By Mike Montemarano, Associate Editor04.04.22
In a joint response to two citizen petitions, FDA said it might undertake rulemaking which would allow products containing N-Acetyl-L-Cysteine (NAC) to be marketed and sold as dietary supplements. However, despite a review that yielded no safety concerns, FDA rejected petitions from the Natural Products Association (NPA) and the Council for Responsible Nutrition (CRN) that had asked the agency to reverse course and confirm NAC is a legal ingredient in dietary supplements.
Discussion about whether NAC has regulatory status as a dietary ingredient began after FDA sent warning letters in 2020 to four companies making disease claims about their products. Within its letters, the agency stated NAC couldn’t be marketed in dietary supplements since it was first used in a drug called Mucomyst.
Since then, several retailers including Amazon and CVS have pulled NAC-containing supplements off of their shelves. Leadership within the dietary supplements industry petitioned against FDA’s position and worked to provide evidence that dietary supplements containing NAC are safe and were sold to consumers prior to its use as a drug.
Rulemaking Being Considered
NPA, in its citizen petition, requested that FDA conduct a Part 15 hearing to take place before the commissioner of the agency. This type of hearing is conducted to determine whether the agency should undertake special rulemaking to allow an ingredient such as NAC to be legally marketed as a dietary supplement.
CRN requested that the “agency should revert to its longstanding policy of allowing manufacturers to market dietary supplements containing [NAC] and rescind the legally invalid position included in warning letters that NAC is precluded […] from being a legal dietary ingredient in dietary supplements.”
FDA said that it is denying CRN’s petition in its entirety, and is denying NPA’s request to reverse its decision that NAC products are excluded based on the drug exclusion clause in DSHEA. Based on that drug exclusion clause, the agency maintained its position that NAC should be considered a drug.
Douglas Stearn, deputy director for regulatory affairs at FDA, stated in the agency’s response that the agency interprets the drug exclusion clause of the Dietary Supplement Health and Education Act (DSHEA) in such a way that exceptions are not to be made for drug exclusions based on approvals that took place prior to its passage in 1994.
“The exclusion clause does not provide an exception for drugs that were approved prior to DSHEA, drugs that were authorized for investigation prior to DSHEA, or dietary supplements or foods that were marketed as such prior to DSHEA,” Stearn wrote. “Thus, if Substance A was approved as a new drug in 1987 and was first marketed as a dietary supplement or as a food in 1992, the exclusion clause precludes Substance A from being a dietary supplement any time after DSHEA’s enactment (unless FDA issues a regulation providing otherwise). FDA’s interpretation of the exclusion clause does not give it retroactive effect.”
However, the agency is considering rulemaking which would expressly change the regulatory status of NAC, in order to make it a dietary ingredient that can be used in dietary supplements.
“Although FDA is still working to complete our review of the available data and information, our review thus far has not identified any safety concerns with respect to the use of NAC in or as a dietary supplement,” the agency wrote. “If, among other considerations, FDA does not identify such safety concerns as we continue our review of the available data and information, we are likely to propose a rule providing that NAC is not excluded from the definition of a dietary supplement.”
In the interim, the agency said it is appropriate to exercise enforcement discretion against products containing NAC, if such products are not otherwise in violation of the Federal Food, Drug, and Cosmetic Act. “We intend to issue guidance on this topic,” Stearn wrote.
‘Extralegal Power Grab’
CRN characterized FDA’s recent response as an attempt at an “extralegal power grab” to apply DSHEA retroactively, setting a precedent that the agency might sideline other dietary ingredients in a similar fashion. The association warned this type of sidelining could favor the pharmaceuticals industry for other ingredients found in food.
“Even though FDA has previously acknowledged NAC as a legal and safe supplement ingredient, the agency is attempting to create the power to remove legitimate dietary supplements from the market that the law plainly does not give it,” Steve Mister, president and CEO of CRN, said, expressing disappointment about the agency’s decision to reject CRN’s petition and open up rulemaking instead.
“While the ingredient at issue now is NAC, a broader issue is at stake—FDA’s ability to declare tried and true dietary ingredients off limits to dietary supplements and to confer drug companies with a monopoly over those ingredients, with few options for the industry to challenge those actions,” CRN said in a statement. “FDA claims to have this authority regardless of whether the dietary ingredient under review is marketed for the same intended uses, in the same delivery forms, or the same dosage as the drug. Today’s decision sets a dangerous and extralegal precedent for other supplement ingredients.”
CRN warned that NAC may spend years in regulatory limbo based on how long the rulemaking process could take. The association welcomed FDA’s decision to exercise enforcement discretion for NAC in the meantime, and said it is “guardedly hopeful” that these products will return to retailer’s shelves, in part due to the agency recognizing a lack of safety issues related to NAC.
