[Federal Register Volume 90, Number 10 (Thursday, January 16, 2025)]
[Proposed Rules]
[Pages 5032-5144]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-00397]
[[Page 5031]]
Vol. 90
Thursday,
No. 10
January 16, 2025
Part V
Department of Health and Human Services
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Food and Drug Administration
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21 CFR Part 1160
Tobacco Product Standard for Nicotine Yield of Cigarettes and Certain
Other Combusted Tobacco Products; Proposed Rule
Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 /
Proposed Rules
[[Page 5032]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 1160
[Docket No. FDA-2024-N-5471]
RIN 0910-AI76
Tobacco Product Standard for Nicotine Yield of Cigarettes and
Certain Other Combusted Tobacco Products
AGENCY: Food and Drug Administration, Department of Health and Human
Services (HHS).
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
proposing a tobacco product standard that would regulate nicotine yield
by establishing a maximum nicotine level in cigarettes and certain
other combusted tobacco products. FDA is proposing this action to
reduce the addictiveness of these products, thus giving people who are
addicted and wish to quit the ability to do so more easily. The
proposed product standard is anticipated to benefit the population as a
whole. For example, it would help to prevent people who experiment with
cigarettes and cigars from developing addiction and using combusted
tobacco products regularly.
DATES: Either electronic or written comments on the proposed rule must
be submitted by September 15, 2025. Submit comments (including
recommendations) on the collection of information under the Paperwork
Reduction Act of 1995 (PRA) by September 15, 2025.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of September 15, 2025. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked, and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2024-N-5471 for ``Tobacco Product Standard for Nicotine Yield of
Cigarettes and Certain Other Combusted Tobacco Products.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday, 240-402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
Go to the Federal eRulemaking Portal at https://www.regulations.gov
for access to the rulemaking docket, including any background documents
and the plain-language summary of the proposed rule of not more than
100 words in length required by the Providing Accountability Through
Transparency Act of 2023.
Submit comments on the information collection under the Paperwork
Reduction Act of 1995 to the Office of Management and Budget (OMB) at
https://www.reginfo.gov/public/do/PRAMain. Find this particular
information collection by selecting ``Currently under Review--Open for
Public Comments'' or by using the search function. The title of this
proposed collection is ``Tobacco Product Standard for Nicotine Yield of
Cigarettes and Certain Other Combusted Tobacco Products.''
FOR FURTHER INFORMATION CONTACT: With regard to the proposed rule: Nate
Mease or Dhanya John, Center for Tobacco Products, Food and Drug
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002,
877-287-1373, [email protected].
With regard to the information collection: JonnaLynn Capezzuto,
Office of Operations, Food and Drug Administration, Three White Flint
North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-
3794, [email protected].
SUPPLEMENTARY INFORMATION:
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Table of Contents
I. Executive Summary
A. Purpose of the Proposed Rule
B. Summary of the Major Provisions of the Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
A. Need for the Regulation
B. Relevant Regulatory History
C. Legal Authority
IV. Nicotine in Cigarettes and Other Combusted Tobacco Products:
Addiction, Initiation, Dependence, Cessation, Relapse, Health
Effects, and Consumer Perceptions
A. Nicotine Is Addictive
B. The Developing Brain's Vulnerability to the Effects of
Nicotine Leads to Progression to Regular Cigarette Use Among Youth
and Young Adults Who Experiment
C. Youth and Adult Cigarette Smoking Cessation and Relapse
D. Smoking Cigarettes and Other Combusted Tobacco Products
Causes Serious Negative Health Effects
E. Tobacco Product Marketing Has Contributed to Disparities in
Use and Health Outcomes
F. Consumer Knowledge, Attitudes, Beliefs, and Perceptions About
Nicotine
V. History and Perceptions of VLNC Cigarettes
A. History of LNC and VLNC Cigarettes
B. Consumer Knowledge, Attitudes, Beliefs, and Perceptions
Regarding VLNC Cigarettes and Regulation of Levels of Nicotine in
Tobacco
VI. Rationale for Products Covered by the Proposed Product Standard
A. Prevalence and Abuse Potential of Cigarettes and Other
Combusted Tobacco Products
B. Potential for Tobacco Product Switching
VII. Discussion of Nicotine-Related Topics
A. Approach To Limiting User Exposure to Nicotine
B. Scientific Evidence Supports the Target Level of Nicotine
C. An Immediate Nicotine Reduction Approach Is Strongly
Supported by Scientific Evidence
D. Scientific Evidence Supports the Use of an Analytical Test
Method To Determine Nicotine Level
E. Scientific Evidence Supports the Technical Achievability of
the Proposed Maximum Nicotine Level Target
F. Proposal Does Not Seek To Limit Nicotine to Zero
VIII. Determination That the Standard Is Appropriate for the
Protection of the Public Health
A. Approach To Estimating Impacts to the Population as a Whole
B. The Likelihood That Nonusers Would Start Using Cigarettes or
Other Combusted Tobacco Products
C. The Likelihood That Existing Users Would Reduce Cigarette and
Other Combusted Tobacco Product Consumption or Stop Smoking
D. Benefits and Risks to the Population as a Whole
E. Approach Concerning Adjustments to Inputs to the Model
Accounting for Other Tobacco Product Standards
F. Benefits and Risks to the Population as a Whole Accounting
for Other Tobacco Product Standards
G. Conclusion
IX. Additional Considerations and Requests for Comment
A. Section 907 of the FD&C Act
B. Pathways to Market
C. Considerations and Request for Comments on Scope of Products
D. Considerations and Request for Comments on the Potential for
Illicit Trade
X. Description of Proposed Regulation
A. General Provisions (Proposed Subpart A)
B. Product Requirements (Proposed Subpart B)
C. Manufacturing Code and Recordkeeping Requirements (Proposed
Subpart C)
XI. Proposed Effective Date
XII. Preliminary Economic Analysis of Impacts
A. Introduction
B. Summary of Costs and Benefits
XIII. Analysis of Environmental Impact
XIV. Paperwork Reduction Act of 1995
XV. Federalism
XVI. Severability
XVII. Consultation and Coordination With Indian Tribal Governments
XVIII. References
I. Executive Summary
A. Purpose of the Proposed Rule
Each year, 480,000 people die prematurely from a smoking-
attributable disease, making tobacco use the leading cause of
preventable disease and death in the United States (Ref. 1). Nearly all
these adverse health effects are ultimately the result of addiction to
the nicotine in combusted tobacco products, leading to repeated
exposure to toxicants from those products. Nicotine, the primary
addictive constituent in tobacco products, can be delivered through a
variety of products along a continuum of risk. To protect youth and
reduce tobacco-related disease and death, the Agency utilizes a
comprehensive approach to tobacco and nicotine regulation (https://www.fda.gov/media/174911/download). As part of this comprehensive
approach, FDA is proposing a tobacco product standard that would
regulate nicotine yield by establishing a maximum nicotine level in
cigarettes \1\ and certain other combusted tobacco products (proposed
product standard).
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\1\ Throughout this document, FDA generally uses the term
``cigarettes'' to refer to combusted cigarettes, unless specifically
stated or context indicates that noncombusted cigarettes are
referenced. In general, the term is not meant to include any
noncombusted tobacco products that meet the definition of cigarette
in section 900(3) of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 387(3)).
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As the U.S. District Court for the District of Columbia recognized
in United States v. Philip Morris USA, Inc. et al., 449 F.Supp.2d 1
(D.D.C. 2006), aff'd in relevant part, 566 F.3d 1095 (D.C. Cir. 2009),
the tobacco industry has long known that nicotine creates and sustains
addiction, and the industry is dependent on maintaining this addiction.
Id. at 307. The court noted how cigarette companies have engaged in
extensive research to understand how nicotine operates within the human
body and then designed their cigarettes to precisely control nicotine
delivery and provide nicotine doses to create and sustain addiction.
Id. at 307-309. Moreover, the court confirmed that industry documents
supported the conclusion that these companies ``knew early on in their
research that if a cigarette did not deliver a certain amount of
nicotine, new smokers would not become addicted, and `confirmed'
smokers would be able to quit.'' Id. at 219. In fact, the tobacco
industry has had programs in place since the 1960s to obtain ``any
level of nicotine desired'' (Ref. 2). These companies sought to
identify the ``optimum'' dose needed to ``satisfy'' people who smoke
cigarettes and, thereby, assure their continued smoking. Philip Morris,
449 F.Supp.2d at 309-10. This proposed product standard would seek to
set a maximum nicotine level such that cigarettes and certain other
combusted tobacco products could no longer create and sustain this
addiction among people who smoke cigarettes and certain other combusted
tobacco products.
The proposed product standard would limit the addictiveness of the
most toxic and widely used tobacco products, which would have
significant public health benefits for all age groups. The proposal
would have cessation benefits for adults who use cigarettes and certain
other combusted tobacco products, most of whom want to quit but are
repeatedly unsuccessful because of the highly addictive nature of these
products (see section IV.A of this document). Because these products
would not create and sustain addiction, users would be able to quit
when they would like, something many who use these products currently
do not have the ability to do. Additionally, combusted tobacco products
at minimally addictive or nonaddictive levels of nicotine would remain
on the market for those who currently smoke and would like to continue
to do so.
It would also help prevent people who experiment with cigarettes or
certain other combusted tobacco
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products (mainly youth) from moving beyond experimentation, developing
an addiction to nicotine, and progressing to regular use of combusted
tobacco products as a result of that addiction (see section VIII.B of
this document). Reducing the number of people who experiment with
cigarettes or certain other combusted tobacco products who then
transition to regular use of these products would prevent severe
adverse health consequences of long-term smoking at the individual
level and result in public health benefits at the population level.
Based on FDA's population health model, by the year 2100, in the United
States, approximately 48 million youth and young adults who would have
otherwise initiated habitual cigarette smoking would not as a result of
the proposed product standard. The model also projects that more than
12.9 million additional people who smoke cigarettes would quit smoking
cigarettes \2\ 1 year after implementation of the proposed product
standard; this estimate increases to 19.5 million additional people
within 5 years of implementation (this includes people who exclusively
smoke cigarettes quitting all tobacco products or completely switching
to noncombusted tobacco product use, as well as people who engage in
dual use of cigarettes and noncombusted tobacco products quitting
cigarette use). In addition, the model estimates that, by the year
2060, in the United States, this proposed product standard would result
in 1.8 million tobacco-related deaths averted, rising to 4.3 million
deaths averted by the end of the century. The reduction in premature
deaths attributable to the proposed product standard would result in
19.6 million life years gained by 2060 and 76.4 million life years
gained by 2100. For the reasons discussed in the preamble, FDA finds
that the proposed product standard would be appropriate for the
protection of the public health.
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\2\ For the purposes of this proposed rule, where describing
expected transition behaviors, we also use the shorter phrase ``quit
smoking'' to refer to stopping use of combusted cigarettes.
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As explained in section VIII.A., the population health model uses
inputs derived from available empirical evidence and expert opinion to
estimate the impact of this proposed rule. To obtain expert opinion for
the model inputs, FDA conducted a formal expert elicitation process in
2015 and repeated it in 2018. FDA is conducting another expert
elicitation process and intends to publish the results of this update
for public review and additional comment on this proposed standard in
light of that update.
B. Summary of the Major Provisions of the Proposed Rule
There are currently no tobacco product standards regulating
nicotine in tobacco products. The proposed rule would establish a
maximum level of nicotine in cigarettes and certain other combusted
tobacco products. FDA issued an Advance Notice of Proposed Rulemaking
regarding a potential nicotine tobacco product standard (Nicotine
ANPRM), and the Agency reviewed and analyzed the comments to that ANPRM
(83 FR 11818 (March 16, 2018)). FDA also conducted an extensive and
robust review of the relevant scientific literature, as discussed
throughout this document. FDA is proposing the following provisions
based on the comments received and the Agency's analysis of relevant
scientific literature.
Proposed scope--Given that approximately 28 million adults and
380,000 youth in the United States currently smoke cigarettes and the
toxicity and addictiveness of these products, cigarettes are the
tobacco product category that causes the largest amount of harm to
public health in the United States (Refs. 3 and 4). However, if a
product standard were to cover only cigarettes, it is likely that a
significant number of addicted people who smoke cigarettes would
migrate to other similar combusted tobacco products after the standard
went into effect to maintain their nicotine exposure, thereby
undermining the public health benefits of the standard (Ref. 5) (see
also section VI.B of this document). Therefore, to increase the public
health benefits, we are proposing to cover the following products under
this proposed product standard: Cigarettes (other than noncombusted
cigarettes, such as heated tobacco products (HTPs \3\) that meet the
definition of a cigarette), cigarette tobacco, roll-your-own (RYO)
tobacco, cigars (including little cigars, cigarillos, and large cigars
but excluding premium cigars \4\), and pipe tobacco (other than
waterpipe tobacco \5\). FDA requests comments, data, and research
regarding this proposed scope.
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\3\ Tobacco products that meet the statutory or regulatory
definition of a cigarette but are not combusted (do not exceed 350
[deg]C) are categorized as ``heated tobacco products'' (HTPs) for
purposes of FDA's premarket review. HTPs that meet the definition of
a cigarette must be in compliance with the applicable statutory and
regulatory requirements for cigarettes, unless otherwise noted in a
marketing authorization order (Ref. 6).
\4\ See section III.B.3 of this document.
\5\ Waterpipe tobacco (also known as hookah tobacco) is a type
of tobacco product that produces smoke that people inhale when a
hookah device is heated. Hookah tobacco (also known as waterpipe
tobacco, maassel, shisha, narghile, or argileh) typically contains a
mixture of tobacco, sweeteners, and flavoring. The hookah device (or
waterpipe) used to smoke the hookah tobacco works by passing
charcoal or electric heated air through the tobacco mixture and
ultimately through a water-filled chamber (Ref. 7).
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FDA is proposing to exclude noncombusted cigarettes, such as HTPs
that meet the definition of a cigarette in section 900(3) of the
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 387(3)) from
the scope of this proposed product standard (proposed Sec. 1160.3
includes a definition of cigarette). Therefore, ``cigarettes'' in this
proposed rule refers to combusted cigarettes, not HTPs. Based on FDA's
experience with application review, certain noncombusted cigarettes
produce fewer or lower levels of some toxicants than combusted
cigarettes. FDA recognizes that tobacco products exist on a continuum
of risk, with combusted cigarettes being the deadliest, and that
certain non-combusted cigarettes pose less risk to individuals who use
cigarettes or certain other combusted tobacco products or to population
health than other products meeting the definition of a cigarette.
Accordingly, FDA requests comments, data, and research regarding the
proposal to exclude noncombusted cigarettes from the scope of this
proposed rule, including any data that could justify otherwise.
FDA also proposes to exclude waterpipe tobacco from the proposed
product standard because, unlike cigarette tobacco, pipe tobacco, RYO
tobacco, and cigars (other than premium cigars), FDA believes there is
little risk of switching under the proposed product standard.
Waterpipes as currently marketed and used generally require substantial
time for preparation and use (i.e., an approximately 1-hour session
with waterpipes compared to 5-7 minutes with cigarettes). In addition,
they are generally large and unwieldy and thus ill-suited for mobile
usage, such as while driving or walking. FDA requests comments, data,
and research regarding the proposal to exclude waterpipe tobacco from
the scope of this proposed rule, including any data that could justify
otherwise.
FDA is also not including noncombusted non-cigarette tobacco
products, such as electronic nicotine delivery systems (ENDS) (which
include e-cigarettes) and smokeless tobacco products, in the scope of
this proposed product standard. As discussed throughout this document,
nicotine is the primary addictive constituent in
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tobacco products, and it is the nicotine in such products that both
creates and sustains addiction and ultimately leads to the significant
adverse health effects caused by these products. While these effects
raise concerns in the context of any tobacco product--none of which is
without risk--at this time, FDA is focusing this proposed rule on
nicotine levels in cigarettes and certain other combusted tobacco
products because combusted tobacco products are responsible for the
majority of death and disease due to tobacco use. FDA expects that, if
this proposed rule is finalized as proposed, many people who smoke
cigarettes will quit smoking, either by quitting all tobacco use or by
completely switching to a noncombusted tobacco product. Those who
switch completely to use of a noncombusted tobacco product may sustain
their nicotine dependence but may significantly reduce their risk of
tobacco-related death and disease because switching completely to a
noncombusted tobacco product would reduce exposure to the chemical
constituents created through combustion, which are currently the
primary contributors of tobacco-related harm (Ref. 8). Importantly,
this action would also help to prevent people who experiment with
cigarettes and cigars (mainly youth) from moving beyond
experimentation, developing an addiction to nicotine, and progressing
to regular use of combusted tobacco products as a result of that
addiction. We request comments, data, and research regarding the
proposed scope of this rule.
For further discussion regarding considerations and request for
comments on the proposed scope of this rule, see section IX.C of this
document.
Proposed product standard for nicotine--FDA is proposing to make
cigarettes and certain other combusted tobacco products minimally
addictive or nonaddictive \6\ by limiting the nicotine yield of these
products. We propose to limit nicotine yield by setting a maximum
nicotine content level of 0.70 milligrams (mg) of nicotine per gram of
total tobacco in these tobacco products. For comparison, the average
nicotine content in the top 100 cigarette brands for 2017 is 17.2 mg/g
of total tobacco (Ref. 9). Nicotine yield is the amount of nicotine in
smoke, in other words, the amount of nicotine to which a smoker
potentially is exposed. While nicotine yield can be measured through
machine-generated smoking methods (e.g., International Organization for
Standardization (ISO) machine smoking method, Canadian Intense (CI)
smoking method, Federal Trade Commission (FTC) smoking method), it can
vary due to a user's compensatory behaviors--e.g., inhaling more
deeply, taking larger puffs, and blocking cigarette features designed
to reduce nicotine yield--such that users can increase the amount of
nicotine yield compared to the machine-generated yield. In contrast,
nicotine ``content,'' which refers to the amount of nicotine present in
tobacco filler, is not affected by smoking behavior or cigarette design
features. Reducing the nicotine content to the proposed 0.70 mg of
nicotine per gram of total tobacco limit in the finished tobacco
products subject to this proposed product standard places an absolute
maximum limit on the amount of nicotine present in tobacco smoke
available for intake by users of these products. There are many
different tobacco product characteristics that can be manipulated to
affect nicotine yield, one of which is nicotine content. Setting a
limit on nicotine content and measuring that content is more effective
in reducing yield (i.e., the amount of nicotine the user is exposed to)
than setting a limit based on a direct measurement of yield under
standardized smoking-machine protocols because nicotine content cannot
be affected by the compensatory behavior described above. Therefore,
limiting nicotine yield through a maximum nicotine content level would
better achieve the public health benefits that come from reducing the
amount of the nicotine to which a user is exposed than would setting a
limit based on a measurement of the maximum machine-measured yield of
tobacco products. For further discussion, see section VII.A.
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\6\ FDA is using the term ``nonaddictive'' throughout this
preamble specifically in the context of the available data on very
low nicotine content cigarettes. We acknowledge the highly addictive
potential of nicotine itself depending upon the route of delivery.
As discussed elsewhere in this preamble, questions remain with
respect to the precise level of nicotine in cigarettes that might
render them either minimally addictive or nonaddictive for specific
individual members or segments of the population.
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The proposed limit of 0.70 mg of nicotine per gram of total tobacco
is based on FDA's analysis of studies regarding the likely effects of
reducing nicotine, which shows that extended exposure to very low
nicotine content (VLNC) combusted cigarettes is associated with reduced
addiction potential, dependence levels, number of cigarettes smoked per
day and increased quit attempts among people who currently smoke
cigarettes, without increasing toxicant exposure, craving, withdrawal,
or compensatory smoking. Throughout this preamble, ``VLNC cigarettes''
refers to combusted cigarettes that have been reported to contain <=
1.0 mg nicotine per gram of total tobacco, ``low nicotine content (LNC)
cigarettes'' refers to cigarettes with > 1.0 mg and < 11.4 mg nicotine
per gram of total tobacco, and ``normal nicotine content (NNC)
cigarettes'' refers to cigarettes with >= 11.4 mg nicotine per gram of
total tobacco.\7\ FDA uses these acronyms in places where we have
confirmed that the nicotine content of the cigarettes referenced meets
these definitions. In documents that reference nicotine content in
tobacco, but do not specify the levels of nicotine and therefore cannot
be confirmed to meet these definitions, we have maintained the full
description that best reflects what was used in the original document
(e.g., low nicotine content tobacco).
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\7\ The term VLNC should not be confused with the cigarette
brand name ``VLN;'' ``VLN'' refers to cigarette products authorized
for marketing by FDA in 2019. See https://www.fda.gov/media/133633/download?attachment and https://www.fda.gov/media/133635/download?attachment.
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FDA is not seeking to require the reduction of nicotine yields in
any tobacco product to zero, which would violate section 907(d)(3) of
the FD&C Act (21 U.S.C. 387g(d)(3)). FDA requests comments, data, and
research regarding this proposed maximum nicotine level.
Immediate nicotine reduction approach--FDA is proposing an
immediate nicotine reduction (i.e., single target) approach to reach
the proposed maximum nicotine level (rather than a gradual reduction,
or stepped-down, approach) to limit additional toxicant exposure. Based
on studies involving VLNC cigarettes and other reduced nicotine content
(RNC) cigarettes, we expect that there would be very little or no
compensatory smoking (and, consequently, additional limited toxicant
exposure) with an immediate reduction approach, as opposed to a gradual
reduction approach which showed evidence of increased compensatory
smoking. As such, an immediate reduction approach would increase the
benefits of the proposed product standard. FDA also notes that this
immediate nicotine reduction approach would reduce manufacturing costs
for those products covered by the proposed standard because
manufacturers would not have reason to formulate multiple products and
then prepare and submit premarket review applications at each phase of
a gradual reduction approach. We request comments, data, and
information regarding the selection of an immediate reduction approach.
Analytical test method--To assist FDA in determining compliance
with this rule, the proposed product standard would require
manufacturers to analyze
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the nicotine levels of cigarettes and certain other combusted tobacco
products covered by the rule using an analytical test method that has
been validated in an analytical test laboratory. In addition, FDA is
proposing to require product testing prior to commercial distribution
in the United States to prevent nonconforming tobacco products from
entering the stream of commerce and reaching consumers.
Sampling plan--The proposed product standard would require tobacco
product manufacturers to design and implement a sampling plan that
covers each batch of finished tobacco product \8\ that they
manufacture. This sampling plan would be based on a valid scientific
rationale (such as representative sampling) to ensure that each product
complies with the proposed product standard. This sampling plan would
provide procedures for the manufacturer to select samples to
demonstrate conformance to the proposed product standard requirement.
The required procedures would help ensure that products that do not
conform to the product standard are not sold or distributed to
consumers.
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\8\ For the purpose of this document, the term ``finished
tobacco product'' refers to those products subject to this proposed
rule. FDA proposes to define a ``finished tobacco product'' to mean
a tobacco product, including all components and parts, sealed in
final packaging (e.g., filters or filter tubes sold to consumers
separately or as part of kits) or in the final form in which it is
intended to be sold to consumers. For a discussion of products FDA
proposes to include within the scope of this product standard, see
sections IX.C and X.A.1 of this document.
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Nonconforming tobacco product--The proposed product standard would
require tobacco product manufacturers to establish procedures for the
control and disposition of tobacco products that do not conform to the
requirements of this rule. These procedures are necessary to help
prevent the distribution of nonconforming tobacco products by ensuring
that all potential nonconforming products are identified, investigated,
and segregated and that appropriate disposition and followup are taken
for products determined to be nonconforming. This proposed requirement
would ensure that any reports of nonconforming products, whether as a
result of manufacturer testing or otherwise, are examined and
investigated and that appropriate measures are taken to ensure that
nonconforming products are not distributed to consumers and to prevent
future nonconformity.
Manufacturing code--Currently, there is no requirement for the use
of a manufacturing code for tobacco products. However, the proposed
regulation Requirements for Tobacco Product Manufacturing Practice
(TPMP) (see https://www.federalregister.gov/documents/2023/03/10/2023-04591/requirements-for-tobacco-product-manufacturing-practice) includes
a requirement for a manufacturing code, and this rulemaking's provision
is modeled on the proposed TPMP provision. The proposed product
standard would require the use of a manufacturing code to serve as a
common identifier for production and distribution records. The purpose
of the manufacturing code is to allow manufacturers and FDA to identify
the production batch of a particular finished product that has been
released for distribution. This information is intended to help
determine the product's history (e.g., batch production records) and
assist manufacturers and FDA in the event of a nonconforming tobacco
product investigation and any corrective actions to be taken by a
manufacturer as a result of the investigation.
Recordkeeping requirements--To assist FDA in determining compliance
with the rule and aid in nonconforming product investigations, the
proposed product standard would require that manufacturers establish
and maintain records regarding the results of testing conducted on each
batch to determine conformance with the proposed standard. In addition,
this proposed product standard would require that manufacturers
maintain records of sampling plans and sampling procedures, records
related to manufacturing controls, and all records related to its
analytical test method validation. FDA also is proposing to require
that it be possible to identify the production batch of a particular
finished product that has been released for distribution.
Proposed effective date--FDA proposes that any final rule that may
issue based on this proposed rule become effective 2 years after the
date of publication of the final rule. Therefore, after the effective
date no person could distribute, sell, or offer for sale or
distribution within the United States finished tobacco products that
are not in compliance with part 1160 (21 CFR part 1160). Prior to the
effective date of any final rule that may issue based on this proposed
rule, wholesalers, retailers, and related entities would be able to
sell available stock of finished tobacco products were not in
compliance with part 1160 while transitioning inventory in anticipation
of the effective date of the final rule; however, they would not be
permitted to sell off such stock after the effective date. FDA believes
this approach would allow adequate time for developing any necessary
changes in technology or inputs to comply with a finalized product
standard. It also would provide sufficient time for tobacco product
manufacturers to submit, and FDA to review, applications for new
tobacco products that comply with the finalized product standard.
Additionally, FDA believes that this approach would allow adequate time
for making any changes to tobacco purchasing choices and curing
methods, and for preparation or changes needed in facilities and
processes. FDA requests comments and data on this proposed effective
date. For further discussion regarding considerations and request for
comments on the proposed effective date of this rule, see section XI of
this document.
Given that any new tobacco products that comply with this product
standard would be required to undergo premarket review, FDA is
considering options for addressing any influx of applications.
C. Legal Authority
Section 907 of the FD&C Act authorizes FDA to adopt tobacco product
standards, including product standards that include provisions for
nicotine yields; for the reduction or elimination of other constituents
(including smoke constituents) or harmful components; respecting the
construction, components, ingredients, additives, constituents
(including smoke constituents), and properties of tobacco products; for
the testing of tobacco products; and for restricting the sale of
tobacco products to the extent consistent with section 906 (21 U.S.C.
387f) (section 907(a)(3), (a)(4)(A)(i) to (iii), and (a)(4)(B)(i) to
(ii) and (iv) to (v)). The FD&C Act also establishes FDA's authority to
require tobacco product manufacturers to establish and maintain records
in section 909 (21 U.S.C. 387i); authority related to adulterated and
misbranded tobacco products in sections 902 and 903 (21 U.S.C. 387b and
387c); authority regarding premarket review of new tobacco products in
section 910 (21 U.S.C. 387j); authority related to prohibited acts in
section 301 (21 U.S.C. 331); and FDA's rulemaking and inspection
authorities in sections 701 and 704 (21 U.S.C. 371 and 374).
D. Costs and Benefits
The main quantified benefits come from averted mortality and
morbidity as a result of reduced prevalence for people who currently
use combusted
[[Page 5037]]
tobacco products, and reduced mortality from reduced exposure to
secondhand smoke among people. Unquantified benefits include medical
cost savings, productivity loss savings, reduced exposure to thirdhand
smoke, and environmental impacts. We expect this proposed rule, if
finalized, to impose costs on industry to follow the product standard,
on the broader economy to repurpose land, labor, and capital, on
consumers impacted by the product standard, and on FDA to enforce this
product standard. In addition to benefits and costs, this rule would
cause transfers from the Federal Government and State governments in
the form of tax revenue, from firms in the form of reduced revenue, and
transfers between or within firms to cover shifts in user fee
obligations.
The annualized monetized benefits over a 40-year time horizon far
exceed the annualized monetized costs over the same time. We estimate
that the annualized benefits over a 40-year time horizon would be $1.1
trillion at a 2 percent discount rate, with a low estimate of $0.27
trillion and a high estimate of $1.2 trillion. Over a 40-year time
horizon, we estimate that the annualized costs would be $2.07 billion
at a 2 percent discount rate, with a low estimate of $0.7 billion and a
high estimate of $2.73 billion.
II. Table of Abbreviations/Commonly Used Acronyms in This Document
------------------------------------------------------------------------
Abbreviation/ acronym What it means
------------------------------------------------------------------------
3-HPMA....................... 3-hydroxypropyl mercapturic acid.
AI/AN........................ American Indians/Alaska Native.
ANPRM........................ Advance Notice of Proposed Rulemaking.
BAP.......................... Benzo[a]pyrene.
CDC.......................... Centers for Disease Control and
Prevention.
CFR.......................... Code of Federal Regulations.
CISNET....................... Cancer Intervention and Surveillance
Modeling Network.
CO........................... Carbon monoxide.
COHb......................... Carboxyhemoglobin.
COPD......................... Chronic obstructive pulmonary disease.
CORESTA...................... Cooperation Centre for Scientific
Research Relative to Tobacco.
CPD.......................... Cigarettes per day.
CPS-I........................ Cancer Prevention Study I.
CPS-II....................... Cancer Prevention Study II.
CRM.......................... CORESTA Recommended Method.
DSM.......................... Diagnostic and Statistical Manual of
Mental Disorders.
ENDS......................... Electronic nicotine delivery systems.
E.O.......................... Executive Order.
FD&C Act..................... Federal Food, Drug, and Cosmetic Act.
FDA.......................... Food and Drug Administration.
FR........................... Federal Register.
FTCD......................... Fagerstr[ouml]m Test for Cigarette
Dependence.
FTND......................... Fagerstr[ouml]m Test for Nicotine
Dependence.
GC-MS........................ Gas chromatography-mass spectrometry.
HHS.......................... U.S. Department of Health and Human
Services.
HPHCs........................ Harmful and potentially harmful
constituents.
HTP.......................... Heated tobacco product.
IOM.......................... Institute of Medicine.
LGBTQI+...................... Lesbian, gay, bisexual, transgender,
queer, and intersex.
LNC.......................... Low nicotine content.
mg........................... milligram.
MNWS......................... Minnesota Nicotine Withdrawal Scale.
MRI.......................... Magnetic resonance imaging.
nAChR........................ Nicotinic acetylcholine receptor.
NATS......................... National Adult Tobacco Survey.
NCI.......................... National Cancer Institute.
NDSS......................... Nicotine Dependence Syndrome Scale.
NHANES....................... National Health and Nutrition Examination
Survey.
NHIS......................... National Health Interview Survey.
NHIS-LMF..................... National Health Interview Survey-Linked
Mortality Files.
NIDA......................... National Institute on Drug Abuse.
NIH.......................... National Institutes of Health.
NJATS........................ New Jersey Adult Tobacco Survey.
NLMS......................... National Longitudinal Mortality Study.
NNAL......................... 4-(methylnitrosamino)-1-(3-pyridyl)-1-
butanol.
NNC.......................... Normal nicotine content.
NNN.......................... N-Nitrosonornicotine.
NPRM......................... Notice of proposed rulemaking.
NRC.......................... National Research Council.
NRT.......................... Nicotine replacement therapy.
NSDUH........................ National Survey on Drug Use and Health.
NYTS......................... National Youth Tobacco Survey.
OOS.......................... Out-of-specification.
PAH.......................... Polycyclic aromatic hydrocarbon.
PATH......................... Population Assessment of Tobacco and
Health.
PET.......................... Position emission tomography.
PD........................... Product static ID number.
QALYs........................ Quality-adjusted life years.
[[Page 5038]]
QSU.......................... Questionnaire of Smoking Urges.
RCT.......................... Randomized clinical trial.
RNC.......................... Reduced nicotine content.
RR........................... Relative risk.
RYO.......................... Roll-your-own.
S-PMA........................ S-phenylmercapturic acid.
SE........................... Substantial Equivalence.
SES.......................... Socioeconomic status.
STN.......................... Submission tracking number.
TNE.......................... Total nicotine equivalents.
TPSAC........................ Tobacco Products Scientific Advisory
Committee.
TUS-CPS...................... Tobacco Use Supplement to the Current
Population Survey.
U.S.......................... United States.
VLNC......................... Very low nicotine content.
WISDM........................ Wisconsin Inventory of Smoking Dependence
Motives.
YRBS......................... Youth Risk Behavior Survey.
------------------------------------------------------------------------
III. Background
A. Need for the Regulation
Cigarettes are responsible for the majority of tobacco-related
death and disease in the United States. Each year, 480,000 people die
prematurely from a smoking-attributable disease, putting a substantial
burden on the U.S. healthcare system and causing massive economic
losses to society (Ref. 1). In terms of a monetary measure of the
impact of cigarette smoking on the public health, in 2018, cigarette
smoking cost the United States more than $600 billion, including more
than $240 billion in healthcare spending (Ref. 10), nearly $185 billion
in lost productivity from smoking-related illnesses and health
conditions (Ref. 10), nearly $180 billion in lost productivity from
smoking-related premature death (Refs. 1 and 10), and $7 billion in
lost productivity from premature death from secondhand smoke exposure
(Refs. 1 and 11). The mortality rate among people who currently smoke
cigarettes is 2 to 3 times as high as that among individuals who never
smoked (Ref. 12). Nicotine, the primary addictive constituent in
tobacco products, can be delivered through a variety of products along
a continuum of risk, with combusted tobacco products at the most
harmful end of this continuum. To protect youth and reduce tobacco-
related disease and death, FDA utilizes a comprehensive approach to
tobacco and nicotine regulation. Shortly after FDA announced its
comprehensive approach in 2017 (https://www.fda.gov/news-events/press-announcements/fda-announces-comprehensive-regulatory-plan-shift-trajectory-tobacco-related-disease-death), the Agency began a public
dialogue about lowering nicotine levels in combusted cigarettes to
minimally addictive or nonaddictive levels through achievable product
standards. On March 16, 2018, FDA issued a Nicotine ANPRM to seek input
on the potential public health benefits and any possible adverse
effects of regulating nicotine yield by lowering nicotine levels in
cigarettes and invited comments on many issues associated with the
development of a product standard to establish a maximum nicotine level
(83 FR 11818). The Nicotine ANPRM also acknowledged that if FDA were to
establish a nicotine tobacco product standard that covered only
cigarettes, some number of people who smoke cigarettes could migrate to
other similar combusted tobacco products to maintain their nicotine
dependence (or engage in dual use with other combusted tobacco
products), potentially reducing the positive public health impact of
such a rule. FDA sought comments on whether the standard therefore
should cover other combusted tobacco products. Based on FDA's
scientific knowledge, extensive research regarding VLNC cigarettes, and
comments submitted in response to this Nicotine ANPRM, FDA is proposing
a tobacco product standard that would regulate nicotine yield by
establishing a maximum nicotine level in cigarettes and certain other
combusted tobacco products.
As the U.S. District Court for the District of Columbia recognized
in United States v. Philip Morris USA, Inc. et al., 449 F.Supp.2d 1
(D.D.C. 2006), aff'd in relevant part, 566 F.3d 1095 (D.C. Cir. 2009),
the tobacco industry has long known that nicotine creates and sustains
addiction, and the industry is dependent on maintaining this addiction.
Id. at 307. The court noted how cigarette companies have engaged in
extensive research to understand how nicotine operates within the human
body and then designed their cigarettes to precisely control nicotine
delivery and provide nicotine doses to create and sustain addiction.
Id. at 307-309. Moreover, the court confirmed that industry documents
supported the conclusion that these companies ``knew early on in their
research that if a cigarette did not deliver a certain amount of
nicotine, new smokers would not become addicted, and `confirmed'
smokers would be able to quit.'' Id. at 219. In fact, the tobacco
industry has had programs in place since the 1960s to obtain ``any
level of nicotine desired'' (Ref. 2). These companies sought to
identify the ``optimum'' dose needed to ``satisfy'' people who smoke
cigarettes and, thereby, assure their continued smoking. Philip Morris
449 F.Supp.2d at 309-11. This proposed product standard would seek to
set a maximum nicotine level requirement such that cigarettes and
certain other combusted tobacco products would no longer be able to
create and sustain this addiction among people who smoke cigarettes.
The proposed product standard would limit the addictiveness of the
most toxic and widely used products, which would have significant
benefits for all age groups. Adults who use tobacco products, most of
whom want to quit, are often unsuccessful because of the highly
addictive nature of these products (Ref. 13). Researchers estimate that
each year, only between 5.4 and 5.6 percent of adults who use
cigarettes successfully quit for good (Ref. 14). Similar analysis of
2022 NHIS data indicates that only 8.8 percent of adults who formerly
smoked cigarettes had quit smoking cigarettes in the past year (Ref.
4). Lowering nicotine to minimally addictive or nonaddictive levels
would improve their ability to successfully quit using the products
within the proposed scope of this rule. It also would prevent people
who experiment with cigarettes and non-premium cigars, including youth,
from moving beyond experimentation, developing an
[[Page 5039]]
addiction to nicotine, and progressing to regular use as a result of
that addiction. Furthermore, it is well-established that secondhand
tobacco smoke causes premature death and disease in children and in
adults who do not smoke (Ref. 15 at p.11). It is estimated that
exposure to secondhand smoke caused 41,280 deaths per year in the
United States from 2005 to 2009 (Ref. 1 at Table 12.4). This increased
cessation and reduced initiation, in turn, would result in a
significant decrease in harms from the products to people who currently
or would otherwise use cigarettes and certain other combusted tobacco
products, as well as harms to people who do not use the products,
including harms caused by secondhand smoke to both adults and children,
harmful perinatal effects due to parental tobacco use, and fires.
Preventing people who do not smoke cigarettes, particularly youth,
from regularly smoking cigarettes due to nicotine addiction would allow
them to avoid the severe adverse health consequences of smoking and
would result in significant public health benefits. Without changes
like those proposed here, an estimated 3.66 million youth under the age
of 18 who were alive in 2018--and 2.54 million youth who are alive in
2024, accounting for the projected continued decline in smoking
prevalence--will die prematurely later in life from a smoking-related
disease (Ref. 16). As a result of the proposed product standard, many
youth and young adults would not be subjected to the impacts of
nicotine addiction from cigarette smoking and certain other combusted
tobacco products (which have a significantly stronger effect on youth
due, in part, to their developing brains, as described in sections IV.B
and IV.C of this document), nor would they suffer from the adverse
health effects and mortality that these products cause.
Nicotine is powerfully addictive, and youth and young adults \9\
are particularly susceptible to developing a nicotine addiction.
Multiple Surgeon General's Reports on smoking and health have noted
that almost 90 percent of adults who regularly smoke cigarettes
initiated smoking by age 18, and 98 percent initiated smoking by age
26, which is notable given that 25 is the approximate age at which the
brain has completed development (Refs. 1, 17 to 19). The developing
brain is more vulnerable to nicotine dependence than the adult brain
is, and the earlier an individual begins smoking the less likely they
are to quit (Ref. 20). Generally, those who begin smoking before the
age of 18 are not aware of the degree of addictiveness and the full
extent of the consequences of smoking (Ref. 21). It is clear that many
youth who smoke cigarettes want to quit but have difficulty doing so.
An analysis of data from the 2015 Youth Risk Behavior Survey (YRBS)
looking at youth cigarette quit attempts found that 45.4 percent of
high school students currently smoking cigarettes had sought to quit in
the previous year (Ref. 22); 2020 National Youth Tobacco Survey (NYTS)
data were congruent, indicating that 68.1 percent of middle and high
school students who smoke cigarettes had sought to quit in the previous
year (Ref. 23).
---------------------------------------------------------------------------
\9\ Though age ranges for youth and young adults vary across
studies, in general, ``youth'' or ``adolescent'' encompasses those
ages 11-17, while those who are ages 18-25 are considered ``young
adults'' (even though, developmentally, the period between 18-20
years of age is often labeled late adolescence); those ages 26 and
or older are considered ``adults'' (Ref. 17).
---------------------------------------------------------------------------
More than half (52.2 percent) of U.S. middle and high school
students who use cigarettes, cigars, smokeless tobacco--including those
with low levels of use--report experiencing at least one symptom of
nicotine dependence (Ref. 24). Notably, 12.7 percent of youth using
tobacco products 1 to 2 days per month and 21.2 percent of youth using
tobacco products 3 to 5 days per month reported sometimes/often/always
feeling irritable or restless when not using tobacco products for a
while, and 15.6 percent of youth using tobacco products 1 to 2 days per
month and 32.0 percent of youth using tobacco products 3 to 5 days per
month reported having strong cravings for a tobacco product during the
past 30 days (Ref. 24). Additionally, other researchers analyzing data
from the 2021 NYTS found that a sizeable proportion of high school
students using tobacco products in the past 30 days report symptoms of
nicotine dependence, including 27.2 percent reporting a strong craving
for tobacco use and 19.5 percent reporting wanting to first use tobacco
products within 30 minutes of waking (Refs. 25 and 26). While
prevalence rates of youth use of noncombusted tobacco products (e.g.,
ENDS) in recent years have exceeded those of cigarettes and other
combusted tobacco products (Refs. 25 and 26), FDA expects that this
proposed product standard would have significant benefits for youth by
reducing the risk that youth who experiment with cigarettes and certain
other combusted tobacco products, or who may consider using these
products as an alternative to noncombusted tobacco products, would
progress to regular use of these products as a result of nicotine
dependence.
The adolescent and young adult brain is more vulnerable to
developing nicotine dependence than the adult brain is; data indicate
that nicotine has stronger rewarding effects in adolescents than in
adults (Ref. 17). Adolescents who use tobacco and initiated use at
earlier ages were more likely than those initiating at older ages to
report symptoms of tobacco dependence, putting them at greater risk for
maintaining tobacco product use into adulthood (Ref. 24). Additionally,
the earlier that individuals begin smoking--and therefore the greater
amount of time that individuals experience nicotine dependence--the
less likely they are to successfully quit (Ref. 27). Evidence indicates
that exposure to substances such as nicotine can disrupt brain
development and have long-term consequences for executive cognitive
functioning (such as decreased attention and working memory and
increased impulsivity) and for the risk of developing a substance use
disorder and various mental health problems (particularly affective
disorders such as anxiety and depression) as an adult (Ref. 27).
Furthermore, the 2010 Surgeon General's report noted that adolescents
report symptoms of dependence even at low levels of cigarette smoking,
and thus may be particularly vulnerable to addiction (Ref. 28). FDA
expects that this proposed product standard, therefore, would have
significant benefits for youth and young adults by reducing the risk
that those who experiment with cigarettes and certain other combusted
tobacco products would progress to regular use as a result of nicotine
dependence.
Research studies involving VLNC cigarettes--defined previously in
this document as cigarettes containing up to 1.0 mg of nicotine per
gram of total tobacco--demonstrate that setting the maximum nicotine
level we are proposing here, would lead to a reduction in nicotine
dependence, which would help people who smoke cigarettes quit smoking.
In studies that immediately reduced the nicotine content of cigarettes
by switching participants from usual brand cigarettes to LNC or VLNC
cigarettes, dependence decreased in people who smoked cigarettes who
were not interested in quitting compared to those who smoked normal
nicotine content (NNC) or usual brand cigarettes for 6 weeks (Ref. 29),
10 weeks (Ref. 30), or 12 weeks (Ref. 31). In smoking cessation studies
in which participants endorsed wanting to quit, VLNC cigarettes were
also associated
[[Page 5040]]
with reductions in nicotine dependence over time (Refs. 32 to 35).
FDA is issuing this proposal because the tobacco products subject
to this proposed product standard remain addictive due to the nicotine
yield they offer users and because combusted tobacco products are
responsible for the majority of tobacco-related death and disease (see
section IV.D of this document for a discussion regarding the serious
negative health effects of smoking cigarettes and other combusted
tobacco products). Cigarettes have been precisely designed to create
and maintain addiction among people who smoke. United States v. Philip
Morris USA, Inc. et al., 449 F.Supp.2d 1, 307 (D.D.C. 2006). To protect
the public health, particularly youth, FDA is proposing this standard,
in part, to ensure that people who smoke these products would be less
likely to: (1) initiate regular use; (2) become addicted to these
products; and (3) suffer from the many diseases and debilitating
effects, including death, caused by combusted tobacco product use.
Similarly, FDA expects that the proposed product standard would
have significant benefits for adults who use combusted tobacco
products, most of whom want to quit but are often unsuccessful because
of the highly addictive nature of these products (Ref. 13). Data from
the 2022 National Health Interview Survey (NHIS) and 2018-2019 Tobacco
Use Supplement to the Current Population Survey (TUS-CPS) indicate that
67.7 and 76.6 percent, respectively, of adults who smoke cigarettes
wanted to quit (Ref. 36), while 2022 NHIS data (Ref. 4) and 2018-2019
TUS-CPS data (Ref. 36) show that 53.3 and 51.3 percent, respectively,
of adults who smoke cigarettes in the United States actually made a
quit attempt within the past year. However, analyses of NHIS and TUS-
CPS data for these years indicate that only 8.8 and 7.5 percent of
adults had successfully quit smoking cigarettes, respectively (Refs. 4
and 36). Adults who smoke cigarettes may make 30 or more quit attempts
before succeeding (Ref. 37). FDA expects that decreasing the nicotine
yield of cigarettes and certain other combusted tobacco products
covered by this rule, by reducing nicotine content, so that they are
minimally addictive or nonaddictive would likely help people who smoke
reduce their dependence on combusted tobacco products, thereby making
it easier for them to quit smoking. As discussed throughout this
document, FDA also expects that decreasing the nicotine content in
these products, and thus the nicotine yield offered to users, would
prevent people who experiment with cigarettes and cigars (mainly youth)
from moving beyond experimentation, developing an addiction to
nicotine, and progressing to regular use as a result of that addiction.
Although many factors contribute to an individual's initial
experimentation with tobacco products, the addictive nature of tobacco
is the key reason people progress to regular use, and scientists agree
that it is the presence of nicotine that causes addiction and sustains
a person's tobacco use (Refs. 1 HHS at p. 113 and 28). While nicotine
is the primary addictive chemical in tobacco, sensorimotor stimuli
(e.g., smell/taste of smoke; airway sensations; holding the cigarette)
repeatedly occur during smoking (Ref. 38). These stimuli often act as
secondary or conditioned reinforcers that contribute to the cycle of
nicotine dependence by motivating and maintaining smoking behavior
(Ref. 38). Once people who use tobacco become addicted to nicotine,
they require nicotine to avoid withdrawal symptoms. In the process of
obtaining their nicotine, people who use combusted tobacco products are
exposed to an array of toxicants in tobacco and tobacco smoke that lead
to a substantially increased risk of morbidity and mortality (Ref. 28).
Because of their nicotine addiction, many people who smoke cigarettes
struggle to stop using these toxic tobacco products despite their
stated desire to quit (Ref. 28).
An advisory report from the World Health Organization notes that
the ultimate health benefits of a nicotine reduction strategy, like the
one FDA is proposing here, would require that the standard cover other
combusted tobacco products--not just cigarettes (Ref. 39). In alignment
with this recommendation from the World Health Organization, this
proposed rule would cover combusted cigarettes and certain other
combusted tobacco products (i.e., cigarette tobacco, RYO tobacco,
cigars other than premium cigars, pipe tobacco). The World Health
Organization report also noted that such a strategy should be
accompanied by the provision of cessation treatments to help people
quit, including behavioral support and nicotine replacement therapy
(NRT) or other medications (Ref. 39). FDA remains committed to
facilitating the development and use of therapeutic nicotine products
for tobacco product cessation and increased availability of services
alongside enhanced outreach efforts to support tobacco use cessation.
For example, FDA's Nicotine Steering Committee, which helps to develop
and implement nicotine policy and regulation for the Agency, held a 21
CFR part 15 hearing in early 2018 on the Agency's approach to
evaluating the safety and efficacy of NRT products, including how they
should be used and labeled (82 FR 56759 (November 30, 2017)). Also, in
May 2023, FDA's Center for Drug Evaluation and Research announced the
availability of a final guidance for industry entitled ``Smoking
Cessation and Related Indications: Developing Nicotine Replacement
Therapy Drug Products,'' which provides guidance to assist sponsors in
the clinical development of NRT drug products, including but not
limited to those intended for smoking cessation and related chronic
conditions (88 FR 26559, May 1, 2023; see https://www.fda.gov/media/167599/download). Additionally, as described further below, the Agency
is contributing to a comprehensive effort coordinated by the U.S.
Department of Health and Human Services (HHS or the Department) to
support tobacco use cessation.
Rendering cigarettes and certain other combusted tobacco products
minimally addictive or nonaddictive through a nicotine product standard
would address the principal reason that people who smoke cigarettes
have difficulty quitting smoking. If this proposed product standard is
finalized, people who use cigarettes and other combusted tobacco
products covered by this rule would be unable to obtain enough nicotine
from those products to sustain addiction no matter how they smoked the
products (e.g., more frequent smoking, intensive puffing) (Refs. 32,
40, and 41), facilitating people who currently smoke cigarettes to make
more successful quit attempts.\10\ At the same time, combusted tobacco
products at minimally addictive or nonaddictive levels of nicotine
would remain on the market for those who currently smoke and would like
to continue to do so.
---------------------------------------------------------------------------
\10\ As stated throughout this preamble, in the event that a
nicotine product standard addresses only cigarettes, FDA expects
that, to maintain their nicotine dependence, some number of people
who are addicted to cigarettes would likely migrate to other similar
combusted tobacco products (or engage in dual use with such
products) after the product standard goes into effect, reducing the
benefits of the standard.
---------------------------------------------------------------------------
FDA expects that, if this proposed rule is finalized and a nicotine
product standard for cigarettes and certain other combusted tobacco
products is in place, many people who smoke cigarettes will either quit
all tobacco-product use or switch to a noncombusted tobacco product.
Those who switch completely to use of a noncombusted tobacco product
may sustain their nicotine dependence but may significantly
[[Page 5041]]
reduce their risk of tobacco-related death and disease because
switching completely to a noncombusted tobacco product would reduce
exposure to the chemical constituents created through combustion, which
are the primary contributors of tobacco-related harm (Ref. 8).
The benefits of this rule have been determined without taking into
consideration the impact of any smoking cessation services that may be
coordinated by HHS, and are expected to be significant. Also, FDA
expects that unassisted cessation attempts, i.e., those made by people
who smoke without help, may be more successful in an environment in
which the product being quit is no longer addictive as compared to
historic quitting success rates where it has been easy to relapse to
the same highly addictive product. Nevertheless, FDA recognizes that
increasing and improving cessation resources, particularly in
communities where access to cessation resources have been historically
lacking, may provide an opportunity to further increase the expected
benefits of this proposed product standard and to enhance the degree to
which such benefits are experienced by people in populations that are
disproportionately impacted by combusted tobacco use. Accordingly, FDA
is contributing to a comprehensive effort being coordinated by HHS to
support and accelerate cessation of combusted tobacco products.\11\
With input from subject matter experts from across HHS Operating
Divisions, the Department has finalized the ``HHS Framework To Support
and Accelerate Smoking Cessation'' (Framework). The Framework aims to
accelerate smoking cessation and reduce smoking-related disparities by
building on current activities and collaborations across the
Department. The Framework vision is to ensure that every person in
America has access to comprehensive, evidence-based cessation treatment
and can benefit from HHS cessation supports, programs, and policies.
Specific Framework goals are to: (1) reduce smoking and cessation-
related disparities; (2) increase awareness and knowledge related to
smoking and cessation; (3) strengthen, expand, and sustain cessation
services and supports; (4) increase access to and coverage of
comprehensive, evidence-based cessation treatment; (5) advance, expand,
and sustain surveillance and strengthen performance measurement and
evaluation; and (6) promote ongoing and innovative research to support
and accelerate smoking cessation (https://www.hhs.gov/about/news/2024/03/08/hhs-announces-new-smoking-cessation-framework-support-quitting.html). With increased availability and accessibility of
services, more people who smoke may be motivated to take advantage of
cessation resources, whether they smoke cigarettes or other combusted
tobacco products. Additionally, FDA has numerous processes and tools at
its disposal to communicate directly with consumers, including
communities that are underserved by cessation services and/or are
disproportionately impacted by tobacco use, and will continue to
evaluate the need for additional public outreach, including targeted
education initiatives, in support of this proposed rule. However, the
Agency does not have evidence to suggest that such an effort is
necessary at this time in order to experience the public health
benefits of this proposed product standard.
---------------------------------------------------------------------------
\11\ See, for e.g., https://www.fda.gov/tobacco-products/ctp-newsroom/fda-and-nih-joint-public-meeting-advancing-smoking-cessation-priorities-registration-open?utm_campaign=ctp-research&utm_content=landingpage&utm_medium=email&utm_source=govdelivery&utm_term=stratcomms.
---------------------------------------------------------------------------
For the reasons stated here and throughout this document, FDA is
proposing this tobacco product standard to: (1) reduce the risk of
progression to regular use and nicotine dependence for those who
experiment with such tobacco products, especially youth and (2) make it
easier for people who are addicted to cigarettes and certain other
combusted tobacco products and who are interested in quitting to quit
by reducing the nicotine in these products to minimally addictive or
nonaddictive levels. FDA expects that this proposed product standard
would significantly reduce the morbidity and mortality caused by
smoking. Based on FDA's population health model, by the year 2100, in
the United States, approximately 48 million youth and young adults who
would have otherwise initiated smoking would not start as a result of
the proposed product standard. The model also projects that more than
12.9 million additional people who smoke cigarettes would quit smoking
(including those who switch to noncombusted tobacco products) 1 year
after implementation of the proposed product standard, increasing to
19.5 million additional people who formerly smoked cigarettes within 5
years of implementation. Section XII discusses that the main quantified
benefits come from averted mortality and morbidity, as a result of
tobacco use transitions, including switching. In terms of mortality
benefits, the model considers a higher risk for people who switch to
noncombusted products compared to those who quit tobacco product use
entirely. Specifically, the model assumes that the risk for people who
switch to noncombusted product use is 8 percent higher than the risk
for those who quit tobacco use entirely. Details of this approach can
be found in the FDA's modeling document (Ref. 42). In addition, the
model estimates that, by the year 2060, in the United States, this
proposed product standard would result in 1.8 million tobacco-related
deaths averted, rising to 4.3 million deaths averted by the end of the
century (Ref. 42). The reduction in premature deaths attributable to
the proposed product standard would result in 19.6 million life years
gained by 2060 and 76.4 million life years gained by 2100 (see section
VIII.A of this document for further discussion of the model) (Ref. 42).
B. Relevant Regulatory History
In its implementation of the Family Smoking Prevention and Tobacco
Control Act (Tobacco Control Act) (Pub. L. 111-31) since its passage in
2009, FDA has engaged in close study and careful consideration of the
scientific evidence and complex policy issues related to nicotine in
cigarettes and other combusted tobacco products. FDA issued an ANPRM to
solicit data and information for consideration in developing a tobacco
product standard to regulate nicotine yield by setting the maximum
nicotine level for cigarettes, conducted a robust scientific assessment
related to a nicotine product standard for combusted tobacco products,
developed a population health model to assess the potential public
health impacts of such a product standard, and sponsored research on a
variety of nicotine-related topics through contracts and interagency
agreements with Federal partners, including the National Institutes of
Health (NIH).\12\ FDA has considered the comments and information
received in response to the ANPRM, scientific assessment, and
population health model in developing this proposed rule. Please see
the remainder of this section for further discussion.
---------------------------------------------------------------------------
\12\ Information on specific projects supported by FDA is
available at https://www.fda.gov/tobacco-products/tobacco-science-research/research.
---------------------------------------------------------------------------
1. ANPRM
In July 2017, FDA announced a comprehensive approach to tobacco and
nicotine regulation to protect youth and reduce tobacco-related disease
and death (Ref. 43). As part of the public dialogue on the
comprehensive approach, in March 2018, FDA issued three ANPRMs related
to the regulation
[[Page 5042]]
of nicotine in combusted cigarettes (83 FR 11818), flavors (including
menthol) in tobacco products (83 FR 12294, March 21, 2018) (Flavors
ANPRM), and premium cigars (83 FR 12901, March 26, 2018). In addition,
FDA announced the availability of a draft concept paper entitled
``Illicit Trade in Tobacco Products After Implementation of a Food and
Drug Administration Product Standard,'' and sought public comment (83
FR 11754, March 16, 2018). This paper analyzes the potential for
illicit trade markets to develop in response to a tobacco product
standard (Ref. 44).
The Nicotine ANPRM requested data and information for consideration
in developing a tobacco product standard to set a maximum nicotine
level for cigarettes to make them minimally addictive or nonaddictive.
Specifically, FDA sought comments, evidence, and other information
regarding whether a potential tobacco product standard should cover
tobacco products other than cigarettes (e.g., cigarette tobacco, RYO
tobacco, some or all cigars, pipe tobacco, waterpipe tobacco); what
maximum level of nicotine would be appropriate for the protection of
the public health, in light of scientific evidence about the addictive
properties of nicotine in cigarettes; whether such a standard should
propose either a single target (i.e., an immediate reduction, where the
nicotine is reduced all at once) or a stepped-down approach (i.e., a
gradual reduction, where the nicotine is reduced gradually over time)
to reach the desired maximum nicotine level; whether such a product
standard should specify a method for manufacturers to use to detect the
level of nicotine in their products; the technical feasibility of
current as well as more recent, novel nicotine reduction techniques;
and the proper timeframe for implementation of a possible nicotine
tobacco product standard to allow adequate time for industry to comply.
The Nicotine ANPRM also requested comment on possible negative effects
that could diminish the population health benefits expected as a result
of a nicotine product standard, such as continued combusted tobacco
product use, where people who currently use tobacco products subject to
a nicotine tobacco product standard could turn to other combusted
tobacco products to maintain their nicotine dependence, both in
combination with cigarettes (i.e., dual use) or in place of cigarettes
(i.e., switching); the potential for increased harm due to continued
VLNC cigarette smoking with altered smoking behaviors (e.g., increase
in number of cigarettes smoked, increased depth of inhalation); people
seeking to add nicotine in liquid or other form to their combusted
tobacco product; and whether illicit trade could occur as a result of a
nicotine product standard and how that could impact public health.
Finally, FDA also sought comments, data, research results, and other
information regarding economic impacts of a potential nicotine tobacco
product standard.
FDA received over 7,700 comments on the Nicotine ANPRM, with
approximately 6,700 of those comments submitted as part of 20 different
organized campaigns. The key ANPRM areas of comments are covered in the
relevant sections in this document and include the possible scope of
products covered by the rule (section IX.C), technical achievability
(section VII.E), illicit trade (section IX.D), and implementation/
effective date (section XI). Some of the issues raised in the comments
to the ANPRM are highlighted below.
Comments generally in support of setting a maximum nicotine level
in cigarettes stated that a nicotine product standard would be
appropriate for the protection of the public health. In particular,
many comments argued that reducing the nicotine content in cigarettes
to minimally addictive or nonaddictive levels would be appropriate for
the following reasons: (1) reduced nicotine content in cigarettes will
contribute to smoking cessation, as well as decreased initiation and
addiction by people newly using cigarettes and certain other combusted
tobacco products and youth and (2) such increased cessation and
decreased initiation will reduce the instances of preventable deaths
and other negative health effects caused by smoking. Some comments also
urged FDA to issue a nicotine product standard as part of a
comprehensive package of tobacco regulatory measures, including
increasing consumer access to reduced risk products, regulating flavors
in tobacco products, taking action as soon as possible, fully reviewing
premarket applications for new tobacco products, and making effective
smoking cessation treatments and ongoing cessation support accessible
and affordable to people who smoke cigarettes.
FDA received many comments expressing concern about the effect of
nicotine on the adolescent brain and its role in addicting those who
experiment with tobacco products, particularly youth and young adults,
leading them to progress to regular use. Some comments recommended
extending the scope of a nicotine product standard to noncombusted
tobacco products (e.g., smokeless, ENDS) to prevent migration to such
products, particularly among youth; a significant number of comments
urged FDA to extend the scope of a nicotine product standard to
combusted tobacco products other than cigarettes. Citing national
survey data trends and various recent studies, numerous comments--
including those from public health associations, government agencies,
and advocacy groups--asserted that including all combusted tobacco
products, not only cigarettes, would prevent potential youth initiation
of, migration to, and dual use with other combusted products with
higher nicotine content that may be harmful to health, thus aligning
with the public health goals of a nicotine product standard.
Additionally, citing studies relating to tobacco use patterns by young
people, a joint submission from several nicotine and tobacco
researchers stated that adolescents who use tobacco are particularly
prone to dual and multiple tobacco product use; therefore, the
potential for adolescents to shift to other nicotine-containing tobacco
products underscores the need for a nicotine reduction policy to cover
all combusted tobacco products. The joint submission comment further
stated that if the scope of a nicotine product standard only covered
combusted cigarettes, there is evidence from adult studies that
cigars--and in particular little cigars--would be an attractive
substitute for full nicotine content combusted cigarettes. These
researchers noted, if the scope of a proposed nicotine product standard
included combusted cigarettes and other combusted products, it would
increase the likelihood that people who use combusted cigarettes,
including youth and young adults, who migrate to other nicotine-
containing products (rather than quit), would transition to
noncombusted products, thereby increasing the health benefits of the
policy.
FDA also received comments from individuals, advocacy groups, and
members of the tobacco industry generally opposing efforts to reduce
nicotine levels in cigarettes to minimally addictive or nonaddictive
levels. These comments generally stated that such a regulation would
stifle free enterprise or would negatively limit consumer freedom of
choice and that the regulation would result in a de facto ban on
cigarettes that would have a devastating impact on tobacco farming, as
well as the manufacturing, distribution, and retail sectors. Some
comments discussed the technical feasibility of achieving lower
nicotine
[[Page 5043]]
levels. Some comments opposed to a nicotine product standard stated
that there is not enough scientific research to support reducing
nicotine in cigarettes. Other comments argued that FDA should instead
focus on giving adults who smoke cigarettes access to a wider choice of
less harmful tobacco products and truthful information about the
benefits of switching to those products, as well as focus resources on
a plan to reduce harm through proven strategies to prevent initiation
and encourage cessation.
FDA has reviewed and closely considered the comments to the
Nicotine ANPRM, as well as additional evidence and information not
available at the time of the Nicotine ANPRM, in developing this
proposed rule.
2. Scientific Review
As the body of evidence has continued to grow, FDA undertook a
robust systematic review of the scientific evidence regarding the
likely effects of reducing nicotine in combusted tobacco products. This
review, entitled ``The Science of a Nicotine Standard for Combusted
Tobacco Products'' (Ref. 45), covers peer-reviewed, publicly available
literature and focuses on the likely effects of reducing nicotine in
combusted tobacco products. This scientific assessment has been peer
reviewed by independent external experts. Taking into consideration
comments from this peer review (Ref. 46), FDA revised the scientific
assessment, and the final peer-reviewed document is available in the
docket for this proposed rule (Ref. 45). Additionally, this final peer-
reviewed document and other related documents such as FDA's response to
the peer review comments can be found at https://www.fda.gov/science-research/peer-review-scientific-information-and-assessments/completed-peer-reviews.
FDA's peer reviewed scientific assessment examined the effects of
reducing the level of nicotine in combusted tobacco products on use
behavior, dependence, and toxicant exposure, as well as the knowledge,
beliefs, and perceptions around nicotine and VLNC cigarettes. This
scientific review found that the totality of the evidence supports that
extended exposure to combusted cigarettes containing VLNC tobacco
filler is associated with reduced addiction potential, dependence
levels, and number of cigarettes smoked per day, and increased quit
attempts among people who currently smoke cigarettes, without evidence
of increased toxicant exposure, craving, withdrawal, or compensatory
smoking. The review also determined that if FDA were to establish a
nicotine product standard that covered only cigarettes, a portion of
people who are currently addicted to cigarettes would likely migrate to
other, similar combusted tobacco products to maintain their nicotine
dependence (or engage in dual use without substantially reducing their
combusted tobacco product use), thereby reducing the positive public
health impact of such a rule. Based on FDA's review of the literature
on combusted tobacco products, including cigarettes, cigarette tobacco,
RYO tobacco, cigars, and pipe tobacco, the final scientific assessment
concluded that use of any of these combusted products is sufficient to
create or sustain nicotine dependence and would therefore continue to
expose people who use these products to toxicants. Further, FDA's
scientific assessment concluded that the establishment of a maximum
nicotine level in combusted tobacco products that would render them
minimally addictive or nonaddictive could increase the likelihood of
successful quit attempts and help prevent people who experiment with
cigarettes and cigars (mainly youth) from progressing to regular use,
thereby significantly reducing the morbidity and mortality caused by
smoking. FDA has considered the scientific assessment conclusions in
the development of this proposed product standard.
In addition, to assess the potential public health impacts of a
nicotine product standard, FDA developed a population health model
using inputs derived from available empirical evidence and expert
opinion to estimate the impact of changes in tobacco product
initiation, cessation, switching, and dual use on tobacco use
prevalence, morbidity, and mortality in the United States. Details of
this modeling approach have been previously published in two peer-
reviewed publications (Refs. 47 and 48), which describe the overall
model in terms of the inputs, transition behaviors, and outputs that it
contains, along with results from simulation studies. In preparation
for this proposed product standard, FDA updated a previously-published
model (Ref. 47), which describes the impact of a potential product
standard that limits the level of nicotine in cigarettes, RYO tobacco,
non-premium cigars, and pipe tobacco so that they are minimally
addictive or nonaddictive. In this updated modeling document, entitled
``Methodological Approach to Modeling the Potential Impact of a
Nicotine Product Standard on Tobacco Use, Morbidity, and Mortality in
the U.S.'' (Ref. 42), we estimated the potential impacts of a nicotine
product standard by modeling a baseline scenario of use of cigarettes
and noncombusted tobacco products including smokeless tobacco, e-
cigarettes, and HTPs. These product classes (cigarettes and
noncombusted products) were selected because of the magnitude of
population health effects from cigarette smoking and the likelihood of
product switching to noncombusted products, especially e-cigarettes.
Estimates of changes in mortality from other exposures including non-
premium cigar and pipe tobacco use are not produced directly by the
model but are derived from model outputs instead. We then compared the
baseline scenario to a product standard scenario characterized by the
introduction of a potential nicotine product standard that would apply
to cigarettes, cigarette tobacco, RYO tobacco, non-premium cigars, and
pipe tobacco. FDA's modeling framework and methodological approach and
the associated data inputs and assumptions have been peer reviewed by
independent external experts. Taking into consideration comments from
this peer review (Ref. 49), FDA revised the modeling document, and the
final modeling document is available in the docket for this proposed
product standard (Ref. 42). FDA's modeling work informed the
development of this proposed product standard. Additionally, the
modeling document, model code, and inputs are publicly available at
https://www.fda.gov/science-research/peer-review-scientific-information-and-assessments/completed-peer-reviews. Further discussion
of FDA's estimates of the public health impact of this proposed product
standard can be found in section VIII of this document.
3. Premium Cigars
On August 9, 2023, the U.S. District Court for the District of
Columbia issued an order vacating FDA's rule deeming tobacco products
to be subject to FDA's tobacco product authorities ``insofar as it
applies to premium cigars.'' \13\ Cigar
[[Page 5044]]
Ass'n of Am. v. FDA, No. 16-cv-01460, 2023 WL 5094869 (D.D.C. Aug. 9,
2023), appeal docketed, No. 23-5220 (D.C. Cir. argued Sept. 13, 2024).
The government has appealed this decision. When the deemed status of
premium cigars is resolved, FDA will consider any impacts with respect
to this proposed rule and take additional steps as warranted, including
for example, by reopening the comment period and/or issuing a
supplemental notice of proposed rulemaking. References to premium
cigars in this document serve merely to clarify the current proposed
scope of products covered, evaluate the scientific evidence related to
non-premium cigars, and describe FDA's approach to modeling the
projected public health impacts of this proposed standard.
---------------------------------------------------------------------------
\13\ For purposes of its ruling, the court specified that a
premium cigar is a cigar that: (1) is wrapped in whole tobacco leaf;
(2) contains a 100 percent leaf tobacco binder; (3) contains at
least 50 percent (of the filler by weight) long filler tobacco
(i.e., whole tobacco leaves that run the length of the cigar); (4)
is handmade or hand rolled (i.e., no machinery was used apart from
simple tools, such as scissors to cut the tobacco prior to rolling);
(5) has no filter, nontobacco tip, or nontobacco mouthpiece; (6)
does not have a characterizing flavor other than tobacco; (7)
contains only tobacco, water, and vegetable gum with no other
ingredients or additives; and (8) weighs more than 6 pounds per
1,000 units.
