Document ID: FDA-2015-N-2002-1943
Agency: fda
Document Type: Rule
Title: Clarification of When Products Made or Derived from Tobacco are Regulated as Drugs, Devices, or Combination Products; Amendments to Regulations Regarding "Intended Uses"
Posted Date: 2017-01-09T05:00Z

[Federal Register Volume 82, Number 5 (Monday, January 9, 2017)]
[Rules and Regulations]
[Pages 2193-2217]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-31950]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 801, and 1100

[Docket No. FDA-2015-N-2002]
RIN 0910-AH19

Clarification of When Products Made or Derived From Tobacco Are 
Regulated as Drugs, Devices, or Combination Products; Amendments to 
Regulations Regarding ``Intended Uses''

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing this final 
rule to describe the circumstances in which a product made or derived 
from tobacco that is intended for human consumption will be subject to 
regulation as a drug, device, or a combination product under the 
Federal Food, Drug, and Cosmetic Act (the FD&C Act). This action is 
intended to provide direction to regulated industry and to help avoid 
consumer confusion.

DATES: This rule is effective February 8, 2017.

ADDRESSES: For access to the docket to read background documents or

[[Page 2194]]

comments received, go to https://www.regulations.gov and insert the 
docket number found in brackets in the heading of this final rule into 
the ``Search'' box and follow the prompts, and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Bryant Godfrey or Darin Achilles, 
Center for Tobacco Products, Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20993-0002, 877-287-1373, 
CTPRegulations@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

Table of Contents

Executive Summary
I. Background
    A. Definition of ``Tobacco Product''
    B. Drug/Device/Combination Product Definitions
    C. Comments and Responses Regarding Definitions
    D. History of 1996 Rulemaking and Relevant Litigation
II. Purpose of Regulatory Action
    A. Intended Uses For Products Made or Derived From Tobacco That 
Bring Products Within the Disease Prong
    B. Comments and Responses Regarding Modified Risk Tobacco 
Products
    C. Intended Uses For Products Made or Derived From Tobacco That 
Bring ProductsWithin the Structure/Function Prong
    D. Comments and Responses Regarding Brown & Williamson and 
Sottera
    E. Comments and Responses Regarding Consumer Confusion
    F. Changes to Existing ``Intended Use'' Regulations
III. Legal Authority
IV. Description of the Final Rule
    A. Exclusion From Tobacco Product Regulation (Sec.  1100.5)
    B. Existing ``Intended Use'' Regulations (Sec. Sec.  201.128 and 
801.4)
    C. Comments and Responses Regarding Intended Use
    D. Comments and Responses Regarding Marketing Concerns
    E. Other Comments and Responses
    F. Other Changes to the Codified Text
    G. Effective Date
V. Federalism
VI. Executive Order 13175: Tribal Consultation
VII. Analysis of Environmental Impact
VIII. Economic Analysis of Impacts
IX. Paperwork Reduction Act of 1995
X. References

Executive Summary

Purpose of the Rule

    The Family Smoking Prevention and Tobacco Control Act (Tobacco 
Control Act) amends the FD&C Act and provides FDA with the authority to 
regulate tobacco products. Section 201(rr) of the FD&C Act (21 U.S.C. 
321(rr)), as amended by the Tobacco Control Act, defines the term 
``tobacco product'' as any product made or derived from tobacco that is 
intended for human consumption, including any component, part, or 
accessory of a tobacco product (except for raw materials other than 
tobacco used in manufacturing a component, part, or accessory of a 
tobacco product). Excluded from the definition of a tobacco product is 
any article that is a drug, device, or combination product. Any article 
that is a drug, device, or combination product will be regulated as 
such rather than as a tobacco product.
    Because some ambiguity surrounds the circumstances under which a 
product that is made or derived from tobacco would be regulated as a 
drug, device, or combination product, and the circumstances under which 
it would be regulated as a tobacco product, FDA is taking this action 
to provide clarity regarding our interpretation of the drug and device 
definitions in the FD&C Act with respect to products made or derived 
from tobacco. This final rule will provide assistance for entities 
intending to market products made or derived from tobacco. FDA expects 
the rule will also assist investigators planning to use products made 
or derived from tobacco for an investigational use in determining the 
investigational use requirements that apply to their proposed studies. 
The final rule is also intended to increase clarity regarding the 
intended uses and supporting evidence that make a product made or 
derived from tobacco subject to regulation as a drug, device, or 
combination product, helping consumers distinguish products made or 
derived from tobacco that are intended for medical use from products 
marketed for other uses.
    In addition, FDA is taking the opportunity to make changes to 
existing regulations at Sec. Sec.  201.128 and 801.4 (21 CFR 201.128 
and 801.4), and to conform them to how the Agency currently applies 
these regulations to drugs and devices generally.

Summary of the Major Provisions of the Regulatory Action

    Conceptually, the final rule follows the disease prong and the 
structure/function prong (with certain specified limitations) of the 
statutory definitions of ``drug'' and ``device'' (section 201(g) and 
(h) of the FD&C Act). Under the final rule, a product made or derived 
from tobacco and intended for human consumption is regulated as a drug, 
device, or combination product in two circumstances: (1) If the product 
is intended for use in the diagnosis of disease or other conditions, or 
in the cure, mitigation, treatment, or prevention of disease; or (2) if 
the product is intended to affect the structure or any function of the 
body in any way that is different from effects related to nicotine that 
were commonly and legally claimed in the marketing of cigarettes and 
smokeless tobacco products prior to March 21, 2000. The final rule also 
clarifies remaining circumstances where a product is subject to 
regulation as a tobacco product.
    In addition, FDA is amending its existing intended use regulations 
for drugs and devices by inserting in Sec. Sec.  201.128 and 801.4 a 
reference to the final rule to clarify the interplay between these 
regulations and this final rule. FDA has made further changes to 
conform Sec. Sec.  201.128 and 801.4 to reflect how the Agency 
currently applies them to drugs and devices.

Costs and Benefits

    The final rule clarifies the regulatory status of products made or 
derived from tobacco and our interpretation and application of the 
existing intended use regulations. This will reduce the ambiguity and 
may create some efficiency gains associated with submitting an 
application for approval or marketing authorization of a new tobacco-
derived product, or with initiating research for a new tobacco-derived 
product. In addition, we assume that the regulation will clarify for 
consumers when products made or derived from tobacco are intended for 
medical uses rather than for other uses.
    We assume that all tobacco-derived product manufacturers would 
incur one-time costs to learn the rule. There may also be a one-time 
cost incurred by a small number of manufacturers of tobacco products to 
review and revise product communications such as labeling and 
associated promotional materials. The following table reports these 
one-time costs.

[[Page 2195]]

                                             Table 1--One-Time Costs
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                                                                        Low          Mid-point         High
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Learning costs..................................................        $117,412        $146,779        $176,147
Review communications, such as labeling and promotional                  486,024         486,024         486,024
 materials......................................................
Revisions to communications, such as labeling and promotional            283,003       1,092,422       1,901,841
 materials......................................................
                                                                 -----------------------------------------------
    Total.......................................................         886,439       1,725,225       2,564,012
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I. Background

    In the Federal Register of September 25, 2015 (80 FR 57756), FDA 
issued a proposed rule entitled ``Clarification of When Products Made 
or Derived From Tobacco Are Regulated as Drugs, Devices, or Combination 
Products; Amendments to Regulations Regarding `Intended Uses.' '' We 
received over 1,900 comments on the proposed rule. Two comments 
requested that the comment period be extended due to the complexity of 
the legal issues involved. One of these comments related to the 
original 60-day comment period. In the Federal Register of November 30, 
2015 (80 FR 74737), FDA reopened the comment period for an additional 
30 days. The second comment appears to relate to the additional 30-day 
comment period announced in 80 FR 74737. With respect to the comment 
requesting an extension beyond the additional 30-day comment period, 
FDA believes this comment to be misplaced as it generally references 
``nine questions'' that are related to a different rulemaking--the 
proposed version of the deeming rule.\1\
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    \1\ ``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; Proposed Rule'' (79 FR 23142, April 25, 2014).
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A. Definition of ``Tobacco Product''

    The Tobacco Control Act was enacted on June 22, 2009 (Pub. L. 111-
31), amending the FD&C Act and providing FDA with the authority to 
regulate tobacco products. Section 101(a) of the Tobacco Control Act 
amends section 201 of the FD&C Act by adding paragraph (rr), which 
defines the term ``tobacco product.'' In general, a ``tobacco product'' 
is defined as any product made or derived from tobacco that is intended 
for human consumption, including any component, part, or accessory of a 
tobacco product (except for raw materials other than tobacco used in 
manufacturing a component, part, or accessory of a tobacco product). 
Section 201(rr)(2) of the FD&C Act excludes from the definition of a 
tobacco product any article that is defined as a drug under section 
201(g)(1), a device under section 201(h), or a combination product 
described in section 503(g) of the FD&C Act (21 U.S.C. 353(g)). Section 
201(rr)(3) of the FD&C Act explains that any article that is a drug, 
device, or combination product shall be subject to chapter V of the 
FD&C Act (the authorities for drugs and devices) rather than chapter IX 
(the authorities for tobacco products).\2\
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    \2\ Section 201(rr)(4) of the FD&C Act prohibits a tobacco 
product from being marketed in combination with any other article or 
product regulated under the FD&C Act. This rulemaking did not 
address section 201(rr)(4).
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B. Drug/Device/Combination Product Definitions

1. Medical Product Definitions
    As noted in section I.A, the definition of ``tobacco product'' 
excludes anything that is a ``drug,'' ``device,'' or ``combination 
product'' under the FD&C Act. The FD&C Act defines ``drug'' (in 
relevant part) as an article intended either: (1) For use in the 
diagnosis, cure, mitigation, treatment, or prevention of disease 
(referred to as the ``disease prong'' of the definition) or (2) to 
affect the structure or any function of the body (the ``structure/
function prong'') (section 201(g)(1) of the FD&C Act). The FD&C Act 
defines a ``device'' (in relevant part) as an instrument, apparatus, 
implement, machine, contrivance, implant, in vitro reagent, or other 
similar or related article, including any component, part, or 
accessory, intended either: (1) For use in the diagnosis of disease or 
other conditions, or in the cure, mitigation, treatment, or prevention 
of disease or (2) to affect the structure or any function of the body, 
and which does not achieve its primary intended purposes through 
chemical action within or on the body of man and which is not dependent 
on being metabolized for the achievement of its primary intended 
purposes (section 201(h) of the FD&C Act).\3\ Combination products are 
products that constitute a combination of a drug, device, or biological 
product (section 503(g) of the FD&C Act). Under the FD&C Act, the 
Secretary's determination of the primary mode of action of a 
combination product determines which Center at FDA will have primary 
jurisdiction over the product (section 503(g) of the FD&C Act).
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    \3\ In this final rule, the cited language may be referred to as 
the ``drug/device definitions.''
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    FDA had previously interpreted the exclusion in the tobacco product 
definition to mean that if a product made or derived from tobacco is 
determined to have a drug or device ``intended use,'' it will be 
regulated as a medical product, not as a tobacco product. As discussed 
in greater detail in this document, this interpretation was qualified 
in Sottera, Inc. v. Food & Drug Administration, 627 F.3d 891 (D.C. Cir. 
2010), in which the D.C. Circuit applied the holding of Food & Drug 
Administration v. Brown & Williamson Tobacco Corp., 529 U.S. 120, 156 
(2000), to all tobacco products. Thus, the determination of whether a 
product is a medical product or a tobacco product is based on the FD&C 
Act and associated regulations and also takes into account relevant 
legal precedent (further described in section I.D).
2. How Intended Use Is Determined
    In determining a product's intended use, the Agency may look to 
``any . . . relevant source,'' including but not limited to the 
product's labeling, promotional claims, and advertising (see, e.g., 
Action on Smoking and Health v. Harris, 655 F.2d 236, 239 (D.C. Cir. 
1980); United States v. Storage Spaces Designated Nos. ``8'' and 
``49,'' 777 F.2d 1363, 1366 (9th Cir. 1985), Hanson v. United States, 
417 F. Supp. 30, 35 (D. Minn.), aff'd, 540 F.2d 947 (8th Cir. 1976)).
    For example, FDA may take into account any claim or statement made 
by or on behalf of a manufacturer that explicitly or implicitly 
promotes a product for a particular use (see, e.g., Sec.  201.128 
(drugs), Sec.  801.4 (devices)).\4\
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    \4\ Under FDA regulations, the term ``intended use'' relates to 
the objective intent of the medical product manufacturer, packer, 
distributor, or seller, including both corporate entities and 
natural individuals (hereinafter ``manufacturers'' or ``firms'').
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    To establish a product's intended use, FDA is not bound by the 
manufacturer or distributor's subjective claims of intent, but rather 
can consider objective

[[Page 2196]]

evidence, which may include a variety of direct and circumstantial 
evidence. Thus, FDA may also take into account any circumstances 
surrounding the distribution of the product or the context in which it 
is sold (see id.; see also United States v. Travia, 180 F.Supp.2d 115, 
119 (D.D.C. 2001)). In the context of medical products, generally, 
circumstantial evidence often ensures that FDA is able to pursue firms 
that attempt to evade FDA medical product regulation by avoiding making 
express claims about their products. As FDA has previously stated, 
however, the Agency would not, absent extraordinary circumstances, 
regard a firm as intending an unapproved new use for an approved drug, 
or a device that has been approved, cleared, granted marketing 
authorization, or is exempt from premarket notification requirements 
(for ease of reference, such a device is referred to as ``an approved 
or cleared device'' (or similar terms) throughout this preamble) based 
solely on the firm's knowledge that such product was being prescribed 
or used by doctors for such use (Ref. 1).
    Thus, when a product made or derived from tobacco is marketed or 
distributed for an intended use that falls within the drug/device 
definitions, it is regulated as a medical product, subject to the 
limitations discussed further in this document. Courts have recognized 
that products made or derived from tobacco marketed with ``disease'' 
claims and certain ``structure/function'' claims are drugs (see United 
States v. 46 Cartons . . . Containing Fairfax Cigarettes, 113 F.Supp. 
336, 337, 338 (D. N.J. 1953) (cigarettes marketed for the prevention of 
respiratory diseases); United States v. 354 Bulk Cartons . . . Trim 
Reducing-Aid Cigarettes, 178 F.Supp. 847, 851 (D. N.J. 1959) 
(cigarettes marketed for weight reduction)).

C. Comments and Responses Regarding Definitions

    Comments were received from tobacco product manufacturers, 
retailers, academia, medical professionals, advocacy groups, and 
consumers. To make it easier to identify comments and our responses, 
the word ``Comment,'' in parentheses, will appear before each comment, 
and the word ``Response,'' in parentheses, will appear before each 
response. We have numbered the comments to make it easier to 
distinguish between comments; the numbers are for organizational 
purposes only and do not reflect the order in which we received the 
comments or any value associated with them. We have combined similar 
comments under one numbered comment. In addition to the comments 
specific to this rulemaking that we address in the following 
paragraphs, we received many general comments expressing support or 
opposition to the rule. These comments express broad policy views and 
do not address specific points related to this rulemaking. Therefore, 
these general comments do not require a response. Other comments 
outside the scope of this rulemaking also have not been addressed here. 
Summaries of the remaining comments, as well as FDA's responses, are 
included in this document.
    (Comment 1) At least one comment stated that FDA is not permitted 
to regulate the nicotine in cigarettes as a drug and should not be 
permitted to regulate electronic nicotine delivery systems (ENDS) as 
medical products.
    (Response) FDA disagrees. Section 201(g) of the FD&C Act defines 
``drug'' as articles intended for use in the diagnosis, cure, 
mitigation, treatment, or prevention of disease in man or other 
animals, and articles (other than food) intended to affect the 
structure or any function of the body of man or other animals. Section 
201(h) of the FD&C Act defines ``device'' (in relevant part) as ``an 
instrument, apparatus, implement, machine, contrivance, implant, in 
vitro reagent, or other similar or related article, including any 
component, part, or accessory,'' that is intended ``for use in the 
diagnosis of disease or other conditions, or in the cure, mitigation, 
treatment, or prevention of disease, in man or other animals, or . . . 
to affect the structure or any function of the body,'' and which does 
not achieve its primary intended purposes through chemical action 
within or on the body of man and which is not dependent on being 
metabolized for the achievement of its primary intended purposes. As 
explained in this final rule, FDA has the authority to regulate a 
product made or derived from tobacco, including cigarettes and ENDS, as 
a medical product if it is distributed or marketed for an intended use 
that falls within the drug/device definitions, unless the product is 
intended to affect the structure or any function of the body in any way 
related to the effects of nicotine that were commonly and legally 
claimed in the marketing of cigarettes and smokeless tobacco products 
prior to March 21, 2000.
    (Comment 2) Several comments stated that there is no need to 
clarify the medical product and tobacco product definitions that govern 
FDA regulation of these products. One of those comments also went on to 
state that there is a clear difference between drug product claims and 
``consumer-oriented marketing statements'' about smoking cessation.
    (Response) FDA disagrees that there is no need for additional 
clarity in this area. The Agency frequently receives inquiries 
regarding jurisdictional distinctions for products made or derived from 
tobacco, and given the broad range of intended uses for products made 
or derived from tobacco and the increasing variety of such products on 
the market, FDA believes that the potential for consumer confusion is 
increasing. This is especially true when tobacco-derived products that 
may otherwise appear to be products intended for recreational use make 
claims related to quitting smoking and treatment of nicotine addiction.
    FDA considers claims about smoking cessation to be more than simply 
``consumer-oriented marketing statements.'' As noted in the preamble to 
the proposed rule, claims related to smoking cessation have long been 
recognized as evidence of intended use, conferring drug or device 
jurisdiction, and smoking cessation claims also have long been 
associated with the intended uses of curing or treating nicotine 
addiction and its symptoms. For example, smoking cessation claims have 
appeared on the approved labeling for nicotine replacement therapies 
since the mid-1990s. FDA believes it is important to clarify and 
reiterate that smoking cessation claims on any product can render that 
product subject to FDA's medical products authorities.
    (Comment 3) Comments had differing opinions on whether ENDS meet 
the definition of ``tobacco product'' as defined in the FD&C Act. 
Several comments stated that ENDS fall under the definition of 
``tobacco product'' as defined in the FD&C Act if they contain nicotine 
derived from tobacco and are not intended to be drugs or devices. 
However, other comments stated that ENDS, including vaping hardware, do 
not fall within the definition of ``tobacco product.''
    (Response) FDA agrees that ENDS meet the definition of ``tobacco 
product'' if they are not drugs, devices, or combination products. The 
term ``tobacco product'' is defined in section 201(rr) of the FD&C Act 
(21 U.S.C. 321(rr)) to mean any product made or derived from tobacco 
that is intended for human consumption, including any component, part, 
or accessory of a tobacco product (except for raw materials other than 
tobacco used in manufacturing a component, part, or accessory of a 
tobacco product), and excluding drugs, devices, and

