Tobacco Product Standard for Nicotine Yield of Cigarettes and Certain Other Combusted Tobacco Products

Federal RegisterJan 16, 2025

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 1160

[Docket No. FDA-2024-N-5471]

RIN 0910-AI76

Tobacco Product Standard for Nicotine Yield of Cigarettes and Certain Other Combusted Tobacco Products

AGENCY:

Food and Drug Administration, Department of Health and Human Services (HHS).

ACTION:

Proposed rule.

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:

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

and certain other combusted tobacco products (proposed product standard).

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)).

As the U.S. District Court for the District of Columbia recognized in

United States

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

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

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.

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.

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

) that meet the definition of a cigarette), cigarette tobacco, roll-your-own (RYO) tobacco, cigars (including little cigars, cigarillos, and large cigars but excluding premium cigars

), and pipe tobacco (other than waterpipe tobacco

). FDA requests comments, data, and research regarding this proposed scope.

Tobacco 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).

See section III.B.3 of this document.

Waterpipe tobacco (also known as hookah tobacco) is a type of tobacco product that produces smoke that people inhale when a hookah device is heated. Hookah tobacco (also known as waterpipe tobacco, maassel, shisha, narghile, or argileh) typically contains a mixture of tobacco, sweeteners, and flavoring. The hookah device (or waterpipe) used to smoke the hookah tobacco works by passing charcoal or electric heated air through the tobacco mixture and ultimately through a water-filled chamber (Ref. 7).

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 non-combusted cigarettes pose less risk to individuals who use cigarettes or certain other combusted tobacco products or to population health than other products meeting the definition of a cigarette. Accordingly, FDA requests comments, data, and research regarding the proposal to exclude noncombusted cigarettes from the scope of this proposed rule, including any data that could justify otherwise.

FDA also proposes to exclude waterpipe tobacco from the proposed product standard because, unlike cigarette tobacco, pipe tobacco, RYO tobacco, and cigars (other than premium cigars), FDA believes there is little risk of switching under the proposed product standard. Waterpipes as currently marketed and used generally require substantial time for preparation and use (

i.e.,

an approximately 1-hour session with waterpipes compared to 5-7 minutes with cigarettes). In addition, they are generally large and unwieldy and thus ill-suited for mobile usage, such as while driving or walking. FDA requests comments, data, and research regarding the proposal to exclude waterpipe tobacco from the scope of this proposed rule, including any data that could justify otherwise.

FDA is also not including noncombusted non-cigarette tobacco products, such as electronic nicotine delivery systems (ENDS) (which include e-cigarettes) and smokeless tobacco products, in the scope of this proposed product standard. As discussed throughout this document, nicotine is the primary addictive constituent in

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

by limiting the nicotine yield of these products. We propose to limit nicotine yield by setting a maximum nicotine content level of 0.70 milligrams (mg) of nicotine per gram of total tobacco in these tobacco products. For comparison, the average nicotine content in the top 100 cigarette brands for 2017 is 17.2 mg/g of total tobacco (Ref. 9). Nicotine yield is the amount of nicotine in smoke, in other words, the amount of nicotine to which a smoker potentially is exposed. While nicotine yield can be measured through machine-generated smoking methods (

e.g.,

International Organization for Standardization (ISO) machine smoking method, Canadian Intense (CI) smoking method, Federal Trade Commission (FTC) smoking method), it can vary due to a user's compensatory behaviors—

e.g.,

inhaling more deeply, taking larger puffs, and blocking cigarette features designed to reduce nicotine yield—such that users can increase the amount of nicotine yield compared to the machine-generated yield. In contrast, nicotine “content,” which refers to the amount of nicotine present in tobacco filler, is not affected by smoking behavior or cigarette design features. Reducing the nicotine content to the proposed 0.70 mg of nicotine per gram of total tobacco limit in the finished tobacco products subject to this proposed product standard places an absolute maximum limit on the amount of nicotine present in tobacco smoke available for intake by users of these products. There are many different tobacco product characteristics that can be manipulated to affect nicotine yield, one of which is nicotine content. Setting a limit on nicotine content and measuring that content is more effective in reducing yield (

i.e.,

the amount of nicotine the user is exposed to) than setting a limit based on a direct measurement of yield under standardized smoking-machine protocols because nicotine content cannot be affected by the compensatory behavior described above. Therefore, limiting nicotine yield through a maximum nicotine content level would better achieve the public health benefits that come from reducing the amount of the nicotine to which a user is exposed than would setting a limit based on a measurement of the maximum machine-measured yield of tobacco products. For further discussion, see section VII.A.

FDA is using the term “nonaddictive” throughout this preamble specifically in the context of the available data on very low nicotine content cigarettes. We acknowledge the highly addictive potential of nicotine itself depending upon the route of delivery. As discussed elsewhere in this preamble, questions remain with respect to the precise level of nicotine in cigarettes that might render them either minimally addictive or nonaddictive for specific individual members or segments of the population.

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.

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).

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.

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

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

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.

For the purpose of this document, the term “finished tobacco product” refers to those products subject to this proposed rule. FDA proposes to define a “finished tobacco product” to mean a tobacco product, including all components and parts, sealed in final packaging (

e.g.,

filters or filter tubes sold to consumers separately or as part of kits) or in the final form in which it is intended to be sold to consumers. For a discussion of products FDA proposes to include within the scope of this product standard, see sections IX.C and X.A.1 of this document.

Nonconforming tobacco product

—The proposed product standard would require tobacco product manufacturers to establish procedures for the control and disposition of tobacco products that do not conform to the requirements of this rule. These procedures are necessary to help prevent the distribution of nonconforming tobacco products by ensuring that all potential nonconforming products are identified, investigated, and segregated and that appropriate disposition and followup are taken for products determined to be nonconforming. This proposed requirement would ensure that any reports of nonconforming products, whether as a result of manufacturer testing or otherwise, are examined and investigated and that appropriate measures are taken to ensure that nonconforming products are not distributed to consumers and to prevent future nonconformity.

Manufacturing code

—Currently, there is no requirement for the use of a manufacturing code for tobacco products. However, the proposed regulation Requirements for Tobacco Product Manufacturing Practice (TPMP) (see

https://www.federalregister.gov/documents/2023/03/10/2023-04591/requirements-for-tobacco-product-manufacturing-practice

) includes a requirement for a manufacturing code, and this rulemaking's provision is modeled on the proposed TPMP provision. The proposed product standard would require the use of a manufacturing code to serve as a common identifier for production and distribution records. The purpose of the manufacturing code is to allow manufacturers and FDA to identify the production batch of a particular finished product that has been released for distribution. This information is intended to help determine the product's history (

e.g.,

batch production records) and assist manufacturers and FDA in the event of a nonconforming tobacco product investigation and any corrective actions to be taken by a manufacturer as a result of the investigation.

Recordkeeping requirements

—To assist FDA in determining compliance with the rule and aid in nonconforming product investigations, the proposed product standard would require that manufacturers establish and maintain records regarding the results of testing conducted on each batch to determine conformance with the proposed standard. In addition, this proposed product standard would require that manufacturers maintain records of sampling plans and sampling procedures, records related to manufacturing controls, and all records related to its analytical test method validation. FDA also is proposing to require that it be possible to identify the production batch of a particular finished product that has been released for distribution.

Proposed effective date

—FDA proposes that any final rule that may issue based on this proposed rule become effective 2 years after the date of publication of the final rule. Therefore, after the effective date no person could distribute, sell, or offer for sale or distribution within the United States finished tobacco products that are not in compliance with part 1160 (21 CFR part 1160). Prior to the effective date of any final rule that may issue based on this proposed rule, wholesalers, retailers, and related entities would be able to sell available stock of finished tobacco products were not in compliance with part 1160 while transitioning inventory in anticipation of the effective date of the final rule; however, they would not be permitted to sell off such stock after the effective date. FDA believes this approach would allow adequate time for developing any necessary changes in technology or inputs to comply with a finalized product standard. It also would provide sufficient time for tobacco product manufacturers to submit, and FDA to review, applications for new tobacco products that comply with the finalized product standard. Additionally, FDA believes that this approach would allow adequate time for making any changes to tobacco purchasing choices and curing methods, and for preparation or changes needed in facilities and processes. FDA requests comments and data on this proposed effective date. For further discussion regarding considerations and request for comments on the proposed effective date of this rule, see section XI of this document.

