`[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]



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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  

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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

[[Page 5036]]

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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

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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A Report of the Surgeon General. Atlanta, GA: HHS, CDC, National 
Center for Chronic Disease Prevention and Health Promotion, Office 
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* 2. Brown & Williamson Tobacco Corporation, and R.B. Griffith. 
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Presentation at Chelwood. British American Tobacco Records; Master 
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* 3. Jamal, A., E. Park-Lee, J. Birdsey, et al. ``Tobacco Product 
Use among Middle and High School Students--National Youth Tobacco 
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and Use of Alternative Nicotine Products: Exploratory Trial.'' 
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* 9. Carmines, E., and I.E. Gillman. ``Comparison of the Yield of 
Very Low Nicotine Content Cigarettes to the Top 100 United States 
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Smoking--Attributable Productivity Losses, U.S., 2018.'' American 
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on Smoking and Health. 2012. Available at https://www.ncbi.nlm.nih.gov/books/NBK99237/.
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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.

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    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`