[[Page 2197]]

combination products as defined under the FD&C Act. Unless they are 
marketed for an intended use that falls within the drug/device 
definitions, ENDS products meet the definition of tobacco product. 
Additionally, as discussed elsewhere in the preamble, if ENDS products 
are intended to affect the structure or function of the body in any way 
related to the effects of nicotine that were commonly and legally 
claimed in the marketing of cigarettes and smokeless tobacco products 
prior to March 21, 2000, they will be regulated as tobacco products. 
(See section II.C.)
    FDA disagrees with comments stating that vaping hardware does not 
fall within the definition of ``tobacco product.'' As the Agency 
explained in the final deeming regulation,\5\ the definition of tobacco 
product includes components and parts. Also included in the final 
deeming regulation is a non-exhaustive list of examples of components 
and parts used with ENDS products. Examples of components and parts 
used with ENDS products includes, but are not limited to: E-liquids; 
atomizers; batteries (with or without variable voltage); cartomizers 
(atomizer plus replaceable fluid-filled cartridge); digital display/
lights to adjust settings; clearomisers, tank systems, flavors, vials 
that contain e-liquids, and programmable software. Thus, vaping 
hardware meets the definition of tobacco product.
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    \5\ ``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; Final Rule'' (81 FR 28973, May 10, 2016).
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D. History of 1996 Rulemaking and Relevant Litigation

    Although the courts have recognized that tobacco-derived products 
can be regulated as medical products under the FD&C Act in certain 
circumstances, courts have also held that there are limitations on how 
the drug and device definitions can be applied to products made or 
derived from tobacco. This section provides a summary of FDA regulatory 
action and related litigation relevant to those limitations.
    In 1996, FDA issued a regulation restricting the sale and 
distribution of cigarettes and smokeless tobacco to children and 
adolescents (the 1996 rule) (61 FR 44396, August 28, 1996). This rule 
included FDA's determination that it had jurisdiction over cigarettes 
and smokeless tobacco under the FD&C Act. The basis for this 
determination was that cigarettes and smokeless tobacco were intended 
to affect the structure or function of the body, within the FD&C Act 
definitions of the terms ``drug'' and ``device,'' because nicotine has 
significant pharmacological effects. In addition, FDA found that 
cigarettes and smokeless tobacco were combination products consisting 
of the drug nicotine and device components intended to deliver nicotine 
to the body. In the 1996 rule, FDA concluded that cigarettes and 
smokeless tobacco should be regulated under the device authorities of 
the FD&C Act. The 1996 rule was challenged in court by a group of 
tobacco manufacturers, retailers, and advertisers on the grounds that 
FDA lacked jurisdiction to regulate tobacco products ``as customarily 
marketed;'' that the regulations exceeded FDA's authority to regulate 
devices; and that the advertising restrictions violated the First 
Amendment.
    The Supreme Court struck down the 1996 rule in Food & Drug 
Administration v. Brown & Williamson Tobacco Corp., 529 U.S. 120, 156 
(2000), holding that FDA lacked jurisdiction over tobacco products ``as 
customarily marketed.'' The Court found that Congress intended to 
exclude tobacco products from FDA's jurisdiction. In Brown & 
Williamson, the Court determined that tobacco products could not be 
made safe and effective for their intended uses, and therefore, if FDA 
had authority over them, FDA would have to remove them from the market, 
but that Congress had foreclosed such action (529 U.S. at 135-139). The 
Court also observed that Congress, in enacting statutes to regulate the 
labeling and advertising of conventional tobacco products, such as 
cigarettes and smokeless tobacco, had ``effectively ratified FDA's 
long-held position'' that the Agency lacked jurisdiction to regulate 
tobacco products ``absent claims of therapeutic benefit by the 
manufacturer'' (529 U.S. at 144).
    In 2008 and early 2009, FDA detained multiple shipments of 
electronic cigarettes from overseas manufacturers and denied them entry 
into the United States on the ground that electronic cigarettes were 
unapproved drug-device combination products under the FD&C Act. In 
April 2009, two of the importers who were affected by this action 
sought a preliminary injunction to enjoin FDA from regulating 
electronic cigarettes as drug-device combination products and from 
denying entry of those products into the United States.\6\ Between the 
filing of the lawsuit and a decision on the motion for a preliminary 
injunction, Congress passed the Tobacco Control Act and the President 
signed it into law. The District Court subsequently granted a 
preliminary injunction, relying on Brown & Williamson and the recently 
enacted Tobacco Control Act (Smoking Everywhere, Inc. v. FDA, 680 F. 
Supp. 2d 62 (D.D.C. 2010)). FDA appealed the decision and the United 
States Court of Appeals for the District of Columbia Circuit (D.C. 
Circuit) affirmed in Sottera, Inc. v. Food & Drug Administration, 627 
F.3d 891 (D.C. Cir. 2010).\7\ The D.C. Circuit determined that the 
decision in Brown & Williamson was not limited to tobacco products that 
were the subject of the specific federal legislation discussed in that 
case. The D.C. Circuit found that under the Tobacco Control Act, all 
products made or derived from tobacco and intended for human 
consumption that are ``marketed for therapeutic purposes'' are subject 
to FDA's drug and/or device provisions, whereas ``customarily marketed 
tobacco products'' are subject to regulation as ``tobacco products'' 
(Sottera, 627 F.3d at 898-899; see also Brown & Williamson, 529 U.S. at 
144-156).
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    \6\ The original district court case was filed by Smoking 
Everywhere, Inc., and the case was joined by Sottera, Inc., which 
does business as NJOY.
    \7\ On January 24, 2011, the D.C. Circuit denied the 
government's petitions for rehearing and rehearing en banc (by the 
full court). See Sottera v. Food & Drug Administration, No. 10-5032 
(D.C. Cir. Jan. 24 2011) (per curiam).
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    The Court in Brown & Williamson frequently referred to ``tobacco 
products as customarily marketed,'' but never defined that phrase. The 
Court contrasted that phrase with ``claims of therapeutic benefit'' 
(see, e.g., 529 U.S. at 127, 158), which it also did not define, 
although it did indicate that tobacco products' purported ``therapeutic 
benefits'' included all four of the structure/function intended uses on 
which FDA had based its 1996 rulemaking: Satisfying addiction, 
stimulation, sedation, and weight control (529 U.S. at 141). Neither of 
these terms is used in the FD&C Act. In Sottera, the D.C. Circuit 
relied on Brown & Williamson and repeated these phrases in describing 
contrasting types of products. The court in Sottera specifically 
equated ``therapeutic uses'' with the disease prong of the drug/device 
definitions in the FD&C Act and said that customarily marketed tobacco 
products were sold without therapeutic claims (627 F.3d at 894) and 
should be regulated as tobacco products under the FD&C Act, as amended 
by the Tobacco Control Act. As noted, the Brown & Williamson decision 
indicated that the four intended structure/function effects FDA had 
identified (satisfying addiction, stimulation, sedation, and

[[Page 2198]]

weight control) were purported tobacco product ``therapeutic benefits'' 
(Brown & Williamson, 529 U.S. at 141). But neither the Brown & 
Williamson nor the Sottera court defined what might constitute claims 
of therapeutic benefit, nor did they explain the relationship between 
``tobacco products as customarily marketed'' and the structure/function 
prong of the drug/device definitions of the FD&C Act. In addition, no 
court has addressed whether certain structure/function claims for 
products made or derived from tobacco that generally were not made for 
``tobacco products as customarily marketed'' should be treated as drug 
or device claims.\8\
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    \8\ In Sottera, there are a few instances where the court's 
opinion could be read to suggest that all products made or derived 
from tobacco ``marketed without claims of therapeutic effect'' are, 
ipso facto, tobacco products ``as customarily marketed'' (627 F.3d 
at 895; see also id. at 898-899). However, because the issue of 
drug/device jurisdiction over structure/function intended uses that 
are not related to the commonly understood effects of nicotine was 
not before the court, this reading--even if it were correct--would 
be dicta.
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II. Purpose of Regulatory Action

    Because some ambiguity surrounds the circumstances under which a 
product that is made or derived from tobacco would be regulated as a 
drug, device, or combination product, and the circumstances under which 
it would be regulated as a tobacco product, we are issuing this final 
rule to provide clarity regarding our interpretation of the drug/device 
definitions in the FD&C Act with respect to products made or derived 
from tobacco. We believe that this final regulation will provide 
assistance for entities intending to market products made or derived 
from tobacco and for entities that plan to study these products. For 
example, the rule is expected to help sponsors determine which FDA 
Center should be consulted as they develop their products and make 
appropriate premarket submissions to bring new products to market. FDA 
expects the rule will also assist investigators planning to use 
products made or derived from tobacco for an investigational use in 
determining the investigational use requirements that apply to their 
proposed studies. In addition, we believe it is important to avoid 
consumer confusion about which products are intended for medical uses 
versus recreational or other uses. The rule is expected to increase 
clarity regarding the types of intended uses and supporting evidence 
that make a product made or derived from tobacco subject to regulation 
as a drug or device, which we expect will help consumers distinguish 
products made or derived from tobacco that are intended for medical use 
from products marketed for other uses. Finally, the rule is intended to 
provide clarity for drug and device manufacturers generally regarding 
FDA's interpretation and application of its existing intended use 
regulations.
    In both the Brown & Williamson and Sottera decisions, the courts 
set forth (but did not define) two poles--``tobacco products as 
customarily marketed'' and ``claims of therapeutic benefit''--and found 
that the ``customarily marketed'' pole was not within FDA's drug/device 
jurisdiction, but that the ``claims of therapeutic benefit'' pole was 
within FDA's drug/device jurisdiction. As noted in section I.D, the 
terminology used by the courts in establishing these two poles is not 
the terminology used by the FD&C Act in defining drugs and devices. 
Instead, the FD&C Act's drug and device definitions reference, in 
relevant part, diagnosis, cure, mitigation, treatment, or prevention of 
disease (disease prong) and effects on the structure or any function of 
the body (structure/function prong). In addition, while certain 
products and claims may fall clearly at one pole or the other, a 
spectrum of products and claims may fall somewhere between the two 
poles. In the sections that follow, we describe our interpretation of 
the jurisdictional lines established by the FD&C Act's drug, device, 
and tobacco product definitions as informed by the decisions in Brown & 
Williamson and Sottera.

A. Intended Uses For Products Made or Derived From Tobacco That Bring 
Products Within the Disease Prong

1. Intended Uses That Bring Products Within the Disease Prong
    As discussed in section I.B, articles intended for use in the 
diagnosis, cure, mitigation, treatment, or prevention of disease are 
drugs, devices, or combination products under the FD&C Act. Products 
made or derived from tobacco have historically been regulated as 
medical products when they are marketed for intended uses that fall 
within the disease prong. For example, FDA has approved a number of 
drug products made or derived from tobacco as nicotine replacement 
therapies with indications to reduce withdrawal symptoms, including 
nicotine craving, associated with quitting smoking. Accordingly, FDA 
has long considered claims related to smoking cessation in the context 
of curing or treating nicotine addiction and its symptoms to bring 
products within FDA's ``disease prong'' jurisdiction.
    FDA has also taken enforcement action against products made or 
derived from tobacco that were marketed with claims of therapeutic 
benefit but that did not have approved new drug applications (NDAs). 
For example, FDA seized cigarettes on the grounds that they were 
misbranded drugs when the manufacturer represented that the cigarettes 
were effective in preventing respiratory diseases, common cold, 
influenza, pneumonia, and various other ailments (United States v. 46 
Cartons . . . Containing Fairfax Cigarettes, 113 F.Supp. 336, 337, 338 
(D. N.J. 1953)); see also United States v. 354 Bulk Cartons Trim 
Reducing-Aid Cigarettes, 178 F.Supp. 847 (D. N.J. 1959) (similar, where 
manufacturer made weight-reduction claims for its cigarettes).
    The ``claims of therapeutic benefit'' language used by the Brown & 
Williamson and Sottera courts has a logical relationship to the disease 
prong of the drug/device definition, in that ``therapeutic'' can be 
defined as ``relating to the treatment of disease or disorders by 
remedial agents or methods'' or to ``providing or assisting in a 
cure.'' \9\ With this rule, FDA is clarifying the categories of claims 
relevant to products made or derived from tobacco that FDA considers to 
be evidence of intended use that brings products within the disease 
prong in light of the Sottera and Brown & Williamson decisions. As 
discussed previously, claims related to smoking cessation have long 
been recognized as evidence of intended use conferring drug or device 
jurisdiction. Smoking cessation claims have also long been associated 
with intended uses of curing or treating nicotine addiction and its 
symptoms. For example, the approved labeling for nicotine replacement 
therapies includes the following statements: ``Purpose: Stop smoking 
aid; Use: reduces withdrawal symptoms, including nicotine craving, 
associated with quitting smoking.'' \10\ Against this backdrop, smoking 
cessation claims on any product generally create a strong suggestion of 
intended therapeutic benefit to the user that generally will be 
difficult to overcome absent clear context indicating that the product 
is not intended for use to cure or treat nicotine addiction or its 
symptoms, or for another therapeutic purpose.
---------------------------------------------------------------------------

    \9\ See, e.g., Merriam-Webster Online Dictionary, available at 
http://www.merriam-webster.com/dictionary/therapeutic.
    \10\ See, e.g., approved labeling for Nicoderm CQ, Nicorette, 
Habitrol.
---------------------------------------------------------------------------

    Given the availability of FDA-approved drugs for smoking cessation,

[[Page 2199]]

FDA believes that consumers are particularly susceptible to confusion 
where products made or derived from tobacco that otherwise appear to be 
products intended for recreational use make claims related to quitting 
smoking. Therefore, FDA considers claims related to smoking cessation 
to require careful scrutiny. Where products making claims related to 
quitting smoking also attempt to disclaim that use in some way, FDA 
intends to view such disclaimers skeptically because of the likelihood 
of consumer confusion. In most cases, as discussed in more detail in 
response to Comment 13, FDA does not believe that disclaimers will 
sufficiently mitigate consumer confusion due to the product's claimed 
therapeutic benefit.
    FDA will treat several other categories of claims for products made 
or derived from tobacco as evidence of intended use that brings the 
products within the disease prong of the drug/device definition. These 
categories of claims are discussed further in section IV, Description 
of the Final Rule). We note that sections 911(c) and 918 of the FD&C 
Act (21 U.S.C. 387k(c) and 387r), as amended by the Tobacco Control 
Act, contemplate that products intended for the treatment of tobacco 
dependence and for relapse prevention, among other things, may be 
subject to FDA's drug/device jurisdiction.
2. Distinction Between Modified Risk Claims and Claims That Are 
Evidence of Disease-Prong Intended Uses
    With this final rule, FDA is also clarifying the relationship 
between FDA's regulation of a certain category of tobacco products--
modified risk tobacco products (MRTPs)--and FDA's regulation of medical 
products that are intended to mitigate disease. MRTPs are tobacco 
products that are sold or distributed for use to reduce harm or the 
risk of tobacco-related disease associated with commercially marketed 
tobacco products (section 911(b)(1) of the FD&C Act). Tobacco products 
that are sold or distributed for use to reduce harm or the risk of 
tobacco-related disease associated with commercially marketed tobacco 
products means a tobacco product:
    (1) That represents in its label, labeling, or advertising, either 
implicitly or explicitly, that:
     The tobacco product presents a lower risk of tobacco-
related disease or is less harmful than one or more other commercially 
marketed tobacco products;
     the tobacco product or its smoke contains a reduced level 
of a substance or presents a reduced exposure to a substance; or
     the tobacco product or its smoke does not contain or is 
free of a substance;
    (2) That uses the descriptors ``light,'' ``mild,'' ``low,'' or 
similar descriptors in its label, labeling, or advertising; or
    (3) For which the tobacco product manufacturer has taken any action 
directed to consumers through the media or otherwise, other than by 
means of the tobacco product's label, labeling, or advertising, after 
June 22, 2009, respecting the product that would be reasonably expected 
to result in consumers believing that the tobacco product or its smoke 
may present a lower risk of disease or is less harmful than one or more 
commercially marketed tobacco products, or presents a reduced exposure 
to, or does not contain or is free of, a substance or substances.
    See section 911(b)(2) of the FD&C Act.\11\
---------------------------------------------------------------------------

    \11\ No smokeless tobacco product shall be considered to be sold 
or distributed for use to reduce harm or the risk of tobacco-related 
disease solely because its label, labeling, or advertising uses the 
following phrases: ``smokeless tobacco,'' ``smokeless tobacco 
product,'' ``not consumed by smoking,'' ``does not produce smoke,'' 
``smokefree,'' ``smoke-free,'' ``without smoke,'' ``no smoke,'' or 
``not smoke'' (section 911(b)(2)(C) of the FD&C Act).
---------------------------------------------------------------------------

    Because MRTPs have the potential to be marketed as less harmful 
than other tobacco products, including as presenting a lower risk of 
tobacco-related disease than another tobacco product, FDA recognizes 
that there might be questions about how these products relate to FDA's 
medical product jurisdiction over products made or derived from tobacco 
that are intended for use in disease mitigation and prevention. MRTPs 
may have the ultimate effect of lowering disease risk for users who 
would otherwise use another, more harmful tobacco product. However, an 
important distinction between MRTPs and medical products is that, while 
medical products approved/cleared for disease mitigation or prevention 
act affirmatively to combat a disease or health condition, MRTPs 
present relatively less risk of disease (e.g., by presenting reduced 
exposure to harmful constituents relative to another tobacco product), 
but do not affirmatively act to mitigate, prevent, or otherwise treat 
disease. In addition, while medical products approved for disease 
mitigation are determined to be both safe and effective for their 
approved use, MRTPs are reviewed based, in part, on a ``benefit the 
health of the population as a whole'' standard, and like other tobacco 
products, still expose users to inherent (if reduced) harms.
    For purposes of illustration, claims of modified risk might include 
claims like ``contains less nicotine than [tobacco product X]'', 
``using [MRTP] reduces your risk of lung cancer compared to using 
[tobacco product X]'', and ``lower level of nitrosamines than other 
smokeless tobacco products.'' In contrast, a claim that a product 
``inhibits the progression of disease in adult patients with chronic 
obstructive pulmonary disease'' is evidence of intended uses that would 
bring the product within drug/device jurisdiction.