Given that any new tobacco products that comply with this product standard would be required to undergo premarket review, FDA is considering options for addressing any influx of applications.

C. Legal Authority

Section 907 of the FD&C Act authorizes FDA to adopt tobacco product standards, including product standards that include provisions for nicotine yields; for the reduction or elimination of other constituents (including smoke constituents) or harmful components; respecting the construction, components, ingredients, additives, constituents (including smoke constituents), and properties of tobacco products; for the testing of tobacco products; and for restricting the sale of tobacco products to the extent consistent with section 906 (21 U.S.C. 387f) (section 907(a)(3), (a)(4)(A)(i) to (iii), and (a)(4)(B)(i) to (ii) and (iv) to (v)). The FD&C Act also establishes FDA's authority to require tobacco product manufacturers to establish and maintain records in section 909 (21 U.S.C. 387i); authority related to adulterated and misbranded tobacco products in sections 902 and 903 (21 U.S.C. 387b and 387c); authority regarding premarket review of new tobacco products in section 910 (21 U.S.C. 387j); authority related to prohibited acts in section 301 (21 U.S.C. 331); and FDA's rulemaking and inspection authorities in sections 701 and 704 (21 U.S.C. 371 and 374).

D. Costs and Benefits

The main quantified benefits come from averted mortality and morbidity as a result of reduced prevalence for people who currently use combusted

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.

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.

Federal Register

FTCD

Fagerström Test for Cigarette Dependence.

FTND

Fagerström 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.

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.

Product static ID number.

QALYs

Quality-adjusted life years.

QSU

Questionnaire of Smoking Urges.

RCT

Randomized clinical trial.

RNC

Reduced nicotine content.

Relative risk.

RYO

Roll-your-own.

S-PMA

S-phenylmercapturic acid.

Substantial Equivalence.

SES

Socioeconomic status.

STN

Submission tracking number.

TNE

Total nicotine equivalents.

TPSAC

Tobacco Products Scientific Advisory Committee.

TUS-CPS

Tobacco Use Supplement to the Current Population Survey.

U.S.

United States.

VLNC

Very low nicotine content.

WISDM

Wisconsin Inventory of Smoking Dependence Motives.

YRBS

Youth Risk Behavior Survey.

III. Background

A. Need for the Regulation

Cigarettes are responsible for the majority of tobacco-related death and disease in the United States. Each year, 480,000 people die prematurely from a smoking-attributable disease, putting a substantial burden on the U.S. healthcare system and causing massive economic losses to society (Ref. 1). In terms of a monetary measure of the impact of cigarette smoking on the public health, in 2018, cigarette smoking cost the United States more than $600 billion, including more than $240 billion in healthcare spending (Ref. 10), nearly $185 billion in lost productivity from smoking-related illnesses and health conditions (Ref. 10), nearly $180 billion in lost productivity from smoking-related premature death (Refs. 1 and 10), and $7 billion in lost productivity from premature death from secondhand smoke exposure (Refs. 1 and 11). The mortality rate among people who currently smoke cigarettes is 2 to 3 times as high as that among individuals who never smoked (Ref. 12). Nicotine, the primary addictive constituent in tobacco products, can be delivered through a variety of products along a continuum of risk, with combusted tobacco products at the most harmful end of this continuum. To protect youth and reduce tobacco-related disease and death, FDA utilizes a comprehensive approach to tobacco and nicotine regulation. Shortly after FDA announced its comprehensive approach in 2017 (

https://www.fda.gov/news-events/press-announcements/fda-announces-comprehensive-regulatory-plan-shift-trajectory-tobacco-related-disease-death

), the Agency began a public dialogue about lowering nicotine levels in combusted cigarettes to minimally addictive or nonaddictive levels through achievable product standards. On March 16, 2018, FDA issued a Nicotine ANPRM to seek input on the potential public health benefits and any possible adverse effects of regulating nicotine yield by lowering nicotine levels in cigarettes and invited comments on many issues associated with the development of a product standard to establish a maximum nicotine level (83 FR 11818). The Nicotine ANPRM also acknowledged that if FDA were to establish a nicotine tobacco product standard that covered only cigarettes, some number of people who smoke cigarettes could migrate to other similar combusted tobacco products to maintain their nicotine dependence (or engage in dual use with other combusted tobacco products), potentially reducing the positive public health impact of such a rule. FDA sought comments on whether the standard therefore should cover other combusted tobacco products. Based on FDA's scientific knowledge, extensive research regarding VLNC cigarettes, and comments submitted in response to this Nicotine ANPRM, FDA is proposing a tobacco product standard that would regulate nicotine yield by establishing a maximum nicotine level in cigarettes and certain other combusted tobacco products.

As the U.S. District Court for the District of Columbia recognized in

United States

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.

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

addiction to nicotine, and progressing to regular use as a result of that addiction. Furthermore, it is well-established that secondhand tobacco smoke causes premature death and disease in children and in adults who do not smoke (Ref. 15 at p.11). It is estimated that exposure to secondhand smoke caused 41,280 deaths per year in the United States from 2005 to 2009 (Ref. 1 at Table 12.4). This increased cessation and reduced initiation, in turn, would result in a significant decrease in harms from the products to people who currently or would otherwise use cigarettes and certain other combusted tobacco products, as well as harms to people who do not use the products, including harms caused by secondhand smoke to both adults and children, harmful perinatal effects due to parental tobacco use, and fires.

Preventing people who do not smoke cigarettes, particularly youth, from regularly smoking cigarettes due to nicotine addiction would allow them to avoid the severe adverse health consequences of smoking and would result in significant public health benefits. Without changes like those proposed here, an estimated 3.66 million youth under the age of 18 who were alive in 2018—and 2.54 million youth who are alive in 2024, accounting for the projected continued decline in smoking prevalence—will die prematurely later in life from a smoking-related disease (Ref. 16). As a result of the proposed product standard, many youth and young adults would not be subjected to the impacts of nicotine addiction from cigarette smoking and certain other combusted tobacco products (which have a significantly stronger effect on youth due, in part, to their developing brains, as described in sections IV.B and IV.C of this document), nor would they suffer from the adverse health effects and mortality that these products cause.

Nicotine is powerfully addictive, and youth and young adults

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).

Though age ranges for youth and young adults vary across studies, in general, “youth” or “adolescent” encompasses those ages 11-17, while those who are ages 18-25 are considered “young adults” (even though, developmentally, the period between 18-20 years of age is often labeled late adolescence); those ages 26 and or older are considered “adults” (Ref. 17).

More than half (52.2 percent) of U.S. middle and high school students who use cigarettes, cigars, smokeless tobacco—including those with low levels of use—report experiencing at least one symptom of nicotine dependence (Ref. 24). Notably, 12.7 percent of youth using tobacco products 1 to 2 days per month and 21.2 percent of youth using tobacco products 3 to 5 days per month reported sometimes/often/always feeling irritable or restless when not using tobacco products for a while, and 15.6 percent of youth using tobacco products 1 to 2 days per month and 32.0 percent of youth using tobacco products 3 to 5 days per month reported having strong cravings for a tobacco product during the past 30 days (Ref. 24). Additionally, other researchers analyzing data from the 2021 NYTS found that a sizeable proportion of high school students using tobacco products in the past 30 days report symptoms of nicotine dependence, including 27.2 percent reporting a strong craving for tobacco use and 19.5 percent reporting wanting to first use tobacco products within 30 minutes of waking (Refs. 25 and 26). While prevalence rates of youth use of noncombusted tobacco products (

e.g.,

ENDS) in recent years have exceeded those of cigarettes and other combusted tobacco products (Refs. 25 and 26), FDA expects that this proposed product standard would have significant benefits for youth by reducing the risk that youth who experiment with cigarettes and certain other combusted tobacco products, or who may consider using these products as an alternative to noncombusted tobacco products, would progress to regular use of these products as a result of nicotine dependence.

