Industry stakeholders cannot sue FDA based merely on its positions asserted in warning letters because courts have found such complaints are premature, several lawyers said.
The court decisions put FDA-regulated companies in a difficult spot when they disagree with the agency’s interpretation of law. A case in point is the lingering dispute between FDA and the dietary supplement industry over the legality of NAC (N-acetyl-L-cysteine) in supplements.
In interviews for this story, more than half a dozen lawyers who practice food law said a warning letter is not considered final agency action. The courts would maintain that a lawsuit filed against FDA, based on 2020 warning letters related to NAC, is not ripe for an adjudication, legal experts said.
“It’s hard, if not impossible, to successfully challenge a warning letter,” said Stuart Pape, an attorney in Washington, D.C., who chairs the FDA practice of the law firm Polsinelli. “The courts have consistently held that a warning letter isn’t final agency action, and you can’t get judicial review unless what you’re challenging is final agency action.”
A lawsuit filed today in U.S. District Court requesting a declaratory judgment over the legality of NAC wouldn’t survive a motion to dismiss by the government, according to several of the lawyers.
“It’s our understanding that if we went to court, our only remedy at this point would be to seek a declaratory judgment,” said Steve Mister, president and CEO of Council for Responsible (CRN), who also is a lawyer. “Our attorneys are telling us that we would likely be dismissed for failure to exhaust our administrative remedies, and the court would say this is not a final agency action.”
That reality has put NAC, CBD and other ingredients flagged by FDA in a “regulatory limbo,” said attorney Rend Al-Mondhiry, a partner in the nation’s capital with Amin Talati Wasserman LLP.
Al-Mondhiry expressed skepticism that a regulatory avenue is available through which industry could obtain a timely resolution on the NAC issue.
“To get something done in a timely way, I think the options are—maybe I shouldn’t even say ‘limited’—nonexistent,” she concluded.
Marc Ullman is of counsel to Rivkin Radler LLP, a New York-based law firm. He said firms “are intimidated” into meeting FDA’s “directives” in the warning letters.
“FDA is essentially browbeating people into complying with these directives,” the lawyer said, “and there’s no avenue to challenge them other than saying, ‘No. We’re ignoring you. Sue us.’”
If FDA, in collaboration with the U.S. Department of Justice, has filed a lawsuit over NAC, that would be news to sources contacted for this article.
Lindsay Haake, an FDA spokeswoman, said the agency “does not comment on whether or not it has commenced enforcement actions.”
That doesn’t mean retailers of NAC shouldn’t be concerned about the risks, Ullman cautioned.
“The risk is huge,” he said. “The risk is FDA sues you and seeks to enjoin you from doing business.”
He shared, “I always tell my clients, ‘This is a really interesting legal question.’ The problem is when a lawyer says a question that you’re trying to grapple with is ‘interesting’ … that’s a pretty good signal that resolving it is going to be really expensive.”
Justin Prochnow, a partner in Denver with the law firm Greenberg Traurig LLP, stressed a warning letter is not official FDA action and only reflects the agency’s interpretation of the law.
Based on the 2020 warning letters, some retailers may believe NAC is an illegal ingredient in supplements. But no “specific law” says NAC cannot be lawfully sold in supplements, Prochnow said.
“That’s the FDA’s stated position,” he added, “and similar to hemp and CBD, the FDA may or may not be correct about it.”
Haake, the FDA spokeswoman, confirmed her agency has not issued “closeout letters” related to the December 2020 warning letters mentioning NAC. None of the companies who received the warning letters responded to requests for comment for this article.
FDA has faced heat for supposedly “regulating by warning letter,” or testing out new legal theories in warning letters. This creates uncertainty for industry and leaves retailers and others with the impression that’s FDA word is final, Mister said.
CRN has challenged FDA’s position regarding NAC and recently met with FDA’s acting commissioner and other officials to discuss the matter.
“FDA has no accountability in the courts for what [officials] have said in the warning letter because it’s not considered final,” Mister said. “But nevertheless, whatever is in that warning letter sits out there, and the rest of the world believes that it’s the final statement from the agency on that topic.
“Retailers are left to say, ‘Should we take these products off the market or not?’ Do we have risk if we don’t take them off? Is FDA going to come after us?’” Mister commented.
In the wake of FDA’s warning letters, Amazon has decided to remove NAC-containing products from its website, and according to CRN, at least one contract manufacturer has stopped producing NAC supplements for its customers.
Perhaps the law should be amended to clarify “the nature of a warning letter,” Mister said, “or we need to give people the ability to go to court if they disagree with a warning letter because right now they can’t do that.”
NAC has been widely sold as a dietary supplement for many years. As of May 17, nearly 1,500 products containing NAC were listed in the Dietary Supplement Label Database, which is maintained by the National Institutes of Health (NIH).