---------------------------------------------------------------------------
C. Legal Authority
1. Product Standard Authority
The Tobacco Control Act was enacted on June 22, 2009, amending the
FD&C Act and providing FDA with the authority to regulate tobacco
products. Section 901 of the FD&C Act (21 U.S.C. 387a) granted FDA the
authority to regulate the manufacture, marketing, and distribution of
cigarettes, cigarette tobacco, RYO tobacco, and smokeless tobacco to
protect the public health and to reduce tobacco use by youth. The
Tobacco Control Act also gave the Agency authority to conduct
rulemaking to ``deem'' any other tobacco products subject to chapter IX
of the FD&C Act (21 U.S.C. 387 to 387t). In 2016, FDA issued a final
rule deeming products meeting the statutory definition of ``tobacco
product'' (including cigars and pipe tobacco), except accessories of
the newly deemed products, to be subject to chapter IX of the FD&C Act,
as amended by the Tobacco Control Act (81 FR 28974) (deeming final
rule).
Among the tobacco product authorities provided to FDA is the
authority to adopt tobacco product standards where FDA determines that
such standard is appropriate for the protection of the public health
(section 907(a)(3)(A) of the FD&C Act). To establish a tobacco product
standard, section 907(a)(3)(A) and (B) of the FD&C Act requires that
FDA find that the standard is appropriate for the protection of the
public health, taking into consideration scientific evidence
concerning:
The risks and benefits to the population as a whole,
including users and nonusers of tobacco products, of the proposed
standard;
The increased or decreased likelihood that existing users
of tobacco products will stop using such products; and
The increased or decreased likelihood that those who do
not use tobacco products will start using such products.
2. Authority To Establish a Maximum Nicotine Level and Related
Provisions
Section 907 of the FD&C Act authorizes FDA to adopt tobacco product
standards that are appropriate for the protection of the public health,
including expressly authorizing FDA to adopt product standards with
provisions for nicotine yields; for the reduction or elimination of
other constituents (including smoke constituents) or harmful
components; and respecting the construction, components, ingredients,
additives, constituents (including smoke constituents), and properties
of tobacco products (section 907(a)(3), (a)(4)(A)(i) to (iii), and
(a)(4)(B)(i)). This includes the authority to issue a new product
standard to establish a maximum level of nicotine in tobacco products.
FDA is proposing to limit nicotine yield by setting a maximum
nicotine content level for finished cigarettes and certain other
finished combusted tobacco products not to exceed 0.70 mg of nicotine
per gram of total tobacco. FDA is not seeking to require the reduction
of nicotine yields in any tobacco product to zero, which is prohibited
under section 907(d)(3) of the FD&C Act. To ensure that tobacco
products subject to the product standard comply with the proposed
maximum nicotine level, FDA also is including provisions that would
require manufacturers to test their products using an analytical test
method for conformance with the maximum nicotine level pursuant to
section 907(a)(4)(B)(ii) and (iv) of the FD&C Act.
3. Sale and Distribution Restrictions
Section 907(a)(4)(B)(v) of the FD&C Act states that product
standards shall, where appropriate for the protection of the public
health, include provisions requiring that the sale and distribution of
tobacco products be restricted but only to the extent that the sale and
distribution of a tobacco product may be restricted under section
906(d) of the FD&C Act. Similar to section 907, section 906(d) of the
FD&C Act gives FDA authority to require restrictions on the sale and
distribution of tobacco products by regulation if the Agency determines
that such regulation would be appropriate for the protection of the
public health. The finding as to whether a regulation is appropriate
for the protection of the public health must be determined with respect
to the risks and benefits to the population as a whole, including users
and nonusers of the tobacco products, and must take into account:
The increased or decreased likelihood that existing users
of tobacco products will stop using such products; and
The increased or decreased likelihood that those who do
not use tobacco products will start using such products (see section
906(d)(1) of the FD&C Act).
Under these authorities and section 701 of the FD&C Act, which
provides FDA with the authority to promulgate regulations for the
efficient enforcement of the FD&C Act, FDA is proposing provisions that
would restrict the manufacture, sale, and distribution of cigarettes
and certain other combusted tobacco products that are not in compliance
with this standard. These provisions are not intended to restrict the
manufacture of cigarettes intended for export. Consistent with section
801(e)(1) of the FD&C Act (21 U.S.C. 381(e)(1)), a tobacco product
intended for export shall not be deemed to be in violation of section
907 of the FD&C Act or this product standard, if it meets the criteria
enumerated in section 801(e)(1) of the FD&C Act, including not being
sold or offered for sale in domestic commerce. These provisions are
critical to maintain the purpose of the standard by helping to ensure
that the tobacco products conform to the proposed maximum nicotine
level when used by consumers.
FDA is also proposing, under these authorities and others described
herein regarding testing and recordkeeping, a requirement that the
labels of tobacco products covered under this proposed product standard
contain a manufacturing code to identify, among other things, the date
of manufacture of a production batch, so that FDA can determine whether
a product on store shelves is in conformance with the proposed product
standard. The proposed manufacturing code would allow manufacturers and
FDA to identify the production batch of a particular finished product
that has been released for distribution. This information is intended
to help determine the product's history (e.g., batch production
records) and assist manufacturers and FDA in the event of a
nonconforming tobacco product investigation and any corrective actions
to be taken by a manufacturer as a result
[[Page 5045]]
of the investigation. The manufacturing code must also contain an ``-
NS'' designation. The ``-NS'' designation will enable retailers to
readily identify that a finished tobacco product conforms with this
standard. Finished tobacco products that do not have this designation
do not conform to this standard. The manufacturing code information
also would aid FDA in ensuring compliance with this proposed product
standard by clearly identifying those products that conform to the
standard and linking those products to records that substantiate their
conformance.
4. Testing Requirements
This proposal contains provisions regarding testing requirements
pursuant to sections 907(a)(4)(A)(iii) and 907(a)(4)(B) of the FD&C Act
to help ensure that finished cigarettes and certain other finished
combusted tobacco products conform to the requirements of the proposed
product standard before they are distributed to consumers.
Section 907(a)(4)(A)(iii) states that product standards shall
include provisions that are appropriate for the protection of the
public health, including provisions, where appropriate, relating to any
requirement under section 907(a)(4)(B) of the FD&C Act. Section
907(a)(4)(B)(ii) of the FD&C Act, in turn, provides that a product
standard shall, where appropriate for the protection of the public
health, include provisions for testing the tobacco product. In
addition, section 907(a)(4)(B)(iv) of the FD&C Act provides that, where
appropriate for the protection of the public health, a product standard
shall include provisions requiring that the results of test(s) required
under section 907(a)(4)(B)(ii) show that the product is in conformity
with the portions of the standard for which the test(s) were required.
FDA is proposing testing requirements because it finds that such
requirements are appropriate for the protection of the public health.
Consistent with these statutory provisions, proposed Sec. Sec.
1160.12, 1160.14, and 1160.16 would establish product testing and
sampling plan requirements. Proposed Sec. 1160.12 would require that a
manufacturer conduct testing on each batch of finished cigarettes and
certain other finished combusted tobacco products to determine whether
the products conform to the proposed maximum nicotine level requirement
and would also require the manufacturer to document all testing.
Proposed Sec. 1160.14 would require manufacturers to use an analytical
test method and to demonstrate that the test method was validated in an
analytical test laboratory. Proposed Sec. 1160.16 would require that
manufacturers design and implement a sampling plan for finished
cigarettes and certain other finished combusted tobacco products to
ensure the batch consistently conforms to the proposed maximum nicotine
level.
To support these proposed requirements, proposed Sec. 1160.18(b)
would require each tobacco product manufacturer to investigate all
potential nonconforming tobacco products to determine if the product is
nonconforming. For example, if any representative samples from a batch
of finished cigarettes or certain other finished combusted tobacco
products are determined to be out of conformance or if FDA notifies a
tobacco product manufacturer that a finished tobacco product in
commercial distribution does not conform to the requirements of this
part, the manufacturer must conduct an investigation to determine the
extent of the nonconformity and locations to which nonconforming
tobacco products have been distributed. This proposed requirement would
ensure that any reports of nonconforming products, whether as a result
of manufacturer testing or otherwise, are examined and investigated and
that appropriate measures are taken to ensure that nonconforming
products are not distributed to consumers and to prevent future
nonconformity.
5. Recordkeeping
Section 909 of the FD&C Act authorizes FDA to require tobacco
product manufacturers to establish and maintain records, make reports,
and provide such information as the Agency may by regulation reasonably
require to assure that a tobacco product is not adulterated or
misbranded and to otherwise protect public health.
FDA is proposing a requirement that manufacturers maintain certain
records, including the results of batch testing and analyses conducted
to determine conformance with the proposed product standard, records of
sampling plans and sampling procedures, records related to
manufacturing controls, and all records related to the analytical test
method used to assess finished cigarettes and certain other finished
combusted tobacco products for conformance with the proposed maximum
nicotine level requirement. FDA is also proposing to require that
manufacturers use a manufacturing code, from which the Agency must be
able to identify the production batch of finished cigarettes and
certain other finished combusted tobacco products that have been
released for distribution. The maintenance of these records for the
time period specified in this proposed product standard is necessary to
help ensure that such tobacco products are in conformance with the
proposed product standard and are not adulterated or misbranded,
consistent with the authority provided in section 909 of the FD&C Act.
FDA has authority to inspect manufacturers, including access to these
records, under, among other authorities, section 704 of the FD&C Act.
In addition, the recordkeeping and record access requirements would
help FDA with the efficient enforcement of the Act, consistent with the
rulemaking authority provided by section 701(a) of the FD&C Act.
IV. Nicotine in Cigarettes and Other Combusted Tobacco Products:
Addiction, Initiation, Dependence, Cessation, Relapse, Health Effects,
and Consumer Perceptions
Tobacco products are addictive, primarily due to the presence of
nicotine, and the magnitude of public health harm caused by tobacco
products is inextricably linked to their addictive nature (Ref. 50 at
p. xi). Some evidence suggests that nicotine is more addictive than
many other addictive substances. For example, one study showed the
probability of transitioning from first use to dependence was 68
percent for nicotine, but less than 23 percent for alcohol, cocaine,
and cannabis (Ref. 51). While cigarettes are the most widely used
tobacco products among adults, other combusted tobacco products that
are possible targets of product migration (i.e., alternatives that
allow people who smoke cigarettes to maintain their nicotine addiction)
or dual use have similar adverse health effects, and also cause
nicotine dependence (Refs. 52 and 53). For example, persons who use
cigars and pipe tobacco are still subject to the addictive effects of
nicotine through nicotine absorption (and to the health impacts of
long-term use that may follow from regular use due to addiction) even
if they report that they do not inhale (Refs. 54 to 56).
A. Nicotine Is Addictive
The scientific evidence is clear that nicotine is the primary
chemical in tobacco products that causes addiction through its
psychoactive and reinforcing effects (Ref. 57). Since 1988, the U.S.
Surgeon General has determined that there is a causal relationship
between smoking and addiction to nicotine (Refs. 1 and 57), and the
earlier that individuals begin smoking, the less likely they are to
successfully quit (Ref.
[[Page 5046]]
27). Upon inhaling smoke from a burning cigarette, nicotine is absorbed
into the lungs and rapidly travels to the brain. Once in the brain,
nicotine produces its initial effects by binding to nicotinic
receptors--the primary targets for nicotine in the brain--and inducing
release of the chemical dopamine (Refs. 58 and 59). Dopamine plays a
major role in the pleasurable and reinforcing effects of smoking that
promote continued use (Refs. 58 and 59). Nicotine addiction occurs as
the result of repeated exposure to nicotine, which induces changes in
the brain (Refs. 58 to 60). Addiction to nicotine can lead to symptoms
of nicotine dependence, which may include tolerance to the effects of
nicotine, withdrawal symptoms upon cessation of use, and craving
cigarettes (Refs. 1 and 58).
The addiction potential of a nicotine delivery system varies as a
function of its total nicotine dosing capability, the speed at which it
can deliver nicotine, the rate of absorption, its palatability and
sensory characteristics, how easy it is for the person using the
product to extract nicotine, and its cost (Ref. 61). The amount of
nicotine delivered and the means through which it is delivered can
either reduce or enhance a product's potential for abuse and
physiological effects (Ref. 28 at p.113). Quicker delivery, higher rate
of absorption, and higher resulting concentration of nicotine increase
the potential for addiction (Ref. 28 at p.113). A cigarette is an
inexpensive and extremely effective nicotine delivery system that
maximizes the cigarette's addicting and toxic effects (Ref. 61).
Tobacco use disorder is a psychiatric disorder, defined by the
Diagnostic and Statistical Manual of Mental Disorders (DSM) as being
characterized by tolerance to the effects of tobacco products,
withdrawal symptoms that are mitigated by the self-administration of
nicotine-containing products, and unsuccessful attempts at reducing or
quitting the use of nicotine-containing products (Ref. 62). Researchers
consider several behaviors indicative of a substance with addictive
properties. These behaviors include reinforcement, tolerance,
withdrawal, and craving--all of which support the fact that nicotine is
the primary addictive constituent in tobacco products. The scientific
evidence is clear that nicotine is the primary chemical in tobacco
products that causes and maintains addiction.
1. Reinforcement
The reinforcement threshold for nicotine can be defined as the
lowest nicotine level that would maintain or increase nicotine self-
administration behavior. Currently, most marketed cigarettes are above
that threshold; people who smoke cigarettes develop and maintain their
addiction through continued smoking (Refs. 17 and 63). Evidence
supports that VLNC cigarettes (see table 1 of this document) are below
that threshold, as studies show a reduction in the level of addiction
based on dependence scales (Ref. 32) and cigarettes per day (CPD)
(Refs. 32, 64, and 65). The maximum nicotine level included in this
proposed product standard is based on FDA's analysis of studies
regarding the likely effects of reducing nicotine, which demonstrates
that extended exposure to VLNC cigarettes, which result in very low
nicotine yield that cannot be overcome by use behaviors, is associated
with reduced addiction potential, dependence levels, number of
cigarettes smoked per day, and increased quit attempts among people who
currently smoke cigarettes, without evidence of increased toxicant
exposure, craving, withdrawal, or compensatory smoking (Ref. 45).
2. Tolerance
Tolerance is defined as a state in which, after repeated exposure,
a substance produces less of an effect than previously (Ref. 66) and
increasing amounts are required to achieve the effect observed with the
first exposure. Both clinical and preclinical research has shown that
nicotine has euphoric effects, produces a ``pleasurable buzz,'' and
directly enhances positive affect or indirectly increases the reward
value of pleasurable situations (Refs. 67 to 70). With repeated
exposure to nicotine, neuroadaptation occurs to some of these positive
effects, and symptoms of craving and withdrawal begin during periods of
abstinence (Ref. 58). Nicotine addiction results from a combination of
positive reinforcement from smoking and avoidance of these withdrawal
symptoms (Ref. 58). Evidence of tolerance in people who smoke
cigarettes is demonstrated as they tend to progressively increase the
number of cigarettes they smoke over a period of several years before
plateauing to a relatively constant level of use (Ref. 71).
3. Withdrawal and Craving
Nicotine produces a characteristic withdrawal syndrome manifested
by irritability/anger/frustration, anxiety, depressed mood, difficulty
concentrating, increased appetite, insomnia, and restlessness (Ref.
72). Symptoms typically emerge within the first 1-2 days following
abstinence, peak within the first week, and last 2-4 weeks (Ref. 73).
The symptoms and time course are consistent with most prototypical
addictive substances (e.g., alcohol, benzodiazepines, opioids,
amphetamines, cocaine, caffeine) (Ref. 74). While some have asserted
that people smoke cigarettes as a ``tool'' or ``resource'' that
provides them with needed ``psychological benefits,'' such as increased
mental alertness and anxiety reduction (Ref. 75), this view is not
borne out by the scientific evidence. In fact, the claimed
``psychological benefits'' (i.e., increased mental alertness, anxiety
reduction, coping with stress) that have been ascribed to a smoking
``habit'' are actually symptoms of withdrawal suppression (Ref. 76).
Craving or urge is described as a motivation for substance use, which
is seen in people who use nicotine (Refs. 77 to 79). Although craving
is often characterized as a symptom of nicotine and tobacco withdrawal,
it is also a prominent symptom of nicotine dependence (Ref. 72), and it
can occur in the absence of other withdrawal symptoms.
4. Nicotine Use Is an Addiction, Not a Habit
A few individual reports have challenged the conclusion that
nicotine is the constituent in tobacco products that causes addiction,
stating that nicotine only causes habitual behavior (Refs. 67 and 75),
and that the craving associated with nicotine is determined by
nonpharmacological factors that are disassociated from smoking
withdrawal (Ref. 80). However, nicotine has been extensively studied
and the evidence overwhelmingly demonstrates that nicotine is an
addictive drug and the fundamental reason that individuals continue
using tobacco products (Refs. 57 and 28). Since 1988, the U.S. Surgeon
General has concluded that nicotine is the substance in tobacco
products that causes addiction through its psychoactive effects,
reinforcing effects, tolerance, and physical dependence/withdrawal, and
that nicotine use is not habitual (Ref. 57). The tobacco industry also
has acknowledged that nicotine is addictive (Refs. 81 and 82).
For these reasons, FDA concludes that the addictiveness of nicotine
in tobacco products leads to regular use (even when people wish to
quit), which is at the root of tobacco-related disease and death from
cigarettes and certain other combusted tobacco products.
[[Page 5047]]
B. The Developing Brain's Vulnerability to the Effects of Nicotine
Leads to Progression to Regular Cigarette Use Among Youth and Young
Adults Who Experiment
Youth and young adults are particularly susceptible to developing
an addiction to nicotine. Due to the brain's ongoing development during
adolescence and young adulthood--until about age 25--it is more
vulnerable to nicotine's effects than the adult brain is (Refs. 83 to
85). The 1994, 2012, 2014, and 2020 Surgeon General's Reports on
smoking and health note that almost 90 percent of adults who currently
and regularly smoke initiated smoking by age 18, and 98 percent
initiated smoking by age 26, which is notable given that 25 is the
approximate age at which the brain has completed development (Refs. 1,
17 to 19). The developing brain is more vulnerable to developing
nicotine dependence than the adult brain is, and the earlier an
individual begins smoking the less likely they are to quit (Ref. 20).
The maximum nicotine level requirement included in this proposed
product standard to regulate nicotine yield would make cigarettes and
certain other combusted tobacco products minimally addictive or
nonaddictive, limiting the number of youth and young adults who
progress from experimentation to regular use and reducing their risk
for smoking-related diseases.
There are three primary stages that occur as an individual
transitions from never smoking to smoking cigarettes regularly:
initiation, experimentation, and regular use. An individual initiates
smoking once he or she first tries a cigarette, even one or two puffs
(Ref. 17). The vast majority of smoking initiation occurs during
adolescence (Ref. 17). Initiation can progress to experimentation,
where individuals continue to occasionally try cigarettes, but do not
smoke every day, and then to smoking regularly (i.e., smoking daily or
on most days) (Ref. 17).
Adolescence is a period of development when individuals who
experiment with tobacco products are more susceptible to transitioning
to regular use and developing addiction to nicotine. Data from the 2024
NYTS found that 10.1 percent of high school students and 5.4 percent of
middle school students reported current use of any tobacco product
(Ref. 3). Each day, approximately 1,200 youth (ages 18 and below) try
their first cigarette (Ref. 86 at Table A.13A). The transition to
regular cigarette use (i.e., smoking on >=20 of the past 30 days) can
occur relatively quickly and can be achieved by smoking as few as 100
cigarettes (Ref. 17). Longitudinal and nationally representative cross-
sectional data indicate that an established pattern of cigarette use--
including those who ``rapidly escalate'' to regular use--typically
occurs by early adulthood (ages 20-22) (Refs. 87 and 88). The Centers
for Disease Control and Prevention (CDC) and other researchers have
estimated that 30 percent or more of people who experiment with
cigarettes transition to regular cigarette use (Refs. 89 to 92).
Researchers applied the 30 percent estimate to the number of
adolescents who were at the early experimentation stage in 2000,
translating to approximately 2.9 million of these adolescents who have
or will become people who regularly smoke cigarettes (Ref. 91). Based
on the number of persons under the age of 18 in 2012 in the United
States, the U.S. Surgeon General estimated that 17,371,000 of that
group would begin smoking cigarettes regularly and 5,557,000 will die
from a smoking-related disease (Ref. 1 at Table 12.2.1). These
concerningly high numbers speak to the extreme vulnerability of youth
and young adults to the health harms of tobacco use resulting from
addiction to nicotine.
Nicotine addiction is a critical factor in the transition of people
who smoke cigarettes from experimentation to regular smoking and in the
continuation of smoking for those who want to quit (Ref. 28 at p.113,
Ref. 1). Although the majority of adolescents who smoke daily meet the
criteria for nicotine dependence, one study found that the most
susceptible youth lose autonomy (i.e., independence in their actions)
regarding tobacco within 1 or 2 days of first inhaling from a cigarette
(Refs. 93 and 94). Another study found that 19.4 percent of adolescents
(initially ages 12-13 and followed over 6 years) who smoked weekly were
dependent on nicotine (Ref. 95). In a study regarding nicotine
dependence among adolescents who recently initiated smoking (9th and
10th grade students), adolescents who smoked cigarettes at the lowest
levels (i.e., smoking on only 1 to 3 days of the past 30 days)
experienced nicotine dependence symptoms such as loss of control over
smoking (42 percent) and irritability after not smoking for a while (23
percent) (Ref. 96). Researchers in a 4-year study of 6th grade students
also found that ``[e]ach of the nicotine withdrawal symptoms appeared
in some subjects prior to daily smoking'' (Ref. 93) (emphasis added).
Ten percent of the study participants showed signs of tobacco
dependence within 1 or 2 days of first inhaling from a cigarette, and
half had done so by the time they were smoking seven cigarettes per
month (Ref. 93).
Similarly, researchers have found that among the 3.9 million middle
and high school students who reported current use of tobacco products
(including cigarettes and cigars) in 2012, 2 million of those
students--including those who used intermittently (e.g., smoking
cigarettes on a monthly basis)--reported at least one symptom of
dependence (Ref. 24). Other researchers analyzing data from the 2021
NYTS found that a sizeable proportion of high school students using
tobacco products in the past 30 days report symptoms of nicotine
dependence, including 27.2 percent reporting a strong craving for
tobacco use and 19.5 percent reporting wanting to first use tobacco
products within 30 minutes of waking (Ref. 25). Overall, these findings
demonstrate that youth and young adults who experiment with cigarettes
(and other tobacco products) are particularly vulnerable to the effects
of nicotine on progression to regular use and dependence, leading to
maintained tobacco product use into adulthood.
C. Youth and Adult Cigarette Smoking Cessation and Relapse
Like adults, many youths who smoke cigarettes want to quit but have
difficulty doing so. An analysis of data from the 2015 YRBS looking at
youth cigarette quit attempts found that 45.4 percent of high school
students currently smoking cigarettes had sought to quit in the
previous year (Ref. 22); 2012 NYTS data were congruent, indicating that
51.5 percent of middle and high school students who smoke cigarettes
had sought to quit all tobacco use in the previous year (Ref. 22).
For adults who smoke who report quit attempts, few are successful.
As of 2019, researchers estimate that only between 5.4 and 5.6 percent
of people who smoked cigarettes successfully quit for good, according
to data from the NHIS and National Survey on Drug Use and Health
(NSDUH), respectively (Ref. 14). According to recent data regarding
adult quit attempts, analyses of 2022 NHIS and 2018-2019 TUS-CPS data
indicate that 67.7 and 76.6 percent of adults, respectively, who smoke
cigarettes were interested in quitting (Refs. 4 and 36), while the 2022
NHIS data and 2018-2019 TUS-CPS data show that only 53.3 and 51.3
percent, respectively, of U.S. adults who smoke actually made a quit
attempt within the past year (Refs. 4 and 36). Analyses of 2022 NHIS
and 2018-2019 TUS-CPS data indicates that only 8.8 and 7.5 percent of
adults who
[[Page 5048]]
formerly smoked cigarettes had successfully quit smoking cigarettes,
respectively (Ref. 4 and 36). Adults who smoke may make 30 or more quit
attempts before succeeding (Ref. 37). Some population groups are less
successful than others: for example, adults with education levels at or
below the equivalent of a high school diploma have the highest smoking
prevalence levels but the lowest quit ratios (i.e., the ratio of
persons who have smoked at least 100 cigarettes during their lifetime
but do not currently smoke to persons who report smoking at least 100
cigarettes during their lifetime) (Ref. 97). Nicotine addiction and
associated withdrawal symptoms make it difficult for people who smoke
cigarettes to quit, and quit rates rarely exceed 25 percent (Ref. 98).
Relapse is the principal limiting factor in the transition from
smoking to nonsmoking status (Ref. 28). Relapse refers to the point
after an attempt to stop smoking when a person's tobacco use again
becomes ongoing and persistent (Ref. 28 citing Brandon et al., 1986).
Most people who relapse do so soon after their quit attempt (Ref. 28).
One study found that 80 to 90 percent of individuals who were smoking
at 6 months following a quit attempt had resumed smoking within 2 weeks
following their quit attempt (Ref. 99). However, even those who quit
smoking for longer periods of time frequently relapse. Long-term
studies of individuals trying to quit smoking reveal that 30 to 40
percent of those who quit smoking for 1 year eventually relapsed (Ref.
99). In addition, one study following 840 participants for more than 8
years found that approximately one-half of people who smoke who stopped
smoking for 1 year relapsed to regular smoking within the subsequent 7
years (Ref. 100). Researchers have found that a higher frequency of
smoking is associated with earlier lapses after cessation (e.g.,
smoking on the first day of cessation or within the first 2 weeks),
which in turn is strongly associated with an increased risk of relapse,
and is also associated with more severe withdrawal symptoms and earlier
relapse after an attempt to quit smoking (Ref. 28 at p.119). These
findings confirm the powerful addictive properties of nicotine in
tobacco products, a principal factor limiting the ability to quit for a
person who uses combusted tobacco products, and further underscore the
public health importance of decreasing the addictiveness of these
products by decreasing nicotine yield, particularly for youth and young
adults who experiment with smoking and for people currently smoking and
who hope to quit.
D. Smoking Cigarettes and Other Combusted Tobacco Products Causes
Serious Negative Health Effects
Nicotine is a powerfully addictive chemical. The effects of
nicotine on the central nervous system occur rapidly after absorption
(Ref. 57 at p.12). People who use cigarettes and other combusted
tobacco products absorb nicotine readily from tobacco smoke through the
lungs (Ref. 57 at p. iii), and, from the lungs, nicotine is then
rapidly transmitted to the brain (Ref. 57 at p.13). In the case of
cigars, nicotine is also absorbed through the mouth. With regular use,
nicotine levels accumulate in the body during the day from tobacco
product use and the nicotine persists overnight, allowing for
continuous exposure throughout the entire 24-hour period (Ref. 57 at
p.38). While mild nicotine intoxication can occur among people who are
smoking for the first time (Ref. 57 at p. 15-16), tolerance to the
effects of nicotine develops rapidly.
Cigarette smoking is responsible for 480,000 premature deaths every
year from many diseases, puts a substantial burden on the U.S.
healthcare system, and causes massive economic losses to society (Ref.
1 at p. 659-666). In terms of a monetary measure of the impact of
cigarette smoking on the public health, in 2018 smoking cost the United
States more than $600 billion, including more than $240 billion in
healthcare spending (Ref. 10), nearly $185 billion in lost productivity
from smoking-related illnesses and health conditions (Ref. 10), nearly
$180 billion in lost productivity from smoking-related premature death
(Refs. 1 and 10), and $7 billion in lost productivity from premature
death from secondhand smoke exposure (Refs. 1 and 11). Current evidence
shows that, while nicotine itself is not the direct cause of most
smoking-related diseases, addiction to the nicotine in tobacco products
is the proximate driver of tobacco-related death and disease because it
sustains tobacco use even when people who smoke want to quit (which
most people who smoke report wanting to do) (Refs. 1, 13, 28, 58, and
61). Inhalation of smoke from cigarettes and other combusted tobacco
products exposes people who use the products to over 7,000 chemicals,
many known to be hazardous to health and lead to disease (Ref. 28).
According to the 2014 Surgeon General's Report, which summarizes
thousands of peer-reviewed scientific studies and is itself peer-
reviewed, smoking remains the leading preventable cause of disease and
death in the United States, and cigarettes have been shown to cause an
ever-expanding number of diseases and health conditions (Ref. 1). Every
year, cigarette smoking is the primary causal factor for 163,700 deaths
from cancer, 160,600 deaths from cardiovascular and metabolic diseases,
and 131,100 deaths from pulmonary diseases (Ref. 1 at p.659). In the
United States, about 87 percent of all lung cancer deaths, 32 percent
of coronary heart disease deaths, and 79 percent of all cases of
chronic obstructive pulmonary disease (COPD) are attributable to
cigarette smoking (Ref. 1). Smoking during pregnancy can result in
negative outcomes for a newborn baby, such as low birth weight, lungs
that fail to develop properly, birth defects such as cleft lip and/or
cleft palate, and Sudden Infant Death Syndrome (Ref. 101). As stated in
the 2014 Surgeon General's Report, ``[c]igarette smoking has been
causally linked to diseases of nearly all organs of the body, to
diminished health status, and to harm to the fetus . . . [and] the
burden of death and disease from tobacco use in the United States is
overwhelmingly caused by cigarettes and other combusted tobacco
products'' (Ref. 1 at p.7).
Tobacco and cigarette smoking-related morbidity and mortality also
have been experienced differentially across different sociodemographic
characteristics, such as race, ethnicity, socioeconomic status,
educational attainment, mental health status, and homelessness. Black
\14\ adults, and in particular Black men, experience the highest rates
of incidence and mortality from many tobacco-related cancers, such as
lung and bronchus cancer and head and neck cancer, compared to those
from other racial and ethnic groups (Refs. 102 to 104). Deaths from
other tobacco-related conditions such as heart disease, stroke, and
hypertension are higher among Black individuals compared to other
racial and ethnic groups regardless of tobacco use status (Refs. 105 to
110). Compared to persons identifying as non-Hispanic White, Hispanic
and Black persons smoke fewer cigarettes (Refs. 111 to 113) and are
more likely to be people who do not smoke daily (Refs. 111 and 114),
yet
[[Page 5049]]
have greater risk of lung cancer morbidity and mortality (Refs. 1, 115
to 118). Additionally, American Indian/Alaska Native (AI/AN)
populations have the highest cigarette use prevalence (Refs. 119 to
121) and are more likely to suffer disproportionate rates of tobacco-
related death (Ref. 119). An analysis of 2001-2009 mortality data for
people living in the Indian Health Service Contract Health Service
Delivery Area counties in the United States indicated that age-adjusted
death rates, smoking-attributable fractions, and smoking-attributable
mortality for all-cause mortality were statistically significantly
higher among AI/AN populations than among White populations for adult
men and women aged 35 years and older (Ref. 122). Cigarette smoking
caused 21 percent of ischemic heart disease, 15 percent of other heart
disease, and 17 percent of stroke deaths in AI/AN men, compared with 15
percent, 10 percent, and 9 percent, respectively, for White men (Ref.
122). Among AI/AN women, smoking caused 18 percent of ischemic heart
disease deaths, 13 percent of other heart disease deaths, and 20
percent of stroke deaths, compared with 9 percent, 7 percent, and 10
percent, respectively, among White women (Ref. 122). Some Asian
populations, Native Hawaiians, and other Pacific Islander populations
also suffer from disproportionate rates of tobacco-related mortality as
compared to non-Hispanic White persons (Refs. 115, 117, 123, and 124).
---------------------------------------------------------------------------
\14\ Throughout this document, FDA uses both the terms ``Black''
and ``African American.'' The term ``African American'' is used to
describe or refer to a person of African ancestral origins or who
identifies as African American. ``Black'' is used to broadly
describe or refer to a person who identifies with that term. Though
these terms may overlap, they are distinct concepts (e.g., a Black
person may not identify as African American). As a result, FDA
relies on the specific term used by researchers when citing to
specific studies. FDA uses the term ``Black'' when not citing to a
specific study.
---------------------------------------------------------------------------
Disparities in tobacco-related morbidity and mortality have also
been observed for additional population groups that have higher levels
of tobacco use. Those with low household income and/or educational
attainment bear a disproportionate burden of myocardial infarction
prevalence and coronary heart disease-related mortality (Ref. 125).
National Health and Nutrition Examination Survey (NHANES) data from
2007 to 2010 indicate that prevalence of co-occurring obesity and
smoking was linearly associated with educational attainment as women
with the lowest levels of education had greater likelihood of being
obese and smoking than women with the highest levels of education (Ref.
126). Some research also indicates that race/ethnicity status interacts
with the effects of higher educational attainment on the likelihood of
current smoking. The protective effect of higher education against
current smoking was shown to be a stronger effect for White as compared
to Black respondents (Ref. 127). Research has also demonstrated that
individuals with behavioral health conditions and other medical
comorbidities have higher prevalence of combusted tobacco use compared
to those without these conditions (Refs. 128 and 129) and have
increased risk of tobacco-related morbidity and mortality (Refs. 120,
130, and 131). Inpatient hospital admission data from 1990 to 2005 from
California indicate that approximately half of the deaths in those who
had been hospitalized for schizophrenia, bipolar disorder, or major
depressive disorder were due to diseases causally linked to tobacco use
(Ref. 130) and that the majority of deaths for those hospitalized for
opioid-related conditions were related to tobacco and alcohol, not to
opioids (Ref. 132). Tobacco-related cancers are a leading cause of
death among adults experiencing homelessness (Ref. 133). While
cigarette smoking and exposure to cigarette smoke are responsible for
significant mortality--480,000 premature deaths annually, as previously
stated--this estimate does not include deaths caused by other tobacco
products, such as cigars and pipes (Ref. 1 at p. 665).\15\
Additionally, for every person who dies from a smoking-related disease
in the United States, approximately 30 more people will suffer from at
least one smoking-related disease (Ref. 1).
---------------------------------------------------------------------------
\15\ Regular cigar smoking was responsible for approximately
9,000 premature deaths and more than 140,000 years of potential life
lost among adults aged 35 years or older in 2010 (Ref. 134). The
2014 Surgeon General's Report states that the methodology for
estimating the current population burden for use of combusted
tobacco products other than cigarettes remains under discussion, but
the number of added deaths is expected to be in the thousands per
year (Refs. 1 and 135).
---------------------------------------------------------------------------
Inhalation of the chemicals produced by combustion results in
numerous adverse health outcomes through mechanisms that include DNA
damage, inflammation, and oxidative stress (Ref. 28). The three leading
causes of smoking-attributable death for people who currently and
formerly smoke cigarettes are lung cancer, heart disease, and COPD
(Ref. 1 at p. 660). Cigarette smoking results in a chronic inflammatory
state in the cardiovascular system that is known to be a powerful
predictor of cardiovascular events including heart disease (Ref. 28).
For COPD, although studies have shown that the disease can be almost
completely prevented with the elimination of smoking (Ref. 63), for
those who have already developed the disease, evidence indicates that
the related morbidity persists long after cessation of smoking (Ref.
28). In addition, it has been established that more than 85 percent of
lung cancers are due to smoking, and lung cancer is the country's
leading cause of cancer death (Refs. 1, 28, 63, and 136).
Cigarettes and other combusted tobacco products also have deadly
effects on people who do not smoke because they produce secondhand
smoke. It is well-established that secondhand tobacco smoke causes
premature death and disease in children and in adults who do not smoke
(Ref. 15 at p.11). Secondhand smoke exposure is currently estimated to
be responsible for over 41,000 deaths annually in the United States
(Ref. 1). For example, an estimated 7,300 lung cancer deaths and nearly
34,000 coronary heart disease deaths annually can be attributed to
secondhand smoke (Ref. 1). Additionally, productivity losses due to
secondhand smoke-attributable deaths are estimated to cost the United
States $5.6 billion each year (Ref. 1).
Secondhand smoke is particularly harmful to children. For instance,
the 2014 Surgeon General's Report estimated that each year, secondhand
smoke is associated with 150,000 to 300,000 lower respiratory tract
infections in infants and children under 18 months of age, 790,000
doctor's office visits related to ear infections, and 202,000 asthma
cases (Refs. 1 and 137). In addition, thirdhand smoke--the chemical
residue from combusted tobacco smoke that can become embedded in the
environment (e.g., carpet, dust)--results in exposure to harmful
constituents such as tobacco specific nitrosamines (Ref. 138). Exposure
to thirdhand smoke is especially concerning for young children given
their size and behaviors, like crawling on the ground and frequently
putting their hands in their mouths.
Additionally, the burden of secondhand smoke exposure is
experienced disproportionately among members of some racial and ethnic
groups and people with lower household income and educational
attainment. Among people who do not smoke, ages 3 and older, findings
from 2011 to 2018 NHANES data indicate that non-Hispanic Black
respondents and those living below the poverty level had the highest
levels of secondhand smoke exposure compared to people of other races
and those living above the poverty level, respectively; these
disparities persisted across all years of the study analysis from 2011
to 2018 (Ref. 139). From 1999 to 2012, the percentage of persons who do
not smoke (ages 3 and older) with detectable serum
[[Page 5050]]
cotinine \16\ levels (defined in the study as levels >=0.05 nanogram
per milliliter to indicate secondhand smoke exposure) declined across
all racial and ethnic groups (Ref. 141). However, a higher proportion
of non-Hispanic Black individuals who do not smoke continued to have
detectable serum cotinine levels, compared to Hispanic and non-Hispanic
White individuals who do not smoke. For example, in 2017-2018, nearly
50 percent of non-Hispanic Black people who do not smoke had detectable
serum cotinine levels, compared with 22 percent of non-Hispanic White
and 17 percent of Mexican American people who do not smoke (Ref. 141).
Moreover, disparities in trends in detectable serum cotinine levels
among people who do not use cigarettes over time have been observed on
the basis of race/ethnicity. One analysis of NHANES data and found that
from 1999 to 2012 among children ages 3-11, comparable levels of
decline were observed among non-Hispanic White (percentage change: 41.2
percent) and Mexican American (percentage change: 39.0 percent) youth,
but a lesser decline was observed among non-Hispanic Black youth
(percentage change: 19.8 percent) (Ref. 141). A more recent analysis of
NHANES data also indicated that, between 2011 and 2018, the percentage
of people who do not use cigarettes with detectable serum cotinine
levels increased among non-Hispanic Black youth ages 12-19 but remained
stagnant among non-Hispanic White youth of the same ages (Ref. 142).
---------------------------------------------------------------------------
\16\ Cotinine is an alkaloid found in tobacco leaves and is the
main metabolite of nicotine. Measuring cotinine in people's blood is
a reliable way to determine exposure to nicotine for both people who
smoke and those exposed to environmental tobacco smoke (Ref. 140).
---------------------------------------------------------------------------
Moreover, there is also some scientific evidence supporting
disparities in secondhand smoke exposure by sexual orientation. An
analysis of NHANES data from 2003-2010 found that secondhand smoke
exposure (defined as a serum continine \17\ levels >=0.05 nanogram per
milliliter) differed by sexual orientation among women 20-59 years of
age (Ref. 143). This study found that among women 20-59 years of age,
secondhand smoke exposure was higher among non-smoking women who
identified as lesbian (56.2 percent) or who reported a lifetime
experience with a same-gender partner (47.7 percent) than those women
who identified as exclusively heterosexual (33.0 percent; p<0.001)
(Ref. 143). However, among men 20-59 years of age, exposure to
secondhand smoke did not significantly differ by sexual orientation.
Disparities in the secondhand smoke exposure are found across
various environmental settings. These disparities speak to the
interrelated influences of individual factors (e.g., age, race and
ethnicity, sexual orientation, income) and existing inequities in
places where members of communities disproportionally impacted by
tobacco-related health disparities are likely to reside, spend time,
and work (Refs. 53 and 120). For example, an analysis of NHANES data
from 2017-2018 found that 87.8 percent of non-smoking persons 3 years
of age and older who lived with someone who smoked inside the home was
exposed to secondhand smoke based on serum cotinine values of 0.05-
10.00 nanogram per milliliter compared to 21.4 percent of non-smoking
persons 3 years of age and older not living with someone who smoked
inside the home (Ref. 142). In terms of race and ethnicity, findings
drawn from the 2013-2016 NHANES data indicate that compared to non-
Hispanic White respondents, non-Hispanic Black respondents had higher
odds of secondhand smoke exposure in homes other than their own (Ref.
144). An analysis of NYTS data indicates that non-Hispanic Black and
non-Hispanic White students both had higher prevalence of secondhand
smoke exposure at home and in vehicles than Hispanic and non-Hispanic
other race/ethnicity students (Ref. 145). While secondhand smoke
exposure in homes and vehicles declined from 2011 to 2018, secondhand
smoke exposure in homes among non-Hispanic Black students did not
change (Ref. 145). Additionally, a study using data from Wave 1 (2013-
2014) of the Population Assessment of Tobacco and Health (PATH) Study
found that the odds of exposure to secondhand smoke at home were higher
for Black adults (OR=1.12, 95 percent CI:1.00-1.24; p-value=0.042) than
White adults; and higher for those adults who self-identified as being
LGBT (OR=1.30, 95 percent CI:1.11-1.52; p-value=0.001) than for
heterosexual adults (Ref. 146). Home smoking bans (i.e., when people
decide to have their own rules that restrict or ban smoking inside
their own home)--can reduce secondhand smoke exposure. For example, a
study using data from the 2009-2010 National Adult Tobacco Survey
(NATS) found the prevalence of exposure to secondhand smoke varied
based on the presence (or absence) of smokefree rules in the home (Ref.
147). This study found that overall, 1.4 percent of people who did not
smoke and had a smokefree rule at home were exposed to secondhand smoke
in their homes in the past 7 days, compared with 43.9 percent of people
who did not smoke and did not have a smokefree rule at home (Ref. 147).
A similar pattern was observed across age groups, race and ethnicity,
and levels of educational attainment. For example, a higher percentage
of Black and Hispanic people were exposed to secondhand tobacco smoke
in homes with and without smokefree rules than White people.
Additionally, a study using 1995-2007 TUS-CPS data found that among two
parent households, higher levels of parental educational level and
annual household income were associated with the higher reporting of a
complete home ban as compared to lower levels of parental educational
and annual household income (Ref. 148). Such findings emphasize the
degree to which certain aspects of disadvantage (such as lower family
income, lack of access to single-family housing, or lack of autonomy
over the home environment) may compound tobacco-related health
disparities.
Individuals who live in multi-unit housing, including apartments,
are particularly susceptible to involuntary secondhand smoke exposure
in the home, as secondhand smoke can infiltrate throughout a building
along various pathways (Refs. 149 to 153). Exposures to secondhand
smoke in multi-unit housing are potentially concerning given a study
drawing on the 2013-2014 National Adult Tobacco Survey (NATS) found
that tobacco use was higher among adults living in multi-unit housing
(24.7 percent) than those in single-family housing (18.9 percent) (Ref.
154). This study also found that smoke-free home rules (i.e., home
smoking bans) were higher among adults living in single-family housing
(86.7 percent) than those in multi-unit housing (80.9 percent) (Ref.
154). However, more than a third (34.4 percent) of multi-unit housing
residents with home smoking bans have experienced secondhand smoke
incursions (Ref. 154). Recent estimates indicate that approximately 80
million residents in the United States are currently living in some
type of multi-unit housing (Ref. 150). Among those living in multi-unit
housing with a home smoking ban, an estimated 27.6-28.9 million are
exposed to secondhand smoke incursions from neighboring units and/or
shared common areas (Ref. 150). Moreover, a 2013 nationally
representative study conducted among U.S. adults living in multi-unit
housing found that 25.2 percent of non-smoking residents who had no
smoking in the home for at least 3 months and who also
[[Page 5051]]
had a child in the home had a recent secondhand smoke incursion into
their unit; 99 percent of these residents also reported being bothered
by the incursion (Ref. 155). Multi-unit housing secondhand smoke
incursions have also been found to be greater among specific
populations that are already disproportionately burdened by tobacco-
related disease and death, including women, younger adults, and non-
Hispanic Black, Hispanic, and lower income populations (Ref. 154).
Workplace secondhand smoke exposure has also been shown to vary
across population groups. A study using data from the 2009-2010 NATS
show the prevalence of secondhand smoke exposure from employed
nonsmoking adults was higher among males, non-Hispanic Black, Hispanic,
and AI/AN people compared with White people, and people with low
education and low income (Ref. 156). Similarly, data from the 2010 and
2015 NHIS show that exposure to secondhand smoke in the workplace was
disproportionately high among non-Hispanic Black respondents, Hispanic
respondents, and workers with low education and low income (Ref. 157).
Additionally, the study findings indicated that ``blue-collar workers''
(defined as those who performed manual labor such as manufacturing,
mining, sanitation, and construction) experienced higher prevalence of
secondhand smoke exposure compared to ``white-collar workers'' (defined
as those who primarily work in an office, with computer and desk
setting, and perform professional, managerial, or administrative work)
(Ref. 157).
The disparities observed in tobacco use, as well as disparities in
secondhand smoke exposure, contribute to the disparities in tobacco-
related morbidity and mortality experienced by some population groups.
This proposed product standard is anticipated to reduce smoking-related
morbidity and mortality for the population as a whole, including these
populations that use tobacco or are exposed to secondhand smoke at
disproportionately high levels.
Other combusted tobacco products, particularly those that could
serve as alternatives to cigarettes if people who smoke cigarettes no
longer had access to normal nicotine cigarettes (NNC), cause similar
negative health effects. For example, cigar smoke contains many of the
same harmful constituents as cigarette smoke, and cigar smoke may have
even higher levels of several harmful compounds compared to cigarette
smoke (Refs. 1, 134 and 158). For example, cigar smoke contains higher
amounts of carcinogenic, tobacco-specific N-nitrosamines than cigarette
smoke due to the relatively high concentration of nitrate in cigar
tobacco, which leads to formation of cancer-causing nitrosamines during
the fermentation process (Refs. 1; 53 at Chapter 3; and 158).
Researchers have found urinary concentrations of 4-(methylnitrosamino)-
1-(3-pyridyl)-1-butanol (NNAL) (a hazardous tobacco-specific
nitrosamine) measured in people who smoke cigars daily to be as high as
those measured in people who smoke cigarettes daily (Refs. 159 and
160). Like exposure to cigarette smoke, exposure to higher levels of
cigar smoke for longer time periods increases the adverse health risks
caused by cigar smoking (Ref. 28).
Consequently, there is a long-standing body of research, including
reports from the U.S. Surgeon General and National Cancer Institute
(NCI), demonstrating that cigar use causes serious adverse health
effects (Ref. 53 at p.119-155; Refs. 55; 161, and 162). NCI's Smoking
and Tobacco Control Monograph No. 9 (``Cigars: Health Effects and
Trends''), which provides a comprehensive, peer-reviewed analysis of
the trends in cigar smoking and potential public health consequences,
as well as other research, demonstrates that cigar smoking leads to an
increased risk of oral, laryngeal, esophageal, pharyngeal, and lung
cancers, as well as coronary heart disease and aortic aneurysm, with
the magnitude of risk a function of the amount smoked and depth of
inhalation (Ref. 53 at p.119-155). Likewise, a systematic review of the
mortality risks associated with cigar smoking that identified 22
studies found that people who regularly smoke cigars are at increased
risk for many of the same diseases as people who smoke cigarettes,
including oral, laryngeal, esophageal, and lung cancer; cardiovascular
diseases; and COPD (Ref. 163).
Research indicates that most people who smoke cigars do inhale some
amount of smoke, even when they do not intend to inhale, and are not
aware of doing so (Refs. 54 and 55). Even when people who smoke cigars
do not breathe smoke into their lungs, they are still subject to the
addictive effects of nicotine through nicotine absorption (Refs. 55 and
56). This nicotine absorption occurs because cigar smoke dissolves in
saliva, allowing the person smoking the cigar to absorb sufficient
nicotine by holding the smoke in their mouths, even if the smoke is not
inhaled (Refs. 53, 56, and 164). Cigar and/or pipe smoking causes
cancers of the lung and upper aerodigestive tract, including the oral
cavity, oropharynx, hypopharynx, larynx and esophagus (Ref. 158).
Additional evidence suggests that cigar and/or pipe smoking is causally
associated with cancers of the pancreas, stomach, and bladder (Ref.
165). People who smoke cigars also have increased risks for coronary
heart disease and COPD compared with people who never used tobacco
(Ref. 166).
One study using NATS data from 2009 to 2010 found that regular
cigar smoking (defined as use on at least 15 of the past 30 days) was
responsible for approximately 9,000 premature deaths and more than
140,000 years of potential life lost among adults aged 35 years or
older in 2010 (Ref. 134). A study of healthcare expenditures from 2000
to 2015 found that cigar-attributable healthcare expenditures for
adults totaled $1.75 billion per year, with $284 million attributed to
exclusive cigar smoking and $1.5 billion attributed to poly tobacco use
(i.e., use of multiple tobacco products) involving cigar smoking plus
cigarette or smokeless tobacco use (Ref. 167). In addition, overall
mortality rates for all people who smoked cigars (i.e., those who
report inhaling as well as those who report not inhaling cigar smoke)
are higher than rates for those who have never smoked, although they
are generally lower than the rates observed for people who smoke
cigarettes (Ref. 53 at p. 112). In an analysis of National Longitudinal
Mortality Study (NLMS) data, researchers also found that the risk of
dying from tobacco-related cancers is higher for people who currently
exclusively use pipe tobacco and those who currently exclusively smoke
cigars than for those who reported never using combusted tobacco
products (Ref. 168). Another similar analysis using the restricted-use
National Health Interview Survey-Linked Mortality Files (NHIS-LMF),
following participants for mortality from 2000 through 2015, observed
that people who currently smoked cigars daily had elevated risk of all-
cause mortality compared to those who had never used tobacco (Ref.
169). In addition, researchers studying people who smoke cigars in 2009
and 2010 found that the average person who smokes cigars or pipes loses
approximately 15 life years (Ref. 134).
Disparities in cigar-related health outcomes have also been
observed by gender and race/ethnicity. Likely due to the greater
prevalence of cigar use among men versus women, one analysis observed a
significantly greater number of years of potential life lost for men
than women (117,440 for men; 22,284 for women) associated with cigar
use, as well as disparate monetary losses associated with cigar use
($19.5 billion
[[Page 5052]]
for men; $3.4 billion for women) based on the value of a statistical
life year (Ref. 134). Studies have shown that levels of nicotine and
other carcinogens in cigars can be higher than those in cigarettes and
may be at levels that lead to increased risk of morbidity and mortality
from conditions such as cancer, cardiovascular disease, and COPD (Refs.
134, 163, and 164). The prevalence of cigar smoking among AI/AN
populations is lower than prevalence among Black populations, but
higher than among Hispanic and Asian populations (Refs. 120 and 121),
contributing to the disproportionate prevalence of lung cancer and
cardiovascular diseases in these populations (Refs. 170 and 171).
E. Tobacco Product Marketing Has Contributed to Disparities in Use and
Health Outcomes
Tobacco companies have long understood the complexities of nicotine
addiction (Ref. 172) and have capitalized on the psychological and
sociological aspects of tobacco use to market their products
disproportionately to specific populations, such as youth and young
adults, some racial and ethnic populations, individuals who identify as
lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+),\17\
those with lower household income and educational attainment, and
individuals with behavioral health conditions (Refs. 173 and 174). For
example, retail advertising for tobacco products is more common in
neighborhoods with greater proportions of Black residents and in lower
income neighborhoods (Refs. 175 to 179). Storefront and outdoor tobacco
marketing, as well as point-of-sale marketing, are all
disproportionately present in Black, Hispanic/Latino, AI/AN, and low-
income communities (Refs. 175, 179, 180 to 187). Higher exposure to
tobacco advertisements and retailing is associated with tobacco use
susceptibility and tobacco use among youth, with observed disparities
impacting youth who are Black, Hispanic, or lower socioeconomic status
(Refs. 188 to 192). For example, a systematic review of 35 studies
found that a higher density of tobacco retailers near the home is
associated with increased combustible tobacco product use among youth
(Ref. 193).
---------------------------------------------------------------------------
\17\ Throughout this document, FDA uses the term ``LGBTQI+''
broadly when referring to lesbian, gay, bisexual, transgender,
queer, and intersex communities. When we describe findings from the
published literature, we refer specifically to the groups that are
studied. For example, some authors examine tobacco-related outcomes
for members who identify as lesbian, gay, bisexual, or transgender
only; as such, the data are limited to those who identify as LGBT,
and authors interpret the findings for those specific groups.
---------------------------------------------------------------------------
Industry marketing tactics have also included the incorporation of
culture-specific imagery, traditional practices, and events that target
specific racial and ethnic groups. For instance, tobacco companies have
sponsored cultural events such as Cinco de Mayo celebrations, Chinese
New Year celebrations, and activities related to Black History Month
(Refs. 173 and 194) and have used the cultural significance of
traditional tobacco to validate the authenticity of commercially
available cigarettes, exploiting the traditions of Native people to
encourage cigarette use (Ref. 195). Tobacco industry documents show
that tobacco companies have strategically marketed their products to
women with lower income, particularly Black and Hispanic women, (Ref.
196), people experiencing homelessness and people with mental illness
(Refs. 197 and 198), and the LGBTQI+ community (Refs. 199 to 201).
Research also demonstrates that since at least the 1960s, the tobacco
industry has made strategic donations to organizations representing and
affiliated with these communities (Refs. 120, 202 to 205). Internal
industry documents reveal that at least one tobacco company considered
such donations to be a ``quid pro quo,'' because they could result in
the normalization of tobacco use, development of brand loyalty, and
opposition to health-protective tobacco control policies (Ref. 206).
The industry's practices have resulted in long-term consequences
for communities. Tobacco marketing influences social norms around
tobacco use, making it more socially acceptable and increasing the
likelihood of use (Refs. 207 to 209). In communities where the tobacco
industry has disproportionately marketed to historically marginalized
populations over decades, these social norms are transferred through
peers and family generations, perpetuating the use of harmful combusted
tobacco products, and contributing to present-day tobacco-related
health disparities in these populations (Refs. 207, 210, and 211).
Moreover, recent scientific evidence indicates that tobacco companies
continue to target populations that experience tobacco-related health
disparities with tobacco marketing (Refs. 178, 180, 191, 207, 212 to
226).
Although targeted marketing is only one factor in the development
and perpetuation of combusted tobacco product use and related harms, it
contributes to disparities that affect public health and are of great
concern to FDA. Advancing health equity is a policy priority and an
important component of fulfilling FDA's mission to protect and promote
public health. FDA and the Federal Government recognize the advancement
of health equity as ``both a moral imperative and pragmatic policy,''
as Executive Order 13995 states. Considerations related to health
equity helped inform FDA's decision to prioritize this proposed product
standard.
F. Consumer Knowledge, Attitudes, Beliefs, and Perceptions About
Nicotine
The science on consumer knowledge, attitudes, beliefs, and
perceptions about nicotine demonstrates that a majority of consumers
correctly understand that nicotine is the substance in cigarettes that
causes addiction. Nationally representative studies that examined
nicotine addiction beliefs in the general population reported that the
belief that nicotine is addictive was endorsed by approximately 85.8
percent of the population, and the belief that nicotine is responsible
for driving continued cigarette use was endorsed by approximately 82.9
percent of the population (Refs. 227 to 233). A nationally
representative survey found that 88 percent of people who currently
smoke cigarettes and 91 percent of people who use e-cigarettes agreed
that nicotine makes people want to smoke (Ref. 227). A nationally
representative study of youth suggests that about 77.1 percent of
respondents believe that nicotine definitely or probably causes
addiction (Ref. 234).
However, in contrast to high rates of correct beliefs about the
addictiveness of nicotine, there are high rates of incorrect beliefs
about the harms of nicotine. Studies that examined nicotine harm
beliefs in the general population reported that the belief that
nicotine causes cancer was endorsed by 40 to 78 percent of adult
participants (Refs. 227, 228, 232, 233, 235 to 245). Additionally, a
nationally representative study of youth suggests that about 74.7
percent believe that nicotine definitely or probably causes cancer
(Ref. 234). Multiple nationally representative studies that examined
nicotine harm perceptions by tobacco use status found that 52 to 61
percent of people who currently use cigarettes and up to 84 percent of
people who do not use cigarettes endorsed the belief that nicotine
itself causes cancer or that nicotine is the major contributing
constituent in cigarettes that causes cancer (Refs. 228, 241, and 245).
A more recent qualitative study of people who currently use little
cigars and cigarillos suggests that the misperception that nicotine has
significant adverse health
[[Page 5053]]
effects is also common among people who use these products (Refs. 228,
241, 245, and 246). Although nicotine creates and sustains addiction
and therefore is the driver of the death and disease associated with
smoking, it is the repeated exposure to toxicants from tobacco products
that directly causes most of the serious health effects among those who
use tobacco products, including fatal lung diseases, such as COPD, and
cancer (Ref. 28).
Consumer misperceptions regarding the harms associated with
nicotine may lead to inaccurate judgments about the risks of using
products that contain nicotine, including NRT. For example, individuals
who hold a misperception about nicotine may be less likely to use NRT
as a smoking cessation aid. Furthermore, there is evidence that
misperceptions of nicotine harm vary by gender, ethnicity, and age, and
may contribute to unequal health outcomes (Ref. 233). FDA recognizes
the importance of addressing nicotine misperceptions in the context of
a proposed product standard that limits the level of nicotine in
cigarettes and certain other combusted tobacco products in order to
make those products minimally addictive or nonaddictive. FDA will
continue to conduct research and develop communication tools (e.g.,
consumer outreach, public education initiatives, engagement with
interested parties) to ensure that consumers are informed of the risks
of using tobacco products that contain nicotine, including the products
covered under this proposed product standard.
V. History and Perceptions of VLNC Cigarettes
A. History of LNC and VLNC Cigarettes
Tobacco companies had the technical expertise to manipulate the
nicotine content in tobacco as early as the 1920s and then began to
market products that may have met very low nicotine content (VLNC) \18\
cigarette levels throughout the late 1970s and early 1980s (Ref. 247).
As discussed above, the term ``VLNC cigarettes'' generally refers to
combusted cigarettes that have been reported to contain <=1.0 mg
nicotine per gram of total tobacco. For a detailed discussion of the
scientific evidence that supports the technical achievability of this
proposed product standard, see section VII.E of this document. In this
section, we describe some of the industry's early and continuing
efforts to develop VLNC cigarettes.
---------------------------------------------------------------------------
\18\ As previously noted in footnote 7, the term VLNC should not
be confused with the cigarette brand name ``VLN;'' ``VLN'' refers to
cigarette products authorized for marketing by FDA in 2019. See
https://www.fda.gov/media/133633/download?attachment and https://www.fda.gov/media/133635/download?attachment.
---------------------------------------------------------------------------
Some of the earliest VLNC cigarettes studied by academic
researchers were produced by Philip Morris and marketed under the brand
name ``Next,'' which was reported to contain 0.4 mg nicotine per gram
of total tobacco (Ref. 248). Later, the National Institute on Drug
Abuse (NIDA) contracted with the Ultratech/Lifetech Corporation \19\ to
produce VLNC cigarettes for research purposes only (Refs. 249 and 250).
The two types of cigarettes produced were: (1) 8.0-10.3 mg nicotine per
gram of total tobacco and (2) 0.6-0.7 mg nicotine per gram of total
tobacco (Ref. 250).
---------------------------------------------------------------------------
\19\ Both Ultratech and Lifetech have been reported as being the
company through which NIDA manufactured research cigarettes.
---------------------------------------------------------------------------
Commercially available Quest cigarettes were produced and marketed
by Vector Tobacco in the early 2000s and utilized genetically
engineered tobacco to create cigarettes with three distinct nicotine
content levels (i.e., Quest 1 (12.7 mg/g), Quest 2 (7.3 mg/g), Quest 3
(0.9 mg/g)) (table 1). These cigarettes were used in much of the VLNC
research conducted prior to the development of SPECTRUM Nicotine
Research Cigarettes; they are no longer on the market. Philip Morris
also manufactured cigarettes with varying nicotine levels for research
only (Ref. 251). In a public statement issued on July, 2018, 22nd
Century Group, Inc. stated that they were already using genetic
engineering and plant breeding to produce VLNC tobacco for cigarettes
(Ref. 252). In 2014, the company was granted patents for its process to
dramatically reduce the nicotine in tobacco plants (Ref. 253). This
tobacco has been used to generate low nicotine content research
cigarettes, produced and distributed by RTI International, under a
contract with the NIDA Drug Supply Program (Ref. 254). 22nd Century
Group, Inc. acts as a vendor for RTI for this contract, manufacturing
SPECTRUM Nicotine Research Cigarettes that were reported to contain 0.4
mg nicotine per gram of tobacco (Ref. 254), and they also manufacture
cigarettes with other reduced levels of nicotine. These SPECTRUM
Nicotine Research Cigarettes are similar in many sensory
characteristics to NNC cigarettes, but with VLNC (Refs. 255 and 256).
In 2019, 22nd Century Group, Inc. received FDA marketing
authorization and, in 2021, received exposure modification orders for
their VLNC cigarettes under the names VLN King and VLN Menthol King.
VLN cigarettes are currently being marketed and sold to consumers in
select U.S. markets as cigarettes with 95 percent less nicotine than
conventional cigarettes. From January 1, 2023, to November 22, 2024,
22nd Century VLN cigarette dollar sales accounted for less than 0.001
percent of total cigarette dollar sales in any 4week period. Menthol
flavored 22nd Century VLN cigarettes over the same time accounted for
less than 0.001percent of any 4-week menthol flavored cigarette dollar
sales.\20\
---------------------------------------------------------------------------
\20\ FDA's own analyses, calculations and conclusions informed
in part by the NielsenIQ Retail Measurement Service (RMS) data
through NielsenIQ's RMS for the tobacco product category
``Cigarettes'' for the time period January 1, 2023 through November
2, 2024 for Total US Expanded All Outlets Combined (xAOC) and
convenience stores are those of FDA and do not reflect the views of
NielsenIQ. NielsenIQ is not responsible for, had no role in, and was
not involved in analyzing and preparing the results reported herein,
or in developing, reviewing, or confirming the research approaches
used in connection with this report. NielsenIQ RMS data consist of
weekly purchase and pricing data generated from participating retail
store point-of-sale systems in all U.S. markets. See https://NielsenIQ.com/global/en/ for more information.
---------------------------------------------------------------------------
Currently, these are the only authorized VLNC cigarettes. As we
discuss in other parts of this document (see section VII.E), we believe
the scientific evidence supports the technical achievability of the
proposed standard; additionally, the tobacco industry and consumer
product companies have developed a range of brands with differing
nicotine levels. Thus, it appears there would be opportunities for any
manufacturer who chooses to enter the market for products covered by
this proposed product standard.
Although many of the studies discussed in this section investigated
the effects of VLNC cigarettes, some studies also investigated the
effects of cigarettes with higher levels of nicotine, often as
comparators. Table 1 displays the reduced nicotine content cigarettes
that were administered in studies summarized in this document and their
reported nicotine levels. The nicotine content values in table 1 are
approximate, and they are primarily based on published reports from the
peer-reviewed scientific literature. Most studies that investigated the
clinical effects of reduced nicotine content cigarettes did not
chemically analyze the study cigarettes. For example, many studies that
examined the effects of VLNC SPECTRUM Nicotine Research Cigarettes did
not chemically characterize these cigarettes, but the authors of these
studies reported that the nicotine content of the cigarettes was 0.4 mg
nicotine per gram of
[[Page 5054]]
tobacco. The actual nicotine content of these cigarettes is expected to
vary around this value. For example, the results of one study that
chemically characterized SPECTRUM Nicotine Research Cigarettes showed
that the nicotine content of the sampled VLNC cigarettes ranged between
0.28 and 0.33 mg nicotine per gram (Ref. 256), which is lower than the
0.4 mg nicotine per gram level typically reported in the literature. In
22nd Century Group, Inc.'s modified risk tobacco product applications,
the company reported that after 9 years of sampling by the company, the
average nicotine content of its genetically engineered VLNC tobacco is
0.6 mg nicotine per gram of total tobacco, with a range of 0.4 to 0.7
mg nicotine per gram of total tobacco. It is likely that the Quest and
SPECTRUM Nicotine Research Cigarettes, used throughout the scientific
literature, also contained between 0.4 to 0.7 mg nicotine per gram of
total tobacco (Ref. 257).
Table 1--Nicotine Content for Normal, Low, and Very Low Nicotine Content Cigarettes Used in the Research Studies
Cited in This Document
----------------------------------------------------------------------------------------------------------------
Nicotine content Nicotine content
Brand Manufacturer category (mg/g)
----------------------------------------------------------------------------------------------------------------
Magic \1\............................. 22nd Century Group, Inc..... VLNC................... * 1.0
Next \2\.............................. Philip Morris International. VLNC................... * 0.4
Philip Morris 1 mg \3\................ Philip Morris Tobacco VLNC................... * 0.7-0.9
Company.
Philip Morris 2 mg \3\................ Philip Morris Tobacco LNC.................... * 2.1-2.4
Company.
Philip Morris 4 mg \3\................ Philip Morris Tobacco LNC.................... * 5.0-5.6
Company.
Philip Morris 8 mg \3\................ Philip Morris Tobacco LNC.................... * 9.3-10.6
Company.
Philip Morris 12 mg \3\............... Philip Morris Tobacco NNC.................... * 14.4-14.7
Company.
Quest 1............................... Vector Group Ltd............ NNC.................... * 12.7
Quest 2............................... Vector Group Ltd............ LNC.................... * 7.3
Quest 3............................... Vector Group Ltd............ VLNC................... * 0.9
SPECTRUM 0.4 mg (NRC102-NRC105) \4\... 22nd Century Group, Inc..... VLNC................... 0.4-0.7
SPECTRUM 1.3 mg (NRC200, NRC201) \5\.. 22nd Century Group, Inc..... LNC.................... 0.9-1.3
SPECTRUM 2.4 mg (NRC300, NRC301) \5\.. 22nd Century Group, Inc..... LNC.................... 1.9-2.4
SPECTRUM 5.2 mg (NRC400, NRC401) \5\.. 22nd Century Group, Inc..... LNC.................... 4.6-5.2
SPECTRUM 15.8 mg (NRC600, NRC601) \5\. 22nd Century Group, Inc..... NNC.................... 15.5-17.3
Ultratech/Lifetech denicotinized \6\.. Ultratech Inc./Lifetech Corp VLNC................... * 0.6-0.7
Ultratech/Lifetech nicotine \6\....... Ultratech Inc./Lifetech Corp LNC.................... * 8.0-10.3
Xodus \7\............................. 22nd Century Ltd., LLC...... LNC.................... * 1.2-1.7
----------------------------------------------------------------------------------------------------------------
Abbreviations: VLNC: <=1.0 mg nicotine per gram of total tobacco; LNC: >1.0 mg and <11.4 mg nicotine per gram of
total tobacco; NNC: >=11.4 mg nicotine per gram of total tobacco.
\1\ Nicotine content from (Ref. 31).
\2\ Nicotine content from (Ref. 248).
\3\ Nicotine content from (Refs. 258 and 259).
\4\ Nicotine content from (Ref. 257).
\5\ Nicotine content from (Ref. 29) (supplement).
\6\ Nicotine content estimated by FDA based on nicotine yield data from (Ref. 250).
\7\ Nicotine content from (Ref. 41).
* For these cigarettes, FDA calculated milligrams of nicotine per gram of total tobacco based on reports of
milligrams of nicotine per cigarette. Calculations were based on an estimate of 0.7 grams of tobacco per
cigarette.
B. Consumer Knowledge, Attitudes, Beliefs, and Perceptions Regarding
VLNC Cigarettes and FDA Regulation of Levels of Nicotine in Tobacco
In this section we describe the science related to consumer
knowledge, attitudes, and beliefs about reduced nicotine content (RNC)
\21\ cigarettes and consumers' perceptions about a hypothetical policy
reducing nicotine levels in cigarettes and certain combustible tobacco
products. These concepts are important because they are associated with
the behavioral responses consumers believe they would take if such a
policy is in effect.