The adolescent and young adult brain is more vulnerable to developing nicotine dependence than the adult brain is; data indicate that nicotine has stronger rewarding effects in adolescents than in adults (Ref. 17). Adolescents who use tobacco and initiated use at earlier ages were more likely than those initiating at older ages to report symptoms of tobacco dependence, putting them at greater risk for maintaining tobacco product use into adulthood (Ref. 24). Additionally, the earlier that individuals begin smoking—and therefore the greater amount of time that individuals experience nicotine dependence—the less likely they are to successfully quit (Ref. 27). Evidence indicates that exposure to substances such as nicotine can disrupt brain development and have long-term consequences for executive cognitive functioning (such as decreased attention and working memory and increased impulsivity) and for the risk of developing a substance use disorder and various mental health problems (particularly affective disorders such as anxiety and depression) as an adult (Ref. 27). Furthermore, the 2010 Surgeon General's report noted that adolescents report symptoms of dependence even at low levels of cigarette smoking, and thus may be particularly vulnerable to addiction (Ref. 28). FDA expects that this proposed product standard, therefore, would have significant benefits for youth and young adults by reducing the risk that those who experiment with cigarettes and certain other combusted tobacco products would progress to regular use as a result of nicotine dependence.

Research studies involving VLNC cigarettes—defined previously in this document as cigarettes containing up to 1.0 mg of nicotine per gram of total tobacco—demonstrate that setting the maximum nicotine level we are proposing here, would lead to a reduction in nicotine dependence, which would help people who smoke cigarettes quit smoking. In studies that immediately reduced the nicotine content of cigarettes by switching participants from usual brand cigarettes to LNC or VLNC cigarettes, dependence decreased in people who smoked cigarettes who were not interested in quitting compared to those who smoked normal nicotine content (NNC) or usual brand cigarettes for 6 weeks (Ref. 29), 10 weeks (Ref. 30), or 12 weeks (Ref. 31). In smoking cessation studies in which participants endorsed wanting to quit, VLNC cigarettes were also associated

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

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.

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.

As stated throughout this preamble, in the event that a nicotine product standard addresses only cigarettes, FDA expects that, to maintain their nicotine dependence, some number of people who are addicted to cigarettes would likely migrate to other similar combusted tobacco products (or engage in dual use with such products) after the product standard goes into effect, reducing the benefits of the standard.

FDA expects that, if this proposed rule is finalized and a nicotine product standard for cigarettes and certain other combusted tobacco products is in place, many people who smoke cigarettes will either quit all tobacco-product use or switch to a noncombusted tobacco product. Those who switch completely to use of a noncombusted tobacco product may sustain their nicotine dependence but may significantly

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.

With input from subject matter experts from across HHS Operating Divisions, the Department has finalized the “HHS Framework To Support and Accelerate Smoking Cessation” (Framework). The Framework aims to accelerate smoking cessation and reduce smoking-related disparities by building on current activities and collaborations across the Department. The Framework vision is to ensure that every person in America has access to comprehensive, evidence-based cessation treatment and can benefit from HHS cessation supports, programs, and policies. Specific Framework goals are to: (1) reduce smoking and cessation-related disparities; (2) increase awareness and knowledge related to smoking and cessation; (3) strengthen, expand, and sustain cessation services and supports; (4) increase access to and coverage of comprehensive, evidence-based cessation treatment; (5) advance, expand, and sustain surveillance and strengthen performance measurement and evaluation; and (6) promote ongoing and innovative research to support and accelerate smoking cessation (

https://www.hhs.gov/about/news/2024/03/08/hhs-announces-new-smoking-cessation-framework-support-quitting.html

). With increased availability and accessibility of services, more people who smoke may be motivated to take advantage of cessation resources, whether they smoke cigarettes or other combusted tobacco products. Additionally, FDA has numerous processes and tools at its disposal to communicate directly with consumers, including communities that are underserved by cessation services and/or are disproportionately impacted by tobacco use, and will continue to evaluate the need for additional public outreach, including targeted education initiatives, in support of this proposed rule. However, the Agency does not have evidence to suggest that such an effort is necessary at this time in order to experience the public health benefits of this proposed product standard.

See, for

e.g., https://www.fda.gov/tobacco-products/ctp-newsroom/fda-and-nih-joint-public-meeting-advancing-smoking-cessation-priorities-registration-open?utm_campaign=ctp-research&utm_content=landingpage&utm_medium=email&utm_source=govdelivery&utm_term=stratcomms.

For the reasons stated here and throughout this document, FDA is proposing this tobacco product standard to: (1) reduce the risk of progression to regular use and nicotine dependence for those who experiment with such tobacco products, especially youth and (2) make it easier for people who are addicted to cigarettes and certain other combusted tobacco products and who are interested in quitting to quit by reducing the nicotine in these products to minimally addictive or nonaddictive levels. FDA expects that this proposed product standard would significantly reduce the morbidity and mortality caused by smoking. Based on FDA's population health model, by the year 2100, in the United States, approximately 48 million youth and young adults who would have otherwise initiated smoking would not start as a result of the proposed product standard. The model also projects that more than 12.9 million additional people who smoke cigarettes would quit smoking (including those who switch to noncombusted tobacco products) 1 year after implementation of the proposed product standard, increasing to 19.5 million additional people who formerly smoked cigarettes within 5 years of implementation. Section XII discusses that the main quantified benefits come from averted mortality and morbidity, as a result of tobacco use transitions, including switching. In terms of mortality benefits, the model considers a higher risk for people who switch to noncombusted products compared to those who quit tobacco product use entirely. Specifically, the model assumes that the risk for people who switch to noncombusted product use is 8 percent higher than the risk for those who quit tobacco use entirely. Details of this approach can be found in the FDA's modeling document (Ref. 42). In addition, the model estimates that, by the year 2060, in the United States, this proposed product standard would result in 1.8 million tobacco-related deaths averted, rising to 4.3 million deaths averted by the end of the century (Ref. 42). The reduction in premature deaths attributable to the proposed product standard would result in 19.6 million life years gained by 2060 and 76.4 million life years gained by 2100 (see section VIII.A of this document for further discussion of the model) (Ref. 42).

B. Relevant Regulatory History

In its implementation of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) (Pub. L. 111-31) since its passage in 2009, FDA has engaged in close study and careful consideration of the scientific evidence and complex policy issues related to nicotine in cigarettes and other combusted tobacco products. FDA issued an ANPRM to solicit data and information for consideration in developing a tobacco product standard to regulate nicotine yield by setting the maximum nicotine level for cigarettes, conducted a robust scientific assessment related to a nicotine product standard for combusted tobacco products, developed a population health model to assess the potential public health impacts of such a product standard, and sponsored research on a variety of nicotine-related topics through contracts and interagency agreements with Federal partners, including the National Institutes of Health (NIH).

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.

Information on specific projects supported by FDA is available at

https://www.fda.gov/tobacco-products/tobacco-science-research/research.

1. ANPRM

In July 2017, FDA announced a comprehensive approach to tobacco and nicotine regulation to protect youth and reduce tobacco-related disease and death (Ref. 43). As part of the public dialogue on the comprehensive approach, in March 2018, FDA issued three ANPRMs related to the regulation

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

levels. Some comments opposed to a nicotine product standard stated that there is not enough scientific research to support reducing nicotine in cigarettes. Other comments argued that FDA should instead focus on giving adults who smoke cigarettes access to a wider choice of less harmful tobacco products and truthful information about the benefits of switching to those products, as well as focus resources on a plan to reduce harm through proven strategies to prevent initiation and encourage cessation.

FDA has reviewed and closely considered the comments to the Nicotine ANPRM, as well as additional evidence and information not available at the time of the Nicotine ANPRM, in developing this proposed rule.

2. Scientific Review

As the body of evidence has continued to grow, FDA undertook a robust systematic review of the scientific evidence regarding the likely effects of reducing nicotine in combusted tobacco products. This review, entitled “The Science of a Nicotine Standard for Combusted Tobacco Products” (Ref. 45), covers peer-reviewed, publicly available literature and focuses on the likely effects of reducing nicotine in combusted tobacco products. This scientific assessment has been peer reviewed by independent external experts. Taking into consideration comments from this peer review (Ref. 46), FDA revised the scientific assessment, and the final peer-reviewed document is available in the docket for this proposed rule (Ref. 45). Additionally, this final peer-reviewed document and other related documents such as FDA's response to the peer review comments can be found at

https://www.fda.gov/science-research/peer-review-scientific-information-and-assessments/completed-peer-reviews.

