Contains Nonbinding Recommendations 
 
 
Policy Regarding N-acetyl-L-cysteine: 
Guidance for Industry 
 
 
Additional copies are available from: 
Office of Dietary Supplement Programs, HFS-810 
Center for Food Safety and Applied Nutrition 
Food and Drug Administration 
5001 Campus Drive 
College Park, MD 20740 
(Tel) 240-402-2375 
 
https://www.fda.gov/FoodGuidances
 
 
You may submit electronic or written comments regarding this guidance at any time. Submit 
electronic comments to https://www/regulations.gov. Submit written comments on the 
guidance to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the 
docket number FDA-2022-D-0490, listed in the notice of availability that publishes in the 
Federal Register.  
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Food Safety and Applied Nutrition 
 
August 2022 
 
 
  Contains Nonbinding Recommendations 
 
Table of Contents 
 
 
I. Introduction ................................................................................... 2
   
II. Background .................................................................................... 2
   
III. Discussion ....................................................................................... 3
   
 
   
  1  Contains Nonbinding Recommendations 
 
Policy Regarding N-acetyl-L-cysteine: 
Guidance for Industry1 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or we) 
on this topic.  It does not establish any rights for any person and is not binding on FDA or the 
public.  You can use an alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
for this guidance as listed on the title page. 
 
 
I.  Introduction  
 
The purpose of this guidance is to advise dietary supplement manufacturers, distributors, and 
other stakeholders of our intent to exercise enforcement discretion with respect to the sale and 
distribution of certain products that contain N-acetyl-L-cysteine (NAC)2 and are labeled as 
dietary supplements.  As described below, the enforcement discretion policy applies to products 
that would be lawfully marketed dietary supplements if NAC were not excluded from the 
definition of dietary supplement and that are not otherwise in violation of the Federal Food, 
Drug, and Cosmetic Act (FD&C Act).  
 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract.  This document is 
intended only to provide clarity to the public regarding existing requirements under the law.  
FDA guidance documents, including this guidance, should be viewed only as recommendations, 
unless specific regulatory or statutory requirements are cited.  The use of the word should in 
FDA guidances means that something is suggested or recommended, but not required. 
 
II.  Background 
 
The term dietary supplement is defined by the FD&C Act (21 U.S.C. 321(ff)(3)(B)) to 
exclude: 
 
(i) an article that is approved as a new drug under section 505 [of the FD&C Act], 
certified as an antibiotic under section 507 [of the FD&C Act], or licensed as a biologic 
under section 351 of the Public Health Service Act (42 U.S.C. 262), or 
 
1 This guidance has been prepared by the Office of Dietary Supplement Programs and the Office of Regulations and 
Policy, both in the Center for Food Safety and Applied Nutrition (CFSAN) at the Food and Drug Administration.  
2 The names for NAC include, but are not limited to: acetylcysteine; L-acetylcysteine; L-alpha-acetamido-beta-
mercaptopropionic acid; N-acetyl cysteine; N-acetyl-3-mercaptoalanine; N-acetyl-L-cysteine; NAC; and 
mercapturic acid.  These names all refer to the same active ingredient.   
  2  Contains Nonbinding Recommendations 
 
 
(ii) an article authorized for investigation as a new drug, antibiotic, or biological for 
which substantial clinical investigations have been instituted and for which the existence 
of such investigations has been made public,  
 
which was not before such approval, certification, licensing, or authorization marketed as 
a dietary supplement or as a food unless the Secretary, in the Secretarys discretion, has 
issued a regulation, after notice and comment, finding that the article would be lawful 
under [the FD&C] Act. 
 
Thus, if an article has been approved as a new drug under section 505 of the FD&C Act (21 
U.S.C. 355), products containing that article are outside the definition of a dietary supplement 
unless either of two exceptions applies.  First, there is an exception if the article was marketed as 
a dietary supplement or as a food before such approval.  Second, there is an exception if FDA 
(under authority delegated by the Secretary of Health and Human Services) issues a regulation, 
after notice and comment, finding that the article would be lawful under the FD&C Act.  
 
FDA has determined that NAC is excluded from the dietary supplement definition under section 
201(ff)(3)(B)(i) of the FD&C Act because NAC was approved as a new drug before it was 
marketed as a dietary supplement or as a food.  Specifically, NAC (i.e., acetylcysteine) was 
approved as a new drug under section 505 of the FD&C Act on September 14, 1963 (see 28 FR 
13509 (Dec. 13, 1963) (announcing the approval)).  FDA is not aware of any evidence that NAC 
was marketed as a dietary supplement or as a food prior to September 14, 1963.  As discussed 
below in Section III, FDA recently confirmed NACs exclusion from the dietary supplement 
definition in response to two citizen petitions.3  However, we are considering initiating 
rulemaking under section 201(ff)(3)(B) of the FD&C Act to permit the use of NAC in or as a 
dietary supplement (i.e., to provide by regulation that NAC is not excluded from the definition of 
dietary supplement).  If, among other considerations, FDA does not identify safety-related 
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 dietary supplement. 
 
