Clarification of When Products Made or Derived From Tobacco Are Regulated as Drugs, Devices, or Combination Products; Amendments to Regulations Regarding “Intended Uses”, 2193-2217 [2016-31950]
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AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Final rule.
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
SUMMARY:
In rule document 2016–28714
appearing on pages 90126–90177 in the
issue of Tuesday, December 13, 2016,
make the following correction:
■ On page 90174, in the third column,
in the 18th through 22nd line,
paragraph (iii) should read
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Clarification of When Products Made
or Derived From Tobacco Are
Regulated as Drugs, Devices, or
Combination Products; Amendments
to Regulations Regarding ‘‘Intended
Uses’’
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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 (§ 1100.5)
B. Existing ‘‘Intended Use’’ Regulations
(§§ 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
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Executive Summary
Purpose of the Rule
The Family Smoking Prevention and
Tobacco Control Act (Tobacco Control
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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 §§ 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/
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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
§§ 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 §§ 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 tobaccoderived 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.
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TABLE 1—ONE-TIME COSTS
Low
Mid-point
High
Learning costs .............................................................................................................................
Review communications, such as labeling and promotional materials .......................................
Revisions to communications, such as labeling and promotional materials ...............................
$117,412
486,024
283,003
$146,779
486,024
1,092,422
$176,147
486,024
1,901,841
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
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
B. Drug/Device/Combination Product
Definitions
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
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
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).
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).
3 In this final rule, the cited language may be
referred to as the ‘‘drug/device definitions.’’
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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).
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.,
§ 201.128 (drugs), § 801.4 (devices)).4
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
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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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
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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
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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
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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 nonexhaustive 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: Eliquids; 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 eliquids, and programmable software.
Thus, vaping hardware meets the
definition of tobacco product.
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
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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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,
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.
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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).
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
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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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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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
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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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.
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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.
Given the availability of FDAapproved drugs for smoking cessation,
9 See, e.g., Merriam-Webster Online Dictionary,
available at https://www.merriam-webster.com/
dictionary/therapeutic.
10 See, e.g., approved labeling for Nicoderm CQ,
Nicorette, Habitrol.
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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
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• 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
Because MRTPs have the potential to
be marketed as less harmful than other
tobacco products, including as
presenting a lower risk of tobaccorelated 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.
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).
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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
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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
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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
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(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.
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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
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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
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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
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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, caseby-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
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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, factspecific 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
12 See https://www.fda.gov/newsevents/
publichealthfocus/ucm252360.htm.
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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.
(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
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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.
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 ecigarettes 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
13 See
61 FR 44619 at 44648, August 28, 1996.
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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
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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
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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.
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F. Changes to Existing ‘‘Intended Use’’
Regulations
FDA is also making changes to
§§ 201.128 and 801.4. First, the final
rule inserts a reference to § 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 §§ 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
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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 tobaccoderived 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 (§ 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
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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
§§ 201.128 and 801.4 a reference to
§ 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 § 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
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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 § 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 § 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
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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 § 1100.5(a).14
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 § 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 § 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
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.
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 § 1100.5.
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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.
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 § 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 § 312.3
may be subject to regulation as
investigational tobacco products.
B. Existing ‘‘Intended Use’’ Regulations
(§§ 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 § 201.128 (drugs),
§ 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 (§§ 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
§ 201.128 is amended to provide that if
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.
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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 § 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
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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.
Before FDA issued the proposed rule,
some drug sponsors had expressed
concern with the last sentence of
§ 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 FDAapproved labeling would transform the
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.
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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 § 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
§§ 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.,
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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 (§§ 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 §§ 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
§ 201.128. Before the amendments
implemented by this rule, both
§§ 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 §§ 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,
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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 §§ 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
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2207
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]elfserving 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)
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(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
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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
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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] § 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
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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 offlabel uses of a drug or device does not
satisfy this test.
Similarly, another comment urged
FDA to confirm that truthful and nonmisleading 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: https://www.fda.gov/
NewsEvents/MeetingsConferences
Workshops/ucm489499.htm). That
examination is ongoing. In contrast, the
purpose of amending §§ 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
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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
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2209
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
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)).
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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.
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.
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).
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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
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 nonpromotional 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 nonmisleading scientific information about
unapproved uses at medical or scientific
conferences when done in nonpromotional 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
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).
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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.
(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
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).
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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 nonmisleading 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:
https://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
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Sorrell held that content- or speakerbased 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 § 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.
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(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 tissuebased 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 § 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 ecigarettes to marketing claims of
‘‘smoking pleasure’’ and ‘‘smoking
satisfaction’’ since that is how
traditional tobacco products were
‘‘customarily marketed’’ prior to March
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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 ecigarettes 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
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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
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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 ecigarette 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
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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
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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 § 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, caseby-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 https://www.fda.gov/
downloads/UCM229175.pdf.