---------------------------------------------------------------------------
\21\ RNC cigarettes in this context refers to any cigarette with
a lower amount of nicotine than NNC cigarettes. FDA notes that
studies focusing on consumer perceptions of RNC cigarettes typically
do not differentiate between RNC, LNC, and VLNC cigarettes. However,
when describing studies that focus on consumer behavior and
perceptions of VLNC cigarettes specifically, FDA uses the term VLNC
cigarettes. FDA notes that studies in this domain typically use
consumer perceptions of RNC cigarettes to form conclusions about
consumer perceptions about VLNC cigarettes and FDA's proposed
reduction of nicotine more broadly.
---------------------------------------------------------------------------
The science on consumer knowledge, attitudes, beliefs, and
perceptions about RNC cigarettes demonstrates that a majority of
consumers perceive that RNC cigarettes are equally or more harmful than
NNC cigarettes. Nationally representative studies suggest that 50 to 71
percent of consumers perceive RNC cigarettes to be as or more harmful
to health than NNC cigarettes, while 25 to 35 percent perceive them to
be less harmful than NNC cigarettes (Refs. 260 to 262). Recent
nationally representative findings estimate that between 12 and 25
percent of people who smoke or use e-cigarettes believe RNC cigarettes
are less harmful than NNC cigarettes (Refs. 227 and 236). In studies
where participants actually use VLNC cigarettes, they tend to perceive
them as significantly less harmful to health and less likely to cause
cancer than NNC cigarettes (Refs. 230, 263 to 265). Furthermore, there
is evidence that perceptions about the harms of VLNC cigarettes
relative to NNC cigarettes vary by race and age (Refs. 236, 266 to
268). The science on consumer knowledge, attitudes, beliefs, and
perceptions about RNC cigarettes also demonstrates that there are
widespread misperceptions about the addictiveness of RNC cigarettes
relative to NNC cigarettes. Studies that use nationally representative
surveys report that 60 to 77 percent of consumers incorrectly believe
that RNC cigarettes are equally or more addictive than NNC cigarettes
(Refs. 260 and 261). Tobacco use status does not appear to
significantly change misperceptions about the addictiveness of RNC
cigarettes (Ref. 228).
A 2019 nationally representative study of consumer support for a
policy ``requiring cigarette makers to lower the
[[Page 5055]]
nicotine levels in cigarettes so that they are less addictive''
reported that 81 percent of study participants favored the policy (52.4
percent strongly favored, 28.6 somewhat favored) and 19 percent opposed
the policy (10.3 percent somewhat opposed, 8.7 percent strongly
opposed) (Ref. 269). However, consumer misperceptions about the harm
and addictiveness of reduced nicotine content combustible tobacco
products impact understanding of the purpose of a reduced nicotine
product standard. For example, respondents in some studies did not
understand why FDA would choose to remove nicotine from cigarettes or
little cigars and cigarillos but not remove other chemicals that are
harmful (Ref. 229, 270, and 271). Respondents also stated that they
believed other chemicals besides nicotine make cigarettes addictive,
and that removing nicotine from cigarettes would not eliminate their
addictiveness (Refs. 229 and 270). Misperceptions may also serve as
potential determinants of consumer responses to a reduced nicotine
product standard. For example, one study suggests that misperceptions
among people who smoke regarding the harm of RNC cigarettes is
correlated with quit intentions in responses to a hypothetical
government policy reducing most of the nicotine in cigarettes (Ref.
267). FDA recognizes the importance of addressing consumers'
misperceptions about the relative harm and addictiveness of VLNC
cigarettes as compared to other products. FDA will continue to conduct
research (e.g., assess changes over time in knowledge, attitudes, and
perceptions relative to tobacco product characteristics including
nicotine content) to inform regulatory decisions and other actions.
VI. Rationale for Products Covered by the Proposed Product Standard
FDA has reviewed and closely considered the comments to the
Nicotine ANPRM, as well as additional evidence and information not
available at the time of the ANPRM, in developing the scope of products
for this proposed product standard. Specifically, we considered several
factors, such as the strength and breadth of the available data on the
likely effects of reducing nicotine derived from studies of VLNC
cigarettes; current prevalence and initiation rates for different
classes of tobacco products; the available data on product toxicity,
addictiveness, and appeal; product use topography \22\ (including
quantity, intensity, and duration of use); and the potential for
migration to different products. These data indicate that reduction of
nicotine in cigarettes would reduce addiction potential, dependence
levels, number of cigarettes smoked per day, and increase quit attempts
among people who currently smoke cigarettes. In light of these data,
FDA also expects that reduction of nicotine would prevent people who
experiment with cigarettes and cigars from developing an addiction to
tobacco and progressing to regular tobacco use.
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\22\ Smoking topography measures provide data on various aspects
of smoking behavior, including number of puffs per cigarette, total
time spent smoking, puff volume (i.e., puff size), puff velocity
(i.e., puff intensity), puff duration, and inter-puff interval
(i.e., length of time between puffs).
---------------------------------------------------------------------------
This proposed product standard is intended to address one of our
nation's greatest public health challenges: the death and disease
caused by combusted tobacco use. Approximately 480,000 people die every
year from smoking cigarettes (Ref. 1 at p. 659) and another 9,000 die
from smoking cigars (Ref. 1 at p. 659; Ref. 134). Cigarettes are the
tobacco product category that causes the greatest amount of harm to the
public health as a result of the prevalence of cigarette use among
adults and cigarette toxicity and addictiveness. This proposed product
standard is expected to increase cessation and switching to potentially
less harmful tobacco products and prevent people who are experimenting
with use--mainly youth and young adults--from transitioning to regular
use of cigarettes. However, if the product standard were only to cover
cigarettes, it would likely be less effective. Specifically, a
significant number of people who are addicted to smoking cigarettes
would likely migrate to similar combusted tobacco products after the
standard went into effect to maintain their nicotine exposure, thereby
undermining the significant health benefits of the proposed product
standard (Ref. 5) (see also section VI.B of this document for further
discussion of the potential for non-cigarette combusted tobacco product
switching). Therefore, to increase public health benefits, FDA also is
proposing to cover certain other combusted tobacco products in addition
to cigarettes.
Based on these considerations, FDA is proposing to cover the
following products under this product standard:
Cigarettes (other than noncombusted cigarettes, such as
HTPs that meet the definition of a cigarette),
Cigarette tobacco,
RYO tobacco,
Cigars (including little cigars, cigarillos, and large
cigars but excluding premium cigars), and
Pipe tobacco (other than waterpipe tobacco).
FDA has determined that research regarding the public health
impacts of potential maximum nicotine level policies applies across the
tobacco products covered under this proposed product standard. As
discussed in greater detail in section VII.B.12 of this document, given
that cigarette tobacco, RYO tobacco, and pipe tobacco can be
effectively used in cigarettes, the VLNC cigarette research discussed
in this proposed rule applies to these products, and any expected
benefits that would accrue as a result of instituting the proposed
product standard for cigarettes would also be expected to accrue for
these product categories. FDA also concludes that the VLNC cigarette
research applies to cigars, given the similarities between cigarettes
and most cigars (e.g., use topography). For further discussion of FDA's
findings that VLNC cigarette research applies to other covered products
under this proposed product standard, see section VII.B.12 of this
document. In addition, as discussed in section VI.A.3 of this document,
FDA finds that the non-cigarette combusted products within the proposed
scope of this rule (i.e., RYO tobacco, cigars, pipe tobacco) could
function as acceptable substitutes for many people who smoke cigarettes
while exposing them to similar risks and toxicity as cigarettes.
As discussed in section VIII of this document, FDA finds that the
proposed product standard, with this scope, is appropriate for the
protection of the public health and would provide substantial benefits
for people who currently use cigarettes and certain other combusted
tobacco products and for people who experiment with cigarettes and
cigars and people who do not use such tobacco products. FDA seeks
comments on this proposed scope, particularly on how it may affect
youth initiation and use of combusted tobacco products.
A. Prevalence and Abuse Potential of Cigarettes and Other Combusted
Tobacco Products
Cigarettes, the most frequently used tobacco products, are the
tobacco product category that causes the greatest burden of harm to
public health given that approximately 28 million adults and 380,000
youth currently smoke cigarettes (Ref. 3); the toxicity and
addictiveness of these products; and the resulting tobacco-related
disease and death across the population, including among people who do
not smoke. Cigarettes are highly addictive and harmful tobacco
products; however, the other combusted tobacco products
[[Page 5056]]
covered in this proposed product standard are similarly addictive and
harmful. If the proposed product standard covered only cigarettes, some
number of people who smoke cigarettes and are addicted to nicotine
would likely migrate to similar combusted tobacco products to maintain
their nicotine exposure (or engage in dual use with other similar
combusted tobacco products), thus reducing the positive public health
impact of this proposed product standard.
Regulating the nicotine yield of cigarettes and certain other
combusted tobacco products through setting a maximum nicotine level for
them would make these dangerous combusted products minimally addictive
or nonaddictive, making cessation easier and helping to prevent people
who are experimenting with smoking from developing nicotine dependence
and progressing to regular use. As stated elsewhere in this document,
FDA's approach in proposing this product standard for cigarettes and
certain other combusted tobacco products protects public health by
reducing combusted tobacco product use (and therefore reducing exposure
to harmful toxicants created through combustion) by making it
considerably easier for people who want to quit cigarette use to quit
all tobacco products or switch to potentially less harmful,
noncombusted tobacco products which remain available. Therefore, to
increase the public health benefits, FDA is focusing this proposed rule
on nicotine levels in cigarettes and certain other combusted tobacco
products because combusted products are responsible for the majority of
death and disease due to tobacco use.
1. Cigarettes
Data from the 2024 NYTS indicate that 1.7 percent of high school
students (approximately 250,000) and 1.1 percent of middle school
students (approximately 120,000) reported current use of cigarettes
(i.e., smoked at least once during the past 30 days) (Ref. 3). In
addition, 11.6 percent of adults reported that they currently smoked
cigarettes in 2022 (i.e., smoked at least 100 cigarettes during their
lifetime and now smoke cigarettes every day or some days); this means
an estimated 28.8 million adults in the United States currently smoke
cigarettes (Ref. 4). Although cigarette smoking is present in all
population groups in the United States, the prevalence of cigarette use
differs based on sociodemographic characteristics.
Findings from the 2024 NYTS show that, among middle and high school
students, 1.4 percent of non-Hispanic White students, 0.9 percent of
non-Hispanic Black students, and 1.6 percent of Hispanic students
currently smoked cigarettes (Ref. 3). Additionally, data from the 2022
NHIS show differences in smoking prevalence on the basis of race/
ethnicity among adults (age 18 and over). Specifically, 4.6 percent of
non-Hispanic Asian, 8.0 percent of Hispanic, 12.7 percent of non-
Hispanic White, 14.2 percent of non-Hispanic Black, 19.3 percent of
non-Hispanic AI/AN, and 11.9 percent of non-Hispanic Other participants
reported current cigarette smoking (Ref. 272). Data from the 2005 and
2015 NHIS also indicate that the prevalence of cigarette smoking has
statistically significantly declined over this time period for non-
Hispanic white, Black, Asian, and AI/AN adults and Hispanic adults
(Ref. 273).
Data from an analysis of the 2005 and 2015 NHIS indicate that the
prevalence of smoking has declined significantly over that time period
among both adult male and female participants (29.9 and 25.2 percent
relative decrease, respectively) (Ref. 273). Currently, according to
data from the 2022 NHIS, smoking remains more prevalent among males
(13.2 percent) as compared to females (10.0 percent) in the United
States (Ref. 272).
Study findings indicate that individuals who identify as lesbian,
gay, or bisexual are more likely to report smoking cigarettes as
compared to those who identify as heterosexual (Refs. 274 to 277).
Among adults in the 2022 NHIS, cigarette smoking among persons
identifying as lesbian, gay, and bisexual was 12.8 percent and among
those identifying as heterosexual/straight it was 11.6 percent (Ref.
272), and smoking was more prevalent among youth identifying as
lesbian, gay, and bisexual (7.0 percent) in the 2020 NYTS than among
those ``not sure'' of their sexual identity (3.5 percent) or youth
identifying as heterosexual (2.7 percent) (Ref. 275). Current tobacco
use for lesbian, gay, bisexual, and transgender youth in the 2022 NYTS
was reported for ``any'' tobacco use (i.e., current use of one or more
of the following: e-cigarettes, cigarettes, cigars, smokeless tobacco,
hookah, HTPs, nicotine pouches, pipe tobacco, or bidis), but not for
individual tobacco products (Ref. 278). Pooled data from the 2015 to
2019 NSDUH indicate that compared to heterosexual/straight respondents,
respondents who identified as gay males, lesbian/gay females, or
bisexual females reported higher prevalence of past 30-day smoking
(Ref. 279). Additionally, in data from the 2015/2016 NSDUH, relative to
same-age heterosexual men, lifetime rates of daily cigarette smoking
were significantly elevated among gay men ages 18-25 (30 percent versus
23 percent) and ages 35-49 years (44 percent versus 38 percent) (Ref.
277). Similarly, relative to same-age heterosexual women, lifetime
daily cigarette smoking was significantly greater among lesbian/gay
women ages 18-25 (37.7 percent versus 16.3 percent), ages 26-34 (42.2
percent versus 30.3 percent), and ages 35-49 (42.7 percent versus 32.6
percent) (Ref. 277).
As evidenced in a systematic review and meta-analysis (Ref. 280),
studies have consistently shown a relationship between socioeconomic
status and the prevalence of cigarette smoking, such that greater
levels of educational attainment and greater total family income are
inversely associated with the prevalence of smoking. Specifically, in
2021 NHIS data, the prevalence of cigarette smoking was 18.3 percent
for adults with a low income, 12.3 percent for those with a medium
income, and 6.7 percent for those with a high income (Ref. 274).
Similarly, by and large, there is an inverse relationship between
educational attainment and the prevalence of smoking. For instance,
according to the 2021 NHIS, the prevalence of smoking was 20.1 percent
among adults with some high school education but no degree, 30.7
percent among persons with a general equivalency degree, 17.1 percent
among those with a high school diploma, 13.7 percent among persons with
an associate's degree, 5.3 percent among those with an undergraduate
degree, and 3.2 percent among persons who had received a graduate
degree (Ref. 274).
The prevalence of cigarette smoking is also higher among adults
with mental health symptoms or substance use disorder (Refs. 281 to
284). Findings from the 2022 NHIS show that 27.2 percent of persons
reporting severe generalized anxiety disorder (GAD) currently smoke
cigarettes, as compared with 10.1 percent who report no or minimal GAD
(Ref. 272). Similarly, 27.1 percent of adults who report severe
depression currently smoke cigarettes, versus 10.1 percent among those
who report no or minimal depression (Ref. 281). Additionally, findings
from the 2021 NHIS show that 28.1 percent of persons reporting serious
psychological distress also reported smoking cigarettes, compared to
10.9 percent of persons not reporting serious psychological distress
(Ref. 274). Analyses of data from the 2015 NSDUH for individuals aged
12 years and over also show that cigarette smoking is significantly
more prevalent among
[[Page 5057]]
persons who use cannabis (daily cannabis use: 54.6 percent; nondaily
cannabis use: 40.2 percent) as compared to those who do not use
cannabis (15.1 percent) (Ref. 282). An analysis of 2016 NSDUH data
indicates that cigarette smoking is more than twice as prevalent among
persons with alcohol use disorder, as compared to those without (37.8
percent versus 16.3 percent) (Ref. 283), while data from the 2014 NSDUH
show that the prevalence of cigarette smoking is also more than twice
as high among persons with mental health and/or substance use problems
than among persons without (38.5 percent versus 15.4 percent) (Ref.
284).
2. Cigars
Cigar smoke contains many of the same constituents as cigarette
smoke, including nicotine, many of which can cause significant harm to
those who use cigars (Ref. 53). According to the 2024 NYTS, 330,000
middle and high school students,\23\ including 1.5 percent (an
estimated 230,000) of high school students (grades 9-12) and 0.8
percent (an estimated 80,000) of middle school students (grades 6-8),
had smoked a cigar (cigar, cigarillo, or little cigar) on at least 1
day during the past 30 days (Ref. 3). Overall, the prevalence of cigar
smoking among middle and high school students is comparable to the
prevalence of cigarette smoking, with 1.7 percent (an estimated
250,000) of high school students and 1.1 percent (an estimated 120,000)
of middle school students having smoked cigarettes on at least 1 day
during the past 30 days (Ref. 3). Cigars are also a popular tobacco
product among adults. In the 2022 NHIS, 3.7 percent of adults aged 18
or older reported currently using cigars some or every day, behind
cigarettes (11.6 percent) and e-cigarettes (6.0 percent) (Ref. 272).
---------------------------------------------------------------------------
\23\ The weighted population estimate reported in the scientific
publication is 500,000 students. As noted in the scientific
publication, overall population estimates might not sum to
corresponding population estimates because of rounding or inclusion
of students who did not self-report sex, race and ethnicity, or
grade level.
---------------------------------------------------------------------------
Evidence from national surveys--including the Monitoring the Future
study and NSDUH--indicate that, similar to cigarettes, cigar use has
been on the decline among U.S. youth and adults in recent years (Refs.
285 to 287). However, among youth, this decrease has not been equitably
experienced. The popularity of cigar use is disproportionately high
among groups such as lesbian, gay, and bisexual youth and young adults
(3.2 percent among transgender youth, 3.2 percent among sexual minority
females, and 3.9 percent among sexual minority males) (Ref. 288), and
youth with disabilities (7.0 percent among those who reported using
little cigars and 2.6 percent among those who reported using large
cigars) (Ref. 289). Cigar smoking also occurs disproportionately among
specific populations of adults as well, with greater prevalence of
cigar smoking reported among non-Hispanic Black adults (5.1 percent)
(Ref. 274), individuals of lower educational attainment and lower
annual household income (Refs. 290 and 291), and LGBTQI+ adults (Refs.
292 to 296).
Additionally, when comparing data from 2011 to 2019, while past
month cigarette smoking and cigar use were both statistically
significantly lower in young adults (ages 18-25), the absolute and
relative declines in cigar use were less than the declines in cigarette
use (33.5 percent in 2011 to 17.5 percent in 2019 for cigarettes; 10.9
percent in 2011 to 7.7 percent in 2019 for cigars) (Ref. 286). For
adults (ages 26 or older), cigarette use in 2011 was statistically
significantly higher compared to in 2019; however, cigar use remained
relatively stable and did not significantly change (21.9 percent in
2011 to 18.2 percent in 2019 for cigarettes; 4.2 percent in 2011 to 4.0
percent in 2019 for cigars) (Ref. 286). The 2023 NSDUH found that among
adults ages 26 or older in 2019, 1,847 individuals initiated cigar use
each day, considerably more than the 282 who initiated cigarette
smoking each day in that year (Ref. 86).
While these data indicate a high burden of current cigar smoking,
the true prevalence of cigar use is likely higher. Little cigars often
closely resemble cigarettes, given their shape, size, filters, and
packaging, and are perceived by many as being healthier than cigarettes
(Refs. 297 and 298). Several studies have shown that youth tend to
underreport cigar smoking if brand name identifiers are not provided
(Refs. 299 to 301). For example, in one study of Virginia high school
students, the reported prevalence of cigar use nearly doubled after
accounting for students who reported smoking Black & Mild (a brand name
of cigarillos); in the original survey results, more than half of the
students who used Black & Mild cigarillos did not report using cigars,
cigarillos, or little cigars (Ref. 299).
Research indicates that most people who smoke cigars unknowingly
inhale some amount of smoke, including people who smoke cigars who
report that they do not inhale (Refs. 54 and 55). Youth more commonly
use cigarillos and little filtered cigars that are designed to be
inhaled, which may increase their risk of poor health outcomes as well
as addiction (Refs. 53 and 163). Even if people who smoke cigars do not
breathe or inhale smoke into their lungs, they are still subject to
nicotine's addictive effects through buccal (oral) absorption of
nicotine or nicotine absorption through the lips due to cigar tobacco's
alkalinity, as well as other harmful health effects (Refs. 55, 56, 302
and 303). Cigar smoke dissolves in saliva and makes it possible for
people who smoke cigars to absorb sufficient amounts of nicotine to
create dependence even if the user does not inhale (Ref. 56).
Nicotine can exist in protonated and freebase (unprotonated) forms.
In the freebase form, it is most addictive because it is readily
absorbed by the buccal mucosa, respiratory tissues, skin, and the
gastrointestinal tract (Refs. 28 and 57). Freebase nicotine amounts are
generally higher in cigars than cigarettes due to the higher pH of
cigar smoke (Ref. 53). Nicotine absorbed across the buccal mucosa, the
mouth's membrane lining, can provide sustained amounts of freebase
nicotine to the person using the tobacco product (Ref. 53). Cigars can
deliver nicotine much like chewing tobacco or oral snuff, with nicotine
extraction absorbed directly through the buccal mucosa and lips (Ref.
53).
A 1998 NCI Monograph chapter (NCI Monograph 9) on cigar
pharmacology and abuse potential concluded that the nicotine delivery
characteristics and daily patterns of smoking among people who smoke
cigars indicate that cigars produce dependence (Refs. 53 and 164).
Since the publication of NCI Monograph 9, several in-person laboratory
studies, where participants use products under observation and have
outcome measures assessed, have provided additional evidence to support
that nicotine exposure from cigar smoking is sufficient to create or
sustain nicotine dependence among people who use cigars. Through cigar
smoke, nicotine can be absorbed by inhalation (like cigarettes) or
through the buccal mucosa (like smokeless tobacco). Multiple studies
found that people who smoke cigars inhale (as evidenced by carbon
monoxide (CO) levels and smoking topography) and that plasma nicotine
levels are similar to those of people who smoke cigarettes (Refs. 304
to 308). Furthermore, using the Questionnaire of Smoking Urges, a
commonly used measure of tobacco craving, several studies found that
cigars reduce craving and urge to smoke to a similar magnitude as
cigarettes (Refs. 306 to 308). Cigars have also been shown to decrease
acute nicotine withdrawal
[[Page 5058]]
symptoms (e.g., craving, anxiousness) (Ref. 304).
Several additional studies have used epidemiological data to
compare nicotine dependence levels among people who use multiple
tobacco products (i.e., poly tobacco use), people who exclusively use
cigarettes, and people who exclusively use cigars (Refs. 309 to 311).
The data show that a significant proportion of people who exclusively
use cigars display characteristics of tobacco dependence such as
craving (Ref. 309); however, people who use multiple tobacco products
and people who exclusively use cigarettes showed the highest levels of
dependence, followed by people who exclusively use cigars (Refs. 309 to
311).
3. Loose Tobacco (Pipe and RYO Tobacco)
Laboratory and survey studies have provided evidence to conclude
that RYO and pipe tobacco smoking is sufficient to create or sustain
nicotine dependence among people who use RYO or pipe tobacco (Ref.
312). Studies show that people who use RYO and pipe tobacco inhale (as
evidenced by smoking topography) (Refs. 312 to 314) and plasma nicotine
levels are similar to those of people who smoke factory-made cigarettes
(Ref. 313). Furthermore, RYO tobacco reduces craving and urge to smoke
at a similar magnitude and is rated similarly with regard to subjective
appeal as factory-made cigarettes (Ref. 313). Evidence also suggests
that RYO tobacco is at least as harmful to health as factory-made
cigarettes (Refs. 315 to 318).
According to data from the 2024 NYTS, 0.5 percent of high school
students (or approximately 70,000 students) reported using pipe tobacco
within the previous 30 days and 0.5 percent of middle school students
(or approximately 50,000 students) reported pipe tobacco use in the
prior 30 days (Ref. 3). Data from the 2021 NHIS indicated that 0.9
percent of adults ages 18 and older (or approximately 2.3 million
adults) currently used pipes (Ref. 274). However, FDA notes that pipe
tobacco prevalence data are likely an underestimate, as the NIHS survey
does not include the number of people who use pipe tobacco to roll
their own cigarettes.\24\ There is also evidence that young adults who
smoke cigarettes are engaging in RYO use for financial reasons (Ref.
319). Studies of RYO tobacco use among youth are limited, but
prevalence of RYO tobacco use among U.S. middle and high school
students in the 2012 NYTS was 3.4 percent (Ref. 320).
---------------------------------------------------------------------------
\24\ People who smoke RYO and pipe tobacco are susceptible to
similar negative health consequences as people who smoke traditional
cigarettes. While there is a paucity of research examining RYO and
pipe tobacco use, FDA is not aware of any data indicating that RYO
cigarettes or pipe tobacco are associated with fewer adverse health
consequences than traditional cigarettes.
---------------------------------------------------------------------------
The lack of data on RYO and pipe tobacco use and the limitations in
how national surveys assess loose tobacco use impact our ability to
draw conclusions regarding appeal of loose tobacco among youth and
adults at this time. However, if such products were not included within
the scope of this proposed product standard, some number of people who
smoke cigarettes and/or cigars and are addicted to nicotine would
likely easily migrate to such products to maintain their nicotine
exposure given that RYO and pipe tobacco have the same addictive
properties and health consequences as factory-made cigarettes (Refs.
168 and 321). For example, more people who smoke cigarettes could use
RYO or pipe tobacco to make NNC cigarettes (or engage in dual use with
certain other combusted tobacco products), reducing the positive public
health impact of this proposed product standard (see section VI.B.1 of
this document) (Ref. 322).
Taken together, these data demonstrate that if FDA did not include
certain other combusted tobacco products within the scope of this
proposed product standard, many people who smoke cigarettes likely
would migrate to, or increase use of, such other tobacco products in an
attempt to replace or supplement the reduction of nicotine in their
VLNC cigarettes.
B. Potential for Non-Cigarette Combusted Tobacco Product Switching
Nicotine can be delivered through products that represent a
continuum of risk, with combusted tobacco products at the most harmful
end of this continuum. FDA's approach in proposing this product
standard for cigarettes and certain other combusted tobacco products
protects public health by reducing combusted tobacco product use (and
therefore reducing exposure to harmful toxicants created through
combustion) while potentially less harmful, noncombusted tobacco
products remain available for people who have not quit all tobacco
products. FDA expects that, if this proposed rule is finalized and a
nicotine product standard for cigarettes and certain other combusted
tobacco products is in place, many people who smoke cigarettes will
either quit smoking or switch to a noncombusted tobacco product. Those
who switch completely to use of a noncombusted tobacco product may
sustain their nicotine dependence and may significantly reduce their
risk of tobacco-related death and disease to the extent that the
products they switch to result in less harm. That is, while dependence
on any tobacco product remains a health concern, nicotine alone is not
directly responsible for tobacco-related cancer, lung disease, and
heart disease (Ref. 323). Switching completely to a noncombusted
tobacco product would reduce exposure to the chemical constituents
created through combustion, which are the primary contributors of
combusted tobacco-related harm (Refs. 28 and 324).
However, as discussed throughout this document, if a nicotine
tobacco product standard were to apply to cigarettes only, it likely
would have substantially less impact on improving health outcomes for
people who use tobacco products. Specifically, FDA expects that, to
maintain their nicotine exposure, some people who smoke cigarettes and
are addicted to nicotine would likely migrate to other combusted
tobacco products (or begin to engage in dual use with such other
products) with similar toxicological risks after such a cigarette-only
standard was in effect. FDA also would expect that people who use non-
cigarette combusted tobacco products would continue their existing use
patterns, thereby maintaining their risk of tobacco-related death and
disease. To ensure maximum benefits for this nicotine tobacco product
standard, FDA is proposing that it apply to cigarettes and certain
other combusted tobacco products.
1. Tobacco Product Switching in Behavioral Intention and Clinical
Studies
Studies involving people who currently use cigarettes predict a
range of tobacco use behaviors in response to a nicotine product
standard. When presented with a hypothetical nicotine reduction policy,
most people who use cigarettes report that they would continue to smoke
VLNC cigarettes or use other combusted tobacco products, or that they
would quit; only a small portion report that they would consider
switching to a noncombusted tobacco product (Refs. 262 and 264). One
experimental study using a nationally representative sample examined
the intended behaviors of people who currently smoke cigarettes if a
nicotine product standard were put in place; overall, 30.5 percent of
the participants intended to quit using all tobacco products, 5.8
percent intended to switch to noncombusted tobacco products, and 61.0
percent indicated they would
[[Page 5059]]
smoke VLNC cigarettes or other combusted tobacco products (Ref. 262).
An in-depth qualitative study assigned a small number of people who use
cigarettes to use VLNC cigarettes for 5 days, then examined their
intended behaviors in response to a nicotine product standard (Ref.
264). Most participants reported that if a product standard was put in
place, they would use VLNC cigarettes if they were the only cigarettes
available, and a few said that they would use VLNC cigarettes to reduce
their smoking over time to eventually quit. Some participants discussed
the possibility of switching to ENDS or other combusted products if a
product standard was put in place. Self-reported intentions to use
tobacco products are a useful predictor of individuals' future tobacco
use behavior (Refs. 325 and 326) and these two studies support FDA
assessments of the likelihood of switching in response to the nicotine
product standard.
In clinical studies that investigated the effects of VLNC
cigarettes, researchers typically instructed participants assigned to
VLNC cigarette groups to use only study-provided cigarettes (i.e., to
refrain from using usual brand cigarettes or other tobacco products
during experimental conditions). Noncompliance with these instructions
during a clinical trial may also indicate the likelihood that people
who smoke VLNC cigarettes would use alternative nicotine-containing
products if a nicotine product standard is implemented. Several studies
reviewed in this document assessed biochemical or self-reported
measures of VLNC cigarette noncompliance (i.e., ongoing NNC cigarette
or other tobacco product use) and showed high levels of noncompliance
with smoking only VLNC cigarettes during the study. Since participants
were provided with VLNC cigarettes at no cost and continued to use non-
study provided tobacco products (particularly NNC cigarettes), these
data suggest that VLNC cigarettes have lower appeal and abuse potential
compared to NNC cigarettes (Refs. 327 to 331). These findings suggest
that once a nicotine product standard covering solely cigarettes is in
place and VLNC cigarettes are the only cigarettes available, people are
likely to use alternative nicotine-containing products including other
combusted products. However, if cigarettes and certain other combusted
products are covered by a product standard, people who use combusted
products are likely to use non-combusted products, therefore
benefitting public health.
A clinical study conducted to compare the use of alternative
nicotine-containing products (i.e., smokeless tobacco, ENDS, NRT,
cigars, cigarillos) and smoking behavior in 136 people who smoked
cigarettes and were unwilling to quit randomly assigned participants to
one of three conditions and instructed them to use only study-assigned
tobacco products for 8 weeks (Ref. 5). The ``LNC1'' group received LNC
cigarettes combined with noncombusted tobacco products (i.e., smokeless
tobacco, ENDS, NRT) and combusted non-cigarette tobacco products (i.e.,
cigars, cigarillos), the ``LNC2'' group received LNC cigarettes
combined with only noncombusted tobacco products, and the NNC cigarette
group received NNC cigarettes combined with noncombusted and combusted
non-cigarette products. Participants who received LNC cigarettes (both
the LNC1 and LNC2 groups) used more alternative combusted tobacco
products and more noncombusted tobacco products (the LNC2 group) than
participants in the NNC cigarette group. However, these participants
also smoked fewer total combusted tobacco products and had more quit
attempts than participants in the NNC cigarette group. The findings
from this study demonstrate that when people who smoke cigarettes are
switched to LNC cigarettes and provided with alternative sources of
nicotine, they will readily use the alternative sources of nicotine.
Moreover, the LNC cigarette group (the LNC2 group) that had access to
noncombusted nicotine sources only (i.e., smokeless tobacco, ENDS, NRT)
had statistically significantly lower biomarker levels of certain
harmful constituents (N-Nitrosonornicotine (NNN) and NNAL) than those
who continued to smoke NNC cigarettes and had access to noncombusted
and combusted non-cigarette products (the LNC1 group) (Ref. 5). The NNN
and NNAL biomarker levels in the LNC1 group with access to both
combusted and noncombusted tobacco products resembled the NNC group
(Ref. 5).
Taken together, these findings suggest that if the proposed product
standard reduces the nicotine level in cigarettes only, but people who
smoke cigarettes still have access to other NNC combusted tobacco
products, they likely would substitute with the NNC combusted tobacco
products. This behavior would negate a significant proportion of the
public health impact of the product standard. If other combusted
tobacco products also are covered by this proposed product standard,
however, data suggest that people who smoke cigarettes would likely
switch from combusted tobacco product use to potentially less harmful
tobacco products. For further discussion of switching to a potentially
less harmful nicotine delivery product, see section VIII.D.3 of this
document.
2. Cigarette Price Increases
Studies investigating the effects of changes in cigarette prices on
product substitution may also be used as an indicator of potential
product switching in response to the proposed nicotine tobacco product
standard, because a reduction in nicotine content could be
conceptualized as an increase in the unit price of nicotine, as the
cost to consumers is increased per unit of nicotine (Ref. 332).
Therefore, studies assessing cigarette taxation may be useful because
they are assessing the influence of changes in the unit price of
cigarettes, through increases in cost, on behavior among people who use
the products. Price increases, including taxation, represent one of the
most effective tobacco control policies associated with significant
declines in overall tobacco consumption as well as reductions in youth
initiation rates (Ref. 333). However, taxation and price increases are
also associated with a range of tax avoidance behaviors, such as
substitution with a less expensive product, purchasing from low or
untaxed sources, or purchasing in bulk (Ref. 334), and this behavior is
more likely to occur among people who smoke and are of lower
socioeconomic status (Ref. 335). It is this potential substitution that
FDA is seeking to mitigate by proposing to cover certain other
combusted tobacco products in addition to cigarettes. FDA expects that
by reducing the nicotine in cigarettes and certain other combusted
tobacco products through this proposed product standard, the effect on
people who smoke will be similar to increasing the price, and, as is
seen in examples of taxation and price increases, people who smoke
would likely turn to alternative sources of nicotine.
An epidemiological study used data from the 2001 and 2002 New
Jersey Adult Tobacco Survey (NJATS) to determine whether people who
smoke cigarettes switched to cigars following an increase in the state
cigarette excise tax (U.S. $0.80 to U.S. $1.50 per pack) (Ref. 336). In
2001, the cigarette smoking prevalence in New Jersey was 22.1 percent.
Following a large cigarette excise tax increase, the cigarette
prevalence decreased to 18 percent (Ref. 336). There were no
statistically significant differences in the cigar smoking prevalence
between 2001 and 2002; however, ever cigar use increased
[[Page 5060]]
statistically significantly for people who currently smoked cigarettes
(50.9 percent versus 60.3 percent, respectively) and increased slightly
for people who recently quit smoking (48.4 percent versus 56.4 percent,
respectively). In 2001, people who currently smoked cigarettes had the
highest prevalence of current cigar use (13.9 percent), while people
who had recently quit cigarette use had the lowest prevalence (2.6
percent). In contrast, in 2002, while people who currently smoked
cigarettes again reported the greatest prevalence of current cigar use
(13.2 percent), people who had recently quit cigarette smoking had the
second highest prevalence of current cigar use (11.1 percent). The
authors concluded that after a cigarette excise tax increase, a small
but notable proportion of people who had recently quit cigarette
smoking tried cigars, substituted cigars for cigarettes, or continued
using combusted tobacco products in the form of cigars (Ref. 336).
Additional indirect evidence assessing trends in internet searches
following the 2009 U.S. Federal tobacco tax increase showed that after
the tax was announced, search queries increased for both combusted and
noncombusted non-cigarette tobacco products (Ref. 337).
Similarly, several studies assessed changes in loose tobacco sales
following a large tax increase in RYO tobacco and found decreases in
RYO tobacco sales and increases in pipe tobacco sales as soon as the
tax rate changed (Refs. 322, 338 to 340). Researchers analyzing
publicly available Federal excise tax data from 2000 to 2015 found that
total RYO tobacco sales statistically significantly decreased by 70.0
percent; however, total pipe tobacco sales increased by 556.4 percent
(Ref. 340). Another study found a similar increase in pipe tobacco
sales and decrease in RYO tobacco sales in response to tax differences
between the products; however, self-reported pipe tobacco use, assessed
via the NSDUH, remained consistent, and RYO consumption increased (Ref.
338). The authors suggested that people who smoke cigarettes may have
bought loose tobacco labeled as pipe tobacco for use as RYO cigarettes
as a tax avoidance strategy. These data suggest that following the
implementation of a new tobacco control policy, manufacturers may
modify their products and a significant proportion of consumers may
modify their behavior to adapt to the changes (e.g., switching to a
similar combusted tobacco product if a final nicotine tobacco product
standard covered cigarettes only), which would reduce the rule's
potential public health effects. If cigarettes were the only product
covered by the proposed product standard, a proportion of people who
smoke cigarettes would likely to turn to certain other combusted
products, thereby reducing the significant public health impact of this
rule. Similarly, people who use certain other combusted products would
not be affected by the reduction in nicotine in cigarettes and would
also not benefit. Further, if cigarettes were the only product covered
by the proposed product standard, the negative health effects of
second- and thirdhand smoke from these other combusted products would
still affect other non-smoking individuals exposed to these combusted
products. However, if these certain other combusted products are
covered, then the alternative products for those who switch (instead of
quitting) likely would not be combusted, therefore benefitting public
health.
3. Behavioral Economics Data
Behavioral economics utilizes principles of psychology and
economics to predict purchasing behavior as a function of different
market constraints (Ref. 341). Several studies have used real or
hypothetical scenarios to investigate the impact of a change in price
or availability of a given tobacco product on subsequent purchasing or
use of another tobacco product. Purchasing behaviors observed in
behavioral economics studies have been shown to be concordant with
actual tobacco consumption and real purchase estimates (Refs. 342 to
344).
Studies have used retail sales data to investigate tobacco
substitution as a function of price (Refs. 345 to 347). One study
investigated relationships between purchasing patterns and price of
cigarettes and little cigars. In 2013, a pack of little cigars was
approximately 32 to 37 percent less expensive than a pack of cigarettes
(Ref. 345). A 10 percent increase in the price of little cigars was
associated with a 31.7 percent decrease in per capita little cigar
sales, while a 10 percent increase in the price of cigarettes was
associated with a 27.3 percent increase in per capita little cigar
sales. The authors concluded that people who smoke cigarettes are price
sensitive and avoided the higher cost of cigarettes by switching to
little cigars. Another study estimated demand for cigarettes, little
cigars/cigarillos, large cigars, e-cigarettes, smokeless tobacco, and
loose tobacco using Nielsen's Convenience Track retail scanner database
(Ref. 347). In this study, a 10 percent increase in the price of
cigarettes resulted in an 18.6 percent increase in e-cigarette demand,
showing that e-cigarettes substituted for cigarettes (Ref. 347).
Although, in this study, large cigars, smokeless tobacco, and loose
smoking tobacco were not associated with increased use in response to
increasing cigarette prices, Nielsen retail sales data that were
analyzed in another study showed that little cigars, RYO tobacco, and
pipe tobacco each serve as substitutes for cigarettes (Ref. 346).
Studies have also used hypothetical purchase tasks to investigate
responses by people who smoke cigarettes to potential tobacco policy
changes or price increases (Refs. 348 and 349). One study used a
simulated tobacco marketplace to measure purchasing behaviors among
people who smoke cigarettes (Ref. 349). Participants could purchase
cigarettes, e-cigarettes, cigarillos, gum, dip, lozenges, and snus.
When cigarette prices increased, e-cigarette purchasing statistically
significantly increased (Ref. 349). A study conducted in the
Netherlands utilized a similar hypothetical tobacco marketplace to
investigate hypothetical purchases for VLNC cigarettes as a function of
varying scenarios (Ref. 348). Most relevant was the scenario where
participants made hypothetical purchases for VLNC cigarettes, e-
cigarettes, and NRT in a marketplace where NNC cigarettes were
unavailable. VLNC cigarettes had the highest rate of purchase, followed
by e-cigarettes, and then NRT. Approximately 20 percent of participants
reported that they would not purchase any of the products if NNC
cigarettes were unavailable (Ref. 348).
These data demonstrate that people who smoke cigarettes are willing
to shift consumption toward both noncombusted and combusted non-
cigarette tobacco products in times of economic or product constraint.
Moreover, this evidence supports the conclusion that many people who
smoke cigarettes likely would switch to other combusted tobacco
products that contain nicotine if a nicotine product standard covered
only cigarettes. Of additional concern is the potential for increased
combusted non-cigarette tobacco product substitution among certain
populations that may be price sensitive, such as individuals with low
socioeconomic status compared to those with higher socioeconomic status
(Ref. 335). One study showed that individuals of low socioeconomic
status are 85 percent more likely to report using discount brands/RYO
compared to participants with higher socioeconomic status (SES) in
order to avoid an increase in the cost of their
[[Page 5061]]
preferred product, combusted cigarettes, and therefore, these
individuals have a history of and comfort with switching to alternative
combusted products when available at a lower cost (Ref. 335). Given
that the research highlighted above has shown that a change in the
availability of a tobacco product influences subsequent purchasing or
use of other tobacco products, FDA is concerned that if the proposed
nicotine product standard is limited to cigarettes, a large portion of
individuals will seek out alternative sources of nicotine by using
other combusted tobacco products if those products are not included
within the scope of this rule.
VII. Discussion of Nicotine-Related Topics
A. Approach To Limiting User Exposure to Nicotine
Nicotine is the primary addictive constituent in all tobacco
products, including cigarettes. FDA is proposing a tobacco product
standard that would limit nicotine yield by establishing a maximum
nicotine level in cigarettes and certain other combusted tobacco
products to make these products minimally addictive or nonaddictive,
using the best available science to determine a level that is
appropriate for the protection of the public health.
After consideration of the scientific literature, comments
submitted in response to the Nicotine ANPRM, and the measured levels of
nicotine content in research cigarettes (as reported in the literature,
as well as in information submitted to FDA from industry), FDA is
proposing that the maximum nicotine level in cigarettes and certain
other combusted tobacco products not exceed 0.70 mg of nicotine content
per gram of total tobacco in order to limit user exposure to nicotine.
Nicotine ``yield'' is the amount of nicotine in smoke, in other
words, the amount of nicotine to which a smoker potentially is exposed.
Nicotine yield is measured by a machine-generated protocol where the
product is smoked by a machine in a prescribed manner and the smoke is
collected in order to measure nicotine with another instrument, such as
a gas chromatograph. Nicotine content refers to the total amount of
nicotine present in the tobacco filler and is typically conveyed as
either milligrams of nicotine per gram of total tobacco or milligrams
of nicotine per product. The nicotine content of a tobacco product
serves as a ceiling on nicotine yield, as it denotes the maximum amount
of nicotine that a user can be exposed to when they smoke the cigarette
or other tobacco product, and it cannot be manipulated by user
behavior.
Setting a limit on nicotine content and measuring that content is
more effective in reducing yield (i.e., the amount of nicotine the user
is exposed to) than setting a limit based on a direct measurement of
yield under standardized smoking-machine protocols. This is because the
way yield is measured by smoking machines does not accurately capture
the amount of nicotine that is taken in by a person using the tobacco
products. For example, manufacturers have developed ``low-yield''
cigarettes designed to markedly reduce yield results as measured by the
Federal Trade Commission (FTC) testing method (Ref. 350). They
decreased yields by manipulating various characteristics of the
cigarettes (e.g., decreasing the length of the available tobacco
column, increasing the burn rate of the column, increasing filter
efficiency, increasing air dilution in mainstream smoke, decreasing
density of tobacco, or changing the concentration of nicotine in the
tobacco) (Ref. 350 at Table 2-2). Many of these design changes led to
the amount of nicotine measured in the machine-generated yield being
different from--and less than--the amount of nicotine received by the
smoker (Ref. 350). This disconnect is a result of smoking compensatory
behaviors, such as smoking more cigarettes per day, increasing the
number of puffs (with a smoker's last few puffs on a cigarette
delivering disproportionately more nicotine than delivered in a smoking
machine's standardized number of puffs), increasing puff volume and
frequency, inhaling more deeply, and covering ventilation holes with
fingers or lips, that enable smokers to overcome, intentionally or
unintentionally, many of these design changes and, thereby, increase
the amount of their nicotine intake compared to the machine-generated
yield. They often do this to obtain adequate nicotine to satisfy their
nicotine cravings (Ref. 350).
While standardized smoking machine puffing regimes in a controlled
laboratory environment are effective in producing reproducible
measurements of nicotine yield, as noted above, human behavior--how
people smoke, including in response to cigarette-design features--
influences the nicotine intake from a cigarette and can overcome
features of a cigarette that lowered the machine-generated nicotine
yield. For example, combusted cigarettes that were once referred to as
``light'' cigarettes achieved a reduction in machine-measured nicotine
yield (e.g., ISO machine smoking method, CI smoking method, FTC smoking
method) through a variety of design changes to the cigarette, including
the use of ventilation holes--although the actual nicotine content of
the tobacco filler was not low. These design changes led to lower tar
and nicotine yields in machine-generated smoke, and therefore, these
products were labeled and marketed as low nicotine yield or ``light,''
``low,'' or ``mild'' cigarettes. However, often unconsciously cigarette
users could and did modify their use behaviors to compensate for these
design changes and extract more nicotine from the products compared to
the machine-generated yields, often to levels comparable to
conventional cigarettes. For example, cigarette makers generally design
cigarettes with ventilation holes far enough down the cigarette that
they are not blocked during the FTC smoking test, but are easily
blocked by users' fingers or mouths, and larger or more frequent puffs
could be taken by consumers (Ref. 351). Through such compensatory
smoking behaviors, cigarette users were able to overcome the changes in
ventilation in these products, resulting in no benefit to public health
(Ref. 350). There is ample research demonstrating that people who use
ventilated cigarettes change their smoking behavior to increase their
smoke intake, including taking larger puffs, inhaling more deeply,
taking more frequent puffs, or increasing the number of cigarettes they
smoke per day \25\ (Refs. 350 to 361). As a result, evidence shows that
many people are exposed to higher yields of smoke constituents,
including nicotine, than the yields estimated by standardized smoking
machine methods (Refs. 362 to 364). Further, researchers have reviewed
the extensive body of literature on filter ventilation and health
effects and concluded that there is strong evidence to suggest that
filter ventilation has contributed to the rise in lung adenocarcinomas
among people who smoke (Ref. 365). Studies that measure nicotine
pharmacokinetics have also found that the relative percentage of free
nicotine in smoke may increase with percent of filter ventilation (Ref.
366), which suggests that greater filter ventilation may expose smokers
to greater free nicotine levels that can lead to greater total nicotine
exposure while smoking as this form of nicotine is more easily absorbed
by the body.
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\25\ See section VII.B 4., Smoking Topography, of this document
for further discussion of compensatory smoking and VLNC cigarettes.
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[[Page 5062]]
In contrast, reducing the nicotine content in cigarettes and
certain other combusted tobacco products places an absolute maximum
limit on the amount of nicotine that can be extracted (i.e., yielded)
by the user. VLNC cigarettes, in contrast to low nicotine yield
cigarettes generated by other design changes, are associated with
minimal and transient compensatory smoking because people who smoke
these cigarettes are unable to obtain adequate amounts of nicotine
through these behaviors; therefore, they stop trying to do so. In sum,
limiting nicotine yield through a maximum nicotine content level would
be more effective in achieving the public health benefits that come
from reducing the amount of the nicotine to which a user is exposed
than would setting a limit based on a measurement of the maximum yield
of tobacco products.\26\
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\26\ Consistent with the proposed limit on nicotine content, FDA
is also proposing testing for nicotine content only, rather than
both content and yield. This testing requirement is less burdensome
yet still effective in measuring the maximum nicotine yield, i.e.,
the maximum amount of nicotine to which a user can be exposed.
---------------------------------------------------------------------------
B. Scientific Evidence Supports the Target Level of Nicotine
Many studies have investigated the effects of VLNC cigarettes on
behavioral outcomes, including smoking cessation, use behaviors,
biomarkers of exposure, and physiological effects. Findings from these
studies are discussed in this section, and they suggest that
individuals who smoke VLNC cigarettes with nicotine levels similar to
what FDA is proposing here are more likely to make a quit attempt,
reduce smoking, demonstrate reduced exposure to harmful and potentially
harmful constituents (HPHCs), and demonstrate similar or reduced
physiological responses to cigarettes relative to individuals who smoke
usual brand or NNC cigarettes. Results from these and other studies
suggest that switching to VLNC cigarettes does not lead to compensatory
smoking (see this section and VII.B.4 of this document for further
discussion of compensatory smoking).
Therefore, the data reported in the scientific literature support a
tobacco product standard limiting nicotine yield by setting a maximum
nicotine content level in cigarettes and certain other combusted
tobacco products to a maximum of 0.70 mg of nicotine per gram of total
tobacco. FDA believes that this maximum nicotine level would provide
the appropriate flexibility to account for variations in tobacco
growing seasons and variations in analytical testing. FDA requests
comments, data, and research regarding this proposed maximum nicotine
level.
1. Origin of the Proposed Product Standard
In 1994, Benowitz and Henningfield proposed the idea of Federal
regulation of nicotine content in combusted tobacco products to a level
too low to sustain addiction (Ref. 367). They considered the smoking
habits of a small population of people who smoke cigarettes
intermittently and who demonstrate reduced nicotine dependence (a group
sometimes referred to as tobacco ``chippers'') to inform indirect
estimates of a nicotine level that they proposed would be too low to
sustain addiction in most people who smoke cigarettes. Chippers are
typically characterized by smoking five or fewer CPD, with limited or
no withdrawal symptoms, and by being able to skip smoking for days at a
time (Ref. 368). Based on their estimates of nicotine exposure among
chippers, the researchers proposed a level of nicotine per cigarette--
approximately 0.5 mg of nicotine per cigarette--that should be low
enough to prevent or limit the development of nicotine addiction in
most young people. The nicotine level proposed by Benowitz and
Henningfield was an initial estimation based on observational data, and
there is individual variability in dose sensitivity to all addictive
substances; however, the initial estimate posed by Benowitz and
Henningfield paved the way for subsequent prospective clinical studies
designed to evaluate the addiction potential of VLNC cigarettes.
Several brands of commercial and research cigarettes were
manufactured to contain a nicotine content similar to that originally
proposed by Benowitz and Henningfield (see table 1 of this document).
Using these cigarettes, researchers have consistently demonstrated that
VLNC cigarettes have reduced addiction potential compared to NNC
cigarettes.
22nd Century Group Inc., the company that developed SPECTRUM
Nicotine Research Cigarettes and whose genetically engineered tobacco
was used to make Quest cigarettes, submitted modified risk tobacco
product applications to FDA that reported that the actual average value
of nicotine content in its genetically engineered VLNC tobacco is 0.6
mg nicotine per gram of total tobacco, with a range of 0.4 to 0.7 mg
nicotine per gram of total tobacco (see section V.A of this document
for a discussion of the history of LNC and VLNC cigarettes, including
the SPECTRUM Nicotine Research Cigarettes).\27\ The natural variation
of this agricultural product resulted in the slight variation in the
nicotine content of the tobacco filler within the company's internal
range of acceptable values. The average value and range were compiled
by the company from 9 years of sampling data of the genetically
engineered tobacco that was used to make SPECTRUM and Quest cigarettes.
It is likely that the cigarettes used throughout the scientific
literature, reported as having 0.4 mg nicotine per gram of total
tobacco, may have, in actuality, been between 0.4 and 0.7 mg of
nicotine per gram of total tobacco. This range is consistent with the
scientific evidence to support a minimally addictive or nonaddictive
level of nicotine content in cigarettes and certain other combusted
tobacco products, and FDA took these data from 22nd Century Group
Inc.'s VLNC cigarettes into consideration when determining the
appropriate, technically feasible maximum level of nicotine content to
propose in this product standard.
---------------------------------------------------------------------------
\27\ On December 23, 2021, FDA issued exposure modification
orders to 22nd Century Group Inc. for VLN King and VLN Menthol King
combusted, filtered cigarettes. See https://www.fda.gov/tobacco-products/advertising-and-promotion/22nd-century-group-inc-modified-risk-tobacco-product-mrtp-applications.
---------------------------------------------------------------------------
2. Smoking Cessation
A number of studies investigated the effects of VLNC or LNC
cigarettes alone or in combination with NRT on smoking cessation among
people who smoke but are interested in quitting (Refs. 32, 35, 41, 369
to 373) and those uninterested in quitting (Refs. 31, 40, 258, and
374). As stated throughout this document, most adults who use tobacco
products wish to quit but are unsuccessful because of the highly
addictive nature of these products (Refs. 1, 13, 28, 58, and 61) (see
section IV.A of this document for a discussion of the addictiveness of
nicotine). Taken together, results from these studies demonstrate that
people who smoke and are interested in quitting who are given VLNC
cigarettes are more likely to achieve initial smoking abstinence
compared to those who continue to smoke their usual brand or NNC
cigarettes. In addition, provision of NRT and/or behavioral
intervention with VLNC cigarettes may further increase smoking
cessation among individuals interested in quitting (Ref. 19).
Research demonstrates the benefits of VLNC cigarettes for those
people who smoke and are interested in quitting. In one of the clinical
trials that has examined the effects of VLNC cigarettes
[[Page 5063]]
alone on smoking cessation in people who smoke cigarettes who were
interested in quitting, 165 people who smoke were randomized to use LNC
cigarettes, VLNC cigarettes, or 4 mg nicotine lozenges for 6 weeks
(Ref. 32). While there were no statistically significant differences
between groups in CO-verified point prevalence abstinence (i.e., quit)
rates at 1-4-week followup visits, abstinence rates at the week 6
followup visit were statistically significantly higher in the VLNC
cigarette group (47.2 percent) and nicotine lozenge group (36.7
percent) relative to the LNC cigarette group (23.1 percent) (Ref. 32).
In another randomized clinical trial (RCT), 346 people who smoked and
were interested in quitting were randomized to receive 6 weeks of (1) a
combination of VLNC cigarettes (nicotine was gradually reduced from NNC
to LNC to VLNC cigarettes every 2 weeks) and nicotine patch (VLNC
cigarettes + NRT); (2) VLNC cigarettes and a placebo patch (VLNC
cigarettes only); or (3) NNC cigarettes and NRT after their quit date
(NNC cigarettes + NRT) (Ref. 369). Following their quit date at week 7,
the VLNC cigarettes + NRT group continued to receive NRT, the VLNC
cigarettes only group received placebo patches, and the NNC cigarettes
+ NRT group was provided with NRT during weeks 7-10. Biochemically
confirmed continuous abstinence rates were 32.8 percent in the VLNC
cigarettes + NRT group, 16.4 percent in the VLNC cigarettes only group,
and 21.9 percent in the NNC cigarettes + NRT group (Ref. 369),
suggesting that the combination of VLNC cigarettes and NRT is more
effective at promoting continuous abstinence than VLNC cigarettes
alone. However, abstinence at 3- and 6-month followups could not be
adequately assessed due to attrition (Ref. 369).
Many other studies conducted in individuals interested in quitting
investigated the effects of LNC or VLNC cigarettes combined with NRT
(Refs. 41, 35, 371 to 373, and 375). For example, in a study conducted
in New Zealand, 1,410 callers to a quitline were randomized to receive
VLNC cigarettes with usual quitline care (8 weeks of NRT and behavioral
support via a quitline) or usual care alone (Ref. 373). Six months
after the quit date, 7-day point-prevalence abstinence rates \28\ were
statistically significantly greater in participants using VLNC
cigarettes with usual quitline care (33 percent) compared to the group
who received usual quitline care alone (28 percent). Continuous
abstinence rates at month 6 also were statistically significantly
higher for participants who received VLNC cigarettes with usual
quitline care (23 percent) compared to those who received usual
quitline care alone (15 percent). Likewise, in another study, 98
persons who reported heavy smoking (i.e., greater than or equal to 20
CPD) received either VLNC cigarettes and a 21 mg nicotine patch or NNC
cigarettes for 2 weeks prior to quitting (Ref. 372). After the quit
date, all study participants wore nicotine patches for up to 8 weeks.
Participants who smoked VLNC cigarettes and received patches reported
less frequent and less intense cravings during the 2 weeks before and
after the quit date, suggesting that use of VLNC cigarettes plus NRT
may aid in cessation by reducing cigarette craving during a quit
attempt. Participants in the VLNC cigarettes + NRT group had a higher
self-reported quit rate compared to those in the NNC cigarettes + NRT
group at 3 months (43 percent vs. 34 percent, respectively) and 6
months (28 percent vs. 21 percent, respectively), but these quit rates
did not differ statistically significantly between groups, likely due
to a small sample size precluding sufficient statistical power.
---------------------------------------------------------------------------
\28\ Seven-day point prevalence abstinence is a measure of, in
this case, tobacco cessation outcomes for quitlines. At a given
point in time (in this case, 6 months after the quit date), study
participants are asked whether they have used cigarettes or other
forms of tobacco in the past 7 days.
---------------------------------------------------------------------------
Several other studies have investigated the effects of VLNC or LNC
cigarettes on smoking cessation among individuals uninterested in
quitting (Refs. 31, 40, 258 and 374). In an RCT, participants received
either NNC cigarettes or VLNC cigarettes (double-blinded, i.e., neither
the participants nor the researchers knew which type of cigarette
participants received), and either received or did not receive a
transdermal nicotine patch (open-label, i.e., participants and
researchers were aware of whether participants received NRT) for 7
weeks. At week 7, participants were provided a daily descending
monetary bonus for refraining from using any cigarettes. Participants
randomized to receive NRT were encouraged to continue using their
patches. Although participants who received VLNC cigarettes smoked
statistically significantly fewer total CPD than participants who
received NNC cigarettes, during the abstinence period, no groups
differed statistically significantly from the NNC cigarette-only group
in time to lapse or number of days abstinent; however, these results
were likely influenced by low adherence to VLNC cigarette use in this
study (Ref. 376). In another series of studies, participants received
gradually reduced nicotine content cigarettes over a period of 6
months, beginning with NNC cigarettes and ending with VLNC cigarettes
(Refs. 258 and 374). In the first study, a statistically significantly
greater proportion of participants who received VLNC cigarettes
considered quitting at the end of the study, compared to those in a
control group who smoked their usual brand cigarettes throughout the
study (Ref. 258). In a followup study in which a subset of participants
was followed for 2 years, cotinine levels in the gradual nicotine
reduction group rose to baseline levels or levels similar to those of
the control group after 12 months during which both groups could freely
smoke usual brand cigarettes (Ref. 374). Although 7.5 percent of
participants in the gradual reduction group quit smoking, compared to
only 2 percent of participants in the usual brand control group, this
difference was not statistically significant (Ref. 374). In another
study, 33 participants were randomized to receive VLNC cigarettes or to
continue to smoke their usual brand cigarettes for 12 weeks (Ref. 31).
The availability of VLNC cigarettes increased quit attempts in people
who smoked cigarettes and had no intention of quitting (Ref. 31).
Furthermore, several extended duration VLNC studies demonstrated
how VLNC cigarettes can increase cessation by assessing self-reported
quit attempts as a secondary study aim. While one study showed no
statistically significant differences in quit rates among people who
smoke cigarettes on a nondaily basis who used VLNC or NNC cigarettes
for 10 weeks (Ref. 377), other studies showed that participants who
smoked VLNC cigarettes were more likely to report a quit attempt after
6 weeks of use (Ref. 29) and had a greater number of cigarette-free
days after 12 (Ref. 378) and 18 weeks (Ref. 379) compared to those who
smoked NNC cigarettes. However, a secondary analysis of the 18 week
study (Ref. 379) found that there were no significant differences in
quit rates or intention to quit at the 6-month followup timepoint (Ref.
380).
Among the studies evaluating smoking cessation following VLNC
cigarette use, few utilized a randomized controlled trial design, and
results were sometimes inconsistent, particularly related to long-term
followup. However, the weight of evidence from these studies suggests
that among people who smoke and are interested in quitting, using VLNC
cigarettes can facilitate initial smoking abstinence, particularly when
used along with NRT and/or behavioral intervention. Among people
[[Page 5064]]
who smoke but are uninterested in quitting, VLNC cigarette use did not
increase quit rates; however, it did increase quit attempts. It is
important to note that studies evaluating smoking cessation following
VLNC cigarette use took place in an environment where NNC cigarettes
and other combusted tobacco products remained readily available. For
this reason, the available data likely underestimates the likelihood of
increased cessation rates following the implementation of a nicotine
product standard because NNC cigarettes would no longer be available,
making relapse to these cigarettes no longer possible.
3. Cigarettes Per Day (CPD)
One concern raised by some with regard to a reduced nicotine policy
is whether people who smoke might alter their smoking behavior by
smoking additional cigarettes in order to attempt to compensate for the
lower amounts of nicotine, but studies show that extended use of VLNC
cigarettes does not produce increases in CPD. Researchers typically
assess CPD via participant self-reporting or by counting cigarette
filters or packs returned by participants. By measuring CPD during an
extended exposure trial, researchers can determine whether switching to
VLNC cigarettes produces changes in CPD compared to usual brand or NNC
cigarette conditions. Research conducted in the absence of the proposed
standard shows that switching to LNC or VLNC cigarettes can produce
modest decreases in CPD. However, as noted previously, studies
evaluating changes in CPD following VLNC cigarette use took place in an
environment where NNC cigarettes and other combusted tobacco products
remained readily available, likely underestimating the potential
reductions in CPD following implementation of a nicotine product
standard because NNC cigarettes and other combusted tobacco products
would no longer be legally available. These findings suggest that, if
the proposed product standard were finalized and implemented, people
who smoke VLNC cigarettes would not increase CPD to compensate for
reduced nicotine exposure, and FDA expects that for many CPD would
decrease over time.
Many studies measured VLNC CPD under conditions of extended
exposure (e.g., several consecutive weeks or longer). These studies
varied in sample size, duration of exposure, average CPD requirements
to enter the study, participants' intentions to quit smoking, and the
method in which participants transitioned from usual brand cigarettes
to VLNC cigarettes (i.e., gradual versus immediate reduction in
nicotine content). Despite these differences in study methods and
participant characteristics, nearly all the studies came to a similar
conclusion: relative to usual brand or NNC cigarette conditions, CPD
was similar (i.e., there was no compensatory smoking) (Refs.31, 35,
329, 369, 374, 381 to 385,) or lower in VLNC cigarette conditions
(Refs. 29, 32, 41, 265, 386, and 387). Notably, studies that found
lower CPD while participants smoked VLNC cigarettes tended to have
larger sample sizes (Refs. 29 and 379), which may have had more
statistical power to detect relatively small but consistent differences
in CPD across conditions.
One limitation of some studies that examined the effects of VLNC
cigarette smoking on CPD is that comparisons between VLNC CPD and usual
brand or NNC CPD were made without taking into account the number of
non-study cigarettes smoked per day in experimental conditions. A
measure of ``total CPD'' in VLNC cigarette conditions would include the
number of study-assigned VLNC cigarettes plus the number of usual brand
or non-study cigarettes smoked by participants who were not fully
compliant with study procedures. Few studies have compared total CPD
across VLNC and usual brand or NNC cigarette conditions. However, one
study found that, relative to usual brand and NNC cigarette conditions,
the combination of study- and non-study-assigned CPD was lower in VLNC
and LNC cigarette conditions when nicotine content was less than or
equal to 2.4 mg nicotine per gram of total tobacco, and that those
participants who used VLNC cigarettes (i.e., 0.4 mg nicotine per gram
of total tobacco), demonstrated reduced use and dependence with minimal
evidence of withdrawal-related discomfort or safety concerns (Ref. 29).
Another study found that fewer combusted tobacco products were smoked
during LNC cigarette conditions relative to an NNC cigarette condition
(Ref. 5). A study where participants were confined to a hotel in order
to limit their access to non-study products assessed the potential
effects of VLNC cigarettes on compensatory smoking behaviors (Ref.
388). Participants completed two 4-night stays; during their first
stay, they were randomized to receive either NNC or VLNC cigarettes and
were randomized to the other group during their second stay.
Furthermore, participants were given an ``account balance'' where they
could purchase study cigarettes from a ``cigarette store'' during the
study. Investigators found that by the end of the four night stays the
number of cigarettes participants smoked did not differ statistically
significantly between the NNC and VLNC cigarette groups, indicating
that people who smoke may not engage in compensatory smoking behavior
when only VLNC cigarettes are available (Ref. 388). Another study
compared the effects of VLNC and NNC cigarettes on CPD in people who
smoke who inhabited a residential research facility throughout the
study. The results showed that when participants had access to only
VLNC cigarettes for 11 days, they smoked statistically significantly
fewer CPD than those who had access to only NNC cigarettes (Ref. 64).
Taken together, these studies indicate that extended use of VLNC
cigarettes does not produce increases in CPD in an attempt to
compensate for the reduced nicotine levels. FDA expects that this may
result in reductions in CPD among people who do not quit, particularly
in an environment where NNC cigarettes are not legally available.
4. Smoking Topography
Smoking topography refers to various aspects of smoking behavior,
including number of puffs per cigarette, total time spent smoking, puff
volume (i.e., puff size), puff velocity (i.e., puff intensity), puff
duration, and inter-puff interval (i.e., length of time between puffs).
Although some of these outcomes (e.g., puffs per cigarette) can be
measured via direct observation, smoking topography is typically
assessed with an electronic puff topography unit attached directly to a
cigarette. Smoking topography measures that indicate more intense
smoking behavior may be attributed to compensatory smoking. A concern
raised by some with regard to a nicotine reduction policy is whether
people who smoke might engage in compensatory smoking behavior to try
to extract more nicotine from the cigarettes, thus increasing exposure
to tobacco-related toxicants. Smoking topography study results are
mixed, but the majority of studies show that individuals who smoke VLNC
cigarettes demonstrate no statistically significant differences in
smoking topography relative to those who smoke usual brand or NNC
cigarettes, or they demonstrate changes in smoking topography measures
that are associated with reductions in tobacco smoke exposure (e.g.,
lower total puff volume) rather than increased compensatory smoking.
Some studies found no differences in smoking topography between
VLNC and NNC or usual brand cigarette conditions (Refs. 389 to 391).
However, many other
[[Page 5065]]
studies found that smoking topography differed between cigarette
conditions. Some of the more reliable findings replicated across
studies were the effects of VLNC cigarettes on total puff volume and
number of puffs per cigarette. Under conditions of both brief (e.g.,
several hours) and extended (e.g., several weeks) exposure, studies
found that total puff volume was lower (Refs. 29, 34, 383, 384, and
392) and number of puffs per cigarette was lower (Refs. 329, 384, 392,
and 393) when participants smoked VLNC cigarettes, relative to usual
brand or NNC cigarettes. However, two brief exposure studies showed
higher puff volumes (Refs. 393 and 394) and puff duration (Ref. 394)
when participants smoked VLNC cigarettes in short laboratory sessions.
Another brief exposure study conducted in adolescents showed that VLNC
cigarettes produced higher numbers of puffs relative to NNC cigarettes;
however, additional measures were not collected to determine whether
this was a transient or lasting effect (Ref. 395). An extended exposure
study showed initial decreases in puff volume when participants smoked
VLNC cigarettes relative to NNC cigarettes, but these differences
dissipated over the course of 7 days (Ref. 383). Finally, limited
evidence suggests that VLNC cigarettes are smoked faster (Refs. 259 and
396), are smoked with increased peak velocity (Ref. 384) and may
decrease inter-puff intervals when compared to NNC cigarettes (Ref.
392).
In all, while smoking topography study results are mixed, the
majority of studies show that individuals who smoke VLNC cigarettes
demonstrate no statistically significant differences in smoking
topography relative to those who smoke usual brand or NNC cigarettes,
or they demonstrate changes in smoking topography measures that are
associated with reductions in tobacco smoke exposure (e.g., lower total
puff volume) rather than increased compensatory smoking.
5. Abuse Potential
Abuse potential refers to the ability of a product to promote
continued use and the development of dependence. Choice studies are
commonly used to measure abuse potential, where preference for one
tobacco product over another indicates greater abuse potential. When
participants are asked to make a real or hypothetical choice between
VLNC cigarettes and NNC cigarettes in research studies, they reliably
choose NNC cigarettes (Refs. 391, 397 to 401). Combined with data
showing that VLNC cigarettes are associated with significantly lower
plasma nicotine exposure (Ref. 402) and decreased positive subjective
effects compared to NNC and usual brand cigarettes (Ref. 391), these
data indicate lower abuse potential of VLNC cigarettes. However,
research has also shown that the choice between VLNC and NNC cigarettes
can be influenced by factors such as cost or effort, such that when the
effort required to obtain NNC cigarettes increases, some people who
smoke cigarettes will switch their preference from NNC cigarettes to
VLNC cigarettes (Ref. 398). For example, one laboratory study
investigating tobacco product choice when participants were provided
with an experimental income found that, although participants rated
VLNC cigarettes as less satisfying than both LNC and NNC cigarettes,
they purchased statistically significantly more puffs of the VLNC
cigarettes when LNC and NNC cigarettes were more expensive (Ref. 403).
