5032 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

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. 

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, CTPRegulations@

fda.hhs.gov. 

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, PRAStaff@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 


ddrumheller on DSK120RN23PROD with PROPOSALS3
Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 5033 

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)). 

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). 

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 


ddrumheller on DSK120RN23PROD with PROPOSALS3
5034 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

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. 

3Tobacco products that meet the statutory or 

regulatory definition of a cigarette but are not 

combusted (do not exceed 350 °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). 

4See section III.B.3 of this document. 

5Waterpipe 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). 

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. 

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. 

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 

§ 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 noncombusted 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 


ddrumheller on DSK120RN23PROD with PROPOSALS3
Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 5035 

6FDA 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. 

7The 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. 

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 machinegenerated 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 machinemeasured yield of tobacco products. For 

further discussion, see section VII.A. 

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). 

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 


ddrumheller on DSK120RN23PROD with PROPOSALS3
5036 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

8For 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. 

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. 

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-productmanufacturing-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 


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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 .................................... Fagerstro ̈m Test for Cigarette Dependence. 

FTND .................................... Fagerstro ̈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. 


ddrumheller on DSK120RN23PROD with PROPOSALS3
5038 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

Abbreviation/ 

acronym What it means 

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 tobaccorelated 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/fdaannounces-comprehensive-regulatoryplan-shift-trajectory-tobacco-relateddisease-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 


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9Though 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). 

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 smokingrelated 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). 

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 


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5040 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

10As 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. 

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. 

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 


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11See, for e.g., https://www.fda.gov/tobaccoproducts/ctp-newsroom/fda-and-nih-joint-publicmeeting-advancing-smoking-cessation-prioritiesregistration-open?utm_campaign=ctp-research&

utm_content=landingpage&utm_medium=email&

utm_source=govdelivery&utm_term=stratcomms. 

12 Information on specific projects supported by 

FDA is available at https://www.fda.gov/tobaccoproducts/tobacco-science-research/research. 

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, evidencebased 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-cessationframework-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. 

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. 

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 


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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 


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13For 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, 

Continued 

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-andassessments/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 previouslypublished 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, ecigarettes, 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 ecigarettes. 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-scientificinformation-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 


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water, and vegetable gum with no other ingredients 

or additives; and (8) weighs more than 6 pounds per 

1,000 units. 

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 nonpremium cigars, and describe FDA’s 

approach to modeling the projected 

public health impacts of this proposed 

standard. 

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 


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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 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 §§ 1160.12, 

1160.14, and 1160.16 would establish 

product testing and sampling plan 

requirements. Proposed § 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 

§ 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 § 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 § 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. 


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5046 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

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. 


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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 smokingrelated 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 


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5048 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

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. 

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 peerreviewed, 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 


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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). 

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 tobaccorelated 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, smokingattributable fractions, and smokingattributable 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). 

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 opioidrelated 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 smokingrelated disease (Ref. 1). 

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 smokeattributable 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 


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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). 

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 nonHispanic 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 nonHispanic 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 nonHispanic Black youth ages 12–19 but 

remained stagnant among non-Hispanic 

White youth of the same ages (Ref. 142). 

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 nonHispanic White respondents, nonHispanic 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 tobaccorelated 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 multiunit 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 


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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, nonHispanic 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 tobaccospecific 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, peerreviewed 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 cigarattributable 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 


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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. 

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). 

Industry marketing tactics have also 

included the incorporation of culturespecific 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 tobaccorelated 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 


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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. 

19 Both Ultratech and Lifetech have been reported 

as being the company through which NIDA 

manufactured research cigarettes. 

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. 

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. 

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). 

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

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 


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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. 

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

Brand Manufacturer 

Nicotine 

content 

category 

Nicotine content 

(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 Company ................ VLNC ...... * 0.7–0.9 

Philip Morris 2 mg 3 ......................................................................... Philip Morris Tobacco Company ................ LNC ......... * 2.1–2.4 

Philip Morris 4 mg 3 ......................................................................... Philip Morris Tobacco Company ................ LNC ......... * 5.0–5.6 

Philip Morris 8 mg 3 ......................................................................... Philip Morris Tobacco Company ................ LNC ......... * 9.3–10.6 

Philip Morris 12 mg 3 ....................................................................... Philip Morris Tobacco Company ................ NNC ........ * 14.4–14.7 

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. 

