By Mike Montemarano, Associate Editor12.06.21
This story was updated on December 7, 2021.
In the latest response to citizen petitions it received from dietary supplement trade associations, the U.S. Food and Drug Administration (FDA) has not provided a conclusive determination on the status of N-Acetyl-Cysteine, and whether it considers it lawful to market it as a dietary ingredient.
Since last year, FDA has made it apparent that it holds a newfound position that NAC, an amino acid metabolite and precursor to glutathione which has been widely incorporated into dietary supplements for several decades, is excluded from meeting the definition of a dietary ingredient.
This revelation came in December 2020 when FDA issued multiple warning letters to companies selling supplements containing NAC. The agency cited that NAC was approved as a new drug in 1963. Since the warning letters were first issued, several major retailers have discontinued the sales of supplements containing NAC on their platforms, including Amazon.
Since the agency issued these warning letters at the end of last year, both the Council for Responsible Nutrition (CRN) and the Natural Products Association (NPA) have each submitted unique citizen petitions to the agency, objecting to this policy reversal on the grounds that it was widely available as a dietary ingredient before the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA).
Additionally, NPA filed a lawsuit against FDA due to the fact that it hasn’t provided a decisive response in the form of scheduling a hearing on its citizen petition.
“We have not reached a decision on your petition because of the complex nature of your request and research that we are still working to complete,” Douglas Stearn, deputy director for regulatory affairs at the Center for Food Safety and Applied Nutrition (CFSAN) at FDA, said in the agency’s response. Stearn invited the trade associations to submit information on the earliest date that NAC was marketed as a dietary supplement or food, as well as studies covering the safety of NAC which could bear the determination of an acceptable daily intake.
‘Going Against Precedent’
A key provision of DSHEA is that ingredients in use in dietary supplements prior to its enactment are grandfathered into the supplement marketplace. According to NPA, the legislation also includes a “race to market” paradigm which indicates that any article marketed as both a drug and dietary ingredient prior to its passage should be allowed to continue to be marketed as both, as is the case with such ingredients as L-carnitine and caffeine, but many others as well.
NAC was approved in 1963 as an inhalant branded as Mucomyst which was intended to be used as treatment for acetaminophen poisoning. However, it was also widely sold as a supplement ingredient prior to DSHEA’s passage. Today, there are hundreds of supplements containing NAC on the market which FDA has taken no action against, and the agency has approved at least one qualified health claim for NAC without objecting to the use of it in dietary supplements.
Furthermore, the trade associations note that FDA, in its warning letters and correspondence, has not provided any indication that its objection stems from safety concerns.
“The legal issues here are clear,” Steve Mister, president and CEO of CRN, said. “The provisions of [DSHEA] may not be interpreted retroactively to remove ingredients that were lawfully marketed in 1994 and have enjoyed a long history of safe use since then. The delay in clearing up the status of NAC by asking for more data and refusing to admit its error disregards the law and disserves consumers who use NAC […] Pharmaceutical manufacturers could not have had any expectation of exclusivity in the years prior to the creation of the provision of the law. Given the long history of safe use of NAC, FDA cannot now try to establish a safety concern in order to award this ingredient exclusively to drug makers.”
What Does This Mean for the Future?
Unique to NPA’s citizen petition to FDA on the issue of this ingredient is its request for a Part 15 hearing, which is an evidentiary public hearing taking place before the commissioner of the agency. The trade association sued FDA due to the fact that the agency did not schedule this hearing, which requests that the agency issue a declaratory judgment that DSHEA’s drug exclusion rule doesn’t retroactively apply to NAC.
In essence, the lawsuit claims that FDA does not have the authority to take final action in applying the drug preclusion component of DSHEA retroactively, as this is contradictory to the legislation. “There was no provision in DSHEA or its legislative history to overcome the presumption against statutory retroactivity. Congress expressed no clear intent in the text of DSHEA or its legislative history to support FDA’s erroneous legal determination. The legislative history shows that the drug provision was not intended to apply retroactively,” the suit reads.