B. Comments and Responses Regarding Modified Risk Tobacco Products

    (Comment 4) At least one comment remarked that research studies and 
public opinion may come to reflect that a tobacco product appears to 
have properties similar to those of a medical drug or MRTP. The comment 
asserted that acceptance of these properties by the scientific and 
medical community or by the public should not subject the product to 
regulation as a medical product or MRTP in the absence of any specific 
claims by the manufacturer.
    (Response) As explained in this final rule, with certain 
exceptions, products made or derived from tobacco are subject to 
regulation as medical products if they are distributed for an intended 
use that falls within the FD&C Act's drug/device definitions, and the 
Agency may look to any relevant source to determine intended use. To 
the extent this comment suggests that manufacturer claims are always 
necessary to establish a medical product's intended use, FDA disagrees. 
As discussed at various points in this final rule (for example, in 
response to Comment 18), FDA is not bound by the manufacturer or 
distributor's subjective claims of intent, but rather can consider 
objective evidence, which may include a variety of direct and 
circumstantial evidence. Nevertheless, FDA agrees with the comment that 
neither the opinions of the scientific and medical communities nor 
public opinion considered alone should dictate when a product made or 
derived from tobacco is regulated as a medical product or MRTP. In 
general, FDA would not regard a manufacturer as intending a medical use 
for a product made or derived from tobacco based solely on study 
findings or widespread belief that the product appears to have 
properties similar to those of a medical product. Similarly, FDA would 
not regard a manufacturer of a product made or derived from tobacco as 
selling or distributing a product for use to reduce harm or the risk of 
tobacco-related disease based solely on study findings

[[Page 2200]]

or widespread belief that the product appears to have properties 
similar to those of an MRTP.

C. Intended Uses For Products Made or Derived From Tobacco That Bring 
Products Within the Structure/Function Prong

    As discussed in section I.B, the drug/device definitions in the 
FD&C Act include articles ``intended to affect the structure or any 
function of the body,'' and FDA's assertion of jurisdiction over 
cigarettes and smokeless tobacco in 1996 was predicated on the 
pharmacological effects of nicotine on the structure or function of the 
body. In addition, as explained previously, the Court in Brown & 
Williamson rejected that assertion of jurisdiction, finding that 
Congress did not intend for FDA to have jurisdiction over cigarettes 
``as customarily marketed.''
    Based on the Brown & Williamson holding and the Sottera court's 
application of that holding to all tobacco products, it is necessary to 
determine whether the intended use of a product made or derived from 
tobacco was the subject of claimed structure or function effects for 
tobacco products ``as customarily marketed''--and therefore outside of 
FDA's drug/device jurisdiction. FDA believes the appropriate inquiry is 
whether the intended structure/function effects relate to effects of 
nicotine that were commonly and legally claimed in the marketing of 
cigarettes and smokeless tobacco products prior to the date of the 
Supreme Court's decision in Brown & Williamson (March 21, 2000).
    For example, as discussed in the 1996 rulemaking, claims related to 
satisfaction, pleasure, enjoyment, and refreshment are euphemisms for 
the delivery of a pharmacologically active dose of nicotine and thus 
relate to effects on the structure or function of the body (61 FR 44396 
at 45101 and 45175-45178). Nonetheless, FDA does not consider these 
tobacco satisfaction and enjoyment claims to bring products within its 
drug and device regulatory authority because these are structure/
function claims related to the effects of nicotine and were commonly 
and legally made before March 21, 2000. Similarly, FDA does not 
consider claims suggesting that a tobacco product provides an 
alternative way of obtaining the effects of nicotine, or that a tobacco 
product will provide the same effects as another tobacco product--such 
as ``satisfying smoking alternative,'' ``provides all the pleasure of 
smoking,'' ``get your nicotine fix,'' or ``provides smokers the same 
delight, physical and emotional feelings''--to bring a tobacco product 
within its drug and device authority.
    The Brown & Williamson and Sottera decisions do not reach the issue 
of intended uses that fall outside the disease prong of the drug/device 
definition and that are outside the area of ``customarily marketed'' 
tobacco product claims. FDA believes certain structure/function 
intended uses for products made or derived from tobacco continue to 
fall within our drug/device regulatory authority. FDA believes these 
structure/function intended uses fall into two main categories: (1) 
Intended uses that are unrelated to the pharmacological effects of 
nicotine and (2) intended uses that were not the subject of claims that 
were commonly and legally made for cigarettes and smokeless tobacco 
products (i.e., the products addressed in the 1996 rule) prior to the 
Supreme Court's decision in Brown & Williamson. Thus, to the extent 
manufacturers intend products made or derived from tobacco to be used 
to affect the structure or function of the body in any way that is not 
related to the effects of nicotine that were commonly and legally 
claimed in the marketing of cigarettes and smokeless tobacco products 
prior to March 21, 2000, FDA would consider these intended uses to 
remain within its drug/device jurisdiction under the final rule. For 
example, FDA's 1996 rulemaking identified ``sedation,'' 
``stimulation,'' and ``weight loss'' as intended structure/function 
effects related to nicotine in cigarettes and smokeless tobacco 
products (61 FR 44396 at 44667; see also Brown & Williamson, 529 U.S. 
at 127). These structure/function effects are similar to ``relieve 
tension,'' ``restore mental alertness,'' and ``promote weight loss,'' 
which the proposed rule gave as examples of potential intended 
structure/function effects (80 FR 57756 at 57760; see also Comment 7 in 
this document). But absent evidence that ``sedation,'' ``stimulation,'' 
or ``weight loss'' is both a structure/function effect related to 
nicotine and was commonly and legally claimed in marketing cigarettes 
or smokeless tobacco products prior to March 21, 2000, FDA will 
consider products made or derived from tobacco, whose intended use 
includes such structure/function effects, to be medical products.
    Similarly, ``maintain memory''--another example of a potential 
intended structure/function effect mentioned in the proposed rule (80 
FR 57756 at 57760)--was (as FDA's 1996 rulemaking observed) a 
pharmacological effect that Philip Morris researchers attributed to 
nicotine and that R.J. Reynolds Tobacco asserted as a ``benefit'' in 
court filings (61 FR 44396 at 44857-44858 and 45029). But once again, 
absent evidence that ``maintaining memory'' is both a structure/
function effect related to nicotine, and was commonly and legally 
claimed in marketing cigarettes or smokeless tobacco products prior to 
March 21, 2000, FDA will consider products made or derived from 
tobacco, intended for use to ``maintain memory,'' to be medical 
products.
    Different facts but a similar analysis apply to the proposed rule's 
other examples of potential intended structure/function effects, 
``maintain healthy lung function'' and ``support the immune system.'' 
(80 FR 57760). In contrast to its findings for ``stimulation,'' 
``sedation,'' and ``weight loss,'' (61 FR 44396 at 44667), FDA's 1996 
rulemaking did not identify ``maintain healthy lung function'' or 
``support the immune system'' as intended structure/function effects of 
cigarettes or smokeless tobacco products. But as with those other 
potential intended uses, absent evidence that ``maintaining healthy 
lung function'' or ``supporting the immune system'' are both structure/
function effects related to nicotine, and were commonly claimed in 
marketing cigarettes or smokeless tobacco products prior to March 21, 
2000, FDA will consider products made or derived from tobacco, intended 
for use to achieve such structure/function effects, to be medical 
products.
    FDA believes that it is important to recognize structure/function 
intended uses that were not commonly and legally claimed in the 
marketing of cigarettes and smokeless tobacco products prior to the 
decision in Brown & Williamson. Structure/function intended uses are a 
longstanding and important aspect of FDA's medical product 
jurisdiction, grounded in the statutory definitions of ``drug'' and 
``device'' in the FD&C Act. We recognize that products made or derived 
from tobacco are unique because of the regulatory regime for tobacco 
products under the FD&C Act, and that some products made or derived 
from tobacco making certain structure/function claims are now outside 
our drug/device jurisdiction. However, we believe it is consistent with 
the FD&C Act, case law, and our public health mission to determine that 
medical products include products made or derived from tobacco whose 
intended use includes effects on the structure or function of the body 
that are distinct from the pharmacological effects related to nicotine 
that were commonly and legally claimed before March 21, 2000.

[[Page 2201]]

    FDA believes this final rule will provide clarity to manufacturers 
about how products made or derived from tobacco will be regulated if 
they are marketed or distributed for certain intended uses. This 
clarification will allow regulated industry to plan accordingly during 
the product development and postmarketing phases and will help 
researchers understand the applicable regulatory requirements 
associated with the investigational use of products made or derived 
from tobacco.
    In addition, we believe this final rule will help to avoid consumer 
confusion about which products made or derived from tobacco are 
intended for a medical use (i.e., as a drug/device) versus for a 
recreational use. Specifically, FDA wishes to avoid situations where 
products intended to be sold as tobacco products are marketed with the 
same claims as products sold as drugs or devices.

D. Comments and Responses Regarding Brown & Williamson and Sottera

    (Comment 5) At least one comment agreed with FDA that the Brown & 
Williamson and Sottera rulings did not define the phrases ``as 
customarily marketed'' or ``claims of therapeutic benefit,'' leaving 
the Agency with some discretion as to what claims fall within each 
category when the distinction is not clear under existing precedent.
    (Response) FDA agrees that the lack of definitions of the terms 
``customarily marketed'' and ``claims of therapeutic benefit'' as they 
apply to products made or derived from tobacco in the relevant case law 
has created ambiguity and resulted in confusion among regulated 
industry, which has led FDA to promulgate this rule. Specifically, in 
the absence of clear judicial direction about what might constitute 
``claims of therapeutic benefit'' and the relationship between tobacco 
products ``as customarily marketed'' and the structure/function prong 
of the drug/device definitions, the Agency believes it is important to 
clarify its statutory interpretations of the drug/device definitions 
with respect to products made or derived from tobacco in light of these 
terms used by the courts.
    (Comment 6) Several comments supported FDA's proposal to treat 
satisfaction, smoking alternative, and nicotine fix claims as tobacco 
product claims. However, these comments assert that all products 
derived from tobacco that lack express therapeutic claims must be 
regulated as tobacco products. These comments maintained that FDA's 
proposed approach--which provides that some structure/function claims 
will cause products derived from tobacco to be regulated as drugs, 
devices, or combination products--is inconsistent with the Brown & 
Williamson and Sottera decisions.
    Specifically, the comments argued that neither decision ``indicates 
that `customarily marketed' means anything other than `not marketed 
with therapeutic claims'.'' They maintained that the Sottera court 
``explicitly concluded that the `better reading' of Brown & Williamson 
was that it deprives FDA of authority to regulate under the FD&C Act 
any tobacco products marketed `without claims of therapeutic effect,' 
viewing such products as `customarily marketed.' '' Accordingly, the 
comments contended that the courts saw only two categories of tobacco 
products--products marketed with or without therapeutic claims. The 
comments asked that FDA clarify that it lacks authority to regulate any 
product made or derived from tobacco as a drug or device absent express 
therapeutic claims.
    (Response) FDA disagrees with these comments and declines to adopt 
their overly narrow reading of Brown & Williamson and Sottera. First, 
Brown & Williamson provides no support for the comments' assertion that 
therapeutic claims must be express for a product to be subject to FDA's 
drug/device jurisdiction. The plaintiffs in Brown & Williamson made 
this very argument, and the dissenting opinion noted that the FD&C Act 
``does not use the word `claimed'; it uses the word `intended'.'' See 
Brown & Williamson, 529 U.S. 120, 170 (2000) (dissenting opinion). The 
majority specifically declined to resolve the question. See Brown & 
Williamson, 529 U.S. 120, 132 (2000).
    In addition, as noted in section I.C of the proposed rule, as well 
as section I.D, neither the Brown & Williamson nor the Sottera 
decisions defined the term ``customarily marketed.'' Although the court 
in Sottera did equate the concept of ``therapeutic claims'' with the 
disease prong of the drug and device definitions, there was no such 
equating of the term ``customarily marketed'' with the structure/
function prong of these definitions. In fact, the term ``customarily 
marketed'' itself suggests that the term has some meaning independent 
of its relationship to the structure/function prong of the drug and 
device definitions. If the Supreme Court had wanted any structure/
function claim to exclude a product made or derived from tobacco from 
FDA's drug/device jurisdiction, it could have said so. The structure of 
section 201(rr) of the FD&C Act, added by the Tobacco Control Act, 
further supports this interpretation. Following the Supreme Court's 
decision in Brown & Williamson, Congress enacted the Tobacco Control 
Act to give FDA explicit authority to regulate tobacco products. Under 
section 201(rr)(2), the term ``tobacco product'' excludes articles that 
are drugs under section 201(g)(1) and devices under section 201(h) of 
the FD&C Act. This statutory carve-out includes the structure/function 
prong of the drug/device definitions.
    Having given FDA regulatory authority over tobacco products, if 
Congress thought that products made or derived from tobacco should 
never be regulated as drugs or devices under the structure/function 
prong of the drug or device definitions in the wake of Brown & 
Williamson, presumably Congress would have written section 201(rr)(2) 
of the FD&C Act differently. The better reading is that Congress 
recognized that products made or derived from tobacco as ``customarily 
marketed'' would be regulated as tobacco products under the Tobacco 
Control Act, but that products made or derived from tobacco meeting the 
drug/device definitions (including the structure/function prong, to the 
extent such products were not ``customarily marketed'') would continue 
to be regulated as drugs or devices.
    (Comment 7) At least one comment disagreed with some of the 
examples in the proposed rule of structure/function intended uses that 
FDA believes remain within its drug/device jurisdiction under the 
proposal. Specifically, the comment argued that claims about nicotine's 
stimulant and weight-loss structure/function effects ``remain 
permissible `tobacco product' claims,'' because FDA's 1996 rulemaking 
found that stimulant and weight-loss structure/function effects were 
among the intended uses of cigarettes and smokeless tobacco products 
(citing 61 FR 44396 at 44630, 44632).
    (Response) FDA disagrees with this comment. In the 1996 rulemaking, 
FDA found that, in addition to causing and sustaining addiction, 
nicotine in cigarettes and smokeless tobacco causes other psychoactive 
(mood-altering) effects, including tranquilization and stimulation; and 
that nicotine in cigarettes and smokeless tobacco controls weight (61 
FR 44396 at 44630). The rulemaking further found that these were 
intended structure/function effects for cigarettes and smokeless 
tobacco products (id. at 44632). But the central holding of Brown & 
Williamson was that ``customarily marketed'' tobacco products were not 
subject to FDA's medical product authority, even

[[Page 2202]]

assuming that such products could be considered to have the intended 
structure/function effects that FDA attributed to them if their 
manufacturers and sellers did not claim such effects (529 U.S. at 131-
32). As discussed in section I.D, this current rulemaking applies Brown 
& Williamson, as relevant here, by looking to marketing claims for 
structure/function effects that were commonly and legally made for 
``customarily marketed'' cigarettes and smokeless tobacco products 
prior to the date the Brown & Williamson decision was issued. To the 
extent the comment read the examples ``relieve tension'' and ``restore 
mental alertness'' as stimulant intended uses, FDA does not believe 
that they are structure/function intended uses relating to effects of 
nicotine that were commonly and legally claimed in the marketing of 
cigarettes and smokeless tobacco products prior to March 21, 2000. 
Similarly, FDA does not believe that ``promotes weight loss'' was a 
``customarily marketed'' tobacco product claim within the meaning of 
Brown & Williamson. Section 1100.5 is written such that, if a 
particular intended structure/function effect for a product made or 
derived from tobacco is related to the effects of nicotine commonly and 
legally claimed prior to March 21, 2000, that product would not be 
subject to FDA's drug/device jurisdiction. FDA expects that in some 
cases this would be a fact-specific, case-by-case inquiry.
    Sponsors should also keep in mind that, regardless of whether a 
product is regulated as a tobacco product or a medical product, the 
claims made for the product would misbrand the product and subject 
manufacturers to enforcement action if the claims are false or 
misleading in any particular, including if the claims are 
unsubstantiated. Thus, if a particular claim related to the effects of 
nicotine was used in the marketing of a tobacco product prior to March 
21, 2000, but that claim is not substantiated by appropriate evidence, 
the use of such a claim in current labeling or advertising would likely 
misbrand the product. In addition, both medical products and tobacco 
products would be subject to enforcement action under section 201(n) of 
the FD&C Act if their labeling or advertising fails to reveal facts 
material in the light of the representations made or material with 
respect to consequences which may result from the use of the article to 
which the labeling or advertising relates.
    (Comment 8) Several comments argued that the proposed rule was an 
improper attempt to undermine the court's holding in Sottera with 
respect to the regulation of electronic cigarettes. These comments 
viewed the proposed rule as an attempt to regulate electronic 
cigarettes as drugs, and characterized it as an effort to bypass the 
D.C. Circuit's ruling in Sottera. They also suggested that Sottera made 
a categorical determination regarding the intended use of electronic 
cigarettes generally, and maintained that FDA declined to appeal the 
D.C. Circuit's decision and instead represented that it intended to 
regulate electronic cigarettes as tobacco products.
    (Response) FDA disagrees with these comments. Although the Sottera 
decision determined that the holding in Brown & Williamson was not 
limited to cigarettes and smokeless tobacco, the court did not say that 
electronic cigarettes could never be regulated as drugs or devices. 
Rather, the court held that FDA can ``regulate tobacco products 
marketed for therapeutic purposes under [the FD&C Act's drug/device 
provisions],'' and observed that ``the FDA may establish that NJOY does 
in fact make therapeutic claims regarding its electronic cigarettes.'' 
See Sottera, 627 F.3d at 899. The rule FDA issues here clarifies the 
circumstances under which a product made or derived from tobacco would 
be regulated as a drug, device, or combination product, and the 
circumstances under which it would be regulated as a tobacco product. 
Manufacturers are free to choose how they would like to market products 
made or derived from tobacco, but do so in the context of the 
regulatory framework set forth in the rule.
    Moreover, the comments appear to misunderstand the nature of 
determinations of intended use with respect to FDA-regulated products. 
As discussed elsewhere in this document, intended use is a case-by-
case, fact-specific inquiry in which the Agency may look to any 
relevant source of evidence, including a variety of direct and 
circumstantial evidence. See, e.g., Response to Comment 18 in section 
IV.C. Intended use is not determined on a categorical basis based on 
product type. Finally, in deciding not to petition for certiorari from 
the D.C. Circuit's decision in Sottera, FDA did not state or signal 
that it intended to regulate electronic cigarettes as tobacco products 
under all circumstances. Rather, in the wake of the Sottera decision, 
FDA issued a letter to stakeholders,\12\ noting that the Agency would 
abide by the jurisdictional lines established by Sottera, and was 
considering issuing a guidance or rulemaking regarding therapeutic 
claims. This final rule is the result of FDA's consideration of the 
issues raised by the Sottera decision and clarifies FDA's 
interpretation of the statutory definitions of drug and medical device 
with respect to products made or derived from tobacco.
---------------------------------------------------------------------------

    \12\ See http://www.fda.gov/newsevents/publichealthfocus/ucm252360.htm.
---------------------------------------------------------------------------