FDA's peer reviewed scientific assessment examined the effects of reducing the level of nicotine in combusted tobacco products on use behavior, dependence, and toxicant exposure, as well as the knowledge, beliefs, and perceptions around nicotine and VLNC cigarettes. This scientific review found that the totality of the evidence supports that extended exposure to combusted cigarettes containing VLNC tobacco filler is associated with reduced addiction potential, dependence levels, and number of cigarettes smoked per day, and increased quit attempts among people who currently smoke cigarettes, without evidence of increased toxicant exposure, craving, withdrawal, or compensatory smoking. The review also determined that if FDA were to establish a nicotine product standard that covered only cigarettes, a portion of people who are currently addicted to cigarettes would likely migrate to other, similar combusted tobacco products to maintain their nicotine dependence (or engage in dual use without substantially reducing their combusted tobacco product use), thereby reducing the positive public health impact of such a rule. Based on FDA's review of the literature on combusted tobacco products, including cigarettes, cigarette tobacco, RYO tobacco, cigars, and pipe tobacco, the final scientific assessment concluded that use of any of these combusted products is sufficient to create or sustain nicotine dependence and would therefore continue to expose people who use these products to toxicants. Further, FDA's scientific assessment concluded that the establishment of a maximum nicotine level in combusted tobacco products that would render them minimally addictive or nonaddictive could increase the likelihood of successful quit attempts and help prevent people who experiment with cigarettes and cigars (mainly youth) from progressing to regular use, thereby significantly reducing the morbidity and mortality caused by smoking. FDA has considered the scientific assessment conclusions in the development of this proposed product standard.

In addition, to assess the potential public health impacts of a nicotine product standard, FDA developed a population health model using inputs derived from available empirical evidence and expert opinion to estimate the impact of changes in tobacco product initiation, cessation, switching, and dual use on tobacco use prevalence, morbidity, and mortality in the United States. Details of this modeling approach have been previously published in two peer-reviewed publications (Refs. 47 and 48), which describe the overall model in terms of the inputs, transition behaviors, and outputs that it contains, along with results from simulation studies. In preparation for this proposed product standard, FDA updated a previously-published model (Ref. 47), which describes the impact of a potential product standard that limits the level of nicotine in cigarettes, RYO tobacco, non-premium cigars, and pipe tobacco so that they are minimally addictive or nonaddictive. In this updated modeling document, entitled “Methodological Approach to Modeling the Potential Impact of a Nicotine Product Standard on Tobacco Use, Morbidity, and Mortality in the U.S.” (Ref. 42), we estimated the potential impacts of a nicotine product standard by modeling a baseline scenario of use of cigarettes and noncombusted tobacco products including smokeless tobacco, e-cigarettes, and HTPs. These product classes (cigarettes and noncombusted products) were selected because of the magnitude of population health effects from cigarette smoking and the likelihood of product switching to noncombusted products, especially e-cigarettes. Estimates of changes in mortality from other exposures including non-premium cigar and pipe tobacco use are not produced directly by the model but are derived from model outputs instead. We then compared the baseline scenario to a product standard scenario characterized by the introduction of a potential nicotine product standard that would apply to cigarettes, cigarette tobacco, RYO tobacco, non-premium cigars, and pipe tobacco. FDA's modeling framework and methodological approach and the associated data inputs and assumptions have been peer reviewed by independent external experts. Taking into consideration comments from this peer review (Ref. 49), FDA revised the modeling document, and the final modeling document is available in the docket for this proposed product standard (Ref. 42). FDA's modeling work informed the development of this proposed product standard. Additionally, the modeling document, model code, and inputs are publicly available at

https://www.fda.gov/science-research/peer-review-scientific-information-and-assessments/completed-peer-reviews.

Further discussion of FDA's estimates of the public health impact of this proposed product standard can be found in section VIII of this document.

3. Premium Cigars

On August 9, 2023, the U.S. District Court for the District of Columbia issued an order vacating FDA's rule deeming tobacco products to be subject to FDA's tobacco product authorities “insofar as it applies to premium

cigars.”

Cigar

Ass'n of Am.

FDA,

No. 16-cv-01460, 2023 WL 5094869 (D.D.C. Aug. 9, 2023),

appeal docketed,

No. 23-5220 (D.C. Cir. argued Sept. 13, 2024). The government has appealed this decision. When the deemed status of premium cigars is resolved, FDA will consider any impacts with respect to this proposed rule and take additional steps as warranted, including for example, by reopening the comment period and/or issuing a supplemental notice of proposed rulemaking. References to premium cigars in this document serve merely to clarify the current proposed scope of products covered, evaluate the scientific evidence related to non-premium cigars, and describe FDA's approach to modeling the projected public health impacts of this proposed standard.

For purposes of its ruling, the court specified that a premium cigar is a cigar that: (1) is wrapped in whole tobacco leaf; (2) contains a 100 percent leaf tobacco binder; (3) contains at least 50 percent (of the filler by weight) long filler tobacco (

i.e.,

whole tobacco leaves that run the length of the cigar); (4) is handmade or hand rolled (

i.e.,

no machinery was used apart from simple tools, such as scissors to cut the tobacco prior to rolling); (5) has no filter, nontobacco tip, or nontobacco mouthpiece; (6) does not have a characterizing flavor other than tobacco; (7) contains only tobacco,

water, and vegetable gum with no other ingredients or additives; and (8) weighs more than 6 pounds per 1,000 units.

C. Legal Authority

1. Product Standard Authority

The Tobacco Control Act was enacted on June 22, 2009, amending the FD&C Act and providing FDA with the authority to regulate tobacco products. Section 901 of the FD&C Act (21 U.S.C. 387a) granted FDA the authority to regulate the manufacture, marketing, and distribution of cigarettes, cigarette tobacco, RYO tobacco, and smokeless tobacco to protect the public health and to reduce tobacco use by youth. The Tobacco Control Act also gave the Agency authority to conduct rulemaking to “deem” any other tobacco products subject to chapter IX of the FD&C Act (21 U.S.C. 387 to 387t). In 2016, FDA issued a final rule deeming products meeting the statutory definition of “tobacco product” (including cigars and pipe tobacco), except accessories of the newly deemed products, to be subject to chapter IX of the FD&C Act, as amended by the Tobacco Control Act (81 FR 28974) (deeming final rule).

Among the tobacco product authorities provided to FDA is the authority to adopt tobacco product standards where FDA determines that such standard is appropriate for the protection of the public health (section 907(a)(3)(A) of the FD&C Act). To establish a tobacco product standard, section 907(a)(3)(A) and (B) of the FD&C Act requires that FDA find that the standard is appropriate for the protection of the public health, taking into consideration scientific evidence concerning:

• The risks and benefits to the population as a whole, including users and nonusers of tobacco products, of the proposed standard;

• The increased or decreased likelihood that existing users of tobacco products will stop using such products; and

• The increased or decreased likelihood that those who do not use tobacco products will start using such products.

2. Authority To Establish a Maximum Nicotine Level and Related Provisions

Section 907 of the FD&C Act authorizes FDA to adopt tobacco product standards that are appropriate for the protection of the public health, including expressly authorizing FDA to adopt product standards with provisions for nicotine yields; for the reduction or elimination of other constituents (including smoke constituents) or harmful components; and respecting the construction, components, ingredients, additives, constituents (including smoke constituents), and properties of tobacco products (section 907(a)(3), (a)(4)(A)(i) to (iii), and (a)(4)(B)(i)). This includes the authority to issue a new product standard to establish a maximum level of nicotine in tobacco products.

FDA is proposing to limit nicotine yield by setting a maximum nicotine content level for finished cigarettes and certain other finished combusted tobacco products not to exceed 0.70 mg of nicotine per gram of total tobacco. FDA is not seeking to require the reduction of nicotine yields in any tobacco product to zero, which is prohibited under section 907(d)(3) of the FD&C Act. To ensure that tobacco products subject to the product standard comply with the proposed maximum nicotine level, FDA also is including provisions that would require manufacturers to test their products using an analytical test method for conformance with the maximum nicotine level pursuant to section 907(a)(4)(B)(ii) and (iv) of the FD&C Act.

