEA.
“NAC would prove an ideal candidate for such a regulation given its demonstrated safety profile and existence in the food supply for decades, including prior to DSHEA’s enactment,” AHPA wrote in its comments. “By promulgating a regulation deeming NAC a lawful dietary supplement, FDA would simply maintain the status quo and allow important, widely-used dietary supplements to remain on the market for consumer use.”
AHPA submitted its comments to FDA in support of two citizen petitions previously filed by the Council for Responsible Nutrition (CRN) and Natural Products Association (NPA). The comments were signed by AHPA President Michael McGuffin and Will Woodlee of the law firm Kleinfeld, Kaplan & Becker LLP, who is outside counsel to AHPA. (Click here and here to read AHPA’s comments in full.)
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 also provided evidence to show NAC was marketed in subsequent years in the 1990s prior to DSHEA’s passage.
FDA stated last year in warning letters that NAC was first approved as a drug in 1963 and consequently cannot be marketed in supplements under section 201(ff)(3)(B)(i) of the Federal Food, Drug & Cosmetic Act (FDCA).
But the provision doesn’t have “retroactive effect,” or apply to drug ingredients on the market before DSHEA’s enactment, according to several industry trade associations including AHPA.
The U.S. Supreme Court “has long ‘embraced a presumption against statutory reactivity’ and ‘declined to give retroactive effect to statutes burdening private rights unless Congress had made clear its intent,’” McGuffin and Woodlee wrote in AHPA’s comments.
However, “nothing in DSHEA requires, or indicates that Congress intended, that the prior drug exclusion provision be interpreted to exclude from the definition of ‘dietary supplement’ products already on the market when DSHEA was enacted,” they added.
Congress was worried that allowing supplements to be marketed after first being studied or approved as drugs would provide a disincentive for the often substantial investment needed to obtain FDA approval of new drugs, according to a 1998 letter from an FDA official to a lawyer representing Pharmanex Inc.
AHPA, however, concluded any such concerns “clearly did not apply to drugs already approved when DSHEA was enacted.” What’s more, no court “has squarely addressed the question of whether the prior drug exclusion provision was intended to have retroactive effect,” the trade association added.
AHPA also referenced a 1994 report in the U.S. Senate to support its position that Congress didn’t intend for the provision to apply to drug ingredients approved prior to DSHEA.
Sens. Orrin Hatch and Tom Harkin—both now retired and widely considered architects of DSHEA—agreed to incorporate additional language in the legislation over concerns “that manufacturers or importers of drugs could avoid the drug approval process by marketing drug products as dietary supplements,” according to the report submitted by Hatch.
However, under substitute language to the bill approved by the Committee on Labor and Human Resources, “a substance which has been marketed as a dietary ingredient in a dietary supplement, or otherwise as a food, does not lose its status as a food … just because FDA approves the substance for use as an active ingredient in a new drug, certifies a finished product containing the substance as an antibiotic, or licenses a finished product containing the substance as a biologic,” the Senate report stated. “Those types of products would be drugs because they would be promoted with drug claims. They would, and should, have no effect on the food status of a properly-labeled dietary supplement.”
For instance, vitamin C would continue to be available as a supplement, even if FDA eventually approved vitamin C as a drug to treat cancer, “so long as it is promoted as a dietary supplement without disease prevention claims,” the report added.
Quoting the Senate report above, AHPA concluded “the prior drug exclusion provision was intended to clarify that the status of existing dietary supplements (as foods) would be unaffected by future drug development.”
AHPA may be the only organization that has filed comments with FDA regarding the citizen petitions filed by CRN and NPA. As of Monday, the dockets associated with these petitions on regulations.gov suggest only one comment has been filed in each case.
FDA previously declined to comment on the citizen petitions, saying it will respond directly to the petitioners. While the agency has 180 days to respond to a citizen petition, it often doesn’t provide a substantive response within that deadline, several lawyers have said.
According to FDA’s own regulations, one of its acceptable responses to a citizen petition within the 180-day time frame is the agency is unable to reach a decision due to such reasons as “the existence of other agency priorities, or a need for additional information.”