    (Comment 9) Several comments asserted that claims that use 
euphemisms for the delivery of a pharmacologically active dose of 
nicotine, or state that a tobacco product provides an alternative way 
of obtaining the effects of nicotine or will provide the same effects 
as another tobacco product, do not fall within FDA's medical product 
authority. Four comments took the opposite view. Three of these latter 
comments remarked that excluding such claims from FDA's medical product 
authority would authorize manufacturers to continue using claims that 
were found to be fraudulent and deceptive by the U.S. District Court 
for the District of Columbia in United States v. Philip Morris USA 
Inc., 449 F. Supp. 2d 1 (D.D.C. 2006). These comments asserted that 
claims suggesting a product made or derived from tobacco provides 
``satisfaction,'' a ``nicotine fix,'' or ``pleasure'' are claims about 
the pharmacological effects of nicotine, and suggested that products 
bearing such claims should be regulated as medical products. Another 
comment suggested that FDA treat such claims as evidence of an 
article's intended use as a drug.
    (Response) The Agency disagrees with any suggestion that FDA is 
authorizing fraudulent claims. The purpose of this rule is to increase 
clarity regarding the types of intended uses and supporting evidence 
that make a product made or derived from tobacco subject to regulation 
as a tobacco product versus as a drug, device, or combination product. 
Regardless of the outcome of that jurisdictional question, the FD&C Act 
prohibits false and misleading claims in FDA-regulated labeling and 
advertising (see sections 502(a), 502(n), 502(r), 903(a)(1), and 
903(a)(7) (21 U.S.C. 352(a), 352(n), 352(r), 387c(a)(1), and 
387c(a)(7)). Similarly, in concluding that certain claims involving 
``satisfaction,'' ``pleasure,'' ``enjoyment,'' and ``refreshment'' are 
claims about the pharmacological effects of nicotine that were commonly 
and legally made prior to March 21, 2000, FDA is not authorizing such 
claims. Rather, the Agency is explaining in more detail its 
understanding of how the D.C. Circuit's interpretation of the Tobacco 
Control Act in Sottera affects the jurisdictional determination. As 
documented in the annex to the 1996 rule, products made

[[Page 2203]]

or derived from tobacco were customarily marketed at that time for the 
pharmacological effects of nicotine, using phrases such as ``smoking 
pleasure'' and ``satisfaction.'' \13\ Such terms, as discussed in 
section II.C, are recognized euphemisms for the delivery of a 
pharmacologically active dose of nicotine to satisfy addiction--an 
intended structure/function effect--and were commonly and legally made 
claims for customarily marketed cigarettes and smokeless tobacco 
products prior to the date of the Brown & Williamson decision. Thus, 
FDA continues to believe that Brown & Williamson, as extended and 
applied to the Tobacco Control Act by Sottera, precludes the Agency 
from regulating products made or derived from tobacco as medical 
products on the basis of such claims.
---------------------------------------------------------------------------

    \13\ See 61 FR 44619 at 44648, August 28, 1996.
---------------------------------------------------------------------------

E. Comments and Responses Regarding Consumer Confusion

    (Comment 10) Comments expressed different opinions about the 
intended uses of products made or derived from tobacco, primarily e-
cigarettes, and whether consumers are able to distinguish products that 
are intended for medical use from products marketed for other uses. 
Several comments asserted that e-cigarettes are not intended for use as 
smoking cessation aids, whereas many other comments asserted that e-
cigarettes are vital smoking cessation aids. One comment averred that 
there is no evidence that consumers are confusing e-cigarette products 
with products that are marketed, labeled, and sold as medical products. 
Two other comments, however, cited studies that purportedly show many 
consumers believe e-cigarettes and smokeless tobacco products are 
effective smoking cessation aids.
    (Response) FDA continues to believe that there is consumer 
confusion about the intended uses of marketed products made or derived 
from tobacco. Evidence that at least some consumers are confused about 
the intended uses of products can be found in the comments themselves. 
We received many comments from individuals who began using e-cigarettes 
because they believed that e-cigarettes would help them quit smoking. 
Moreover, as noted in two comments, studies have shown that many 
consumers are using e-cigarettes to attempt to quit smoking (Ref. 2) 
despite the fact that no e-cigarette has been approved for use as a 
smoking cessation aid. We believe that the rule will help to mitigate 
this confusion and help ensure that consumers do not mistakenly use 
tobacco products, which are inherently dangerous, for medical uses.
    (Comment 11) Several comments expressed concern that this 
regulation would increase consumer confusion by not allowing ENDS 
manufacturers to communicate truthful claims to their customers. These 
comments believed that the regulation would harm, rather than protect 
public health. Comments also expressed concern that ENDS manufacturers 
would not be able to state that e-cigarettes could be used for smoking 
cessation, and ENDS manufacturers would be forced to deceptively market 
their products. Several comments discussed FDA's authority under 
section 911 of the FD&C Act to require premarket authorization of 
modified risk tobacco products. Some commenters urged FDA to implement 
section 911 in a manner that does not restrict truthful and non-
misleading speech.
    (Response) FDA disagrees with concerns that ENDS manufacturers will 
not be able to make claims that accurately represent their products' 
intended uses. Manufacturers are free to decide how they would like to 
market their products, but must meet the appropriate statutory and 
regulatory standards governing the regulatory pathway they choose. 
Additionally, the proposed rule would not force e-vapor manufacturers 
to ``deceptively'' market their products or risk ``being categorized as 
unapproved medical products and forced off the market.'' FDA believes 
that manufacturers of products made or derived from tobacco, including 
e-vapor manufacturers, could make many types of claims under the rule 
that would subject them only to tobacco product jurisdiction; the 
preamble to the proposed rule provides examples of such tobacco product 
claims, but is not intended to be an exhaustive list. Moreover, section 
911 of the FD&C Act allows manufacturers to make truthful and non-
misleading modified risk claims with appropriate authorization. 
Manufacturers that have data to substantiate modified risk claims for a 
particular product can submit an MRTP application so that FDA can 
determine whether the product meets the statutory standard and if 
appropriate, can issue an order authorizing it to be marketed as an 
MRTP.
    FDA continues to believe that smoking cessation claims require 
close examination. FDA has long considered claims related to smoking 
cessation in the context of curing or treating nicotine addiction to be 
evidence of intended uses that confer drug or device jurisdiction. 
Manufacturers that have data to substantiate cessation claims for a 
particular product can submit an NDA so that FDA can determine whether 
the product meets the statutory standard and can approve the 
application, if appropriate. The rule's treatment of smoking cessation 
claims as generally suggestive of a therapeutic purpose means that 
products marketed with such claims would generally be regulated as 
medical products. Treating these products as medical products will help 
assure that such claims are supported by data demonstrating that a 
product is safe and effective for this intended use. Otherwise, 
consumers may attempt to quit smoking with unproven products, 
threatening both individual consumers' health and the public health 
generally.
    (Comment 12) At least one comment suggested that a disclaimer 
stating that FDA has not approved e-cigarettes for medical use would be 
sufficient to mitigate any confusion over the intended use of such 
products. In contrast, several comments argued that disclaimers are 
insufficient to mitigate any confusion over whether a product made or 
derived from tobacco is intended for medical use. One of these comments 
suggested that disclaimers would foster confusion because they often 
contain statements that conflict with claims that are made elsewhere in 
the marketing materials and labeling for e-cigarettes and other 
products.
    (Response) FDA does not believe that disclaimers will be sufficient 
in most cases to mitigate consumer confusion about whether a product 
made or derived from tobacco is intended for medical use. Studies have 
shown that disclaimers are frequently ineffective and can actually 
increase confusion for consumers (Refs. 3 and 4). Thus, where products 
making claims related to quitting smoking also attempt to disclaim that 
use in some way, FDA intends to view such disclaimers skeptically.
    (Comment 13) Several comments suggested that excluding claims that 
are euphemisms for the delivery of a pharmacologically active dose of 
nicotine and those that suggest a tobacco product provides an 
alternative way of obtaining the effects of nicotine from regulation 
under the Agency's drug/device authorities would create consumer 
confusion because such claims may not be distinguishable from drug or 
device claims related to the symptoms of nicotine addiction or could be 
perceived as modified risk claims.
    (Response) As stated previously in this section, FDA has determined 
that

[[Page 2204]]

the types of claims described in these comments generally do not bring 
products made or derived from tobacco within its drug and device 
authority. We acknowledge that there are circumstances in which 
consumers might be confused by such claims. A consumer might be 
confused about a product's intended use, for example, if a ``satisfying 
smoking alternative'' claim is accompanied by other text or images 
indicating that the product can help smokers reduce withdrawal symptoms 
associated with quitting smoking. In that case, the product may be 
subject to regulation as a drug or device. But as a general matter, FDA 
does not expect claims that use euphemisms for the delivery of a 
pharmacologically active dose of nicotine or suggest that a tobacco 
product provides an alternative way of obtaining the effects of 
nicotine to cause much confusion. FDA will continue to monitor consumer 
perception and will take appropriate regulatory action if evidence 
accumulates showing that consumers are confused by such claims.

F. Changes to Existing ``Intended Use'' Regulations

    FDA is also making changes to Sec. Sec.  201.128 and 801.4. First, 
the final rule inserts a reference to Sec.  1100.5 to clarify the 
interplay between these regulations and the final rule. Second, as 
discussed previously, the Agency does not, absent extraordinary 
circumstances, regard a firm as intending an unapproved new use for an 
approved or cleared medical product based solely on that firm's 
knowledge that the product was being prescribed or used by doctors for 
such use (see Ref. 1). Accordingly, FDA is taking this opportunity to 
amend Sec. Sec.  201.128 and 801.4 to better reflect FDA's 
interpretation and application of these regulations. These changes do 
not reflect a change in FDA's approach regarding evidence of intended 
use for drugs and devices. These clarifying changes to the intended use 
regulations apply to drugs and devices generally, and not just to 
products made or derived from tobacco and intended for human 
consumption.

III. Legal Authority

    Among the provisions that provide authority for this final rule are 
sections 201, 503(g), and 701(a) of the FD&C Act (21 U.S.C. 321, 
353(g), 371(a)). Section 201 of the FD&C Act defines ``drug,'' 
``device,'' and ``tobacco product'' (subsections (g)(1), (h), and 
(rr)(1) to (rr)(2)), and section 503(g) of the FD&C Act provides that 
combination products are those ``that constitute a combination of a 
drug, device, or biological product.'' Under section 701(a) of the FD&C 
Act, FDA has authority to issue regulations for the efficient 
enforcement of the FD&C Act. FDA believes this rule will assist the 
Agency with efficient enforcement of the FD&C Act because it provides 
increased clarity to stakeholders, particularly regulated entities, 
regarding FDA's interpretation of which regulatory framework will apply 
to particular products and will help consumers differentiate between 
products that are intended for medical use and products marketed for 
other uses.
    FDA regulates the manufacture, sale, and distribution of drugs, 
devices, combination products, and tobacco products under the authority 
of the FD&C Act. Although the regulatory pathways for each product 
category differ, each product category is subject to similar types of 
regulatory requirements. For example, FDA's regulatory authority for 
drugs, devices, combination products, and tobacco products includes 
authority to review and authorize the marketing of new products as well 
as to oversee product labeling and advertising. Thus, whether a product 
meets the definition of a drug, device, or tobacco product under the 
FD&C Act and this final regulation, the manufacture, sale, and 
distribution of the product are subject to the applicable requirements 
of the FD&C Act.
    (Comment 14) At least one comment stated that the proposed rule 
exceeds FDA's authority.
    (Response) FDA disagrees. As described in the proposed rule, FDA 
has the authority to regulate as a medical product any product that 
meets the definition of drug, device, or combination product in the 
FD&C Act, including cigarettes and other tobacco-derived products 
unless their intended use was the subject of claimed structure/function 
effects of nicotine commonly and legally claimed in the marketing of 
cigarettes and smokeless tobacco products prior to March 21, 2000. FDA 
also has tobacco product jurisdiction over all other products made or 
derived from tobacco intended for human consumption. The final rule 
seeks to clarify how products containing nicotine derived from tobacco 
will be regulated.

IV. Description of the Final Rule

A. Exclusion From Tobacco Product Regulation (Sec.  1100.5)

    As described in section II, the goal of this final rule is to 
provide clarity regarding the types of intended uses of products made 
or derived from tobacco that may fall within the drug/device 
definitions and therefore cause those products to be regulated as 
medical products under the FD&C Act. In describing these intended uses, 
the final rule aims to assist regulated entities in the research and 
development of products made or derived from tobacco by clarifying 
which regulatory framework (i.e., the drug/device frameworks or the 
tobacco framework) will apply to particular products based on their 
intended use. The final rule is also intended to reduce consumer 
confusion regarding which products are intended for medical use (i.e., 
as a drug, device, or combination product) and which may be marketed 
for recreational or other purposes. The final rule reflects the legal 
and regulatory considerations discussed in sections I and II, including 
the Brown & Williamson and Sottera holdings. Finally, the final rule 
amends the existing intended use regulations for drugs and devices by 
inserting in Sec. Sec.  201.128 and 801.4 a reference to Sec.  1100.5 
to clarify the interplay among these regulations and this final rule.
    The codified language states the circumstances in which a product 
made or derived from tobacco would be excluded from the definition of 
``tobacco product'' and be subject to regulation as a drug, device, or 
combination product. Under the final rule, this exclusion could apply 
in two circumstances: (1) If the product is intended for use in the 
diagnosis of disease or other conditions, or in the cure, mitigation, 
treatment, or prevention of disease or (2) if the product is intended 
to affect the structure or any function of the body in any way that is 
different from effects related to nicotine that were commonly and 
legally claimed in the marketing of cigarettes and smokeless tobacco 
products prior to March 21, 2000.
    Conceptually, the codified language follows the disease prong and 
the structure/function prong (with certain limitations) of the drug and 
device definitions.
1. Disease Prong
    Section 1100.5(a) follows the disease prong. The paragraph 
elaborates on the statutory language for the disease prong by 
describing several categories of intended uses that would cause a 
product made or derived from tobacco to be regulated as a medical 
product. The categories identified in Sec.  1100.5(a) are not intended 
to constitute an exhaustive list; nor are these categories necessarily 
mutually exclusive. In addition, these categories are intended to 
capture concepts, rather than to suggest that the use (or omission) of

[[Page 2205]]

particular words is dispositive with respect to FDA's medical product 
jurisdiction. These categories are included as examples of types of 
intended uses that we believe are particularly relevant for products 
made or derived from tobacco and that fall within the disease prong.
2. Structure/Function Prong
    Section 1100.5(b) follows the structure/function prong, but with 
some changes to reflect the court decisions in Brown & Williamson and 
Sottera. Specifically, the language in Sec.  1100.5(b) beginning ``in 
any way that is different from . . . .'' reflects the fact that, under 
Brown & Williamson and Sottera, intended structure/function effects 
related to nicotine will not confer drug/device jurisdiction to the 
extent they reflect claims that were commonly and legally made for 
``customarily marketed'' tobacco products before the date of the Brown 
& Williamson decision. This language also references ``the marketing of 
cigarettes and smokeless tobacco products'' because these were the 
product categories considered by the Supreme Court in Brown & 
Williamson. March 21, 2000, is the date of the Supreme Court's ruling 
in Brown & Williamson.
    FDA believes that it is important to include a date limitation in 
Sec.  1100.5(b) to provide greater certainty about the universe of 
historic structure/function claims the Agency intends to consider when 
determining whether an intended use of a product made or derived from 
tobacco is different from effects related to nicotine that were 
commonly and legally claimed for ``customarily marketed'' cigarettes 
and smokeless tobacco products. This bright-line limitation also avoids 
creating a shifting standard that will cause confusion among consumers 
and regulated industry. FDA intends to look to the marketing of 
cigarettes and smokeless tobacco products prior to March 21, 2000, to 
determine the types of structure/function claims that constitute 
customary tobacco product marketing. Cigarettes and smokeless tobacco 
products provide a reasonable proxy for determining how nicotine-
related structure/function claims were conveyed in tobacco product 
marketing generally. The codified language, however, applies to all 
products made or derived from tobacco, not just cigarettes and 
smokeless tobacco.
3. Intended Use
    As noted in section I.B.2, intended use may be determined from any 
relevant source and is not based solely on claims made in a product's 
labeling or advertising materials. For purposes of illustration, 
however, claims such as ``treatment of tobacco dependence,'' ``wean 
yourself off of nicotine,'' ``for people who wish to quit smoking,'' 
``stop smoking aid,'' ``prevent relapse,'' or ``stay quit'' generally 
will bring a product within the intended uses described in Sec.  
1100.5(a).\14\
---------------------------------------------------------------------------

    \14\ These and other specific claims mentioned in this document 
are provided solely as examples. Other claims not mentioned in this 
document could also reflect an intended use described in the 
codified language. In addition, as discussed elsewhere in this 
document, FDA intends to consider the full context of claims for 
products made or derived from tobacco in making jurisdictional 
determinations.
---------------------------------------------------------------------------

    Claims such as ``to reduce withdrawal symptoms,'' ``helps reduce 
symptoms including things like [list of withdrawal symptoms]'' and 
``relieve withdrawal symptoms when you are prohibited from smoking'' 
would be associated with an intended use for relief of nicotine 
withdrawal symptoms, and would also fall within the intended uses 
described in Sec.  1100.5(a). Withdrawal symptoms that are medically 
recognized as relevant to nicotine addiction may be determined by 
reference to standard classification and diagnostic tools such as the 
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition 
(DSM-5) and the tenth revision of the International Statistical 
Classification of Diseases and Related Health Problems (ICD-10).
    Certain structure/function claims that were not commonly and 
legally made in the marketing of cigarettes and smokeless tobacco 
products before March 21, 2000, such as ``promotes weight loss,'' would 
fall within the intended uses described in Sec.  1100.5(b).
    In contrast to the examples of medical product intended use claims 
given in the previous paragraphs, certain other claims made about 
products made or derived from tobacco would not on their own create an 
intended use that falls within the codified language.\15\ For example, 
claims such as ``smoke free, spit free tobacco pleasure'' or ``full 
taste and satisfaction'' may be associated with the marketing of 
tobacco products for refreshment, satisfaction, or enjoyment (which, as 
discussed in section II.C, are recognized euphemisms for the delivery 
of a pharmacologically active dose of nicotine to satisfy addiction--an 
intended structure/function effect--and were commonly and legally made 
claims for customarily marketed cigarettes and smokeless tobacco 
products prior to the date of the Brown & Williamson decision). Claims 
such as ``great tasting tobacco satisfaction when you can't smoke,'' 
``satisfying tobacco alternative,'' or ``provides the look, feel, and 
experience of a cigarette'' may be associated with the marketing of 
tobacco products as smoking substitutes. And claims such as ``healthier 
alternative to smoking,'' ``contains less nicotine than [another 
product],'' or ``reduces your risk of lung cancer compared to 
cigarettes'' might be associated with MRTPs, as discussed in section 
II.A.2.
---------------------------------------------------------------------------

    \15\ As previously, the specific claims mentioned in this 
paragraph are provided solely as examples. Other claims not 
mentioned here could fall outside the intended uses described in 
Sec.  1100.5.
---------------------------------------------------------------------------

    For products made or derived from tobacco that are intended for 
investigational use, FDA will consider whether the product is being 
used in a clinical investigation for an intended use that brings it 
within the codified language. If it is, the product would meet the 
definition of ``investigational new drug'' in Sec.  312.3 (21 CFR 
312.3), and the clinical investigation would be subject to the 
applicable requirements in part 312 (21 CFR part 312).\16\ Products 
made or derived from tobacco that are intended for investigational use 
but that do not meet the definition of ``investigational new drug'' in 
Sec.  312.3 may be subject to regulation as investigational tobacco 
products.
---------------------------------------------------------------------------