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 


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22 Smoking topography measures provide data on 

various aspects of smoking behavior, including 

number of puffs per cigarette, total time spent 

smoking, puff volume (i.e., puff size), puff velocity 

(i.e., puff intensity), puff duration, and inter-puff 

interval (i.e., length of time between puffs). 

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. 

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 


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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 nonHispanic 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: ecigarettes, 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 sameage 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 


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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 selfreport sex, race and ethnicity, or grade level. 

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). 

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 


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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. 

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 factorymade 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). 

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 tobaccorelated 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 tobaccorelated 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 


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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. Selfreported 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 nicotinecontaining 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 studyassigned 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 


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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, ecigarette 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, ecigarettes, 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 noncigarette 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 


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25 See section VII.B 4., Smoking Topography, of 

this document for further discussion of 

compensatory smoking and VLNC cigarettes. 

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 machinemeasured nicotine yield (e.g., ISO 

machine smoking method, CI smoking 

method, FTC smoking method) through 

a variety of design changes to the 

cigarette, including the use of 

ventilation holes—although the actual 

nicotine content of the tobacco filler 

was not low. These design changes led 

to lower tar and nicotine yields in 

machine-generated smoke, and 

therefore, these products were labeled 

and marketed as low nicotine yield or 

‘‘light,’’ ‘‘low,’’ or ‘‘mild’’ cigarettes. 

However, often unconsciously cigarette 

users could and did modify their use 

behaviors to compensate for these 

design changes and extract more 

nicotine from the products compared to 

the machine-generated yields, often to 

levels comparable to conventional 

cigarettes. For example, cigarette makers 

generally design cigarettes with 

ventilation holes far enough down the 

cigarette that they are not blocked 

during the FTC smoking test, but are 

easily blocked by users’ fingers or 

mouths, and larger or more frequent 

puffs could be taken by consumers (Ref. 

351). Through such compensatory 

smoking behaviors, cigarette users were 

able to overcome the changes in 

ventilation in these products, resulting 

in no benefit to public health (Ref. 350). 

There is ample research demonstrating 

that people who use ventilated 

cigarettes change their smoking 

behavior to increase their smoke intake, 

including taking larger puffs, inhaling 

more deeply, taking more frequent 

puffs, or increasing the number of 

cigarettes they smoke per day 25 (Refs. 

350 to 361). As a result, evidence shows 

that many people are exposed to higher 

yields of smoke constituents, including 

nicotine, than the yields estimated by 

standardized smoking machine methods 

(Refs. 362 to 364). Further, researchers 

have reviewed the extensive body of 

literature on filter ventilation and health 

effects and concluded that there is 

strong evidence to suggest that filter 

ventilation has contributed to the rise in 

lung adenocarcinomas among people 

who smoke (Ref. 365). Studies that 

measure nicotine pharmacokinetics 

have also found that the relative 

percentage of free nicotine in smoke 

may increase with percent of filter 

ventilation (Ref. 366), which suggests 

that greater filter ventilation may expose 

smokers to greater free nicotine levels 

that can lead to greater total nicotine 

exposure while smoking as this form of 

nicotine is more easily absorbed by the 

body. 


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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. 

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/tobaccoproducts/advertising-and-promotion/22nd-centurygroup-inc-modified-risk-tobacco-product-mrtpapplications. 

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

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. 

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 


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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. 

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. 