Thus, if the proposed product standard is implemented and the cost,
effort, or risk associated with obtaining NNC cigarettes increases,
individual preference may shift to VLNC cigarettes or more readily
available tobacco products rather than attempting to seek out illicitly
marketed NNC products. If the proposed product standard were to apply
only to cigarettes, these findings also indicate that people who smoke
cigarettes who do not quit after a final rule goes into effect would
likely be willing to switch to other NNC combusted tobacco products
rather than using VLNC cigarettes. If this were the case, the public
health benefit of the proposed product standard would be reduced.
Hypothetical choice tasks (e.g., cigarette purchase task, multiple
choice questionnaire) are used to characterize reinforcing efficacy by
determining how changes in the cost of a commodity affect its
consumption. These tasks typically involve prior experience with the
product or brief laboratory exposure, followed by a series of questions
asking participants to either (1) report how many cigarettes they would
consume at a variety of escalating prices; or (2) choose between
cigarettes or money at a variety of prices. Studies that used
hypothetical choice tasks to assess VLNC cigarette reinforcement showed
that participants find VLNC cigarettes to be less reinforcing than NNC
cigarettes (Refs. 265, 343, and 391). In one study, the reinforcing
efficacy of cigarettes varying in nicotine content following 6 weeks of
access to the products was examined (Ref. 343). Compared to the NNC
cigarette group, those in the VLNC cigarette group estimated that they
would smoke fewer cigarettes even if the cigarettes were free, spend
less for the VLNC cigarettes, and quit smoking VLNC cigarettes at a
lower price point (i.e., a price point at which participants would
continue to pay for NNC cigarettes). Responses on the hypothetical
choice task were highly correlated with the actual number of cigarettes
smoked during week 6 of the study.
Hypothetical choice tasks can also be used to investigate the
substitutability of tobacco products. For example, another study
employed a cross-price elasticity task in which the price of VLNC
cigarettes was held constant while the price for usual brand cigarettes
was manipulated (Ref. 404). When usual brand cigarette price increased,
demand for VLNC cigarettes increased and demand for usual brand
cigarettes decreased, indicating that VLNC cigarettes are a partial
substitute for usual brand cigarettes (Ref. 404).
Rather than directly assessing choice between tobacco products,
some studies evaluate how much people who smoke are willing to work to
earn puffs from cigarettes when the number of responses required to
earn a puff progressively increases (i.e., a progressive ratio task).
One study that used this method found that participants assigned to an
NNC cigarette group were willing to work statistically significantly
harder to earn puffs from their NNC cigarette than participants
assigned to a VLNC cigarette group, indicating greater abuse liability
(i.e., ability to promote continued use and the development of
dependence) of the NNC cigarette (Ref. 64).
These studies demonstrate that VLNC cigarettes are consistently
shown to be of lower abuse potential compared to NNC cigarettes, as
evidenced by responses to behavioral and hypothetical choice
procedures. Behavioral and hypothetical choice research has also shown
that the choice between VLNC and NNC cigarettes can be influenced such
that some people will switch their preference from NNC cigarettes to
VLNC cigarettes when the price or effort required to obtain the
products increases. See section VI.B of this document for further
discussion on the impact of cigarette price on switching behavior.
6. Biomarkers of Exposure
Research demonstrates that, following VLNC cigarette use, some
biomarkers of exposure (e.g., CO, measured as breath CO or
carboxyhemoglobin (COHb)) are typically similar to those observed
following NNC cigarette use, while other biomarkers (e.g., total
nicotine
[[Page 5066]]
equivalents (TNE), which are a combination of nicotine, cotinine, and
other nicotine metabolites collected through plasma, saliva, or urine)
are typically lower following VLNC cigarette use. However, no
biomarkers of exposure are reliably observed to be higher following
VLNC cigarette use relative to NNC cigarette use, meaning that study
participants are not engaging in compensatory smoking behaviors.
Some of the most commonly measured biomarkers of tobacco smoke
exposure are CO, plasma nicotine, cotinine (collected through plasma,
saliva, or urine), TNE, and other HPHCs or their metabolites (e.g.,
NNN, NNAL, Benzo[a]pyrene (BAP), 3-hydroxypropyl mercapturic acid (3-
HPMA), S-phenylmercapturic acid (S-PMA)). While nicotine and its
metabolites would be expected to decrease in individuals who switch
from NNC to VLNC cigarettes, other biomarkers of exposure would be
expected to remain the same if smoking behavior remained unchanged.
Thus, any changes in biomarker levels observed between NNC and VLNC
cigarette conditions in clinical studies may indicate differences in
smoking behavior (e.g., changes in CPD or smoking topography) between
these two groups. Notably, due to the short half-lives of some
biomarkers (e.g., breath CO), decreases in smoking can produce
decreases in these biomarkers during brief exposure studies. However,
decreases in smoking may not produce decreases in some biomarkers
(e.g., NNAL) under such conditions due to the prolonged half-lives of
these biomarkers.
Most studies have found no differences in CO exposure between
participants who smoke VLNC cigarettes and those who smoke usual brand
or NNC cigarettes (Refs. 5, 29, 32, 34, 40, 258, 374, 376, 383, 387,
388, 390, 391, 393, 395, 396, 402, 405 to 417,). This finding may be
somewhat unexpected as many studies have found that participants smoke
fewer CPD when they smoke VLNC cigarettes relative to NNC or usual
brand cigarettes. However, although CO is positively associated with
CPD, research has shown that the correlation may only be of moderate
strength (Ref. 418). Furthermore, CO may be impacted by noncompliance
with study cigarettes (see section VI.B of this document for a
discussion about noncompliance).
Nevertheless, differences were observed between VLNC and NNC
cigarette conditions in a few studies. Two brief exposure studies in
which participants were given limited access to reduced nicotine
content cigarettes over the course of several hours under controlled
laboratory conditions found increases in breath CO following VLNC
cigarette use relative to NNC cigarette use (Refs. 419 and 420). In
addition, an extended exposure study (over the course of 35 days)
showed that CO levels initially increased when participants switched
from usual brand cigarettes during baseline to VLNC cigarettes;
however, these effects dissipated over time as CO levels eventually
returned to baseline levels (Ref. 384). As discussed in section
VIII.D.7 of this document, these limited increases in CO exposure may
be due to changes in smoking topography. At least one extended exposure
study found decreases in CO boost (the difference between measured CO
levels before and after smoking a cigarette) after VLNC cigarette use
compared to usual brand cigarettes (Ref. 329). In another study, one
group of participants smoked NNC cigarettes throughout the study, a
second group smoked study cigarettes with gradually reduced nicotine
contents, and a third group immediately switched to VLNC cigarettes
(Ref. 421). This study found that subjects in the immediate VLNC
cigarette group had statistically significantly lower CO than did the
NNC cigarette or gradual reduction groups. Breath CO for participants
in the NNC cigarette and gradual reduction groups did not differ
statistically significantly from each other (Ref. 421). Moreover, the
only study to date that examined the effects of VLNC cigarettes on
breath CO in people who smoke who inhabited a residential research
facility found that when participants only had access to study
cigarettes for 11 days, those who were assigned VLNC cigarettes had
statistically significantly lower breath CO than those who were
assigned NNC cigarettes. Furthermore, these differences increased over
the course of each day such that they were much larger in the afternoon
than in the morning (Ref. 64).
Notwithstanding the differing CO studies, studies that examined
nicotine, cotinine, or TNE levels had overwhelming concurrence
regarding the effects of either brief or extended exposure to VLNC
cigarettes compared to usual brand or NNC cigarettes. VLNC cigarette
use resulted in substantially lower levels of nicotine, cotinine, and
TNE than usual brand or NNC cigarettes (Refs. 5, 29, 32 to 34, 40, 258,
329, 370, 374, 376, 382 to 384, 387, 388, 390, 402, 403, 406, 407, 410,
413, 417, and 419 to 425). One within-subjects laboratory study
compared the nicotine pharmacokinetic profile of VLNC, LNC, NNC, and
usual brand cigarettes in 12 participants who smoked cigarettes daily
(Ref. 402). While each of the four cigarettes produced statistically
significant increases in plasma nicotine boost (i.e., peak plasma
nicotine level minus baseline level) after smoking, the VLNC and LNC
cigarettes had statistically significantly lower plasma nicotine boost
and AUC0-120 (i.e., plasma nicotine area under the curve
calculated for the first 120 minutes following product use, indicating
extent of exposure to nicotine and its clearance rate from the body)
compared to the NNC and usual brand cigarettes. These data show that
although VLNC cigarettes are associated with significantly lower
nicotine uptake compared to NNC and usual brand cigarettes, the
cigarettes still deliver a measurable amount of nicotine.
The effects of VLNC cigarette exposure on other HPHCs were less
reliable across studies. Nevertheless, studies consistently found that
VLNC cigarette exposure either reduced or did not change exposure to
NNN, NNAL, urinary 1-hydroxypyrene, or BAP relative to NNC or usual
brand cigarettes (Refs. 5, 29, 32, 40, 258, 382, 384, and 329). Two
studies also examined 3-HPMA and S-PMA levels and found that these
biomarkers decreased in VLNC cigarette conditions compared to LNC and
NNC cigarette conditions (Ref. 32). Another study found that an
immediate switch to VLNC cigarettes statistically significantly reduced
exposure to acrolein and phenanthrene tetraol (both are biomarkers of
smoke exposure) throughout a 20-week study duration compared to a
gradual reduction approach (Ref. 379). The reductions in biomarkers
that were observed in some of these studies following VLNC cigarette
exposure were typically correlated with decreases in CPD or other
smoking behaviors. Thus, as expected, VLNC cigarette use resulted in
fewer CPD, which resulted in overall reductions in HPHC exposure.
Importantly, none of the studies found that VLNC cigarette use resulted
in increases in any of these other HPHCs or their biomarkers. Taken
together, these studies support that VLNC cigarette use is associated
with biomarker exposure that is similar to or lower than NNC cigarette
use.
7. Physiological Effects
Physiological measures may be proxy measures for the stimulant
effects of nicotine. Pharmacodynamic effects of nicotine include
central and peripheral nervous system stimulation, arousal, and
increased heart rate or blood pressure. Nicotine is a known stimulant,
but physiological effects may occur in
[[Page 5067]]
response to combusted tobacco products even in the absence of nicotine
in those who regularly use cigarettes and certain other combusted
tobacco products due to behavioral conditioning or other psychoactive
chemicals in tobacco smoke. Data show that physiological effects
related to VLNC cigarettes are similar or less pronounced than those
produced by NNC cigarettes, suggesting that the nicotine in the VLNC
cigarettes is able to produce physiological effects.
There is slight variability in the data assessing the physiological
effects of VLNC cigarettes. Some studies show that, regardless of
nicotine content, acute cigarette smoking is associated with an
increase in baseline heart rate (Refs. 259, 407, 411, and 419);
however, these increases were either less pronounced following VLNC
cigarette use compared to NNC cigarette use (Refs. 259 and 407) or were
less consistent (i.e., observed at some but not all time points
following use) (Ref. 411). Some research has shown that escalations in
heart rate dissipate after repeated exposure to VLNC cigarettes but not
usual brand cigarettes (Ref. 407). In contrast, other studies did not
observe increases in heart rate when participants smoked VLNC
cigarettes (Refs. 250, 413, 417, and 426), and several studies showed
statistically significantly reduced escalations in heart rate compared
to acute LNC, NNC, or usual brand cigarette administration (Refs. 64,
249, 265, 390, 405, 415, 427, and 428).
Some studies also investigated the effects of VLNC cigarettes on
blood pressure. Several studies found no differences in blood pressure
after smoking a VLNC cigarette compared to an LNC cigarette (Refs. 249
and 419), NNC cigarette (Ref. 259), or usual brand cigarette (Refs.
249, 259, and 419). However, other studies showed statistically
significantly greater increases in blood pressure after smoking NNC or
usual brand cigarettes relative to VLNC cigarettes (Refs. 265 and 390).
A small number of studies examined the effects of VLNC cigarettes
on skin temperature and skin conductance (a measure of sympathetic
nervous system activity indicating psychological or physiological
arousal). Although one study showed that skin temperature decreased to
a greater extent with NNC cigarettes compared to VLNC cigarettes (Ref.
259), another study found no differences in skin temperature as a
function of nicotine content in cigarettes (Ref. 426). Another study
found no statistically significant differences in skin conductance
between VLNC and NNC cigarettes (Ref. 429).
Taken together, findings from these studies suggest that VLNC
cigarettes produce physiological responses that are similar to or less
pronounced than those produced by NNC cigarettes. These data suggest
that the nicotine in the VLNC cigarettes is able to elicit
physiological responses in people who smoke cigarettes, although a
portion of the response may also be due to sensorimotor cues, or other
stimuli associated with smoking, that may have conditioned participants
to produce these physiological effects due to the historical repeated
pairings with nicotine.
8. Neurological Effects
The main target of nicotine in the central nervous system is the
nicotinic acetylcholine receptor (nAChR). Positron emission tomography
(PET) and magnetic resonance imaging (MRI) data obtained from humans
who smoke using an nAChR-specific radiotracer indicates that after
smoking a VLNC cigarette, nAChR receptors located in numerous areas of
the brain are occupied despite the lower nicotine content of VLNC
cigarettes (Ref. 430).
Nicotine also activates the dopaminergic brain reward system, which
results in dopamine release and a pleasure response. The release of
dopamine also initiates an adaptive process in which an individual
forms learned associations between the subjective state (e.g.,
pleasure) and the object or context that led to that state (e.g., the
act of smoking a cigarette) (Ref. 389). Through this process, both
nicotine administration and smoking stimuli (e.g., a cigarette, a
lighter) contribute to the cycle of nicotine dependence (Ref. 38).
Smoking NNC cigarettes to satiety results in near-complete occupancy of
nAChRs in the brain (Refs. 431 and 432). In contrast, although studies
have shown there is enough nicotine in VLNC cigarettes to bind to
nAChRs in the brain (Ref. 430) and to release dopamine (Ref. 389),
results from these studies have also shown the effects are smaller than
those observed from smoking NNC cigarettes. These differences in nAChR
occupancy and dopamine release between VLNC and NNC cigarettes may
explain, in part, why many studies have shown smoking VLNC cigarettes
does not consistently produce the same magnitude of subjective craving
and withdrawal responses observed following use of NNC cigarettes
(Refs. 398, 406, 407, 411, 413, 415, 417, 419, 422, 433 to 439). Taken
together, these findings demonstrate that nicotine from smoking VLNC
cigarettes binds to nAChRs located in numerous areas of the brain;
however, nAChR receptor occupancy and the magnitude of craving and
withdrawal responses observed following use of VLNC cigarettes are not
as high as those following use of NNC cigarettes.
9. Dependence
Combusted tobacco product use can lead to symptoms of nicotine
dependence, which may include tolerance to the effects of nicotine,
withdrawal upon cessation of use, craving, and unsuccessful efforts to
quit smoking. Because dependence may take time to develop or change, it
is often measured under conditions of extended exposure. Studies
typically assess dependence with questionnaires, including the
Fagerstr[ouml]m Test for Nicotine Dependence (FTND), Fagerstr[ouml]m
Test for Cigarette Dependence (FTCD), Nicotine Dependence Syndrome
Scale (NDSS), and Wisconsin Inventory of Smoking Dependence Motives
(WISDM). Although some studies found no evidence of a change in
dependence when the nicotine content of cigarettes was gradually
reduced, most studies found evidence indicating that switching to VLNC
cigarettes decreases dependence. Moreover, the evidence suggests that
immediate nicotine reduction is more likely to lead to decreases in
dependence than gradual reduction. These findings support the
hypothesis that lowering the nicotine levels in cigarettes and certain
other combusted tobacco products would reduce nicotine exposure and,
thereby, nicotine dependence in people who do not to switch to another
nicotine-containing tobacco product.
In studies that gradually reduced the nicotine content of
cigarettes over the course of weeks or months, the effects of VLNC
cigarettes on dependence were somewhat mixed. In a study wherein
nicotine content was gradually reduced (using NNC, LNC, and VLNC
cigarettes) over the course of 4 weeks, there was a trend towards
statistical significance (i.e., if more participants had been tested,
the results may have become statistically significant) in overall
reduction of dependence scores across conditions (Ref. 329). Another
gradual reduction study found no difference in dependence when
comparing data from baseline to week 26 in 135 participants who smoked
either gradually reduced nicotine content cigarettes over the course of
6 months or their own brand cigarettes for the same duration (Ref.
258). However, when comparing only data from week 14 to week 26, while
participants were primarily smoking VLNC cigarettes, there was a
statistically
[[Page 5068]]
significant decrease in dependence in the group that received gradually
reduced nicotine content cigarettes (Ref. 258). A secondary analysis of
data from 51 people who smoke demonstrated that participants with
higher FTND scores at baseline were more likely to demonstrate signs of
dependence during the study, regardless of the nicotine content of
their study cigarettes (Ref. 381). In a followup study, participants
assigned to receive gradually reduced nicotine content cigarettes were
given VLNC cigarettes for an additional 6 months, and no statistically
significant changes in dependence were observed (Ref. 374).
In studies that immediately reduced the nicotine content of
cigarettes by switching participants from usual brand cigarettes to LNC
or VLNC cigarettes, dependence decreased in people who smoked
cigarettes who were not interested in quitting compared to those who
smoked NNC or usual brand cigarettes for 6 weeks (Ref. 29), 10 weeks
(Ref. 30), or 12 weeks (Ref. 31). In smoking cessation studies in which
participants endorsed wanting to quit, VLNC cigarettes were also
associated with reductions in nicotine dependence over time (Refs. 32
to 35). Conversely, a trial in which people with serious mental illness
who smoke and were not seeking smoking cessation treatment were
randomized to use either VLNC or NNC cigarettes for 6 weeks showed no
statistically significant differences in FTCD scores across VLNC and
NNC cigarette groups (Ref. 440). However, these results may be
explained by the high level of noncompliance (i.e., ongoing use of NNC
cigarettes or other tobacco products) reported in the VLNC cigarette
condition (Ref. 440) (see section VI.B of this document for further
discussion of noncompliance).
To date, one study compared the effects of gradual versus immediate
nicotine reduction on FTND and WISDM dependence scores (Ref. 379). In a
20-week double-blind, parallel design study, adults who smoke
cigarettes (n=1,250) were randomized to an immediate reduction group
that received VLNC cigarettes, a gradual reduction group that received
cigarettes containing progressively decreased nicotine content every 4
weeks (15.5, 11.7, 5.2, 2.4, and 0.4 mg nicotine per gram of total
tobacco, respectively), or a control group that received NNC
cigarettes. At the conclusion of 20 weeks, the immediate reduction
group showed statistically significantly lower FTND and WISDM
dependence scores compared with the gradual reduction group and the NNC
cigarette control group; no statistically significant differences in
dependence scores were observed between the gradual reduction and
control groups. These results suggest that immediate nicotine reduction
is associated with reduced nicotine dependence compared to gradual
reduction or continued use of NNC cigarettes (Ref. 379).
The delay to smoking the first cigarette of the day is a strong
predictor of dependence. In the only study to date that examined the
effects of VLNC cigarettes on latency (i.e., delay) to smoke in
participants inhabiting a residential research facility, time to first
cigarette was statistically significantly longer among people who smoke
who only had access to VLNC cigarettes for 11 days compared to those
who only had access to NNC cigarettes, supporting the potential for
less dependence over time among those who switch to VLNC cigarettes
(Ref. 64).
Accordingly, despite some mixed results in studies using a gradual
decrease in nicotine content, most evidence shows that switching to
VLNC cigarettes decreases dependence among people who smoke cigarettes.
The evidence also suggests that immediate nicotine reduction is more
likely than gradual reduction to lead to decreases in dependence. For
more discussion of the scientific evidence supporting an immediate
nicotine reduction approach, see section VII.C of this document.
10. Subjective Effects of VLNC Cigarettes
Self-reported subjective effects (e.g., drug ``liking,''
``satisfaction'') are widely used measures of reinforcing efficacy and
abuse liability of drugs and tobacco products. Drug ``liking'' is
associated with drug self-administration and has been shown to be the
most sensitive and reliable subjective effects measure of abuse
liability (Ref. 441). Many studies have compared the subjective effects
of VLNC, LNC, NNC, and participants' usual brand cigarettes using self-
reported measures of drug effects (e.g., Cigarette Evaluation Scale,
Smoking Effects Questionnaire, Visual Analogue Scale items). These
studies typically found that VLNC cigarettes are ``liked'' less than
NNC and usual brand cigarettes and, therefore, subject to lower abuse
potential than NNC cigarettes.
Under conditions of brief exposure when participants were given
limited access to cigarettes that varied in nicotine content, typically
over the course of several hours under controlled laboratory
conditions, studies generally found that VLNC cigarettes were rated
lower in cigarette ``liking'' compared to NNC or usual brand cigarettes
(Refs. 265, 383, 398, 399, 403, 410, 413, 428, 435, 437, 440, 442 to
448). However, a few studies found no statistically significant
differences in ``liking'' as a function of nicotine content in
cigarettes (Refs. 415, 419, 420, and 449). Many studies also have
evaluated other subjective effects (such as ``good'' or ``positive''
effects and ``bad'' or ``negative'' effects) and found that they vary
together with drug ``liking.'' A number of studies have shown that VLNC
cigarettes were rated lower on other positive subjective effects items
(e.g., ``satisfaction,'' ``pleasure,'' ``taste,'' ``strength,''
``stimulation'') compared to LNC cigarettes (Refs. 265, 412, 419, and
450), NNC cigarettes (Refs.265, 394, 396, 437, and 451) and usual brand
cigarettes (Refs. 390, 407, 413, and 452). VLNC cigarettes were also
rated lower on effects such as ``aversiveness,'' ``sickness,'' and
``dizziness'' (Refs. 390, 396, 414, 453, and 454), and higher on items
such as ``dislike'' and ``unpleasant'' compared to NNC or usual brand
cigarettes (Refs. 265 and 383). These seemingly contradictory findings
are likely due to the constructs that these subjective effects measure;
``aversiveness,'' ``sickness,'' and ``dizziness'' are used to measure
direct sensory and physical effects of nicotine, while ``dislike'' and
``unpleasant'' are used to measure general product liking.
Although often assumed, recent findings confirm that greater
immediate positive subjective effect ratings (e.g., ``liking,''
``satisfaction'') predict greater acute reinforcing effects of
cigarettes of varying nicotine content (Ref. 455). Several factors have
been shown to influence subjective effects ratings of VLNC and NNC
cigarettes. These factors include participants' ability to discriminate
the nicotine content of cigarettes. For example, NNC cigarettes have
increased ratings of positive subjective effects when participants are
able to discriminate them from VLNC cigarettes (Refs. 400 and 401).
Individuals who smoke menthol cigarettes rated both VLNC and NNC
cigarettes higher in positive subjective effects compared to people who
smoke nonmenthol cigarettes (Ref. 456). In addition, positive
subjective effects ratings are higher when participants are told that
they are receiving a nicotine-containing cigarette, regardless of the
actual nicotine content of the cigarette (Refs. 428, 435, 444, 445, and
457).
Several studies assessed subjective effects of VLNC cigarettes
following extended exposure when participants were given less
restricted access to cigarettes of varying nicotine content in their
natural environments (e.g., homes, workplaces), typically over the
course of
[[Page 5069]]
several weeks. Findings from these studies were relatively similar to
findings from brief exposure studies. On average, VLNC cigarettes were
rated as less appealing (e.g., lower ratings of ``liking,''
``satisfaction,'' or ``pleasure'') compared to LNC and NNC cigarettes
(Refs. 249 and 384). However, at least one study found no differences
in subjective effects as a function of cigarette nicotine content (Ref.
258). Positive subjective effects ratings for VLNC cigarettes were
shown to remain constant or decrease over time (Refs. 249 and 373).
In a study where people who smoke inhabited a residential research
facility, during 11 days of exposure, participants who received NNC
cigarettes rated positive subjective effects lower and negative
subjective effects higher than baseline subjective effects of usual
brand cigarettes (indicative of a general dislike of research
cigarettes); however, subjective ratings of NNC study cigarettes
increased and were similar to usual brand cigarettes by the end of the
study (Ref. 64). In contrast, participants assigned to the VLNC
cigarette group rated positive subjective effects of cigarettes (e.g.,
``enjoyable'') lower and negative subjective effects (e.g.,
``unpleasant'') higher than baseline subjective effects of usual brand
cigarettes throughout the entire study period (Ref. 64).
Finally, gender may influence differences in subjective effects. In
one study, women rated all cigarettes as more flavorful than men, and
an interaction was observed between gender and nicotine content such
that women demonstrated less sensitivity than men to the differential
subjective effects of NNC and VLNC cigarettes (Ref. 447). Another study
found that women reported increased satisfaction with VLNC or LNC
cigarettes alone, while men reported greater satisfaction when these
cigarettes were combined with NRT (Ref. 458). Finally, one study found
that women reported higher psychological reward than men across all
nicotine contents tested (Ref. 459).
In sum, subjective effects data consistently show that VLNC
cigarettes have equal or lower abuse potential compared to NNC and
usual brand cigarettes under conditions of brief and extended exposure.
FDA is not aware of any studies that found that VLNC cigarettes had
greater abuse potential than NNC or usual brand cigarettes.
11. The Effects of VLNC Cigarettes on Relief From Craving and
Withdrawal Symptoms
Symptoms of nicotine and tobacco withdrawal may include
irritability, depression, insomnia, headache, and increased craving.
Although craving is often characterized as a symptom of nicotine and
tobacco withdrawal, it is also a symptom of dependence, and it can
occur in the absence of other withdrawal symptoms. Thus, craving is
usually measured and reported separately from withdrawal. Studies
typically assess craving and withdrawal using the Questionnaire of
Smoking Urges (QSU), QSU-Brief, Minnesota Nicotine Withdrawal Scale
(MNWS), Shiffman-Jarvik Withdrawal Scale, and Visual Analogue Scale
items. Despite their lower nicotine content, VLNC cigarettes typically
do not produce greater reports of craving or other withdrawal symptoms.
Although findings from some brief exposure studies are mixed, the
results of many studies suggest that brief and extended exposure to
VLNC cigarettes can suppress craving and withdrawal just as effectively
as NNC and usual brand cigarettes. The ability of VLNC cigarettes to
suppress craving and withdrawal in people who smoke cigarettes is
likely at least partially due to the long history of pairings between
nicotine and the sensorimotor stimuli associated with smoking. Through
conditioning, these stimuli can suppress craving and some other
withdrawal symptoms even in the absence of nicotine (Ref. 38).
In brief exposure studies where participants were given limited
access to reduced nicotine content cigarettes, typically over the
course of several hours under controlled laboratory conditions, VLNC
cigarettes suppressed craving and withdrawal relative to baseline
measures that were typically assessed following overnight abstinence
(Refs. 452, 460 to 467). Furthermore, many studies showed that VLNC
cigarettes can reduce craving and withdrawal as much as usual brand or
NNC cigarettes (Refs. 391, 406, 407, 411, 413, 415, 417, 419, 422, 433
to 439). However, some studies observed that suppression of craving and
withdrawal was lower after smoking VLNC cigarettes compared to usual
brand or NNC cigarettes (Refs. 265, 396, 388, 402, 427, 440, 453, 454,
468, and 469). In addition, results from a few studies suggest that
VLNC cigarettes influence craving more than withdrawal. One study found
that VLNC cigarettes suppressed craving similarly to NNC cigarettes,
but also produced an increase in other withdrawal symptoms (Ref. 470).
Other studies have found no effects of VLNC cigarettes on withdrawal
symptoms (Refs. 414, 428, and 448). Notably, some of these brief
exposure studies reported differences between genders and generally
found that females who smoke experienced greater reductions in craving
(Refs. 265, 463 and 464) or withdrawal (Refs. 436 and 462) compared to
males who smoke after smoking VLNC cigarettes. However, another study
found that, after smoking VLNC cigarettes, males who smoke had greater
reductions in craving compared to females who smoke (Ref. 435).
During extended exposure studies, when participants smoked VLNC
cigarettes from 4 days to 1 year, ratings of withdrawal (Refs. 249 and
258) and craving (Refs. 249 and 383) were generally similar to ratings
observed in usual brand and NNC cigarette conditions. In one study,
researchers found that, after switching to VLNC cigarettes from usual
brand cigarettes for 1 week, withdrawal symptoms increased with no
reported change in craving (Ref. 32). However, these effects were
relatively brief, and, within 6 weeks, withdrawal symptoms returned to
baseline levels, and craving steadily decreased below baseline levels.
Results from another study showed that VLNC cigarettes can produce
persistent reductions in craving characterized by participants as
``moderate'' or ``a lot'' after 3 and 6 weeks of exposure; however,
some participants reported that no relief from craving occurred during
the 6-week study (Ref. 373). In addition, one study demonstrated that 6
weeks of exposure to LNC and VLNC cigarettes resulted in less craving
and no difference in other withdrawal symptoms compared to NNC
cigarettes (Ref. 471). Finally, during week 1 of a 20-week trial,
people who smoke and were randomized to immediately reduce nicotine
with VLNC cigarettes reported statistically significantly more
withdrawal symptoms compared to those who gradually reduced nicotine
content every 4 weeks (15.5 (NNC), 11.7 (NNC), 5.2 (LNC), 2.4 (LNC),
and 0.4 (VLNC) mg nicotine per gram of total tobacco, respectively) and
compared to a control group using NNC cigarettes (Ref. 379). However,
at the conclusion of 20 weeks, the immediate reduction group reported
statistically significantly lower smoking urges compared with the
gradual reduction group and the NNC cigarette control group. No
statistically significant differences in smoking urges were observed
between the gradual reduction group and the NNC cigarette control
group, suggesting that gradual reduction may be less effective than
immediate reduction in reducing urge to smoke. Similar to findings from
brief exposure studies, female participants
[[Page 5070]]
experienced a reduction in craving after switching to LNC cigarettes
for 1 week, whereas male participants showed no change in craving upon
switching. Overall, withdrawal symptoms increased in both males and
females who smoke cigarettes after 1 week. However, these differences
from baseline were short-lived. Ratings of both craving and withdrawal
symptoms were no different than baseline over the remaining 6 weeks of
the study (Ref. 458).
Craving and withdrawal were also assessed in several smoking
cessation studies wherein participants were provided VLNC cigarettes
along with pharmacotherapies (e.g., NRT, varenicline) before a
designated quit date. In these studies, participants who received VLNC
cigarettes plus a nicotine patch experienced less severe cravings, with
no statistically significant difference in withdrawal (Ref. 472), a
greater reduction in craving and withdrawal (Ref. 35), and less
frequent and less intense cravings before and after the quit date (Ref.
372) compared to those who received NNC cigarettes before the quit
date. Another study found that LNC cigarettes plus either varenicline
or NRT resulted in decreases in craving compared to pharmacotherapy
alone, with no differences in withdrawal across groups (Ref. 371).
Accordingly, findings from these studies suggest that the maximum
nicotine level in this proposed product standard, consistent with VLNC
cigarette levels, would not result in substantial increases in craving
or other withdrawal symptoms.
12. VLNC Cigarette Data Applies to Other Covered Products Under This
Proposed Product Standard
Research regarding the public health impacts of this proposed
maximum nicotine level applies across the tobacco products covered
under this proposed product standard. People who smoke cigarettes who
have lower SES have a greater likelihood of choosing to use RYO tobacco
as a cheaper alternative to factory-made cigarettes (Ref. 312, Ref.
319). Also, literature shows that tobacco manufactures reformulate or
re-label pipe tobacco as ``dual purpose'' and sell it for RYO use to
capitalize on disparities between tax rates on different types of
tobacco products (Ref. 322). Given that cigarette tobacco, RYO tobacco,
and pipe tobacco can be effectively used in cigarettes, the VLNC
cigarette research applies to these products, and any expected benefits
that would accrue as a result of instituting the proposed product
standard for cigarettes also would be expected to accrue for these
product categories.
While the current published literature regarding very low nicotine
products discusses only cigarettes, the many similarities between
cigarettes and most cigars (in both appearance and use topography)
support the application of VLNC cigarette research to the coverage of
these cigars. For example, little cigars are often indistinguishable
from cigarettes given their shape, size, filters, and packaging, and
are perceived as being healthier than cigarettes (Refs. 297 and 298).
Little cigars and certain cigarillos also ``are packaged and consumed
in a manner similar to cigarettes'' (Ref. 473 at p. 584). The close
resemblance of little cigars and many cigarillos to cigarettes have led
consumers, particularly children and young adults, to mistake them for
cigarettes (Ref. 474). Because they are physically similar to
cigarettes, little cigars are generally smoked the same way as
cigarettes, with deeper inhalation than large cigars (Refs. 53 and
475). Secondhand smoke from cigars also contains many of the same
toxins and carcinogens as cigarette smoke, including carbon monoxide,
nicotine, ammonia, benzene, nitrosamines, and formaldehyde, all of
which are on FDA's list of HPHCs (HPHC Established List, 77 FR 20034
(2012)). Moreover, people who smoke cigarettes who switch to products
like cigars to sustain their addiction tend to engage in deeper
inhalation, making them even more susceptible to the dangers associated
with tobacco product use (Ref. 53).
Studies also suggest that people smoke some cigarillos like
cigarettes, inhaling and smoking them every day (Refs. 53 and 475).
Research has found that little cigars deliver nicotine levels similar
to, and sometimes higher than, cigarettes, as well as similar or higher
levels of carcinogens compared to cigarettes (Refs. 476 and 477). Large
cigars can deliver as much as ten times the nicotine of a filtered
cigarette (Ref. 53). Even if people who smoke cigars do not breathe or
inhale smoke into their lungs, they are still subject to nicotine's
addictive effects through buccal absorption of nicotine or nicotine
absorption through the lips due to cigar tobacco's alkalinity (Refs. 54
to 56, 302 and 303). Cigar smoke dissolves in saliva and makes it
possible for people who smoke cigars to absorb sufficient amounts of
nicotine to create dependence (Ref. 56). People who smoke cigars
regularly are at increased risk for many of the same diseases as people
who smoke cigarettes, including oral, esophageal, laryngeal, and lung
cancer; cardiovascular diseases; and COPD (Ref. 163). Accordingly, FDA
believes it is appropriate to bridge these VLNC cigarette studies to
cigars.
C. An Immediate Nicotine Reduction Approach Is Strongly Supported by
Scientific Evidence
Two approaches have been suggested for implementing a nicotine
product standard that would limit nicotine yield by establishing a
maximum level of nicotine content in cigarettes and certain other
combusted tobacco products. One is a gradual reduction approach, which
decreases the nicotine content in the tobacco products over time until
it reaches minimally addictive or nonaddictive levels. The other is an
immediate reduction approach, or single target approach, which would
immediately reduce the nicotine content to minimally addictive or
nonaddictive levels. Available research indicates that both approaches
are associated with noncompliance (i.e., use of NNC cigarettes) when
participants reach the VLNC cigarette phase of the intervention, which
supports findings from other studies that show people who use VLNC
cigarettes are more likely to use alternative nicotine-containing
products when such products are concurrently available. However, the
available scientific evidence suggests that the gradual approach can
lead to compensatory smoking during the intermediate steps when people
are smoking products with low to moderate nicotine content.
Based on scientific evidence, as well as comments and information
submitted in response to the Nicotine ANPRM, FDA is proposing an
immediate reduction approach to reach the maximum nicotine level in
this proposed product standard. We expect that there would be very
little compensatory smoking with an immediate reduction approach and
that any compensatory smoking would be self-limiting and transient
(i.e., research shows that people who smoke would be unable to obtain
their nicotine dose from VLNC cigarettes no matter how they smoked them
and would quickly stop trying to do so), which would increase the
benefits of the proposed product standard. We anticipate most people
who smoke will maintain usual smoking behavior during these 2 years. An
attempt to taper nicotine intake could involve switching to VLNC
cigarettes already on the commercial market (i.e., VLN[supreg]
cigarettes), reducing the number of cigarettes smoked per day, or
switching to another tobacco product. Tapering nicotine intake while
[[Page 5071]]
NNC cigarettes are on the market may facilitate abstinence in smokers
by increasing motivation to quit and quit attempts. However, we do not
expect most people who smoke to switch to VLNC cigarettes while NNC
cigarettes are available. We request comments, data, and information
regarding the selection of an immediate reduction approach.
Several studies have investigated the effects of a gradual approach
to reducing cigarette nicotine content on compensatory smoking (Refs.
40, 258, 329, and 384). In these studies, participants were not
interested in quitting and did not receive NRT or alternative tobacco
products. For example, a pilot study and a clinical trial examined
whether a gradual reduction in cigarette nicotine content would
increase exposure to tobacco smoke toxins due to compensatory smoking
(Refs. 40 and 258). Participants smoked their usual brand cigarettes
during baseline and then were switched to five types of research
cigarettes containing gradually reduced nicotine content (i.e., 10.3
(NNC), 6.5 (LNC), 3.9 (LNC), 1.7 (LNC), and 0.5 (VLNC) mg nicotine per
cigarette). In the 10-week pilot study, participants were switched
weekly, and in the 6-month trial, participants were switched monthly
(Refs.40 and 258). Little change in smoking behavior was observed;
however, plasma cotinine concentration (a biomarker of nicotine
exposure) decreased as a function of cigarette nicotine content, such
that cotinine was lowest while participants were smoking VLNC
cigarettes. The smaller pilot study showed little evidence of
compensation, as calculated based on cigarette consumption, CO, and
polycyclic aromatic hydrocarbon (PAH) metabolites (Ref. 40); however,
the 6-month trial showed a slight increase in compensatory smoking, as
measured by CO and CPD, while participants were in the intermediate
phase of the study. This increase was no longer evident once
participants reached the VLNC cigarette phase of the study (Ref. 258).
Another study showed that compensatory smoking may increase when
participants smoke cigarettes with intermediate levels of nicotine
(e.g., LNC cigarettes) compared to usual brand cigarettes (Ref. 384).
Taken together, these studies demonstrate that people who smoke
cigarettes may engage in compensatory smoking during the early stages
of a gradual reduction approach by smoking more intensely in an attempt
to obtain their desired level of nicotine (Refs. 258, 329, and 369).
Several studies have investigated whether an immediate reduction
approach to nicotine reduction would increase compensatory smoking
(Refs. 29 and 31). Like the gradual reduction studies discussed in this
section, participants in these immediate reduction studies were not
interested in quitting and did not receive NRT or alternative tobacco
products. In the most comprehensive immediate nicotine reduction study
to date, 839 participants were randomized to one 6-week condition,
during which they smoked their usual brand cigarettes or immediately
switched to research cigarettes containing either 15.8 (NNC), 5.2
(LNC), 2.4 (LNC), 1.3 (LNC), or 0.4 (VLNC) mg nicotine per gram of
total tobacco (Ref. 29). Participants assigned to the LNC or VLNC
cigarette groups, who received cigarettes with nicotine content less
than or equal to 2.4 mg nicotine per gram of total tobacco, smoked
statistically significantly fewer CPD than participants assigned to the
usual brand and NNC cigarette groups. Those who received LNC or VLNC
cigarettes containing 5.2 mg nicotine per gram of total tobacco or less
had statistically significantly lower urinary TNE than those who
received NNC cigarettes. There were no differences in breath CO
measures, an indicator of compensatory smoking, between the cigarette
groups. The total puff volume at week 6 was statistically significantly
lower among participants who smoked VLNC cigarettes compared to those
who smoked NNC cigarettes. However, much like the gradual reduction
studies, a secondary analysis showed that noncompliance (i.e., ongoing
use of NNC cigarettes or other tobacco products) was high in
participants randomized to the VLNC cigarette group, suggesting that
VLNC cigarettes have lower appeal and abuse liability compared to NNC
cigarettes and that people who smoke VLNC cigarettes are likely to
obtain nicotine from other tobacco product use (Ref. 330).
In another study, 33 participants were randomized to receive VLNC
cigarettes at no charge or to continue smoking their usual brand
cigarettes for 12 weeks (Ref. 31). Overall, participants in both groups
smoked a similar total number of CPD, even though only the participants
in the VLNC cigarette group received free cigarettes. These data
demonstrate that an immediate reduction in cigarette nicotine content
is unlikely to lead to significant compensation or increased toxicant
exposure.
A secondary analysis pooled data from five clinical studies to
examine the relationship between compensatory smoking and gradual
versus immediate nicotine reduction approaches (Ref. 387). Two of the
studies utilized a gradual reduction approach, and three of the studies
utilized an immediate reduction approach. CPD, breath CO, and cotinine
levels were compared between the immediate reduction group, the gradual
reduction group, and a control group that received usual brand
cigarettes. Relative to baseline, statistically significant decreases
in CPD were observed in participants in the gradual reduction groups (5
percent decrease in CPD) and immediate reduction groups (11 percent
decrease in CPD), whereas statistically significant increases in CPD
were observed in participants in the usual brand groups (12 percent
increase in CPD). Although statistically significant changes in breath
CO were not observed relative to baseline in any group, statistically
significant decreases in cotinine were observed among both gradual and
immediate reduction groups, but not in the usual brand group.
The largest study designed to directly investigate gradual versus
immediate nicotine reduction on toxicant exposure was a 10-site,
randomized, double-blind clinical study in 1,250 adults who smoke and
had no intention to quit (Ref. 379). Participants were randomly
assigned to an immediate reduction group that received VLNC cigarettes
for 20 weeks, a gradual reduction group that received cigarettes
containing progressively decreased nicotine content every 4 weeks
(15.5, 11.7, 5.2, 2.4, 0.4 mg nicotine per gram of total tobacco) for
20 weeks, or a control group that received NNC cigarettes for 20 weeks.
Notably, in this study (and virtually all clinical studies of reduced
nicotine content cigarettes), research cigarettes were free to
participants. Any changes in biomarker levels observed between these
two groups would indicate differences in smoking behavior (e.g., CPD,
smoking topography). Completion rates were statistically significantly
lower for the immediate reduction group (68 percent) compared to the
gradual reduction group (81 percent) and control group (86 percent).
The immediate reduction group had statistically significantly lower
levels of three primary biomarker outcomes (i.e., CO, 3-HPMA, and r-
1,t-2,3,c-4-tetrahydroxy-1,2,3,4 tetrahydrophenanthrene) compared to
the gradual reduction group, which did not differ from the control
group. In addition, statistically significantly lower levels of other
biomarkers (i.e., TNE, NNAL, 2-cyanoethylmercapturic acid, 3-hydroxy-1-
methylpropylmercapturic acid, S-PMA) were observed in the immediate
reduction group compared to the gradual reduction and the control
[[Page 5072]]
groups. The immediate reduction group smoked cumulatively fewer CPD
over the course of the 20-week study and had lower nicotine dependence
scores compared to the gradual reduction group, with no statistically
significant differences in CPD or dependence in the gradual reduction
versus control groups. While there was no statistically significant
difference between the immediate and gradual reduction groups in the
proportion of participants with any ``cigarette-free days'' during the
study, the immediate reduction group had a statistically significantly
higher number of ``cigarette-free days'' compared to the gradual
reduction group. The immediate reduction group had statistically
significantly higher withdrawal scores at week 1 compared to the
gradual reduction group; however, these differences dissipated after
the first week. The immediate reduction group had higher rates of
noncompliance with non-study cigarette use and a higher drop-out rate,
which may have impacted the various outcome measures (e.g., biomarkers
of exposure). Additionally, the immediate reduction group had an
increased number of adverse events (predominantly related to
withdrawal) compared to the gradual reduction group. Nevertheless, this
study provides further evidence that immediate nicotine reduction is
associated with reduced toxicant exposure and nicotine dependence and
increased smoking abstinence compared to gradual nicotine reduction.
This suggests that with immediate nicotine reduction, the potential
health benefits could occur sooner than gradual nicotine reduction.
While the immediate reduction group had increased levels of nicotine
withdrawal, this effect was time-limited, dissipating after 1 week
(Ref. 379).
Higher study attrition and noncompliance with study cigarettes are
common within VLNC cigarette conditions in clinical studies (Refs. 327,
329, and 330), especially studies such as the one described above (Ref.
379), wherein participants are not interested in quitting smoking, and
they are asked to refrain from using alternative sources of nicotine.
Because of the lower abuse liability of VLNC cigarettes, participants
in these studies may drop out or use non-study cigarettes that contain
nicotine. These conditions would not exist if the proposed product
standard is implemented. People who smoke would not be able to readily
obtain NNC cigarettes, but they would be able to obtain alternative
noncombusted products with nicotine content that they could switch to
or use with VLNC cigarettes.
In sum, evidence from studies involving VLNC cigarettes suggests it
is likely that there would be very little or no compensatory smoking
with an immediate reduction approach to a maximum nicotine level, which
would increase the public health impact of a nicotine reduction policy.
Additionally, FDA believes an immediate reduction approach would have a
lesser impact on manufacturers as compared to a gradual approach by
limiting any changes necessary for compliance to a single occasion.
Although FDA believes this is a benefit of the immediate reduction
approach, it is not a determinative factor given the strength of the
scientific evidence.
D. Scientific Evidence Supports the Use of an Analytical Test Method To
Determine Nicotine Level
In its considerations regarding the use of an analytical test
method, FDA determined that any analytical method to measure compliance
must accurately and reliably detect nicotine at low concentrations
(i.e., below 0.70 mg nicotine per gram of total nicotine). In addition,
FDA determined that it is important that the proposed product standard
permit comparison of test results among finished tobacco products and
testing facilities. FDA also concluded that it is important that the
test method demonstrate its suitability and reliability in accurately
measuring a range of nicotine concentrations across a wide variety of
tobacco blends and products. Accordingly, FDA is proposing to require
manufacturers use an analytical test method that would satisfy these
preceding factors and demonstrate that the test method was validated in
an analytical test laboratory. In lieu of requiring a specified test
method, we are recommending manufacturers consider using one of the
three following analytical test methods FDA has determined satisfy the
preceding factors: FDA's Tobacco Products Laboratory method (Ref. 478),
Cooperation Centre for Scientific Research Relative to Tobacco
(CORESTA) Recommended Method (CRM) No. 62 (Determination of nicotine in
tobacco and tobacco products by gas chromatographic analysis; (Ref.
479)), or CRM No. 87 (Determination of nicotine in tobacco products by
gas chromatography-mass spectrometry (GC-MS); (Ref. 480)). However, an
analytical test method that meets the requirements of the regulation,
even if it is not one of the recommended methods, would be acceptable.
FDA's Tobacco Products Laboratory, located in Atlanta, Georgia, has
developed an analytical test method, entitled ``Quantitation of
Nicotine in Tobacco Products--Update to LIB No. 4550'' (LIB #4692),
that is capable of quantifying nicotine levels that include
concentrations well above and below the proposed nicotine standard
level and also meets formal intralaboratory validation criteria (Ref.
478). The method utilizes GC-MS with a run time of 4.1 minutes.
Analysis is conducted on extracted tobacco or spiked surrogate matrix
samples treated with a base (sodium hydroxide) to obtain the total
nicotine content for each sample. Quinoline is used as the internal
standard. Tomato leaves are used as a surrogate matrix for tobacco to
examine recovery amounts for spiked samples. Validation was performed
using Moonlight brand VLN Menthol King ground tobacco and NIST 1573a
(Tomato Leaves) as a blank spiking matrix. The range of the method was
0.1 to 2.0 mg of nicotine per gram of total tobacco, meaning nicotine
concentrations in this range can be accurately measured. Tobacco
samples with nicotine concentrations expected to be higher than 2.0 mg
nicotine per gram of total tobacco were analyzed after dilution of the
extraction sample by a factor of ten. The method detection limit is
0.05 mg nicotine per gram of total tobacco, which is more than an order
of magnitude below the proposed maximum nicotine concentration of 0.70
mg per gram of total tobacco. The limit of quantitation is 0.1 mg
nicotine per gram of total tobacco, which is also well below the limit
of the proposed product standard. Furthermore, this method was proven
to be applicable to a wide range of tobacco products. Tobacco filler
and total tobacco from various marketed tobacco products including
cigarettes, large cigars, cigarillos, little cigars, RYO cigarettes and
pipe tobacco were analyzed successfully using FDA's Tobacco Products
Laboratory method.
CORESTA updated CRM No. 62 (Determination of Nicotine in Tobacco
and Tobacco Products by Gas Chromatographic Analysis) in December 2021
and CRM No. 87 (Determination of Nicotine in Tobacco Products by Gas
Chromatography-Mass Spectrometry (GC-MS)) in April 2020 to extend the
scope of the methods to include VLNC tobacco by lowering the
calibration range for these analytical test methods (Refs. 479 and
480). A study determined that the updated versions of CRM No. 62 and
CRM No. 87 are suitable for the analysis of nicotine content in VLNC
[[Page 5073]]
tobacco and tobacco products (Ref. 481). These methods can reliably
measure nicotine content as low as 0.117 mg per gram of total tobacco.
FDA's Tobacco Products Laboratory method, entitled ``Quantitation
of Nicotine in Tobacco Products--Update to LIB No. 4550'' (LIB #4692),
is publicly available at https://www.fda.gov/science-research/field-science-and-laboratories/laboratory-information-bulletins. In addition
to the Tobacco Products Laboratory method, CRM No.62 (https://www.coresta.org/determination-nicotine-tobacco-and-tobacco-products-gas-chromatographic-analysis-29185.html) and CRM No. 87 (https://www.coresta.org/determination-nicotine-tobacco-products-gc-ms-33537.html) are also publicly available methods that include the
proposed nicotine level in the range of concentrations that can be
accurately measured. FDA recommends manufacturers use one of these
analytical test methods to demonstrate compliance with this proposed
product standard.
It is reasonable to expect some manufacturers may prefer to use
other test methods. If developed and validated, such methods may have
different advantages in ease of use, upper and lower bounds of
detection, equipment, and expertise. We would evaluate data from
analytical test methods as part of a premarket submission in accordance
with section 910 of the FD&C Act.
FDA requests comments, including data or other scientific support,
regarding FDA's Tobacco Products Laboratory method, CRM No. 62, CRM No.
87, or other available methods, that could test the proposed scope of
tobacco products at the proposed maximum nicotine level.
E. Scientific Evidence Supports the Technical Achievability of the
Proposed Maximum Nicotine Level Target
While FDA has analyzed various methods of technical achievability
for this proposed product standard, section 907(b)(1) of the FD&C Act
also requires FDA to consider information submitted in connection with
the proposed product standard regarding the technical achievability of
compliance. Therefore, pursuant to section 907(d)(2) of the FD&C Act,
FDA requests comments by interested parties, including manufacturers
and tobacco growers, regarding the technical achievability of
compliance with this proposed product standard, including information
concerning the existence of patents that may impact the ability to
comply by the proposed 2-year effective date of this proposed rule (see
section XI of this document).
The tobacco industry has developed a range of brands with differing
nicotine levels. Tobacco product manufacturers have extensive
experience blending tobaccos with different nicotine levels to ensure
that products will have precise levels of nicotine and using continuous
quality testing throughout the entire process to ensure that nicotine
levels vary only minimally within cigarette packs and from pack to pack
(Ref. 482). A cigarette is an inexpensive and extremely effective
nicotine delivery system that maximizes the cigarette's addicting and
toxic effects (Ref. 61).
In fact, the tobacco industry has had programs in place since the
1960s to obtain ``any level of nicotine desired'' (Ref. 2) (see section
V.A for a detailed discussion). Indeed, the tobacco industry conducted
research on consumer perceptions of RNC cigarettes to determine the
optimal amount of nicotine in cigarettes to maintain appeal. Reviews of
industry documents indicate that user experience, such as poor taste
and reduced throat sensations, impacted the commercial viability of
VLNC cigarettes (Refs. 247, 483, and 484). Internal industry strategies
to mitigate these issues and maintain VLNC cigarette appeal to
consumers included adding menthol to enhance the flavor of RNC
cigarettes (Ref. 484) and maintaining or increasing tar levels to
improve taste (Ref. 483).
As discussed in this section, there are numerous methods for
altering the concentration of nicotine in cigarettes and certain other
combusted tobacco products, and FDA anticipates that manufacturers and
tobacco farmers may choose to use a variety of approaches to meet the
proposed maximum nicotine concentration. Significant reduction of
nicotine in the tobacco products covered by this proposed product
standard can be achieved principally through tobacco blending, chemical
extraction, or genetic engineering. Other practices such as modified
growing conditions (e.g., discontinue the practice of topping where the
flowering head of the tobacco plant is removed to produce leaves with a
significantly higher nicotine content, increase plant density, decrease
nitrogen application), as well as more recent novel techniques, can
also help to reduce nicotine levels. One or a combination of these
processes can be used to achieve the nicotine target concentration in
this proposed product standard.
1. Genetically Engineered Tobacco
Tobacco industry scientists have long recognized the potential for
genetic engineering to control nicotine content (Ref. 485). The first
practical application of biotechnology by a major tobacco manufacturer
was the development of low nicotine content tobacco in the 1980s, which
led to the receipt of a patent for biotechnology for altering nicotine
in tobacco plants (Refs. 483 and 486). Other tobacco researchers and
major manufacturers also recognized the value of biotechnology for
developing low nicotine content tobacco for cigarettes, including for
use as part of a smoking cessation program (Ref. 487).
In the 1930s, some Havana and Cuban cigar tobacco varieties were
discovered to have naturally lower nicotine levels. Genetic analysis of
these low nicotine containing plants identified a mutation in the nic1
and nic2 genes that are responsible for the production of reduced
nicotine in some tobacco variety leaves (Ref. 488). These varieties of
low nicotine content cigar tobacco were crossbred with burley tobacco
to produce varieties of cigarette tobacco with low nicotine content to
meet the health demands of the time (Ref. 489).
Several American and international tobacco companies genetically
engineered low-nicotine strains in the 1960s and 1970s (Refs. 490 to
493), including a strain with a nicotine concentration as low as 0.15
percent (i.e., 1.5 mg nicotine per gram of total tobacco), which was
much lower than the 3.15 percent (31.5 mg nicotine per gram of total
tobacco) observed in the comparator strain (Ref. 492). During that time
period, the Kentucky Tobacco Research Board worked on genetic strains
of low nicotine content tobacco (with a nicotine content of 0.2
percent) to be used for experimental studies on the role of nicotine in
smoking behavior (Refs. 493 to 497). In addition, Canadian researchers
examined low nicotine strains of tobacco, particularly in association
with efforts to develop a strain of flue-cured or air-cured tobacco
that would be suitable as the base material for reconstituted tobacco
(Refs. 493, 498, and 499). Although the early strains of low-nicotine
tobacco that were developed by these researchers and companies
contained far less nicotine than strains that were traditionally used
to make cigarettes, the nicotine content is even lower in strains that
have been developed more recently through genetic engineering.
Genetic engineering has resulted in up to a 98 percent reduction in
nicotine levels (Ref. 483). In 2003, Vector Tobacco began marketing the
Quest
[[Page 5074]]
cigarette produced from genetically modified tobacco containing only
trace amounts of nicotine (this product is no longer on the market)
(Ref. 483). In 2014, the U.S. Patent and Trademark Office granted a
patent for two genes that may be suppressed to substantially decrease
nicotine in tobacco plants (Ref. 500). Additionally, in 2020, the U.S.
Patent and Trademark Office granted another patent for methods of
manipulating plant metabolism and alkaloid levels by controlling
transcription factor NbTF7, which regulates the nicotinic alkaloid
biosynthetic pathway in the Nicotiana tabacum plant (Ref. 501). This
method appears to be able to introduce very low nicotine traits in any
variety of Nicotiana tabacum; therefore, this method may be applicable
to other combusted tobacco products that use Nicotiana tabacum (e.g.,
cigars).
Significant progress has been made in the genetic modification of
nicotine and other alkaloid production in tobacco. One powerful gene
editing technology, CRISPR-Cas9, has been used to delete or silence
various genes involved in the production of nicotine in tobacco plants
resulting in several ultra-low nicotine CRISPR tobacco lines that have
been grown experimentally (Ref. 502). However, challenges have
presented themselves in transitioning these ultra-low nicotine content
tobacco plants to fields, such as severely stunted plants and high
insect infestation rates (Ref. 503). Studies on the impact of
genetically engineered low-level nicotine are ongoing and this method
has not been accomplished on a large scale.
FDA is aware that genetically engineered tobacco seed has been
created and may be available for purchase on the market. If this
proposed rule is finalized, licensing agreements may be needed to
support production of VLNC tobacco, at least initially. FDA notes that
similar agreements with tobacco manufacturers are common within the
tobacco industry.
2. Chemical Extraction
Another method to achieve lower nicotine concentrations in tobacco
products is through chemical extraction technology. By the 1970s,
tobacco manufacturers were regularly practicing nicotine extraction as
a method to control nicotine delivery (Refs. 493 and 504 to 506).
Extraction methods include water extraction (coupled with steam or oven
drying), solvent extraction, and extractions of nicotine without usable
leaf (Ref. 493). For example, one company, Ultratech, Inc., produced
VLNC cigarettes by extracting nicotine with an alkaline solution (Ref.
507). Supercritical fluid extraction (which extracts chemical compounds
using supercritical carbon dioxide instead of an organic solvent) also
yielded success in the 1990s, allowing for optimum extraction times and
the elimination of more time-consuming steps (Ref. 508). FDA notes that
existing patents for chemical extraction reveal that more than 96
percent of nicotine can be successfully extracted from tobacco while
retaining ``a strong characteristic aroma . . . not different from the
unextracted blend,'' achieving a product that ``was subjectively rated
as average in nicotine characteristics'' (Refs. 509 and 510). A major
tobacco manufacturer also has used a high-pressure carbon dioxide
process similar to the process used to decaffeinate coffee. In this
process, tobacco leaf is treated with ammonium salt, and then treated
with carbon dioxide/water vapor, to achieve a 95 to 98 percent
reduction in nicotine (Refs. 483 and 511).
Water extraction also can be used for nicotine reduction. Although
some manufacturers believe that some water extraction practices may
have rendered the tobacco ``unsuitable for use'' in cigarettes, other
water extraction projects have yielded suitable smoking material with
sizeable nicotine reductions (80 to 85 percent reduction in leaf
nicotine) (Refs. 493, 505, 512, and 513).
3. Tobacco Farming Practices
Different types of farming practices also can lower nicotine
concentrations in tobacco plants. One example is alkaloid-minimizing
farming practices. Industry studies have shown that changes to growing
and harvesting practices affect the development of tobacco chemistry,
including nicotine content (Ref. 493). Some manufacturers have revised
their agricultural practices specifically to meet new product
development goals, such as the production of low nicotine content
tobacco (Ref. 493). For example, one manufacturer evaluated how various
experimental agricultural practices including bulk-curing, once-over
harvesting, and high plant density could affect the tobacco's chemistry
(Refs. 493 and 514). In other cases, chemical agents were observed to
reduce nicotine content (Refs. 493, 515 to 517).
Modification of tobacco growth practices can result in reduced
levels of nicotine in tobacco plants. In traditional tobacco
production, plants are topped and suckered (removing the growth at the
apex and axillary buds) to slow the ripening rate of the leaves
resulting in increased nicotine content. Therefore, discontinuing these
practices results in a significant decrease in nicotine production
(Ref. 518). It has been found that plant density is conversely
correlated to nicotine production in the plant as increased plant
density creates a competition for resources, particularly nitrogen.
Therefore, higher plant densities lead to lower nitrogen availability
and stunted plant growth, thus resulting in lower nicotine tobacco
(Ref. 519).
Nightshades are a botanical family that naturally contain
alkaloids, including nicotine. In addition to tobacco plants, tomatoes,
eggplants, potatoes, and peppers are in the nightshade category.
Nicotine synthesis begins in the root of the tobacco plant and
researchers have studied whether replacing tobacco root with other
nightshades via grafting could affect nicotine biosynthesis (Ref. 519).
Studies have been performed where grafting tobacco shoots on rootstocks
of eggplant was shown to reduce nicotine production drastically without
significant changes to the development of the plants (Ref. 520).
Eggplant grafting results in differential expression of hundreds of
genes involved in the nicotine biosynthetic pathway (Ref. 520). In
these studies, no significant differences in plant height, leaf length,
leaf width, or stalk circumference were observed between the tobacco/
tobacco and tobacco/eggplant groups up to 80 days after grafting.
However, the grafted tobacco/eggplant leaves resulted in a 95 percent
reduction in nicotine content as compared to the tobacco/tobacco
control plants (Ref. 520).
4. Tobacco Blending/Crossbreeding
One way to achieve lower nicotine concentrations in tobacco
products is to selectively blend the tobacco filler. Most cigarettes
sold in the United States are blended from several different types of
tobacco (Ref. 359). A tobacco industry executive previously testified
that the main component of a cigarette that contributes to nicotine
delivery is the tobacco blend, and year-to-year crop variation does not
determine the nicotine content in a cigarette (Ref. 521). The term
``leaf blending'' describes the selection of tobaccos to be used in a
product by tobacco type (e.g., flue-cured, burley, oriental),
geographical origin, year, and tobacco grade (Ref. 493). Blend
differences can produce significant variations in nicotine
concentration in the tobacco rod, leading to differences in smoke
composition and yield (Ref. 82 at p. 469).
Many tobacco strains are available, including approximately 1,000
different
[[Page 5075]]
tobacco varieties (Ref. 359). The tobacco industry has used breeding
and cultivation practices to develop high nicotine tobacco plants to
give manufacturers greater flexibility in blending and in controlling
the amount of nicotine to be delivered (Ref. 522 at 41694). These
practices could be used to develop low nicotine content tobacco plants
as well. Tobacco industry documents show that in the 1960s, tobacco
companies recognized the increasing demand for low nicotine content
tobacco and began instituting projects that found low nicotine content
cigarettes can be made by selecting grades of tobacco with low nicotine
content (Refs. 523 and 524).
Because the nicotine content of tobacco plants varies,
manufacturers could replace more commonly used nicotine-rich varieties
like Nicotiana rustica with lower nicotine varieties (Ref. 525). For
example, oriental Turkish-type cigarettes also deliver substantially
less nicotine than cigarettes that contain air-cured burley tobacco
(Refs. 82 and 526). Even without this selective breeding, manufacturers
could use careful tobacco leaf purchasing plans to control the nicotine
content in their products (Ref. 522 at 41694). By maintaining awareness
of the differences and monitoring the levels in purchased tobacco,
companies could produce cigarettes with nicotine deliveries consistent
to one-tenth of 1 percent (despite annual variations of up to 25
percent in the nicotine content of the raw material grown in the same
area) (Ref. 522 at 41694).
Grading, which is used to evaluate and identify differences within
tobacco types, is a function of both plant position (i.e., higher or
lower leaf position on the stalk) and quality (i.e., ripeness), and
segregation of grades by nicotine content has become common practice
(Ref. 493). The position of leaves on the plant stalk affects nicotine
levels: tobacco leaves located near the top of the plant can contain
higher concentrations of nicotine, and lower stalk leaves generally
contain lower nicotine levels (Refs. 493, 525, and 527). For example,
flue-cured tobacco leaves harvested from the lowest stalk position may
contain from 0.08 to 0.65 percent nicotine (i.e., 0.8 to 6.5 mg
nicotine per gram of total tobacco), whereas leaves from the highest
positions may contain from 0.13 to 4.18 percent nicotine (i.e., 1.3 to
41.8 mg nicotine per gram of total tobacco) (Refs. 359, 528 and 529).
Therefore, substituting leaves found lower on the plants (commonly
called ``priming'') could reduce the nicotine content of tobacco
products (Ref. 525).
Internal tobacco industry documents describe the use of leaf
blending and tobacco selection to control cigarette nicotine content
(Ref. 493). For example, one company project determined that
manufacturers could reduce cigarette nicotine content by selecting
grades of tobacco with naturally low nicotine content (Ref. 523).
Another observed that the demand for low nicotine content tobacco has
increased worldwide and necessitated a shift in purchasing standards
(Ref. 524).
5. Other Practices
After tobacco is harvested, it is cured and aged before being used
in tobacco products. The aging process naturally changes the chemistry
of the tobacco, including some reduction in nicotine content (Ref.
493). At least one manufacturer has explored efforts to speed the
tobacco aging process, in part to alter or limit the changes in
chemistry that naturally occur (Refs. 493 and 530). Other approaches to
curing and fermenting tobacco have been explored as methods for
altering nicotine content. For example, in one manufacturer's report,
researchers observed that the properties of tobacco, including nicotine
content, could be altered without the need for nontobacco additives by
modifying curing practices (Ref. 531). In addition, manufacturers have
explored other approaches to identify microbial bacteria that actively
degrade nicotine while leaving other components of the leaf intact
(Refs. 532 and 533). Consumer product testing showed that the ``product
acceptability'' of that tobacco was equal to that of untreated tobacco
(Ref. 534).
Researchers also have developed novel approaches to reducing the
nicotine in tobacco products in recent years. An example of one such
approach is enzymatic digestion utilizing glucose oxidase harvested
from the salivary excretion produced by a specific species of
herbivorous caterpillar, helicoverpa zea (Ref. 535). The extracted
enzyme is applied to the harvested tobacco leaves, reducing the
nicotine in the tobacco leaf by up to 75 percent, providing an
``effective and economical system for producing tobacco products which
contain about 0.01 mg nicotine per cigarette or less . . . while
maintaining the other desirable ingredients for good taste and flavor''
(Ref. 535). Another novel approach is the use of microwave-assisted
technology to extract nicotine from tobacco, including cigar filler
(Ref. 536), that also could be effective for reducing the nicotine
content for other tobacco products such as RYO tobacco and pipe
tobacco.
By using one or a combination of methods described above, FDA
concludes there is ample evidence of the technical feasibility of
complying with this proposed product standard to reduce the nicotine
level in cigarettes and certain other combusted tobacco products.
6. Applicability to Other Combusted Tobacco Products and Smaller
Manufacturers
FDA anticipates that manufacturers of non-cigarette tobacco
products covered by this proposed product standard may also choose to
use a variety of approaches to meet the proposed maximum nicotine
level. Given the similarities between the tobacco used in cigarettes
and in other combusted tobacco products that FDA proposes to include
within the scope of this product standard, FDA expects that it is
similarly technically feasible for non-cigarette tobacco products to
comply with the proposed maximum nicotine level. FDA requests comments,
data, and research regarding the feasibility of using the techniques
discussed in this section, or other nicotine reduction techniques, for
the non-cigarette products covered under this proposed product
standard.
Although industry documents contain little information regarding
feasibility of VLNC levels for non-cigarette products, an early 1962
patent does indicate a tobacco storage process that dramatically
reduced nicotine levels, including in shade-grown Connecticut tobacco
used for cigars, from 0.85 percent to 0.075 percent nicotine content
(i.e., from 8.5 to 0.75 mg nicotine per gram of total tobacco) (Ref.
537). In 1975, a large tobacco manufacturer also discussed development
of a low nicotine cigar or cigarillo, including processed low nicotine
content tobaccos such as a burley filler in the range of 0.34 percent
nicotine (i.e., 3.4 mg nicotine per gram of total tobacco) and methods
for reducing nicotine in the cigar wrapper (Ref. 538).
FDA expects that smaller manufacturers may use a variety of methods
to comply with the proposed product standard, including purchasing
tobacco blends that are lower in nicotine or have already undergone
extraction. FDA believes that the supply chain should be capable of
adapting to the purchasing needs of smaller manufacturers as well as
larger manufacturers, particularly given the prevalence of genetically
engineered tobacco, as discussed in this section. FDA requests
comments, including data and research, regarding the methods and
[[Page 5076]]
options smaller manufacturers may use to comply with this proposed
product standard.
F. Proposal Does Not Seek To Limit Nicotine to Zero
Section 907(d)(3) of the FD&C Act expressly prohibits FDA from
requiring the reduction of the nicotine yield of a tobacco product to
zero, and consistent with that provision FDA is not seeking to do so.
However, section 907(a)(4)(A)(i) of the FD&C Act expressly authorizes
FDA to establish product standards with provisions ``for nicotine
yields,'' which includes the authority to include a provision, such as
the one in this proposed rule, to require reduction of nicotine yield
to a level other than zero. The information provided in this section
demonstrates that the proposed product standard does not require the
level of nicotine to be zero. The level of nicotine proposed in this
product standard is measurable in the tobacco filler and in the smoke
yield. Research shows that after use of VLNC cigarettes, nicotine is
measurable in the body via biomarkers of exposure and neurological
receptor occupancy.