    \16\ Note that studies performed to meet statutory requirements 
in chapter IX of the FD&C Act relating to the impact of tobacco 
products on cessation behavior are not required to be designed as 
clinical investigations subject to the investigational new drug 
application requirements in part 312. Whether a study is considered 
a clinical investigation of an ``investigational new drug'' would 
depend on the study's design and specific objectives.
---------------------------------------------------------------------------

B. Existing ``Intended Use'' Regulations (Sec. Sec.  201.128 and 801.4)

    In the proposed rule, FDA proposed certain changes to FDA's 
existing regulations describing the types of evidence that may be 
considered in determining a medical product's intended uses (see Sec.  
201.128 (drugs), Sec.  801.4 (devices)). These changes were intended to 
revise the language of the regulations to better reflect how the Agency 
applies them. As explained in the preamble to the proposed rule, these 
amendments were intended to clarify FDA's existing position on intended 
use, not to change it (80 FR 57756 at 57761). Some comments, however, 
misunderstood FDA's proposal, particularly with respect to the proposed 
deletion of the last sentence of both regulations (Sec. Sec.  201.128 
and 801.4). FDA has now determined that its clarification goals can be 
better achieved by amending the last sentence of each regulation, 
rather than deleting them.
    Accordingly, the last sentence of Sec.  201.128 is amended to 
provide that if

[[Page 2206]]

the totality of the evidence establishes that a manufacturer 
objectively intends that a drug introduced into interstate commerce by 
him is to be used for conditions, purposes, or uses other than ones for 
which it is approved (if any), he is required, in accordance with 
section 502(f) of the FD&C Act, or, as applicable, duly promulgated 
regulations exempting the drug from the requirements of section 
502(f)(1), to provide for the drug adequate labeling that accords with 
such other intended uses.
    Similarly, the last sentence of Sec.  801.4 is amended to provide 
that if the totality of the evidence establishes that a manufacturer 
objectively intends that a device introduced into interstate commerce 
by him is to be used for conditions, purposes, or uses other than ones 
for which it has been approved, cleared, granted marketing 
authorization, or is exempt from premarket notification requirements 
(if any), he is required, in accordance with section 502(f) of the FD&C 
Act, or, as applicable, duly promulgated regulations exempting the 
device from the requirements of section 502(f)(1), to provide for the 
device adequate labeling that accords with such other intended uses.
    As described in the preamble to the proposed rule, FDA's 
longstanding position is that, in determining a product's intended use, 
the Agency may look to any relevant source of evidence. This position 
has solid support in the case law (see, e.g., United States v. Storage 
Spaces Designated Nos. 8 and 49, 777 F.2d 1363, 1366 (9th Cir. 1985); 
Action on Smoking and Health v. Harris, 655 F.2d 236, 239 (D.C. Cir. 
1980); Nat'l Nutritional Foods Ass'n v. Matthews, 557 F.2d 325, 334 (2d 
Cir. 1977); United States v. Article of 216 Cartoned Bottles, ``Sudden 
Change,'' 409 F.2d 734, 739 (2d Cir. 1969); V.E. Irons, Inc. v. United 
States, 244 F.2d 34, 44 (1st Cir. 1957); Hanson v. United States, 417 
F. Supp. 30, 35 (D. Minn.), aff'd, 540 F.2d 947 (8th Cir. 1976)). This 
position is unchanged.
    In the preamble to the proposed rule, FDA also stated ``the Agency 
would not regard a firm as intending an unapproved new use for an 
approved or cleared medical product based solely on the firm's 
knowledge that such product was being prescribed or used by doctors for 
such use'' (80 FR 57756 at 57757). Health care providers prescribe or 
use approved/cleared medical products for unapproved uses when they 
judge that the unapproved use is medically appropriate for their 
individual patients.\17\ In these limited circumstances, FDA does not 
consider a firm's knowledge that a health care provider has used or 
prescribed its approved/cleared medical product for an unapproved use, 
by itself, as sufficient to establish the intended use element of a 
prohibited act related to the lack of premarket approval/clearance of 
that use or the lack of adequate directions for use.\18\ Instead, FDA 
examines all relevant evidence, which could include, among other facts, 
a manufacturer's knowledge that health care providers are prescribing 
or using its approved/cleared medical product for an unapproved use, to 
determine whether there is sufficient evidence to establish a new 
intended use.
---------------------------------------------------------------------------

    \17\ FDA generally does not seek to interfere with the exercise 
of the professional judgment of health care providers in prescribing 
or administering, for unapproved uses for individual patients, most 
legally marketed medical products. This longstanding position has 
been codified with respect to devices (see 21 U.S.C. 396). While FDA 
generally does not seek to interfere with the exercise of the 
professional judgment of veterinarians, certain unapproved uses of 
drugs in animals are not permitted and result in the drug being 
deemed unsafe under section 512 of the FD&C Act (see section 
512(a)(4) and (5) of the FD&C Act (21 U.S.C. 360b(a)(4) and (5)) and 
21 CFR part 530).
    \18\ See 21 U.S.C. 331(d), 351(f), 352(f)(1), 355(a). That 
position does not apply to products that are not already legally 
marketed as medical products for at least one use. Similarly, 
nothing in this regulation or preamble is intended to impact the 
application of 21 U.S.C. 333(e), which, subject to limited 
exceptions, penalizes anyone who ``knowingly distributes, or 
possesses with intent to distribute, human growth hormone for any 
use in humans other than the treatment of disease or other 
recognized medical conditions, where such use has been authorized by 
the Secretary of Health and Human Services under section 505 and 
pursuant to the order of a physician.'' Further, Congress or the 
Agency could promulgate other provisions regarding specific products 
or classes of medical products that recognize knowledge as 
sufficient evidence of a particular element of a prohibited act.
---------------------------------------------------------------------------

    Before FDA issued the proposed rule, some drug sponsors had 
expressed concern with the last sentence of Sec.  201.128. That 
sentence provided, ``if a manufacturer knows, or has knowledge of facts 
that would give him notice, that a drug introduced into interstate 
commerce by him is to be used for conditions, purposes, or uses other 
than the ones for which he offers it, he is required to provide 
adequate labeling for such a drug which accords with such other uses.'' 
(Section 801.4 contains comparable language.) They asserted that, 
literally read, this sentence would require that, whenever a 
manufacturer knew that its approved drug was being prescribed for an 
unapproved use, it would be required to alter the labeling of a drug to 
provide adequate directions for an off-label use. They further asserted 
that this addition to FDA-approved labeling would transform the drug 
into a new drug that cannot be sold without first obtaining approval of 
a supplemental new drug application pursuant to 21 U.S.C. 321(p) and 
355(a). From this they concluded that, under the last sentence of Sec.  
201.128, a manufacturer's mere knowledge of an unapproved use of its 
approved drug automatically triggers requirements for new labeling that 
in turn render distribution of that approved product unlawful without 
approval of a supplemental NDA.
    In the proposed rule, the proposed deletion of the last sentence of 
Sec. Sec.  201.128 and 801.4 was intended to clarify the following: 
Where a manufacturer is distributing an approved or cleared medical 
product, evidence that the manufacturer knows that health care 
providers are prescribing or using that approved or cleared medical 
product for an unapproved use would not, by itself, automatically 
trigger obligations for the manufacturer to provide labeling for the 
uses for which the health care providers are prescribing or using the 
product.
    FDA's clarification of its position and proposed deletion of the 
last sentence of these regulations in the proposed rule did not suggest 
that FDA sought to otherwise narrow the scope of evidence of intended 
use that FDA may consider. However, some of the comments misunderstood 
the proposal. For example, some comments asserted--incorrectly--that 
FDA intended to eliminate manufacturer knowledge altogether as a source 
of evidence of intended use.
    FDA has determined that its clarification goals can be better 
achieved by amending the last sentence of each regulation, rather than 
by deleting them. The amended language no longer suggests that a 
manufacturer's mere knowledge that its approved or cleared product was 
being prescribed or used for an unapproved use was sufficient to 
trigger the requirement to provide adequate labeling. In addition, this 
amended language provides further clarification by reminding 
manufacturers that, where the totality of evidence is sufficient to 
establish a new intended use for a medical product, relevant provisions 
of the FD&C Act and its implementing regulations will be triggered.
    In addition, these amendments reflect FDA's longstanding position, 
upheld by the courts, that FDA may consider a variety of direct and 
circumstantial evidence to establish intended use. For example, FDA may 
also take into account any circumstances surrounding the distribution 
of the product or the context in which it is sold (see, e.g.,

[[Page 2207]]

United States v. Travia, 180 F. Supp. 2d 115, 119 (D.D.C. 2001)). In 
the context of medical products, generally, circumstantial evidence 
often ensures that FDA is able to hold accountable firms that attempt 
to evade FDA medical product regulation by avoiding making express 
claims about their products.

C. Comments and Responses Regarding Intended Use

    (Comment 15) Some comments stated that this clarification of the 
Agency's interpretation and application of the intended use regulations 
(Sec. Sec.  201.128 and 801.4) was helpful because it clarifies a point 
that has been confusing to industry. Another comment stated that the 
proposed changes to Sec. Sec.  201.128 and 801.4 provide less 
information to manufacturers, not more clarity.
    (Response) FDA agrees that clarification was warranted because of 
the apparent confusion over this point. With this final rule, the 
Agency is making additional changes to the codified language and 
providing more explanation to further clarify the meaning of the 
regulations.
    (Comment 16) Some comments asserted that FDA should eliminate 
another reference to ``knowledge'' in Sec.  201.128. Before the 
amendments implemented by this rule, both Sec. Sec.  201.128 and 801.4 
contained the following sentence: ``[Intended use] may be shown by the 
circumstances that the article is, with the knowledge of such persons 
or their representatives, offered and used for a purpose for which it 
is neither labeled nor advertised.'' The comments recommended that FDA 
delete either the phrase ``with the knowledge of such person or their 
representatives'' or the entire sentence from the regulation. At least 
one comment asserted that its recommended change to delete that phrase 
is consistent with FDA's intent in amending the regulations.
    (Response) FDA disagrees with these comments. It was not the 
Agency's intention to entirely remove manufacturer knowledge from the 
types of evidence that may be considered in determining a product's 
intended use. FDA's proposed and final rule not only retained this 
sentence containing the other reference to ``knowledge'' in the text of 
both Sec. Sec.  201.128 and 801.4, but also added ``for example'' to 
emphasize that FDA may rely on any relevant source of evidence of 
intended use. Accordingly, the amended version of this sentence (in 
both regulations) now reads that ``intended use may be shown, for 
example, by circumstances in which the article is, with the knowledge 
of such person or their representatives, offered and used for a purpose 
for which it is neither labeled nor advertised.''
    In the context of medical products, generally, varied types of 
evidence, including evidence of a manufacturer's knowledge that a 
product is being used for an unapproved use, often enables FDA to 
pursue medical product manufacturers who attempt to evade FDA 
jurisdiction by avoiding express claims with respect to their products. 
In addition, as courts have recognized, evidence of a manufacturer's 
knowledge that a product is being used for an unapproved use can also 
be used to corroborate other evidence of intended use (see, e.g., 
United States v. An Article of Device Toftness Radiation Detector, 731 
F.2d 1253, 1257 (7th Cir. 1984) (intended use established in part by 
witness testimony that device had been used to treat patients, together 
with other evidence regarding a training program and financial 
arrangements offered by the defendant).
    FDA's intention in proposing to amend Sec. Sec.  201.128 and 801.4 
was more focused than these comments suggest. First, FDA's statement 
about not relying solely on manufacturer knowledge was limited to 
approved and cleared products because health care practitioners can 
generally use and prescribe such products for unapproved uses. That 
position does not apply to products that are not already legally 
marketed as medical products for at least one use. Second, manufacturer 
knowledge may be relevant to intended use, but the Agency would not 
bring an enforcement action based solely on manufacturer knowledge that 
an approved/cleared product was being prescribed or used by doctors for 
an unapproved use. If there is other evidence of intended use, FDA may 
consider manufacturer knowledge as well as other evidence. Third, FDA 
proposed deleting, and is now amending, the last sentence of the 
regulations to avoid the potential misinterpretation that a 
manufacturer's knowledge of an unapproved use of an approved/cleared 
medical product, without more, automatically triggers requirements for 
that manufacturer to provide additional labeling.
    (Comment 17) At least one comment suggested that the First 
Amendment requires the exclusion of knowledge as a category of evidence 
that may be considered as evidence of intended use.
    (Response) FDA disagrees. The First Amendment protects, among other 
things, freedom of speech, and knowledge and speech are not 
coextensive. A variety of direct and circumstantial evidence can 
establish a person's knowledge; a person's speech can be one source--
but is not the only source--of evidence of that person's knowledge. 
Thus, the inclusion of evidence of knowledge within the types of 
evidence that may be relevant to establishing intended use does not in 
itself implicate the First Amendment.
    (Comment 18) At least one comment asserted that, under relevant 
statutory text, legislative history, and case law, evidence of intended 
use is limited to a manufacturer's promotional claims. Another comment 
similarly proposed that the Agency focus principally on statements in 
the product labeling to establish intended use (using advertising 
material only to a lesser extent). In contrast, still another comment 
urged FDA to consider manufacturer statements in a variety of contexts, 
including advertising; press statements; official or unofficial 
statements made by corporate officials; statements made in social media 
and other online arenas; and statements made in point-of-sale locations 
(both traditional retail and online).
    (Response) FDA disagrees with the comments urging FDA to narrow the 
scope of evidence it will consider in determining intended use, and FDA 
agrees with the comment asserting that evidence relevant to intended 
use should include a manufacturer's statements in a variety of 
contexts. Under the former set of comments, FDA could not consider, for 
example, evidence of a manufacturer's marketing plans or directions to 
its sales force, evidence of the well-known uses and abuses of its 
products, and circumstantial evidence relating to the sale and 
distribution of the product. These comments' suggested narrow view of 
evidence of intended use would not only create a loophole for 
manufacturers and distributors to evade FDA oversight of the marketing 
of approved/cleared medical products for unapproved uses but would also 
open the door to the marketing of wholly unapproved medical products--
all to the detriment of the public health.
    As courts have recognized, ``[s]elf-serving labels cannot be 
allowed to mask the vendor's true intent as indicated by the overall 
circumstances'' (United States v. Storage Spaces Designated Nos. 8 and 
49, 777 F.2d 1363, 1366 n.5 (9th Cir. 1985)). As one court explained, 
``[a] disease claim made with a wink and a nudge is still a disease 
claim. To hold otherwise would create an `obviously wide loophole' that 
would defeat the `high purpose of the Act to protect consumers.' '' 
(United States v. Cole, 84 F. Supp. 3d 1159, 1166 (D. Or. 2015)

[[Page 2208]]

(citation omitted)). Examples of cases where the government has relied 
on circumstantial evidence to establish intended use include situations 
where products were labeled as herbal supplements, leather cleaner, 
incense, potpourri, bath salts, or `for research purposes only,' but in 
fact contained a pharmacological ingredient such as the active 
ingredient from approved erectile dysfunction and hair-loss products, 
albuterol, steroids, or street-drug pharmacological agents (``synthetic 
marijuana'' or ``imitation cocaine''). Similar examples for devices 
include products labeled as laser pointers, massagers, exercise 
equipment or diving chambers, but actually intended to treat serious 
conditions such as cancer, HIV, and autism. The government has also 
considered manufacturers' directions to their sales forces in 
determining intended use.
    Nothing in the statute requires the narrow scope the comments 
suggest. As four justices of the Supreme Court recognized in rejecting 
the arguments reflected in these comments, ``The [FD&C Act] . . . does 
not use the word `claimed'; it uses the word `intended' '' (FDA v. 
Brown & Williamson Tobacco Corp., 529 U.S. 120, 170 (2000) (dissenting 
opinion) (the majority declined to resolve the issue, id. at 131-32)). 
The language of the regulations is consistent with the statutory 
framework. As one court recently explained, ``[N]owhere does the 
regulation state that such statements or claims cannot be used to show 
objective intent unless they were published to the marketplace. To see 
the absurdity of defendants' argument, consider a hypothetical in which 
a medical device manufacturer sells device D, which is approved for use 
A but frequently prescribed by doctors for off-label use B. If the 
manufacturer creates a bumper sticker with the words `I intend D to be 
used for B: Prescribe D for B Today,' by defendants' logic that poster 
is inadmissible evidence of subjective intent so long as it sits in his 
briefcase, but admissible evidence of objective intent once he sticks 
it on his car. The Court is not persuaded that there is a legally 
relevant distinction here; in either scenario, the defendant has 
manifested into the physical world `oral or written statements' that 
may be weighed as evidence of objective intent'' (United States v. 
Vascular Solutions, Inc., 181 F. Supp. 3d 342, 347 (W.D. Tex. 2016)).
    FDA also disagrees that the case law requires that evidence of 
intended use be limited to marketing representations by firms, to the 
exclusion of other types of evidence such as internal firm documents 
and circumstances surrounding the sale of products. Courts have 
repeatedly held that intended use is determined by looking to all 
relevant evidence, including statements and circumstances surrounding 
the manufacture and distribution of a medical product (see, e.g., 
United States v. Article of 216 Cartoned Bottles, ``Sudden Change,'' 
409 F.2d 734, 739 (2d Cir. 1969) (``It is well settled that the 
intended use of a product may be determined from its label, 
accompanying labeling, promotional material, advertising and any other 
relevant source.'') (citations omitted); V.E. Irons, Inc. v. United 
States, 244 F.2d 34, 44 (1st Cir. 1957) (observing that a court is 
``free to look to all relevant sources in order to ascertain what is 
the `intended use' of a drug'')). As explained by one court: ``Whether 
a product's intended use makes it a device depends, in part, on the 
manufacturer's objective intent in promoting and selling the product. 
All of the circumstances surrounding the promotion and sale of the 
product constitute the `intent'. It is not enough for the manufacturer 
to merely say that he or she did not `intend' to sell a particular 
product as a device. Rather, the actual circumstances surrounding the 
product's sale . . . determine the `intended' use of the product as a 
device under the Act'' (United States v. 789 Cases, More or Less, of 
Latex Surgeons' Gloves, 799 F. Supp. 1275, 1285 (D. Puerto Rico 1992) 
(emphasis in original) (internal citations omitted)).
    Indeed, courts have rejected the comments' proposition that 
evidence of intended use is limited to a manufacturer's public claims 
concerning a device or drug (see Nat'l Nutritional Foods Ass'n v. 
Matthews, 557 F.2d 325, 334 (2d Cir. 1977) (``In determining whether an 
article is a `drug' because of an intended therapeutic use, the FDA is 
not bound by the manufacturer's subjective claims of intent but can 
find actual therapeutic intent on the basis of objective evidence. Such 
intent also may be derived or inferred from labeling, promotional 
material, advertising, and any other relevant source.'') (internal 
citation and quotations omitted); United States v. Travia, 180 F. Supp. 
2d 115, 119 (D.D.C. 2001) (``Labeling is not exclusive evidence of the 
sellers' intent. Rather, as the very language quoted by the defendants 
themselves states, `it is well established `that the intended use of a 
product, within the meaning of the [FD&C Act], is determined from its 
label, accompanying labeling, promotional claims, advertising, and any 
other relevant source' . . . even consumer intent could be relevant, so 
long as it was pertinent to demonstrating the seller's intent . . . 
[I]f the government's allegations are true, the sellers did not need to 
label or advertise their product, as the environment provided the 
necessary information between buyer and seller. In this context, 
therefore, the fact that there was no labeling may actually bolster the 
evidence of an intent to sell a mind-altering article without a 
prescription--that is, a misbranded drug.'') (citations omitted); 
United States v. Vascular Solutions, Inc., 181 F. Supp. 3d 342, 347 
(W.D. Tex. 2016) (``Even were this Court at liberty to depart from the 
Fifth Circuit's position, however, it would still deny defendants' 
motion; though [21 CFR] Sec.  801.4 indeed says that `objective intent 
may, for example, be shown by labeling claims, advertising matter, or 
oral or written statements by such persons or their representatives,' 
nowhere does the regulation state that such statements or claims cannot 
be used to show objective intent unless they were published to the 
marketplace.''); see also United States v. Storage Spaces Designated 
Nos. 8 and 49, 777 F.2d 1363, 1366 n.5 (9th Cir. 1985) (concluding that 
products innocuously labeled as ``incense'' and ``not for drug use'' 
were in fact drugs where the ``overall circumstances'' demonstrated 
vendor's intent that products be used as cocaine substitutes); United 
States v. An Article of Device Toftness Radiation Detector, 731 F.2d 
1253, 1257 (7th Cir. 1984) (intended use established in part by witness 
testimony that device had been used to treat patients, together with 
other evidence regarding a training program and financial arrangements 
offered by the defendant); United States v. Undetermined Quantities of 
an Article of Drug Labeled as ``Exachol'', 716 F. Supp. 787, 791 
(S.D.N.Y. 1989) (explaining that ``FDA is not bound by the vendor's 
subjective claims of intent'' and that ``[a]n article intended to be 
used as a drug will be regulated as a drug . . . even if the products 
labeling states that it is not a drug'')).
    (Comment 19) At least two comments asserted that FDA should 
significantly contract its proposed definitions of ``intended uses'' 
because the First Amendment protects truthful speech. One comment 
stated that, under Central Hudson Gas and Electric Corp. v. Public 
Services Commission, 447 U.S. 557, 566 (1980), government regulation of 
truthful speech concerning a lawful activity violates the First 
Amendment unless government regulators can