“We are concerned that a safe, legal natural product that has been sold for over 30 years is under what appears to be a regulatory sneak attack by the FDA, and even more concerned if this illegal approach may be used for other ingredients,” Dr. Daniel Fabricant, president and CEO of NPA, said. “The FDA has gotten this wrong at every step of the way, and we’ve been left with no choice but to seek relief from the courts. The FDA’s actions against NAC represent a reckless misuse of government resources and will to nothing to protect public health. We are hopeful that the agency will get back to its job of appropriately regulating the U.S. food and drug supply.”
Prior to NPA filing suit Fabricant spoke with Nutraceuticals World about what FDA’s treatment of NAC in this case could mean for any ingredient whose use was first documented archivally as a pharmaceutical drug.
“FDA sat on the fence in their letter back to us, which they really can’t do by law, they either have to initiate a rulemaking process or deny it,” Daniel Fabricant, president and CEO of NPA, said. “Like any other federal agency, FDA is governed by rules of procedure, and they can’t leave it hanging forever; that’s not how that works.”
No other dietary supplement has received the kind of targeting that NAC experienced starting at the end of 2020, Fabricant said, and it sets a very concerning premise for a plethora of ingredients which have been investigated in the past for usage in drug applications, including letter vitamins, and even in theory, table salt and caffeine.
“This could lead to a whole myriad of problems for other ingredients,” Fabricant said. “We could look at prescription niacin (vitamin B3) for example, which dates back to the late 40s. I don’t know anyone who has catalogs of niacin being sold as a dietary supplement which date that far back, so what should we do? Should niacin never again be available as a dietary supplement? They’ve never done this before, because it’s completely at odds with DSHEA and is a misinterpretation of the law.”
“Any alphabet vitamin, minerals, and more have been cataloged as drugs before they were as supplements. The whole premise is crazy when you think about it,” Fabricant continued.
The precise basis for why FDA is acting relatively quickly to remove NAC from the marketplace is unknown, Fabricant noted, and whatever safety concerns the agency might have with it are not being made clear if they do exist.
“I don’t know what’s driving the agency on NAC in particular, it’s a complete black box, and when we try to get information and go through processes such as the citizen’s petition, we get the response that they’ll maybe write a regulation. The agency should either do it or not, because we don’t know if the way forward will be through the courts, or through a regulation. I’m not sure why this is the hill that FDA considers worth dying on, and we don’t know exactly what it is they’re fighting for here.”
In the latest response to citizen petitions it received from dietary supplement trade associations, the U.S. Food and Drug Administration (FDA) has not provided a conclusive determination on the status of N-Acetyl-Cysteine, and whether it considers it lawful to market it as a dietary ingredient.
Since last year, FDA has made it apparent that it holds a newfound position that NAC, an amino acid metabolite and precursor to glutathione which has been widely incorporated into dietary supplements for several decades, is excluded from meeting the definition of a dietary ingredient.
This revelation came in December 2020 when FDA issued multiple warning letters to companies selling supplements containing NAC. The agency cited that NAC was approved as a new drug in 1963. Since the warning letters were first issued, several major retailers have discontinued the sales of supplements containing NAC on their platforms, including Amazon.
Since the agency issued these warning letters at the end of last year, both the Council for Responsible Nutrition (CRN) and the Natural Products Association (NPA) have each submitted unique citizen petitions to the agency, objecting to this policy reversal on the grounds that it was widely available as a dietary ingredient before the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA).
Additionally, NPA filed a lawsuit against FDA due to the fact that it hasn’t provided a decisive response in the form of scheduling a hearing on its citizen petition.
“We have not reached a decision on your petition because of the complex nature of your request and research that we are still working to complete,” Douglas Stearn, deputy director for regulatory affairs at the Center for Food Safety and Applied Nutrition (CFSAN) at FDA, said in the agency’s response. Stearn invited the trade associations to submit information on the earliest date that NAC was marketed as a dietary supplement or food, as well as studies covering the safety of NAC which could bear the determination of an acceptable daily intake.
‘Going Against Precedent’
A key provision of DSHEA is that ingredients in use in dietary supplements prior to its enactment are grandfathered into the supplement marketplace. According to NPA, the legislation also includes a “race to market” paradigm which indicates that any article marketed as both a drug and dietary ingredient prior to its passage should be allowed to continue to be marketed as both, as is the case with such ingredients as L-carnitine and caffeine, but many others as well.