1. Nicotine Biomarkers of Exposure
Studies have shown that levels of nicotine biomarkers increase in
people who smoke cigarettes containing nicotine equivalent to FDA's
proposed nicotine level, thereby demonstrating exposure to nicotine
from smoking VLNC cigarettes (Refs. 259, 402, and 539). Short-term
studies that measure nicotine exposure in people who smoke cigarettes
who smoke one or two VLNC cigarettes have generally found increases in
plasma nicotine levels that follow similar, but less dramatic, patterns
seen following smoking regular nicotine cigarettes. For example, one
study evaluated plasma nicotine exposure before and repeatedly after
smoking a single NNC, LNC, VLNC, or usual brand cigarette (Ref. 402).
While the LNC and VLNC cigarettes were associated with lower plasma
nicotine levels compared to the NNC and usual brand cigarettes, all
cigarettes were associated with statistically significant increases in
plasma nicotine compared to baseline levels (Ref. 402). Similarly, 22nd
Century Group, Inc. submitted modified risk tobacco product
applications to FDA containing data from two clinical studies showing
that peak plasma nicotine levels following use of a single VLNC
cigarette ranged from 0.4-0.5 nanograms of nicotine per milliliter of
plasma and total nicotine levels (i.e., plasma nicotine area under the
curve calculated using the trapezoidal rule to 180 minutes) ranged from
26.2-30.4 nanograms of nicotine per milliliter of plasma (Ref. 539).
Researchers observed similar effects among participants who smoked a
single VLNC cigarette made by Philip Morris for research purposes only
(Ref. 259).
Studies with longer exposure to VLNC cigarettes have also found
evidence of nicotine exposure within study participants. For example,
studies showed that after several days or weeks of smoking VLNC
cigarettes, biomarkers of nicotine exposure--such as urinary cotinine
and TNE (i.e., the sum of nicotine and various nicotine metabolites)--
in people who smoke cigarettes were drastically reduced but were still
detectable (Refs. 32 and 265). Notably, if participants in these
studies were noncompliant with study-assigned cigarettes, then some of
the biomarkers of nicotine exposure could be attributed to the use of
other tobacco products. However, evidence from studies in which
participants were confined to hotels or residential research facilities
without access to other tobacco products also demonstrate that extended
exposure to VLNC cigarettes produces biomarkers of nicotine exposure
and physiological responses consistent with nicotine exposure (Refs. 64
and 423). Taken together, these data consistently show that levels of
nicotine biomarkers of exposure in people who smoke VLNC cigarettes are
still detectable. For further discussion of biomarkers of exposure, see
section VII.B.6 of this document.
2. Receptor Occupancy and Cerebral Response From the Use of VLNC
Cigarettes
Studies have shown that the nicotine provided by VLNC cigarettes is
enough to occupy sufficient numbers of nicotine receptors in the brain
(i.e., [alpha]4[beta]2 nAChRs) to mitigate feelings of withdrawal and
craving. PET and MRI data obtained from people who smoke cigarettes
indicate that after smoking a VLNC cigarette, nicotine receptors
located in numerous areas of the brain are occupied despite the lower
nicotine content of VLNC cigarettes, and these participants reported a
statistically significant reduction in craving compared to before
smoking the VLNC cigarette (Ref. 430). In another study that compared
VLNC and NNC cigarettes, exposure to both types of cigarettes resulted
in the binding of nicotine to receptors in the brain and the release of
dopamine (Ref. 425). However, the magnitude of subjective craving or
withdrawal responses observed following use of VLNC cigarettes was
lower than use of NNC cigarettes (Refa. 425 and 461). For further
discussion of receptor occupancy, see section VII.B.8 of this document.
3. VLNC Cigarette Nicotine Smoke Yield
Nicotine ``yield'' refers to the amount of nicotine in tobacco
smoke as measured through machine-generated smoking methods (e.g., ISO
machine smoking method, CI smoking method, FTC smoking method), and is
typically measured and reported in milligrams per cigarette. The
maximum level of nicotine set by this proposed product standard would
result in nicotine yield in tobacco smoke that is at detectable levels
above zero. For example, SPECTRUM NNC cigarettes that contain 15.8-16.6
mg of nicotine per gram tobacco filler have machine-measured nicotine
yields of 0.7-0.8 mg of nicotine per cigarette. SPECTRUM VLNC research
cigarettes that contain 0.3-0.4 mg of nicotine per gram tobacco filler
have quantifiable machine-measured nicotine yields greater than zero,
ranging from 0.03-0.04 mg of nicotine per cigarette (Ref. 254).
Similarly, Quest[supreg] 3 VLNC cigarettes had quantifiable machine-
measured nicotine yields of approximately 0.03 mg of nicotine per
cigarette (Ref. 540).
In summary, the data indicate that nicotine is measurable in both
the tobacco filler and the smoke yield of VLNC cigarettes and therefore
does not equal zero. After using VLNC cigarettes, nicotine exposure has
been shown to occur as evidenced by studies measuring biomarkers of
nicotine exposure and neurological receptor occupancy. Consequently,
FDA finds that the proposed product standard would not require the
reduction of nicotine yields to zero.
VIII. Determination That the Standard Is Appropriate for the Protection
of the Public Health
The Tobacco Control Act authorizes FDA to adopt tobacco product
standards by regulation if it finds that such tobacco product standards
are appropriate for the protection of the public health (section
907(a)(3)(A) of the FD&C Act). The notice of proposed rulemaking (NPRM)
for such a product standard must set forth this finding with supporting
justification, which FDA is providing here (section 907(c)(2)(A)) of
the FD&C Act.
In order to make this finding, FDA must consider scientific
evidence concerning:
The risks and benefits to the population as a whole,
including users and nonusers of tobacco products, of the proposed
standard;
[[Page 5077]]
The increased or decreased likelihood that existing users
of tobacco products will stop using such products; and
The increased or decreased likelihood that those who do
not use tobacco products will start using such products.
Section 907(a)(3)(B)(i) of the FD&C Act.
FDA has considered scientific evidence related to all three
factors. Based on these considerations, as discussed below, we find
that the proposed standard is appropriate for the protection of the
public health because it would increase the likelihood that many people
who currently smoke cigarettes and/or certain other combusted tobacco
products would stop smoking altogether, yielding significant health
benefits from smoking cessation. Additionally, we find that the
proposed standard is appropriate for the protection of the public
health because it would decrease the likelihood that people who do not
smoke cigarettes and/or use certain other combusted tobacco products--
including youth and young adults--who experiment with combusted tobacco
products will become addicted to these products, thereby decreasing
progression to regular use, resulting in reduced tobacco-related
morbidity and mortality associated with combusted tobacco product use.
Increased cessation, as well as decreased initiation, progression to
regular use, and consumption would lead to lower disease and death in
the U.S. population, due to decreased use of cigarettes and certain
other combusted tobacco products. Furthermore, the rule is appropriate
for the protection of the public health because the population as a
whole would likely experience additional health benefits as a result of
reduced secondhand smoke exposure, smoking-related fires, and smoking-
related perinatal conditions.
A. Approach To Estimating Impacts to the Population as a Whole
Current evidence shows that, while nicotine itself is not the
direct cause of most smoking-related diseases, addiction to the
nicotine in tobacco products is the proximate driver of tobacco-related
death and disease because it sustains tobacco use (Refs. 1, 28, 58, and
61). The addiction caused by nicotine in tobacco products is critical
in the transition of people who smoke cigarettes from experimentation
to sustained smoking and in the maintenance of smoking for those who
want to quit (Refs. 1 at p. 113 and 28). Combusted tobacco products,
including cigarettes, are responsible for the overwhelming burden of
disease and death from tobacco product use (Refs. 1 and 28). As a
result, FDA expects that making cigarettes and certain other combusted
tobacco products minimally addictive or nonaddictive would reduce
tobacco-related harms by promoting smoking cessation or complete
migration to alternative, potentially less harmful noncombusted tobacco
products and by reducing initiation. In this section, we summarize the
approach used to estimate the possible impact of a potential nicotine
tobacco product standard to the population as a whole and present the
findings of this analysis.
To assess the potential public health impacts of a nicotine product
standard, FDA developed a population health model using inputs derived
from available empirical evidence and expert opinion to estimate the
impact of changes in tobacco product initiation, cessation, switching,
and dual use on tobacco use prevalence, morbidity, and mortality in the
United States. Details of this modeling approach have been previously
published in two peer-reviewed publications (Refs. 47 and 48), which
describe the overall model in terms of the inputs, transition
behaviors, and outputs that it contains, along with results from
simulation studies. In preparation for this proposed product standard,
FDA updated the model published previously (Ref. 47), which describes
the impact of a potential product standard that limits the level of
nicotine in cigarettes, RYO tobacco, non-premium cigars, and pipe
tobacco so that they are minimally addictive or nonaddictive.\29\ The
details of this analysis are presented in an updated modeling document,
entitled ``Methodological Approach to Modeling the Potential Impact of
a Nicotine Product Standard on Tobacco Use, Morbidity, and Mortality in
the U.S.'' (Ref. 42). We estimated the potential impacts of a nicotine
product standard by modeling a baseline scenario of use of cigarettes
and noncombusted tobacco products including smokeless tobacco, e-
cigarettes, HTPs, and oral nicotine products. We then compared the
baseline scenario to a product standard scenario characterized by the
introduction of a potential nicotine product standard that would apply
to cigarettes, RYO tobacco, non-premium cigars, and pipe tobacco. FDA's
modeling framework and methodological approach and the associated
inputs and assumptions have been peer reviewed by independent external
experts. Taking into consideration comments from this peer review (Ref.
49), FDA revised the modeling document, and the final modeling document
is available in the docket for this proposed rule (Ref. 42). FDA's
modeling work informed the development of this proposed product
standard. FDA requests comments on the methodology and analysis
(including the overall model in terms of the inputs, transition
behaviors, and outputs) presented in the scientific modeling document.
---------------------------------------------------------------------------
\29\ The policy scenario presented in Apelberg et al. 2018 (Ref.
47) did not define a specific level of nicotine as minimally
addictive or nonaddictive. Rather, the policy scenario simulated
implementation of a hypothetical standard in which cigarettes and
certain other combusted tobacco products were made minimally
addictive or nonaddictive, informed by a formal expert elicitation
process, and used to estimate the impact of decreasing the
addictiveness of cigarettes on certain tobacco use behaviors.
---------------------------------------------------------------------------
FDA's population health model incorporates the following tobacco
use transitions to estimate the impact of the policy: (1) cigarette
smoking cessation; (2) people who smoke cigarettes switching to
noncombusted tobacco products rather than quitting tobacco use
entirely; (3) people who continue to smoke cigarettes beginning dual
use of cigarettes and noncombusted tobacco products; (4) people who do
not smoke initiating regular cigarette smoking; and (5) people who do
not smoke who have been dissuaded from smoking cigarettes and certain
other combusted tobacco products, who instead initiate use of a
noncombusted tobacco product. The model, based on input parameters
derived from empirical evidence and expert estimates, projected the
impact of a potential nicotine product standard on four main outcomes:
(1) prevalence of cigarette smoking and noncombusted tobacco use; (2)
tobacco-attributable mortality; (3) life years lost due to tobacco use;
and (4) quality-adjusted life years (QALYs) lost due to cigarette
smoking-attributable morbidity in the U.S. population over time. The
model explores various baseline scenarios via sensitivity analyses,
including with and without projections that incorporate implementations
of other future tobacco product standards (e.g., flavored cigar and
menthol cigarette product standards).
More detailed information regarding modeling study methodology,
including descriptions of the model inputs, data sources, and
assumptions used to derive estimates of the potential impact of a
nicotine product standard on population health can be found in FDA's
modeling document (Ref. 42). Briefly, the simulation began with an
initial population that reflected the sex and age (based on 2021 U.S.
Census Bureau estimates) and cigarette use distribution (i.e., never,
current, former
[[Page 5078]]
use; estimated from the 2020 NHIS data and 2020 NYTS data) in the U.S.
population. Next, we incorporated sex-specific rates for smoking
initiation and cessation for year 2021 modeled using cigarette smoking
histories for birth cohorts reconstructed from NHIS data by Cancer
Intervention and Surveillance Modeling Network (CISNET) researchers
(Ref. 541). Recent analyses using data from the Population Assessment
of Tobacco and Health (PATH) Study (Ref. 542) provide data on
initiation of ENDS from Wave 4 (2016-2017) to Wave 5 (2018-2019);
however, those estimates are related to transitions from never use to
ever use of a specific product at the current wave, rather than
transitions to established use, as defined in the population model. In
the absence of up-to-date estimates of exclusive noncombusted product
initiation rates from the published scientific literature, data
regarding exclusive initiation of noncombusted tobacco products and
dual use were derived by scaling the sex- and age-specific smoking
initiation rates from CISNET using youth (ages 9-17) prevalence
estimates from the 2017-2020 NYTS, and young adult (ages 18-24)
prevalence estimates from the 2020 NHIS (Ref. 542). NYTS prevalence
estimates for noncombusted product use correspond to frequent use,
defined as use at least 20 days in the past 30 days.\30\ Additional
details regarding the estimation of scaling factors to compute
noncombusted product initiation rates can be found in FDA's modeling
document (Ref. 42). CISNET sex- and age-specific cigarette smoking
cessation rates derived from NHIS data were utilized as cessation rates
for all product categories, including noncombusted tobacco use. Age-
specific rates of switching from cigarettes to noncombusted tobacco
products were derived from prior research (Ref. 543). Overall U.S.
death rates from 2019 vital statistics data were used to reflect the
death rates at baseline for individuals under age 35 who never smoked,
since smoking-related mortality is minimal before this age (Ref. 544).
For ages 35 and older at baseline, FDA estimated annual death rates
from 2019 NHIS-LMF data among participants who have never smoked in
NHIS from 1997 through 2018 who were followed for mortality through
linkage with the National Death Index from 2002 through 2019 (Ref.
545). NHIS-LMF never-user death rates are adjusted for low mortality in
the NHIS's civilian noninstitutionalized population, due to the
survey's exclusion of people in institutionalized settings such as
long-term care institutions (e.g., nursing homes, hospitals for the
chronically ill or physically or intellectually disabled, wards for
abused or neglected children), persons in correctional facilities
(e.g., prisons or jails, juvenile detention centers, halfway houses),
and U.S. nationals living in foreign countries. The adjustment was done
by using the ratio of U.S. death rates from the 2019 vital statistics
data to NHIS-LMF death rates by sex and age (Ref. 546). Death rates for
people who have never smoked cigarettes are projected for the period
from 2022 through 2100 using mortality scaling factors obtained from
the Lee-Carter mortality forecasting method (Refs. 547 to 549). To
estimate mortality for e-cigarettes and other noncombusted tobacco
products, we apply the same risks that are used for smokeless tobacco.
Our assumptions about all-cause mortality risk among people who use
smokeless tobacco in the United States were informed by the first
NHANES, Cancer Prevention Study I (CPS-I), and Cancer Prevention Study
II (CPS-II). Mortality probabilities for people who currently use and
formerly used tobacco are obtained by multiplying never-user
probabilities of dying by relative risk according to tobacco use
status.
---------------------------------------------------------------------------
\30\ While past 30-day use is the conventional definition of
current use of a tobacco product in the NYTS, we utilized the
corresponding definition of frequent use (20 or more days of use in
past 30 days) to correspond with initiation of regular use that is
more closely associated with longer-term health outcomes. In this
context, we have scaled the initiation rates to reflect the
initiation of regular, longer-term use. This approach is consistent
with that for adult initiation to regular use and long-term
cessation as defined by CISNET.
---------------------------------------------------------------------------
Quantitative inputs for tobacco use transitions following
implementation of the proposed product standard were obtained through a
formal expert elicitation process that was first conducted in 2015 and
then repeated in 2018. FDA is conducting another expert elicitation to
obtain updated quantitative inputs for tobacco use transitions and
intends to publish the results for public review and comment. For the
2015 and 2018 expert elicitations, the methodology used to identify
experts, develop the protocol, conduct the elicitation, and summarize
the findings can be found in a previous peer-reviewed publication (Ref.
47) and in FDA's modeling document (Ref. 42). Briefly, the initial
elicitation process centered around three online conferencing sessions
held during January and February 2015, following a written protocol
designed to elicit opinions using a structured, standardized approach.
Briefing books with key papers on the topics of interest as well as
background data on tobacco use and policy were provided to a panel of
eight experts prior to the conference sessions. Experts were asked to
identify any other relevant information to share with the panel.
Detailed written questionnaires were completed by each expert as
independent take-home exercises. To maintain the independence of the
experts and encourage open discussion, involvement of FDA staff was
limited. This general process was repeated in 2018 to ensure that
estimates reflected the experts' current assessment of the research
literature and potential effects of a hypothetical product standard.
Seven of the original eight experts agreed to participate in the second
elicitation. Participants received updated briefing materials, and an
online workshop was held in April 2018. The experts, once again,
subsequently completed a detailed questionnaire.
To explore the possible impact of a hypothetical policy reducing
nicotine levels, the experts were asked to assume that combusted
tobacco products that could be viewed as highly likely to serve as
substitutes for traditional cigarettes (i.e., RYO tobacco, pipe
tobacco, non-premium cigars) would be included in the policy, while
other tobacco products (i.e., premium cigars, waterpipe/hookah, e-
cigarettes, smokeless tobacco) would be excluded. While the policy
scenario presented in FDA's modeling document (Ref. 42) is based on a
reduction of the nicotine level in cigarettes, cigarette tobacco, RYO
tobacco, certain cigars and pipe tobacco, the estimated population
impact in the main analysis is solely based on reductions in cigarette
smoking. Cigarettes are the only one of these combusted products to be
incorporated directly in the model, given that cigarette smoking is
responsible for the bulk of morbidity and mortality caused by combusted
tobacco product use. Estimates of mortality benefits due to reductions
in non-premium cigar and pipe tobacco use are derived from model
outputs, as explained below, although these estimates would not include
other population health benefits such as reduced morbidity.
The experts were asked to predict and quantify the anticipated
impact of the policy on the following model parameters: (1) cigarette
smoking cessation rates; (2) switching from cigarette smoking to other
tobacco products excluded from the hypothetical policy scenario (i.e.,
premium cigars, waterpipe/hookah tobacco, smokeless tobacco, e-
cigarettes or other ENDS); (3) dual use rates; (4)
[[Page 5079]]
cigarette smoking initiation rates; and (5) initiation rates for other
tobacco products excluded from the hypothetical policy scenario. Each
of the experts was asked to provide his or her best estimate of the
parameters' true value, estimates of the minimum and maximum plausible
values, and estimates of the 5th, 25th, 75th, and 95th percentile
values. Experts were asked first about impacts in the first year
immediately following the potential product standard's implementation
and then about impacts in the years following the first full year of
implementation. Experts had the option of providing separate estimates
of impacts for males and females for the initial and subsequent years.
For each question, experts were asked to provide the factors they
considered pertinent to answering the question, including the studies
and research findings most influential to informing their views, and to
rate their familiarity with the relevant literature. The elicitation
process provided the experts with opportunities to interact and discuss
divergent views, from which each expert generated their initial and
final estimates. In the updated elicitation, experts were also asked to
assess the potential effects of an alternative product standard that
would only apply to cigarettes, cigarette tobacco, and RYO tobacco,
although they were not required to provide quantitative estimates of
the effects of such a standard.
While parameter estimates and their probability distributions
varied somewhat among participants, most experts had the view that
making cigarettes and certain other combusted tobacco products
minimally addictive would lead to substantial initial and long-term
increases in smoking cessation among people who smoke cigarettes and
decreased initiation among people who do not smoke cigarettes. The
experts' parameter estimates fell within a broad range, although the
updated estimates were often somewhat more consistent and found greater
effects from the potential policy than in the original elicitation. In
general, estimates of the effects of a nicotine product standard on use
behaviors such as smoking cessation, product switching, and smoking
initiation were greater in magnitude in the 2018 expert elicitation
than in the previous 2015 elicitation. For example, the median
estimates of smoking cessation were 36 percent in the first year
following implementation of a nicotine product standard and 34 percent
in subsequent years in the 2018 elicitation, compared to 25 and 22
percent, respectively, in 2015. For product switching (from cigarettes
to noncovered tobacco products), the median estimates were 56 and 58
percent in the first and subsequent years following implementation in
the 2018 expert elicitation and 41 and 40 percent in 2015. Median
estimates of reductions in smoking initiation were 63 and 65 percent in
the first and subsequent years in the 2018 elicitation, and 46 and 49
percent in 2015. Overall, the experts' estimates indicate that the
proposed product standard would introduce substantial changes in
tobacco use behaviors which would result in substantial public health
benefits. Given the inherent uncertainty associated with projecting the
long-term impact of a future regulatory action, FDA conducted a range
of analyses to examine the impact of uncertainty around key model
inputs and assumptions on tobacco use prevalence and premature
mortality. First, in the main analysis, we examined uncertainty in the
behavioral responses to a potential nicotine product standard by
conducting a Monte Carlo simulation (Ref. 550). For the product
standard scenario, a Latin hypercube sampling design with 1,000
simulations was conducted for each set of expert-defined distributions,
resulting in a total of 7,000 simulations (Ref. 551 at p. 524). The
resulting outputs were aggregated to create an overall set of output
distributions, and distribution percentiles were calculated across all
7,000 simulations. For each simulation, the policy scenario was
compared to the baseline scenario to estimate changes in the outcomes.
Key distribution responses in FDA's modeling document highlight the
positive impacts to the public health of the proposed product standard
(Ref. 42). More information on this topic can be found throughout this
document.
In addition, we conducted sensitivity analyses to assess the impact
of specific data input assumptions, including those related to baseline
trends in noncombusted product use, noncombusted product mortality
risk, dual product use mortality risk, and switching to non-covered
combusted products. Specifically, we conducted sensitivity analyses to
examine the impact of increased initiation of noncombusted tobacco
product use among those who would otherwise not have used tobacco; the
impact of an increase in switching from cigarettes to noncombusted
tobacco product use; the impact of a varying mortality risk associated
with dual use of cigarettes and noncombusted tobacco products; the
impact of lower and higher noncombusted tobacco product risk; and the
effects of a nicotine product standard, accounting for the emergence of
an illicit market for normal nicotine content cigarettes. Additional
detailed information concerning these sensitivity analyses can be found
in FDA's modeling document (Ref. 42). Overall, the results from FDA's
population health modeling, even accounting for the impacts of the
factors utilized in FDA's sensitivity analyses, clearly demonstrate the
public health benefit of the proposed product standard.
In 2022, FDA issued proposed product standards to prohibit menthol
as a characterizing flavor in cigarettes (87 FR 26454, May 4, 2022) and
to prohibit all characterizing flavors (other than tobacco) in cigars
(87 FR 26396, May 4, 2022). If finalized, these rules are anticipated
to reduce overall youth initiation and increase cessation among
individuals who smoke cigarettes and non-premium cigars. In sections
VIII.E and VIII.F of this document, we describe how we adjusted our
model by utilizing estimates of the likely population health impact of
these rules, quantified in peer-reviewed publications and discussed in
the proposed rules, to adjust the baseline inputs for initiation of
combusted and noncombusted products, as well as cessation of combusted
products and likelihood of switching to incorporate the impact of the
rules in this proposed nicotine product standard.
B. The Likelihood That Nonusers Would Start Using Cigarettes or Other
Combusted Tobacco Products
Nicotine is an addictive chemical and the primary constituent in
cigarettes and other tobacco products that causes and maintains
addiction. It is a significant contributor to youth and young adult
initiation of smoking cigarettes and other combusted tobacco products.
In section IV.A of this document, we summarize evidence from multiple
study designs, incorporating findings from experimental and laboratory-
based studies, clinical trials, and pre-clinical research that
illustrate the role that nicotine plays in facilitating initiation of
and addiction to cigarettes and other combusted tobacco products. As
discussed in section IV.B of this document, scientific research
demonstrates that adolescence is a period of development when
individuals who experiment with tobacco products are more susceptible
to developing nicotine dependence and progressing to regular use of
such products. Indeed, almost 90 percent of adults who currently and
regularly smoke initiated smoking by age 18, and
[[Page 5080]]
98 percent initiated smoking by age 26, which is notable given that 25
is the approximate age at which the brain has completed development
(Refs. 1 and 17 to 19). The developing brain is more vulnerable to
developing nicotine dependence than the adult brain is, and the earlier
an individual begins smoking the less likely they are to quit (Ref.
20). Compounding this are the findings described in section IV.C of
this document that demonstrate that many youth and adults who smoke
want to quit smoking but have difficulty doing so. Further, the
scientific literature on relapse in those who try to quit confirms the
powerful addictive properties of nicotine in tobacco products, a
principal factor limiting a person who smokes' ability to quit, and
further underscores the public health importance of decreasing the
addictiveness of these products, particularly to reduce susceptibility
to addiction for youth and young adults who experiment with smoking. In
this section, we discuss how, given this scientific evidence, as well
as the findings from our population health model, FDA expects the
proposed nicotine product standard for cigarettes and certain other
combusted tobacco products would decrease experimentation and
progression to regular use of these products among people who currently
do not use these products.
Data from the 2023 NSDUH found that, in the United States,
approximately 452,000 youth (ages 12-17) smoked their first cigarette
and approximately 245,000 youth tried a cigar for the first time during
2023 (Ref. 86 Table A.13A). The 2023 NSDUH also found that
approximately 945,000 young adults (ages 18 to 25) initiated with
cigarettes and 1,065,000 young adults initiated with cigars in 2021
(Ref. 552 see Table 4.7B). Additionally, nearly 90 percent of U.S.
adults who currently smoke cigarettes daily report having smoked their
first cigarette by age 18 (Ref. 1). Given that nicotine is highly
addictive and present in all cigarettes and cigars, as people who
experiment with cigarettes and cigars continue to use these products,
there is a substantial risk of the development of nicotine dependence
and progression to regular use.
Nicotine is a highly addictive substance, and multiple studies have
shown that symptoms of nicotine dependence can arise early after youth
start smoking cigarettes, even among people who infrequently use the
products (Refs. 24, 93, and 553). Although the majority of adolescents
who smoke daily meet the criteria for nicotine dependence, one study
found that the most susceptible youth lose autonomy (i.e., independence
in their actions) regarding tobacco within 1 or 2 days of first
inhaling from a cigarette (Ref. 93). Another study found that 19.4
percent of adolescents (initially aged 12-13 years and followed over 6
years) who smoked weekly were dependent on nicotine (Ref. 95). In a
study regarding nicotine dependence among adolescents who recently
initiated smoking (9th and 10th grade students), adolescents who smoked
cigarettes at the lowest levels (i.e., smoking on only 1 to 3 days of
the past 30 days) experienced nicotine dependence symptoms such as loss
of control over smoking (42 percent) and irritability after not smoking
for a while (23 percent) (Ref. 96). Researchers in a 4-year study of
6th grade students also found that ``[e]ach of the nicotine withdrawal
symptoms appeared in some subjects prior to daily smoking'' (Ref. 93)
(emphasis added). Ten percent of the study participants showed signs of
tobacco dependence within 1 or 2 days of first inhaling from a
cigarette, and half had done so by the time they were smoking seven
cigarettes per month (Ref. 93). Moreover, nicotine can disrupt brain
development and have long-term consequences for executive cognitive
functioning (e.g., decreased attention and working memory and increased
impulsivity) and increases the risk of developing a substance use
disorder and various mental health problems--particularly affective
disorders such as anxiety and depression--as an adult (Refs. 554 to
556). Therefore, progressing to regular use during adolescence can have
lasting consequences and signs of nicotine dependence are evident in
youth who smoke cigarettes. Taken together, this research suggests that
even infrequent experimentation can lead to early signs of dependence,
which underscores the public health importance of decreasing the
likelihood of cigarette experimentation among youth and young adults in
the United States.
If this proposed rule is finalized, cigarettes and the other
combusted tobacco products covered would be rendered minimally
addictive or nonaddictive, thereby breaking the link between
experimentation, nicotine dependence, and progression to regular use.
As a result, FDA expects a significant reduction in youth initiation
and progression to regular cigarette smoking and use of other combusted
tobacco products, which would ultimately protect youth from a lifetime
of addiction, disease, and premature death attributable to combusted
tobacco use. To the extent that youth and young adults in the United
States who would have initiated use of cigarettes and other combusted
tobacco products covered by the scope of this proposed rule do not
initiate with such tobacco products, the proposed standard would
prevent future cigarette- and combusted tobacco product-related disease
and death.
Findings from FDA's population health model, previously described
in section VIII.A of this document and in the docket (Ref. 42),
estimate the likelihood that youth and young adults who do not smoke
would initiate regular cigarette smoking use under the proposed
standard. Table 2 provides an estimated projection of the cumulative
number of youth and young adults who would not initiate regular
cigarette use as a result of implementation of this proposed product
standard over time (Ref. 42 Appendix J for annual estimates). Since a
sustained decrease in smoking initiation rates is expected, the
cumulative number of people dissuaded from initiating smoking would
continue to increase over time. By 2100, we estimate that, as a result
of this proposed nicotine product standard, over 47 million youth and
young adults who would have otherwise initiated smoking would not start
smoking.
Table 2--Projected Cumulative Number of Youth and Young Adults Who Would
Not Initiate Smoking as a Result of a Nicotine Product Standard
Implemented in 2027
[Millions]
------------------------------------------------------------------------
Year Median (5th, 95th percentiles)
------------------------------------------------------------------------
2028........................... 1.3 (0.4, 1.7)
2030........................... 2.6 (0.7, 3.4)
2040........................... 8.6 (2.3, 11.5)
2050........................... 14.8 (4.0, 19.8)
2060........................... 21.1 (5.6, 28.3)
[[Page 5081]]
2070........................... 27.5 (7.3, 37.0)
2080........................... 34.1 (9.1, 45.9)
2090........................... 40.8 (10.8, 54.9)
2100........................... 47.6 (12.6, 64.1)
------------------------------------------------------------------------
For these reasons, FDA expects that establishing a maximum limit of
the nicotine content in cigarettes and certain other combusted tobacco
products, as described in this proposed rule, would reduce the
likelihood that youth and young adults would initiate with and progress
to regular cigarette smoking and use of other combusted tobacco
products, thereby protecting many youth and young adults from a
lifetime of addiction and disease, and premature death, attributable to
the use of combusted tobacco (see section VIII.D of this document for a
discussion of life years gained and other public health benefits as a
result of decreased initiation). Thus, from the expected impact on
people who would not initiate smoking cigarettes, especially youth and
young adults, this proposed product standard is appropriate for the
protection of public health.
C. The Likelihood That Existing Users Would Reduce Cigarette and Other
Combusted Tobacco Product Consumption or Stop Smoking
In addition to the long-term public health benefits that would
accrue from the prevention of cigarette smoking and other combusted
tobacco use among youth and young adults, FDA anticipates that the
proposed standard also would increase the likelihood that many people
who currently smoke cigarettes and certain other combusted tobacco
products would stop smoking altogether, yielding health benefits from
smoking cessation. FDA expects that the proposed standard would result
in substantial changes in tobacco use patterns among people who
currently use tobacco. Given that tobacco products are addictive
primarily due to the presence of nicotine, FDA expects that the
proposed standard would lead many people who currently smoke cigarettes
and certain other combusted tobacco products to: (1) quit using these
tobacco products altogether, (2) transition to dual use of cigarettes
or other combusted tobacco products with other potentially less harmful
tobacco products, or (3) transition completely to use of other
potentially less harmful tobacco products.
As discussed in section IV of this document, the scientific
evidence is clear that nicotine is an addictive chemical and is the
primary constituent that causes and maintains addiction to cigarettes
and other combusted tobacco products. The U.S. Surgeon General has
concluded that there is a causal relationship between smoking and
addiction to nicotine (Ref. 1), and the earlier that individuals begin
smoking, the less likely they are to successfully quit (Ref. 27). FDA
expects that, if this proposed rule is finalized, many people who smoke
cigarettes will either quit smoking entirely, switch to a noncombusted
tobacco product entirely, or transition to dual use. As discussed
previously, those who switch completely to a noncombusted product may
sustain their nicotine dependence but would significantly reduce their
risk of tobacco-related death and disease to the extent that the
products they switch to result in less harm. That is, while dependence
on any tobacco product remains a health concern, the vast majority of
tobacco-related cancer, lung disease, and heart disease is due to
exposure to constituents of tobacco smoke (Ref. 323). Switching
completely to a noncombusted tobacco product would reduce exposure to
the chemical constituents created through combustion (Ref. 8).
There are multiple sources of evidence to inform FDA's analysis of
how the proposed standard would affect the likelihood that people who
smoke would reduce cigarette and combusted tobacco product consumption
or stop smoking altogether. Findings from clinical studies offer
insight into tobacco product switching, as well as cigarette smoking
cessation behaviors occurring following the implementation of the
proposed product standard. As described previously in section VI.B of
this document, a clinical trial intended to assess the use of
noncombusted and non-cigarette combusted tobacco products among
participants randomized to receive LNC and NNC cigarettes found that
participants who received LNC cigarettes used alternative combusted and
noncombusted tobacco products on a statistically significantly higher
percentage of days compared to those who received NNC cigarettes (Ref.
5). Another analysis of switching behavior in the context of a clinical
study examined the influence of LNC cigarette use on alternative
tobacco product use in participants who did not smoke cigarettes daily.
Among participants who did not use e-cigarettes at baseline, new use of
e-cigarettes was statistically significantly more prevalent in the LNC
cigarette group compared to the NNC cigarette group (Ref. 377). Both
findings suggest that people who smoke cigarettes, and do not quit
tobacco use altogether, are likely to seek alternative sources of
nicotine once a nicotine product standard for combusted tobacco
products is in place.
As discussed in section VII.B.2 of this document, numerous studies
have investigated the effects of VLNC or LNC cigarettes--alone or in
combination with NRT products--on smoking cessation among people who
smoke cigarettes and are interested in quitting (Refs. 32, 35, 41, 369
to 373), as well as among samples of people who smoke cigarettes and
are not interested in quitting (Refs. 31, 40, 258, and 374). Taken
together, results from these studies demonstrate that people who smoke
cigarettes and are interested in quitting who are given VLNC cigarettes
are more likely to achieve initial smoking abstinence compared to those
who continue to smoke their usual brand or NNC cigarettes. In addition,
provision of NRT and/or behavioral intervention with VLNC cigarettes
can further increase smoking cessation among individuals interested in
quitting (Ref. 19).
Estimates from FDA's population health model--described in section
VIII.A of this document--indicate that in the first year following the
implementation of the proposed standard in 2027, smoking prevalence
would decline from 9.1 percent in the baseline scenario to a median of
4.5 percent in the product standard scenario, due to the large increase
in
[[Page 5082]]
smoking cessation in the first year after implementation. In subsequent
years, the difference in smoking prevalence between the scenarios would
continue to grow due to sustained increases in cessation and decreases
in initiation relative to baseline. The projected smoking prevalence
drops to 0.2 percent under the product standard scenario by 2050,
compared to 5.3 percent under baseline. By 2100, smoking prevalence is
estimated at 0.2 percent in the product standard scenario, compared to
4.6 percent under baseline. Estimates of the projected cumulative
number of people who quit smoking are depicted in table 3. Within the
first year of the proposed standard implementation, 12.9 million
additional people who smoke cigarettes are estimated to either quit
tobacco altogether or switch from cigarette smoking to using
noncombusted tobacco products, signifying a considerable gain over the
estimated 1.6 million people who smoke that would have quit under the
baseline scenario. The mortality risk of switching is greater than
quitting all tobacco products, therefore the public health model
assumes the risk for people who switch to noncombusted products as 8
percent higher than the risk for those who quit tobacco use entirely
based on evidence in the literature (Ref. 557), see section VIII.D of
this document for a more detailed discussion. The number of additional
people who quit smoking would increase to approximately 19.5 million
within 5 years after the implementation of the proposed standard,
representing a gain of more than the 7.3 million people who quit
smoking than would be anticipated under the baseline scenario. The
median estimates grow closer to the 95th percentile estimates than to
the 5th percentile estimates over time. A closer analysis of this
pattern indicates that the 5th percentile estimates are affected by
lower estimates given by two experts in the expert elicitation. Those
estimates indicate that a lower percentage of people who currently use
cigarettes will quit smoking cigarettes, following a nicotine product
standard's implementation.
Table 3--Cumulative Net People Who Quit Smoking \1\ (Millions) as a
Result of a Nicotine Product Standard Implemented in 2027
------------------------------------------------------------------------
Period Median (5th, 95th percentiles)
------------------------------------------------------------------------
Within 1st year (2027)......... 12.9 (0.8, 24.8)
Within 2 years (2027-2028)..... 17.5 (1.2, 24.1)
Within 3 years (2027-2029)..... 19.3 (1.6, 23.2)
Within 4 years (2027-2030)..... 19.8 (1.8, 22.3)
Within 5 years (2027-2031)..... \2\ 19.5 (2.0, 21.4)
------------------------------------------------------------------------
\1\ Net people who quit smoking cigarettes (including those who switch
to noncombusted tobacco products), defined as people who quit smoking
cigarettes in addition to baseline, is computed as: (number of people
who quit smoking cigarettes under the nicotine product standard
scenario) - (number of people who quit smoking cigarettes under
baseline scenario).
\2\ Cumulative net people who quit smoking declines slightly in year 5
of the simulation because there are more people who quit smoking
cigarettes in the baseline scenario compared with the product standard
scenario. Since there are millions of fewer people smoking cigarettes
in the product standard scenario as the years continue, eventually
there are fewer people available to quit smoking cigarettes compared
to baseline.
We also examined the potential for an illicit market for NNC
cigarettes to develop in response to the proposed product standard (see
section IX.D of this document for a discussion on illicit trade). In
order to examine the potential impact of such an illicit market,
sensitivity analyses were conducted for the effects of diversion from
cessation to illicit trade, and initiation into illicit products, on
the estimated benefits of a nicotine product standard. These analyses
demonstrate that increasing the assumed proportion of people who smoke
who may divert to the use of illicit NNC cigarettes (for purposes of
illustration, we use a low-end estimate (3.8 percent), a midpoint
estimate (5.9 percent), and a high-end estimate (21.0 percent)),\31\
and allowing youth and young adults (who would have otherwise initiated
NNC cigarette use) to initiate into illicit NNC cigarette use (0
percent, 2.6 percent, and 10 percent) \32\ under the proposed nicotine
standard, resulted in reductions in the projected cumulative net people
who quit smoking following the implementation of the nicotine product
standard policy (table 4). However, even in the case of significant
diversion to illicit NNC cigarettes, the number of people projected to
quit smoking remains substantial.
---------------------------------------------------------------------------
\31\ We use 3.8 percent as a low-end estimate based on 2017
estimates of illicit trade volume in cigarettes from (Ref. 558).
This estimate excludes interstate smuggling for purposes of tax
avoidance. For a midpoint estimate, using findings from the
International Tobacco Control United States Survey (Ref. 559), we
estimate that 5.9 percent of U.S. people who use cigarettes last
purchased cigarettes from low-tax locations. We use these figures as
proxies for the proportions of people who use cigarettes who may
actively seek out illicit NNC cigarettes under a nicotine product
standard, although we note that the product standard would be
implemented nationwide, avoiding disparate pricing/availability
between states. We use 21.0 percent as a high-end estimate based on
the difference in non-compliance rates between reduced nicotine
intervention groups (78 percent) and control groups assigned to NNC
cigarettes (57 percent) in clinical trial data from (Ref. 29, Ref.
330). This estimate of 21.0 percent also represents the high-end of
the range estimated in (Ref. 560), which reflected the methodology
of the pack return survey by (Ref. 561). While FDA uses this 21.0
percent high-end estimate for the purpose of analyzing potential
impacts, we note that it represents a highly unlikely upper bound,
because for such a substantial percentage of people who use
cigarettes to acquire NNC cigarettes, convenient and consistent
access to an illicit market would be needed, which is highly
unlikely. We also note that basing a high-end estimate on non-
compliance rates found in studies (where NNC cigarettes are legally
available outside the confines of the study environment) is not
equivalent to real-world conditions where NNC cigarettes would not
be legally available in the U.S. marketplace.
\32\ We use findings from an expert elicitation developed to
gauge the impact of a menthol cigarette and cigar prohibition in the
United States (Ref. 562), which indicates that among people ages 12-
24 who would have otherwise initiated menthol cigarette use, 2.6
percent would initiate illicit menthol cigarette use (estimate
ranged from 0 percent to 10 percent).
[[Page 5083]]
Table 4--Cumulative Net People Who Quit Smoking Combusted Cigarettes (Millions) as a Result of a Nicotine
Product Standard Implemented in 2027 Under Illicit Trade Scenarios. Median (5th, 95th Percentiles) Estimates
----------------------------------------------------------------------------------------------------------------
Illicit trade impact scenarios
---------------------------------------------------------------------------
Period Main scenario (no
impact) Low Impact \1\ Medium Impact \2\ High Impact \3\
----------------------------------------------------------------------------------------------------------------
Within 1st year (2027).............. 12.9 (0.8, 24.8) 12.4 (0.7, 24.6) 12.1 (0.7, 24.4) 9.9 (0.3, 22.6)
Within 5th year (2027-2031)......... 19.5 (2.0, 21.4) 19.3 (1.7, 21.3) 19.2 (1.5, 21.4) 18.1 (0.3, 21.4)
----------------------------------------------------------------------------------------------------------------
\1\ Low Impact: 3.8 percent people who smoke would divert to use illicit NNC cigarettes, and 0 percent youth and
young adults would initiate illicit NNC cigarettes.
\2\ Medium Impact: 5.9 percent people who smoke would divert to use illicit NNC cigarettes, and 2.6 percent
youth and young adults would initiate illicit NNC cigarettes.
\3\ High Impact: 21.0 percent people who smoke would divert to use illicit NNC cigarettes, and 10.0 percent
youth and young adults would initiate illicit NNC cigarettes.
The sum of the available evidence--including the current use of
cigarettes by millions of Americans, findings from studies assessing
the effects of VLNC or LNC cigarettes on smoking cessation, and
findings from FDA's population health model--supports FDA's finding
that the proposed product standard would increase the likelihood that
many people who smoke cigarettes and/or other combusted tobacco
products would stop smoking altogether, yielding significant health
benefits from smoking cessation. Additionally, we find that the
proposed standard is appropriate for the protection of the public
health because it would decrease the likelihood that people who do not
smoke cigarettes and/or use certain other combusted tobacco products--
particularly youth and young adults--who experiment with combusted
tobacco products will become addicted to these products, thereby
decreasing progression to regular use, resulting in reduced tobacco-
related morbidity and mortality associated with combusted tobacco
product use. As of 2021, more than 48 million people in the United
States ages 12 and older used tobacco products within the past 30 days
(Refs. 25 and 274). Further, in 2021, 35.6 million U.S. adults (14.5
percent) and nearly 1 million middle and high school students (3.2
percent) used any combustible tobacco product (Ref. 274). Thus, even
small changes in initiation and cessation would result in a significant
reduction in the burden of death and disease caused by smoking.
D. Benefits and Risks to the Population as a Whole
We expect that the proposed nicotine product standard, if
finalized, would reduce tobacco-related harms. As discussed in section
IV of this document, nicotine is the primary constituent in cigarettes
and other tobacco products that causes and maintains addiction. By
enacting a product standard that would seek to limit the nicotine
content in cigarettes and certain other combusted tobacco products to
minimally addictive or nonaddictive levels, FDA anticipates that
reductions in population harm would be realized through long-term
health benefits resulting from prevention of cigarette uptake and
progression to regular cigarette smoking among young people, as well as
shorter-term health benefits resulting from increased cessation of
cigarette smoking among people who currently smoke. Each of these
impacts alone would result in significant health benefits to the U.S.
population. In totality, they provide overwhelming evidence that the
proposed standard would result in substantial health benefits over both
the short- and long-term. In this section, we summarize the health
benefits of never progressing to regular cigarette smoking and
combusted tobacco product use, the health benefits of quitting smoking,
the population health benefits of switching from cigarettes to
potentially less harmful tobacco products, and the health benefits of
not being exposed to secondhand smoke. We also describe additional
public health benefits of the proposed standard not addressed in FDA's
population health model. Finally, we describe potential risks or
limiting effects of the product standard, including risks of
compensatory smoking. Based on the available evidence, FDA concludes
that any such potential risks or limiting effects would be
significantly outweighed by the anticipated substantial benefits of
this proposed nicotine product standard.
1. Given the Harmful Effects of Cigarette Smoking and Combusted Tobacco
Use, Never Progressing to Regular Smoking Prevents Death and Disease
and Improves Quality of Life
Never progressing to regular cigarette smoking prevents death and
disease caused by smoking. Any effects of a nicotine product standard
in cigarettes and certain other combusted tobacco products on
preventing youth, young adult, and even adults who have never smoked
from initiating/experimenting and progressing to regular cigarette
smoking will have a population health benefit. Youth and young adults
would experience the greatest benefits from a nicotine product
standard, because it is likely that most of them would not progress
beyond experimentation or occasional use and, therefore, may not
experience the dangerous and deadly tobacco-related health effects
associated with combusted tobacco product use. Fetuses and children
also would benefit if their parents quit smoking or using most
combusted tobacco products, given the negative health consequences to
the fetus of a smoking mother and the dangers of secondhand smoke (Ref.
19). Children of parents who smoke, when compared with children whose
parents do not smoke, have an increased frequency of respiratory
infections like pneumonia and bronchitis (Ref. 563). Smoking cessation
reduces the rates of these respiratory symptoms and of respiratory
infections among children (Ref. 63 at p. 467). Children exposed to
tobacco smoke in the home also are more likely to develop acute otitis
media (middle ear infections) and persistent middle ear effusions
(thick or sticky fluid behind the eardrum) (Ref. 563). If parents were
more readily able to quit because these products were minimally
addictive or nonaddictive, the incidence of these health problems among
youth would be expected to decline. Additionally, such health problems
would not occur in future years, as fewer individuals would initiate
and progress to regular smoking.
According to the 2014 Surgeon General's Report, which summarizes
thousands of peer-reviewed scientific studies and is itself peer-
reviewed, smoking remains the leading preventable cause of disease and
death
[[Page 5084]]
in the United States, and cigarettes have been shown to cause an ever-
expanding number of diseases and health conditions (Ref. 1). As stated
in the report, ``cigarette smoking has been causally linked to disease
of nearly all organs of the body, to diminished health status, and to
harm to the fetus'' and ``[t]he burden of death and disease from
tobacco use in the United States is overwhelmingly caused by cigarettes
and other combusted tobacco products'' (Ref. 1). The 2014 Surgeon
General's Report estimates that 16 million people live with diseases
caused by smoking cigarettes (Ref. 1). Additionally, the burden of
tobacco-related addiction and disease disproportionately impacts
certain populations, such as individuals experiencing poverty, those of
lower educational attainment, in historically marginalized racial and
ethnic groups, in the LGBTQI+ community, people living with a mental
health condition, in the military, and in certain geographic areas
(Ref. 120). In particular, Black individuals experience the highest
rates of incidence and mortality from tobacco-related cancers compared
to people from other racial and ethnic groups (Refs. 102 and 103).
Additionally, mortality related to other tobacco-related diseases such
as heart disease, stroke, and hypertension is higher among Black
individuals than other racial and ethnic groups (Refs. 105, 106, 108 to
110, and 123).
Moreover, when comparing mortality to morbidity, for every person
who dies from smoking, 30 more are living with a smoking-attributable
disease (Ref. 1). Smoking is causally associated with a number of
diseases affecting nearly all organs in the body, such as numerous
types of cancer, heart disease, stroke, lung diseases such as COPD, and
diabetes, in addition to putting individuals at increased risk for
tuberculosis, certain eye diseases, and immune system issues (Ref. 1).
One study estimated that individuals in the United States have had 14.0
million major smoking-attributable medical conditions, including more
than 7.4 million cases of COPD, nearly 2.3 million heart attacks, 1.8
million cases of diabetes, nearly 1.2 million stroke events, more than
300,000 cases of lung cancer, and nearly 1 million cases of other
smoking-attributable cancers (bladder, cervix, colon/rectum, kidney,
larynx, mouth, tongue, lip, throat, pharynx, stomach) (Ref. 564).
Therefore, increased smoking cessation, reduced cigarette consumption,
and lower progression to regular use would reduce not only the
mortality from smoking, but also the enormous burden of cigarette-
attributable disease in the United States.
In addition to the years of life gained due to reduced premature
mortality from tobacco, the substantial reductions in smoking
initiation and increases in smoking cessation will result in
improvements in quality of life for those who quit or do not initiate
smoking because of the product standard. To estimate the potential
impact of the proposed standard on morbidity and mortality, we used
estimates from FDA's population health model, which is described in
section VIII.A of this document. Table 5 presents cumulative estimates
of mortality and morbidity avoided as a result of the proposed nicotine
product standard, for certain years in the simulation period (Ref. 42
at Appendix J). By 2060, we estimate that approximately 1.8 million
deaths due to tobacco would be avoided, rising to 4.3 million by the
end of the century. The reduction in premature deaths attributable to
the proposed product standard would result in 19.6 million life years
gained by 2060 and 76.4 million life years gained by 2100. Based on
previously reported quality of life scores derived for people who do
and do not smoke, stratified by age group (Ref. 565), we estimate that
the proposed nicotine product standard would result in 24.0 million
QALYs gained by 2060 due to reduced smoking morbidity. By 2100, this
estimate is projected to increase to 53.1 million QALYs gained due to
reduced smoking morbidity (Ref. 42 at Section 2.3).
Table 5--Projected Number of Tobacco-Attributable Deaths Avoided, Life Years Gained, and QALYs Gained Due to
Reduced Smoking as a Result of a Nicotine Product Standard Implemented in 2027
----------------------------------------------------------------------------------------------------------------
Cumulative Cumulative QALYs
tobacco- Cumulative life gained due to
Year Scenario attributable years gained reduced smoking
deaths avoided (millions) morbidity
(millions) (millions)
----------------------------------------------------------------------------------------------------------------
2040................................ Median (5th, 0.4 (0.1, 0.5) 2.0 (0.2, 2.7) 9.6 (2.7, 10.0)
95th)
2060................................ Median (5th, 1.8 (0.4, 2.0) 19.6 (3.6, 22.7) 24.0 (10.1, 24.7)
95th)
2080................................ Median (5th, 3.1 (1.0, 3.4) 47.4 (12.5, 52.5) 38.2 (18.5, 39.2)
95th)
2100................................ Median (5th, 4.3 (1.6, 4.6) 76.4 (26.5, 82.5) 53.1 (27.5, 54.4)
95th)
----------------------------------------------------------------------------------------------------------------
In addition to the main analyses concerning projected death and
disability, we examined the sensitivity of modeled results to
underlying assumptions related to baseline product use projections and
mortality risk estimates. Sensitivity analyses accounted for the
following: an increase in noncombusted product initiation; different
assumptions of people who smoke switching to noncombusted products per
year; decrease in smoking initiation; lower and higher noncombusted
product mortality risk compared to baseline; different assumptions for
dual product use mortality risk; changes in baseline mortality rate
projections; and the potential impact of a substantial illicit market
for NNC cigarettes. Changes to baseline inputs of noncombusted product
use trajectories and health risks had minimal impact on smoking
prevalence and attributable morbidity and mortality, and the nicotine
product standard still resulted in substantial public health benefits.
Assuming increasing initiation rates for noncombusted product use until
year 2030 implies that the number of people who use tobacco will be
higher under the baseline and nicotine product standard scenarios, with
a higher proportion being people who use noncombusted tobacco products.
In terms of mortality risk, we applied a relative risk of 1.18 for
people who use noncombusted tobacco products as compared with people
who have never smoked (i.e., the risk of death associated with
noncombusted tobacco use is assumed to be 1.18 times greater than the
risk of death associated with never smoking). For combusted cigarette
smoking, the relative mortality risk varies with age, but is generally
around 2.5, as compared to people who have never smoked (i.e., the risk
of death associated with smoking is estimated to be 2.5 times greater
than the risk of
[[Page 5085]]
death associated with never smoking). Mortality risk for people who
have never used tobacco is 1, so the excess mortality risk of using a
product beyond that of those who have never used tobacco, and therefore
related to the product used, can be calculated by subtracting 1 from
the mortality risk (i.e., excess mortality risk for noncombusted
tobacco use is 1.18-1 = 0.18, and for combusted cigarette use it is
2.5-1=1.5). Thus, in our main modeling projections, we apply an excess
risk of using noncombusted tobacco products that is 12 percent that of
the excess risk associated with cigarette smoking (i.e., 100 x (0.18/
1.5) = 12 percent).
Table 6--Impact of Varying Baseline Assumptions on Projected Smoking Prevalence and Avoided Mortality and
Morbidity by 2100. Median (5th, 95th Percentiles) Estimates
----------------------------------------------------------------------------------------------------------------
Projections through year 2100
---------------------------------------------------------------------------
Cumulative Cumulative QALYs
Scenario tobacco- Cumulative life gained from
Cigarette smoking attributable years gained reduced smoking
prevalence (%) mortality avoided (millions) morbidity
(millions) (millions)
----------------------------------------------------------------------------------------------------------------
Main scenario....................... 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 76.4 (26.5, 82.5) 53.1 (27.5, 54.4)
----------------------------------------------------------------------------------------------------------------
Baseline noncombusted tobacco product trajectory
----------------------------------------------------------------------------------------------------------------
Increased noncombusted initiation... 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 76.5 (26.7, 82.5) 53.1 (27.5, 54.4)
50% increased complete switching.... 0.13 (0.06, 1.7) 4.2 (1.7, 4.5) 74.9 (28.6, 80.7) 51.9 (29.0, 52.9)
100% increased complete switching... 0.12 (0.06, 1.5) 4.2 (1.8, 4.4) 73.6 (30.3, 79.0) 50.8 (30.2, 51.6)
----------------------------------------------------------------------------------------------------------------
Baseline smoking initiation trajectory
----------------------------------------------------------------------------------------------------------------
25% decrease in smoking initiation 0.13 (0.1, 1.6) 4.1 (1.5, 4.4) 72.9 (24.3, 79.0) 45.2 (22.9, 46.4)
during the period 2021-2030........
----------------------------------------------------------------------------------------------------------------
Baseline smoking cessation
----------------------------------------------------------------------------------------------------------------
10% increase in smoking cessation... 0.15 (0.1, 1.8) 4.0 (1.5, 4.3) 70.9 (24.9, 76.4) 50.1 (26.3, 51.2)
----------------------------------------------------------------------------------------------------------------
Baseline noncombusted mortality relative risk (RR)
----------------------------------------------------------------------------------------------------------------
Higher RR than main scenario (RR = 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 75.0 (26.0, 81.4) 53.1 (27.5, 54.4)
1.3)...............................
Lower RR than main scenario (RR = 0.2 (0.1, 1.9) 4.4 (1.6, 4.7) 77.2 (26.9, 83.2) 53.1 (27.5, 54.4)
1.1)...............................
----------------------------------------------------------------------------------------------------------------
Baseline dual use RR
----------------------------------------------------------------------------------------------------------------
Dual use RR is 18% greater than for 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 75.9 (25.0, 82.4) 53.1 (27.5, 54.4)
cigarette smoking..................
Dual use RR is the average of 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 77.0 (28.6, 82.6) 53.1 (27.5, 54.4)
cigarette and noncombusted use RR..
Dual use RR is equal to the 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 77.6 (30.7, 82.7) 53.1 (27.5, 54.4)
noncombusted use RR................
----------------------------------------------------------------------------------------------------------------
Baseline mortality rate projections
----------------------------------------------------------------------------------------------------------------
Keep mortality rates constant 0.2 (0.1, 2.0) 4.7 (1.9, 5.1) 77.9 (28.2, 83.9) 53.0 (27.4, 54.2)
starting at 2060...................
----------------------------------------------------------------------------------------------------------------
As shown in table 6, varying baseline input parameter values had
very small effects on estimates of the potential population health
effects of a nicotine product standard. Assuming a 25 percent decrease
in cigarette smoking initiation during the period from 2021 to 2030
resulted in modest decreases in smoking prevalence and health benefits,
in particular reductions in morbidity due to smoking, by 2100 in the
policy scenario compared to the main analysis. Increases in baseline
complete switching to noncombusted tobacco product use resulted in
similar small decreases in smoking prevalence and health benefits in
terms of life years gained and reduced smoking morbidity by 2100
compared to the main analysis. Different assumptions about baseline
relative risks also produced modest changes in differences in life
years gained. Additional details regarding the sensitivity analyses can
be found in FDA's modeling document (Ref. 42).
Sensitivity analyses were also conducted examining assumptions
about the potential effect of the nicotine product standard on smoking
cessation. In addition to the modeling results obtained through expert-
derived inputs, we also generated projections based on results from
clinical studies of VLNC cigarette use and cessation. Based on these
studies, we applied a two-fold increase in cessation (estimates ranged
from 6.4 percent to 19.8 percent), as compared to the baseline
cessation rate (estimates ranged from 3.2 percent to 9.9 percent), as
an alternative estimate of the long-term impact of the proposed product
standard on cessation, while maintaining the median of the expert-
derived values for the other parameters (Ref. 42 at Section 2.3). Given
the wide variation in the expert-derived cessation rates, the projected
health impacts assuming a two-fold increase in cessation fell within
the range of results obtained from expert-derived inputs (see table 6).
Additionally, increasing the assumed proportion of people who smoke
who may divert to the use of illicit NNC cigarettes (3.8 percent, 5.9
percent, and 21.0 percent),\33\ and allowing youth and
[[Page 5086]]
young adults (who would have otherwise initiated NNC cigarette use) to
initiate into illicit NNC cigarette use (0 percent, 2.6 percent, and 10
percent) \34\ under the proposed nicotine standard resulted in
reductions in the projected cumulative attributable morbidity and
mortality outcomes following the implementation of the policy (table
7). It is noteworthy that significant benefits in terms of reduced
morbidity and mortality are realized as a result of this product
standard, even in a scenario in which greater proportions of the
population who smoke are assumed to divert to use of illicit NNC
cigarettes.
---------------------------------------------------------------------------
\33\ We use 3.8 percent as a low-end estimate based on 2017
estimates of illicit trade volume in cigarettes from Euromonitor
International (Ref. 558). This estimate excludes interstate
smuggling for purposes of tax avoidance. Using findings from the
International Tobacco Control United States Survey, we estimate that
5.9 percent of U.S. people who use cigarettes last purchased
cigarettes from low-tax locations (Ref. 559). We use these figures
as proxies for the proportions of people who use cigarettes who may
actively seek out illicit NNC cigarettes under a nicotine product
standard, although we note that the product standard would be
implemented nationwide, avoiding disparate pricing/availability
between states. We use 21 percent as a high-end estimate based on
the difference in non-compliance rates between reduced nicotine
intervention groups (78 percent) and control groups assigned to NNC
cigarettes (57 percent) in clinical trial data (Refs. 29 and 330).
This estimate of 21 percent also represents the high-end of the
range estimated by the National Research Council, which reflected
the methodology of the pack return survey by Fix, et al. (Refs. 560
and 561).
\34\ We use findings from an expert elicitation developed to
gauge the impact of a menthol cigarette and cigar prohibition in the
United States, which indicates that among people ages 12-24 who
would have otherwise initiated menthol cigarette use, 2.6 percent
would initiate illicit menthol cigarette use (estimate ranged from 0
percent to 10 percent) (Ref. 562).
Table 7--Projected Health Benefits as a Result of a Nicotine Product Standard Implemented in 2027 Under Illicit
Trade Scenarios
[Median (5th, 95th percentiles) estimates]
----------------------------------------------------------------------------------------------------------------
Illicit trade impact scenarios
---------------------------------------------------------------------------
Year Main scenario (no
impact) Low impact \1\ Medium impact \2\ High impact \3\
----------------------------------------------------------------------------------------------------------------
Tobacco-Attributable Deaths Avoided (Millions)
----------------------------------------------------------------------------------------------------------------
2040................................ 0.4 (0.1, 0.5) 0.4 (0.04, 0.5) 0.4 (0.04, 0.5) 0.4 (0.01, 0.5)
2060................................ 1.8 (0.4, 2.0) 1.8 (0.4, 2.0) 1.8 (0.3, 2.0) 1.7 (0.1, 2.0)
2080................................ 3.1 (1.0, 3.4) 3.1 (0.8, 3.4) 3.1 (0.8, 3.4) 3.0 (0.4, 3.3)
2100................................ 4.3 (1.6, 4.6) 4.3 (1.5, 4.6) 4.3 (1.4, 4.6) 4.2 (0.9, 4.5)
----------------------------------------------------------------------------------------------------------------
Cumulative Life Years Gained (Millions)
----------------------------------------------------------------------------------------------------------------
2040................................ 2.0 (0.2, 2.7) 2.0 (0.1, 2.7) 2.0 (0.1, 2.7) 1.8 (0.01, 2.6)
2060................................ 19.6 (3.6, 22.7) 19.4 (3.2, 22.6) 19.3 (3.0, 22.6) 18.4 (1.2, 22.0)
2080................................ 47.4 (12.5, 52.5) 47.1 (11.4, 52.4) 46.9 (10.7, 52.3) 45.3 (5.3, 51.5)
2100................................ 76.4 (26.5, 82.5) 76.0 (24.6, 82.3) 75.8 (23.4, 82.2) 73.9 (13.7, 81.3)
----------------------------------------------------------------------------------------------------------------
Cumulative QALYs Gained from Reduced Smoking Morbidity (Millions)
----------------------------------------------------------------------------------------------------------------
2040................................ 9.6 (2.7, 10.0) 9.6 (2.5, 10.0) 9.5 (2.4, 10.0) 9.2 (1.5, 9.9)
2060................................ 24.0 (10.1, 24.7) 24.0 (9.6, 24.7) 23.9 (9.2, 24.7) 23.4 (6.5, 24.6)
2080................................ 38.2 (18.5, 39.2) 38.2 (17.7, 39.2) 38.0 (17.0, 39.2) 37.3 (12.6, 39.0)
2100................................ 53.1 (27.5, 54.4) 53.0 (26.6, 54.4) 52.8 (25.5, 54.3) 51.9 (19.3, 54.1)
----------------------------------------------------------------------------------------------------------------
\1\ Low Impact: 3.8 percent people who smoke would divert to use illicit NNC cigarettes, and 0 percent youth and
young adults would initiate illicit NNC cigarettes.
\2\ Medium Impact: 5.9 percent people who smoke would divert to use illicit NNC cigarettes, and 2.6 percent
youth and young adults would initiate illicit NNC cigarettes.
\3\ High Impact: 21.0 percent people who smoke would divert to use illicit NNC cigarettes, and 10.0 percent
youth and young adults would initiate illicit NNC cigarettes.
As previously discussed, nicotine is the primary driver of
addiction in tobacco products and facilitates progression to regular
cigarette smoking and other regular combusted tobacco product use. FDA
anticipates that establishing a maximum level of nicotine in cigarettes
and certain other combusted tobacco products will prevent a substantial
number of youth and young adults who experiment with combusted tobacco
products from developing an addiction to these products, thereby
decreasing progression to regular use, resulting in reduced tobacco-
related morbidity and mortality associated with combusted tobacco
product use.
2. Given the Harmful Effects of Cigarette Smoking and Other Combusted
Tobacco Product Use, Quitting Smoking Reduces Death and Disease
Although the health benefits are greater for people who stop
smoking at earlier ages (Refs. 63 and 563), researchers estimate that
people who regularly smoke can gain years of additional life expectancy
no matter when they quit (Ref. 566). Quitting cigarette smoking and use
of other combusted tobacco products substantially reduces the
likelihood of tobacco-related death and disease. As stated in the 2004
Surgeon General's Report, ``[q]uitting smoking has immediate as well as
long-term benefits, reducing risks for diseases caused by smoking and
improving health in general'' (Ref. 63). The 2020 Surgeon General's
Report also concluded that ``[s]moking cessation is beneficial at any
age. Smoking cessation improves health status and enhances quality of
life.'' (Ref. 19). As previously noted, FDA expects that, if this
proposed rule is finalized, there will be a significant increase in
smoking cessation in the U.S. population (see section VIII.C of this
document).
The benefits associated with smoking cessation happen quickly (Ref.
63). Within 2 to 12 weeks of quitting smoking, an individual's lung
function and blood circulation improve (Ref. 63). During the first 1 to
9 months following cessation, coughing and shortness of breath decrease
(Ref. 63). Within several
[[Page 5087]]
months of quitting smoking, individuals can expect further improvement
in lung function (Ref. 63). Additionally, the benefits of cessation
continue for those who remain smoke-free. Smoking cessation reduces the
risk of cancers and other diseases (Ref. 19). For example, the risk of
fatal lung cancer in adults over age 55 is about 25 times higher among
people who smoke cigarettes relative to people who have never smoked
(Ref. 567). After 10-15 years of abstinence from smoking, the risk of
lung cancer is about 50 percent of the risk for individuals who
continue to smoke (Ref. 19). The risk of cancer of the mouth, throat,
esophagus, stomach, bladder, cervix, pancreas, liver, kidney, colon,
and rectum, and the risk of acute myeloid leukemia also decreases
(Refs. 19 and 568). The evidence is also sufficient to infer that the
risk of stroke decreases after smoking cessation and approaches that of
people who have never smoked cigarettes over time (Ref. 569).
Furthermore, the evidence is sufficient to infer that the relative risk
of coronary heart disease among people who formerly smoked cigarettes
falls rapidly after cessation and then declines more slowly (Ref. 19).
In addition, smoking cessation substantially reduces the risk of
other dangerous diseases that can lead to death or disability and cause
a financial strain on healthcare resources. For example, quitting
smoking substantially reduces the risk of peripheral artery occlusive
disease (which can cause complications that lead to loss of limbs)
(Ref. 563). It also reduces the relative risk of coronary heart disease
and stroke morbidity and mortality among people who formerly smoked
compared with people who have never smoked (Ref. 19). People who
formerly smoked cigarettes also have half the excess risk of
experiencing an abdominal aortic aneurysm compared to people who
currently smoke cigarettes (Ref. 563). Furthermore, cigarette smoking
complicates many diseases (e.g., people who smoke and have diabetes
have higher risk of complications, including heart and kidney disease,
poor blood flow in the legs and feet, retinopathy, and peripheral
neuropathy), and smoking cessation can alleviate those complications as
well (Ref. 28).
Even people who smoke and quit smoking after the onset of a life-
threatening disease experience significant health benefits from
cessation. Quitting smoking after a diagnosis reduces the chance of
recurrences and future health problems. For example, people who quit
smoking after having a heart attack can reduce their chances of having
a second heart attack by 50 percent (Ref. 568). For those persons who
have already developed cancer, quitting smoking reduces the risk of
developing a second cancer (Refs 563, 570 to 572). Additionally,
quitting smoking after a diagnosis of lung cancer reduces the risk of
cancer progression and mortality (Ref. 573). Researchers also estimate
that for people who currently smoke and have been diagnosed with
coronary heart disease, quitting smoking reduces the risk of death
overall and reduces the risk of recurrent heart attacks and
cardiovascular death by 30 to 40 percent (Refs. 19 and 563). The 2020
Surgeon General's Report concluded that quitting smoking reduces the
risk of fatal and non-fatal stroke, and earlier reports have also
stated that it is reasonable to assume that quitting smoking would
reduce the risk of recurrent strokes (Refs.19 and 563). Quitting
smoking helps the body tolerate the surgery and treatments, such as
chemotherapy and radiation, associated with certain smoking-related
diseases, and quitting also improves the likelihood of responding to
those treatments (Refs. 63, 563, 570, and 574) and reduces the risk of
respiratory infections compared to continued smoking (Refs. 563 and
575).
Given the reduction in risk of smoking-related death and disease
associated with cessation, those who successfully quit smoking also
increase their life expectancy. Using data from the CPS-II--an ongoing
study of 1.2 million adults--scientists have found that, among men who
smoke cigarettes, men who smoked at age 35 and continued to smoke until
death had a life expectancy of 69.3 years, compared with a life
expectancy of 76.2 years for those who stopped smoking at age 35 (Ref.
576). After adjusting for the subsequent quit rate among people who
currently smoke cigarettes at baseline (to account for the possibility
that some people who currently smoke at baseline quit smoking or some
people who formerly smoked relapsed during followup and, thus, were
incorrectly classified as people who continue to smoke in the
unadjusted analysis), the life expectancy for males who formerly smoked
increased to 77.8 years (a life extension of 8.5 years) (Ref. 576).
Women who smoked at age 35 and continued to smoke until death had a
life expectancy of 73.8 years, compared with a life expectancy of 79.7
years for those who stopped smoking at age 35 (Ref. 576). After
adjustment for the subsequent quit rate among people who currently
smoke at baseline, the life expectancy for females who formerly smoked
increased to 81 years (a life extension of 7.7 years) (Ref. 576).
Furthermore, a man aged 60-64 years who smokes 20 cigarettes (one pack)
or more per day and then quits smoking reduces his risk of dying during
the next 15 years by 10 percent (Ref. 563).