[[Page 2209]]

establish that: (1) They have identified a substantial government 
interest; (2) the regulation directly advances that asserted interest; 
and (3) the regulation is no more extensive than is necessary to serve 
that interest. The comment then argued that a complete prohibition of 
truthful speech by manufacturers and their representatives concerning 
the off-label uses of a drug or device does not satisfy this test.
    Similarly, another comment urged FDA to confirm that truthful and 
non-misleading speech cannot form the basis of a manufacturer's 
intended use of a medical product. That comment asserted that courts 
have recently held that enforcement actions based on truthful, non-
misleading speech to health care professionals violates core First 
Amendment values, citing United States v. Caronia, 703 F.3d 149 (2d 
Cir. 2012) and Amarin Pharma, Inc. v. FDA, 119 F. Supp. 3d 196 
(S.D.N.Y. 2015).
    (Response) FDA is separately examining its rules and policies 
relating to firm communications regarding unapproved uses of approved/
cleared medical products, with the goal of determining how best to 
integrate the significant and sometimes competing public health and 
safety interests served by FDA's regulatory approach related to 
unapproved uses of medical products with ongoing developments in 
science and technology, medicine, health care delivery, and 
constitutional law. To that end, FDA held a two-day public hearing on 
November 9 and 10, 2016, to obtain input on these issues, and created a 
docket for the submission of written comments (see, e.g., 81 FR 60299, 
Sept 1, 2016, announcing a public hearing and request for comments on 
Manufacturer Communications Regarding Unapproved Uses of Approved or 
Cleared Medical Products, available at: http://www.fda.gov/NewsEvents/MeetingsConferences Workshops/ucm489499.htm). That examination is 
ongoing. In contrast, the purpose of amending Sec. Sec.  201.128 and 
801.4 in this rulemaking is to clarify the scope of these regulations 
in response to assertions by industry that they did not understand the 
meaning of the regulations in their previous form.
    The broader policy questions and the related First Amendment issues 
are thus being considered in a separate proceeding. Nevertheless, it is 
important to note here that we do not agree with the assertion that the 
current case law allows FDA to consider speech as evidence of intended 
use only when it is false or misleading. Courts have held that the 
government's reliance on speech as evidence of intended use under the 
FD&C Act does not infringe the right of free speech under the First 
Amendment based on Supreme Court precedent establishing that ``[t]he 
First Amendment . . . does not prohibit the evidentiary use of speech 
to establish the elements of a crime or to prove motive or intent'' 
(Wisconsin v. Mitchell, 508 U.S. 476, 489 (1993)). The D.C. Circuit 
applied that precedent in the context of the FD&C Act and held that 
``th[e] use of speech to infer intent, which in turn renders an 
otherwise permissible act unlawful, is constitutionally valid'' and 
hence ``it is constitutionally permissible for the FDA to use speech 
[by the manufacturer] . . . to infer intent for purposes of determining 
that [the manufacturer's] proposed sale . . . would constitute the 
forbidden sale of an unapproved drug'' (Whitaker v. Thompson, 353 F.3d 
947, 953 (D.C. Cir. 2004); see also Flytenow, Inc. v. FAA, 808 F.3d 
882, 894 (D.C. Cir. 2015) (upholding ``us[e of] speech (postings on 
Flytenow.com) as evidence that pilots are offering service that exceeds 
the limits of their certifications'')). Courts applying that reasoning 
have found that the government's reliance on speech as evidence of 
intended use under the FD&C Act does not infringe the right of free 
speech under the First Amendment (see United States v. Lebeau, 654 Fed. 
App'x 826, 830-31 (7th Cir. 2016) (per curiam), petition for cert. 
filed, NO. 16-7125 (U.S. Oct. 13, 2016); Whitaker v. Thompson, 353 F.3d 
947, 953 (D.C. Cir. 2004); United States v. Article of Drug Designated 
B-Complex Cholinos Capsules, 362 F.2d 923, 927 (3d Cir. 1966); United 
States v. Cole, 84 F. Supp. 3d 1159, 1166 (D. Or. 2015); United States 
v. Regenerative Sciences, LLC, 878 F. Supp. 2d 248, 255-56 (D.D.C. 
2012), aff'd, 741 F.3d 1314 (D.C. Cir. 2014); United States v. Livdahl, 
459 F. Supp. 2d 1255, 1268 (S.D. Fla. 2005); United States v. Lane 
Labs-USA, Inc., 324 F. Supp. 2d 547, 579-80 (D.N.J. 2004); United 
States v. General Nutrition, Inc., 638 F. Supp. 556, 562 (W.D.N.Y. 
1986); see also Spectrum Pharms., Inc. v. Burwell, 824 F.3d 1062 (D.C. 
Cir. 2016) (manufacturer promotion of a generic drug for use approved 
for the sponsor but not for the generic may lead to enforcement action 
for misbranding)).
    Although the district court in Amarin Pharma, Inc. v. FDA held that 
the Caronia decision foreclosed reliance (in the Second Circuit) on 
this doctrine in the context of an FDA enforcement action where the 
misbranding was based solely on truthful, non-misleading speech 
regarding the unapproved use of an approved drug, the Second Circuit 
has more recently confirmed that ``Caronia left open the government's 
ability to prove misbranding on a theory that promotional speech 
provides evidence that a drug is intended for a use that is not 
included on the drug's FDA-approved label'' (United States ex rel. 
Polansky v. Pfizer, Inc., 822 F.3d 613 n.2 (2d Cir. 2016)).
    In addition, FDA's consideration of speech as evidence of intended 
use under its statutory and regulatory framework advances substantial 
public health interests relevant to analyses under Central Hudson Gas & 
Electric Corp. v. Public Service Comm'n, 447 U.S. 557, 563-64 (1980). 
The medical products FDA regulates have the potential to adversely 
impact public health and safety. Congress specifically developed the 
premarket review frameworks for medical products in response to public 
health tragedies \19\ and after determining that: (1) Exclusive 
reliance on postmarket remedies, such as enforcement actions for false 
or misleading labeling, is unacceptable as a public health strategy for 
medical products because it does not sufficiently prevent harm and 
injury to patients and (2) safety and effectiveness must be evaluated 
for each marketed intended use of a medical product to prevent the harm 
that occurs when patients are prescribed or use ineffective treatments 
and to ensure that the benefits of an intended use outweigh its risks. 
The premarket review requirements of the FD&C Act and the Public Health 
Service Act provide mechanisms to help ensure that protections are in 
place that will allow the public to obtain the benefits of these 
products while mitigating the risks. More specifically, FDA's statutory 
authorities, regulations, and implementation policies advance 
substantial public health interests including: Motivating the 
development of robust scientific data on safety and

[[Page 2210]]

efficacy; \20\ maintaining the premarket review process for safety and 
efficacy of each intended use in order to prevent harm, protect against 
fraud, misrepresentation, and bias, and prevent the diversion of 
healthcare resources toward ineffective treatments; \21\ ensuring 
required labeling is accurate and informative; protecting the integrity 
and reliability of promotional information regarding medical product 
uses; protecting human subjects receiving experimental treatments; 
ensuring informed consent; maintaining incentives for clinical trial 
participation; protecting innovation incentives, including statutory 
grants of exclusivity; and promoting the development of products for 
underserved patients.
---------------------------------------------------------------------------

    \19\ The Federal Food, Drug, and Cosmetic Act of 1938, which 
introduced the requirement that firms demonstrate a drug product to 
be safe before being marketed, followed the deaths of approximately 
100 people from ingesting ``Elixir Sulfanilamide,'' in which the 
lethal substance diethylene glycol was used as a solvent. Prior to 
1938, there were no premarket requirements that mandated that the 
firm test its product's safety. The passage of the 1962 drug 
amendments was precipitated in part by the distribution of 
thalidomide, a sleeping pill that caused birth defects when taken by 
pregnant women. See W.F. Janssen article (Ref. 20). Significant 
problems with medical devices likewise preceded the Medical Device 
Amendments of 1976, including significant defects in cardiac 
pacemakers that led to 34 voluntary recalls involving 23,000 units, 
and serious side effects following implantation of intraocular 
lenses, including serious impairment of vision and the need to 
remove the eyes of some patients (H.R. Rep. No. 94-853, at 8 
(1976)).
    \20\ See R. Eisenberg article (Ref. 11) (``By requiring that 
firms conduct rigorous clinical trials before bringing their 
products to market and before making promotional claims for their 
products, the FDA plays an important structural role in promoting a 
valuable form of biomedical R&D that private firms are 
undermotivated to perform on their own.''); A. Kesselheim and M. 
Mello article (Ref. 12) (``There [would] be no need for companies to 
design these studies to meet the FDA's standards for methodological 
rigor if the companies have no intention of submitting an 
application for approval of the new use but rather intend to use the 
study findings only in marketing communications. Companies [could] 
design studies in ways that maximize the chances of obtaining a 
desired result and select which studies to emphasize in promotional 
communications, ignoring others that do not support their 
promotional message.''); R. Stafford article (Ref. 13) (Encouraging 
unapproved uses ``undermines the incentives for manufacturers to 
perform rigorous studies--and instead subtly encourages them to game 
the system by seeking approval for secondary indications for which 
clinical trials are less complicated and less expensive. And off-
label use may discourage evidence-based practice.'').
    \21\ See, e.g., S. Kesselheim and J. Avorn article (Ref. 5) 
(``In the pharmaceutical market, determining whether a drug is safe 
and effective for an intended use can involve dozens of FDA 
scientists poring over extensive databases of studies in animals, 
toxicologic evaluations, and clinical trials. In essence, the agency 
acts as a learned intermediary on behalf of prescribing 
physicians.''); C. Good and W. Gellad article (Ref. 6) (``Even in 
situations where an off-label indication has been studied, 
pharmacokinetics, drug-disease interactions, and other safety 
considerations are unlikely to have been studied systematically to 
the level required during the FDA drug approval process. Likewise, 
few clinicians have the time or the motivation to review evidence 
for those off-label indications to arrive at a balanced assessment 
of the risks and benefits to support the appropriate use of that 
drug''); T. Eguale et al. article (Ref. 7) (summarizing study across 
cohort of 46,000 patients, and concluding that unapproved use of 
prescription drugs is associated with adverse drug events, 
particularly where those uses lack strong scientific evidence in the 
form of at least one randomized controlled trial).
---------------------------------------------------------------------------

    At the same time, health care providers also prescribe and use 
approved/cleared medical products for unapproved uses when they judge 
that the unapproved use is medically appropriate for their individual 
patients. Scientific or medical information regarding unapproved uses 
of products may in some cases help health care providers make better 
decisions regarding patients, such as where the patient has a disease 
for which there is no approved/cleared treatment, where the patient is 
part of a population that has not been studied, or where all approved/
cleared treatments have been exhausted. However, in other cases, the 
use of approved/cleared medical products for unapproved uses has also 
been associated with significant harm to patients, fraud, and waste of 
health care resources.\22\
---------------------------------------------------------------------------

    \22\ See J. Avorn et al. article (Ref. 8) (``Considerable 
research shows that marketing can drive prescribing practices, which 
in turn can lead to adverse patient outcomes if those decisions are 
not evidence-based.''); A. Kapczynski article (Ref. 9) (``To be 
effective, a company's marketing must also influence the prescribing 
patterns of physicians. . . . [T]here is a strong and specific 
association between pharmaceutical marketing and physician behavior, 
independent of the evidence supporting the products.''); R. 
Cardarelli et al. article (Ref. 10) (pharmaceutical industry 
marketing to prescribing physician creates the potential for 
prescribing practices that may not benefit the patient, which 
contribute to escalating health care costs); T. Eguale et al. 
article (Ref. 7).
---------------------------------------------------------------------------

    FDA's current implementation approach seeks to integrate the 
complex mix of numerous and sometimes competing interests at play while 
also taking into account First Amendment issues. For example, FDA has 
issued guidance documents to describe some of the circumstances when it 
would not consider a firm's distribution of reprints, clinical practice 
guidelines, or reference texts regarding unapproved uses of approved/
cleared medical products to be evidence of intended use; and issued a 
draft guidance on unsolicited requests, confirming FDA's longstanding 
position that it would not consider a firm's providing truthful, 
balanced, non-misleading, and non-promotional scientific or medical 
information (including information about an unapproved use) that is 
responsive to unsolicited requests for information about FDA-regulated 
medical products to be evidence of intended use. FDA takes the same 
view of firms' presenting truthful and non-misleading scientific 
information about unapproved uses at medical or scientific conferences 
when done in non-promotional settings and not accompanied by 
promotional materials.
    There are several points worth noting regarding the Central Hudson 
evaluation conducted by Second Circuit panel majority in United States 
v. Caronia. First, the panel majority's analysis was limited to 
addressing the constitutionality of a specific ``construction of the 
FDCA's misbranding provisions to prohibit and criminalize off-label 
promotion'' (see 703 F.3d 149, 161-64, 166-69 (2d Cir. 2012)). The 
Caronia majority did not conduct a Central Hudson evaluation of FDA's 
actual approach to manufacturer communications regarding unapproved 
uses of approved medical products, as described in the preceding 
paragraph. Second, the panel majority did not consider the multiple 
facets of public health advanced by FDA's statutory authorities, 
regulations, and implementation policies, which include motivating the 
development of reliable scientific evidence that enables the evaluation 
of the safety and effectiveness of each intended use of a medical 
product; maintaining the premarket review process for safety and 
efficacy of each intended use in order to prevent harm, protect against 
fraud, misrepresentation, and bias, and prevent the diversion of 
healthcare resources toward ineffective treatments; ensuring required 
labeling is accurate and informative; protecting the integrity and 
reliability of promotional information regarding medical product uses; 
protecting human subjects receiving experimental treatments; ensuring 
informed consent; maintaining incentives for clinical trial 
participation; protecting innovation incentives, including statutory 
grants of exclusivity; and promoting the development of products for 
underserved patients. The court's limited review of the interests at 
stake necessarily affected the rest of its Central Hudson analysis. 
Furthermore, the results of an exceptionally large Canadian study 
showing an association between unapproved uses and adverse drug events 
\23\ were released more than three years after the Caronia decision. 
Accordingly, the Caronia court, in conducting its Central Hudson 
evaluation, did not have the benefit of considering the significant 
findings of this study.
---------------------------------------------------------------------------

    \23\ T. Eguale et al. article (Ref. 7) (as noted above, 
summarizing study across cohort of 46,000 patients, and concluding 
that unapproved use of prescription drugs is associated with adverse 
drug events, particularly where those uses lack strong scientific 
evidence in the form of at least one randomized controlled trial).
---------------------------------------------------------------------------

    (Comment 20) Several comments asserted that FDA should take this 
opportunity to bring other related regulations and guidance documents 
into conformance with modern First Amendment case law. These comments 
suggested, for example, that FDA reconsider its approach to substantial 
evidence to support manufacturer communications to health care 
professionals about approved drugs, reconsider its interpretation of 
the term