3. Sale and Distribution Restrictions

Section 907(a)(4)(B)(v) of the FD&C Act states that product standards shall, where appropriate for the protection of the public health, include provisions requiring that the sale and distribution of tobacco products be restricted but only to the extent that the sale and distribution of a tobacco product may be restricted under section 906(d) of the FD&C Act. Similar to section 907, section 906(d) of the FD&C Act gives FDA authority to require restrictions on the sale and distribution of tobacco products by regulation if the Agency determines that such regulation would be appropriate for the protection of the public health. The finding as to whether a regulation is appropriate for the protection of the public health must be determined with respect to the risks and benefits to the population as a whole, including users and nonusers of the tobacco products, and must take into account:

• The increased or decreased likelihood that existing users of tobacco products will stop using such products; and

• The increased or decreased likelihood that those who do not use tobacco products will start using such products (see section 906(d)(1) of the FD&C Act).

Under these authorities and section 701 of the FD&C Act, which provides FDA with the authority to promulgate regulations for the efficient enforcement of the FD&C Act, FDA is proposing provisions that would restrict the manufacture, sale, and distribution of cigarettes and certain other combusted tobacco products that are not in compliance with this standard. These provisions are not intended to restrict the manufacture of cigarettes intended for export. Consistent with section 801(e)(1) of the FD&C Act (21 U.S.C. 381(e)(1)), a tobacco product intended for export shall not be deemed to be in violation of section 907 of the FD&C Act or this product standard, if it meets the criteria enumerated in section 801(e)(1) of the FD&C Act, including not being sold or offered for sale in domestic commerce. These provisions are critical to maintain the purpose of the standard by helping to ensure that the tobacco products conform to the proposed maximum nicotine level when used by consumers.

FDA is also proposing, under these authorities and others described herein regarding testing and recordkeeping, a requirement that the labels of tobacco products covered under this proposed product standard contain a manufacturing code to identify, among other things, the date of manufacture of a production batch, so that FDA can determine whether a product on store shelves is in conformance with the proposed product standard. The proposed manufacturing code would allow manufacturers and FDA to identify the production batch of a particular finished product that has been released for distribution. This information is intended to help determine the product's history (

e.g.,

batch production records) and assist manufacturers and FDA in the event of a nonconforming tobacco product investigation and any corrective actions to be taken by a manufacturer as a result

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.

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.

B. The Developing Brain's Vulnerability to the Effects of Nicotine Leads to Progression to Regular Cigarette Use Among Youth and Young Adults Who Experiment

Youth and young adults are particularly susceptible to developing an addiction to nicotine. Due to the brain's ongoing development during adolescence and young adulthood—until about age 25—it is more vulnerable to nicotine's effects than the adult brain is (Refs. 83 to 85). The 1994, 2012, 2014, and 2020 Surgeon General's Reports on smoking and health note that almost 90 percent of adults who currently and regularly smoke initiated smoking by age 18, and 98 percent initiated smoking by age 26, which is notable given that 25 is the approximate age at which the brain has completed development (Refs. 1, 17 to 19). The developing brain is more vulnerable to developing nicotine dependence than the adult brain is, and the earlier an individual begins smoking the less likely they are to quit (Ref. 20). The maximum nicotine level requirement included in this proposed product standard to regulate nicotine yield would make cigarettes and certain other combusted tobacco products minimally addictive or nonaddictive, limiting the number of youth and young adults who progress from experimentation to regular use and reducing their risk for smoking-related diseases.

There are three primary stages that occur as an individual transitions from never smoking to smoking cigarettes regularly: initiation, experimentation, and regular use. An individual initiates smoking once he or she first tries a cigarette, even one or two puffs (Ref. 17). The vast majority of smoking initiation occurs during adolescence (Ref. 17). Initiation can progress to experimentation, where individuals continue to occasionally try cigarettes, but do not smoke every day, and then to smoking regularly (

i.e.,

smoking daily or on most days) (Ref. 17).

Adolescence is a period of development when individuals who experiment with tobacco products are more susceptible to transitioning to regular use and developing addiction to nicotine. Data from the 2024 NYTS found that 10.1 percent of high school students and 5.4 percent of middle school students reported current use of any tobacco product (Ref. 3). Each day, approximately 1,200 youth (ages 18 and below) try their first cigarette (Ref. 86 at Table A.13A). The transition to regular cigarette use (

i.e.,

smoking on ≥20 of the past 30 days) can occur relatively quickly and can be achieved by smoking as few as 100 cigarettes (Ref. 17). Longitudinal and nationally representative cross-sectional data indicate that an established pattern of cigarette use—including those who “rapidly escalate” to regular use—typically occurs by early adulthood (ages 20-22) (Refs. 87 and 88). The Centers for Disease Control and Prevention (CDC) and other researchers have estimated that 30 percent or more of people who experiment with cigarettes transition to regular cigarette use (Refs. 89 to 92). Researchers applied the 30 percent estimate to the number of adolescents who were at the early experimentation stage in 2000, translating to approximately 2.9 million of these adolescents who have or will become people who regularly smoke cigarettes (Ref. 91). Based on the number of persons under the age of 18 in 2012 in the United States, the U.S. Surgeon General estimated that 17,371,000 of that group would begin smoking cigarettes regularly and 5,557,000 will die from a smoking-related disease (Ref. 1 at Table 12.2.1). These concerningly high numbers speak to the extreme vulnerability of youth and young adults to the health harms of tobacco use resulting from addiction to nicotine.

Nicotine addiction is a critical factor in the transition of people who smoke cigarettes from experimentation to regular smoking and in the continuation of smoking for those who want to quit (Ref. 28 at p.113, Ref. 1). Although the majority of adolescents who smoke daily meet the criteria for nicotine dependence, one study found that the most susceptible youth lose autonomy (

i.e.,

independence in their actions) regarding tobacco within 1 or 2 days of first inhaling from a cigarette (Refs. 93 and 94). Another study found that 19.4 percent of adolescents (initially ages 12-13 and followed over 6 years) who smoked weekly were dependent on nicotine (Ref. 95). In a study regarding nicotine dependence among adolescents who recently initiated smoking (9th and 10th grade students), adolescents who smoked cigarettes at the lowest levels (

i.e.,

smoking on only 1 to 3 days of the past 30 days) experienced nicotine dependence symptoms such as loss of control over smoking (42 percent) and irritability after not smoking for a while (23 percent) (Ref. 96). Researchers in a 4-year study of 6th grade students also found that “[e]ach of the nicotine withdrawal symptoms appeared in some subjects

prior

to daily smoking” (Ref. 93) (emphasis added). Ten percent of the study participants showed signs of tobacco dependence within 1 or 2 days of first inhaling from a cigarette, and half had done so by the time they were smoking seven cigarettes per month (Ref. 93).

Similarly, researchers have found that among the 3.9 million middle and high school students who reported current use of tobacco products (including cigarettes and cigars) in 2012, 2 million of those students—including those who used intermittently (

e.g.,

smoking cigarettes on a monthly basis)—reported at least one symptom of dependence (Ref. 24). Other researchers analyzing data from the 2021 NYTS found that a sizeable proportion of high school students using tobacco products in the past 30 days report symptoms of nicotine dependence, including 27.2 percent reporting a strong craving for tobacco use and 19.5 percent reporting wanting to first use tobacco products within 30 minutes of waking (Ref. 25). Overall, these findings demonstrate that youth and young adults who experiment with cigarettes (and other tobacco products) are particularly vulnerable to the effects of nicotine on progression to regular use and dependence, leading to maintained tobacco product use into adulthood.

C. Youth and Adult Cigarette Smoking Cessation and Relapse

Like adults, many youths who smoke cigarettes want to quit but have difficulty doing so. An analysis of data from the 2015 YRBS looking at youth cigarette quit attempts found that 45.4 percent of high school students currently smoking cigarettes had sought to quit in the previous year (Ref. 22); 2012 NYTS data were congruent, indicating that 51.5 percent of middle and high school students who smoke cigarettes had sought to quit all tobacco use in the previous year (Ref. 22).