III.  Discussion  
 
FDA received two citizen petitions, one from the Council for Responsible Nutrition (CRN) dated 
June 1, 2021, and one from the Natural Products Association (NPA) dated August 18, 2021, 
requesting that we conclude that NAC is not excluded from the definition of dietary supplement 
under section 201(ff)(3)(B) of the FD&C Act.  In addition, the NPA citizen petition asked FDA 
in the alternative, to recommend and support to the Secretary of HHS, that they issued [sic] a 
regulation, after notice and comment, finding that NAC, would be lawful under the [FD&C 
Act]. 
 
FDA issued tentative responses to these petitions on November 24, 2021, stating that we had not 
reached a decision on the petitions because of the complex nature of the requests and ongoing 
research we are working to complete.  In addition, to help us evaluate NPAs request to initiate 
 
3 Docket Nos. FDA-2021-P-0523 & FDA-2021-P-0938.   
  3  Contains Nonbinding Recommendations 
 
rulemaking, we asked that interested parties submit information to the NPA docket (FDA-2021-
P-0938) regarding the safe use of NAC as or in dietary supplements and data regarding potential 
safety concerns. 
 
FDA issued a joint final response to both petitions on March 31, 2022, denying the CRN petition 
in its entirety and denying the NPA petitions first request.  FDA stated that NAC products are 
excluded from the dietary supplement definition under section 201(ff)(3)(B)(i) of the FD&C Act.  
In addition, we explained that we had not yet reached a final decision on the NPA petitions 
request to initiate rulemaking and that we are considering initiating rulemaking under section 
201(ff)(3)(B) of the FD&C Act to permit the use of NAC in or as a dietary supplement.  While 
FDAs full safety review of NAC remains ongoing, our initial review has not revealed safety 
concerns with respect to the use of this ingredient in or as a dietary supplement.  In addition, 
NAC-containing products represented as dietary supplements have been sold in the U.S. for over 
30 years, and consumers continue to seek access to such products.  
 
Accordingly, as described below, we intend to exercise enforcement discretion with respect to 
the sale and distribution of certain products that contain NAC and are labeled as dietary 
supplements.  The enforcement discretion policy applies to products that would be lawfully 
marketed dietary supplements if NAC were not excluded from the definition of dietary 
supplement and that are not otherwise in violation of the FD&C Act.  For example, with respect 
to the sale of an NAC-containing product that is labeled as a dietary supplement, FDA does not 
intend to object solely because the product is intended to affect the structure or any function of 
the body of man and, therefore, is a drug under section 201(g)(1)(C) of the FD&C Act (21 
U.S.C. 321(g)(1)(C)).4  However, this enforcement discretion policy does not apply to an NAC-
containing product that is labeled as a dietary supplement but is intended for use in the diagnosis, 
cure, mitigation, treatment, or prevention of disease and, therefore, is a drug under section 
201(g)(1)(B) of the FD&C Act.  Likewise, for example, the enforcement discretion policy does 
not apply to NAC-containing products that are adulterated or misbranded under the FD&C Act 
(other than those misbranded only because they contain NAC and are labeled as dietary 
supplements).  
 
Unless we identify safety-related concerns during our ongoing review, FDA intends to exercise 
enforcement discretion until either of the following occurs: we complete notice-and-comment 
rulemaking to allow the use of NAC in or as a dietary supplement (should we move forward with 
such proceedings) or we deny the NPA citizen petitions request for rulemaking.  Should we 
determine that this enforcement discretion policy is no longer appropriate, we will withdraw or 
revise this guidance in accordance with 21 CFR 10.115. 
  
 
4 Under section 201(g)(1)(C) of the FD&C Act, the term drug includes articles (other than food) intended to 
affect the structure or any function of the body of man or other animals.  However, section 201(g)(1) of the FD&C 
Act provides that a dietary supplement for which a truthful and not misleading statement is made in accordance with 
section 403(r)(6) of the FD&C Act (e.g., a statement that describes the role of a nutrient or dietary ingredient 
intended to affect the structure or function in humans or characterizes the documented mechanism by which a 
nutrient or dietary ingredient acts to maintain such structure or function) is not a drug under section 201(g)(1)(C) of 
the FD&C Act solely because the label or the labeling contains such a statement.  This exception does not apply to a 
product that is or contains an article that is excluded from the definition of dietary supplement, even if such product 
is labeled as a dietary supplement.   
  4