NAC was approved in 1963 as an inhalant branded as Mucomyst which was intended to be used as treatment for acetaminophen poisoning. However, it was also widely sold as a supplement ingredient prior to DSHEA’s passage. Today, there are hundreds of supplements containing NAC on the market which FDA has taken no action against, and the agency has approved at least one qualified health claim for NAC without objecting to the use of it in dietary supplements.
Furthermore, the trade associations note that FDA, in its warning letters and correspondence, has not provided any indication that its objection stems from safety concerns.
“The legal issues here are clear,” Steve Mister, president and CEO of CRN, said. “The provisions of [DSHEA] may not be interpreted retroactively to remove ingredients that were lawfully marketed in 1994 and have enjoyed a long history of safe use since then. The delay in clearing up the status of NAC by asking for more data and refusing to admit its error disregards the law and disserves consumers who use NAC […] Pharmaceutical manufacturers could not have had any expectation of exclusivity in the years prior to the creation of the provision of the law. Given the long history of safe use of NAC, FDA cannot now try to establish a safety concern in order to award this ingredient exclusively to drug makers.”
What Does This Mean for the Future?
Unique to NPA’s citizen petition to FDA on the issue of this ingredient is its request for a Part 15 hearing, which is an evidentiary public hearing taking place before the commissioner of the agency. The trade association sued FDA due to the fact that the agency did not schedule this hearing, which requests that the agency issue a declaratory judgment that DSHEA’s drug exclusion rule doesn’t retroactively apply to NAC.
In essence, the lawsuit claims that FDA does not have the authority to take final action in applying the drug preclusion component of DSHEA retroactively, as this is contradictory to the legislation. “There was no provision in DSHEA or its legislative history to overcome the presumption against statutory retroactivity. Congress expressed no clear intent in the text of DSHEA or its legislative history to support FDA’s erroneous legal determination. The legislative history shows that the drug provision was not intended to apply retroactively,” the suit reads.
“We are concerned that a safe, legal natural product that has been sold for over 30 years is under what appears to be a regulatory sneak attack by the FDA, and even more concerned if this illegal approach may be used for other ingredients,” Dr. Daniel Fabricant, president and CEO of NPA, said. “The FDA has gotten this wrong at every step of the way, and we’ve been left with no choice but to seek relief from the courts. The FDA’s actions against NAC represent a reckless misuse of government resources and will to nothing to protect public health. We are hopeful that the agency will get back to its job of appropriately regulating the U.S. food and drug supply.”
Prior to NPA filing suit Fabricant spoke with Nutraceuticals World about what FDA’s treatment of NAC in this case could mean for any ingredient whose use was first documented archivally as a pharmaceutical drug.
“FDA sat on the fence in their letter back to us, which they really can’t do by law, they either have to initiate a rulemaking process or deny it,” Daniel Fabricant, president and CEO of NPA, said. “Like any other federal agency, FDA is governed by rules of procedure, and they can’t leave it hanging forever; that’s not how that works.”
No other dietary supplement has received the kind of targeting that NAC experienced starting at the end of 2020, Fabricant said, and it sets a very concerning premise for a plethora of ingredients which have been investigated in the past for usage in drug applications, including letter vitamins, and even in theory, table salt and caffeine.
“This could lead to a whole myriad of problems for other ingredients,” Fabricant said. “We could look at prescription niacin (vitamin B3) for example, which dates back to the late 40s. I don’t know anyone who has catalogs of niacin being sold as a dietary supplement which date that far back, so what should we do? Should niacin never again be available as a dietary supplement? They’ve never done this before, because it’s completely at odds with DSHEA and is a misinterpretation of the law.”
“Any alphabet vitamin, minerals, and more have been cataloged as drugs before they were as supplements. The whole premise is crazy when you think about it,” Fabricant continued.
The precise basis for why FDA is acting relatively quickly to remove NAC from the marketplace is unknown, Fabricant noted, and whatever safety concerns the agency might have with it are not being made clear if they do exist.
“I don’t know what’s driving the agency on NAC in particular, it’s a complete black box, and when we try to get information and go through processes such as the citizen’s petition, we get the response that they’ll maybe write a regulation. The agency should either do it or not, because we don’t know if the way forward will be through the courts, or through a regulation. I’m not sure why this is the hill that FDA considers worth dying on, and we don’t know exactly what it is they’re fighting for here.”