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 (doubleblinded, 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 cigaretteonly 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 


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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-studyassigned 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 


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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 


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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), Sphenylmercapturic 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 


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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 nearcomplete 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 Fagerstro ̈m Test for 

Nicotine Dependence (FTND), 

Fagerstro ̈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 nicotinecontaining 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 


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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 selfreported 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 nicotinecontaining 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 


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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 


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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® cigarettes), reducing 

the number of cigarettes smoked per 

day, or switching to another tobacco 

product. Tapering nicotine intake while 


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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,t2,3,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 


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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 


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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/fieldscience-and-laboratories/laboratoryinformation-bulletins. In addition to the 

Tobacco Products Laboratory method, 

CRM No.62 (https://www.coresta.org/ 

determination-nicotine-tobacco-andtobacco-products-gas-chromatographicanalysis-29185.html) and CRM No. 87 

(https://www.coresta.org/determinationnicotine-tobacco-products-gc-ms33537.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 


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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 ultralow 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., fluecured, 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 


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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 microwaveassisted 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 noncigarette 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 


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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., a4b2 

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® 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; 


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29The 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. 

• 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 smokingrelated 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 peerreviewed 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. 

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 


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30While 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. 

use; estimated from the 2020 NHIS data 

and 2020 NYTS data) in the U.S. 

population. Next, we incorporated sexspecific 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 upto-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 longterm 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 LeeCarter 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 allcause 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. 

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) 


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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 peerreviewed 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 


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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) 


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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—Continued 

[Millions] 

Year Median (5th, 95th percentiles) 

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 


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31We 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). 

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. 


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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

Period 

Illicit trade impact scenarios 

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 shorterterm 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 


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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 

Year Scenario 

Cumulative tobacco-attributable 

deaths avoided 

(millions) 

Cumulative life 

years gained 

(millions) 

Cumulative 

QALYs gained 

due to reduced 

smoking morbidity 

(millions) 

2040 ......................................................................................... Median (5th, 95th) 0.4 (0.1, 0.5) 2.0 (0.2, 2.7) 9.6 (2.7, 10.0) 

2060 ......................................................................................... Median (5th, 95th) 1.8 (0.4, 2.0) 19.6 (3.6, 22.7) 24.0 (10.1, 24.7) 

2080 ......................................................................................... Median (5th, 95th) 3.1 (1.0, 3.4) 47.4 (12.5, 52.5) 38.2 (18.5, 39.2) 

2100 ......................................................................................... Median (5th, 95th) 4.3 (1.6, 4.6) 76.4 (26.5, 82.5) 53.1 (27.5, 54.4) 

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 


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33We 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 

Continued 

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 × (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

Scenario 

Projections through year 2100 

Cigarette smoking 

prevalence 

(%) 

Cumulative 

tobacco-attributable mortality 

avoided 

(millions) 

Cumulative 

life years gained 

(millions) 

Cumulative 

QALYs gained 

from reduced 

smoking morbidity 

(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 during the period 2021– 

2030 ..................................................................................... 0.13 (0.1, 1.6) 4.1 (1.5, 4.4) 72.9 (24.3, 79.0) 45.2 (22.9, 46.4) 

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 = 1.3) .............................. 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 75.0 (26.0, 81.4) 53.1 (27.5, 54.4) 

Lower RR than main scenario (RR = 1.1) ............................... 0.2 (0.1, 1.9) 4.4 (1.6, 4.7) 77.2 (26.9, 83.2) 53.1 (27.5, 54.4) 

Baseline dual use RR 

Dual use RR is 18% greater than for cigarette smoking ........ 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 75.9 (25.0, 82.4) 53.1 (27.5, 54.4) 

Dual use RR is the average of cigarette and noncombusted 

use RR ................................................................................. 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 77.0 (28.6, 82.6) 53.1 (27.5, 54.4) 

Dual use RR is equal to the noncombusted use RR .............. 0.2 (0.1, 1.9) 4.3 (1.6, 4.6) 77.6 (30.7, 82.7) 53.1 (27.5, 54.4) 

Baseline mortality rate projections 

Keep mortality rates constant starting at 2060 ....................... 0.2 (0.1, 2.0) 4.7 (1.9, 5.1) 77.9 (28.2, 83.9) 53.0 (27.4, 54.2) 

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 expertderived 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 


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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 highend 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). 

34We 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). 

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. 

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] 

Year 

Illicit trade impact scenarios 

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 


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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 lifethreatening 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. 