While cessation is beneficial for people of all ages, the health
benefits are greatest for people who stop smoking at earlier ages
(Refs. 63 and 563). Scientists in the United Kingdom found that people
who quit smoking at age 30 reduce their risk of dying prematurely
(i.e., dying before their expected average life expectancy) from
smoking-related diseases by more than 90 percent (Refs. 544 and 577).
Those who quit at age 50 reduce their risk of dying prematurely by 50
percent compared to those who continue to smoke (Ref. 544). Using NHIS
data, researchers also estimated that life expectancy in the United
States would increase by 4 years among people who smoke who quit at
ages 55-64, and 10 years among people who smoke who quit at ages 25-34
(Ref. 566). Scientists using the CPS-II data (while accounting for the
possibility that some people who currently smoke at baseline quit
smoking and some people who formerly smoked relapsed during followup)
found that even people who smoke who quit at age 65 had an expected
life increase of 2 years for men and 3.7 years for women (Ref. 576).
The benefits continue for those who remain smoke-free. At year one,
an individual's risk of coronary heart disease becomes half that of a
person who smokes cigarettes (Refs. 219 and 578). Beginning 2 and 5
years after cessation, an individual's stroke risk is reduced to that
of a person who does not smoke cigarettes (Refs. 19 and 578). In
addition, the risk of cancers of the mouth, throat, esophagus, and
bladder for a person who formerly smoked is halved within 5 years (Ref.
578). By 10 years post-cessation, an individual's risk of cancers of
the kidney and pancreas decreases (Ref. 578). The risk of coronary
heart disease becomes that of a person who does not smoke after 15
years of abstinence (Ref. 578). FDA anticipates that limiting nicotine
yield by setting a maximum level of nicotine in cigarettes and certain
other combusted tobacco products would improve smoking cessation
outcomes in adults who smoke and result in longer life expectancies for
more individuals. Additionally, FDA anticipates that this proposed
product standard will benefit populations that use tobacco products at
disproportionately high levels by reducing tobacco-related morbidity
and mortality by improving quitting and cessation among these
populations.
[[Page 5088]]
Research has shown that people from specific population groups who
smoke cigarettes bear a disproportionate burden of tobacco-related
morbidity and mortality. Black individuals, and in particular Black
men, experience the highest rates of incidence and mortality from
tobacco-related cancers compared to people from other racial and ethnic
groups (Refs. 102 and 103). Additionally, mortality due to tobacco-
related disease such as heart disease, stroke, and hypertension is
higher among Black individuals compared to other racial and ethnic
groups (Refs. 105, 106, 108 to 110, 123, and 579). Furthermore,
individuals with symptoms of mental health disorders and persons who
have substance use disorders smoke cigarettes in disproportionately
large numbers (Refs. 128, 580 to 585), resulting in increased risk for
tobacco-related morbidity and mortality (Ref. 585). Based on these
collective findings, FDA anticipates that the proposed product standard
will improve smoking cessation outcomes across the U.S. population,
including among populations at increased risk for tobacco-related
morbidity and mortality, leading to a reduction in adverse tobacco-
related health effects.
3. Given the Harmful Effects of Cigarette Smoking, Switching to a
Potentially Less Harmful Nicotine Delivery Product May Reduce Death and
Disease
Some people who smoke and who want to quit use NRT products, or
other smoking cessation products that do not contain nicotine, that FDA
has approved as safe and effective for smoking cessation. These
products have been shown to significantly increase the success of
smoking cessation (Ref. 586). FDA continues to be committed to enabling
the development of safe and effective drug product innovations that
help smokers quit combustible cigarettes and improve their health.
FDA also recognizes, however, that other people may seek to switch
from cigarette smoking to using other noncombusted tobacco products
that deliver nicotine. People who smoke and switch completely to a
potentially less harmful noncombusted tobacco product to maintain their
nicotine dependence also could, to the extent that use of those
products result in less harm, significantly reduce their risk of
tobacco-related death and disease (Ref. 8).
As described in section VI.B of this document, studies have
reported on the ways in which people who use tobacco have predicted how
their patterns of tobacco use would change in response to the
implementation of a nicotine product standard. While most people who
use tobacco in these studies indicated that they would continue to
smoke cigarettes--or other combusted products--or simply quit tobacco
use, some participants reported that they would switch to using or
increase use of a noncombusted product (Refs. 262, 264, and 587).
One clinical trial compared use of NRT and alternative tobacco
products (i.e., smokeless tobacco, e-cigarettes, cigars, cigarillos)
among people who smoke cigarettes and were randomized to one of three
groups (Ref. 5). One group received LNC cigarettes along with access to
NRT, noncombusted tobacco products (i.e., smokeless tobacco, e-
cigarettes), and combusted non-cigarette products (i.e., cigars,
cigarillos); a second group received LNC cigarettes, and NRT, and
noncombusted tobacco products only; and a third group received NNC
cigarettes along with NRT, noncombusted tobacco products, and combusted
tobacco products. Overall, those who received the LNC cigarettes used
more alternative combusted and noncombusted tobacco products as well as
NRT. These participants also smoked fewer total combusted tobacco
products and had a greater number of quit attempts. Tobacco toxicant
levels in participants who received LNC cigarettes and only NRT and
noncombusted products were statistically significantly lower than those
of participants who received NNC cigarettes, while toxicant levels in
those who received LNC cigarettes and had access to NRT, combusted, and
noncombusted products did not differ from the NNC cigarette group (Ref.
5). Findings demonstrate that when people who smoke cigarettes are
switched to LNC cigarettes and are provided with alternative sources of
nicotine, they will readily use the alternative sources of nicotine.
Moreover, the LNC cigarette group that had access to NRT and
noncombusted nicotine sources only had statistically significantly
reduced biomarker levels of certain harmful constituents (NNN and NNAL)
compared to those who continued to smoke NNC cigarettes (Ref. 5). The
LNC cigarette group with access to NRT and both combusted and
noncombusted tobacco products resembled the NNC cigarette group (Ref.
5).
Moreover, in general, the high levels of noncompliance with study-
issued VLNC cigarettes in the context of clinical trials, and continued
use of non-study provided tobacco products (particularly NNC
cigarettes), suggest that VLNC cigarettes have lower appeal and abuse
potential compared to NNC cigarettes (Refs. 327 to 331). As a result,
these findings suggest that people who smoke VLNC cigarettes are likely
to use alternative nicotine-containing products, if such products are
concurrently available, once a nicotine product standard for combusted
tobacco products is in place.
Under FDA's population health model's product standard scenario, an
increase in noncombusted product use would occur concurrently with a
dramatic reduction in cigarette smoking. Although the model assumes
that noncombusted product initiation would remain constant until the
end of the projection period (i.e., 2100), the product standard
scenario shows that noncombusted use continues to climb due to higher
switching rates from combusted products as compared to the baseline
scenario. This is because the number of people who start using
noncombusted tobacco products would be much higher compared to the
number of people who quit using noncombusted products. That is, there
would be more people who currently use noncombusted tobacco products
every year than people who quit using noncombusted products, which
would cause an increase in noncombusted tobacco use prevalence
throughout the projection period. According to the model, adult
noncombusted tobacco use would increase from 7.7 percent in the
baseline scenario to 12.8 percent in the product standard scenario
within 1 year after policy implementation, due to the increase in
switching from cigarette smoking and dual use as a result of a nicotine
product standard. The prevalence of noncombusted tobacco use would
remain higher in the product standard scenario over time due both to
increased uptake among people who smoke and increased initiation due to
some dissuaded initiation of cigarette use, compared to those
individuals taking up noncombusted products instead.
Under the product standard scenario in the model, dual use of
cigarettes and noncombusted tobacco products also would increase
immediately, since a greater proportion of people who continue to smoke
cigarettes would take up noncombusted products than in the baseline
scenario, but this pattern would not continue over time with dual use
prevalence reaching levels below 0.1 percent by the year 2035. Although
the increase in noncombusted tobacco product use trend changes over
time (i.e., results showed a spike increase in noncombusted use
prevalence within the first 3 years after implementation of a nicotine
product standard), the decrease in smoking prevalence becomes greater
than the increase in
[[Page 5089]]
noncombusted use following the implementation of a nicotine product
standard. Consequently, overall tobacco use under the product standard
scenario would remain lower than in the baseline scenario.
As described in section VIII.A of this document, in addition to the
aforementioned main analyses, FDA conducted a series of sensitivity
analyses to examine the impact of key modeling assumptions on the main
outcome metrics of interest. In these analyses, we examined the
sensitivity of modeled results to underlying assumptions related to
baseline product use projections and mortality risk estimates.
Sensitivity analyses included examining the impact of increased
initiation of noncombusted tobacco product use among those who would
otherwise not have used tobacco, the impact of an increase in switching
from cigarettes to noncombusted tobacco product use, the impact of a
varying mortality risk associated with dual use of cigarettes and
noncombusted tobacco products, the impact of lower and higher
noncombusted tobacco product risk, and the emergence of an illicit
market for full nicotine content cigarettes.
In general, changes to baseline inputs of noncombusted product use
trajectories and health risks had minimal impact on smoking prevalence
and attributable morbidity and mortality and the nicotine product
standard policy scenario still resulted in substantial public health
benefits. In the main modeling analysis, we account for people who
would have initiated on smoking cigarettes initiating on noncombusted
tobacco products instead because of the product standard. It is also
possible that there could be increased initiation of noncombusted
tobacco use among those who would otherwise not have used tobacco under
the product standard scenario; for example, due to increased marketing
of noncombusted products because of the policy or changes in public
perceptions of the harms of noncombusted products. In a sensitivity
analysis, starting at 2027 (year of the proposed standard
implementation), we assumed a 20 percent increase in the initiation of
noncombusted tobacco products among those who would otherwise have not
used tobacco. Table 8 provides the projected impacts on tobacco-related
mortality and morbidity through the year 2100. Compared with the main
results, a 20 percent increase in initiation of noncombusted tobacco
use had minimal impact in mortality outcomes given the substantial
reduction in adverse health effects projected under a potential
nicotine product standard. For example, by year 2100, cumulative life
years gained decreased by less than 1 percent compared with the main
results, while cumulative tobacco-attributable deaths avoided remained
almost the same. It is important to note that, because we only have
data on the effect of cigarette smoking (and not noncombusted product
use) on quality of life, the projected changes in QALYs gained from
reduced smoking morbidity are not affected by increasing noncombusted
product use initiation.
Table 8--Impact of Increased Initiation of Noncombusted Tobacco Products as a Result of the Proposed Nicotine
Product Standard Implemented in 2027 on Projected Smoking Prevalence and Tobacco-Related Mortality and Morbidity
by 2100
[Median (5th, 95th percentiles) estimates]
----------------------------------------------------------------------------------------------------------------
Projections through year 2100
---------------------------------------------------------------------------
Cumulative Cumulative QALYs
Scenario Noncombusted tobacco- Cumulative life gained from
tobacco use attributable years gained reduced smoking
prevalence (%) mortality avoided (millions) morbidity
(millions) (millions)
----------------------------------------------------------------------------------------------------------------
Main scenario....................... 14.1 (12.7, 14.9) 4.3 (1.6, 4.6) 76.4 (26.5, 82.5) 53.1 (27.5, 54.4)
20% increased initiation of 15.4 (14.0, 16.1) 4.3 (1.6, 4.6) 75.9 (26.1, 82.1) 53.1 (27.5, 54.4)
noncombusted products..............
----------------------------------------------------------------------------------------------------------------
Taken together, findings from prior research, as well as FDA's
population health model, suggest that if the proposed product standard
reduces the nicotine yield by setting a maximum level of nicotine in
cigarettes only, but people who smoke cigarettes still have access to
other NNC combusted tobacco products, they likely would substitute with
the NNC combusted tobacco products and negate a significant proportion
of the public health impact of the product standard. If other combusted
tobacco products also are covered by this proposed product standard,
however, data suggest that people who smoke may switch from combusted
tobacco product use to potentially less harmful tobacco products.
Moreover, findings indicate that switching from combusted cigarette use
to noncombusted tobacco product use has the potential to impart
significant health-related benefits on a population level. The
population health model estimates that on average approximately 50
percent of people who smoke cigarettes will switch to noncombusted
tobacco products use per year, and although we estimate that such
switching carries an 8 percent higher risk than quitting tobacco use
entirely (based on findings from Henley et al. 2007 (Ref. 557)), this
is still a significant health-related benefit compared to continuing to
use combusted tobacco products.
4. Having Fewer People Smoke Cigarettes and Other Combusted Tobacco
Products Will Reduce Death and Disease Associated With Secondhand Smoke
Exposure
Cigarettes and other combusted tobacco products also have deadly
effects on people who do not smoke because they produce secondhand
smoke. It is well-established that secondhand tobacco smoke causes
premature death and disease in children and in adults who do not smoke
(Ref. 15 at p.11). Secondhand smoke exposure is currently estimated to
be responsible for over 41,000 deaths annually in the United States
(Ref. 1). For example, an estimated 7,300 lung cancer deaths and nearly
34,000 coronary heart disease deaths annually can be attributed to
secondhand smoke (Ref. 1). Additionally, productivity losses due to
secondhand smoke-attributable deaths are estimated to cost the United
States $5.6 billion each year (Ref. 1).
Children are one group disproportionately exposed to and impacted
by secondhand smoke. The 2014 Surgeon General's Report estimated that
secondhand smoke is
[[Page 5090]]
associated with 150,000 to 300,000 lower respiratory tract infections
in infants and children under age 18 months, 790,000 doctor's office
visits related to ear infections per year, and 202,000 asthma cases
each year (Refs. 1 and 137). In 2014, the U.S. Surgeon General reported
that 400 sudden infant death syndrome (SIDS) deaths annually are
related to perinatal smoking or exposure to secondhand smoke; the
``Reproductive Outcomes'' section describes the impact of perinatal
smoking (Ref. 1). Children of parents who smoke, when compared with
children of parents who do not smoke, have an increased frequency of
respiratory infections like pneumonia and bronchitis (Ref. 563).
Children exposed to tobacco smoke in the home are also more likely to
develop acute otitis media (middle ear infections) and persistent
middle ear effusions (fluid behind the eardrum) (Ref. 563). More recent
data from the 2013-2014 NHANES estimates that approximately 58 million
Americans who do not smoke (1 in 4) were exposed to secondhand smoke,
including 14 million children (Ref. 588). Approximately half of all
U.S. children ages 3-18 are exposed to cigarette smoke regularly at
home or other locations that still permit smoking (Ref. 1). In 2019,
approximately one-quarter of middle and high school students reported
breathing in secondhand smoke in their homes or in a vehicle (Ref.
145).
The burden of secondhand smoke exposure is experienced
disproportionately among members of some racial and ethnic groups and
lower income groups. Among people who do not smoke and were ages 3 and
older, findings from 2011 to 2018 NHANES data indicate that non-
Hispanic Black persons and those living below the poverty level had the
highest levels of secondhand smoke exposure compared to people of other
races and those living above the poverty level, respectively; these
disparities persisted across all years of the study analysis from 2011
to 2018 (Ref. 139). From 1999 to 2012, the percentage of people who do
not smoke and were age 3 and older exposed to secondhand smoke (defined
in the study as levels 0.05-10 nanogram per milliliter) declined across
all racial and ethnic groups (Ref. 141). However, a significantly
higher proportion of non-Hispanic Black persons who do not smoke
continued to have detectable serum cotinine levels compared to Mexican
American and non-Hispanic White persons who do not smoke. For example,
in 2011-2012, nearly 50 percent of non-Hispanic Black people who do not
smoke had detectable serum cotinine levels, compared with 22 percent of
non-Hispanic White and 24 percent of Mexican American people who do not
smoke (Ref. 141). Additionally, disparities in secondhand smoke
exposure are found across various environmental settings, including
homes, vehicles, workplaces, and public places. These disparities speak
to the interrelated influences of individual factors (e.g., age, race
and ethnicity, income) and existing inequities in places where members
of communities impacted by tobacco-related health disparities are
likely to reside, spend time, and work (Ref. 174). The proposed product
standard is anticipated to reduce smoking-related morbidity and
mortality for specific population groups that do not smoke that are
disproportionately exposed to secondhand smoke, especially youth.
Moreover, there is also some scientific evidence supporting
disparities in secondhand smoke exposure by sexual orientation. An
analysis of NHANES data from 2003-2010 found that secondhand smoke
exposure (defined as a serum continine \17\ levels >=0.05 nanogram per
milliliter) differed by sexual orientation among women 20-59 years of
age (Ref. 143). This study found that among women 20-59 years of age,
secondhand smoke exposure was higher among non-smoking women who
identified as lesbian (56.2 percent) or who reported a lifetime
experience with a same-gender partner (47.7 percent) than those women
who identified as exclusively heterosexual (33.0 percent; p<0.001)
(Ref. 143). However, among men 20-59 years of age, exposure to
secondhand smoke did not significantly differ by sexual orientation.
FDA anticipates that the overall public health benefits of this
proposed nicotine product standard would be far greater than those
described above once we account for the impacts of reduced cigarette
smoking on secondhand smoke exposure. As evidenced by evaluations of
smoke-free policies, decreasing exposure to secondhand smoke will
decrease smoking-related death and disease among people who do not
smoke (Refs. 589 and 590).
To estimate the potential impact of the proposed standard on
morbidity and mortality, FDA evaluated the existing scientific
literature as well as findings from our population health model, which
is described in section VIII.A of this document. Estimation of the
mortality benefits of a nicotine product standard for secondhand smoke
exposure used a similar approach. This approach relied on scaling the
estimate of 437,400 deaths annually attributable to direct cigarette
smoking from 2005-2009 (Ref. 1), to the number of deaths attributed to
secondhand smoke exposure. That ratio was then applied to the model-
derived projected changes in avoided cigarette-attributable deaths
under the main product standard scenario to project the number of
avoided deaths over time from secondhand smoke exposure. In the
population health model, the impacts of a nicotine product standard on
mortality from secondhand smoke exposure were estimated by first
calculating the ratio of secondhand smoke (41,280 deaths; (Ref. 1)) to
primary smoking-attributable deaths. That value, 9.4 percent, was then
applied to the projections of cigarette-attributable deaths avoided
yielding an estimate of approximately 169,000 cumulative deaths from
secondhand smoke exposure avoided by 2060, rising to approximately
415,600 cumulative deaths avoided by the end of the century (see table
9).
Table 9--Projected Number of Tobacco-Attributable Deaths Avoided for Secondhand Smoke as a Result of a Nicotine
Product Standard Implemented in 2027
----------------------------------------------------------------------------------------------------------------
Cumulative secondhand smoking-
Year Scenario attributable deaths avoided
----------------------------------------------------------------------------------------------------------------
2040.......................................... Median (5th, 95th)............... 39,800 (4,900, 49,200)
2060.......................................... Median (5th, 95th)............... 169,000 (38,500, 189,000)
2080.......................................... Median (5th, 95th)............... 297,000 (91,200, 323,200)
2100.......................................... Median (5th, 95th)............... 415,600 (159,700, 444,400)
----------------------------------------------------------------------------------------------------------------
[[Page 5091]]
5. Estimated Mortality Impact of Reduced Smoking-Related Fires,
Smoking-Related Perinatal Conditions, and Use of Non-Premium Cigars and
Pipe Tobacco as a Result of Implementation of the Proposed Standard
FDA anticipates that the overall public health benefits of this
proposed nicotine product standard would be greater than those
described above once we account for the impacts of reduced cigarette
smoking on smoking-related fires and perinatal conditions, in addition
to the impacts of reduced use of other combusted tobacco products. To
estimate the potential impact of the proposed standard on mortality,
FDA evaluated the existing scientific literature, as well as findings
from the population health model--which is described in section VIII.A.
of this document. Similar to the approach taken to estimate the
mortality benefits of a nicotine product standard for secondhand smoke
exposure, estimation of the mortality benefits of a nicotine product
standard for smoking-related fires, smoking-related perinatal
conditions, and use of non-premium cigars and pipe tobacco used a
consistent approach. This approach relied on scaling the estimate of
437,400 deaths annually attributable to direct cigarette smoking from
2005-2009 (Ref. 1), to the number of deaths attributed to each of the
following causes: smoking-related fires, smoking-related perinatal
conditions, and use of non-premium cigars and pipe tobacco. That ratio
was then applied to the model-derived projected changes in avoided
cigarette-attributable deaths under the main product standard scenario
to project the number of avoided deaths over time from each of these
causes (i.e., smoking-related fires, smoking-related perinatal
conditions, and use of non-premium cigars and pipe tobacco) (see table
10).
During 2012-2016, an estimated annual average of 18,100 reported
home structure fires in the United States were caused by smoking
materials, which killed an average of 590 people annually (Ref. 591).
Moreover, smoking materials remain a leading cause of fatal home fires
in the United States, and people who smoke are not the only victims
(Ref. 592). By one estimate, one out of every four fatal victims of
smoking-material fires is not the person whose cigarette initiated the
fire (Ref. 593). A lower prevalence of cigarette smoking and reduced
cigarette consumption is likely to decrease the occurrence of fires
caused by smoking materials, including cigarettes and other combusted
tobacco products. To estimate the impact of a nicotine product standard
on the number of deaths caused by smoking-related fires, we applied the
average of 590 deaths annually from 2012-2016 from home structure fires
started by smoking materials (Ref. 591). We calculated the ratio of
smoking-related fire deaths to cigarette-attributable deaths to be
approximately 0.1 percent and applied that value to the projections of
avoided cigarette-attributable deaths, yielding an estimate of
approximately cumulative 2,400 deaths due to smoking-related fires
avoided by 2060, rising to approximately cumulative 5,900 deaths
avoided by the end of the century (table 10).
Cigarette smoking is responsible for approximately 1,000 deaths
from perinatal conditions annually, including over 600 deaths from
prenatal conditions and 400 deaths from SIDS (Ref. 1). Exposure to
secondhand smoke can also cause adverse health effects in infants and
children. Currently, approximately half of all U.S. children and
adolescents ages 3-18 years are exposed to cigarette smoke regularly at
home or other locations that still permit smoking (Ref. 1). Exposure to
cigarette smoke among children and adolescents can trigger asthma
attacks and lead to more frequent respiratory infections compared to
those not exposed to smoke (Ref. 1). Prenatal tobacco exposure and
postnatal secondhand smoke exposure increase the risks of fetal deaths,
fetal growth restriction/low birth weight, respiratory conditions, and
SIDS (Ref. 15, Ref. 1). In addition, thirdhand smoke--the chemical
residue from combusted tobacco smoke that can become embedded in the
environment (e.g., carpet, dust)--results in exposure to harmful
constituents, such as tobacco specific nitrosamines (Ref. 138).
Exposure to thirdhand smoke is especially concerning for young
children, given their size and behaviors, like crawling on the ground
and frequently putting their hands in their mouths.
FDA estimated the impacts of a potential nicotine product standard
on perinatal mortality by first calculating the ratio of perinatal
deaths (1,013 deaths; (Ref. 1)) to primary smoking-attributable deaths.
That value, 0.2 percent, was then applied to the projections of
cigarette-attributable deaths avoided yielding an estimate of
approximately 4,100 cumulative perinatal deaths avoided by 2060, rising
to approximately 10,200 cumulative deaths avoided by the end of the
century (table 10). Since decreases in cigarette smoking prevalence
under the proposed product standard would have immediate, rather than
lagged, impacts on fetal health and the health of newborn children, we
expect avoided smoking-attributable perinatal deaths to accrue more
rapidly than the estimates presented here.
The smoke of other combusted tobacco products, particularly those
that could be alternatives to cigarettes, such as cigars and pipes,
contains many of the same toxic constituents as cigarette smoke,
sometimes at even greater concentrations, and consequently carries
significant health risks (Refs. 53 and 594). In fact, NNAL
concentrations measured in people who smoke cigars daily were found to
be as high as those measured in people who smoke cigarettes daily (Ref.
160). Cigar and/or pipe smoking cause cancers of the lung and upper
aerodigestive tract, including the oral cavity, oropharynx,
hypopharynx, larynx and esophagus (Ref. 158). Additional evidence
suggests that cigar and/or pipe smoking is causally associated with
cancers of the pancreas, stomach, and bladder (Ref. 165). People who
smoke cigars also have increased risks for coronary heart disease and
COPD compared with people who have never used tobacco (Ref. 166). In a
2014 publication, researchers estimated that regular cigar smoking was
the cause of approximately 9,000 premature deaths in the year 2010, and
more than 140,000 years of potential life lost in the United States in
2010 (Ref. 134). The total number of cigar-attributable deaths may be
even larger for several reasons. For example, the analysis included
only causes of death found to be statistically significantly higher in
two cohorts that studied people who smoke cigars, although there may be
additional causes of death that are attributable to cigar smoking. In
addition, there may be increases in cigar smoking relative risks over
time, due to greater variety of cigar products and differences in
inhalation patterns (Ref. 134). Therefore, cessation and reduced
initiation of combusted tobacco products other than cigarettes as a
result of the proposed product standard could yield even greater public
health impacts than those presented.
To estimate the impacts of a potential nicotine product standard on
avoided deaths attributable to covered cigar products, we used
estimates of premature deaths attributable to regular cigar smoking
from a prior publication (Ref. 134). Given that the prior analysis
included all cigar types in its estimate of 9,246 premature deaths for
the year 2010 and that we did not include premium cigars in our current
analysis, we estimated the fraction of deaths attributed to cigar
products other than premium cigars. We estimate that
[[Page 5092]]
among people who ever smoked cigars fairly regularly and now smoke
every day or some days in Wave 4 of the PATH Study, 80 percent reported
smoking non-premium cigars and 20 percent reported smoking premium
cigars, using a classification methodology described previously (Ref.
290) and subsequently updated (Ref. 595). On that basis, 7,397 (i.e.,
9,246 x 0.8) deaths annually are attributed to using non-premium cigar
products. By considering a relatively stable trend in adult cigar use
\35\ and assuming that adult cigar use is the main driver of cigar-
attributable deaths in the close future, we assumed that non-premium
cigar-attributable mortality would remain constant at 7,397 cigar-
attributable deaths per year through 2065 (or roughly the time at which
people who use cigars aged 26 and older in 2021 would all have reached
age 70 and older). However, as youth and young adult cigar smoking has
declined in recent years, we adopt a different trend in baseline cigar-
attributable mortality in the further future (after 2065). To obtain
baseline non-premium cigar-attributable mortality from 2066 through the
end of the modeling period (2100), we assume non-premium cigar-
attributable mortality will eventually follow the observed relative
decline in cigar use among young adults as they reach older ages.
Specifically, we assume that non-premium cigar smoking-attributable
deaths among youth who initiate cigar smoking will decrease on average
by 37.5 percent \36\ over 40 years (from 2078 to 2117).\37\ That is,
the cigar smoking-attributable deaths will decrease on average to 4,600
([ap] 7,397 x (1-0.375)) deaths per year over the period from 2078 to
2117.
---------------------------------------------------------------------------
\35\ Adult cigar smoking has historically remained stable. Data
from the NHIS over 2000-2015 has shown that prevalence of current
cigar smoking has remained generally stable at around 2.3 percent
among U.S. adults aged 18 years and older (Ref. 596). Adult (ages 26
or older) cigar use also remained relatively stable in NSDUH data
for 2011 and 2019 and did not significantly change (4.2 percent in
2011 to 4.0 percent in 2019 for cigars) (Ref. 286).
\36\ According to data from the PATH Study, young adult (ages
18-24) past 30-day cigar use declined from 15.7 percent during Wave
1 (2013-2014) to 11 percent during Wave 5 (2018-2019), representing
a 30 percent relative decline in prevalence. Additionally, data from
the PATH Study Waves 3 (2015-2016) and 5 (2018-2019) indicate that
cigar use among 18-year-olds declined from 7.2 percent to 3.9
percent, implying a steeper decline of approximately 45 percent in
more recent years within this smaller age cohort. We use these two
data points to estimate the decrease in cigar smoking among young
people because both provide relevant information from a national
survey that is specific to tobacco use and average them to produce
an estimate of 37.5 percent (i.e., (30 + 45)/2).
\37\ For youth, we assume that initiation occurs by the age of
18, followed by a cigar smoking-attributable death 52 years later.
We then assume cigar use initiation occurs during years 2025 to 2064
(40-year period), and cigar smoking-attributable deaths begin to
occur a year after the period from 2077 (i.e., 2025 + 52) through
2116 (i.e., 2064 + 52); that is, over the period from 2078 to 2117.
---------------------------------------------------------------------------
Assuming a linear decrease in cigar smoking-attributable mortality
from 2065 to 2117, and an average of approximately 4,600 deaths per
year over the period from 2078 to 2117, implies non-premium cigar
smoking-attributable mortality will decline linearly from 7,397 in 2065
to approximately 4,390 deaths in 2100. We assume a linear decrease for
simplicity and because trends for cigar use considered in this post-
processing strategy come from a short interval (PATH Study data, Waves
1 to 5, and Waves 3 to 5). We then calculate the ratio of non-premium
cigar to cigarette-attributable deaths for each year in the projection
period and apply those values to the projections of avoided cigarette-
attributable deaths to estimate non-premium cigar-attributable deaths
under the nicotine policy scenario. Using this approach, by 2060, we
estimate approximately 54,800 cumulative deaths due to non-premium
cigar products would be avoided, rising to approximately 214,700
cumulative deaths avoided by 2100 (see table 10). Similar methods were
used to calculate estimates accounting for the mortality effects of a
product standard prohibiting characterizing flavors other than tobacco
in cigars. These estimates reduced baseline non-premium cigar-
attributable deaths in a phased-in manner reaching a constant reduction
of 780 deaths averted per year after 30 years (Ref. 597). These
estimates and results are presented in detail in sections VIII.E and
VIII.F of this document.
To estimate the impacts of a nicotine product standard on avoided
deaths attributable to pipe tobacco smoking, we used the estimate of
1,095 premature deaths per year provided by a prior analysis (Ref.
598). We calculated the ratio of pipe tobacco to cigarette-attributable
deaths to be 0.3 percent and applied that value to the projections of
avoided cigarette-attributable deaths, yielding an estimate of
approximately 4,500 cumulative deaths due to pipe tobacco smoking
avoided by 2060, rising to approximately 11,000 cumulative deaths
avoided by the end of the century (see table 10).
Based on these collective findings and estimates, FDA anticipates
that the proposed product standard will further improve public health
due to the impacts of reduced cigarette smoking on smoking-related
fires and perinatal conditions, in addition to the impacts of reduced
use of other, non-cigarette combusted tobacco products covered by this
proposed rule.
Table 10--Projected Number of Tobacco-Attributable Deaths Avoided for Smoking Related Fires, Smoking Related Perinatal Conditions, Non-Premium Cigar and
Pipe Tobacco Use as a Result of a Nicotine Product Standard Implemented in 2027
--------------------------------------------------------------------------------------------------------------------------------------------------------
Cumulative smoking- Cumulative non-premium Cumulative pipe tobacco-
Year Scenario related fire deaths Cumulative perinatal cigar-attributable deaths attributable deaths
avoided deaths avoided avoided avoided
--------------------------------------------------------------------------------------------------------------------------------------------------------
2040............................ Median (5th, 95th). 600 (100, 700) 1,000 (100, 1,200) 8,900 (1,000, 11,000) 1,100 (130, 1,300)
2060............................ Median (5th, 95th). 2,400 (600, 2,700) 4,100 (900, 4,600) 54,800 (13,200, 60,500) 4,500 (1,000, 5,000)
2080............................ Median (5th, 95th). 4,200 (1,300, 4,600) 7,300 (2,200, 7,900) 134,700 (46,000, 144,100) 7,900 (2,400, 8,600)
2100............................ Median (5th, 95th). 5,900 (2,300, 6,400) 10,200 (3,900, 10,900) 214,700 (91,600, 225,800) 11,000 (4,200, 11,800)
--------------------------------------------------------------------------------------------------------------------------------------------------------
6. Public Health Benefits of the Proposed Standard Not Addressed in
FDA's Population Health Model
While FDA's population health model's estimates of the potential
impact from a nicotine product standard suggest a significant public
health benefit to the United States resulting from substantial
reductions in smoking prevalence, these analyses do not address other
additional benefits. The overall public health benefits of this
proposed product standard are likely to be even greater than those
quantified, since our analysis does not account for the full range of
impacts that smoking has on public health in the United States.
[[Page 5093]]
First, although we estimated the impact of self-reported quality of
life, this may not capture the full breadth and depth of smoking-
attributable morbidity. Tobacco smoke exposure can cause immediate and
long-term adverse health effects (Ref. 1). Cigarette smoking ``has been
causally linked to diseases of nearly all organs of the body, to
diminished health status, and to harm to the fetus'' (Ref. 1). Each
year, an estimated 480,000 people in the United States die from
smoking; the U.S. Surgeon General has reported that for every person
that dies from smoking, about 30 individuals will suffer from at least
one smoking-related disease (Ref. 1). One study estimated that
individuals in the United States have had 14.0 million major smoking-
attributable conditions, including more than 7.4 million cases of COPD,
nearly 2.3 million heart attacks, 1.8 million cases of diabetes, nearly
1.2 million stroke events, more than 300,000 cases of lung cancer, and
nearly 1 million cases of other smoking-attributable cancers (i.e.,
bladder, cervix, colon/rectum, kidney, larynx, mouth, tongue, lip,
throat, pharynx, stomach) (Ref. 564). Cigarette smoking, in addition to
causing disease, can diminish overall health status leading to higher
risks for surgical complications, including wound healing and
respiratory complications, increased absenteeism from work, and greater
use of healthcare services (Ref. 1). In terms of a monetary measure of
the impact of cigarette smoking on the public health, in 2018,
cigarette smoking cost the United States more than $600 billion,
including more than $240 billion in healthcare spending (Ref. 10),
nearly $185 billion in lost productivity from smoking-related illnesses
and health conditions (Ref. 10), nearly $180 billion in lost
productivity from smoking-related premature death (Refs. 1 and 10), and
$7 billion in lost productivity from premature death from secondhand
smoke exposure (Refs. 1 and 11). Increased smoking cessation, reduced
cigarette consumption, and lower progression to regular use will reduce
both mortality from smoking and the enormous burden of cigarette-
attributable diseases in the United States.
Second, the estimated impacts to public health do not include the
reductions in morbidity associated with reduced exposure to secondhand
smoke among infants and children. A report of the U.S. Surgeon General
(Ref. 1) found that approximately half of all children and adolescents
ages 3-18 in the United States are exposed to cigarette smoke regularly
at home or other locations that still permit smoking. Also, a recent
study using NYTS data reported that, in 2019, 25.3 percent and 23.3
percent of students were exposed to home and vehicle secondhand smoke,
respectively (Ref. 145). Exposure to cigarette smoke among children and
adolescents can trigger asthma attacks and lead to more frequent
respiratory infections compared to those not exposed to smoke (Ref. 1).
Third, a lower prevalence of cigarette smoking and reduced
cigarette consumption will decrease the occurrence of fire-related
injuries and damages caused by smoking materials, including cigarettes
and other combusted tobacco products. From 2012 to 2016, an estimated
average of 18,100 home structure fires in the United States annually
were caused by smoking materials (Ref. 591). Reductions in smoking as a
result of the proposed nicotine product standard are likely to lead to
not only fewer fatalities (as described previously) but also reductions
in the annual average of 1,130 injuries (Ref. 591).
Fourth, these projections did not include the potential health
benefits associated with people who smoke cutting down on the number of
cigarettes smoked as a result of the proposed nicotine product
standard. Quitting cigarette smoking entirely clearly leads to the
greatest reductions in disease risk, and duration of smoking has been
shown to be a greater driver of disease risk than frequency of use
(Ref. 28). Although some studies have not found evidence of lower
disease risk after cutting down on cigarettes (Refs. 28, 266, 599 to
601), others have shown that substantial reductions in cigarette
consumption can lead to some reductions in disease risk, especially for
lung cancer, for those who would have otherwise continued to smoke
(Ref. 602). Such studies have found decreased risk of lung cancer
deaths (Ref. 603) and decreased risk of lung cancer among people who
smoke who reduce cigarette consumption (Refs. 604 and 605). As
described above, studies of VLNC cigarettes have shown that their use
results in reductions in cigarettes smoked per day and exposure to
toxic constituents among individuals who continue to smoke, which may
reduce smoking-related disease risks. Consequently, additional public
health benefits may be observed among those who continue to smoke
cigarettes (but substantially fewer CPD) after a nicotine product
standard is in place.
7. Potential Risks to the Population as a Whole of the Proposed
Nicotine Product Standard Versus the Potential Benefits of the Proposed
Product Standard
There are possible countervailing effects that could occur from the
proposed product standard, if finalized, and potential factors that
could limit its population health effect. Potential risks to the
population, however, would generally only occur among individuals
currently smoking cigarettes and other combusted tobacco products
covered by the scope of this proposed rule, as FDA concludes there are
little to no risks to those who do not use tobacco. These potential
risks do not offset the anticipated benefits of the rule. The
countervailing or limiting effects on people who currently use tobacco
products could include compensatory smoking. As part of this
rulemaking, FDA is required by the Tobacco Control Act to consider
information submitted on such possible countervailing effects,
including among populations that are disproportionately impacted by
tobacco-related morbidity and mortality, such as adolescents who use
tobacco and other populations.
With a lower level of nicotine in cigarettes, some people who use
cigarettes and certain other combusted tobacco products could alter
their smoking behavior in the form of compensatory smoking (i.e., a
change in normal smoking behavior that would increase exposure to
cigarette smoke to compensate for reduced nicotine intake) when
switching from usual brand or NNC cigarettes to VLNC cigarettes. This
concern is echoed in qualitative research of people who currently use
tobacco who report fears that a potential reduction in nicotine will
cause them to engage in compensatory smoking (Refs. 264, 606 to 608).
Compensatory smoking--or compensation--occurs when people who smoke
seek to obtain the amount of nicotine needed to sustain their addiction
by smoking more CPD, taking more and deeper puffs, or puffing with a
faster draw rate. In both brief and extended exposure studies with VLNC
cigarettes, compensation was measured using CPD, puff topography
measures, and biomarkers of CO exposure, such as breath CO or COHb.
Some transient compensatory smoking may occur following initial VLNC
cigarette exposure. However, after continued use of VLNC cigarettes,
people who smoke stop attempting to compensate for the reduced nicotine
content, because they are unable to obtain adequate amounts of nicotine
through these behaviors. The following
[[Page 5094]]
paragraphs discuss data demonstrating this outcome. See also section
VII.B of this document discussing compensatory smoking with an
immediate nicotine reduction approach versus a gradual reduction
approach.
When exposure to VLNC cigarettes is brief (e.g., the first few uses
of VLNC cigarettes), transient compensatory smoking may occur. In brief
exposure studies, changes in smoking topography (Refs. 393 to 395) and
increases in CO (Refs. 393, 411, and 420) have been observed. For
example, one study demonstrated the transient nature of compensatory
smoking by showing increases in smoking topography and CO exposure
during the first and second exposures to VLNC cigarettes, followed by
the subsequent dissipation of these effects by the third and fourth
exposures ((Ref. 394). Similarly, another study found that during a 5-
day study where participants checked into a hotel and were restricted
to only study-issued cigarettes, mouth-level nicotine exposure
indicated that participants initially puffed VLNC cigarettes with
greater intensity than NNC cigarettes, although this effect diminished
across sessions (Ref. 609). However, results from the majority of
studies show no compensatory smoking as a result of switching from
usual brand or NNC cigarettes to VLNC cigarettes. Although not all
studies examined every measure of compensatory smoking, most studies
found no differences between control and VLNC cigarette conditions
regarding CPD (Refs. 5, 32, 34, 40, 41, 265, 331, 374, 387, 386, 390,
396, and 415), CO exposure (Refs. 5, 32, 34, 40, 41, 265, 374, 381,
390, 391, 396, 402, 409, 410, 412 to 414, 467, and 610), smoking
topography (Refs. 381, 391, 403, 411, 415, and 611), or all three
measures (Refs. 329, 382 to 384).
Notably, compensatory smoking has been observed with some reduced
nicotine content cigarettes containing intermediate levels of nicotine
(e.g., LNC cigarettes). For example, in a study of 165 people who use
cigarettes assigned to switch to LNC cigarettes or VLNC cigarettes,
researchers found small but statistically significant differences in
CPD between the LNC and VLNC cigarette conditions, such that LNC CPD
increased over the course of the 6-week intervention, while VLNC CPD
decreased (Ref. 32). However, one of the largest studies involving
reduced nicotine content cigarettes found no compensatory smoking
behavior for cigarettes containing intermediate levels of nicotine
(Ref. 29). Therefore, FDA concludes the nicotine level proposed for
this standard would result in limited, if any, compensatory smoking
that would likely dissipate over time. These data also support FDA's
proposed immediate nicotine reduction approach (see section VII.C of
this document).
Studies consistently report that consumers have misperceptions
about the harms of nicotine and VLNC cigarettes (see sections IV.F and
V.B of this document). A majority of U.S. consumers incorrectly believe
that nicotine is the primary cause of cancer and health harms from
cigarettes (Refs. 227 to 229, 232, 233, 235 to 245, 264, and 612 to
618), and a proportion of consumers with this misperception also
believe that RNC cigarettes are less harmful than NNC cigarettes (Refs.
260 to 262). Additionally, while a majority of consumers understand
that nicotine is addictive (Refs. 227 to 229, 232, 233, and 619), they
do not necessarily believe that RNC cigarettes would be less addictive
than NNC cigarettes (Refs. 260 and 261). There is also evidence from
qualitative studies showing that some consumers do not understand the
technical feasibility of reducing nicotine in cigarettes to minimally
addictive or nonaddictive levels, which may impact consumers' ability
to comprehend and accept messages communicating the policy (Refs. 270
and 229). FDA recognizes the importance of addressing consumer
misperceptions of the harm and addictiveness of nicotine and VLNC
cigarettes to minimize the unintended effects of a proposed product
standard that limits the level of nicotine in cigarettes and certain
other combusted tobacco products to make those products minimally
addictive or nonaddictive. FDA will continue to conduct research on
consumer perceptions of tobacco product harms, use communication tools
(e.g., consumer outreach, public education initiatives, engagement with
interested parties), and consider further regulatory options within our
authorities (e.g., potential future labeling and advertising
regulations) to ensure that all consumers are informed of the risks of
using tobacco products that contain nicotine, including VLNC
cigarettes.
Prior work also has explored whether the proposed product standard
may have a differential impact on specific populations. Studies that
have investigated the effects of VLNC cigarettes in adolescents who
smoke cigarettes have done so under conditions of brief exposure (e.g.,
single exposure to a VLNC cigarette in a laboratory setting). A study
comparing VLNC and LNC cigarette smoking topography in adolescents who
smoke cigarettes found that participants took statistically
significantly more puffs from the VLNC cigarette compared to the LNC
cigarette, and a non-significant trend emerged such that increases in
breath CO were higher after smoking the VLNC cigarette compared to the
LNC cigarette (Refs. 395 and 416). However, the LNC cigarette was rated
as statistically significantly more pleasant than the VLNC cigarette
(Ref. 395).
Similar to studies in adults who smoke cigarettes, studies in youth
and young adults who smoke cigarettes have shown that positive
subjective effects ratings (e.g., ``satisfaction,'' ``pleasure,''
``taste,'' ``strength,'' and ``stimulation'') are lower for VLNC
cigarettes compared to LNC and NNC cigarettes. A laboratory study of
people ages 15-19 who smoke found no effect of nicotine content on
withdrawal, negative affect, or CO boost; however, NNC cigarettes were
associated with greater reductions in craving and increased smoking
satisfaction relative to VLNC cigarettes (Ref. 442). A similar
laboratory study in young adults (age 18-25) found no influence of
nicotine content on total nicotine withdrawal score, affect, or smoking
topography; however, NNC cigarettes were associated with increased
subjective effects ratings compared to LNC and VLNC cigarettes (Ref.
620). Notably, a secondary analysis of data from a clinical trial (Ref.
29) found that, at the end of the 6-week trial, there was no influence
of age on subjective effects, TNE levels, or puff volume in
participants who smoked LNC or VLNC cigarettes (Ref. 621).
Several studies have examined the effects of nicotine content in
cigarettes on adolescents and young adults who smoke. One laboratory
study that assessed the effects of nicotine content and menthol
preference among adolescents (ages 15-19) who smoke found that VLNC
cigarettes were rated statistically significantly lower than NNC
cigarettes, and menthol preference did not affect subjective effects
ratings of VLNC cigarettes (Ref. 408). One study also found that young
adults (ages 18-24) who smoke exhibited lower demand for LNC and VLNC
cigarettes than adults, but there were no other differences between the
two age groups in smoking topography, breath CO, cigarette puffs,
craving, withdrawal, or smoking urge measures (Ref. 622). Another study
investigating how nicotine exposure contributes to relief of craving
and negative affect among young adults (ages 18-25) who smoke found
that smoking reduced craving and negative affect regardless of nicotine
content, and smoking topography did not vary as a function of nicotine
content (Ref. 611). Finally, a study of youth and young adults who
smoke found that two-thirds of participants
[[Page 5095]]
believed that study cigarettes had lower health risks than usual brand
cigarettes, that they were largely concerned with compensatory smoking
following a nicotine reduction policy, and that half stated an
intention to quit smoking after the policy is put in place while the
other half would continue to smoke or switch to another tobacco product
(Ref. 606).
One study assessed longer duration effects (i.e., 3 weeks) of VLNC
cigarettes in adolescent daily smokers (ages 15-19) not currently
intending to quit. Participants assigned to smoke VLNC cigarettes
smoked significantly fewer total CPD than those in the NNC cigarette
group. VLNC cigarettes were associated with lower levels of craving
reduction than NNC cigarettes; however, there were no differences
nicotine dependence or TNE levels among VLNC and NNC cigarette groups
at the end of the study (Ref. 623). A secondary analysis of this study
showed that participants assigned to smoke VLNC cigarettes had
significantly lower demand for study cigarettes than those assigned to
smoke NNC cigarettes, suggesting that a nicotine reduction policy may
reduce the reinforcing value of combusted cigarettes in adolescents
(Ref. 624).
In summary, while existing data suggest that adolescents prefer LNC
cigarettes over VLNC cigarettes, and that they may display compensatory
smoking behaviors in response to VLNC cigarettes, these data are
limited. As discussed in section VII.B of this document, compensation
typically dissipates after repeated exposure. Thus, in the absence of
extended exposure studies, it is difficult to draw conclusions
regarding the effects of VLNC cigarette use on compensatory smoking in
adolescents and young adults.
Individuals with symptoms of mental health disorders smoke
cigarettes in disproportionately large numbers. People with symptoms of
mental health disorders who smoke cigarettes have increased nicotine
withdrawal symptoms (Refs. 625 and 626) and are more likely to smoke to
ameliorate negative mood (Ref. 627). As a result, this population has
increased risk of tobacco-related mortality (Ref. 130).
Researchers have investigated the effects of VLNC cigarettes in
people who use cigarettes with symptoms of mental health disorders to
determine whether VLNC cigarettes are associated with differential
effects on craving, withdrawal, smoking topography, or use behavior
among this group compared to the general population. In this group, as
in the general population, NNC cigarettes were associated with greater
reductions in craving and withdrawal symptoms compared to VLNC
cigarettes. In this group, VLNC cigarettes were not associated with
increased markers of compensatory smoking (e.g., smoking topography,
CO) compared to the general population. Researchers also assessed
psychiatric symptomatology as a function of VLNC cigarette use and
found that VLNC cigarettes were associated with improvements in mood
symptoms, likely due to the anxiety-increasing properties of nicotine.
Several studies investigated the effects of LNC and VLNC cigarettes
on mood following mood induction (i.e., an experimental method for
inducing a specific mood state) in people who use cigarettes with
symptoms of mental health disorders (Refs. 434, 450, and 628). These
studies found that, following positive mood induction, LNC cigarettes
compared to VLNC cigarettes were associated with an enhancement of
positive mood among people who smoke and are prone to depression, but
not control participants (Refs. 450 and 628). In addition, LNC
cigarettes, but not VLNC cigarettes, were associated with a worsening
of negative mood in response to negative mood induction among people
who smoke, regardless of baseline mental health status (Ref. 628).
Similarly, following an anxiety-eliciting mood induction, participants
with post-traumatic stress disorder self-reported greater relief of
anxiety after smoking LNC cigarettes compared to VLNC cigarettes;
however, LNC cigarettes increased physical autonomic symptoms of
anxiety (e.g., skin becomes a better conductor of electricity, heart
rate) relative to VLNC cigarettes (Ref. 434).
A secondary analysis of an extended exposure study assessed the
effects of cigarettes varying in nicotine content on changes in
psychiatric symptomatology among those with and without elevated
depression symptoms (Ref. 629). Among participants with elevated
depression symptoms, those assigned to smoke LNC or VLNC cigarettes for
6 weeks had lower depressive symptoms at the end of the study compared
to those assigned to smoke NNC cigarettes. Another study that assigned
participants with serious mental illness to receive either NNC or VLNC
cigarettes saw no change in participants' psychiatric symptoms at the
end of 6 weeks (Ref. 440).
Several studies assessed the effects of VLNC cigarettes on smoking
rates, nicotine craving, dependence, withdrawal, and subjective effects
among those with symptoms of mental health disorders (Refs. 391, 409,
434, 467, 468, 629, and 630). While some studies found no statistically
significant differences in craving or withdrawal as a function of
nicotine content following brief smoking abstinence in those with
symptoms of mental health disorders (Refs. 391, 434, and 467), others
showed that use of usual brand cigarettes was associated with larger
decreases in craving and withdrawal compared to VLNC cigarettes (Ref.
468). An extended exposure study found that, relative to NNC
cigarettes, use of LNC and VLNC cigarettes reduced smoking rates,
nicotine dependence, and cigarette craving, and these effects were not
moderated by baseline depressive symptoms (Ref. 629). In addition,
similar to the general population, people who smoke with poor mental
health rate NNC cigarettes as more rewarding (e.g., taste,
satisfaction) and reinforcing compared to VLNC cigarettes (Refs. 391,
450, 467, and 628). Additionally, a 33-week study that randomized
participants to either NNC cigarettes or a gradual nicotine reduction
to VLNC levels found that the gradual reduction group exhibited
significantly lower cotinine levels, CPD, and exhaled CO compared to
the NNC cigarette group. Mental health effects and adverse events did
not significantly differ between the two groups, and significantly more
participants in the gradual nicotine reduction group were abstinent at
the end of the treatment compared to the NNC cigarette group (Ref.
631).
A study that compared the effects of VLNC, LNC, and NNC cigarettes
on smoking behavior in people with opioid use disorder who smoke
cigarettes, women of childbearing age with a high school education or
less who smoke cigarettes, or individuals with affective disorders who
smoke cigarettes found no statistically significant differences in
smoking topography or breath CO as a function of nicotine content (Ref.
391). Subsequent analyses of this study also found that cannabis use
status, presence of chronic health conditions, and sex did not
correlate with differences in smoking topography or the reinforcing
effects of nicotine among people who smoke (Refs. 459 and 632). A
larger 12-week RCT among these same three populations found
statistically significantly lower CPD and nicotine dependence levels
across study weeks among those assigned to received VLNC or LNC
cigarettes compared to those assigned to receive NNC cigarettes (Ref.
633). A secondary analysis of this study found no statistically
significant effects of nicotine dose or population on tests of
cognitive performance, suggesting that cognitive performance was not
[[Page 5096]]
significantly impaired with prolonged exposure to VLNC cigarettes among
vulnerable populations (Ref. 634). A study among participants with
schizophrenia found that both people with schizophrenia who smoke and
control participants smoked fewer puffs and had lower total puff
volumes, shorter inter-puff intervals, longer puff durations, and
marginally higher individual puff volumes when smoking VLNC cigarettes
compared to usual brand cigarettes (Ref. 467). However, a subsequent
analysis using data from this same study showed that these differences
were not associated with increases in breath CO boost (Ref. 392).
A 33-week randomized clinical study evaluated the effects of
gradually reducing the nicotine content in cigarettes to VLNC cigarette
levels on ratings of dependence, biomarkers, and cessation in 245
adults of low socioeconomic status. CPD, plasma cotinine, CO, and NNAL
levels were significantly lower for the gradual reduction group
compared to the NNC cigarette group; however, there were no significant
differences in dependence or withdrawal as a function of group. Those
who received VLNC cigarettes were statistically significantly more
likely to make a quit attempt during the study compared to those in the
NNC cigarette group; however, there was no statistically significant
difference in quit rates as a function of group among those who chose
to make a quit attempt (Ref. 635). A secondary analysis of this study
showed that outcomes did not differ as a function of menthol status,
except that those participants who smoked menthol cigarettes had less
of a cotinine reduction (Ref. 636).
Several studies used laboratory paradigms to assess the effects of
alcohol on specific components of smoking behavior for nicotine versus
non-nicotine factors in people who consume alcohol heavily. One study
found that alcohol increased smoking urge and subjective ratings of
smoking for both NNC and VLNC cigarettes (Ref. 637), while another
study found that NNC cigarettes were associated with increases in
subjective effects and a greater reduction in cigarette craving than
VLNC cigarettes, and these effects were enhanced by ethanol self-
administration (Ref. 448). In addition, in a sample of people who
smoked who also regularly consumed alcohol, NNC cigarettes reduced
craving and increased cognitive performance compared to VLNC cigarettes
(Ref. 448). Furthermore, several secondary analyses of clinical studies
found no evidence that alcohol or marijuana use moderates the effects
of VLNC cigarettes, and VLNC cigarette use does not increase
compensatory alcohol, marijuana, or other illicit drug use (Refs. 386,
632, and 638). However, one secondary analysis found that although 20-
weeks of VLNC cigarette use reduced CPD compared to NNC cigarette use,
co-users of marijuana and cigarettes showed increased marijuana use
when assigned to VLNC cigarettes (Ref. 639).
In summary, research has shown that VLNC cigarettes reduce the
number of cigarettes smoked per day among populations that use tobacco
at disproportionately high levels, including those of low socioeconomic
status, and those with mental or behavioral health conditions.
Importantly, there has been little to no evidence that VLNC cigarettes
increase risk of adverse effects (e.g., exacerbations of psychiatric
symptomatology, drug use) in these populations. The proposed nicotine
product standard is not anticipated to be detrimental to these
populations; rather, it is anticipated to benefit these groups, as well
as the general population as a whole.
FDA recognizes that actors participating in illicit markets are
unlikely to conform their products and sales to Federal, State, and
local laws. As discussed elsewhere in this document, the available
evidence suggests that the health impacts of counterfeit products
should be minimal. As the National Research Council (NRC) and the
Institute of Medicine (IOM) (NRC/IOM) Report notes, ``Research on
counterfeit cigarettes to date has shown some differences in levels of
tar and selected toxicants in comparison with conventional cigarettes .
. . but these elevated levels have not been shown to affect overall
toxicity and, based on current evidence, are unlikely to significantly
increase the health risk of an already dangerous product'' (Ref. 560).
Even in studies (Ref. 640) that suggest that counterfeit cigarettes can
contain higher levels of harmful substances, the studies cannot make
conclusions about the individual or population-wide health risks from
such substances, in part because of the variations between them,
inconsistent distribution of the products among the population, and
inconsistent use among consumers. FDA will continue to monitor the best
available science to determine if this changes in the future.
Based on the available evidence, FDA finds that, while there may be
potential risks that could diminish the expected population health
benefits of the proposed standard, such effects would be significantly
outweighed by the potential benefits of the proposed nicotine product
standard. FDA requests additional information concerning the potential
risks discussed in this section, as well as any other negative effects
that could result from this rule, and how they could be minimized.
E. Approach Concerning Adjustments to Inputs to the Model Accounting
for Other Tobacco Product Standards
In 2022, FDA issued proposed tobacco product standards to prohibit
menthol as a characterizing flavor in cigarettes and to prohibit all
characterizing flavors (other than tobacco) in cigars (87 FR 26454, May
4, 2022). If finalized, these rules are anticipated to reduce overall
youth initiation and increase cessation among individuals who smoke
cigarettes and cigars. In this adjusted model, we utilized estimates of
the likely population health impact of these rules, quantified in peer-
reviewed publications and discussed in the rules, to adjust the
baseline inputs for initiation of combusted and noncombusted products,
as well as cessation of combusted products and likelihood of switching
to incorporate the impact of the final rules in this proposed nicotine
product standard.
We quantified the potential impact of a menthol cigarette product
standard on the U.S. population (87 FR 26454), assuming that the
implementation of a rule prohibiting menthol affects baseline model
input parameters associated with smoking initiation, smoking cessation,
noncombusted initiation, and switching from cigarettes to noncombusted
products. To avoid confusion with the main analysis baseline scenario,
we called this new scenario a ``menthol product standard baseline
scenario.'' First, we assumed that a menthol product standard is
implemented in 2025, 2 years before the implementation of a potential
nicotine product standard in 2027. Changes in tobacco use behaviors due
to the implementation of a menthol product standard (primarily for
people who would initiate future menthol cigarette use and people who
currently use menthol cigarettes) were derived from an expert
elicitation that was developed to assess the impact of a menthol
product standard on smoking initiation and cessation, and on
noncombusted use (Ref. 562). Specifically, 11 experts were asked to
estimate anticipated behaviors under a menthol product standard,
including transitioning to illicit menthol combusted products,
switching to non-menthol combusted products, switching to ENDS products
or HTPs, or quitting use of all tobacco products. We used the results
of the expert elicitation (finalized in September 2020) to
[[Page 5097]]
compute factors that can be used to scale smoking initiation and
cessation rates, as well as switching and noncombusted initiation,
accounting for a potential reduction/increase in rates. People who
currently smoke non-menthol cigarettes were assumed to be unaffected by
a menthol product standard. We used the average impact scenario from
Levy et al. 2023 (Ref. 562) to be consistent with the approach taken in
the proposed menthol product standard rule. Details regarding the
calculation of scaling factors, considering the expert elicitation
data, can be found in Appendix K of FDA's modeling document (Ref. 42).
In the menthol product standard baseline scenario, baseline smoking
initiation and noncombusted initiation rates were adjusted starting in
2025 (i.e., year of a potential menthol prohibition implementation)
until the end of the simulation period. Also, baseline smoking
cessation and complete switching (from cigarettes to noncombusted
products) were adjusted only at the first year of such a potential
menthol product standard implementation. After the first year, when a
sudden increase in smoking cessation and complete switching was
incorporated, the remaining people who smoke initiated use of non-
menthol or illicit menthol cigarettes, subject to the cessation and
complete switching rates for people who smoke non-menthol cigarettes
(Ref. 641). We conducted the analysis considering a mean decrease in
cigarette smoking initiation (based on estimates from an expert
elicitation), a mean increase in noncombusted product initiation, and a
mean increase in smoking cessation and switching, as presented in Levy
et al. 2023 (Ref. 562). It is important to note that the menthol-
adjusted population health model does not directly estimate the public
health impacts of a prohibition on menthol as characterizing flavor in
cigarettes. In other words, the difference between the unadjusted
baseline scenario and menthol-adjusted baseline scenario of the model
should not be expected to approximate the impact of a potential menthol
product standard. FDA's determination of the estimated public health
impact of the menthol product standard is discussed in detail in the
preamble to the proposed menthol product standard. In the nicotine
population health model, FDA utilizes results from an expert
elicitation (Ref. 562) developed to estimate changes in tobacco use
behaviors resulting from a menthol product standard (such as changes in
smoking initiation or cessation) to adjust for the effect of a menthol
rule over time. One important assumption of the FDA model is that the
nicotine product standard would be implemented in 2027, whereas a
menthol rule would be implemented in 2025. This is important to keep in
mind as public health benefits attributable to a menthol rule (such as
mortality and morbidity health impacts) will be accruing for 2 years
before implementation of the nicotine product standard (and, therefore,
not captured in this model).
A more comprehensive analysis of the public heath impact of the
menthol cigarette product standard can therefore be found in the
proposed menthol product standard. There are also other important
differences between the menthol-adjusted FDA model and the Levy et al.
modeling approach that can impact comparability, such as input model
parameters, modeling frameworks, assumptions, and source data. For
these reasons, it is not appropriate to expect that the difference
between public health impact estimates of the nicotine product standard
with and without the menthol adjustment would directly approximate the
potential public health benefits of the menthol product standard as
presented in the proposed menthol product standard.
In 2022, FDA also issued a proposed product standard to prohibit
characterizing flavors (other than tobacco) in cigars (87 FR 26396, May
4, 2022). It is estimated that such a standard would prevent 780 deaths
due to cigar smoking in the United States each year (Ref. 134). A post-
processing analysis of cumulative non-premium cigar-attributable deaths
avoided was conducted to account for the effects of such a product
standard, considering the adjustments due to the menthol cigarette
product standard. For this analysis, we assumed both rules--the menthol
cigarette and flavored cigar product standards--to be implemented in
2025. Specifically, we assumed that the avoided cigar-attributable
deaths expected to result from the flavored cigar rule begin to occur 2
years after the rule's effective date (2027) and would increase in a
phased-in manner over a 30-year period. We then assumed a full annual
mortality benefit of 780 avoided deaths would continue after 30 years
(from 2026 to 2055), with a constant benefit of 780 deaths avoided
until year 2064. We also assumed avoided cigar-attributable deaths will
increase from 780 in 2064 to 1,120 in 2100.
Details regarding the calculation of avoided cigar-attributable
deaths because of the flavored cigar rule can be found in Appendix L of
FDA's modeling document (Ref. 42). The estimated deaths averted by a
flavored cigar product standard were subtracted from baseline non-
premium cigar deaths in the United States each year to produce yearly
estimates for non-premium cigar deaths with a flavored cigar standard.
We used these estimates to calculate a ratio of non-premium cigar to
cigarette-attributable deaths for each year in the projection period
and applied those values to the projections of avoided cigarette-
attributable deaths to estimate non-premium cigar-attributable deaths
under the nicotine product standard scenario.
F. Benefits and Risks to the Population as a Whole Accounting for Other
Tobacco Product Standards
Table 11 presents the impact results of the nicotine product
standard using baseline assumptions adjusted for the effect of a
menthol cigarette product standard for years 2040, 2060, 2080, and
2100. In general, changes to baseline inputs of initiation and
cessation of combusted products as well as switching to noncombusted
products as a result of implementation of a menthol cigarette product
standard slightly reduced projected smoking prevalence and avoided
mortality and morbidity, compared to the main analysis results.
Specifically, we estimate that by 2060, the proposed nicotine product
standard would avert approximately 1.6 million deaths due to tobacco,
rising to approximately 3.4 million by 2100. These estimates are
approximately 11 percent and 21 percent less than the corresponding
estimates that do not account for the potential impact of a menthol
product standard. The reduction in premature deaths as a result of the
nicotine product standard, when accounting for a menthol product
standard, would result in 17.9 million life years gained by 2060,
raising to 60.6 million life years gained by 2100. These estimates
represent a 9 percent and 21 percent reduction compared with the
corresponding estimates under the main analysis.
[[Page 5098]]
Table 11--Impact of Proposed Nicotine Product Standard Implemented in
2027 on Projected Smoking Prevalence and Avoided Mortality and Morbidity
From the Main Analysis (Unadjusted Baseline Scenario) and With
Adjustment for a Menthol Cigarette Product Standard Implemented in 2025
[Median (5th, 95th percentiles) estimates]
------------------------------------------------------------------------
Estimates with
Estimates from adjustment for a
Year/period main analysis menthol cigarette
standard
------------------------------------------------------------------------
Cigarette Smoking Prevalence (%)
------------------------------------------------------------------------
2040.............................. 0.2 (0.07, 4.0) 0.1 (0.06, 2.8)
2060.............................. 0.2 (0.07, 2.2) 0.1 (0.05, 1.4)
2080.............................. 0.2 (0.06, 2.0) 0.1 (0.05, 1.3)
2100.............................. 0.2 (0.06, 1.9) 0.1 (0.05, 1.2)
------------------------------------------------------------------------
Cumulative Tobacco-Attributable Deaths Avoided (Millions)
------------------------------------------------------------------------
2040.............................. 0.4 (0.1, 0.5) 0.4 (0.1, 0.5)
2060.............................. 1.8 (0.4, 2.0) 1.6 (0.4, 1.7)
2080.............................. 3.1 (1.0, 3.4) 2.6 (0.7, 2.8)
2100.............................. 4.3 (1.6, 4.6) 3.4 (1.1, 3.6)
------------------------------------------------------------------------
Cumulative Life Years Gained (Millions)
------------------------------------------------------------------------
2040.............................. 2.0 (0.2, 2.7) 2.0 (0.2, 2.6)
2060.............................. 19.6 (3.6, 22.7) 17.9 (3.4, 20.4)
2080.............................. 47.4 (12.5, 52.5) 40.6 (10.3, 44.5)
2100.............................. 76.4 (26.5, 82.5) 60.6 (19.2, 65.3)
------------------------------------------------------------------------
Cumulative QALYs Gained from Reduced Smoking Morbidity (Millions)
------------------------------------------------------------------------
2040.............................. 9.6 (2.7, 10.0) 7.8 (2.1, 8.1)
2060.............................. 24.0 (10.1, 24.7) 17.5 (7.0, 17.9)
2080.............................. 38.2 (18.5, 39.2) 26.1 (11.9, 26.6)
2100.............................. 53.1 (27.5, 54.4) 34.9 (17.0, 35.7)
------------------------------------------------------------------------
Table 12 presents the impact results of the nicotine product
standard implemented in 2027, using baseline assumptions adjusted for
the effect of a flavored cigar product standard implemented in 2024. We
estimate that by 2060, in the United States, approximately 45,600
deaths due to non-premium cigar use will be averted, rising to
approximately 164,000 deaths avoided by 2100 (table 12). In general,
these estimates are approximately 17 and 30 percent less than the
corresponding estimates without the potential impact of a product
standard for flavored cigars.
Table 12--Projected Number of Tobacco-Attributable Deaths From Non-Premium Cigar Use Avoided for as a Result of
a Nicotine Product Standard Implemented in 2027 From the Main Analysis and With Adjustment for Flavored Cigar
and Menthol Cigarette Product Standards Implemented in 2025
----------------------------------------------------------------------------------------------------------------
Cumulative non-premium cigar-
Cumulative non-premium cigar- attributable deaths avoided with
Year Percentiles attributable deaths avoided flavored cigar and menthol
from main analysis cigarette standards
----------------------------------------------------------------------------------------------------------------
2040.......................... Median (5th, 8,900 (1,000, 11,000) 8,000 (1,000, 9,500)
95th).
2060.......................... Median (5th, 54,800 (13,200, 60,500) 45,600 (11,100, 49,700)
95th).
2080.......................... Median (5th, 134,7000 (46,000, 144,100) 107,700 (35,000, 114,500)
95th).
2100.......................... Median (5th, 214,700 (91,600, 225,800) 164,000 (65,000, 172,100)
95th).
----------------------------------------------------------------------------------------------------------------
G. Conclusion
FDA has considered scientific evidence related to the likely impact
of the proposed rule establishing a maximum nicotine level in
cigarettes and certain other combusted tobacco products on people who
currently do not use these products, people who currently use these
products, and the U.S. population as a whole. The impact of the
proposed standard was considered alone, as well as adjusted for the
inclusion of other tobacco product standards: prohibition of menthol as
a characterizing flavor in cigarettes and prohibition of all
characterizing flavors (other than tobacco) in cigars. Based on these
considerations, we find that the proposed tobacco product standard is
appropriate for the protection of the public health because it would
increase the likelihood that many people who currently smoke cigarettes
and/or certain other combusted tobacco products would stop smoking
altogether, yielding significant health benefits from smoking
cessation. Additionally, we find that the proposed standard is
appropriate for the protection of the public health because it would
decrease the likelihood that people who do not smoke cigarettes and/or
use certain other combusted
[[Page 5099]]
tobacco products--particularly youth and young adults--who experiment
with combusted tobacco products will become addicted to these products,
thereby decreasing progression to regular use, resulting in reduced
tobacco-related morbidity and mortality associated with combusted
tobacco product use. The proposed standard would also yield benefits in
terms of reduced mortality as a result of reduced secondhand smoke
exposure, smoking-related fires, smoking-related perinatal conditions,
and use of alternative tobacco products.
Tobacco use is the leading preventable cause of disease and death
in the United States. Cigarettes are responsible for 480,000 premature
deaths every year from many diseases, put a substantial burden on the
U.S. healthcare system, and cause massive economic losses to society
(Ref. 1 at p. 659-666). Even modest reductions in the percentage of
people initiating and modest increases in the percentage of people
quitting smoking would lead to substantial reductions in the annual
smoking-attributable deaths and fewer cases of disease attributed to
combustible tobacco products in the United States.