[[Page 2211]]

labeling, and revise its regulations to confirm that FDA will abide by 
restrictions on FDA authority imposed by federal courts in United 
States v. Caronia, 703 F.3d 149 (2d Cir. 2012), and similar First 
Amendment decisions. At least one comment asserted, citing United 
States v. Caronia, that FDA's interpretation and implementation of the 
FD&C Act restricts speech based on the identity of the speaker. The 
comment further asserted that any restrictions on truthful and non-
misleading speech are subject to ``heightened judicial scrutiny'' and 
are ``presumptively invalid'' under Sorrell v. IMS Health Inc., 564 
U.S. 552, 565, 571 (2011), Reed v. Town of Gilbert, 135 S. Ct. 2218, 
2226 (2015), and Rosenberger v. Rector & Visitors of the Univ. of Va., 
515 U.S. 819, 828 (1995). Another comment, quoting Bolger v. Youngs 
Drug Prods., 463 U.S. 60, 66 (1983), asserted that FDA should recognize 
that commercial speech is limited to speech that ``does no more than 
propose a commercial transaction.'' Another comment urged FDA to open a 
separate docket related to free speech issues regarding medical 
products.
    (Response) To the extent these comments propose that FDA consider, 
in this rulemaking, issues that are beyond the scope of this 
rulemaking, FDA declines the suggestion. FDA agrees with the comment 
that suggests that broader First Amendment issues should be considered 
in the context of separate proceedings. FDA notes that there are 
separate proceedings that are currently ongoing (see, e.g., 81 FR 
60299, Sept 1, 2016, announcing a public hearing and request for 
comments on Manufacturer Communications Regarding Unapproved Uses of 
Approved or Cleared Medical Products, available at: http://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm489499.htm).
    In addition, FDA notes its disagreement with certain 
characterizations of the existing case law. First, as discussed 
earlier, the court in Caronia based its analysis on a legal theory that 
is more proscriptive than the one FDA actually holds. Second, the cited 
Supreme Court cases did not overrule the Central Hudson test for 
commercial speech. The Supreme Court in Sorrell confirmed that, where, 
as here, the speech in question is commercial, the Court applies the 
``commercial speech inquiry'' as outlined in Central Hudson (Sorrell v. 
IMS Health Inc., 564 U.S. 552, 571-72 (2011); see also 1-800-411-Pain 
Referral Service, LLC v. Otto, 744 F.3d 1045, 1055 (8th Cir. 2014) 
(observing that Sorrell held that content- or speaker-based 
restrictions on commercial speech are subject to ``heightened 
scrutiny,'' and using the Central Hudson test to determine the 
constitutionality of such restrictions)). The Sorrell Court also 
confirmed that ``content-based restrictions on protected expression are 
sometimes permissible, and that principle applies to commercial 
speech'' (Sorrell, 564 U.S. at 579).
    In Reed v. Town of Gilbert, the Court applied strict scrutiny to 
content-based restrictions on non-commercial speech in public fora. 
That holding has no bearing on the commercial speech at issue here 
(see, e.g., Sarver v. Chartier, 813 F.3d 891, 903 n.5 (9th Cir. 2016) 
(stating that Reed does not apply to laws governing commercial speech); 
Mass. Ass'n of Private Career Sch. v. Healey, 159 F. Supp. 3d 173, 192-
93 (D. Mass. 2016) (same); San Francisco Apt. Ass'n v. City & Cnty. of 
San Francisco, 142 F. Supp. 3d 910, 922 (N.D. Cal. 2015) (same), appeal 
docketed, No. 15-17381 (9th Cir. Dec. 3, 2015). The Supreme Court's 
1995 decision, Rosenberger v. Rector & Visitors of the Univ. of Va., 
515 U.S. 819, likewise did not involve commercial speech.
    Third, we disagree with the one comment that asserts, quoting 
Bolger v. Youngs Drug Prods., 463 U.S. 60, 66 (1983), that the Supreme 
Court limited the application of the Central Hudson test to speech that 
literally ``does no more than propose a commercial transaction.'' 
Although the Court in Bolger referred to speech that proposes a 
commercial transaction as ``the core notion of commercial speech,'' the 
Court then explained that ``informational pamphlets'' that ``cannot be 
characterized merely as proposals to engage in commercial 
transactions'' were nevertheless commercial speech based on a 
combination of relevant circumstances, such as mentioning the seller's 
product in the pamphlet and the economic motivation of the seller (see 
Bolger, 463 U.S. at 66-68 (emphasis added); see also Conn. Bar Ass'n v. 
United States, 620 F.3d 81, 93-94 (2d Cir. 2010)).
    (Comment 21) Several comments suggested that FDA replace the phrase 
``is intended for use'' in the first sentence of Sec.  1100.5 with 
other phrases, such as ``is commonly used'' or ``is primarily used.''
    (Response) FDA declines this suggestion. The phrase ``is intended 
for use'' is necessary because it reflects the fact that FDA's 
regulatory authority over a product made or derived from tobacco is, in 
the context of regulating them as medical products, dependent upon the 
product's intended use.
    (Comment 22) Several comments urged FDA not to consider a 
manufacturer's knowledge when determining a manufacturer's intent with 
respect to the regulation of human cells, tissues, and cellular and 
tissue-based products (HCT/Ps). The comments also request that the 
Agency use notice and comment rulemaking instead of guidance to make 
changes regarding manufacturer intent related to HCT/Ps.
    (Response) These comments concern regulations and guidance 
documents relating specifically to HCT/Ps and are outside the scope of 
this rulemaking.

D. Comments and Responses Regarding Marketing Concerns

    (Comment 23) At least one comment suggested that FDA amend Sec.  
1100.5(a) to incorporate the following points: (1) Products intended 
for use in the cure and treatment of smoking or any other tobacco 
product use are subject to regulation as medical products; (2) products 
intended for use for the prevention of relapse into any smoking, 
tobacco product, or nicotine relapse are subject to regulation as 
medical products; and (3) relief from nicotine withdrawal symptoms also 
includes relief from smoking or tobacco use withdrawal symptoms.
    (Response) FDA agrees that the three uses identified in the comment 
appear to be intended uses that would render the products subject to 
regulation as medical products. Section 1100.5(a) explains that a 
product made or derived from tobacco is subject to regulation as a 
medical product if it is intended for use in the diagnosis of disease 
or other conditions, or in the cure, mitigation, treatment, or 
prevention of disease. For illustrative purposes, the section also 
provides several examples of intended uses that will subject a product 
to regulation as a medical product. We believe the list of examples, 
which is not intended to be exhaustive, adequately illustrates the 
types of intended uses that will subject a product made or derived from 
tobacco to regulation as a medical product. Thus, while we agree that 
the three identified uses appear to be intended uses that would render 
the products subject to regulation as medical products, we decline to 
amend the list to incorporate the uses identified by the comment.
    (Comment 24) At least one comment objected that the rule would 
limit e-cigarettes to marketing claims of ``smoking pleasure'' and 
``smoking satisfaction'' since that is how traditional tobacco products 
were ``customarily marketed'' prior to March

[[Page 2212]]

21, 2000. The comment asserted that the rule would either force e-
cigarettes off the market as unapproved medical products, or require e-
cigarettes to be marketed similar to how traditional tobacco products 
were marketed prior to March 21, 2000, which would be deceptive because 
e-cigarettes are not intended for smoking pleasure or tobacco 
satisfaction. The comment argued that FDA should treat e-cigarettes 
differently from products that both contain tobacco leaf and were 
commercially available before March 21, 2000, when considering the 
types of claims that will subject a product made or derived from 
tobacco to regulation as a medical product.
    (Response) FDA disagrees. As explained elsewhere in this document, 
we believe that the rule gives manufacturers and retailers ample 
flexibility to market e-cigarettes in a manner that is distinct from 
how cigarettes were marketed prior to March 21, 2000. The date of March 
21, 2000, is relevant only to considering claims about a product's 
effects related to nicotine on the structure or function of the body as 
evidence of a product's intended use. E-cigarette manufacturers' and 
retailers' claims related to customizability, number of puffs per 
cartridge or charge, and various other differentiating features that do 
not relate to nicotine structure/function effects, irrespective of 
whether such claims were customarily and legally made in the marketing 
of cigarettes and smokeless tobacco products before March 21, 2000, 
should generally not affect the determination of a product's intended 
use. A manufacturer's making a modified risk claim for a specific 
tobacco product renders the product an MRTP, which can be marketed only 
after the manufacturer substantiates any modified risk claims in an 
MRTP application and after FDA determines that the product meets the 
statutory standard. Additionally, if a manufacturer intends that its 
product be used for cessation, it can submit an NDA, Abbreviated New 
Drug Application (ANDA), Premarket Approval Application (PMA), or 
premarket notification submission so that FDA can determine whether the 
product meets the statutory standard and can approve the application or 
clear the submission, if appropriate.
    (Comment 25) At least one comment questioned whether the marketing 
for tobacco products that are not MRTPs may contain useful contextual 
information (e.g., ingredient information).
    (Response) This comment is outside the scope of this rulemaking 
because it does not relate to the circumstances in which a product that 
is made or derived from tobacco will be regulated as a medical product 
or a tobacco product.
    (Comment 26) Several comments stated that ENDS manufacturers need 
to be able to inform and explain how to properly use vaping devices to 
help novices to prevent them from having accidents. The comments stated 
that vape shops need to be able to correctly educate consumers on how 
to use the products they sell.
    (Response) FDA agrees. FDA recognizes that manufacturers may wish 
to provide instructions to consumers on how to use novel tobacco 
products, and instructions may be helpful in some cases in preventing 
consumer injury, such as nicotine poisoning or injuries from exploding 
batteries. Manufacturers may provide instructions to the consumer in 
many ways, including verbal instruction. However, if the instructions 
provided by the manufacturer convey that the product is to be used as a 
cessation device, then the product will generally be regulated as a 
medical product. Additionally, if the instructions make a modified risk 
claim, then the manufacturer must submit an MRTP application so that 
FDA can determine whether the product meets the statutory standard and 
can issue an order authorizing it to be marketed as an MRTP.
    (Comment 27) Several commenters noted that tobacco products are 
advertised in a variety of media, including traditional print or 
mainstream media, blogs, social media, testimonials, and links to 
studies or media reports on Web sites. One comment observed that 
manufacturers of ENDS products often use online blogs as a way to make 
implicit or explicit cessation claims, and in some cases such 
assertions run counter to disclaimers posted on the same Web site that 
hosts the blog. Another comment noted that manufacturers used consumer 
testimonials that make cessation or MRTP claims on their company Web 
sites. Commenters observed that conflicting claims in advertising 
caused confusion among consumers regarding whether ENDS products are 
FDA-approved smoking cessation aids.
    (Response) FDA agrees. Tobacco products are advertised in a variety 
of media, and advertisements may include conflicting information 
regarding whether the product is a recreational tobacco product or an 
FDA-approved smoking cessation product. When conflicting claims are 
made to the consumer, consumers can be confused by those claims. Thus, 
FDA believes that manufacturers' making smoking cessation claims for 
any product creates a strong suggestion of therapeutic benefit to the 
user that would subject the product to regulation under FDA's medical 
products authority. Such a suggestion generally will be difficult to 
overcome absent clear context indicating that the product is not 
intended for use to cure or treat nicotine addiction or its symptoms, 
or for another therapeutic purpose. As discussed in response to Comment 
12, where products making claims related to quitting smoking also 
attempt to disclaim that use in some way, FDA intends to view such 
disclaimers skeptically because of the likelihood of consumer 
confusion. In most cases, FDA does not believe that disclaimers will 
sufficiently mitigate consumer confusion related to the intended 
therapeutic use of the product.
    (Comment 28) Several comments stated that adolescent smokers are 
especially vulnerable to cessation and therapeutic claims in tobacco 
product marketing. These comments believe that adolescents misperceive 
the supposed benefits and underestimate the relative harms, risks, and 
addictive properties of e-cigarettes and other non-cigarette products.
    (Response) FDA agrees that youth and young adults generally 
``underestimate the tenacity of nicotine addiction and overestimate 
their ability to stop smoking when they choose'' (Ref. 14). For 
example, one survey found that ``nearly 60 percent of adolescents 
believed that they could smoke for a few years and then quit'' (Ref. 
15). FDA also believes that unsubstantiated cessation claims that reach 
adolescents may confuse teens and lead teens to believe that these 
products are FDA-approved smoking cessation products. For example, a 
teenager in a recent qualitative study said, ``I heard that the only 
reason they were made is to help people get off from cigarettes for 
people that want to quit. You would use an e-cigarette to help you quit 
supposedly. It was on the news'' (Ref. 16). FDA believes it is 
important to avoid consumer confusion about which products are intended 
for medical uses versus recreational or other tobacco product uses 
among both adolescents and adults, and this rule will help consumers.
    (Comment 29) At least one comment stated that users consider ENDS 
and smokeless tobacco products effective cessation interventions. The 
comment believed that many people use these products to try to stop 
smoking because they are influenced by manufacturers' and sellers' 
marketing messages that

[[Page 2213]]

make cessation and therapeutic claims about ENDS and other non-
cigarette tobacco products.
    (Response) FDA agrees that marketing can influence how consumers 
perceive tobacco products, and products advertised with cessation 
claims can lead consumers to believe that the product is an FDA-
approved smoking cessation device. FDA also agrees that many consumers 
are using ENDS products for therapeutic purposes. One study concluded 
that, among State tobacco cessation quitline callers, the most common 
reported reason for using e-cigarettes was to cut down on, or quit, 
traditional tobacco use (Ref. 17). Another study concluded that some 
smokers who were interested in quitting were using ENDS for cessation 
purposes, possibly discouraging the use of proven smoking cessation 
treatments, delaying cessation, and thus prolonging exposure to harmful 
agents in combusted tobacco as an unintended consequence. Additionally, 
FDA received a large number of comments from individuals using ENDS for 
therapeutic purposes. One purpose of this regulation is to avoid 
consumer confusion about which products made or derived from tobacco 
are intended for a medical use versus for a recreational use.

E. Other Comments and Responses

    (Comment 30) At least one comment expressed concern that since the 
Sottera decision, FDA has not taken action against products made or 
derived from tobacco and making claims that were ``clearly 
therapeutic.'' In order to protect consumers from ``false, misleading, 
and confusing tobacco industry claims,'' the comment asks that products 
made or derived from tobacco making claims without an MRTP order be 
regulated as drug/device products in the Center for Drug Evaluation and 
Research.
    (Response) FDA disagrees with the comment to the extent that the 
comment suggests that tobacco products properly regulated as MRTPs be 
regulated as drugs or devices in the absence of an MRTP order. Tobacco 
products making modified risk claims are regulated under the tobacco 
product authorities in the FD&C Act, and an MRTP marketed without an 
MRTP order would be subject to enforcement as a tobacco product, rather 
than subject to regulation as a drug or medical device product. With 
respect to enforcement generally, FDA notes that it is issuing this 
rule to clarify its interpretation of the drug and device definitions 
with respect to products made or derived from tobacco, and that it 
expects this clarification to assist industry in determining the 
applicable regulatory framework for particular products and help 
consumers differentiate between products that are intended for medical 
use and products intended for other uses.
    (Comment 31) At least one comment observed that researchers may 
wish to study the effects that a product made or derived from tobacco 
has on health outcomes (e.g., withdrawal symptoms, hypertension, etc.) 
or on the structure and function of the body (e.g., blood pressure, 
lung function), or the effects of substituting one product made or 
derived from tobacco for another product. The comment asserted that the 
methods and measures of such studies are not evidence that the product 
being investigated is a drug and that FDA should not require an 
investigational new drug application (IND) for these studies unless 
they are sponsored by a manufacturer with the intention of supporting a 
health or medical drug claim.
    (Response) The regulations in part 312 set forth the circumstances 
in which an IND is required for clinical investigations in which a drug 
is administered to human subjects. The IND requirement applies 
irrespective of whether the investigation is sponsored by a 
manufacturer or an academic institution. A study involving a product 
made or derived from tobacco will generally require an IND if the 
product, as used in the study, is subject to regulation as a drug. 
Whether the product, as used in the study, is subject to regulation as 
a drug depends on whether the product is being investigated for any of 
the purposes described in Sec.  1100.5(a) or (b) of this rule. To 
determine if a product made or derived from tobacco is being 
investigated for one of these purposes, FDA generally would review the 
protocol for the study, including the proposed methods and measures. In 
the Agency's experience, the proposed methods and measures for a study 
can provide insight into the purposes for which a product is being 
investigated. Ultimately, however, whether a product is being 
investigated for a therapeutic purpose, and thus whether the study 
requires an IND, is a fact-specific, case-by-case inquiry. Additional 
information about the IND requirement can be found in the FDA guidance 
document entitled ``Investigational New Drug Applications (INDs)--
Determining Whether Human Research Studies Can Be Conducted Without an 
IND.'' We encourage researchers to review this guidance document, which 
is available on FDA's Web site at http://www.fda.gov/downloads/UCM229175.pdf.
    (Comment 32) At least one comment encouraged FDA to coordinate 
between centers to promote development of safer tobacco products as 
well as more effective medical products for the treatment of nicotine 
addiction. This comment also argued that FDA should not allow similar 
or identical products to be marketed as both tobacco products and 
medical products, and should consider approving categories of products, 
rather than individual products, for smoking cessation. This comment 
also expressed concern about dual use between tobacco product 
categories.
    (Response) FDA agrees with this comment to the extent the comment 
considers the proposed rule to promote effective coordination between 
centers by clarifying which center should take the lead in review of 
premarket applications and postmarketing regulation of particular 
products. We note that FDA currently interprets the standards in 
various medical and tobacco product premarket review pathways to refer 
to individual products rather than product categories, and the question 
of whether a particular product could obtain marketing authorization as 
both a tobacco product and as a medical product is beyond the scope of 
this rule. By clarifying the jurisdictional lines between tobacco and 
medical products, FDA believes that finalization of this rule will make 
it less likely that manufacturers will attempt to market products made 
or derived from tobacco both as tobacco products and as medical 
products--for example, if a tobacco product manufacturer attempts to 
add claims to a currently marketed tobacco product that would require 
the product to be regulated as drug, device, or combination product.
    (Comment 33) Several comments recommended that the Center for 
Tobacco Products (CTP) have sole regulatory jurisdiction over tobacco 
and nicotine-containing products and provided suggestions for how CTP 
should structurally reorganize itself to better regulate these 
products.
    (Response) CTP oversees the regulation of products made or derived 
from tobacco that are intended for human consumption. As stated in this 
preamble, when a product made or derived from tobacco is marketed or 
distributed for an intended use that falls within the drug/device 
definitions, it would be regulated as a medical product unless it is 
intended to affect the structure or any function of the body in any way 
related to the effects of nicotine that were commonly and legally 
claimed prior to March 21, 2000. In this situation, one of FDA's 
medical product

