Harmful and Potentially Harmful 
Constituents in Tobacco Products as 
Used in Section 904(e) of the Federal 
Food, Drug, and Cosmetic Act
 
(Revised)* 
 
 
Guidance for Industry and FDA Staff 
 
 
 
Comments may be submitted at any time for Agency consideration.  Electronic comments may 
be submitted to http://www.regulations.gov.  Alternatively, submit written comments to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.  All comments should be identified with Docket No. 
FDA-2010-D-0281.   
 
For questions regarding this guidance, contact the Center for Tobacco Products at (Tel) 1-877-
CTP-1373 (1-877-287-1373) Monday  Friday, 9 a.m. - 4 p.m. EDT.  
 
Additional copies are available online at 
http://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/default.htm.  You 
may send an e-mail request to SmallBiz.Tobacco@fda.hhs.gov to receive an electronic copy of 
this guidance.  You may send a request for hard copies to U.S. Food and Drug Administration, 
Center for Tobacco Products, Attn:  Office of Small Business Assistance, 10903 New Hampshire 
Ave., Silver Spring, MD 20993-2000.  
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Tobacco Products 
 
August 2016 
 
This is a revision to this guidance, which originally issued in January 2011.  Revisions are 
noted by date at the end of the guidance. 
  Contains Nonbinding Recommendations 
 
 
 
 
 
Table of Contents 
 
 
I.  INTRODUCTION .............................................................................................................. 1 
II.  BACKGROUND ................................................................................................................ 1 
III.  DISCUSSION ..................................................................................................................... 2 
i  Contains Nonbinding Recommendations 
 
 
Harmful and Potentially Harmful Constituents in Tobacco 
Products as Used in Section 904(e) of the Federal Food, Drug, and 
Cosmetic Act 
 
 
 
1
Guidance for Industry and FDA Staff  
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) 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 
 
Section 904(e) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 387d(e)), 
as amended by the Family Smoking Prevention and Tobacco Control Act (Tobacco Control 
Act)(Public Law 111-31), requires FDA to establish a list of harmful and potentially harmful 
constituents, including smoke constituents, to health in each tobacco product by brand and by 
quantity in each brand and subbrand (the HPHC list).  This guidance discusses the meaning of 
harmful and potentially harmful constituent in the context of the HPHC list requirement and is 
a revision of the guidance of the same title, dated January 2011 (76 FR 5387, January 31, 2011).   
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited.  The use of the word should in FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
II.  BACKGROUND 
 
On June 22, 2009, the President signed the Tobacco Control Act into law.  The Tobacco Control 
Act granted FDA important new authority to regulate the manufacture, marketing and 
distribution of tobacco products to protect the public health generally and to reduce tobacco use 
by minors.  Among its many provisions, the Tobacco Control Act added section 904(e) to the 
FD&C Act, requiring FDA to establish, and periodically revise as appropriate, a list of harmful 
                                                 
1  This guidance has been prepared by the Office of Science and the Office of Regulations in the Center for Tobacco 
Products at FDA.   
1  Contains Nonbinding Recommendations 
 
and potentially harmful constituents, including smoke constituents, to health in each tobacco 
product by brand and by quantity in each brand and subbrand.   
 
Cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco were immediately 
covered by FDAs tobacco product authorities in Chapter IX of the FD&C Act (21 U.S.C. 387 
through 387u) when the Tobacco Control Act went into effect.  For other kinds of tobacco 
products, the statute authorizes FDA to issue regulations deeming them to be subject to such 
authorities.  These regulations published on May 10, 2016 (81 FR 28974).2  We therefore are 
updating this guidance to better reflect the current range of tobacco products subject to our 
authority.   
 
III.  DISCUSSION 
 
For the purpose of establishing a list of harmful and potentially harmful constituents, including 
smoke constituents, to health in each tobacco product by brand and by quantity in each brand and 
subbrand, as required under section 904(e) of the FD&C Act, FDA believes that the phrase 
harmful and potentially harmful constituent includes any chemical or chemical compound in a 
tobacco product or in tobacco smoke that:  
a) is, or potentially is, inhaled, ingested, or absorbed into the body, including as an 
aerosol (vapor) or any other emission; and 
b) causes or has the potential to cause direct or indirect harm to users or non-users of 
tobacco products.  Examples of constituents that have the potential to cause direct harm 
to users or non-users of tobacco products include constituents that are toxicants, 
carcinogens, and addictive chemicals and chemical compounds.  Examples of 
constituents that have the potential to cause indirect harm to users or non-users of 
tobacco products include constituents that may increase the exposure to the harmful 
effects of a tobacco product constituent by:  1) potentially facilitating initiation of the use 
of tobacco products; 2) potentially impeding cessation of the use of tobacco products; or 
3) potentially increasing the intensity of tobacco product use (e.g., frequency of use, 
amount consumed, depth of inhalation).  Another example of a constituent that has the 
potential to cause indirect harm is a constituent that may enhance the harmful effects of 
a tobacco product constituent. 
 
Document History 
  January 2011  First edition of guidance was issued. 
  August 2016  The guidance was updated to reflect the issuance of the deeming 
rule and the current range of tobacco products now subject to our authority.  Note 
                                                 
2 Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the 
Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco 
Products and Required Warning Statements for Tobacco Products (the deeming rule).   
 
2  Contains Nonbinding Recommendations 
 
that the phrase including as an aerosol (vapor) or any other emission was added 
to the text under paragraph (a) in section III of this document.   
 
 
3