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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 tobaccorelated 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 nonstudy 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 


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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] 

Scenario 

Projections through year 2100 

Noncombusted 

tobacco use 

prevalence 

(%) 

Cumulative 

tobaccoattributable 

mortality avoided 

(millions) 

Cumulative life 

years gained 

(millions) 

Cumulative 

QALYs gained 

from reduced 

smoking morbidity 

(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 noncombusted products ............... 15.4 (14.0, 16.1) 4.3 (1.6, 4.6) 75.9 (26.1, 82.1) 53.1 (27.5, 54.4) 

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 smokeattributable 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 


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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 nonHispanic 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 tobaccorelated 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 

Year Scenario 

Cumulative secondhand 

smoking-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) 


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Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 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: smokingrelated 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 cigaretteattributable deaths under the main 

product standard scenario to project the 

number of avoided deaths over time 

from each of these causes (i.e., smokingrelated 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 smokingmaterial 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 smokingrelated 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 smokingattributable 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 


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5092 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

35Adult 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). 

36According 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). 

37For youth, we assume that initiation occurs by 

the age of 18, followed by a cigar smokingattributable death 52 years later. We then assume 

cigar use initiation occurs during years 2025 to 

2064 (40-year period), and cigar smokingattributable 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. 

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 × 

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 cigarattributable 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 cigarattributable 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 

(≈ 7,397 × (1¥0.375)) deaths per year 

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 smokingattributable 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 cigaretteattributable 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 cigaretteattributable 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 

Year Scenario 

Cumulative 

smoking-related 

fire deaths avoided 

Cumulative perinatal 

deaths avoided 

Cumulative non-premium 

cigar-attributable 

deaths avoided 

Cumulative pipe 

tobacco-attributable 

deaths 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. 


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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 cigaretteattributable 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 tobaccorelated 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 


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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 


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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 anxietyincreasing 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 posttraumatic 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 


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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 selfadministration (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 nonmenthol 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 


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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 nonmenthol 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 mentholadjusted 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 cigarattributable 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 cigaretteattributable 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. 


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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] 

Year/period Estimates from 

main analysis 

Estimates with 

adjustment for a 

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 

Year Percentiles 

Cumulative non-premium 

cigar-attributable deaths 

avoided from main analysis 

Cumulative non-premium 

cigar-attributable deaths 

avoided with flavored cigar 

and menthol cigarette standards 

2040 .............................. Median (5th, 95th) .............................................. 8,900 (1,000, 11,000) 8,000 (1,000, 9,500) 

2060 .............................. Median (5th, 95th) .............................................. 54,800 (13,200, 60,500) 45,600 (11,100, 49,700) 

2080 .............................. Median (5th, 95th) .............................................. 134,7000 (46,000, 144,100) 107,700 (35,000, 114,500) 

2100 .............................. Median (5th, 95th) .............................................. 214,700 (91,600, 225,800) 164,000 (65,000, 172,100) 

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 


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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, smokingrelated 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 tobaccorelated 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 tobaccorelated 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 


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38 Products that were commercially marketed in 

the United States as of February 15, 2007 (referred 

to as ‘‘pre-existing tobacco products,’’ previously 

referred to as ‘‘grandfathered products’’), are not 

considered new tobacco products and do not 

require prior authorization to be legally marketed 

(section 910(a) of the FD&C Act). 

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 foreigngrown 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. 

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. 


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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 § 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 tobaccorelated 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 timeconsuming 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 


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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 


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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). 

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 taxevading 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

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 § 1160.1) 

Proposed § 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 

§ 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 § 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 § 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 § 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 § 1160.3) 

Proposed § 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 


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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 originallyregulated 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-productmanufacturing-practice) includes a 

proposed definition of ‘‘batch,’’ and this 

rulemaking’s provision is modeled on 

the proposed TPMP provision. Pursuant 

to proposed § 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 § 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 


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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 § 1160.10 (nicotine 

level specifications) or § 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 ‘‘rollyour-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 

§ 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 § 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 

§ 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 § 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 


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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. 

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 § 1160.12) 

Proposed § 1160.12 contains 

provisions for the testing of finished 

tobacco products that would be subject 

to this proposed rule. Specifically, 

proposed § 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 

§ 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 

§ 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 § 1160.16. 