“However, enforcement discretion and a vague promise of future rulemaking do not provide industry and consumers adequate assurances of future access to this ingredient,” the association continued. “CRN also acknowledges that FDA has made clear its decision on NAC is now a final agency action, ripe for judicial interpretation. We are pleased to get this finality and clarity, while we respectfully disagree with the agency’s analysis, so CRN and our members can evaluate our options going forward. We are presently in consultation with our members about next steps, but every option, including immediate legal action, remains on the table.”
Discussion about whether NAC has regulatory status as a dietary ingredient began after FDA sent warning letters in 2020 to four companies making disease claims about their products. Within its letters, the agency stated NAC couldn’t be marketed in dietary supplements since it was first used in a drug called Mucomyst.
Since then, several retailers including Amazon and CVS have pulled NAC-containing supplements off of their shelves. Leadership within the dietary supplements industry petitioned against FDA’s position and worked to provide evidence that dietary supplements containing NAC are safe and were sold to consumers prior to its use as a drug.
Rulemaking Being Considered
NPA, in its citizen petition, requested that FDA conduct a Part 15 hearing to take place before the commissioner of the agency. This type of hearing is conducted to determine whether the agency should undertake special rulemaking to allow an ingredient such as NAC to be legally marketed as a dietary supplement.
CRN requested that the “agency should revert to its longstanding policy of allowing manufacturers to market dietary supplements containing [NAC] and rescind the legally invalid position included in warning letters that NAC is precluded […] from being a legal dietary ingredient in dietary supplements.”
FDA said that it is denying CRN’s petition in its entirety, and is denying NPA’s request to reverse its decision that NAC products are excluded based on the drug exclusion clause in DSHEA. Based on that drug exclusion clause, the agency maintained its position that NAC should be considered a drug.
Douglas Stearn, deputy director for regulatory affairs at FDA, stated in the agency’s response that the agency interprets the drug exclusion clause of the Dietary Supplement Health and Education Act (DSHEA) in such a way that exceptions are not to be made for drug exclusions based on approvals that took place prior to its passage in 1994.
“The exclusion clause does not provide an exception for drugs that were approved prior to DSHEA, drugs that were authorized for investigation prior to DSHEA, or dietary supplements or foods that were marketed as such prior to DSHEA,” Stearn wrote. “Thus, if Substance A was approved as a new drug in 1987 and was first marketed as a dietary supplement or as a food in 1992, the exclusion clause precludes Substance A from being a dietary supplement any time after DSHEA’s enactment (unless FDA issues a regulation providing otherwise). FDA’s interpretation of the exclusion clause does not give it retroactive effect.”
However, the agency is considering rulemaking which would expressly change the regulatory status of NAC, in order to make it a dietary ingredient that can be used in dietary supplements.
“Although FDA is still working to complete our review of the available data and information, our review thus far has not identified any safety concerns with respect to the use of NAC in or as a dietary supplement,” the agency wrote. “If, among other considerations, FDA does not identify such safety concerns as we continue our review of the available data and information, we are likely to propose a rule providing that NAC is not excluded from the definition of a dietary supplement.”
In the interim, the agency said it is appropriate to exercise enforcement discretion against products containing NAC, if such products are not otherwise in violation of the Federal Food, Drug, and Cosmetic Act. “We intend to issue guidance on this topic,” Stearn wrote.
‘Extralegal Power Grab’
CRN characterized FDA’s recent response as an attempt at an “extralegal power grab” to apply DSHEA retroactively, setting a precedent that the agency might sideline other dietary ingredients in a similar fashion. The association warned this type of sidelining could favor the pharmaceuticals industry for other ingredients found in food.
“Even though FDA has previously acknowledged NAC as a legal and safe supplement ingredient, the agency is attempting to create the power to remove legitimate dietary supplements from the market that the law plainly does not give it,” Steve Mister, president and CEO of CRN, said, expressing disappointment about the agency’s decision to reject CRN’s petition and open up rulemaking instead.
“While the ingredient at issue now is NAC, a broader issue is at stake—FDA’s ability to declare tried and true dietary ingredients off limits to dietary supplements and to confer drug companies with a monopoly over those ingredients, with few options for the industry to challenge those actions,” CRN said in a statement. “FDA claims to have this authority regardless of whether the dietary ingredient under review is marketed for the same intended uses, in the same delivery forms, or the same dosage as the drug. Today’s decision sets a dangerous and extralegal precedent for other supplement ingredients.”
CRN warned that NAC may spend years in regulatory limbo based on how long the rulemaking process could take. The association welcomed FDA’s decision to exercise enforcement discretion for NAC in the meantime, and said it is “guardedly hopeful” that these products will return to retailer’s shelves, in part due to the agency recognizing a lack of safety issues related to NAC.
“However, enforcement discretion and a vague promise of future rulemaking do not provide industry and consumers adequate assurances of future access to this ingredient,” the association continued. “CRN also acknowledges that FDA has made clear its decision on NAC is now a final agency action, ripe for judicial interpretation. We are pleased to get this finality and clarity, while we respectfully disagree with the agency’s analysis, so CRN and our members can evaluate our options going forward. We are presently in consultation with our members about next steps, but every option, including immediate legal action, remains on the table.”