For adults who smoke who report quit attempts, few are successful. As of 2019, researchers estimate that only between 5.4 and 5.6 percent of people who smoked cigarettes successfully quit for good, according to data from the NHIS and National Survey on Drug Use and Health (NSDUH), respectively (Ref. 14). According to recent data regarding adult quit attempts, analyses of 2022 NHIS and 2018-2019 TUS-CPS data indicate that 67.7 and 76.6 percent of adults, respectively, who smoke cigarettes were interested in quitting (Refs. 4 and 36), while the 2022 NHIS data and 2018-2019 TUS-CPS data show that only 53.3 and 51.3 percent, respectively, of U.S. adults who smoke actually made a quit attempt within the past year (Refs. 4 and 36). Analyses of 2022 NHIS and 2018-2019 TUS-CPS data indicates that only 8.8 and 7.5 percent of adults who

formerly smoked cigarettes had successfully quit smoking cigarettes, respectively (Ref. 4 and 36). Adults who smoke may make 30 or more quit attempts before succeeding (Ref. 37). Some population groups are less successful than others: for example, adults with education levels at or below the equivalent of a high school diploma have the highest smoking prevalence levels but the lowest quit ratios (

i.e.,

the ratio of persons who have smoked at least 100 cigarettes during their lifetime but do not currently smoke to persons who report smoking at least 100 cigarettes during their lifetime) (Ref. 97). Nicotine addiction and associated withdrawal symptoms make it difficult for people who smoke cigarettes to quit, and quit rates rarely exceed 25 percent (Ref. 98).

Relapse is the principal limiting factor in the transition from smoking to nonsmoking status (Ref. 28). Relapse refers to the point after an attempt to stop smoking when a person's tobacco use again becomes ongoing and persistent (Ref. 28 citing Brandon et al., 1986). Most people who relapse do so soon after their quit attempt (Ref. 28). One study found that 80 to 90 percent of individuals who were smoking at 6 months following a quit attempt had resumed smoking within 2 weeks following their quit attempt (Ref. 99). However, even those who quit smoking for longer periods of time frequently relapse. Long-term studies of individuals trying to quit smoking reveal that 30 to 40 percent of those who quit smoking for 1 year eventually relapsed (Ref. 99). In addition, one study following 840 participants for more than 8 years found that approximately one-half of people who smoke who stopped smoking for 1 year relapsed to regular smoking within the subsequent 7 years (Ref. 100). Researchers have found that a higher frequency of smoking is associated with earlier lapses after cessation (

e.g.,

smoking on the first day of cessation or within the first 2 weeks), which in turn is strongly associated with an increased risk of relapse, and is also associated with more severe withdrawal symptoms and earlier relapse after an attempt to quit smoking (Ref. 28 at p.119). These findings confirm the powerful addictive properties of nicotine in tobacco products, a principal factor limiting the ability to quit for a person who uses combusted tobacco products, and further underscore the public health importance of decreasing the addictiveness of these products by decreasing nicotine yield, particularly for youth and young adults who experiment with smoking and for people currently smoking and who hope to quit.

D. Smoking Cigarettes and Other Combusted Tobacco Products Causes Serious Negative Health Effects

Nicotine is a powerfully addictive chemical. The effects of nicotine on the central nervous system occur rapidly after absorption (Ref. 57 at p.12). People who use cigarettes and other combusted tobacco products absorb nicotine readily from tobacco smoke through the lungs (Ref. 57 at p. iii), and, from the lungs, nicotine is then rapidly transmitted to the brain (Ref. 57 at p.13). In the case of cigars, nicotine is also absorbed through the mouth. With regular use, nicotine levels accumulate in the body during the day from tobacco product use and the nicotine persists overnight, allowing for continuous exposure throughout the entire 24-hour period (Ref. 57 at p.38). While mild nicotine intoxication can occur among people who are smoking for the first time (Ref. 57 at p. 15-16), tolerance to the effects of nicotine develops rapidly.

Cigarette smoking is responsible for 480,000 premature deaths every year from many diseases, puts a substantial burden on the U.S. healthcare system, and causes massive economic losses to society (Ref. 1 at p. 659-666). In terms of a monetary measure of the impact of cigarette smoking on the public health, in 2018 smoking cost the United States more than $600 billion, including more than $240 billion in healthcare spending (Ref. 10), nearly $185 billion in lost productivity from smoking-related illnesses and health conditions (Ref. 10), nearly $180 billion in lost productivity from smoking-related premature death (Refs. 1 and 10), and $7 billion in lost productivity from premature death from secondhand smoke exposure (Refs. 1 and 11). Current evidence shows that, while nicotine itself is not the direct cause of most smoking-related diseases, addiction to the nicotine in tobacco products is the proximate driver of tobacco-related death and disease because it sustains tobacco use even when people who smoke want to quit (which most people who smoke report wanting to do) (Refs. 1, 13, 28, 58, and 61). Inhalation of smoke from cigarettes and other combusted tobacco products exposes people who use the products to over 7,000 chemicals, many known to be hazardous to health and lead to disease (Ref. 28). According to the 2014 Surgeon General's Report, which summarizes thousands of peer-reviewed scientific studies and is itself peer-reviewed, smoking remains the leading preventable cause of disease and death in the United States, and cigarettes have been shown to cause an ever-expanding number of diseases and health conditions (Ref. 1). Every year, cigarette smoking is the primary causal factor for 163,700 deaths from cancer, 160,600 deaths from cardiovascular and metabolic diseases, and 131,100 deaths from pulmonary diseases (Ref. 1 at p.659). In the United States, about 87 percent of all lung cancer deaths, 32 percent of coronary heart disease deaths, and 79 percent of all cases of chronic obstructive pulmonary disease (COPD) are attributable to cigarette smoking (Ref. 1). Smoking during pregnancy can result in negative outcomes for a newborn baby, such as low birth weight, lungs that fail to develop properly, birth defects such as cleft lip and/or cleft palate, and Sudden Infant Death Syndrome (Ref. 101). As stated in the 2014 Surgeon General's Report, “[c]igarette smoking has been causally linked to diseases of nearly all organs of the body, to diminished health status, and to harm to the fetus . . . [and] the burden of death and disease from tobacco use in the United States is overwhelmingly caused by cigarettes and other combusted tobacco products” (Ref. 1 at p.7).

Tobacco and cigarette smoking-related morbidity and mortality also have been experienced differentially across different sociodemographic characteristics, such as race, ethnicity, socioeconomic status, educational attainment, mental health status, and homelessness. Black

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

have greater risk of lung cancer morbidity and mortality (Refs. 1, 115 to 118). Additionally, American Indian/Alaska Native (AI/AN) populations have the highest cigarette use prevalence (Refs. 119 to 121) and are more likely to suffer disproportionate rates of tobacco-related death (Ref. 119). An analysis of 2001-2009 mortality data for people living in the Indian Health Service Contract Health Service Delivery Area counties in the United States indicated that age-adjusted death rates, smoking-attributable fractions, and smoking-attributable mortality for all-cause mortality were statistically significantly higher among AI/AN populations than among White populations for adult men and women aged 35 years and older (Ref. 122). Cigarette smoking caused 21 percent of ischemic heart disease, 15 percent of other heart disease, and 17 percent of stroke deaths in AI/AN men, compared with 15 percent, 10 percent, and 9 percent, respectively, for White men (Ref. 122). Among AI/AN women, smoking caused 18 percent of ischemic heart disease deaths, 13 percent of other heart disease deaths, and 20 percent of stroke deaths, compared with 9 percent, 7 percent, and 10 percent, respectively, among White women (Ref. 122). Some Asian populations, Native Hawaiians, and other Pacific Islander populations also suffer from disproportionate rates of tobacco-related mortality as compared to non-Hispanic White persons (Refs. 115, 117, 123, and 124).

Throughout this document, FDA uses both the terms “Black” and “African American.” The term “African American” is used to describe or refer to a person of African ancestral origins or who identifies as African American. “Black” is used to broadly describe or refer to a person who identifies with that term. Though these terms may overlap, they are distinct concepts (

e.g.,

a Black person may not identify as African American). As a result, FDA relies on the specific term used by researchers when citing to specific studies. FDA uses the term “Black” when not citing to a specific study.