Due to the widespread availability of NAC supplements on the U.S. market, many stakeholders concluded FDA had made a sudden 180—to the detriment of the supplement sector and benefit of the pharmaceutical industry.
While Polsinelli’s Pape stopped short of saying a rulemaking was necessary, he said FDA could have engaged in a public process to assert its position regarding NAC in supplements—providing industry and other stakeholders an opportunity to comment on the relevant issues.
“This was not one person surreptitiously marketing something, and they managed to do it off the radar for a number of years, and then when it pops up on the radar, [FDA says], ‘No. No. No. You can’t do that,’” said Pape, who previously served in FDA’s Office of Chief Counsel. “That’s not remotely what this case is.”
He added, “When you have process issues, they tend to undermine the legitimacy of the substantive decision.”
On the other hand, FDA expressed its view about the legality of NAC in supplements about a decade before the warning letters were issued.
Responding to a new dietary ingredient notification (NDIN), FDA stated in an Oct. 21, 2010 letter that NAC was first approved as a new drug in 1985. To FDA’s knowledge, NAC hadn’t been previously marketed as a food or supplement prior to FDA’s approval—or its authorization for investigation—of a new drug, according to the letter to Tiara Pharmaceuticals. Based on these determinations, FDA concluded NAC couldn’t be marketed as a supplement.
FDA proclaimed in its 2020 warning letters that NAC was first approved as a drug in 1963, not 1985.
Steven Tave, then-director of FDA’s Office of Dietary Supplement Programs (ODSP), said in a 2020 interview that FDA’s warning letters simply reiterate its previous conclusions that NAC is excluded from the definition of a supplement.
“To the extent that any stakeholders and anyone in industry or anyone else has facts that they think would cause us to rethink our conclusion, then we would welcome that evidence,” he said. “We’re happy to review it, and we would invite them to submit it to us.”
In a December 2020 letter to FDA, CRN raised several legal arguments challenging FDA’s position. The agency has not yet substantively responded to the letter.
An FDA official—Cara Welch, Ph.D, acting director of ODSP—recently advised CRN that FDA officials "are closely reviewing" CRN's 2020 letter regarding NAC "and will provide a more substantive response once our evaluation is complete."
Miriam Guggenheim is a partner with the law firm Covington & Burling LLP and outside counsel to CRN. She and others said the dispute between FDA and industry over the legality of NAC in supplements has not been settled.
“The agency’s position is incorrect here as a matter of law,” Guggenheim said.
CRN has signaled it may eventually file a citizen petition with FDA related to NAC. Although Pape said the agency’s rejection of a citizen petition can form the basis for judicial review, he and other legal professionals said such petitions can languish at the agency for years.
FDA has 180 days to respond to a citizen petition. However, it often doesn’t provide a substantive response within that deadline, lawyers 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.”
Although petitioners have sued FDA under the Administrative Procedure Act (APA) to compel the agency to respond to a citizen petition, such litigation can take years to be resolved. Even if the petitioner prevails, the best-case scenario is an order that FDA substantively respond to a petition within a certain date.
“Now, you’re three years or more from the time that you submitted a citizen’s petition,” Pape remarked. “I view that as entirely unsatisfactory.”
Asked about the possibility of filing a citizen petition on NAC, Ullman responded, “Nothing [is] going to happen with that. We know what FDA does with citizen’s petitions.”
Mister, nevertheless, said filing a citizen petition related to NAC would start the 180-day clock for FDA to respond and demonstrate to retailers the issue hasn’t been resolved.
“I’m not in disagreement with Stuart that citizen’s petitions often languish at the agency for years and never get answered,” Mister acknowledged. “But at least on paper, [FDA officials] are supposed to respond in 180 days. That would at least give retailers a little breathing room to say, ‘OK, for the next six months, the ball is back in FDA’s court.’”
Theoretically, industry stakeholders also could petition the U.S. Department of Health and Human Services (HHS) to issue a regulation, finding NAC is lawful in dietary supplements even if the ingredient was first approved as a drug. The secretary of HHS—presently Xavier Becerra—has such authority under the Dietary Supplement Health and Education Act of 1994 (DSHEA).
Legal professionals said HHS’ secretaries have never invoked this authority in DSHEA’s 27-year history, and a regulation through notice and comment would likely take years to complete.
“Putting aside the merits” of NAC’s legal status in supplements, Pape suggested “FDA isn’t necessarily playing fairly.”
“It takes an action that has this cascade of consequences and does so in a way that really deprives the industry of meaningful participation before the action is taken, or judicial recourse after the action is taken,” he said.
NAC stakeholders might not get into court until 2024 or 2025. By then, Pape observed, “FDA will have killed the market for this ingredient long before that.”