Proposed § 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 § 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 § 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 § 1160.16(b) would be 

integrated into the proposed 

§ 1160.12(b) records (i.e., proposed 

§ 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 § 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 

§ 1160.10 that would reduce costs for 

manufacturers. 

3. Analytical Test Method (Proposed 

§ 1160.14) 

Proposed § 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 fitfor-purpose is applicable for use under 

this tobacco product standard.40

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. 


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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 § 1160.16) 

Proposed § 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 § 1160.10. This sampling plan 

would be used in conjunction with the 

analytical test method in proposed 

§ 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 § 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 § 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 § 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 § 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 § 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 § 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 § 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 


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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 

§ 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 § 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 § 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 

§ 1160.16(b)(8). They also would 

document the start of the chain of 

custody for the samples. 

Proposed § 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 § 1160.16(b)(5). 

Proposed § 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 § 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 

§ 1160.32, which includes the 

information in proposed 

§ 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 

§ 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 

§ 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 § 1160.12(b) to provide 

information across the batch. 

Proposed § 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 § 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 §§ 1160.12 and 1160.16, the 

reporting requirements in proposed 

§§ 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 

§ 1160.16. Testing for nonconforming 

tobacco product under proposed 

§ 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. 


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5. Nonconforming Tobacco Product 

(Proposed § 1160.18) 

Proposed § 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 

§ 1160.10 (nicotine level specifications) 

or § 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 § 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 § 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 § 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 § 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 

§ 1160.10, the manufacturer would 

determine that the batch and related 

products must be identified and 

segregated as they may be 

nonconforming products. 

Proposed § 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 § 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 § 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 inprocess 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 § 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 § 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 


ddrumheller on DSK120RN23PROD with PROPOSALS3
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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. 

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 § 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 § 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 § 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 § 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 

§ 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 § 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 § 1160.18(d) would require 

manufacturers to determine the 

disposition of all nonconforming 

tobacco products and any necessary 

followup. Under proposed § 1160.18(d), 

nonconforming product cannot be 

released for distribution without rework 

or an adequate justification (developed 

and maintained in accordance with 

§ 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 § 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 § 1160.18(e) would require 

each tobacco product manufacturer to 

maintain records of all activities 

required under § 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 § 1160.30) 

Proposed § 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 § 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 § 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 § 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). 

FDA requests comment on the 

manufacturing code requirements in 

this proposed rule. 

2. Recordkeeping Requirements 

(Proposed § 1160.32) 

Proposed § 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 § 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: 


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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. 

(1) The source data and results of 

analyses conducted to determine 

conformance with § 1160.10, including 

all information identified in 

§ 1160.12(b); 

(2) All source data used to validate an 

analytical test method; 

(3) All sampling plans and sampling 

reports under § 1160.16; 

(4) Documentation that the persons 

performing sampling under § 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 § 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 § 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 

§ 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 § 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. 

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 phasein 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 


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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). 


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43For 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. 

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/economicsstaff/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 highimpact 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 (lowimpact 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 


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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. 

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 (lowimpact scenario of $6.2 billion; highimpact 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] 

Category Primary 

estimate 

Low 

estimate 

High 

estimate 

Dollar 

year 

Discount 

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 budgetary 

transfers.

4,092 1,386 4,313 2023 2 2025–2064 (40 years).

Bearers of transfer gain and loss? ............. Transfers of Excise Tax Revenues from Federal Governments to Consumers 

Annualized monetized State budgetary 

transfers.

8,414 2,848 8,877 2023 2 2025–2064 (40 years).

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 governments.Significant transfer of tax revenues for State governments. Potential transfer of tax 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. 


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44FDA 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). 

TABLE 13—SUMMARY OF BENEFITS, COSTS, AND DISTRIBUTIONAL EFFECTS OF THE PROPOSED RULE—Continued 

[Millions of 2023 dollars over a 40-year time horizon] 

Category Primary 

estimate 

Low 

estimate 

High 

estimate 

Dollar 

year 

Discount 

rate 

(%) 

Time horizon Notes 

Category Effects Notes 

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. 