Disparities in tobacco-related morbidity and mortality have also been observed for additional population groups that have higher levels of tobacco use. Those with low household income and/or educational attainment bear a disproportionate burden of myocardial infarction prevalence and coronary heart disease-related mortality (Ref. 125). National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2010 indicate that prevalence of co-occurring obesity and smoking was linearly associated with educational attainment as women with the lowest levels of education had greater likelihood of being obese and smoking than women with the highest levels of education (Ref. 126). Some research also indicates that race/ethnicity status interacts with the effects of higher educational attainment on the likelihood of current smoking. The protective effect of higher education against current smoking was shown to be a stronger effect for White as compared to Black respondents (Ref. 127). Research has also demonstrated that individuals with behavioral health conditions and other medical comorbidities have higher prevalence of combusted tobacco use compared to those without these conditions (Refs. 128 and 129) and have increased risk of tobacco-related morbidity and mortality (Refs. 120, 130, and 131). Inpatient hospital admission data from 1990 to 2005 from California indicate that approximately half of the deaths in those who had been hospitalized for schizophrenia, bipolar disorder, or major depressive disorder were due to diseases causally linked to tobacco use (Ref. 130) and that the majority of deaths for those hospitalized for opioid-related conditions were related to tobacco and alcohol, not to opioids (Ref. 132). Tobacco-related cancers are a leading cause of death among adults experiencing homelessness (Ref. 133). While cigarette smoking and exposure to cigarette smoke are responsible for significant mortality—480,000 premature deaths annually, as previously stated—this estimate does not include deaths caused by other tobacco products, such as cigars and pipes (Ref. 1 at p. 665).

Additionally, for every person who dies from a smoking-related disease in the United States, approximately 30 more people will suffer from at least one smoking-related disease (Ref. 1).

Regular cigar smoking was responsible for approximately 9,000 premature deaths and more than 140,000 years of potential life lost among adults aged 35 years or older in 2010 (Ref. 134). The 2014 Surgeon General's Report states that the methodology for estimating the current population burden for use of combusted tobacco products other than cigarettes remains under discussion, but the number of added deaths is expected to be in the thousands per year (Refs. 1 and 135).

Inhalation of the chemicals produced by combustion results in numerous adverse health outcomes through mechanisms that include DNA damage, inflammation, and oxidative stress (Ref. 28). The three leading causes of smoking-attributable death for people who currently and formerly smoke cigarettes are lung cancer, heart disease, and COPD (Ref. 1 at p. 660). Cigarette smoking results in a chronic inflammatory state in the cardiovascular system that is known to be a powerful predictor of cardiovascular events including heart disease (Ref. 28). For COPD, although studies have shown that the disease can be almost completely prevented with the elimination of smoking (Ref. 63), for those who have already developed the disease, evidence indicates that the related morbidity persists long after cessation of smoking (Ref. 28). In addition, it has been established that more than 85 percent of lung cancers are due to smoking, and lung cancer is the country's leading cause of cancer death (Refs. 1, 28, 63, and 136).

Cigarettes and other combusted tobacco products also have deadly effects on people who do not smoke because they produce secondhand smoke. It is well-established that secondhand tobacco smoke causes premature death and disease in children and in adults who do not smoke (Ref. 15 at p.11). Secondhand smoke exposure is currently estimated to be responsible for over 41,000 deaths annually in the United States (Ref. 1). For example, an estimated 7,300 lung cancer deaths and nearly 34,000 coronary heart disease deaths annually can be attributed to secondhand smoke (Ref. 1). Additionally, productivity losses due to secondhand smoke-attributable deaths are estimated to cost the United States $5.6 billion each year (Ref. 1).

Secondhand smoke is particularly harmful to children. For instance, the 2014 Surgeon General's Report estimated that each year, secondhand smoke is associated with 150,000 to 300,000 lower respiratory tract infections in infants and children under 18 months of age, 790,000 doctor's office visits related to ear infections, and 202,000 asthma cases (Refs. 1 and 137). In addition, thirdhand smoke—the chemical residue from combusted tobacco smoke that can become embedded in the environment (

e.g.,

carpet, dust)—results in exposure to harmful constituents such as tobacco specific nitrosamines (Ref. 138). Exposure to thirdhand smoke is especially concerning for young children given their size and behaviors, like crawling on the ground and frequently putting their hands in their mouths.

Additionally, the burden of secondhand smoke exposure is experienced disproportionately among members of some racial and ethnic groups and people with lower household income and educational attainment. Among people who do not smoke, ages 3 and older, findings from 2011 to 2018 NHANES data indicate that non-Hispanic Black respondents and those living below the poverty level had the highest levels of secondhand smoke exposure compared to people of other races and those living above the poverty level, respectively; these disparities persisted across all years of the study analysis from 2011 to 2018 (Ref. 139). From 1999 to 2012, the percentage of persons who do not smoke (ages 3 and older) with detectable serum

cotinine

levels (defined in the study as levels ≥0.05 nanogram per milliliter to indicate secondhand smoke exposure) declined across all racial and ethnic groups (Ref. 141). However, a higher proportion of non-Hispanic Black individuals who do not smoke continued to have detectable serum cotinine levels, compared to Hispanic and non-Hispanic White individuals who do not smoke. For example, in 2017-2018, nearly 50 percent of non-Hispanic Black people who do not smoke had detectable serum cotinine levels, compared with 22 percent of non-Hispanic White and 17 percent of Mexican American people who do not smoke (Ref. 141). Moreover, disparities in trends in detectable serum cotinine levels among people who do not use cigarettes over time have been observed on the basis of race/ethnicity. One analysis of NHANES data and found that from 1999 to 2012 among children ages 3-11, comparable levels of decline were observed among non-Hispanic White (percentage change: 41.2 percent) and Mexican American (percentage change: 39.0 percent) youth, but a lesser decline was observed among non-Hispanic Black youth (percentage change: 19.8 percent) (Ref. 141). A more recent analysis of NHANES data also indicated that, between 2011 and 2018, the percentage of people who do not use cigarettes with detectable serum cotinine levels increased among non-Hispanic Black youth ages 12-19 but remained stagnant among non-Hispanic White youth of the same ages (Ref. 142).

Cotinine is an alkaloid found in tobacco leaves and is the main metabolite of nicotine. Measuring cotinine in people's blood is a reliable way to determine exposure to nicotine for both people who smoke and those exposed to environmental tobacco smoke (Ref. 140).

Moreover, there is also some scientific evidence supporting disparities in secondhand smoke exposure by sexual orientation. An analysis of NHANES data from 2003-2010 found that secondhand smoke exposure (defined as a serum continine

levels ≥0.05 nanogram per milliliter) differed by sexual orientation among women 20-59 years of age (Ref. 143). This study found that among women 20-59 years of age, secondhand smoke exposure was higher among non-smoking women who identified as lesbian (56.2 percent) or who reported a lifetime experience with a same-gender partner (47.7 percent) than those women who identified as exclusively heterosexual (33.0 percent; p<0.001) (Ref. 143). However, among men 20-59 years of age, exposure to secondhand smoke did not significantly differ by sexual orientation.