[[Page 2214]]

centers would have regulatory oversight over these products because CTP 
does not oversee the regulation of medical products. As these comments 
relate to potentially undertaking a structural re-organization, CTP is 
not considering a structural reorganization at this time.
    (Comment 34) At least one comment suggested that FDA create a 
separate regulatory category for e-cigarettes that is based on the 
Agency's medical product regulations, but with less stringent quality 
standards.
    (Response) This recommendation is not consistent with the statutory 
definitions in the FD&C Act. Under the FD&C Act, a product made or 
derived from tobacco is subject to regulation as a tobacco product 
unless it meets the definition of a drug or device or is a combination 
product, in which case it is subject to regulation as a medical 
product.
    (Comment 35) Several comments stated that the cost and resources 
required to complete FDA's drug application process would be simply too 
great and would shut down many small manufacturers.
    (Response) This regulation simply clarifies the circumstances under 
which a product made or derived from tobacco would be regulated as a 
drug, device, or combination product, and the circumstances under which 
it would be regulated as a tobacco product; it does not create new 
jurisdictional lines or impose new obligations on product 
manufacturers. Because the jurisdictional lines already exist, tobacco 
product manufacturers currently making claims that would render their 
product subject to regulation as a medical product or who wish to make 
such claims in the future are within FDA's drug and device 
jurisdiction, absent limited exceptions, and they must follow the 
applicable statutory and regulatory requirements.
    (Comment 36) Many comments believed that the regulation would make 
e-cigarettes less available to consumers.
    (Response) FDA disagrees. This regulation simply clarifies the 
circumstances under which a product made or derived from tobacco will 
be regulated as a drug, device, or combination product, and the 
circumstances under which it will be regulated as a tobacco product. 
This regulation will not add any additional burden to manufacturers who 
sell ENDS for recreational use. However, if a manufacturer is selling 
ENDS and making medical product claims, then the product would be 
subject to regulation as a drug, device, or combination product if 
those claims are not structure/function claims related to the effects 
of nicotine that were commonly and legally claimed prior to March 21, 
2000.
    (Comment 37) At least one comment suggested that the final rule 
should include a discussion of how the regulation will affect public 
health.
    (Response) The preamble to the proposed rule contained some 
discussion of this topic, and this preamble to the final rule further 
expands on various public health protections.
    (Comment 38) FDA proposed that a product made or derived from 
tobacco that is intended for use in smoking cessation be subject to 
regulation as a medical product. Several comments objected that smoking 
is not a disease, but a behavior, and that a product that claims to 
help individuals quit smoking should not be regulated as a medical 
product absent any assertions that it will prevent disease or treat 
nicotine dependence. One comment asserted that promoting a product as 
suitable for continued nicotine use after stopping smoking traditional 
cigarettes is the functional equivalent of a ``smoking alternative'' 
claim, which FDA has said does not fall within the Agency's medical 
product authority, and, therefore, should not subject the product to 
regulation as a medical product.
    (Response) Over the past 50 years, smoking has been causally linked 
to diseases of nearly all organs of the body, diminished health status, 
and fetal harm. Most current adult smokers want to quit smoking 
completely for health reasons (Ref. 18). Given these facts, we believe 
that statements related to quitting smoking generally create a strong 
suggestion that a product is intended for a therapeutic purpose. We 
recognize, however, that public perception can change and evidence may 
be developed showing that, in some situations, ``smoking cessation'' is 
understood in context as referring to ending the use of traditional 
cigarettes and switching to a non-combustible product made or derived 
from tobacco. We have revised the codified language in Sec.  1100.5(a) 
in the final rule, to reflect that ``smoking cessation'' is one type of 
intended use related to ``the cure or treatment of nicotine 
addiction.'' FDA intends to closely scrutinize ``smoking cessation'' 
claims to ensure that consumers are not misled about the intended use 
of a product made or derived from tobacco.
    (Comment 39) One comment stated that this regulation should not 
require companies that handle raw materials to determine whether those 
raw materials would be used in tobacco products or whether those 
materials would be used in medical products. The comment stated that 
the intended use of the product is completely within the discretion of 
the sellers and distributors of the finished products, and the Agency 
should not extend regulations to cover companies that handle raw 
materials.
    (Response) This comment is beyond the scope of this rule. This 
regulation does not create new jurisdictional lines or impose new 
obligations on product manufacturers or companies that handle raw 
materials. Rather, this rulemaking simply clarifies the circumstances 
under which a product made or derived from tobacco would be regulated 
as a drug, device, or combination product, and the circumstances under 
which it would be regulated as a tobacco product. If FDA were to 
consider extending its authority in such a way that would place 
additional requirements on companies handling raw materials, the Agency 
would do so through a separate rulemaking.

F. Other Changes to the Codified Text

    To eliminate redundancy, we deleted ``or prevention or mitigation 
of disease'' from the end of Sec.  1100.5(a), as the opening text 
already includes similar language. Because of this deletion, we 
inserted the word ``or'' in front of ``relief of nicotine withdrawal 
symptoms.''

G. Effective Date

    This final rule will become effective 30 days after the date of its 
publication in the Federal Register. During those 30 days, 
manufacturers will continue to be under an obligation to comply with 
all applicable provisions of the FD&C Act and applicable regulations.

V. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the final 
rule does not contain policies that would have substantial direct 
effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government. Accordingly, 
the Agency concludes that the final rule does not contain policies that 
have federalism implications as defined in the Executive order and, 
consequently, a federalism summary impact statement is not required.

VI. Executive Order 13175: Tribal Consultation

    We have analyzed this rule in accordance with the principles set 
forth

[[Page 2215]]

in Executive Order 13175. We have determined that the rule does not 
contain policies that have substantial direct effects on one or more 
Indian tribes, on the relationship between the Federal Government and 
Indian tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian tribes. Accordingly, we 
conclude that the rule does not contain policies that have tribal 
implications as defined in the Executive order and, consequently, a 
tribal summary impact statement is not required.

VII. Analysis of Environmental Impact

    FDA has determined under 21 CFR 25.30(h) and (k) that this action 
is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

VIII. Economic Analysis of Impacts

    We have examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct us to assess all costs 
and benefits of available regulatory alternatives and, when regulation 
is necessary, to select regulatory approaches that maximize net 
benefits (including potential economic, environmental, public health 
and safety, and other advantages; distributive impacts; and equity). We 
have developed a comprehensive Economic Analysis of Impacts that 
assesses the impacts of the final rule. We believe that this final rule 
is not a significant regulatory action as defined by Executive Order 
12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because, as described in detail in the section entitled 
``Final Small Entity Analysis'' in the full analysis of economic 
impacts available in the docket for this final rule (Ref. 19) and at 
http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm, the clarifications in this final rule 
will not significantly increase costs on manufacturers of products made 
or derived from tobacco, we certify that the final rule will not have a 
significant economic impact on a substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before issuing ``any rule that includes 
any Federal mandate that may result in the expenditure by State, local, 
and tribal governments, in the aggregate, or by the private sector, of 
$100,000,000 or more (adjusted annually for inflation) in any one 
year.'' The current threshold after adjustment for inflation is $146 
million, using the most current (2015) Implicit Price Deflator for the 
Gross Domestic Product. This final rule would not result in expenditure 
in any year that meets or exceeds this amount.
    The final rule will reduce ambiguity in the market for products 
made or derived from tobacco and clarify FDA's interpretation and 
application of its existing intended use regulations. The rule 
clarifies the intended uses and supporting evidence that would result 
in these products being regulated as drugs, devices, or combination 
products rather than tobacco products. Products derived from tobacco 
that are intended to: (1) Diagnose, cure, mitigate, treat or prevent 
disease, including use in smoking cessation or (2) affect the structure 
or any function of the body in any way that is different from effects 
related to nicotine that were commonly and legally claimed in the 
marketing of cigarettes and smokeless tobacco prior to March 21, 2000, 
such as an intended use for improving respiratory function, will be 
subject to regulation as drugs, devices, or combination products. We 
estimate that there would be one-time costs for tobacco manufacturers 
to evaluate current product communications such as labeling and 
associated promotional materials in light of the clarifications in this 
final rule, and to revise them if needed. We expect that only a small 
number of product communications such as labeling and associated 
materials will undergo a one-time change as a result of this rule.
    The final rule will provide greater clarity to producers regarding 
the regulatory requirements for products made or derived from tobacco 
and to consumers to distinguish products intended for medical uses from 
those marketed for other uses. The reduction in ambiguity will enhance 
consumers' understanding of the products they purchase and may increase 
consumer welfare as a result.

                                                  Table 2--Economic Data: Costs and Benefits Statement
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                               Units
                                              Primary                                    ------------------------------------------------
                Category                     estimate      Low estimate    High estimate                   Discount rate  Period covered       Notes
                                                                                           Year dollars         (%)           (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                        Benefits
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized..............................  ..............  ..............  ..............  ..............               7  ..............
Monetized ($millions/year)..............  ..............  ..............  ..............  ..............               3  ..............
Annualized..............................  ..............  ..............  ..............  ..............               7  ..............
Quantified                                ..............  ..............  ..............  ..............               3  ..............
                                         ---------------------------------------------------------------------------------------------------------------
Qualitative.............................            Reduce regulatory ambiguity
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                          Costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized..............................          $0.246          $1.126          $0.365            2014               7              10
Monetized ($millions/year)..............           0.202           0.202           0.202  ..............  ..............  ..............
                                                   0.202           0.104           0.301            2014               3              10
Annualized                                ..............  ..............  ..............  ..............               7  ..............
Quantified..............................  ..............  ..............  ..............  ..............               3  ..............
Qualitative.............................  ..............  ..............  ..............  ..............  ..............  ..............

[[Page 2216]]

 
Transfers...............................  ..............  ..............  ..............  ..............  ..............  ..............
Federal.................................  ..............  ..............  ..............  ..............               7  ..............
Annualized..............................  ..............  ..............  ..............  ..............               3  ..............
Monetized ($millions/year)
                                         ---------------------------------------------------------------------------------------------------------------
From/To                                   From:
                                          To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Other...................................  ..............  ..............  ..............  ..............               7  ..............
Annualized..............................  ..............  ..............  ..............  ..............               3  ..............
Monetized ($millions/year)
                                         ---------------------------------------------------------------------------------------------------------------
From/To                                   From:
                                          To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects
State, Local or Tribal Government: No Effect
Small Business: No effect
Wages: No estimated effect
Growth: No estimated effect
--------------------------------------------------------------------------------------------------------------------------------------------------------

    The full analysis of economic impacts is available in the docket 
for this final rule (Ref. 19) and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

IX. Paperwork Reduction Act of 1995

    FDA concludes that this final rule contains no collection of 
information. Therefore, clearance by the Office of Management and 
Budget under the Paperwork Reduction Act of 1995 is not required.

X. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m. Monday through Friday; they are also 
available electronically at https://www.regulations.gov. FDA has 
verified the Web site addresses, as of the date this document publishes 
in the Federal Register, but Web sites are subject to change over time.

1. Defendants' Memorandum of Points and Authorities in Support of 
Motion to Dismiss or for Summary Judgment. Allergan Inc. v. United 
States of America, et al., 1:09-cv-01879-JDB (D.D.C. Jan. 11, 2010), 
2010 WL 11211158.
2. Etter, J.-F., C. Bullen, ``Electronic Cigarette: Users Profile, 
Utilization, Satisfaction and Perceived Efficacy,'' Addiction, 
106(11):2017-2028, 2011.
3. Byron, M.J., S.A. Baig, K.E. Moracco, and N.T. Brewer, 
``Adolescents' and Adults' Perceptions of `Natural', `Organic' and 
`Additive-Free' Cigarettes, and the Required Disclaimers,'' Tobacco 
Control, Dec 1:tobaccocontrol-2015, 2015.
4. Green, K.C. and J.S. Armstrong, ``Evidence on the Effects of 
Mandatory Disclaimers in Advertising,'' Journal of Public Policy & 
Marketing, 31(2):293-304, 2012.
5. Kesselheim, A.S. and J. Avorn, ``Pharmaceutical Promotion to 
Physicians and First Amendment Rights,'' New England Journal of 
Medicine, 358:1727-1732, 2008.
6. Good, C.B. and W.F. Gellad, ``Off-Label Drug Use and Adverse 
Events: Turning up the Heat on Off-Label Prescribing,'' Journal of 
American Medical Association Internal Medicine, 176(1):63-64, 2016.
7. Eguale, T., D.L. Buckeridge, A. Verma, et al., ``Association of 
Off-Label Drug Use and Adverse Drug Events in an Adult Population,'' 
Journal of American Medical Association Internal Medicine, 
176(1):55-63, 2016.
8. Avorn, J., A. Sarpatwari, and A.S. Kessleheim, ``Forbidden and 
Permitted Statements About Medications--Loosening the Rules,'' New 
England Journal of Medicine, 373:967-973, 2015.
9. Kapczynski, A., ``Free Speech and Pharmaceutical Regulation--
Fishy Business,'' Journal of American Medical Association Internal 
Medicine, 176(3):295-296, 2016.
10. Cardarelli, R., J.C. Licciardone, and L.G. Taylor, ``A Cross-
Sectional Evidence-Based Review of Pharmaceutical Promotional 
Marketing Brochures and Their Underlying Studies: Is What They Tell 
Us Important and True?,'' BMC Family Practice, 7(1):13, 2006.
11. Eisenberg, R.S., ``The Role of the FDA in Innovation Policy,'' 
Michigan Telecommunications and Technology Law Review, 13:2:345, 
370, 2007.
12. Kesselheim, A.S., and M.M. Mello, ``Healthcare Decisions in the 
New Era of Healthcare Reform: Prospects for Regulation of Off-Label 
Drug Promotion in an Era of Expanding Commercial Speech 
Protection,'' North Carolina Law Review, 92:1539, 1585, 2014.
13. Stafford, R.S., ``Regulating Off-Label Drug Use--Rethinking the 
Role of the FDA,'' New England Journal of Medicine, 358:1427-1429, 
2008.
14. President's Cancer Panel, ``Promoting Healthy Lifestyles,'' 
2007, available at http://deainfo.nci.nih.gov/advisory/pcp/annualReports/pcp07rpt/pcp07rpt.pdf.
15. Institute of Medicine of the National Academies, ``Ending the 
Tobacco Problem: A Blueprint for the Nation,'' 2007, available at 
https://www.nap.edu/read/11795/chapter/1.
16. Roditis, M.L., and B. Halpern-Felsher, ``Adolescents' 
Perceptions of Risks and Benefits of Conventional Cigarettes, E-
Cigarettes and Marijuana: A Qualitative Analysis,'' Journal of 
Adolescent Health, 57(2):179-185, 2015.
17. Vickerman, K.A., K.M. Carpenter, T. Altman, et al., ``Use of 
Electronic Cigarettes Among State Tobacco Cessation Quitline 
Callers,'' Nicotine & Tobacco Research, 15(10):1787-1791, 2013.
18. Gallup Consumption Habits poll, July 2013 (see http://www.gallup.com/poll/163763/smokers-quit-tried-multiple-times.aspx).
19. Clarification of When Products Made or Derived From Tobacco Are 
Regulated as Drugs, Devices, or Combination; Amendments to 
Regulations Regarding ``Intended Uses,'' Final Rule; Final 
Regulatory Impact Analysis.
20. Janssen, W.F., ``Outline of the History of U.S. Drug Regulation 
and Labeling,'' Food Drug Cosmetic Law Journal, 36: 420, 437-438, 
1981.

[[Page 2217]]

List of Subjects

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 801

    Labeling, Medical devices, Reporting and recordkeeping 
requirements.

21 CFR Part 1100

    Combination products, Devices, Drugs, Smoking, Tobacco.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR 
chapter 1 is amended as follows:

PART 201--LABELING

0
1. The authority citation for part 201 continues to read as follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360, 
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.

0
2. Revise Sec.  201.128 to read as follows:

Sec.  201.128  Meaning of ``intended uses''.

    The words intended uses or words of similar import in Sec. Sec.  
201.5, 201.115, 201.117, 201.119, 201.120, 201.122, and 1100.5 of this 
chapter refer to the objective intent of the persons legally 
responsible for the labeling of drugs. The intent is determined by such 
persons' expressions or may be shown by the circumstances surrounding 
the distribution of the article. This objective intent may, for 
example, be shown by labeling claims, advertising matter, or oral or 
written statements by such persons or their representatives. It may be 
shown, for example, by circumstances in which the article is, with the 
knowledge of such persons or their representatives, offered and used 
for a purpose for which it is neither labeled nor advertised. The 
intended uses of an article may change after it has been introduced 
into interstate commerce by its manufacturer. If, for example, a 
packer, distributor, or seller intends an article for different uses 
than those intended by the person from whom he received the drug, such 
packer, distributor, or seller is required to supply adequate labeling 
in accordance with the new intended uses. And if the totality of the 
evidence establishes that a manufacturer objectively intends that a 
drug introduced into interstate commerce by him is to be used for 
conditions, purposes, or uses other than ones for which it is approved 
(if any), he is required, in accordance with section 502(f) of the 
Federal Food, Drug, and Cosmetic Act, or, as applicable, duly 
promulgated regulations exempting the drug from the requirements of 
section 502(f)(1), to provide for such drug adequate labeling that 
accords with such other intended uses.

PART 801--LABELING

0
3. The authority citation for part 801 continues to read as follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 360d, 360i, 360j, 371, 
374.

0
4. Revise Sec.  801.4 to read as follows:

Sec.  801.4  Meaning of intended uses.

    The words intended uses or words of similar import in Sec. Sec.  
801.5, 801.119, 801.122, and 1100.5 of this chapter refer to the 
objective intent of the persons legally responsible for the labeling of 
devices. The intent is determined by such persons' expressions or may 
be shown by the circumstances surrounding the distribution of the 
article. This objective intent may, for example, be shown by labeling 
claims, advertising matter, or oral or written statements by such 
persons or their representatives. It may be shown, for example, by 
circumstances in which the article is, with the knowledge of such 
persons or their representatives, offered and used for a purpose for 
which it is neither labeled nor advertised. The intended uses of an 
article may change after it has been introduced into interstate 
commerce by its manufacturer. If, for example, a packer, distributor, 
or seller intends an article for different uses than those intended by 
the person from whom he received the device, such packer, distributor, 
or seller is required to supply adequate labeling in accordance with 
the new intended uses. And if the totality of the evidence establishes 
that a manufacturer objectively intends that a device introduced into 
interstate commerce by him is to be used for conditions, purposes, or 
uses other than ones for which it has been approved, cleared, granted 
marketing authorization, or is exempt from premarket notification 
requirements (if any), he is required, in accordance with section 
502(f) of the Federal Food, Drug, and Cosmetic Act, or, as applicable, 
duly promulgated regulations exempting the device from the requirements 
of section 502(f)(1), to provide for such device adequate labeling that 
accords with such other intended uses.

PART 1100--TOBACCO PRODUCTS SUBJECT TO FDA AUTHORITY

0
5. The authority citation for part 1100 is revised to read as follows:

    Authority:  21 U.S.C. 387a(b), 387f(d); Secs. 901(b) and 906(d), 
Pub. L. 111-31; 21 CFR 16.1 and 1107.1; 21 CFR 1.1, 1.20, 14.55, 
17.1, and 17.2. Section 1100.5 is issued under 21 U.S.C. 321, 
353(g), and 371(a); 21 CFR 1.1.

0
6. Part 1100 is amended by adding Sec.  1100.5 to read as follows:

Sec.  1100.5  Exclusion from tobacco regulation.

    If a product made or derived from tobacco that is intended for 
human consumption is intended for use for any of the purposes described 
in paragraph (a) or (b) of this section, the product is not a tobacco 
product as defined in section 201(rr) of the Federal Food, Drug, and 
Cosmetic Act and will be subject to regulation as a drug, device, or 
combination product.
    (a) The product is intended for use in the diagnosis of disease or 
other conditions, or in the cure, mitigation, treatment or prevention 
of disease, including use in the cure or treatment of nicotine 
addiction (e.g., smoking cessation), relapse prevention, or relief of 
nicotine withdrawal symptoms;
    (b) The product is intended to affect the structure or any function 
of the body in any way that is different from effects related to 
nicotine that were commonly and legally claimed in the marketing of 
cigarettes and smokeless tobacco products prior to March 21, 2000.

    Dated: December 29, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-31950 Filed 1-6-17; 8:45 am]
 BILLING CODE 4164-01-P