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 thirdparty 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 (§ 1160.12), 

sampling plans (§ 1160.16), analytical 

test methods (§ 1160.14), 

nonconforming tobacco products 

(§ 1160.18), package label requirements 

(§ 1160.30) and recordkeeping 

requirements (§ 1160.32). 

Subpart C contains manufacturing 

code (§ 1160.14) and recordkeeping 

(§ 1160.32) requirements. 

Proposed § 1160.12 contains 

provisions for the testing of finished 

tobacco products that would be subject 

to this proposed rule. Specifically, 

proposed § 1160.12(a) would require 

that tobacco product manufacturers 

conduct testing on each batch of 

finished tobacco products. 

Proposed § 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 § 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; 


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(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 § 1160.12(b) would be 

integrated with the proposed 

§ 1160.18(b) records (i.e., proposed 

§ 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 § 1160.12(b) records also 

would document the ultimate 

disposition of the batch based on the 

testing of the representative samples. 

Proposed § 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 

§ 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 

§ 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 § 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 

§ 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 

§ 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 § 1160.18(e) would require 

each tobacco product manufacturer to 

maintain records of all activities 

required under § 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 

§ 1160.12(b) would be integrated with 

the proposed § 1160.18(b) records (i.e., 

proposed § 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 § 1160.12(b) records also 

would document the ultimate 

disposition of the batch based on the 

testing of the representative samples. 

Proposed § 1160.30 would require the 

use of a manufacturing code to serve as 


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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 § 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 § 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 § 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 § 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 § 1160.10, including 

all information identified in 

§ 1160.12(b); 

(2) All source data used for analytical 

test method validation; 

(3) All sampling plans and sampling 

reports under § 1160.16; 

(4) Documentation that the persons 

performing sampling under § 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 § 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 § 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 § 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-yourown (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 


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45There are no capital costs or operating and 

maintenance costs associated with this collection of 

information. 

production capacity and so represent 

the majority of recordkeeping burden. 

The proposed provision § 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 § 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 § 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 § 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 § 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

21 CFR section or activity Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average 

burden per 

recordkeeping 

Total hours 

§ 1160.12 Product Testing ......................................... 143 50.84 7,270 9 65,430 

§ 1160.14 Analytical Test Method .............................. 143 4 572 1 572 

§ 1160.16 Sampling Plan ........................................... 143 4 572 1 572 

§ 1160.18 Procedures for Nonconforming Tobacco 

Products and Related Investigations; Procedures 

for Control and Disposition of Nonconforming Tobacco Products ....................................................... 143 1 143 14 2,002 

§ 1160.30 Package Label Requirements (Manufacturing Code) ............................................................ 143 4 572 7 4,004 

§ 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 


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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. 

We estimate a total of 7,270 batches 

per year are required to be tested under 

§ 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 § 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 § 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 § 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 § 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 § 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

Activity Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

Total hours 

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 


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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 

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List of Subjects in 21 CFR Part 1160 

Administrative practice and 

procedure, Labeling, Smoke, Smoking, 

Tobacco, Tobacco products. 

■ 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 

§ 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. 

§ 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 § 1160.10 

or § 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 tobaccoderived 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 

§ 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. 

§ 1160.12 Product testing. 

(a) Batch testing. Tobacco product 

manufacturers must conduct testing on 

finished tobacco products to ensure that 

the batch conforms with § 1160.10. The 

manufacturer must use an analytical test 

method that meets the requirements set 

forth in § 1160.14. Samples for testing 

each batch to determine if it conforms 

with § 1160.10 must be selected in 

accordance with the requirements set 

forth in § 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 § 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 


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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. 

§ 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. 

§ 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 

§ 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 § 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 

§ 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. 

§ 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 


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5144 Federal Register / Vol. 90, No. 10 / Thursday, January 16, 2025 / Proposed Rules 

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 

§ 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 

§ 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. 

§ 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 § 1160.10, including 

all information specified in § 1160.12(b); 

(2) All source data for analytical test 

method validation; 

(3) All sampling plans and reports 

under § 1160.16; 

(4) Documentation that the persons 

performing sampling under § 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 § 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 


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