In the United States, approximately 362,000 youth (ages 12-17)
smoked their first cigarette in 2021 (Ref. 552). Additionally, nearly
90 percent of adults who currently smoke cigarettes daily in the United
States report having smoked their first cigarette by the age of 18
(Ref. 1). Nicotine is a highly addictive substance, and multiple
studies have shown that symptoms of nicotine dependence can arise early
after youth start smoking cigarettes, even among those who smoke
cigarettes infrequently (Refs. 24, 65, and 93).
Reducing the addictive potential of combusted cigarettes and
certain other tobacco products via establishing a maximum level of
nicotine in these products would help to decrease the likelihood that
people who do not smoke cigarettes and/or use certain other combusted
tobacco products--particularly youth and young adults--who experiment
with them will develop addiction to nicotine and progress to regular
use, thereby greatly reducing the chances of suffering from tobacco-
related disease and death. FDA anticipates that the proposed standard
would produce substantial health benefits. Even small changes in
initiation and cessation would result in a significant reduction in the
burden of death and disease in the United States caused by smoking,
including reductions in smoking-related morbidity and mortality,
diminished exposure to secondhand smoke among people who do not smoke
cigarettes, decreased potential years of life lost, decreased
disability, and improved quality of life for current and future
generations to come.
While preventing initiation to regular cigarette smoking and
combusted tobacco product use by even modest amounts carries the
greatest potential from this proposed standard to improve population
health in the long term, FDA anticipates that the proposed standard
would produce substantial short- and long-term health benefits
resulting from decreased consumption and increased cessation among
people who currently smoke cigarettes or other combusted tobacco
products and wish to decrease use or quit. In the United States, there
are currently approximately 39 million people ages 12 and older who
smoke combusted tobacco products (Refs. 275 and 281). As previously
described, the health benefits of smoking cessation are substantial.
FDA's population health model estimates that approximately 1.8 million
deaths in the United States due to tobacco would be avoided by the year
2060, rising to 4.3 million by the end of the century. The reduction in
premature deaths attributable to the product standard would result in
19.6 million life years gained by 2060 and 76.4 million life years
gained by 2100. Beyond averted deaths, societal benefits would include
reduced smoking-related morbidity and health disparities, diminished
exposure to secondhand smoke among people who do not smoke cigarettes,
decreased potential years of life lost, decreased disability, and
improved quality of life among people who formerly smoked cigarettes.
FDA's finding that the proposed product standard would be
appropriate for the protection of the public health is reasonable and
well-supported by scientific evidence. Cigarettes are the most toxic
consumer product when used as intended, and nicotine is the primary
constituent in cigarettes and other tobacco products that causes and
maintains addiction. Given the existing scientific evidence described
in sections VIII.B and VIII.C of this document, FDA finds that the
proposed product standard is appropriate for the protection of the
public health because it would increase the likelihood that many people
who currently smoke cigarettes and/or certain other combusted tobacco
products who wish to stop smoking altogether, would be able to do so,
yielding significant health benefits from smoking cessation.
Additionally, we find that the proposed standard is appropriate for the
protection of the public health because it would decrease the
likelihood that people who do not smoke cigarettes and/or certain other
combusted tobacco products--particularly youth and young adults--who
experiment with them and initiate use, develop an addiction to
nicotine, and progress to regular use as result of that addiction,
thereby greatly reducing the chances of suffering from tobacco-related
disease or death. Across the population, these changes in cigarette
smoking behavior and combusted tobacco product use would lead to lower
disease and death in the United States in both the short-term and in
the future, due to diminished exposure to tobacco smoke among both
people who smoke cigarettes and people who do not smoke cigarettes.
In addition to the determination that the proposed product is
appropriate for the public health, FDA anticipates the proposed product
standard also will improve health outcomes among populations that are
disproportionately impacted by tobacco use and tobacco-related
morbidity and mortality, such as adolescents as well as those with
mental health and substance use disorders. As previously described,
adolescence is a period of significant vulnerability regarding the
onset and progression of tobacco use. Additionally, cigarette smoking
is disproportionately prevalent among persons with symptoms of mental
health disorders and substance use disorders, resulting in increased
risk of tobacco-related morbidity and mortality in these groups.
Accordingly, the proposed product standard is anticipated to promote
better public health outcomes across these population groups.
IX. Additional Considerations and Requests for Comment
A. Section 907 of the FD&C Act
FDA is required by section 907 of the FD&C Act to consider the
following information submitted in connection with a proposed product
standard:
For a proposed product standard to require the reduction
or elimination of an additive, constituent (including smoke
constituent), or other component of a tobacco product because FDA has
found that the additive, constituent (including a smoke constituent),
or other component is or may be harmful, scientific evidence submitted
by any party objecting to the proposed standard demonstrating that the
proposed standard will not reduce or eliminate the risk of illness or
injury (section 907(a)(3)(B)(ii) of the FD&C Act).
Information submitted regarding the technical
achievability of compliance with the standard, including with regard
[[Page 5100]]
to any differences related to the technical achievability of compliance
with such standard for products in the same class containing nicotine
not made or derived from tobacco and products containing nicotine made
or derived from tobacco (section 907(b)(1) of the FD&C Act).
All other information submitted, including information
concerning the countervailing effects of the tobacco product standard
on the health of adolescent tobacco users, adult tobacco users, or
nontobacco users, such as the creation of a significant demand for
contraband or other tobacco products that do not meet the requirements
of chapter IX of the FD&C Act and the significance of such demand
(section 907(b)(2) of the FD&C Act).
As required by section 907(c)(2) of the FD&C Act, FDA invites
interested persons to submit a draft or proposed tobacco product
standard for the Agency's consideration (section 907(c)(2)(B)) and
comments on and information regarding structuring the standard so as
not to advantage foreign-grown tobacco over domestically grown tobacco
(section 907(c)(2)(C)) of the FD&C Act. In addition, FDA invites the
Secretary of Agriculture to provide any information or analysis that
the Secretary of Agriculture believes is relevant to the proposed
tobacco product standard (section 907(c)(2)(D) of the FD&C Act).
With this proposed rule, FDA is requesting all relevant documents
and information described in this section. Such documents and
information may be submitted in accordance with the ``Instructions''
included in the preliminary information section of this document.
Section 907(d)(5) of the FD&C Act allows FDA to refer a proposed
regulation for the establishment of a tobacco product standard to the
Tobacco Products Scientific Advisory Committee (TPSAC) at the Agency's
own initiative or in response to a request that demonstrates good cause
for a referral and is made before the expiration of the comment period.
Sections 917(c)(2) and (c)(3) (21 U.S.C. 387q(c)(2) and (c)(3)) also
provide that TPSAC shall provide advice, information, and
recommendations on the effects of the alteration of the nicotine yields
from tobacco products and regarding whether there is a threshold level
below which nicotine yields do not produce dependence on the tobacco
product involved, respectively.
B. Pathways to Market
To legally market a new tobacco product \38\ in the United States,
a tobacco product must receive authorization from FDA permitting the
marketing of the new tobacco product under one of three premarket
review pathways: (1) the applicant obtains an order under section
910(c)(1)(A)(i) of the FD&C Act (order after review of a premarket
tobacco product application under section 910(b)); (2) the applicant
obtains an order finding the new tobacco product to be substantially
equivalent to a predicate tobacco product and in compliance with the
requirements of the FD&C Act under section 910(a)(2)(A)(i) (order after
review of a Substantial Equivalence (SE) Report submitted under section
905(j) of the FD&C Act (21 U.S.C. 387e(j))); or (3) the applicant makes
a request under 21 CFR 1107.1 and obtains an exemption from the
requirements related to SE (section 905(j)(3)(A)), and at least 90 days
before commercially marketing the product, submits a report under
section 905(j) including the information required in section
905(j)(1)(A)(ii) and (B) of the FD&C Act.
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\38\ Products that were commercially marketed in the United
States as of February 15, 2007 (referred to as ``pre-existing
tobacco products,'' previously referred to as ``grandfathered
products''), are not considered new tobacco products and do not
require prior authorization to be legally marketed (section 910(a)
of the FD&C Act).
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Applicants may be able to use the SE pathway for products seeking
to comply with this proposed product standard (if finalized) by making
modifications to their products in a manner that FDA finds does not
cause the new tobacco product to raise different questions of public
health. Applicants may be able to submit a streamlined SE Report
containing information sufficient to demonstrate that the changes to
the subject of that SE Report do not cause the new tobacco product to
raise different questions of public health and to certify that no other
changes were made to the new tobacco product as compared with the
predicate product and that all other characteristics are identical (see
relevant provisions of the SE final rule codified at 21 CFR
1107.18(l)(2)). FDA has received numerous successful applications where
the manufacturer described all modification(s) between the new and
predicate tobacco product and provided a certification statement that
all other characteristics are identical. For example, for products
modified to comply with this product standard, the applicant could
demonstrate how the modification was made to the tobacco filler,
provide test data to show that the modification reduced the nicotine
content to meet the standard and did not cause the new product to raise
any different questions of public health, and provide a certification
that no other modifications were made to the new tobacco product other
than those made to reduce the level of nicotine.
An applicant may also be able to use the SE Exemption pathway under
section 905(j)(3)(A) of the FD&C Act to the extent the applicant is
modifying a legally marketed tobacco product by adding or deleting a
tobacco additive, or increasing or decreasing the quantity of an
existing tobacco additive if such modification would be a minor
modification. While the SE Exemption pathway may be a viable option in
limited circumstances, FDA notes that the statutory definition of
``additive'' excludes tobacco or a pesticide chemical residue in or on
raw tobacco or a pesticide chemical (section 900(1) of the FD&C Act).
Therefore, to the extent modifications to a tobacco product involve
changes to the tobacco (e.g., changes to the nicotine content of the
tobacco used in a tobacco product), such changes would render section
905(j)(3) of the FD&C Act inapplicable.
If a currently legally marketed tobacco product is already in
compliance with this proposed product standard, a premarket
authorization application would not be needed.
FDA requests comments regarding changes manufacturers may make to
their tobacco products to comply with this proposed product standard
and what information and evidence they might provide to satisfy the
premarket review requirements of the Tobacco Control Act.
C. Considerations and Request for Comments on Scope of Products
As indicated throughout this document, FDA has determined that the
proposed standard, which would apply to cigarettes and certain other
combusted finished tobacco products, is appropriate for the protection
of the public health. It would cover the products that are responsible
for the greatest amount of tobacco-related morbidity and mortality. The
proposed scope of this rule--applying to cigarettes (other than
noncombusted cigarettes, such as HTPs that meet the definition of a
cigarette), cigarette tobacco, RYO tobacco, cigars (other than premium
cigars), and pipe tobacco--is appropriate to protect the public health
and is justified by existing evidence. We request comments, data, and
research regarding the proposed scope of this rule.
[[Page 5101]]
FDA is not proposing to include noncombusted cigarettes, such as
HTPs that meet the definition of a cigarette in section 900(3) of the
FD&C Act (proposed Sec. 1160.3 includes a definition of cigarette),
within the scope of this proposed product standard. While noncombusted
cigarettes (such as HTPs) that meet the definition of cigarette in the
FD&C Act must adhere to existing restrictions for cigarettes under FDA
regulations, some of these products may deliver fewer or lower levels
of some toxicants than combusted cigarettes (Ref. 642). FDA recognizes
that tobacco products exist on a continuum of risk, with combusted
cigarettes being the deadliest, and that certain specific products
meeting the definition of a cigarette (e.g., some that are not
combusted) may pose less risk to individuals who use these products or
to population health than other products meeting the definition of a
cigarette.
In general, as discussed in this document, nicotine is the primary
addictive constituent in tobacco products, and it is the nicotine in
such products that both creates and sustains addiction, playing a
significant role in creating and perpetuating tobacco-related negative
health consequences. While these effects raise concerns in the context
of any tobacco product--none of which is without risk--FDA recognizes
that certain products that meet the definition of cigarette in the FD&C
Act may present different considerations with respect to this proposed
product standard. Accordingly, FDA requests comments, data, and
research regarding the proposal to exclude noncombusted cigarettes
(such as HTPs that are cigarettes) from the scope of this proposed
rule, including any data that could justify otherwise.
FDA considered including waterpipe tobacco products within the
scope of this proposed product standard; however, the Agency has
determined that waterpipe tobacco involves profoundly different use
behaviors than combusted cigarettes, which makes it an unlikely
substitute for cigarettes. We therefore do not propose including
waterpipe tobacco products within the scope of this proposed rule.
Data on frequency of use differentiates waterpipe tobacco from
cigarettes. For instance, according to the 2024 NYTS, 0.7 percent of
middle and high school students (or approximately 190,000 students)
reported using waterpipe tobacco within the previous 30 days, compared
with estimates for previous 30-day cigarette use (1.4 percent; 380,000
students) and cigar use (1.2 percent; 330000 students) (Ref. 3).
However, waterpipe tobacco is significantly less likely to be smoked
daily. In fact, given the relative infrequency of waterpipe use, it is
often reported in terms of monthly versus less than monthly use, rather
than daily versus non-daily. Data from Waves 1 (2013-2014) and 2 (2014-
2015) of the PATH Study indicated that, among adults who used
waterpipes in the past year, 77.1 percent reported less than monthly
use at Wave 1; by Wave 2, 44.9 percent of these adults continued using
waterpipe less than monthly, while 6.4 percent progressed to monthly or
more frequent use (Ref. 643). For comparison, 59.1 percent of adults in
the 2018 NHIS who smoke cigarettes report daily use (Ref. 644). Wave 3
(2015-2016) PATH Study data also indicate the infrequency of daily
waterpipe use: 0.1 percent of youth, 0.3 percent of young adults, and 0
percent of adults 25 and older reported daily waterpipe use (Ref. 645).
Comparatively, analysis from Wave 3 of the PATH study found that 0.6
percent of youth, 11.4 percent of young adults, and 15.3 percent of
adults older than 25 reported daily cigarette smoking (Ref. 646).
FDA acknowledges that the health consequences of waterpipe usage
are far from innocuous. People who use waterpipes are exposed to many
of the same toxicants as people who smoke cigarettes, and due to the
extended duration of each waterpipe session (i.e., approximately 1
hour), waterpipe use may lead to higher toxicant exposure per session
than toxicant exposure from one cigarette (Refs. 647 and 648). Thus,
people who use waterpipes are likely subject to many of the same severe
negative health effects as people who smoke cigarettes (Ref. 649).
However, FDA does not anticipate significant migration to waterpipe
usage under the proposed product standard. Waterpipes as currently
marketed are generally large and require time-consuming preparation,
leading to an approximate waterpipe smoking session of 1 hour (Ref.
650). The limited accessibility and mobility of waterpipes as generally
currently used contribute to their predominant intermittent usage
patterns (Ref. 650). FDA assesses that these aspects of waterpipe
design would similarly substantially limit their utility as a
substitute for cigarettes and other combusted tobacco products that
would be subject the proposed product standard, especially as compared
to the portability and ease of use of many HTP, ENDS, and other
noncombusted tobacco products that are currently legally marketed and
not subject to the proposed product standard.
FDA requests information and data regarding the proposal to exclude
waterpipe tobacco from the scope of this proposed rule.
FDA is not including noncombusted tobacco products, such as ENDS
(which include e-cigarettes) and smokeless tobacco products, in the
scope of this proposed product standard. FDA's approach in proposing
this product standard for cigarettes and certain other combusted
tobacco products seeks to protect public health by reducing combusted
tobacco product use (and therefore reducing exposure to harmful
toxicants created through combustion) while potentially less harmful,
noncombusted tobacco products remain available for people who do not
quit all tobacco-product use. As such, at this time, FDA is focusing
this proposed rule on nicotine levels in cigarettes and certain other
combusted products because combusted tobacco products are responsible
for the majority of death and disease due to tobacco use. Importantly,
this action would also help to prevent people who experiment with
cigarettes and cigars (mainly youth) from moving beyond
experimentation, developing an addiction to nicotine, and progressing
to regular use of combusted tobacco products as a result of that
addiction. We request comments, data, and research regarding the
proposed scope of this rule.
D. Considerations and Request for Comments on the Potential for Illicit
Trade
The implementation of a maximum nicotine level in cigarettes and
certain other combusted tobacco products could result in some people
seeking NNC combusted tobacco products through illicit trade markets.
FDA is also considering whether illicit trade could occur as a result
of a nicotine product standard and whether such activity could
significantly undermine the public health benefits of the product
standard.
Since the enactment of the Tobacco Control Act, FDA has been
committed to studying and understanding the potential effects of a
product standard on the illicit tobacco market. As part of FDA's
consideration of possible regulations, the Agency asked the NRC and IOM
of the National Academy of Sciences (now the National Academies) to
assess the international illicit tobacco market, including variations
by country; the effects of various policy mechanisms on the market; and
the applicability of international experiences to the United States
(Ref. 560). In 2015, the NRC/IOM issued its final report entitled
``Understanding the U.S. Illicit Tobacco
[[Page 5102]]
Market: Characteristics, Policy Context, and Lessons from International
Experiences,'' finding that, although there is insufficient evidence to
draw firm conclusions regarding how the U.S. illicit tobacco market
would respond to regulations requiring a reduction in the nicotine
content of these products, demand for illicit cigarettes would be
limited because some people who smoke would quit, and others would use
modified products (e.g., VLNC cigarettes) or seek legal alternatives
(Ref. 560 2015 at p. 9). In addition, in March 2018, FDA issued a draft
concept paper, entitled ``Illicit Trade in Tobacco Products after
Implementation of a Food and Drug Administration Product Standard,'' as
an initial step in assessing the possible health effects of a tobacco
product standard in the form of demand for contraband or nonconforming
tobacco products (83 FR 11754). Among other issues, the draft concept
paper examined the factors that might support or hinder the
establishment of a persistent illicit trade market related to a product
standard (Ref. 44). Additionally, in the Nicotine ANPRM, FDA expressed
interest in data regarding possible increases in illicit trade and its
effect on the marketplace in the event that a nicotine tobacco product
standard is finalized. Comments were submitted by members of the
tobacco industry, public health organizations, academic researchers,
and the public. Comments varied in their conclusions as to how
significant illicit trade might be after implementation of an FDA
product standard, but no information was submitted in response to the
Nicotine ANPRM that caused FDA to revise its overall assessment about
the difficulties in establishing sustained, significant illicit trade
markets that are able to evade enforcement authorities.
Establishing and maintaining illicit markets in relevant tobacco
products will be challenging, and to the extent that they emerge, it is
unlikely they will be significant enough to outweigh the benefits of
the product standard. Although some people who smoke may seek to
purchase illicit products if available and accessible, the NRC/IOM
report stated that this ``would require established distribution
networks and new sources of product (which would either have to be
smuggled from other countries or produced illegally) to create a supply
of cigarettes with prohibited features'' (Ref. 560 at p. 9). The
current illicit cigarette trade in the United States is predominantly
based on tax evasion and is facilitated by ease of access to tobacco
products close to where the sales to consumers take place (e.g., across
State lines). Enforcement against such illicit trade is outside the
scope of FDA's authority (as FDA does not enforce tax laws) and is
complicated by the inability to distinguish tax-paid from tax-evading
cigarette packs in most instances. However, due to the reduction of
nicotine in combusted tobacco products nationwide, a lack of supply
would likely limit illicit trade of NNC cigarettes and certain other
combusted tobacco products once a product standard is in place. Illicit
manufacturing of NNC cigarettes at a scale large enough to diminish the
public health benefits of this proposed product standard would be
difficult to disguise from Federal, State, and local enforcement
authorities. Moreover, importation across international borders is
substantially more difficult than across State borders, particularly
for the volume necessary to sustain nicotine addiction in people who
smoke. Additionally, while it would remain legal for domestic cigarette
manufacturers to produce NNC cigarettes and certain other combusted
tobacco products for export (as previously described in section III.C
of this document), it is unclear the extent to which there would be
diversion of legally manufactured products for export that are
subsequently sold illegally domestically. As noted in multiple FDA
reports to Congress regarding U.S. tobacco product exports, after the
product standard prohibiting characterizing flavors (other than tobacco
or menthol) in cigarettes was implemented, the U.S. Census Bureau
surveyed the vast majority of domestic manufacturers and found no
evidence that any continued to manufacture flavored cigarettes or their
components or parts (Ref. 651). Importantly, and relevant to any
continued domestic manufacture for export, section 920(d) of the FD&C
Act (21 U.S.C. 387t(d)) requires that manufacturers and distributors
notify the Attorney General and the Secretary of the Treasury of
illicit trade activities (such as import, export, distribution, or
diversion), increasing the overall vigilance on the matter. Finally, as
the NRC/IOM Report explains, comprehensive interventions by several
countries show it is possible to reduce the size of the illicit tobacco
market through enforcement mechanisms and collaborations across
jurisdictions (Ref. 560).
Research also has shown that the choice between VLNC and NNC
cigarettes can be influenced by factors such as cost (see section VI.B
of this document for further discussion). It is well-established that
people who smoke are price-sensitive, and there is a direct correlation
with the increased price of cigarettes and reductions in consumption
(Ref. 652), showing for every ten percent increase in price, there is
an overall reduction in consumption of 3-5 percent, and youth smoking
decreases by 6-7 percent. This price sensitivity also contributes to
the willingness of people who smoke cigarettes to shift consumption
toward non-cigarette tobacco products in times of economic or product
constraint (Refs. 345, 346, and 349). Additionally, there is an
``inconvenience cost'' to the purchase of illicit tobacco products that
rises and falls depending upon the location of illegal sales,
reliability of supply, fear of embarrassment and legal penalties, and
more (Ref. 560 at p. 67). Although illicit NNC cigarettes and certain
other combusted tobacco products will not be subject to taxes,
participants in any illicit market will demand profits sufficient to
cover both their costs as well as compensate for the risks of
enforcement, limiting how low they can price the illicit tobacco
products. As a result, when the cost or effort required to obtain
illicit products increases, people who smoke may switch their
preference from NNC combusted tobacco products to VLNC versions (Ref.
391), to other legal tobacco products, and/or renew their cessation
efforts. Each of these alternatives reduces the number of potential
buyers of illicit products, lowering the incentives to try, create, and
sustain such markets.
Related to concerns about enforcement against individual consumers
for possessing or using nonconforming tobacco products acquired through
an illicit market, FDA's enforcement will only address manufacturers,
distributors, wholesalers, importers, and retailers. This regulation
does not include a prohibition on individual consumer possession or use
of nonconforming product acquired through an illicit market, and FDA
cannot and will not enforce against individual consumers for possession
or use of NNC cigarettes or other combusted tobacco products covered by
this proposed product standard. In addition, State and local law
enforcement agencies do not enforce the FD&C Act. These entities do not
and cannot take enforcement actions against any violation of chapter IX
of the Act or this regulation on FDA's behalf. FDA recognizes concern
about how State and local law enforcement agencies enforce their own
laws in a manner that may impact equity and
[[Page 5103]]
community safety and seeks comments on how FDA can best make clear the
respective roles of FDA and State and local law enforcement.
FDA is not proposing to ban any category of tobacco products with
this proposed product standard, and authorized products that are not
subject to the proposed product standard will remain legally available.
Therefore, this proposed product standard is not expected to lead to a
surge in illicit tobacco product use. In reaching this conclusion, FDA
has considered several factors that are likely to affect the potential
for illicit trade. For example, FDA anticipates that a nationwide
standard that prohibits the manufacture (other than for export as
previously described in section III.C of this document) and sale of
cigarettes and certain other combusted tobacco products that exceed the
maximum nicotine level set by this proposed product standard, coupled
with FDA's authority to take enforcement actions and other steps
regarding the sale and distribution of illicit tobacco products, would
limit the manufacture and distribution of these products. FDA also
expects that a nationwide product standard would eliminate the use of
online retailers to purchase illicit tobacco products as well as any
incentive to travel within the United States in search of jurisdictions
without a nicotine product standard because no such jurisdictions would
exist. FDA thus anticipates that the rule would result in much less
illicit trade than observed in the case of a State or local requirement
and that any such trade would be significantly outweighed by the
benefits of the rule. Even if some amount of illicit trade develops
(Refs. 42 and 653 discuss projected impacts of various rates of
potential illicit trade), it would have to be of significantly greater
magnitude than any previously seen illicit markets in order to outweigh
the significant public health benefits of this proposed standard, and
it would have to continue to exist at those levels despite the various
enforcement agencies and tools involved.
FDA requests comments, including supporting data and research,
regarding whether and to what extent this proposed rule would result in
an increase in illicit trade in NNC cigarettes and certain other
combusted tobacco products covered by the proposed nicotine product
standard and how any such increase could impact public health. Data or
other reliable information that do not rely on estimates of current,
interstate tax-evading illicit trade would be particularly relevant. If
an illicit market develops after this proposed product standard is
finalized, FDA has the authority to take enforcement actions and other
steps regarding the sale and distribution of illicit tobacco products,
including those imported or purchased online. FDA conducts routine
surveillance of sales, distribution, marketing, and advertising related
to tobacco products and takes appropriate actions when violations
occur. If this product standard is finalized as proposed and goes into
effect, it would be illegal to import cigarettes and certain other
combusted tobacco products that exceed 0.70 mg nicotine per gram of
total tobacco, and such products would be subject to import examination
and refusal of admission under the FD&C Act. Similarly, it would be
illegal to sell or distribute cigarettes and certain other combusted
tobacco products that do not comply with this product standard,
including those sold online, and doing so may result in FDA initiating
enforcement or regulatory actions. We note that the Prevent All
Cigarette Trafficking Act of 2009 establishes restrictions that make
cigarettes generally nonmailable through the U.S. Postal Service,
subject to certain exceptions (18 U.S.C. 1716E). Outside of these
exceptions, the U.S. Postal Service cannot accept or transmit any
package that it knows, or has reasonable cause to believe, contains
nonmailable cigarettes, smokeless tobacco, or ENDS.\39\
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\39\ These restrictions were updated to include similar
prohibitions on the shipment of ENDS in 2021 (86 FR 58399, October
21, 2021).
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X. Description of Proposed Regulation
This proposed rule would establish a new part 1160 that would set a
maximum level of nicotine in finished cigarettes and certain other
finished combusted tobacco products. Part 1160 would describe the scope
of the proposed regulation, applicable definitions, the establishment
of a maximum nicotine level in products covered by this proposed rule,
product testing and related requirements, and recordkeeping
requirements.
A. General Provisions (Proposed Subpart A)
1. Scope (Proposed Sec. 1160.1)
Proposed Sec. 1160.1(a) would provide that this part sets out a
tobacco product standard under the FD&C Act to limit nicotine yield by
setting a maximum nicotine content level for certain finished tobacco
products. We are proposing that this product standard would cover the
following finished tobacco products: cigarettes (other than
noncombusted cigarettes, such as HTPs that meet the definition of a
cigarette), cigarette tobacco, RYO tobacco, cigars (other than premium
cigars), and pipe tobacco (other than waterpipe tobacco). These
products are defined in proposed Sec. 1160.3. As stated throughout
this preamble, this proposed product standard focuses on cigarettes and
certain other combusted tobacco products given their addictiveness,
availability as migration and dual use candidates with cigarettes, and
the extent of tobacco-related death and disease associated with such
products. As stated in section IX.C of this document, FDA requests
comment regarding the scope of products covered by this proposed rule.
Proposed Sec. 1160.1(b) would prohibit the distribution, sale, or
offering for distribution or sale within the United States finished
tobacco products within the scope of the rule that are not in
compliance with the tobacco product standard. For example, FDA would
consider such finished tobacco products to be noncompliant if they
contain a nicotine level that exceeds the proposed maximum nicotine
level set forth in proposed Sec. 1160.10. Additionally, manufacturers
and importers would not be allowed to enter or introduce into domestic
commerce any finished tobacco product (i.e., cigarettes, cigarette
tobacco, RYO tobacco, cigars, and pipe tobacco) that does not comply
with the requirements of the final rule, irrespective of the date of
manufacture.
Proposed Sec. 1160.1(c) would prohibit the manufacture within the
United States of finished tobacco products within the scope of the rule
that are not in compliance with the tobacco product standard unless
such tobacco products are intended for export and are eligible for
export under section 801(e)(1) of the FD&C Act (21 U.S.C. 381(e)(1)). A
tobacco product intended for export shall not be deemed to be in
violation of section 907 of the FD&C Act or this product standard if it
meets the criteria enumerated in section 801(e)(1), including not being
sold or offered for sale in domestic commerce.
2. Definitions (Proposed Sec. 1160.3)
Proposed Sec. 1160.3 provides the definitions for the terms used
in the proposed product standard. Several of these definitions are
included in the FD&C Act or have been used in other regulatory
documents.
Accessory: Consistent with 21 CFR 1140.3 and the
Consolidated Appropriations Act, 2022 (Pub. L. 117-103), FDA proposes
to define ``accessory'' as any product that is intended or reasonably
expected to be
[[Page 5104]]
used with or for the human consumption of a tobacco product; does not
contain tobacco or nicotine from any source and is not made or derived
from tobacco; and meets either of the following: (1) is not intended or
reasonably expected to affect or alter the performance, composition,
constituents, or characteristics of a tobacco product; or (2) is
intended or reasonably expected to affect or maintain the performance,
composition, constituents, or characteristics of a tobacco product; but
(i) solely controls moisture and/or temperature of a stored product; or
(ii) solely provides an external heat source to initiate but not
maintain combustion of a tobacco product. Accessories of cigarettes,
cigarette tobacco, and RYO tobacco, as three of the originally-
regulated products under the FD&C Act, are considered ``tobacco
products'' and, therefore, would be subject to this proposed product
standard (if finalized). However, accessories of other tobacco products
(e.g., cigars) are not regulated as ``tobacco products'' pursuant to
FDA's final deeming rule (81 FR 28974 at 29015-29016, May 10, 2016)
and, therefore, would not be subject to this proposed product standard.
Examples of such accessories would be ashtrays, cigar clips, and pipe
pouches, because they do not contain tobacco or nicotine from any
source, are not made or derived from tobacco, and do not affect or
alter the performance, composition, constituents, or characteristics of
a tobacco product. However, if such a product was intended or
reasonably expected to affect the performance of a tobacco product
(e.g., nicotine impregnated ash tray), it would no longer be considered
an accessory and would be subject to the proposed product standard.
Batch: FDA proposes to define ``batch'' as a specific
identified amount of a finished tobacco product produced in a unit of
time or quantity and that is intended to have the same specifications.
FDA proposes to give tobacco product manufacturers flexibility to
determine what unit of time or quantity is appropriate for their
product, and how batches would be designated. For example,
manufacturers likely would have, as part of existing manufacturing
processes, defined a ``batch'' for cigarette production, which is
almost continuous, differently than a batch for smokeless tobacco,
which likely would be defined based on the amount processed in a vat
through the fermentation process. Currently, there is no definition of
``batch'' for tobacco products. However, the proposed regulation
Requirements for Tobacco Product Manufacturing Practice (TPMP) (see
https://www.federalregister.gov/documents/2023/03/10/2023-04591/requirements-for-tobacco-product-manufacturing-practice) includes a
proposed definition of ``batch,'' and this rulemaking's provision is
modeled on the proposed TPMP provision. Pursuant to proposed Sec.
1160.12, manufacturers would be required to conduct batch testing and
maintain those records.
Cigar: FDA proposes to define a ``cigar'' as a tobacco
product that: (1) is not a cigarette and (2) is a roll of tobacco
wrapped in leaf tobacco or any substance containing tobacco. This
definition was used in the seven consent orders that the FTC entered
into with the largest mass marketers of cigars (see, e.g., In re
Swisher International, Inc., Docket No. C-3964 (FTC August 18, 2000))
and also is codified at 21 CFR 1143.1. The cigar wrapper would be
considered a ``component or part'' of a cigar (see definition herein)
and, therefore, would be covered by this proposed product standard. As
discussed elsewhere in this document and in proposed Sec. 1160.1,
premium cigars are excluded from the scope of this proposed rule.
Cigarette: As defined in section 900(3) of the FD&C Act,
the term ``cigarette'': (1) means a product that: (i) is a tobacco
product; and (ii) meets the definition of the term ``cigarette'' in
section 3(1) of the Federal Cigarette Labeling and Advertising Act (15
U.S.C. 1332(1)); and (2) includes tobacco, in any form, that is
functional in the product, which, because of its appearance, the type
of tobacco used in the filler, or its packaging and labeling, is likely
to be offered to, or purchased by, consumers as a cigarette or as RYO
tobacco.
Cigarette tobacco: As defined in section 900(4) of the
FD&C Act, the term ``cigarette tobacco'' means any product that
consists of loose tobacco that is intended for use by consumers in a
cigarette. Unless otherwise stated, the requirements applicable to
cigarettes under this chapter also apply to cigarette tobacco.
Commercial distribution: Consistent with 21 CFR 1107.12,
FDA proposes to define ``commercial distribution'' as any distribution
of a finished tobacco product, whether domestic or imported, to
consumers or to any person, but does not include interplant transfers
of a tobacco product between establishments within the same parent,
subsidiary, and/or affiliate company, nor does it include providing a
tobacco product for product testing where such product is not made
available for consumption or resale. ``Commercial distribution'' does
not include the handing or transfer of a tobacco product from one
consumer to another for personal consumption.
Component or part: Consistent with 21 CFR 1140.3, FDA
proposes to define ``component or part'' as any software or assembly of
materials intended or reasonably expected: (1) to alter or affect the
tobacco product's performance, composition, constituents, or
characteristics or (2) to be used with or for the human consumption of
a tobacco product. The term excludes anything that is an accessory of a
tobacco product. Components or parts of cigarettes, cigarette tobacco,
and RYO tobacco, as three of the originally regulated products under
the FD&C Act, are considered ``tobacco products'' and, therefore, would
be subject to this proposed product standard (if finalized). Examples
of cigarette components or parts that would be subject to this proposed
product standard include cigarette paper and filters. In addition,
components or parts of other tobacco products (e.g., cigars) are
regulated as ``tobacco products'' pursuant to FDA's final deeming rule
(81 FR 28974 at 29015-29016) and, therefore, would be subject to this
proposed product standard (if finalized). Some examples of such
components or parts include cigar blunt wraps, removable tips,
mouthpieces, and filters. These examples generally are intended or
reasonably expected to alter or affect the performance, composition,
constituents, or characteristics of a tobacco product. If a liquid
nicotine product or other tobacco product is intended or reasonably
expected to alter the nicotine content of any tobacco product covered
by this proposed rule, such liquid nicotine or other tobacco product
would be considered a component or part of a finished tobacco product
covered under the rule's scope and, therefore, would be in violation of
the rule if the amount of nicotine in the finished tobacco product
exceeds 0.70 mg of nicotine per gram of total tobacco. With respect to
these definitions, FDA notes that ``component'' and ``part'' are
separate and distinct terms within chapter IX of the FD&C Act. However,
for purposes of this rule, FDA is using the terms ``component'' and
``part'' interchangeably and without emphasizing a distinction between
the terms. FDA may clarify the distinctions between ``component'' and
``part'' in the future.
Finished tobacco product: Consistent with 21 CFR 1107.12,
FDA proposes to define a ``finished tobacco product'' to mean a tobacco
product, including all components and parts, sealed in final packaging
(e.g., filters or
[[Page 5105]]
filter tubes sold to consumers separately or as part of kits) or in the
final form in which it is intended to be sold to consumers (e.g.,
tobacconists selling cigars individually from a box or pipe tobacco
filler by weight). Examples of finished tobacco products include a pack
of cigarettes or a bag of RYO or pipe tobacco.
Manufacturing code: FDA proposes to define ``manufacturing
code'' as any distinctive sequence or combination of letters, numbers,
or symbols that begins with the manufacturing date, followed by the
batch number, and concludes with ``-NS.'' This information would help
determine the product's history (e.g., batch testing records) and
assist manufacturers and FDA in the event of a nonconforming tobacco
product investigation and any corrective actions that stem from such
investigation.
Manufacturing date: FDA proposes to define ``manufacturing
date'' as the month, day, and year in 2-digit numerical values in the
format (MMDDYY) that a finished tobacco product is packaged for
distribution. The manufacturing date is included in the manufacturing
code, which can be used by the manufacturer and FDA to help determine
the product's history (e.g., batch testing history) in the event of a
nonconforming tobacco product investigation. As stated in section X.C
of this document, FDA requests comment regarding the manufacturing code
requirements in this proposed rule.
Nicotine: FDA proposes to define ``nicotine'' as the
chemical substance named 3-1(1-methyl-2-pyrrolidinyl) pyridine or
C[10]H[14]N[2], including any salt or complex of nicotine, derived from
any source.
Nonconforming tobacco product: FDA proposes to define
``nonconforming tobacco product'' as any tobacco product that does not
meet the requirements of Sec. 1160.10 (nicotine level specifications)
or Sec. 1160.30 (manufacturing code).
Package or packaging: As defined in section 900(13) of the
FD&C Act, the term ``package'' means a pack, box, carton, or container
of any kind or, if no other container, any wrapping (including
cellophane) in which a tobacco product is offered for sale, sold, or
otherwise distributed to consumers.
Person: As defined in section 201(e) of the FD&C Act (21
U.S.C. 321(e)), the term ``person'' includes an individual,
partnership, corporation, or association.
Pipe tobacco: FDA proposes to define the term ``pipe
tobacco'' as any tobacco that, because of its appearance, type,
packaging, or labeling, is suitable for use and likely to be offered
to, or purchased by, consumers as tobacco to be smoked in a pipe.
However, this definition specifically excludes tobacco labeled and sold
exclusively for use in a waterpipe (i.e., hookah tobacco). As discussed
in section IX.C of this document, FDA is not proposing to include
waterpipe tobacco within the scope of this product standard.
Rework: FDA proposes to define ``rework'' as action taken
on a nonconforming tobacco product to ensure that the product meets the
specifications and other requirements of this part before it is
released for commercial distribution.
Roll-your-own tobacco: As modeled after section 900(15) of
the FD&C Act, FDA proposes to define the term ``roll-your-own tobacco''
(or RYO) as any tobacco product which, because of its appearance, type,
packaging, or labeling, is suitable for use and likely to be offered
to, or purchased by, consumers as tobacco for making cigarettes or
cigars. This product is frequently used interchangeably with cigarette
tobacco and pipe tobacco (as defined in this section).
Specification: We propose to define ``specification'' as
any requirement with which a product, process, service, or other
activity must conform. A tobacco product specification is a requirement
established by the manufacturer, including a requirement established to
ensure that the tobacco product meets any applicable product standard
under section 907 of the FD&C Act.
Tobacco filler: FDA proposes to define ``tobacco filler''
as cut, ground, powdered, or leaf tobacco or other nicotine-containing
substances in a finished tobacco product. For portioned tobacco
products, the material enclosing any tobacco or nicotine-containing
substances (e.g., cigarette paper) is not considered tobacco filler.
Tobacco product: As defined in section 201(rr) of the FD&C
Act, the term ``tobacco product'' means any product made or derived
from tobacco, or containing nicotine from any source, 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).
The term ``tobacco product'' does not mean an article that is: a drug
under section 201(g)(1); a device under section 201(h); a combination
product described in section 503(g) (21 U.S.C. 353(g)); or a food under
section 201(f) of the FD&C Act if such article contains no nicotine, or
no more than trace amounts of naturally occurring nicotine.
Tobacco product manufacturer: As defined in section
900(20) of the FD&C Act, the term ``tobacco product manufacturer''
means any person, including a repacker or relabeler, who: (1)
manufactures, fabricates, assembles, processes, or labels a tobacco
product or (2) imports a finished tobacco product for sale or
distribution in the United States.
Total tobacco: FDA proposes to define the term ``total
tobacco'' as the tobacco filler (defined in proposed Sec. 1160.3) and
any other tobacco or tobacco-derived material used as part of a tobacco
product. For cigars (i.e., those cigars that are covered by this
proposed product standard, as defined in proposed Sec. 1160.3), the
tobacco included in the wrapper and binder would be part of the ``total
tobacco.'' The nicotine content in the total tobacco of the finished
tobacco product must not exceed the proposed maximum nicotine level.
United States: As defined in section 900(22) of the FD&C
Act, the term ``United States'' means the 50 States of the United
States of America and the District of Columbia, the Commonwealth of
Puerto Rico, Guam, the Virgin Islands, American Samoa, Wake Island,
Midway Islands, Kingman Reef, Johnston Atoll, the Northern Mariana
Islands, and any other trust territory or possession of the United
States.
B. Product Requirements (Proposed Subpart B)
1. Maximum Nicotine Level (Proposed Sec. 1160.10)
FDA is proposing to regulate nicotine yield by requiring that a
finished tobacco product contain no more than 0.70 mg of nicotine per
gram of total tobacco. As stated in proposed Sec. 1160.3, the term
``total tobacco'' means both the tobacco filler and any other tobacco
or tobacco-derived material used as part of a tobacco product. This
level would be based on the nicotine content of the tobacco product, as
the means to regulate nicotine yield in the tobacco smoke or emissions.
If a liquid nicotine product or other tobacco product (including a
tobacco product containing nicotine from any source) is intended or
reasonably expected to alter the nicotine content of any tobacco
product covered by this proposed rule, such liquid nicotine or other
tobacco product would be considered a component or part of a tobacco
product covered under the rule's scope and, therefore, would be in
violation of the rule if the total amount of nicotine in the finished
tobacco
[[Page 5106]]
product exceeds 0.70 mg of nicotine per gram of total tobacco.
As stated previously, the term ``finished tobacco product'' refers
to those products subject to this regulation, including any components,
parts, or accessories that are regulated as tobacco products and sealed
in a final package, except for components, parts, or accessories not
made or derived from tobacco. For cigarettes, cigarette tobacco, and
RYO tobacco, all of which were covered under Congress's original grant
of authority (section 901(b) of the FD&C Act), all components, parts,
and accessories of such products would be covered under this proposed
product standard and subject to the proposed maximum nicotine level.
Accessories of deemed tobacco products (i.e., accessories for cigars,
pipe tobacco) would not be covered. FDA intends to use its premarket
review authority under sections 905 and 910 of the FD&C Act to ensure
that manufacturers do not reengineer their products in a way that would
circumvent the proposed maximum nicotine level.
2. Product Testing (Proposed Sec. 1160.12)
Proposed Sec. 1160.12 contains provisions for the testing of
finished tobacco products that would be subject to this proposed rule.
Specifically, proposed Sec. 1160.12(a) would require that tobacco
product manufacturers conduct testing on each batch of finished tobacco
products to ensure that the batch conforms with proposed Sec. 1160.10.
Under this provision, the manufacturer of the finished tobacco product
would be required to use an analytical test method that meets the
requirements set forth in proposed Sec. 1160.14. FDA recommends
manufacturers use one of three analytical test methods described in
section VII.D of this document (i.e., FDA's Tobacco Products Laboratory
method, CRM No. 62, or CRM No. 87). This section also states that
samples for such testing would need to be selected in accordance with
proposed Sec. 1160.16.
Proposed Sec. 1160.12(b) would require that a full report of the
source data and results of all batch testing be maintained by the
tobacco product manufacturer in accordance with proposed Sec. 1160.32.
These reports would be generated for test samples from each batch and
would not be required for each individual finished tobacco product.
This report would have to include the following information:
(1) Full identification of the finished tobacco product that is the
subject of the report, including, if applicable, the submission
tracking number (STN) associated with marketing authorization
(including the static product ID (PD), if applicable), product name(s)
(including brand and subbrand and the original name described in the
premarket application, if different), product category, subcategory,
package type, package quantity, and nicotine source;
(2) Nicotine level of each sample tested from the batch and
standard deviation;
(3) The batch manufacturing date and location, including facility
name and address, for each sample;
(4) The testing date and location, including the facility name and
address;
(5) The manufacturing code of each sample tested (in accordance
with proposed Sec. 1160.30(c));
(6) The test method and sampling procedure used;
(7) Names and qualifications of the person(s) conducting the
testing and any laboratory accreditation;
(8) The manufacturing and testing equipment used (including
documentation to show that the equipment is appropriate for its
intended purpose and has been calibrated to ensure accurate and
reliable results); and
(9) The criteria used to make a decision to accept or reject each
batch and the decision made with respect to each batch (e.g., accept,
reject) based on the results of the product testing. This information
would constitute the documentation of the source data and actual
results of the product testing conducted on each batch.
The main purpose of this report would be to verify that products
subject to this proposed product standard do not exceed the maximum
nicotine level and to document the company's decision for each batch
with respect to acceptance, rejection, and reworking of the products.
FDA expects that information collected pursuant to proposed Sec.
1160.16(b) would be integrated into the proposed Sec. 1160.12(b)
records (i.e., proposed Sec. 1160.16(b) records would be the basis for
documenting background information about the product being tested,
including, for example, the product category and subcategory, brand and
subbrand, packaging information, nicotine source, manufacturing date,
and the manufacturing code). These proposed Sec. 1160.12(b) records
also would document the ultimate disposition of the batch based on the
testing of the representative samples. Section III.C of this document
describes FDA's rulemaking and inspection authorities related to these
records.
While the proposed batch testing and sampling requirements would
provide FDA with critical information, the Agency also recognizes
concerns that it could be costly for certain manufacturers to test each
batch. Therefore, FDA requests comment, including supporting data,
regarding potential alternatives to batch testing and sampling to
ensure finished tobacco product compliance with proposed Sec. 1160.10
that would reduce costs for manufacturers.
3. Analytical Test Method (Proposed Sec. 1160.14)
Proposed Sec. 1160.14 would require that tobacco product
manufacturers use an analytical test method and demonstrate that the
test method was validated in an analytical test laboratory.
Validation means a process of demonstrating or confirming that the
analytical test method is suitable and reliable for its intended
purpose. Validation of an analytical method applies to a specific
laboratory, for a specific product, and equipment performing the
analytical test method for an intended use over a reasonable period.
Although there are various approaches to demonstrate that an analytical
test method is validated (e.g., ICH Guideline Validation of Analytical
Procedures: Text and Methodology Q2), FDA intends to use the approach
outlined in the draft guidance entitled ``Validation and Verification
of Analytical Testing Methods Used for Tobacco Products'' to determine
if a submitted test method is fit-for-purpose. In March 2024, FDA
published a final guidance for industry entitled ``Q2(R2) Validation of
Analytical Procedures'' and although it is not specific to tobacco
products, FDA's approach under that guidance to determine if a method
is fit-for-purpose is applicable for use under this tobacco product
standard.\40\
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\40\ FDA has announced the availability of a draft guidance for
industry entitled ``Validation and Verification of Analytical
Testing Methods Used for Tobacco Products'' (86 FR 72603, December
22, 2021; see https://www.fda.gov/media/155033/download). The draft
guidance, when finalized, would represent FDA's current thinking on
method validation for tobacco products. FDA final guidance ``Q2(R2)
Validation of Analytical Procedures'' is available at https://www.fda.gov/media/161201/download.
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As described in section VII.D of this document, FDA recommends
manufacturers use one of three publicly available analytical test
methods--FDA's Tobacco Products Laboratory method, CRM No. 62, or CRM
No. 87--to demonstrate compliance with this proposed product standard.
Each of these analytical test methods includes the proposed nicotine
level in the range of levels that can be accurately measured.
[[Page 5107]]
It is reasonable to expect some manufacturers may prefer to use
other test methods. If they are developed and validated, such methods
may have different advantages in ease of use, upper and lower bounds of
detection, equipment, and expertise. Thus, under this proposal we would
evaluate analytical test methods and data as part of a manufacturer's
premarket submission in accordance with section 910 of the FD&C Act.
4. Sampling Plans and Procedures (Proposed Sec. 1160.16)
Proposed Sec. 1160.16 would require each tobacco product
manufacturer to design and implement a sampling plan that covers each
finished tobacco product that it manufactures. This sampling plan must
be based on a valid statistical rationale to ensure that the finished
tobacco product complies with proposed Sec. 1160.10. This sampling
plan would be used in conjunction with the analytical test method in
proposed Sec. 1160.14 and would provide procedures for the
manufacturer to select samples to demonstrate conformance to the
proposed maximum nicotine level requirement.
The required procedures are intended to help ensure that tobacco
products containing more than the maximum nicotine level are not sold
or distributed to consumers. Manufacturers would be required to ensure
that all finished tobacco products comply with the requirements of this
proposed product standard. Products that do not conform to this
standard would be deemed adulterated under section 902(5) of the FD&C
Act and subject to enforcement action.
Proposed Sec. 1160.16(a) provides the general requirements for
sampling plans. The proposed provision would require manufacturers to
design and implement a sampling plan or plans for each finished tobacco
product based on a valid scientific rationale to ensure that the
product consistently conforms to the requirements set forth in Sec.
1160.10. This provision also explains that the sampling plan must
ensure that samples taken are representative of an entire batch (i.e.,
randomized or systematically selected across the entire batch) and
collected from each batch for testing. To account for the variability
of nicotine in finished tobacco products, the following factors must be
based on adequate statistical criteria: the confidence intervals, the
level of necessary precision, and the number of finished products
sampled. The sampling plan must take into account the manufacturing
quality history of the manufacturer (e.g., batch testing records,
nonconforming tobacco product investigations). For example, a
manufacturer that has a high number of nonconforming tobacco product
investigations or a high number of batch rejections may decide to
create a more robust sampling plan because of its history of producing
nonconforming tobacco products.
The basic principles of an adequate sampling plan include the
following: the samples are representative of the batch or quantity
being sampled; the number of samples is based on a valid scientific
rationale; and the number of samples is sufficient for the intended
purpose. ``Valid scientific rationale'' refers to scientific techniques
or methods used to establish the number of representative samples and
should take into account tolerance for variability, confidence levels,
and the degree of precision required (Refs. 654 to 656). FDA believes
that requiring the number of samples to be based on a ``valid
scientific rationale'' would provide manufacturers with the flexibility
to determine the appropriate number of representative samples for any
sampling plan. While FDA is proposing this flexibility, this provision
would require that manufacturers have support for the scientific
technique or methods used to establish the number of representative
samples used and to show that the sampling size is representative of
the material being sampled. FDA requests comment, including supporting
data, regarding whether a final rule should provide a more detailed
definition of or criteria for what constitutes ``valid scientific
rationale'' (such as representative sampling) with regard to an
adequate sampling plan.
Proposed Sec. 1160.16(a) also would require that the sampling plan
describe the sampling methodology (including scientific rationale),
incorporate all sources of variability (including variability of the
analytic method and nicotine levels), and describe the sample size
needed (including a full description of how the sample size is
calculated) consistent with the sampling plan to achieve the sampling
objective. The sampling plan must also describe the criteria the
manufacturer would use to make a decision to accept or reject each
batch. FDA proposes to give tobacco product manufacturers flexibility
to determine what unit of time or quantity is appropriate for their
product and how batches would be designated. For example, manufacturers
likely would define a batch for cigarette production, which is almost
continuous, differently than a batch for machine or hand-rolled cigars.
With regard to the variability of the tobacco product, confidence
intervals, level of necessary precision, and number of finished tobacco
products sampled must be based on adequate statistical criteria. This
provides manufacturers flexibility to determine the appropriate number
of representative samples for any sampling plan. While FDA is proposing
this flexibility, this provision would require that manufacturers have
the support for the scientific technique or methods used to establish
the representative samples used and to show that the sampling size is
representative of the material being sampled. The manufacturer must
maintain a nicotine content level no greater than 0.70 mg nicotine per
gram of total tobacco for any products within the batch.
Proposed Sec. 1160.16(b) would require that test samples from each
batch be collected and examined in accordance with certain procedures.
These procedures are consistent with ISO 8243, an international
standard that specifies two methods of providing representative samples
of a population of cigarettes manufactured for sale.
Under proposed Sec. 1160.16(b)(1), test samples would have to
consist of the finished tobacco product as it is intended to be sold or
distributed to consumers and not of a separate production sample.
Proposed Sec. 1160.16(b)(2) would require that all test samples be
stored according to the intended storage conditions for the finished
tobacco product. In addition, the manufacturer would have to include
all of its factories, stock rooms, warehouses, and other locations
containing finished tobacco products among the population to be
sampled. Because a batch may include product that is in the warehouse
and product that is in the factory, or in a place between the warehouse
and factory, this requirement would ensure that the sample is
representative of the entire population (batch) of finished tobacco
products packaged for consumer use. This practice is consistent with
the ISO 8243 standard (for sampling nicotine) and ensures that the
samples are representative of the population of finished tobacco
products packaged for consumer use.
Under proposed Sec. 1160.16(b)(3), the manufacturer would have to
take test samples from each batch within 30 calendar days of the date
the product is manufactured. Based on FDA's experience, any protracted
time between manufacturing and testing will add uncertainty in the
accuracy of reported results. Thus, we are proposing a 30 calendar day
timeframe from the
[[Page 5108]]
manufacture date for the manufacturer to take test samples from each
batch. The amount of material acquired during sampling must be
sufficient to complete all testing required by proposed Sec. 1160.14,
including any repeat testing that may be necessary. The sample
materials would have to be selected from each batch in accordance with
the applicable sampling plan. This would ensure that there has not been
any degradation or change in part of the samples.
Proposed Sec. 1160.16(b)(4) would require that sampling be
performed by persons who have sufficient education, training, and
experience to accomplish their assigned functions.
Under proposed Sec. 1160.16(b)(5), each test sample would need to
be identified so that the following information can be determined:
Full identification of the finished tobacco product
sampled, including, if applicable, the STN associated with marketing
authorization (including the PD, if applicable), product name(s)
(including brand and subbrand and the original name described in the
premarket application, if different), product category, subcategory,
package type, package quantity, and nicotine source;
The manufacturing code;
The date on which the sample was taken;
The sampling location (including the address of the
facility and specific location within the facility where the sample was
taken);
The name of the person(s) who collected the sample; and
The location where the sample will be tested (including
the facility name and address).
This information would be generated at the time the samples are
pulled for testing and for each sample pulled, rather than reflecting
aggregate information for all the samples in a particular batch. The
purpose of this information is to fully identify each sample, including
what the product is, when and where it was taken, and the batch from
which it was taken. These records would serve dual purposes. First,
they could be used to verify that a company is following its sampling
plan and the required procedures in the codified including number of
samples pulled, when they are pulled, and locations from where they are
pulled. Second, these records would be used to generate some of the
information for the records required under proposed Sec.
1160.16(b)(8). They also would document the start of the chain of
custody for the samples.
Proposed Sec. 1160.16(b)(6) provides packaging requirements for
when samples are sent for testing. Test samples would have to be packed
securely with adequate protection against damage that might occur,
including mechanical damage or adverse changes in humidity or
temperature. The manufacturer also would have to send, under separate
cover, a list of the samples included in each shipment to the testing
facility. These samples should be identified by the relevant
information required by proposed Sec. 1160.16(b)(5).
Proposed Sec. 1160.16(b)(7) would require that all samples from a
single batch be tested at the same testing facility. This requirement
is designed to ensure consistency in the procedures used and to protect
against sample degradation.
Proposed Sec. 1160.16(b)(8) provides sampling requirements for the
testing facility. If samples will be transported to a different
facility from the manufacturing facility for testing, once test samples
arrive at the testing facility, samples must be inspected, accounted
for, and properly stored under the finished tobacco product's intended
storage conditions. The facility also would be responsible for
generating a report for the batch test, maintained by the manufacturer
in accordance with Sec. 1160.32, which includes the information in
proposed Sec. 1160.16(b)(8)(i) through (vi):
Full identification of the finished tobacco product
sampled, including, if applicable, the STN associated with marketing
authorization (including the PD, if applicable), product name(s)
(including brand and subbrand and the original name described in the
premarket application, if different), product category, subcategory,
package type, package quantity; and nicotine source;
The manufacturing code;
The date on which the samples were taken, if available;
The sampling location (including the address and specific
locations within any facilities where the samples were taken);
The number of test samples drawn from the batch; and
Complete records of the samples received and tested,
including the date of receipt, the identifier of all persons who tested
the samples, and the test results.
This information would be generated once the test samples arrive at
the testing facility. Unlike the information required under proposed
Sec. 1160.16(b)(5), this report would be an aggregate report for all
the samples taken from a batch. The primary purpose of this
information, along with the information required by proposed Sec.
1160.16(b)(5), would be to establish the chain of custody for the
samples from the time they were taken through their transfer to the
testing facility where they will be tested. FDA expects that this
information would be integrated into the records required by proposed
Sec. 1160.12(b) to provide information across the batch.
Proposed Sec. 1160.16(b)(9) explains that each batch must be
withheld from commercial distribution until it has been sampled and
tested, and a decision has been made by the tobacco product
manufacturer that the batch conforms to the requirements of this part
and may be released for commercial distribution. As discussed in
proposed Sec. 1160.18, the manufacturer would be required to reject
any nonconforming tobacco products unless a disposition decision and
justification to release the batch is made after an investigation
determines that the batch meets the requirements of this part.
As noted in the discussion of proposed Sec. Sec. 1160.12 and
1160.16, the reporting requirements in proposed Sec. Sec. 1160.12(b),
1160.16(b)(5), and 1160.16(b)(8) are interrelated but intended for
different purposes.
Because this tobacco product standard defines the amount of
nicotine relative to the amount of total tobacco, manufacturers may be
able to base sampling plans on batch sizes based on the tobacco filler.
For example, cigarettes of two different lengths made from the same
tobacco filler blend may be able to be considered a single batch for
the purposes of calculating the sampling plan under proposed Sec.
1160.16. Testing for nonconforming tobacco product under proposed Sec.
1160.16 would require the manufacturer to adequately sample from the
entire batch in proportion to production. For example, if two-thirds of
the batch is produced as cigarette length A and one-third as cigarette
length B, then two-thirds of the samples for testing for conformance
would have to be sampled from cigarette length A and one-third from
cigarette length B.
Manufacturers that purchase bulk tobacco filler can utilize results
of filler testing by the seller in designing and implementing their
sampling plan. Reliance on the seller's filler testing would not
relieve the manufacturer of the finished tobacco product from its
responsibility to test finished tobacco products or from responsibility
for complying with this proposed product standard.
[[Page 5109]]
5. Nonconforming Tobacco Product (Proposed Sec. 1160.18)
Proposed Sec. 1160.18 would require finished tobacco product
manufacturers to establish procedures for the control and disposition
of nonconforming tobacco products. A ``nonconforming tobacco product''
is proposed to be defined as any tobacco product that does not meet the
requirements of Sec. 1160.10 (nicotine level specifications) or Sec.
1160.30 (manufacturing code). These procedures are necessary to help
prevent the distribution of nonconforming tobacco products by ensuring
that all potential nonconforming products are identified, investigated,
and segregated, and that appropriate disposition and followup are taken
for products determined to be nonconforming. These provisions are also
intended to help manufacturers determine the extent of any
nonconformity and, in cases in which nonconforming product has already
been released for distribution, determine where it was distributed.
Proposed Sec. 1160.18 would require tobacco product manufacturers
to establish and maintain procedures to identify, investigate,
segregate, and make disposition decisions (i.e., acceptance, rejection,
rework) about nonconforming tobacco products to prevent their release
for commercial distribution. ``Establish and maintain'' for purposes of
proposed Sec. 1160.18 means define, document (in writing or
electronically), implement, follow, and, when necessary, update. This
section allows manufacturers the flexibility to determine how they
would perform these activities.
Proposed Sec. 1160.18(a) would require tobacco product
manufacturers to identify and segregate potential nonconforming tobacco
product to prevent the commercial distribution of such products prior
to investigation and disposition. Identification of potential
nonconforming product can be accomplished in many ways (e.g., applying
a label with the relevant information directly to the product
container; if an electronic system is utilized, associating the
nonconforming product information with the relevant barcode).
Identification is a critical first step to preventing further
processing, production, or distribution of potential nonconforming
tobacco products.
Proposed Sec. 1160.18(a) also would require potential
nonconforming tobacco product to remain segregated pending an
investigation until it is determined to be conforming. If a potential
nonconforming product is determined to be nonconforming, it would need
to remain segregated throughout investigation and disposition,
including any rework. For purposes of proposed part 1160,
``segregation'' means setting the identified potential nonconforming
product apart from other product (i.e., placing it away from conforming
finished product). This segregation could be accomplished by placing it
in a quarantined or specifically marked-off area. Manufacturers should
use prudence and segregate potential nonconforming tobacco product in a
manner that is appropriate, given the nature of the potential
nonconformity. The requirements to identify and segregate would be
triggered upon discovery of a potential nonconforming product. For
example, if a tobacco product manufacturer tests samples of finished
tobacco product and determines that the representative samples from
that batch do not conform to the requirement set forth in proposed
Sec. 1160.10, the manufacturer would determine that the batch and
related products must be identified and segregated as they may be
nonconforming products.
Proposed Sec. 1160.18(b) would require tobacco product
manufacturers to investigate all potential nonconforming tobacco
products. This may include, for example if:
The nicotine level of a test sample from any batch of
finished tobacco products is determined to be out of conformance with
the requirements of proposed Sec. 1160.10;
FDA notifies the manufacturer that a finished tobacco
product in commercial distribution does not conform to the requirements
of part 1160; or
The manufacturer has come to know through any other means
that a product is nonconforming.
In this context, a test sample would consist of a number of
individual test units that are drawn based on a valid scientific
rationale (such as representative sampling) and intended to ensure that
the sample accurately reflects the material being sampled. The purpose
of a nonconforming product investigation would be to determine the
extent and the cause, if possible, of the nonconformity so that
additional nonconforming products are not produced or released for
commercial distribution. In addition, it would help to prevent
recurrence of the nonconformity.
Under proposed Sec. 1160.18(b), the manufacturer would be required
to conduct an investigation to determine the extent of the
nonconformity upon identification of a nonconforming product and, as
applicable, the locations where the nonconforming products have been
distributed. We expect the manufacturer would be able to determine the
locations of initial consignees (e.g., wholesalers, distributors,
retailers) where the affected products were shipped in the event a
corrective action needs to be taken. The investigation would have to
include an examination of all relevant processes and controls,
laboratory testing, complaints, and any other relevant records and
sources of information concerning the nonconforming product. For
example, a manufacturer could determine the extent of the nonconformity
by examining records and in-process control records for any batches, or
portions of batches, that have been rejected during either in-process
or finished inspection for failing to meet any or all of the product's
specifications. Furthermore, in the event that a similar nonconforming
product is identified in a different batch, a manufacturer's
investigation could include any applicable information and records from
the previous nonconforming product investigation that are relevant to
determining the extent of the nonconformity of the affected batch.
Proposed Sec. 1160.18(b) would also require that, for products
determined to be nonconforming, the investigation must also determine
the scope and cause of nonconformance. Examination of relevant
production processes and controls and any other relevant records and
sources of information could help a manufacturer determine if any other
batches are affected or if nonconforming product has been distributed.
For example, if a manufacturer's sampling plan and subsequent repeat
testing under proposed Sec. 1160.18 determines that a batch of
finished cigarettes fail to meet the established nicotine level
specification and acceptance criteria, the manufacturer will have to
investigate the scope and cause of the nonconformance under this
proposed section. If the investigation determines that the cause of the
nonconformance is attributed to cut filler received from its supplier
that contain nicotine levels that exceed the maximum nicotine level
established by the proposed product standard, the manufacturer must
also determine the scope of the nonconformance, such as all batches of
finished cigarettes that used the affected cut filler.
The manufacturer would have to document any investigation,
including any material review, name of the person(s) making the
disposition decisions, justification for the
[[Page 5110]]
disposition decisions, results of retesting, decisions with respect to
reworking, and followup results from the investigation (e.g.,
corrective actions). FDA may inspect these records to verify that the
manufacturer has performed an adequate investigation.
For example, if a manufacturer uses a laboratory to perform product
testing under proposed Sec. 1160.12, and there is an out-of-
specification (OOS) laboratory test result, the manufacturer would need
to investigate the OOS test result under proposed Sec. 1160.18(b) to
determine whether the product is nonconforming or the OOS result is due
to another cause, such as laboratory error. Under proposed Sec.
1160.18(b), the investigation would be required to include an
examination of relevant processes, operations, and any other relevant
sources of information such as the laboratory method and review of
initial testing and calibration of the laboratory equipment. Such an
investigation could determine that the OOS test results came from an
aberration of the measurement process (e.g., laboratory error,
defective testing equipment, deviation from an established laboratory
test method) and that the potential nonconforming tobacco product is
not nonconforming. Alternatively, an investigation could conclude that
the OOS test result was valid, and that the product was nonconforming
as a result of, for example, the manufacturing process. If the
manufacturer's nonconforming product investigation determines that the
OOS result is due to a legitimate reason such as a testing aberration,
e.g., instrument malfunction, and the re-test or rework establishes
that the finished tobacco product conforms to the nicotine level of the
product standard, such product could be released for commercial
distribution.
Proposed Sec. 1160.18(c) would require tobacco product
manufacturers to reject a batch of a finished tobacco product if the
nicotine level of the test sample does not meet the requirements of
Sec. 1160.10, unless a disposition decision and justification to
release the batch is made after an investigation shows the batch meets
the requirements of part 1160. This might occur in the event of a
laboratory or sampling error. Manufacturers would not be able to simply
resample a batch until the batch conforms with the proposed maximum
nicotine level in Sec. 1160.10 if previous test samples did not the
meet the requirements of part 1160. If the initial test samples of the
batch were not in conformance, the manufacturer must conduct a
nonconforming tobacco product investigation. If the manufacturer, for
instance, determines that the nicotine levels were erroneously high due
to a malfunction of the testing equipment, the manufacturer could
determine that the batch is acceptable for release for commercial
distribution.
Proposed Sec. 1160.18(d) would require manufacturers to determine
the disposition of all nonconforming tobacco products and any necessary
followup. Under proposed Sec. 1160.18(d), nonconforming product cannot
be released for distribution without rework or an adequate
justification (developed and maintained in accordance with Sec.
1160.32). Thus, nonconforming product could be reworked, distributed
with an adequate justification, or discarded. Additionally,
nonconforming product could be exported if it meets the requirements of
section 801(e)(1) of the FD&C Act. Proposed Sec. 1160.18(d) also would
require the manufacturer to develop an adequate written justification
before releasing such product for commercial distribution. An adequate
written justification would be required to address how the
nonconforming product meets all requirements under this part.
Nonconforming product cannot be released for commercial distribution
without rework or an adequate written justification supporting its
release. An example of reworking a nonconforming product would be a
manufacturer reblending the cut filler and retesting to ensure that it
conforms to the established product standard.
Proposed Sec. 1160.18(e) would require each tobacco product
manufacturer to maintain records of all activities required under Sec.
1160.18. Records must include the date and time of the activity, the
individual performing the activity, the type of activity performed, any
information that demonstrates the requirement was met, and any data or
calculations necessary to reconstruct the results.
C. Manufacturing Code and Recordkeeping Requirements (Proposed Subpart
C)
1. Manufacturing Code Requirements (Proposed Sec. 1160.30)
Proposed Sec. 1160.30 would require that the packaging of all
finished tobacco products include a manufacturing code. The
manufacturing code would allow manufacturers and FDA to identify the
production batch of a particular finished product that has been
released for distribution. This information is intended to help
determine the product's history (e.g., batch production records) and
assist manufacturers and FDA in the event of a nonconforming tobacco
product investigation and any corrective actions to be taken by a
manufacturer as a result of the investigation. The ``-NS'' designation
will enable retailers to readily identify that a finished tobacco
product conforms with this standard. Finished tobacco products that do
not have this designation do not conform to this standard. The
manufacturing code information also would aid FDA in ensuring
compliance with this proposed product standard by clearly identifying
those products that conform to the standard and linking those products
to records that substantiate their conformance.
As stated in proposed Sec. 1160.30(a), the manufacturing code
would be required to be permanently affixed to the packaging or label
of all finished tobacco products. The manufacturing code must be
affixed in a manner that ensures it will remain on the packaging or
label through the expected duration of use of the product by the
consumer. In addition, proposed Sec. 1160.30(b) would require that the
manufacturing code be permanently affixed, legible, conspicuous,
prominent, and appear in the English language.
As stated in proposed Sec. 1160.30(c), the manufacturing code must
contain the following information listed in the following order:
The manufacturing date in 2-digit numerical values in the
month-day-year format (MMDDYY);
The finished tobacco product batch number; and
The designation ``-NS'' at the end \41\ (to signify that
the product was manufactured in accordance with this nicotine product
standard).
---------------------------------------------------------------------------
\41\ The ``-NS'' designation will enable retailers to readily
identify that a finished tobacco product conforms with this
standard. Finished tobacco products that do not have this
designation do not conform to this standard.
---------------------------------------------------------------------------
FDA requests comment on the manufacturing code requirements in this
proposed rule.
