Two citizen petitions submitted to FDA last year essentially challenged the agency’s position in 2020 warning letters that NAC (N-acetyl-L-cysteine) cannot be lawfully marketed in dietary supplements.
In November, in responses to the citizen petitions submitted by the Council for Responsible Nutrition (CRN) and the Natural Products Association (NPA), FDA disclosed plans to assess “both petitions concurrently” as a result of the “overlap” between the two documents.
But this week, CRN requested the agency separately review its petition, asserting the two associations are seeking different actions from FDA.
CRN requested FDA reverse its “position that NAC-containing products cannot be dietary supplements,” while NPA called for the agency to either decide “NAC is not excluded from the definition of a dietary supplement or, in the alternative, initiate rulemaking to make NAC a lawful dietary supplement under the Federal Food, Drug and Cosmetic Act [FDCA],” according to a Nov. 24 constituent update from FDA.
FDA received a citizen petition from CRN on June 1, 2021, then NPA followed up with its own petition in August.
Applicability of exclusionary clause to NAC
In a Jan. 4 letter to Douglas Stearn, FDA’s deputy director of regulatory affairs within the Center for Food Safety and Applied Nutrition (CFSAN), CRN representatives concluded “NPA’s citizen petition raises issues beyond the facial legal challenge presented by CRN.”
“It is inappropriate for FDA to review the CRN and NPA citizen [petitions] concurrently, as they request different actions from the agency,” Steve Mister, president and CEO of CRN, and Megan Olsen, CRN’s vice president and associate general counsel, wrote to Stearn.
“CRN asks only for a review of the applicability of section 201(ff)(3)(B)(i) to NAC,” they added.
Under the so-called exclusionary clause in the law, which essentially created a race to market, an “article” or ingredient cannot be marketed in dietary supplements if it was first approved or studied as a drug.
That much is clear.
What’s less clear is whether the exclusionary clause has “retroactive” effect and consequently applies to ingredients like NAC, on the market in supplements before passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA), which amended the FDCA.
“Retroactive application basically means that you don’t know you’re in the race [to market] until you get told that you lost the race that you didn’t know that you were in,” observed Riëtte van Laack, a director with the law firm Hyman, Phelps & McNamara P.C., in an interview.
‘A detour into safety concerns’
CRN and NPA have made several arguments for why FDA’s position on NAC is incorrect, including citing a presumption in case law that legislation doesn’t have retroactive effect unless Congress clearly intended otherwise. FDA has yet to address any of their substantive arguments.
Instead, the agency has requested 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.
FDA disclosed its request for the information in the Nov. 24 constituent update and in Nov. 24 letters to CRN and NPA tentatively responding to their petitions. The agency also signaled it would review the information in helping to decide whether it’s proper to initiate a rulemaking for NAC.
But the agency’s tentative responses did not placate industry stakeholders.
“Much to the frustration of the industry, the tentative response did not address the legal issue crucial to the future of NAC, i.e., that NAC is a legal (grandfathered) dietary ingredient because DSHEA does not apply retroactively to exclude dietary supplements that were on the market before the enactment of the law,” van Laack wrote last month in a blog. “FDA merely indicated that it was still considering that issue.”
CRN reps told Stearn FDA has failed to tackle “the single legal issue” CRN raised in a December 2020 letter to the agency and in its subsequent citizen petition: “whether the drug preclusion provision in section (201)(ff)(3)(B)(i) properly precludes NAC from being marketed in dietary supplements.”
“Instead, the agency has attempted to deflect the facial legal defects of its position with a detour into safety concerns that do not exist and are not relevant to this inquiry,” Mister and Olsen wrote to Stearn. “As such, the agency is now also in violation of its own requirement to respond to CRN’s citizen’s petition within 180 days of receipt.”
Mister and Olsen requested FDA reverse its decision to review the two citizen petitions simultaneously, and “at a minimum,” pledge to “substantively respond to the concerns raised in CRN’s June 2021 citizen petition within 30 days” of the deadline FDA specified for requested comments in its constituent update: Jan. 25.
‘Six months is long enough’
In an interview, Mister reiterated he was disappointed with FDA’s tentative response in November to his citizen petition because the agency has failed to answer a legal question raised over a year ago.
“Rather than face that question and potentially acknowledge that their warning letters overstepped the law, [FDA officials] continue to deflect and look at other things,” Mister said.
FDA’s request for safety data and other information is “completely irrelevant to that legal question, and it’s just a way to kick the can down the road and not answer” it, he added. “And in the meantime, the industry is suffering and consumers are suffering because it’s harder to get products with NAC.”
CRN’s letter to FDA referenced Amazon’s decision last year to stop selling NAC supplements, as well as more recent moves by large payment processing platforms to block the use of their platforms for sales of NAC supplements.
Mister contended FDA has had ample time to answer the legal question raised by his association.
“This is not an issue that requires fact-finding or data-gathering,” he said. “This is a pure legal question. Six months is long enough to answer a legal question.”
FDA could drag its feet providing any substantive responses to the citizen petitions for several years, according to industry lawyers. Asked whether FDA will respond to the legal argument raised by CRN, van Laack said if she was betting on it, “not anytime soon.” Her recent blog pointed out FDA has yet to respond to a citizen petition submitted by her law firm in the year 2000.
Mister said he wasn’t willing to comment, or share his “playbook,” when asked whether his trade group is considering filing a lawsuit if FDA doesn’t respond to the legal question within CRN’s requested timeframe.
FDA declined to comment on CRN’s latest letter. Marianna Naum, an FDA spokeswoman, said the agency “continues to carefully review the citizen petitions, the comments in the dockets for these petitions, and all other relevant information, and will respond to the petitions when our review is complete.”
Mounting pressure on FDA
NPA is seeking a declaratory judgment that the drug exclusionary provision in DSHEA does not retroactively apply to NAC. The lawsuit also is seeking a preliminary and permanent injunction, barring FDA from taking any regulatory action against distributors, manufacturers or sellers of NAC based on the claim that the drug exclusion applies retroactively to NAC.
On Dec. 28, a trial attorney with the U.S. Department of Justice, Noah T. Katzen, entered his appearance in the case on behalf of the government.
DOJ has yet to formally respond to NPA’s complaint against FDA, the U.S. Department of Health and Human Services and top-level government officials. The government has until Feb. 7 to file its response to the complaint, according to attorney Kevin Bell, a partner with Arnall Golden Gregory LLP (AGG), which is representing NPA in its lawsuit.
“The bottom line is … what the FDA did was inappropriate and incorrect under the law,” Bell said in an interview. “We want it reversed, changed.”
He added the industry cannot tolerate a “situation where the FDA [continuously says], ‘We’re still thinking about it,’ and drags things out [until] the third decade of DSHEA.”
Asked about CRN’s latest request to FDA, Bell and NPA’s CEO, Dan Fabricant, agreed they were not concerned with whether FDA reviews the two citizen petitions concurrently or separately.
Instead, they are focused on getting relief in the judiciary through NPA’s lawsuit against the government.
“I would think at this point every association in our space would be lockstep with us to push FDA to get good answers on these [issues],” Fabricant said. “Is this really how the law should be interpreted? Ultimately, that’s the question that needs to be answered, and that’s what we asked in court.”