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2213
(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
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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 reorganization, 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
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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 § 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
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Fmt 4700
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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 § 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
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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 https://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
2215
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
Category
Primary
estimate
Low
estimate
High
estimate
Year
dollars
Discount
rate
(%)
Period
covered
(years)
Notes
Benefits
Annualized ...................
Monetized ($millions/
year) .........................
Annualized ...................
Quantified
........................
........................
........................
........................
7
........................
........................
........................
........................
........................
........................
........................
........................
........................
........................
........................
........................
........................
3
7
3
........................
........................
........................
sradovich on DSK3GMQ082PROD with RULES
Qualitative ....................
Reduce regulatory ambiguity
Costs
Annualized ...................
Monetized ($millions/
year) .........................
Annualized
Quantified .....................
Qualitative ....................
VerDate Sep<11>2014
$0.246
$1.126
$0.365
2014
7
10
0.202
0.202
........................
........................
........................
0.202
0.104
........................
........................
........................
0.202
0.301
........................
........................
........................
........................
2014
........................
........................
........................
........................
3
7
3
........................
........................
10
........................
........................
........................
16:50 Jan 06, 2017
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2216
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TABLE 2—ECONOMIC DATA: COSTS AND BENEFITS STATEMENT—Continued
Units
Category
Primary
estimate
Low
estimate
High
estimate
Transfers ......................
Federal .........................
Annualized ...................
Monetized ($millions/
year)
........................
........................
........................
........................
........................
........................
........................
........................
........................
From/To
From:
Other ............................
Annualized ...................
Monetized ($millions/
year)
........................
........................
From/To
From:
Year
dollars
Discount
rate
(%)
Period
covered
(years)
........................
........................
........................
........................
7
3
........................
........................
........................
7
3
Notes
........................
........................
To:
........................
........................
........................
........................
........................
........................
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 https://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
sradovich on DSK3GMQ082PROD with RULES
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
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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 EvidenceBased 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
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Fmt 4700
Sfmt 4700
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
https://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, ECigarettes 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 https://www.gallup.com/poll/
163763/smokers-quit-tried-multipletimes.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.
E:\FR\FM\09JAR1.SGM
09JAR1
Federal Register / Vol. 82, No. 5 / Monday, January 9, 2017 / Rules and Regulations
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.
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
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.
■
2. Revise § 201.128 to read as follows:
sradovich on DSK3GMQ082PROD with RULES
§ 201.128
Meaning of ‘‘intended uses’’.
The words intended uses or words of
similar import in §§ 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
VerDate Sep<11>2014
16:50 Jan 06, 2017
Jkt 241001
2217
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.
PART 801—LABELING
■
■
3. The authority citation for part 801
continues to read as follows:
§ 1100.5 Exclusion from tobacco
regulation.
Authority: 21 U.S.C. 321, 331, 351, 352,
360d, 360i, 360j, 371, 374.
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.
■
6. Part 1100 is amended by adding
§ 1100.5 to read as follows:
4. Revise § 801.4 to read as follows:
§ 801.4
Meaning of intended uses.
The words intended uses or words of
similar import in §§ 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
5. The authority citation for part 1100
is revised to read as follows:
■
PO 00000
Frm 00025
Fmt 4700
Sfmt 9990
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 888
[Docket No. FDA–2014–N–1205]
Orthopedic Devices; Reclassification
of Pedicle Screw Systems, Henceforth
To Be Known as Thoracolumbosacral
Pedicle Screw Systems, Including
Semi-Rigid Systems
Correction
In rule document 2016–31670
beginning on page 96366 in the issue of
Friday, December 30, 2016, make the
following correction:
On page 96372, in the second column,
in the 25th, 51st, and 67th lines, and in
the third column, in the tenth line,
‘‘June 28, 2018’’ should read ‘‘July 1,
2019’’.
[FR Doc. C1–2016–31670 Filed 1–6–17; 8:45 am]
BILLING CODE 1301–00–D
E:\FR\FM\09JAR1.SGM
09JAR1
Agencies
[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]
=======================================================================
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
Low Mid-point High
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
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).
---------------------------------------------------------------------------
\3\ In this final rule, the cited language may be referred to as
the ``drug/device definitions.''
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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'').
---------------------------------------------------------------------------
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.
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
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).
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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
https://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 https://www.fda.gov/newsevents/publichealthfocus/ucm252360.htm.
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(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\
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\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.
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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: https://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: https://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 https://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
https://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 https://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 https://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 https://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