2. Recordkeeping Requirements (Proposed Sec. 1160.32)
Proposed Sec. 1160.32 contains recordkeeping requirements. This
information is necessary for FDA to ascertain and confirm that finished
tobacco products are in compliance with the proposed product standard.
First, proposed Sec. 1160.32(a) would require that each facility
that manufactures tobacco products subject to this part (i.e.,
cigarettes and certain other finished tobacco products) establish and
maintain records related to compliance with this part, including the
following:
[[Page 5111]]
(1) The source data and results of analyses conducted to determine
conformance with Sec. 1160.10, including all information identified in
Sec. 1160.12(b);
(2) All source data used to validate an analytical test method;
(3) All sampling plans and sampling reports under Sec. 1160.16;
(4) Documentation that the persons performing sampling under Sec.
1160.16 have sufficient education, training, and experience to
accomplish the assigned functions; and
(5) All nonconforming tobacco product identification, segregation,
investigation, rework, and disposition decision procedures, including
justifications under Sec. 1160.18.
This information is necessary for FDA to ascertain and confirm that
the products are in compliance with the proposed product standard.
Second, proposed Sec. 1160.32(b) provides certain specifications
for these records. All records required under this part, regardless of
storage medium, would need to be attributable (i.e., traceable to its
source), legible (i.e., in a readable format), contemporaneously
recorded (i.e., recorded at the time of performance), original (i.e.,
first capture of the data), and accurate (i.e., correct, truthful,
complete, valid, and reliable). In addition, these records would be
required to be written in English; alternatively, an accurate English
translation must be made available upon request. Documents that have
been translated from a foreign language into English would have to be
accompanied by the foreign language version of the document and a
certification by the manufacturer's authorized representative (which
could be a U.S. agent for the manufacturer) that the English language
translation is complete and accurate, and a brief statement of the
qualifications of the person who made the translation (e.g., education,
experience). These records would need to be maintained at the
manufacturing establishment or another location that is readily
accessible to responsible officials of the manufacturer and to FDA.
These records, including those not stored at the establishment, would
need to be readily accessible to FDA during the retention period (as
discussed in Sec. 1160.32(c)) for inspection and photocopying or other
means of reproduction. Original or true copies of these records that
can be immediately retrieved from another location, including by
computer or other electronic means, would satisfy the requirements of
this section.
FDA expects that requested records that are maintained offsite
would be made available within 24 hours or, if that is not feasible, as
soon as possible before the close of the inspection. While the Agency
expects that most records can be made available to FDA within 24 hours,
FDA recognizes that, in some cases, additional time may be needed to
retrieve records from a third party or archival storage. Records that
can be immediately retrieved from another location, including by
computer or other electronic means, would meet the requirement that the
records be readily available.
Proposed Sec. 1160.32(c) would require that the records kept under
this part be retained for at least 4 years from the date of commercial
distribution of the finished tobacco product that is the subject of the
record. FDA has selected 4 years to help ensure that the records would
be available for at least one biennial FDA inspection under sections
704 and 905(g) of the FD&C Act.
FDA believes that detailed recordkeeping requirements are necessary
to confirm that finished tobacco products are in compliance with the
proposed product standard. For example, requiring manufacturers to
document their test results would enable FDA to confirm that the
manufacturer's analytical test method is adequate to meet the
requirements of part 1160. In addition, requiring nonconforming tobacco
product records would help the manufacturer and FDA determine the
extent of the nonconformity with the product standard and, as
applicable, the locations where the nonconforming products have been
distributed, for example, in the event of a recall.
XI. Proposed Effective Date
In accordance with section 907(d)(2) of the FD&C Act,\42\ FDA
proposes that any final rule that may issue based on this proposal
become effective 2 years after the date of publication of the final
rule. Therefore, after the effective date, no manufacturer or importer
would be allowed to distribute, sell, or offer for distribution or sale
within the United States any finished tobacco product that does not
comply with proposed part 1160. After the effective date of the final
rule, manufacturers and importers would not be allowed to enter or
introduce into domestic commerce any finished tobacco product (i.e.,
cigarettes, cigarette tobacco, RYO tobacco, cigars, and pipe tobacco)
that does not comply with the requirements of the final rule,
irrespective of the date of manufacture. Prior to the effective date of
any final rule that may issue based on this proposed rule, wholesalers,
retailers, and related entities would be able to sell available stock
of finished tobacco products that are not in compliance with part 1160
while transitioning inventory in anticipation of the effective date of
the final rule; however, they would not be permitted to sell off such
stock after the effective date. FDA notes that keeping products subject
to this proposed rule with higher nicotine levels on the market for an
extended period of time is not in the interest of public health.
---------------------------------------------------------------------------
\42\ Section 907(d)(2) of the FD&C Act states that a regulation
establishing a tobacco product standard shall set forth the date or
dates upon which the standard shall take effect, but no such
regulation may take effect before 1 year after the date of its
publication unless the Secretary determines that an earlier
effective date is necessary for the protection of the public health.
---------------------------------------------------------------------------
The Nicotine ANPRM requested comment on a proposed effective date
for a nicotine tobacco product standard. Several comments recommended
that FDA establish a 1-year timeframe for implementation. Other
comments urged FDA to set a 2-year timeframe for implementation, which
they stated would be the minimum required by section 907 of the FD&C
Act due to the impact on farmers. A few comments argued that an
implementation period should be required for all manufacturers,
regardless of the number of employees and/or annual revenues, because
the long time to develop the regulation plus the implementation period
would be sufficient warning for all companies. However, many comments
argued that the implementation period should be significantly longer
than a 1- or 2-year period to allow farmers, tobacco intermediaries,
and manufacturers to develop and implement the methods of reduction.
The comments differed as to whether FDA should allow manufacturers
any time to sell off nonconforming tobacco product. Several comments
urged FDA to allow manufacturer sell-off of existing nonconforming
inventory, with some stating that a 6-month or 12-month selloff period
should be sufficient for nonconforming product to move through the
supply chain. Nevertheless, several comments opposed provisions that
would allow sell-off of existing inventory, arguing that the extensive
period of the development of the standard combined with a 2-year phase-
in period would give the companies more than enough time to sell-off or
recall existing inventory. Some comments stated that a 60-day selloff
period would be a sufficient selloff period while still maintaining the
public health goals of the standard. FDA requests comments, including
[[Page 5112]]
supportive data and research, regarding a selloff period (e.g., 60 days
after the effective date of the final rule) for retailers to sell
through their current inventory of nonconforming product.
FDA considered many factors in determining an appropriate proposed
effective date. Pursuant to section 907(d)(2) of the FD&C Act, FDA
considered the technical achievability of compliance with the proposed
product standard and the existence of patents that would make it
impossible to comply in the proposed 2-year timeframe. For example, for
manufacturers that may not want to use chemical extraction, FDA
considered how long it would likely take for a tobacco product
manufacturer to acquire sufficient VLNC tobacco to meet the proposed
product standard. Industry documents indicate that the timing of
availability of leaf once commercial seed is provided is one growing
season (Ref. 657). Seed production and germination testing can be
conducted in multiple seasons within a single year with small-scale
trial to commercial availability taking place over the course of 1 year
(Ref. 658). For example, industry documents indicate that a request for
purchase of low alkaloid nicotine in March 1990 would be expected to
result in leaf delivery during August and September (Ref. 657).
Once purchased, FDA considered how long tobacco must be stored
prior to use in cigarettes and other combusted tobacco products.
Industry documents suggest a minimum storage age (particularly for
burley and flue-cured tobaccos) of around 12 months (Refs. 659 to 663).
Other tobacco manufacturers suggest that tobaccos should be stored for
22 months, although other studies suggest that aging beyond 12 months
has minimal effects (Refs. 662 and 664). Industry documents also
indicate that processed tobaccos do not appear to require long-term
inventory or aging in the same manner as whole-leaf tobaccos (Ref.
659). FDA requests comments, including supportive data and research, on
the technical achievability of compliance with the proposed product
standard and the existence of patents that would make it impossible to
comply in the proposed 2-year timeframe.
FDA also finds that a 2-year effective date will ``minimize,
consistent with the public health, economic loss to, and disruption or
dislocation of, domestic and international trade'' pursuant to section
907(d)(2) of the FD&C Act. As discussed extensively throughout this
document, tobacco use is the leading cause of preventable disease and
death in the United States, and nearly all of the adverse health
effects are ultimately the result of addiction to the nicotine in
cigarettes and certain other combusted tobacco products, which leads to
repeated exposure to toxicants from these products. Given the
tremendous public health risks presented--particularly to youth who
experiment with these products, develop an addiction to nicotine, and
progress to regular use--by combusted tobacco products, FDA finds that
any balancing of impacts to domestic and international trade is far
outweighed by the significant public health benefits of this proposed
product standard for all age groups. FDA also believes that a 2-year
effective date would allow adequate time for implementing any necessary
changes in technology to achieve the proposed nicotine level, for
making any changes to tobacco purchasing choices and curing methods,
and for preparation or changes needed in facilities, which can be
accomplished simultaneously. In addition, this timeframe should provide
adequate time for manufacturers to seek and obtain marketing
authorization from FDA for their new tobacco products. FDA believes
that this 2-year period would provide sufficient time for a tobacco
product manufacturer to submit, and FDA to review, applications for new
tobacco products that comply with this provision. This is particularly
true given our expectation that most manufacturers that reduce the
nicotine levels of their products to comply with the proposed standard
would be submitting SE Reports, which may decrease the amount of data
required for authorization. See section IX.B of this document regarding
pathways to market tobacco products that have been modified to meet the
proposed standard. FDA requests comments, including supportive data and
research, on the timeframe for manufacturers to prepare applications
and obtain marketing authorization from FDA for their new tobacco
products.
FDA finds this proposed effective date to be appropriate for the
protection of the public health, given that current nicotine levels in
the finished tobacco products cause addiction and repeated exposure to
toxicants, which ultimately result in the majority of tobacco-related
disease and death in the United States. Additional delay, past 2 years,
would only increase the number of youth and young adults who transition
to regular use of cigarettes and certain other combusted tobacco
products and would delay switching to potentially less harmful tobacco
products or cessation by people who currently smoke cigarettes.
Pursuant to section 907(d)(2), FDA requests comments by interested
parties, including manufacturers and tobacco growers, regarding the
technical achievability of compliance with this proposed product
standard, including information concerning the existence of patents
that make it impossible to comply in the proposed 2-year timeframe. FDA
also requests comment on the timeframe for manufacturers to prepare
applications and obtain marketing authorization from FDA for their new
tobacco products. Further, FDA requests comments and data regarding
whether 2 years is sufficient to comply with this standard or whether
this effective date should be later to provide additional time for
manufacturers to develop any necessary changes in technology,
facilities, farming methods, or other factors or business practices
affecting compliance. FDA also requests comments and supporting data as
to whether a shorter effective date would be necessary for the
protection of the public health.
XII. Preliminary Economic Analysis of Impacts
A. Introduction
We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, Executive Order 14094, 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, 13563, and 14094 direct us to assess all
benefits, costs, and transfers 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). Rules are ``significant'' under Executive Order 12866
Section 3(f)(1) (as amended by Executive Order 14094) if they ``have an
annual effect on the economy of $200 million or more (adjusted every 3
years by the Administrator of [the Office of Information and Regulatory
Affairs (OIRA)] for changes in gross domestic product); or adversely
affect in a material way the economy, a sector of the economy,
productivity, competition, jobs, the environment, public health or
safety, or State, local, territorial, or tribal governments or
communities.'' OIRA has determined that this proposed rule is a
significant regulatory action under Executive Order 12866 Section
3(f)(1).
[[Page 5113]]
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because businesses, including small businesses, would incur
costs to comply with the proposed product standard, we find that the
proposed rule will 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 proposing ``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 2023 threshold after adjustment for
inflation is $183 million, using the 2023 Implicit Price Deflator for
the Gross Domestic Product. This proposed rule would result in an
expenditure in at least 1 year that meets or exceeds this amount.
B. Summary of Costs and Benefits
We have developed a comprehensive Preliminary Economic Analysis of
Impacts that assesses the impacts of the proposed rule. The full
preliminary analysis of economic impacts is available in the docket for
this proposed rule (Ref. 653) and at https://www.fda.gov/about-fda/economics-staff/regulatory-impact-analyses-ria. The summary of costs,
benefits, and transfers is presented in table 13. Benefits occur
because the proposed rule would discourage people who do not use
tobacco products from initiating combusted tobacco products and
progressing to regular use and increase cessation or switching to
potentially lower risk tobacco products among people who currently use
covered combusted tobacco products and wish to quit. Lower prevalence
of combusted tobacco product use would lead to reduced health
consequences for people who formerly used combusted tobacco products
and those who were previously exposed to secondhand smoke. The main
quantified benefits come from averted mortality and morbidity as a
result of reduced prevalence for people who currently use combusted
tobacco products, and reduced mortality from reduced exposure to
secondhand smoke among people. As described in section VIII.A above, to
assess the potential public health impacts of a nicotine product
standard, FDA developed a population health model using inputs derived
from available empirical evidence and expert opinion to estimate the
impact of changes in tobacco product initiation, cessation, switching,
and dual use on tobacco use prevalence, morbidity, and mortality in the
United States. We use output from this population health model to
estimate averted mortality and preliminarily apply the value of a
statistical life while requesting feedback about how to follow HHS
guidance (see PRIA Section II.M.6). The morbidity estimates come from
population health model output that evaluates the health difference for
being in the state of smoking verse not smoking. Unquantified benefits
include medical cost savings, productivity loss savings, reduced
exposure to thirdhand smoke, and environmental impacts. We estimate
that the present value of the quantified benefits over a 40-year time
horizon ranges between $7.6 trillion and $33.2 trillion with a primary
estimate of $30.6 trillion at a 2 percent discount rate. The primary
annualized quantifiable benefits equal $1.1 trillion at a 2 percent
discount rate.
As most of the benefits from avoided initiation among youth and
young adults due to this proposed product standard are expected to fall
outside of the 40-year time horizon of the main analysis, we present an
extended analysis over a period beyond the 40-year time horizon to
capture the impact on youth and young adults. The present value of
quantified benefits, mostly attributable to youth and young adults,
over this extended period range between $8.4 trillion and $19.7
trillion with a primary estimate of $19.1 trillion at a 2 percent
discount rate. Additionally, we present the incidence of benefits for
specific populations in the Distributional Effects section.
We expect this proposed rule, if finalized, to impose costs on
industry to follow the product standard, on the broader economy to
repurpose land, labor, and capital, on consumers impacted by the
product standard, and on FDA to enforce this product standard. The
tobacco market faces a one-time primary cost with a present value of
$374 million at a 2 percent discount rate (low-impact scenario estimate
of $112 million to a high-impact scenario estimate of $700 million) to
read and understand the rule.\43\ We also use population health model
output on prevalence to estimate the baseline and policy market size.
These estimates feed into cost estimates, such as lost producer
surplus. Producers of combusted tobacco products incur a primary
annualized producer surplus loss of $1.7 billion (low-impact scenario
of $0.2 billion and a high-impact scenario of $2 billion) at a 2
percent discount rate. We expect that some manufacturers would
reformulate their products to comply with this standard. We estimate a
one-time reformulation cost with present value of $0.6 billion (low-
impact scenario estimate of $8.8 billion to a high-impact scenario
estimate of $0.04 billion). Manufacturers that reformulate would
collectively incur a one-time cost to submit their new tobacco product
for FDA review, estimated at a present value $1 million at a 2 percent
discount rate (low-impact scenario estimate of $15 million to a high-
impact scenario estimate of $0.1 million). In addition, these
manufacturers would also incur recurring costs to test the nicotine
level of their products with a primary annualized estimate of $0.3
million (low-impact scenario estimate of $1.9 million to a high-impact
scenario estimate of $0.1 million) at a 2 percent discount rate. We
estimate a one-time cost for FDA to review submissions for new tobacco
products at a present value of $1.0 million at a 2 percent discount
rate (low-impact scenario estimate of $15.3 million to a high-impact
scenario estimate of $0.1 million). The economy faces a one-time
economic transition cost with a present value of $7.2 billion at a 2
percent discount rate (low-impact scenario estimate of $4.3 billion to
a high-impact scenario estimate of $9.1 billion) to reallocate
productive resources (such as labor and capital) currently devoted to
the manufacture of NNC covered combusted tobacco products to other
tobacco products or to non-tobacco products. We estimate transition
cost based on average industry capital expenditures and literature on
the cost of labor transition. Consumers of NNC covered combusted
tobacco products would face a one-time search cost with a present value
of $1.4 billion at a 2 percent discount rate (low-impact scenario
estimate of $0.46 billion to a high-impact scenario estimate of $2.8
billion) to find other tobacco products or NRT as a replacement for the
prohibited NNC products. We estimate one-time withdrawal costs for
[[Page 5114]]
consumers who quit tobacco products, with a primary estimate of $1.4
billion at a 2 percent discount rate (low-impact scenario estimate of
$0.02 billion to a high-impact scenario estimate of $8.99 billion), at
a 2 percent discount rate. We estimate additional costs associated with
FDA enforcement of the product standard to range from an annualized
value of $3.3 million to $7 million at a 2 percent discount rate.
Unquantified costs may include changes in consumer surplus for some
people who smoke NNC products, including potential utility changes for
consumers who switch from NNC to VLNC combusted tobacco products. The
present value of the costs over a 40-year time horizon has a primary
estimate of $58 billion (low-impact scenario estimate of $19.3 billion
to a high-impact scenario of $76.2 billion) at a 2 percent discount
rate. The primary estimates for the annualized costs are $2.1 billion
at a 2 percent discount rate.
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\43\ For the purposes of our analysis, we use the population
health model described in section VIII.A of this document to
estimate impacts for a range of averted mortality and tobacco
prevalence. The ``high impact scenario'', generally referred to as
the upper bound, corresponds to the scenario where the policy has
95th percentile averted mortality projected by the population health
model, which also corresponds with the lowest (5th percentile) post-
policy combusted tobacco prevalence. For some costs (product
reformulation, premarket submission, and review, and testing costs),
the ``upper bound'' corresponds to the scenario with the fewest
products and, thus, would reflect the lowest estimate of costs.
---------------------------------------------------------------------------
In addition to benefits and costs, this rule would cause transfers
from the Federal Government, State governments, and firms to consumers,
who in turn would spend this money in other sectors of the economy
(including savings), in the form of reduced revenue and tax revenue. We
also estimate transfers between or within firms to cover shifts in user
fee obligation. The primary estimate for the annualized transfers from
the Federal Government, in the form of reduced excise tax, ranges from
$1.4 billion to $4.3 billion, with a primary estimate of $4.1 billion
at a 2 percent discount rate. The primary estimate for the annualized
transfers from State governments, in the form of reduced excise tax,
ranges from $2.8 billion to $8.9 billion, with a primary estimate of
$8.4 billion at a 2 percent discount rate. The primary estimate for the
annualized transfers from the firms, in the form of reduced revenue, is
$20.0 billion at a 2 percent discount rate (low-impact scenario of $6.2
billion; high-impact scenario of $17.6 billion). The primary estimate
for the annualized user fee obligation shifted from combusted tobacco
products to noncombusted tobacco products has a range from $26.3
million to $461.1 million with a primary estimate of $332.6 million at
a 2 percent discount rate. Transfers are summarized in table 13.
Table 13--Summary of Benefits, Costs, and Distributional Effects of the Proposed Rule
[Millions of 2023 dollars over a 40-year time horizon]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Primary Low High Discount
Category estimate estimate estimate Dollar year rate (%) Time horizon Notes
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized benefits........ $1,097,053 $273,521 $1,190,582 2023 2 2025-2064 (40 years).... See footnote.\44\
Annualized quantified, but non- ........... ........... ........... ........... .........
monetized, benefits.
------------------------------------------------------------------------------------------------------------------
Unquantified benefits................ Medical cost savings, productivity loss savings, reductions in smoking-related fires (excluding mortality),
reduced litter, and other associated harms to the environment
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized costs........... 2,077 690 2,729 2023 2 2025-2064 (40 years)....
Annualized quantified, but non- ........... ........... ........... ........... .........
monetized, costs.
------------------------------------------------------------------------------------------------------------------
Unquantified costs................... Changes in consumer surplus for some people who smoke normal nicotine content combusted tobacco products,
including potential utility changes for consumers who switch from NNC to VLNC combusted tobacco products.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized Federal 4,092 1,386 4,313 2023 2 2025-2064 (40 years)....
budgetary transfers.
------------------------------------------------------------------------------------------------------------------
Bearers of transfer gain and loss?... Transfers of Excise Tax Revenues from Federal Governments to Consumers
------------------------------------------------------------------------------------------------------------------
Annualized monetized State budgetary 8,414 2,848 8,877 2023 2 2025-2064 (40 years)....
transfers.
------------------------------------------------------------------------------------------------------------------
Bearers of transfer gain and loss?... Transfers of Excise Tax Revenues from State Governments to Consumers
------------------------------------------------------------------------------------------------------------------
Other annualized monetized transfers. 19,964 6,235 17,603 2023 2 2025-2064 (40 years)....
------------------------------------------------------------------------------------------------------------------
Bearers of transfer gain and loss?... Transfers of Revenues from Tobacco Firms to Consumers
------------------------------------------------------------------------------------------------------------------
Other annualized monetized transfers. 333 26 461 2023 2 2025-2064 (40 years)....
------------------------------------------------------------------------------------------------------------------
Bearers of transfer gain and loss?... Transfers from User Fees Owed by Combusted Tobacco Firms to s Owed by Noncombusted Tobacco Firms
--------------------------------------------------------------------------------------------------------------------------------------------------------
Net benefits
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annualized monetized net benefits.... 1,094,976 272,831 1,187,853 2023 2 2025-2064 (40 years)....
--------------------------------------------------------------------------------------------------------------------------------------------------------
Category Effects Notes
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects on State, local, or Tribal Significant transfer of tax revenues for State governments. Potential transfer of tax
governments. revenue for local and Tribal governments.
------------------------------------------------------------------------------------------------------------------
Effects on small businesses.......... Significant revenue reductions and compliance costs for small, combusted tobacco
product manufacturers. We expect most small, combusted manufacturers would shut down or
switch industries.
------------------------------------------------------------------------------------------------------------------
Effects on wages..................... No significant wage impacts.
------------------------------------------------------------------------------------------------------------------
[[Page 5115]]
Effects on growth.................... Anticipated growth in the noncombusted tobacco sector.
--------------------------------------------------------------------------------------------------------------------------------------------------------
We request comment on our estimates of benefits, costs, and
transfers of this proposed rule.
---------------------------------------------------------------------------
\44\ FDA notes that these results hinge on an expert elicitation
in which the experts were provided peer reviewed literature on VLNC
and NNC cigarette use in experiments. The expert elicitation and
much of the literature specifically referenced the nicotine level of
0.4 mg nicotine per gram total tobacco. However, in 22nd Century
Group, Inc.'s modified risk tobacco product applications, the
company reported that after 9 years of sampling by the company, the
average nicotine content of its genetically engineered VLNC tobacco
is 0.6 mg nicotine per gram of total tobacco, with a range of 0.4 to
0.7 mg nicotine per gram of total tobacco. It is likely that the
Quest and SPECTRUM Nicotine Research Cigarettes, used throughout the
scientific literature, also contained between 0.4 to 0.7 mg nicotine
per gram of total tobacco (Ref. 257). This suggests the literature
the experts reviewed studied cigarettes in the range of 0.4-0.7 mg
nicotine per gram total tobacco as opposed to only 0.4 mg nicotine
per gram total tobacco. Therefore, the results of the expert
elicitation are still applicable to a nicotine level of 0.7 mg
nicotine per gram total tobacco. For reference, nicotine content in
the top 100 cigarette brands (2017) is 17.2 mg nicotine per gram
total tobacco (Ref. 9).
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XIII. Analysis of Environmental Impact
The Agency has carefully considered the potential environmental
effects of this action. FDA has concluded that the action will not have
a significant impact on the human environment, and that an
environmental impact statement is not required. The Agency's finding of
no significant impact and the evidence supporting that finding is
available in the docket for this proposed rule (Refs. 665 and 666) and
may be seen in Dockets Management Staff (see ADDRESSES) between 9 a.m.
and 4 p.m., Monday through Friday; it is also available electronically
at https://www.regulations.gov. Under FDA's regulations implementing
the National Environmental Policy Act (21 CFR part 25), an action of
this type would require an environmental assessment under 21 CFR 25.20.
XIV. Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). A
description of these provisions is given in the Description section of
this document with an estimate of the annual reporting, recordkeeping,
and third-party disclosure burden. Included in the estimate is the time
for reviewing instructions, searching existing data sources, gathering
and maintaining the data needed, and completing and reviewing each
collection of information. If finalized, this proposed rule will seek
approval of a new information collection.
FDA invites comments on these topics: (1) whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; (4) ways to
minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology; and (5) the
standard and customary business practices of tobacco manufacturers as
it relates to capital, operating, and maintenance costs associated with
this collection of information.
Title: Tobacco Product Standard for Nicotine Yield of Cigarettes
and Certain Other Combusted Tobacco Products (0910-NEW).
Description: The FD&C Act authorizes FDA to adopt tobacco product
standards, including product standards that include provisions for
nicotine yields and for the reduction or elimination of other
constituents (including smoke constituents) or harmful components
(section 907(a)(3)(A) and (4) of the FD&C Act). FDA is proposing to
limit nicotine yield by setting a maximum nicotine content level for
finished cigarettes and certain other finished combusted tobacco
products not to exceed 0.70 mg of nicotine per gram of total tobacco.
Subpart A contains the general provisions of this proposed product
standard including scope, prohibited activities, and definitions.
Subpart B contains the proposed product standard requirements
pertaining to finished tobacco products that cover product testing
(Sec. 1160.12), sampling plans (Sec. 1160.16), analytical test
methods (Sec. 1160.14), nonconforming tobacco products (Sec.
1160.18), package label requirements (Sec. 1160.30) and recordkeeping
requirements (Sec. 1160.32).
Subpart C contains manufacturing code (Sec. 1160.14) and
recordkeeping (Sec. 1160.32) requirements.
Proposed Sec. 1160.12 contains provisions for the testing of
finished tobacco products that would be subject to this proposed rule.
Specifically, proposed Sec. 1160.12(a) would require that tobacco
product manufacturers conduct testing on each batch of finished tobacco
products.
Proposed Sec. 1160.12(b) would require that a full report of the
source data and results of all batch testing be maintained by the
tobacco product manufacturer. Based on FDA subject matter expertise and
experience from tobacco inspections, we expect that manufacturers would
discuss in these reports how their product is batched. These reports
would be generated for test samples from each batch and would not be
required for each individual finished tobacco product. This report
would have to include the following information:
(1) Full identification of the finished tobacco product that is the
subject of the report, including the product category, subcategory,
product name (brand and subbrand), package type, package quantity, and
nicotine source;
(2) Nicotine level of each sample tested from the batch and
standard deviation;
(3) The batch manufacturing date and location, including facility
name and address, for each sample;
(4) The testing date and location, including the facility name and
address;
(5) The manufacturing code of each sample tested (in accordance
with proposed Sec. 1160.30(c));
(6) The test method and sampling procedure used;
(7) Names and qualifications of the person(s) conducting the
testing and any laboratory accreditation;
[[Page 5116]]
(8) The equipment used (including documentation to show that the
equipment is appropriate for its intended purpose and has been
calibrated to ensure accurate and reliable results); and
(9) The criteria used to make a decision to accept or reject each
batch and the decision made with respect to each batch (e.g., accept,
reject) based on the results of the product testing. This information
would constitute the documentation of the source data and actual
results of the product testing conducted on each batch.
The main purpose of this report would be to verify that products
subject to this proposed product standard do not exceed the maximum
nicotine level and to document the company's decision for each batch
with respect to acceptance, rejection, and reworking of the products.
FDA expects that information collected pursuant to proposed Sec.
1160.12(b) would be integrated with the proposed Sec. 1160.18(b)
records (i.e., proposed Sec. 1160.12(b) records regarding the product
being tested, including, for example, the product category and
subcategory, brand and subbrand, packaging information, nicotine
source, manufacturing date, and the manufacturing code would inform the
1160.18(b) investigation). These proposed Sec. 1160.12(b) records also
would document the ultimate disposition of the batch based on the
testing of the representative samples.
Proposed Sec. 1160.14 would require that manufacturers analyze the
nicotine levels of cigarettes and certain other finished combusted
tobacco products covered by the rule using a validated analytical test
method. Manufacturers would be required to demonstrate that the test
method used was validated in an analytical test laboratory. Proposed
Sec. 1160.16 would require each tobacco product manufacturer to design
and implement a sampling plan that covers each finished tobacco product
that it manufactures. This sampling plan would provide procedures for
the manufacturer to select samples to demonstrate conformance to the
proposed maximum nicotine level requirement. The required procedures
would help ensure that products that exceed the maximum level of
nicotine are not sold or distributed to consumers. This provision also
explains that the sampling plan must ensure samples taken are
representative of an entire batch and are randomly selected and
collected from each batch for testing.
This section would also require test samples from each batch be
collected and examined in accordance with certain procedures (proposed
Sec. 1160.16(b)). Each test sample would need to be identified so that
the following information can be determined:
Full identification of the finished tobacco product
sampled, including product category, subcategory, product name (brand
and subbrand), package type, package quantity, and nicotine source;
The manufacturing code;
The date on which the sample was taken;
The sampling location (including the address of the
facility and specific location within the facility where the sample was
taken);
The name of the person(s) who collected the sample; and
The location where the sample will be tested (including
the facility name and address).
Proposed Sec. 1160.18 would require finished tobacco product
manufacturers to establish procedures for the control and disposition
of nonconforming tobacco products. The proposed procedures would
require tobacco product manufacturers to establish and maintain
procedures to identify, investigate, segregate, and make disposition
decisions (i.e., acceptance, rejection, rework) about nonconforming
finished tobacco products to prevent their release for commercial
distribution. FDA interprets ``establish and maintain'' for purposes of
proposed Sec. 1160.18 to mean define, document (in writing or
electronically), implement, follow, and, when necessary, update.
Identification of potential nonconforming product (i.e., a tobacco
product that does not conform to the proposed maximum nicotine level
requirement) can be accomplished in many ways (e.g., applying a label
with the relevant information directly to the product container; if an
electronic system is utilized, associating the nonconforming product
information with the relevant barcode). If a potential nonconforming
product is determined to be nonconforming, it would need to remain
segregated throughout investigation and disposition, including any
rework. For purposes of proposed part 1160, ``segregation'' means
setting the identified potential nonconforming product apart from other
product (i.e., placing it away from conforming finished product). This
segregation could be accomplished by placing it in a quarantined or
specifically marked-off area.
The manufacturer would be required to conduct an investigation to
determine the extent of the nonconformity upon identification of a
nonconforming product and, as applicable, the locations where the
nonconforming products have been distributed. We expect the
manufacturer would be able to determine the locations of initial
consignees (e.g., wholesalers, distributors, retailers) where the
affected products were shipped in the event a corrective action needs
to be taken. The investigation would have to include an examination of
all relevant processes and controls, laboratory testing, complaints,
and any other relevant records and sources of information concerning
the nonconforming product. Tobacco product manufacturers would be
required to reject a batch of a finished tobacco product if the
nicotine level of the test sample does not meet the requirements unless
a disposition decision and justification to release the batch is made
after an investigation shows the batch meets the requirements.
Tobacco product manufacturers would be required to determine the
disposition of all nonconforming tobacco products and any necessary
followup. Nonconforming product cannot be released for commercial
distribution without rework or an adequate justification (developed and
maintained in accordance with Sec. 1160.32). Thus, nonconforming
product could be reworked, distributed with an adequate justification,
or discarded. An adequate written justification would be required to
address how the nonconforming product meets all requirements under this
part.
Proposed Sec. 1160.18(e) would require each tobacco product
manufacturer to maintain records of all activities required under Sec.
1160.18. Records must include the date and time of the activity, the
individual performing the activity, the type of activity performed, any
information that demonstrates the requirement was met, and any data or
calculations necessary to reconstruct the results.
FDA expects that information collected pursuant to proposed Sec.
1160.12(b) would be integrated with the proposed Sec. 1160.18(b)
records (i.e., proposed Sec. 1160.12(b) records regarding the product
being tested, including, for example, the product category and
subcategory, brand and subbrand, packaging information, nicotine
source, manufacturing date, and the manufacturing code would inform the
1160.18(b) investigation). These proposed Sec. 1160.12(b) records also
would document the ultimate disposition of the batch based on the
testing of the representative samples.
Proposed Sec. 1160.30 would require the use of a manufacturing
code to serve as
[[Page 5117]]
a common identifier for production and distribution records. The
purpose of the manufacturing code is to allow manufacturers and FDA to
identify the production batch of a particular finished product that has
been released for distribution. This information is intended to help
determine the product's history (e.g., batch production records) and
assist manufacturers and FDA in the event of a nonconforming product
investigation and any corrective actions to be taken as a result of the
investigation.
The manufacturing code would be required to be permanently affixed
to the packaging or labeling of all finished tobacco products. The
manufacturing code must be affixed in a manner that ensures it will
remain on the packaging or label through the expected duration of use
of the product by the consumer. In addition, proposed Sec. 1160.30(b)
would require that the manufacturing code be permanently affixed,
legible, conspicuous, prominent, and appear in the English language.
As stated in proposed Sec. 1160.30(c), the manufacturing code must
contain the following information listed in the following order:
The manufacturing date in 2-digit numerical values in the
month-day-year format (MMDDYY);
The finished tobacco product batch number; and
The designation ``-NS'' at the end.
The manufacturing code would allow manufacturers and FDA to
identify the production batch of a particular finished product that has
been released for distribution. This information is intended to help
determine the product's history (e.g., batch production records) and
assist manufacturers and FDA in the event of a nonconforming product
investigation and any corrective actions to be taken as a result of the
investigation.
Proposed Sec. 1160.32 contains recordkeeping requirements that are
necessary for FDA to ascertain and confirm that finished tobacco
products are in compliance with the proposed product standard. The
proposed product standard would require that manufacturers establish
and maintain records regarding the results of testing conducted on each
batch to determine conformance with the proposed standard. In addition,
this proposed product standard would require that manufacturers
maintain records of batch testing, source data for analytical test
method validation, sampling plans and sampling procedures, and
nonconforming tobacco products.
First, proposed Sec. 1160.32(a) would require that each facility
that manufactures tobacco products subject to this part (i.e., finished
tobacco products) establish and maintain records related to compliance
with this part, including the following:
(1) The source data and results of analyses conducted to determine
conformance with Sec. 1160.10, including all information identified in
Sec. 1160.12(b);
(2) All source data used for analytical test method validation;
(3) All sampling plans and sampling reports under Sec. 1160.16;
(4) Documentation that the persons performing sampling under Sec.
1160.16 have sufficient education, training, and experience to
accomplish the assigned functions; and
(5) All nonconforming tobacco product identification, segregation,
investigation, rework, and disposition decision procedures, including
justifications, under Sec. 1160.18. This information is necessary for
FDA to ascertain and confirm that the products are in compliance with
the proposed product standard.
Second, proposed Sec. 1160.32(b) provides certain specifications
for these records. All records required under this part, regardless of
storage medium, would need to be attributable, legible,
contemporaneously recorded, original, and accurate. In addition, these
records would be required to be written in English; alternatively, an
accurate English translation must be made available upon request.
Documents that have been translated from a foreign language into
English would have to be accompanied by the foreign language version of
the document and a certification by the manufacturer's authorized
representative (which could be a U.S. agent for the manufacturer) that
the English language translation is complete and accurate, and a brief
statement of the qualifications of the person who made the translation
(e.g., education, experience). These records would need to be
maintained at the manufacturing establishment or another location that
is readily accessible to responsible officials of the manufacturer and
to FDA.
Proposed Sec. 1160.32(c) would require that the records kept under
this part be retained for at least 4 years from the date of commercial
distribution of the finished tobacco product that is the subject of the
record. FDA has selected 4 years as a means to help ensure that the
records would be available for at least one biennial FDA inspection
under sections 704 and 905(g) of the FD&C Act.
FDA believes that detailed recordkeeping requirements are necessary
to confirm that finished tobacco products are in compliance with the
proposed product standard. For example, requiring manufacturers to
document their test results would enable FDA to confirm the
manufacturer's test method is adequate to meet the requirements of part
1160. In addition, requiring nonconforming product records would help
the manufacturer and FDA determine the extent of the nonconformity with
the product standard and, as applicable, the locations where the
nonconforming products have been distributed; for example, in the event
of a recall.
Description of Respondents: The information collection requirements
in the proposed standard would apply to tobacco product manufacturers,
which means any person, including a repacker or relabeler, who (1)
manufactures, fabricates, assembles, processes, or labels a tobacco
product; or (2) imports a finished tobacco product for sale or
distribution in the United States. Specifically, the information
collection would apply to manufacturers of cigarettes (other than
noncombusted cigarettes, such as heated tobacco products that meet the
definition of a cigarette), cigarette tobacco, roll-your-own (RYO)
tobacco, cigars (including little cigars, cigarillos, and large cigars,
but excluding ``premium cigars''), and pipe tobacco (other than
waterpipe tobacco). FDA recognizes that many of the proposed provisions
of the proposed rule are in accordance with the quality control and
manufacturing practices that manufacturers have already adopted on a
voluntary basis. Application requirements are set by the final
Substantial Equivalence (0910-0673) and Premarket Tobacco Product
Application (0910-0879) rules. For products covered by this proposed
standard, we expect most manufacturers will seek authorization using
the substantial equivalence premarket pathway, which may decrease the
amount of data required for authorization. See section IX.B of this
document regarding pathways to market tobacco products that have been
modified to meet the proposed standard. Based on FDA's subject matter
expertise and industry data, we recognize that between 85 and 90
percent of all cigarette production is conducted by large
manufacturers. We also find that the other tobacco product categories,
such as non-premium cigars, pipe, and RYO tobacco, have similar levels
of market concentration. We assume that large tobacco product
manufacturers represent the bulk of tobacco product
[[Page 5118]]
production capacity and so represent the majority of recordkeeping
burden.
The proposed provision Sec. 1160.12 (batch testing), is part of
standard and customary business practices of tobacco manufacturers. As
such, there are no capital costs or operating and maintenance costs
associated with this collection of information. Batch testing is
conducted either by the manufacturer in-house or by a 3rd-party
accredited laboratory. If sent to a 3rd-party laboratory, we do not
expect any capital, operating, or maintenance costs associated with
batch testing to be incurred by the manufacturer. We expect a
manufacturer would only test their products in-house if they already
possess an in-house laboratory accredited to conduct scientific tests.
We would not anticipate capital, operating, or maintenance costs for
these in-house laboratories as capital and maintenance are components
of maintaining accreditation. We do not expect any manufacturers
currently without an in-house laboratory to newly establish an in-house
accredited laboratory as a result of this product standard.
The proposed provision Sec. 1160.14 (analytical test method), is
also part of standard and customary business practices of tobacco
manufacturers. As such, there are no capital costs or operating and
maintenance costs associated with this collection of information.
Manufacturers are already required to submit test results of analytical
testing for nicotine and other relevant harmful and potentially harmful
constituents (HPHCs) as part of premarket submissions. As the
establishment and use of analytical testing is already generally
required for premarket submissions, we do not anticipate capital,
operating, or maintenance cost from these provisions.
The proposed provision Sec. 1160.16 (sampling plans), is part of
standard and customary business practices of tobacco manufacturers. As
such, there are no capital costs or operating and maintenance costs
associated with this collection of information. Manufacturers already
routinely conduct analytical testing to check for consistency in their
finished products. To conduct such testing, manufacturers would have
needed to establish a sampling plan to generate a representative sample
of their product for testing. As such, we do not anticipate capital,
operating, or maintenance cost from these provisions.
The proposed provision Sec. 1160.18 (nonconforming tobacco
products), is part of standard and customary business practices of
tobacco manufacturers. As such, there are no capital costs or operating
and maintenance costs associated with this collection of information.
Based on FDA subject matter expertise and inspections, we find that
almost all manufacturers already check for consistency and conformance
of their products and rework product as necessary to supply information
for internal quality checks and distribution purposes, we do not
anticipate capital, operating, or maintenance cost from these
provisions.
The proposed provision Sec. 1160.30 (manufacturing code labeling),
is part of standard and customary business practices of tobacco
manufacturers. As such, there are no capital costs or operating and
maintenance costs associated with this collection of information. Based
on FDA subject matter expertise and industry information, we find that
almost all manufacturers already apply a manufacturing code to their
products. Because a manufacturing code also supplies information that
the manufacturer needs for internal quality and distribution purposes
(standard and customary practices), we do not anticipate additional
capital, operating, or maintenance cost from these provisions.
FDA specifically invites comments on our discussion of the standard
and customary business practices of tobacco manufacturers as it relates
to capital, operating, and maintenance costs associated with this
collection of information.
FDA estimates the burden of this collection of information as
follows:
Table 14--Estimated Annual Recordkeeping Burden 45
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Average burden
21 CFR section or activity Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sec. 1160.12 Product Testing..................................... 143 50.84 7,270 9 65,430
Sec. 1160.14 Analytical Test Method.............................. 143 4 572 1 572
Sec. 1160.16 Sampling Plan....................................... 143 4 572 1 572
Sec. 1160.18 Procedures for Nonconforming Tobacco Products and 143 1 143 14 2,002
Related Investigations; Procedures for Control and Disposition of
Nonconforming Tobacco Products....................................
Sec. 1160.30 Package Label Requirements (Manufacturing Code)..... 143 4 572 7 4,004
Sec. 1160.32 Recordkeeping Requirements (Batch Testing Records).. 143 50.84 7,270 6 43,620
------------------------------------------------------------------------------------
Total Annual Burden............................................ ............... ............... ............... ............... 116,200
--------------------------------------------------------------------------------------------------------------------------------------------------------
Table 14 displays the recordkeeping burden associated with this
proposed rule. Included in this estimate is the recordkeeping burden
for establishing and maintaining records regarding the results of
testing conducted on each batch to determine conformance with the
proposed standard, sampling plans and sampling procedures, and records
related to manufacturing controls. FDA's burden estimates are based on
CTP's Tobacco Registration and Listing Module Next Generation (TRLM NG)
data and Dun & Bradstreet firm data (D&B). The requirements in the
Tobacco Product Standard for Nicotine Yield of Cigarettes and Certain
Other Combusted Tobacco Products proposed rule would apply to both
domestic and foreign manufacturers of finished tobacco products that
are distributed or sold in the United States. We estimate the number of
affected entities, by tobacco product category and size of operation
group. We estimate that there are a total of 143 entities potentially
affected by the proposed rule (domestic manufacturers and importers of
impacted tobacco products, including 133 manufacturers and importers of
[[Page 5119]]
cigarettes, cigars, pipe tobacco, and RYO tobacco and 10 dual operation
facilities that manufacture both combusted and noncombusted products).
For purposes of the PRA estimates, FDA used the entities affected and a
weighted average of the median hours to calculate the respondents and
total burden hours.
---------------------------------------------------------------------------
\45\ There are no capital costs or operating and maintenance
costs associated with this collection of information.
---------------------------------------------------------------------------
We estimate a total of 7,270 batches per year are required to be
tested under Sec. 1160.12 (product testing). Based on information from
inspections and other FDA subject matter expertise, including typical
batch sizes and projected combusted tobacco production by year, FDA
estimates that there will be 50.84 records per recordkeeper with 9
hours of average burden per recordkeeping. FDA assumes respondents will
establish a total of 7,270 annual records for a total of annual 65,430
hours.
Based on information from inspections and other FDA subject matter
expertise, we expect that core blends are the products that
manufacturers will choose to reformulate to meet the product standard.
Manufacturers would incur a burden to establish an analytical test
method and sampling plan for each reformulated core blend. FDA experts
assume that each manufacturer, on average, utilizes four different core
blends per tobacco category that they manufacture. Under Sec. 1160.14
(analytical test method), respondents would determine an analytical
test method to use for complying with the product standard. During
validation of the analytical test method within the laboratory to be
used, the respondent would record and collect the data generated and
maintain these records. FDA estimates there will be 4 records per
recordkeeper with 1 hour of average burden per recordkeeping and
respondents will establish a total of 572 annual records for a total of
annual 572 hours. Under Sec. 1160.16 (sampling plan), FDA estimates
there will be 4 records per recordkeeper with 1 hour of average burden
per recordkeeping. FDA assumes respondents will establish a total of
572 annual records for a total of annual records for a total of annual
572 hours.
Under Sec. 1160.18 (procedures for nonconforming products), FDA
assumes there will be 1 record per recordkeeper with 14 hours of
average burden per recordkeeping for a total of 143 annual records and
a total of annual 2,002 hours. This estimate is based on information
from tobacco inspections and FDA experience in developing good
manufacturing practices in non-tobacco industries. Further, as stated
above, based on FDA subject matter expertise and inspections, we find
that almost all manufacturers already check for consistency and
conformance of their products and rework product as necessary to supply
information for internal quality checks and distribution purposes.
Proposed Sec. 1160.30 would require manufacturers to apply a
manufacturing code to the packaging and label of tobacco products.
Based on FDA subject matter expertise and market tracking information,
we find that almost all manufacturers already apply a manufacturing
code to their products. FDA assumes 4 records per recordkeeper with 7
hours of average burden per recordkeeping, and a total of 572 annual
records for a total of annual 4,004 hours.
Under Sec. 1160.32 (batch testing records), FDA assumes 50.84
records per recordkeeper with 6 hours of average burden per
recordkeeping. This estimate is based on establishing the format and
maintaining batch test records for detailed recordkeeping requirements,
including English translation and accessibility, that are necessary to
confirm that finished tobacco products are in compliance with the
proposed product standard. FDA assumes that respondents will maintain a
total of 7,270 annual records for a total of annual 43,620 hours.
FDA expects the additional one-time (i.e., occurring only in the
first year) reporting burden for the information collection that will
result from this rule, to be as follows:
Table 15--Estimated One-Time Reporting Burden
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
Activity Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Review and familiarization with the rule........................... 1,465 1 1,465 10 14,650
------------------------------------------------------------------------------------
Total One-Time Burden.......................................... ............... ............... ............... ............... 14,650
--------------------------------------------------------------------------------------------------------------------------------------------------------
Based on FDA subject matter expertise, we assume that all entities
affected by this proposed rule would spend time to read and understand
the rule, resulting in a one-time reporting burden. FDA estimates that
there will be 293 entities and 5 individuals at each entity that will
read the final rule. It is estimated that each respondent will spend up
to 10 hours reading and understanding the rule for a total of 14,650
one-time burden hours. Per the requirements of this proposed rule, FDA
estimates the total burden will be 130,850 hours (116,200 + 14,650).
FDA invites comments on the estimates in this section and
specifically any burden specific to small manufacturers to whom this
proposed standard would apply. To ensure that comments on information
collection are received, OMB recommends that written comments be
submitted through reginfo.gov (see ADDRESSES). All comments should be
identified with the title of the information collection.
In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3407(d)), we have submitted the information collection provisions of
this proposed rule to OMB for review. These information collection
requirements will not be effective until FDA publishes a final rule,
OMB approves the information collection requirements, and the rule goes
into effect. FDA will announce OMB approval of these requirements in
the Federal Register.
XV. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. Section 4(a) of the
Executive order requires Agencies to ``construe . . . a Federal statute
to preempt State law only where the statute contains an express
preemption provision or there is some other clear evidence that the
Congress intended preemption of State law, or where the exercise of
State authority conflicts with the exercise of Federal authority under
the Federal statute.'' We have determined that the proposed rule, if
finalized, would not contain policies that 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 tentatively concludes that the rule does not contain
policies that have
[[Page 5120]]
federalism implications as defined in the Executive order and,
consequently, a federalism summary impact statement is not required.
This rule is being issued under section 907 of the FD&C Act, which
enables FDA to prescribe regulations relating to tobacco product
standards, and the sale and distribution restriction in this rule is
also being issued under section 906(d) of the FD&C Act, which enables
FDA to prescribe regulations restricting the sale and distribution of a
tobacco product. If this proposed rule is made final, the final rule
would create requirements whose preemptive effect would be governed by
section 916 of the FD&C Act (21 U.S.C. 387p) entitled ``Preservation of
State and local authority.''
Section 916 of the FD&C Act broadly preserves the authority of
States and localities to protect the public against the harms of
tobacco use. Specifically, section 916(a)(1) of the FD&C Act
establishes a general presumption that FDA requirements do not preempt
or otherwise limit the authority of States, localities, or tribes to,
among other things, enact and enforce laws regarding tobacco products
that relate to certain activities (e.g., sale, distribution) and that
are in addition to or more stringent than requirements established
under chapter IX of the FD&C Act.
Section 916(a)(2)(A) of the FD&C Act is an express preemption
provision that establishes an exception to the preservation of State
and local governmental authority over tobacco products established in
section 916(a)(1). Specifically, section 916(a)(2)(A) of the FD&C Act
provides that ``[n]o State or political subdivision of a State may
establish or continue in effect with respect to a tobacco product any
requirement which is different from, or in addition to, any requirement
under the provisions of this chapter relating to tobacco product
standards . . . .''
However, section 916(a)(2)(B) limits the applicability of section
916(a)(2)(A) of the FD&C Act, narrowing the scope of State and local
requirements that are subject to express preemption. Paragraph
(a)(2)(B) provides that preemption under paragraph (a)(2)(A) does not
apply to State or local ``requirements relating to the sale,
distribution, possession, information reporting to the State, exposure
to, access to, the advertising and promotion of, or use of, tobacco
products by individuals of any age, or relating to fire safety
standards for tobacco products.''
If this proposed rule is finalized as proposed, the final rule
would create requirements that fall within the scope of section
916(a)(2)(A) of the FD&C Act because they are ``requirements under the
provisions of the chapter relating to tobacco product standards.''
Accordingly, the preemptive effect of those requirements on any State
or local requirement would be determined by the nature of the State or
local requirement at issue--specifically, whether the State or local
requirement is preserved under section 916(a)(1) of the FD&C Act, and/
or excepted under section 916(a)(2)(B) of the FD&C Act (such as if it
relates to the ``sale, distribution, possession, information reporting
to the State, exposure to, access to, the advertising and promotion of,
or use of, tobacco products''). State and local prohibitions on the
sale and distribution of tobacco products would not be preempted by
this rule, if finalized, because such prohibitions would be preserved
by section 916(a)(1) of the FD&C Act or, as applicable, excepted from
express preemption by section 916(a)(2)(B) of the FD&C Act. FDA invites
comments on how State or local laws may be implicated if this proposed
rule is finalized.
XVI. Severability
In accordance with section 5 of the Tobacco Control Act, which
provides for the severability of, inter alia, all ``regulations
promulgated under'' the authorities provided by that Act, FDA would
consider the various requirements and prohibitions established by this
rule, if finalized, to be severable. It is FDA's interpretation and
position that the invalidity of any provision of a final rule would not
affect the validity of any other part of the rule. In the event any
court or other lawful authority were to temporarily or permanently
invalidate, restrain, enjoin, or suspend any provision of a final rule,
FDA intends for the remaining parts to continue to be valid.
Additionally, as further stated in section 5 of the Tobacco Control
Act, if certain applications of a final rule to persons or
circumstances (discussed in the preamble or otherwise) are held to be
invalid, application of such provisions to any other person or
circumstance will not be affected and will continue to be enforced to
the fullest extent possible. Each provision of the rule is
independently supported by data and analysis as described or referenced
in this preamble and, if issued separately, would remain a proper
exercise of FDA authority.
XVII. Consultation and Coordination With Indian Tribal Governments
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule contains policies that may have a substantial
direct effect 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. We expect some tribal governments to be impacted given that
some are manufacturers and retailers of cigarettes. The Agency solicits
comments from tribal officials on any potential impact on Indian Tribes
from this proposed action.
XVIII. References
The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. Although FDA verified the website addresses
in this document, please note that websites are subject to change over
time.
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List of Subjects in 21 CFR Part 1160
Administrative practice and procedure, Labeling, Smoke, Smoking,
Tobacco, Tobacco products.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act, and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that chapter I of title 21 of the Code of Federal Regulations
be amended by adding part 1160 to subchapter K to read as follows:
PART 1160--TOBACCO PRODUCT STANDARD FOR NICOTINE YIELD OF
CIGARETTES AND CERTAIN OTHER COMBUSTED TOBACCO PRODUCTS
Subpart A--General Provisions
Sec.
1160.1 Scope.
1160.3 Definitions.
Subpart B--Product Requirements
1160.10 Nicotine level.
1160.12 Product testing.
1160.14 Analytical test method.
1160.16 Sampling plans and procedures.
1160.18 Nonconforming tobacco product.
Subpart C--Manufacturing Code and Recordkeeping Requirements
1160.30 Manufacturing code requirements.
1160.32 Recordkeeping requirements.
Authority: 21 U.S.C. 331, 371(a), 374, 381(e), 381(p)(2), 387b,
387c, 387f(d), 387f(e), 387g, 387i, 387j.
Subpart A--General Provisions
Sec. 1160.1 Scope.
(a) This part sets forth the product standard to limit nicotine
yield by setting a maximum nicotine content level for certain finished
tobacco products. The provisions of this part are applicable to
cigarettes (other than noncombusted cigarettes, such as heated tobacco
products that meet the definition of a cigarette), cigarette tobacco,
roll-your-own tobacco, cigars (other than premium cigars), and pipe
tobacco (other than waterpipe tobacco).
(b) No person may distribute, sell, or offer for sale or
distribution within the United States finished tobacco products, as
described in paragraph (a) of this section, that are not in compliance
with this part.
(c) No person may manufacture within the United States finished
tobacco products, as described in paragraph (a) of this section, that
are not in compliance with this part, unless such tobacco products are
intended for export and are eligible for export under section 801(e)(1)
of the Federal Food, Drug, and Cosmetic Act.
Sec. 1160.3 Definitions.
For purposes of this part:
Accessory means any product that is intended or reasonably expected
to be used with or for the human consumption of a tobacco product; does
not contain tobacco or nicotine from any source and is not made or
derived from tobacco; and meets either of the following:
(1) Is not intended or reasonably expected to affect or alter the
performance, composition, constituents, or characteristics of a tobacco
product; or
(2) Is intended or reasonably expected to affect or maintain the
performance, composition, constituents, or characteristics of a tobacco
product; but
(i) Solely controls moisture and/or temperature of a stored tobacco
product; or
(ii) Solely provides an external heat source to initiate but not
maintain combustion of a tobacco product.
Batch means a specific identified amount of a finished tobacco
product produced in a unit of time or quantity and that is intended to
have the same specifications.
Cigar means a tobacco product that:
(1) Is not a cigarette; and
(2) Is a roll of tobacco wrapped in leaf tobacco or any substance
containing tobacco.
[[Page 5142]]
Cigarette, as used in this part:
(1) Means a product that:
(i) Is a tobacco product; and
(ii) Meets the definition of the term ``cigarette'' in section 3(1)
of the Federal Cigarette Labeling and Advertising Act; and
(2) Includes tobacco, in any form, that is functional in the
product, which, because of its appearance, the type of tobacco used in
the filler, or its packaging and labeling, is likely to be offered to,
or purchased by, consumers as a cigarette or as roll-your-own tobacco.
Cigarette tobacco means any tobacco product that consists of loose
tobacco that is intended for use by consumers in a cigarette. Unless
otherwise stated, the requirements applicable to cigarettes under this
chapter also apply to cigarette tobacco.
Commercial distribution means any distribution of a finished
tobacco product, whether domestic or imported, to consumers or to any
person, but does not include interplant transfers of a tobacco product
between establishments within the same parent, subsidiary, and/or
affiliate company, nor does it include providing a tobacco product for
product testing where such product is not made available for personal
consumption or resale. ``Commercial distribution'' does not include the
handing or transfer of a tobacco product from one consumer to another
for personal consumption.
Component or part means any software or assembly of materials
intended or reasonably expected:
(1) To alter or affect the tobacco product's performance,
composition, constituents, or characteristics; or
(2) To be used with or for the human consumption of a tobacco
product. The term excludes anything that is an accessory of a tobacco
product.
Finished tobacco product means a tobacco product, including all
components and parts, sealed in final packaging (e.g., filters or
filter tubes sold to consumers separately or as part of kits) or in the
final form in which it is intended to be sold to consumers.
Manufacturing code means any distinctive sequence or combination of
letters, numbers, or symbols that begins with the manufacturing date,
followed by the batch number, and concludes with ``-NS.''
Manufacturing date means the month, day, and year in 2-digit
numerical values in the format (MMDDYY) that a finished tobacco product
is packaged for distribution.
Nicotine means the chemical substance named 3-(1-methyl-2-
pyrrolidinyl) pyridine or C[10]H[14]N[2], including any salt or complex
of nicotine, derived from any source.
Nonconforming tobacco product means any tobacco product that does
not meet the requirements of Sec. 1160.10 or Sec. 1160.30.
Package or packaging means a pack, box, carton, or container of any
kind or, if no other container, any wrapping (including cellophane) in
which a tobacco product is offered for sale, sold, or otherwise
distributed to consumers.
Person includes an individual, partnership, corporation, or
association.
Pipe tobacco means any tobacco product that, because of its
appearance, type, packaging, or labeling, is suitable for use and
likely to be offered to, or purchased by, consumers as tobacco to be
smoked in a pipe.
Rework means action taken on a nonconforming tobacco product to
ensure the product meets the specifications and other requirements of
this part before it is released for commercial distribution.
Roll-your-own tobacco means any tobacco product which, because of
its appearance, type, packaging, or labeling, is suitable for use and
likely to be offered to, or purchased by, consumers as tobacco for
making cigarettes or cigars.
Specification means any requirement with which a product, process,
service, or other activity must conform.
Tobacco filler means cut, ground, powdered, or leaf tobacco or
other nicotine-containing substances in a finished tobacco product.
Tobacco product means any product made or derived from tobacco, or
containing nicotine from any source, 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).
The term ``tobacco product'' does not mean an article that under the
Federal Food, Drug, and Cosmetic Act is: a drug (section 201(g)(1)); a
device (section 201(h)); a combination product (section 503(g)); or a
food under section 201(f) if such article contains no nicotine, or no
more than trace amounts of naturally occurring nicotine.
Tobacco product manufacturer means any person, including a repacker
or relabeler, who:
(1) Manufactures, fabricates, assembles, processes, or labels a
tobacco product; or
(2) Imports a finished tobacco product for sale or distribution in
the United States.
Total tobacco means tobacco filler and any other tobacco or
tobacco-derived material used as part of a tobacco product.
United States means the 50 States of the United States of America
and the District of Columbia, the Commonwealth of Puerto Rico, Guam,
the Virgin Islands, American Samoa, Wake Island, Midway Islands,
Kingman Reef, Johnston Atoll, the Northern Mariana Islands, and any
other trust territory or possession of the United States.
Subpart B--Product Requirements
Sec. 1160.10 Nicotine level.
A finished tobacco product must not exceed a nicotine content of
0.70 milligrams of nicotine per gram of total tobacco.
Sec. 1160.12 Product testing.
(a) Batch testing. Tobacco product manufacturers must conduct
testing on finished tobacco products to ensure that the batch conforms
with Sec. 1160.10. The manufacturer must use an analytical test method
that meets the requirements set forth in Sec. 1160.14. Samples for
testing each batch to determine if it conforms with Sec. 1160.10 must
be selected in accordance with the requirements set forth in Sec.
1160.16.
(b) Documentation of test results. A full report of the source data
and results of all batch testing must be maintained by the tobacco
product manufacturer in accordance with Sec. 1160.32, including the
following:
(1) Full identification of the finished tobacco product that is the
subject of the report, including, if applicable, the submission
tracking number (STN) associated with marketing authorization
(including the static product ID (PD), if applicable), product name(s)
(including brand and subbrand and the original name described in the
premarket application, if different), product category, subcategory,
package type, package quantity, and nicotine source;
(2) Nicotine level of each sample tested and standard deviation;
(3) The batch manufacturing date and location, including facility
name and address, for each sample;
(4) The testing date and location, including the facility name and
address;
(5) The manufacturing code of each sample tested;
(6) The test method and sampling procedure used;
(7) The names and qualifications of the person(s) conducting the
testing and any laboratory accreditation;
(8) The equipment used (including documentation to show that the
[[Page 5143]]
equipment is appropriate for its intended purpose and has been
calibrated to ensure accurate and reliable results); and
(9) The criteria used to make a decision to accept or reject each
batch and the decision made with respect to each batch (e.g., accept,
reject) based on the results of the product testing.
Sec. 1160.14 Analytical test method.
Tobacco product manufacturers must use an analytical test method
and must demonstrate that the test method used was validated in an
analytical test laboratory.
Sec. 1160.16 Sampling plans and procedures.
(a) Sampling plans. Each tobacco product manufacturer must design
and implement a sampling plan or plans that cover each finished tobacco
product based on a valid scientific rationale to ensure that the
product consistently conforms to the requirement set forth in Sec.
1160.10. The sampling plan must ensure that samples taken are
representative of an entire batch (i.e., randomized or systematically
selected across the entire batch) and collected from each batch for
testing. To account for the variability of nicotine in finished tobacco
products, the following factors must be based on adequate statistical
criteria: the confidence intervals, the level of necessary precision,
and the number of finished products sampled. The sampling plan must
take into account the manufacturing quality history of the manufacturer
(e.g., batch testing records, nonconforming tobacco product
investigations). Each sampling plan must describe the sampling
methodology, with scientific rationale, incorporate all sources of
variability (including variability of the analytic method and nicotine
levels), and describe the sample size needed (including a full
description of how the sample size is calculated) consistent with the
sampling plan to achieve the sampling objective. The sampling plan must
also describe the criteria the tobacco product manufacturer will use to
make a decision to accept or reject each batch.
(b) Sampling procedures. Test samples must be collected from each
batch and examined in accordance with the following procedures:
(1) Test samples are to consist of the finished tobacco product as
it is intended to be sold or distributed to consumers and not of a
separate production sample.
(2) All test samples must be stored according to the intended
storage conditions for the finished tobacco product. A tobacco product
manufacturer must include all of its factories, stock rooms,
warehouses, and other locations containing finished tobacco products in
the population to be sampled.
(3) Test samples must be taken from each batch and tested within 30
calendar days of the manufacturing date. The amount of material
acquired during sampling must be sufficient for all testing required by
Sec. 1160.14, including any repeat testing that may be necessary.
Samples must be selected from each batch in accordance with the
applicable sampling plan.
(4) Sampling must be performed by persons who have sufficient
education, training, and experience to accomplish the assigned
functions.
(5) Each test sample must be identified so that the following
information can be determined:
(i) Full identification of the finished tobacco product sampled,
including, if applicable, the STN associated with marketing
authorization (including the PD, if applicable), product name(s)
(including brand and subbrand and the original name described in the
premarket application, if different), product category, subcategory,
package type, package quantity, and nicotine source;
(ii) The manufacturing code;
(iii) The date on which the sample was taken;
(iv) The sampling location (including the address of the facility
and specific location within the facility where the sample was taken);
(v) The name of the person(s) who collected the sample; and
(vi) The location where the sample will be tested (including the
facility name and address).
(6) Samples sent for testing must be packed securely with adequate
protection against damage (e.g., mechanical damage, adverse changes in
humidity or temperature). A list of the samples in each shipment must
be sent to the testing facility under separate cover.
(7) All samples for a batch test must be tested at the same
facility.
(8) If samples will be transported to a different facility from the
manufacturing facility for testing, once test samples arrive at the
testing facility, they must be inspected, accounted for, and properly
stored under the finished tobacco product's intended storage
conditions, and a report that includes the following information must
be generated for the batch test and be maintained by the tobacco
product manufacturer in accordance with Sec. 1160.32:
(i) Full identification of the finished tobacco product sampled,
including, if applicable, the STN associated with marketing
authorization (including the PD, if applicable), product name(s)
(including brand and subbrand and the original name described in the
premarket application, if different), product category, subcategory,
package type, package quantity, and nicotine source;
(ii) The manufacturing code;
(iii) The date on which samples were taken, if available;
(iv) The sampling location (including the address and specific
locations within any facilities where samples were taken);
(v) The number of test samples drawn; and
(vi) Complete records of the samples received and tested, including
the date of receipt, the identifier of all persons who tested the
samples, and the test results.
(9) Each batch must be withheld from commercial distribution until
it has been sampled and tested and a decision has been made by the
tobacco product manufacturer that it conforms to the requirements of
this part and may be released for commercial distribution.
Sec. 1160.18 Nonconforming tobacco product.
Each tobacco product manufacturer must establish and maintain
procedures for the control and disposition of nonconforming tobacco
product. The procedures must include the following requirements:
(a) Identification and segregation. Each tobacco product
manufacturer must identify and segregate potential nonconforming
product in a manner that prevents commercial distribution of potential
nonconforming product prior to investigation and disposition.
(b) Investigation. Each tobacco product manufacturer must
investigate all potential nonconforming tobacco products to determine
if the product is nonconforming. The investigation must include an
examination of relevant production processes and controls, laboratory
testing, complaints, and any other relevant records and sources of
information. For products determined to be nonconforming, the
investigation must also determine the scope and cause of
nonconformance.
(c) Rejection of nonconforming product. Tobacco product
manufacturers must reject a batch of a finished tobacco product if the
nicotine level of a test sample from the batch does not conform to the
requirements of this part unless a disposition decision and
justification to release the batch is
[[Page 5144]]
made after an investigation determines that the batch meets the
requirements of this part.
(d) Disposition and followup. Each tobacco product manufacturer
must determine the disposition of all nonconforming tobacco products
and any necessary followup. If the disposition decision is that the
tobacco product can be released for distribution without rework, an
adequate written justification must be developed and maintained in
accordance with Sec. 1160.32. An adequate written justification must
address why releasing the nonconforming product would not result in the
tobacco product being adulterated or misbranded. Nonconforming product
cannot be released for distribution without rework or an adequate
justification.
(e) Records. Each tobacco product manufacturer must maintain
records of all activities required under this section. Records must
include the date and time of the activity, the individual performing
the activity, the type of activity performed, any information that
demonstrates that the requirement was met, and any data or calculations
necessary to reconstruct the results.
Subpart C--Manufacturing Code and Recordkeeping Requirements
Sec. 1160.30 Manufacturing code requirements.
(a) Each tobacco product manufacturer must permanently affix a
manufacturing code to the packaging or labeling of all finished tobacco
products. For a finished tobacco product, the manufacturing code must
be affixed in a manner that assures it will remain on the packaging or
labeling through the expected duration of use of the tobacco product by
the consumer.
(b) The manufacturing code for each finished tobacco product must
be permanently affixed, legible, conspicuous, prominent, and appear in
the English language.
(c) The manufacturing code must contain the following information
listed in the following order:
(1) The manufacturing date in 2-digit numerical values in the
month-day-year format (MMDDYY);
(2) The finished tobacco product batch number; and
(3) The designation ``-NS'' at the end.
Sec. 1160.32 Recordkeeping requirements.
(a) Each facility that manufactures tobacco products subject to
this part must establish and maintain records related to compliance
with this part, including the following:
(1) The source data and results of batch testing conducted to
determine conformance with Sec. 1160.10, including all information
specified in Sec. 1160.12(b);
(2) All source data for analytical test method validation;
(3) All sampling plans and reports under Sec. 1160.16;
(4) Documentation that the persons performing sampling under Sec.
1160.16 have sufficient education, training, and experience to
accomplish the assigned functions; and
(5) All nonconforming tobacco product identification, segregation,
investigation, rework, and disposition decision procedures, including
justifications, under Sec. 1160.18.
(b) All records required under this part, regardless of storage
medium, must be attributable, legible, contemporaneously recorded,
original, and accurate. These records must be written in English, or an
accurate English translation must be made available upon request.
Documents that have been translated from another language into English
must be accompanied by the original language version of the document, a
signed statement by the authorized representative of the manufacturer
certifying that the English language translation is complete and
accurate, and a brief statement of the qualifications of the person
that made the translation. These records must be maintained at the
manufacturing establishment or another location that is readily
accessible to responsible officials of the tobacco product manufacturer
and to FDA. These records, including those not stored at the
establishment, must be made readily accessible to FDA during the
retention period for inspection and photocopying or other means of
reproduction. Original or true copies of these records that can be
immediately retrieved from another location, including by computer or
other electronic means, meet the requirements of this paragraph.
(c) All records required under this part must be retained for a
period of at least 4 years from the date of commercial distribution of
the finished tobacco product that is the subject of the record.
Dated: January 6, 2025.
Robert M. Califf,
Commissioner of Food and Drugs.
[FR Doc. 2025-00397 Filed 1-15-25; 8:45 am]
BILLING CODE 4164-01-P