Disparities in the secondhand smoke exposure are found across various environmental settings. These disparities speak to the interrelated influences of individual factors (

e.g.,

age, race and ethnicity, sexual orientation, income) and existing inequities in places where members of communities disproportionally impacted by tobacco-related health disparities are likely to reside, spend time, and work (Refs. 53 and 120). For example, an analysis of NHANES data from 2017-2018 found that 87.8 percent of non-smoking persons 3 years of age and older who lived with someone who smoked inside the home was exposed to secondhand smoke based on serum cotinine values of 0.05-10.00 nanogram per milliliter compared to 21.4 percent of non-smoking persons 3 years of age and older not living with someone who smoked inside the home (Ref. 142). In terms of race and ethnicity, findings drawn from the 2013-2016 NHANES data indicate that compared to non-Hispanic White respondents, non-Hispanic Black respondents had higher odds of secondhand smoke exposure in homes other than their own (Ref. 144). An analysis of NYTS data indicates that non-Hispanic Black and non-Hispanic White students both had higher prevalence of secondhand smoke exposure at home and in vehicles than Hispanic and non-Hispanic other race/ethnicity students (Ref. 145). While secondhand smoke exposure in homes and vehicles declined from 2011 to 2018, secondhand smoke exposure in homes among non-Hispanic Black students did not change (Ref. 145). Additionally, a study using data from Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study found that the odds of exposure to secondhand smoke at home were higher for Black adults (OR=1.12, 95 percent CI:1.00-1.24; p-value=0.042) than White adults; and higher for those adults who self-identified as being LGBT (OR=1.30, 95 percent CI:1.11-1.52; p-value=0.001) than for heterosexual adults (Ref. 146). Home smoking bans (

i.e.,

when people decide to have their own rules that restrict or ban smoking inside their own home)—can reduce secondhand smoke exposure. For example, a study using data from the 2009-2010 National Adult Tobacco Survey (NATS) found the prevalence of exposure to secondhand smoke varied based on the presence (or absence) of smokefree rules in the home (Ref. 147). This study found that overall, 1.4 percent of people who did not smoke and had a smokefree rule at home were exposed to secondhand smoke in their homes in the past 7 days, compared with 43.9 percent of people who did not smoke and did not have a smokefree rule at home (Ref. 147). A similar pattern was observed across age groups, race and ethnicity, and levels of educational attainment. For example, a higher percentage of Black and Hispanic people were exposed to secondhand tobacco smoke in homes with and without smokefree rules than White people. Additionally, a study using 1995-2007 TUS-CPS data found that among two parent households, higher levels of parental educational level and annual household income were associated with the higher reporting of a complete home ban as compared to lower levels of parental educational and annual household income (Ref. 148). Such findings emphasize the degree to which certain aspects of disadvantage (such as lower family income, lack of access to single-family housing, or lack of autonomy over the home environment) may compound tobacco-related health disparities.

Individuals who live in multi-unit housing, including apartments, are particularly susceptible to involuntary secondhand smoke exposure in the home, as secondhand smoke can infiltrate throughout a building along various pathways (Refs. 149 to 153). Exposures to secondhand smoke in multi-unit housing are potentially concerning given a study drawing on the 2013-2014 National Adult Tobacco Survey (NATS) found that tobacco use was higher among adults living in multi-unit housing (24.7 percent) than those in single-family housing (18.9 percent) (Ref. 154). This study also found that smoke-free home rules (

i.e.,

home smoking bans) were higher among adults living in single-family housing (86.7 percent) than those in multi-unit housing (80.9 percent) (Ref. 154). However, more than a third (34.4 percent) of multi-unit housing residents with home smoking bans have experienced secondhand smoke incursions (Ref. 154). Recent estimates indicate that approximately 80 million residents in the United States are currently living in some type of multi-unit housing (Ref. 150). Among those living in multi-unit housing with a home smoking ban, an estimated 27.6-28.9 million are exposed to secondhand smoke incursions from neighboring units and/or shared common areas (Ref. 150). Moreover, a 2013 nationally representative study conducted among U.S. adults living in multi-unit housing found that 25.2 percent of non-smoking residents who had no smoking in the home for at least 3 months and who also

had a child in the home had a recent secondhand smoke incursion into their unit; 99 percent of these residents also reported being bothered by the incursion (Ref. 155). Multi-unit housing secondhand smoke incursions have also been found to be greater among specific populations that are already disproportionately burdened by tobacco-related disease and death, including women, younger adults, and non-Hispanic Black, Hispanic, and lower income populations (Ref. 154).

Workplace secondhand smoke exposure has also been shown to vary across population groups. A study using data from the 2009-2010 NATS show the prevalence of secondhand smoke exposure from employed nonsmoking adults was higher among males, non-Hispanic Black, Hispanic, and AI/AN people compared with White people, and people with low education and low income (Ref. 156). Similarly, data from the 2010 and 2015 NHIS show that exposure to secondhand smoke in the workplace was disproportionately high among non-Hispanic Black respondents, Hispanic respondents, and workers with low education and low income (Ref. 157). Additionally, the study findings indicated that “blue-collar workers” (defined as those who performed manual labor such as manufacturing, mining, sanitation, and construction) experienced higher prevalence of secondhand smoke exposure compared to “white-collar workers” (defined as those who primarily work in an office, with computer and desk setting, and perform professional, managerial, or administrative work) (Ref. 157).

The disparities observed in tobacco use, as well as disparities in secondhand smoke exposure, contribute to the disparities in tobacco-related morbidity and mortality experienced by some population groups. This proposed product standard is anticipated to reduce smoking-related morbidity and mortality for the population as a whole, including these populations that use tobacco or are exposed to secondhand smoke at disproportionately high levels.

Other combusted tobacco products, particularly those that could serve as alternatives to cigarettes if people who smoke cigarettes no longer had access to normal nicotine cigarettes (NNC), cause similar negative health effects. For example, cigar smoke contains many of the same harmful constituents as cigarette smoke, and cigar smoke may have even higher levels of several harmful compounds compared to cigarette smoke (Refs. 1, 134 and 158). For example, cigar smoke contains higher amounts of carcinogenic, tobacco-specific N-nitrosamines than cigarette smoke due to the relatively high concentration of nitrate in cigar tobacco, which leads to formation of cancer-causing nitrosamines during the fermentation process (Refs. 1; 53 at Chapter 3; and 158). Researchers have found urinary concentrations of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) (a hazardous tobacco-specific nitrosamine) measured in people who smoke cigars daily to be as high as those measured in people who smoke cigarettes daily (Refs. 159 and 160). Like exposure to cigarette smoke, exposure to higher levels of cigar smoke for longer time periods increases the adverse health risks caused by cigar smoking (Ref. 28).

Consequently, there is a long-standing body of research, including reports from the U.S. Surgeon General and National Cancer Institute (NCI), demonstrating that cigar use causes serious adverse health effects (Ref. 53 at p.119-155; Refs. 55; 161, and 162). NCI's Smoking and Tobacco Control Monograph No. 9 (“Cigars: Health Effects and Trends”), which provides a comprehensive, peer-reviewed analysis of the trends in cigar smoking and potential public health consequences, as well as other research, demonstrates that cigar smoking leads to an increased risk of oral, laryngeal, esophageal, pharyngeal, and lung cancers, as well as coronary heart disease and aortic aneurysm, with the magnitude of risk a function of the amount smoked and depth of inhalation (Ref. 53 at p.119-155). Likewise, a systematic review of the mortality risks associated with cigar smoking that identified 22 studies found that people who regularly smoke cigars are at increased risk for many of the same diseases as people who smoke cigarettes, including oral, laryngeal, esophageal, and lung cancer; cardiovascular diseases; and COPD (Ref. 163).

Research indicates that most people who smoke cigars do inhale some amount of smoke, even when they do not intend to inhale, and are not aware of doing so (Refs. 54 and 55). Even when people who smoke cigars do not breathe smoke into their lungs, they are still subject to the addictive effects of nicotine through nicotine absorption (Refs. 55 and 56). This nicotine absorption occurs because cigar smoke dissolves in saliva, allowing the person smoking the cigar to absorb sufficient nicotine by holding the smoke in their mouths, even if the smoke is not inhaled (Refs. 53, 56, and 164). Cigar and/or pipe smoking causes cancers of the lung and upper aerodigestive tract, including the oral cavity, oropharynx, hypopharynx, larynx and esophagus (Ref. 158). Additional evidence suggests that cigar and/or pipe smoking is causally associated with cancers of the pancreas, stomach, and bladder (Ref. 165). People who smoke cigars also have increased risks for coronary heart disease and COPD compared with people who never used tobacco (Ref. 166).

One study using NATS data from 2009 to 2010 found that regular cigar smoking (defined as use on at least 15 of the past 30 days) was responsible for approximately 9,000 premature deaths and more than 140,000 years of potential life lost among adults aged 35 years or older in 2010 (Ref. 134). A study of healthcare expenditures from 2000 to 2015 found that cigar-attributable healthcare expenditures for adults totaled $1.75 billion per year, with $284 million attributed to exclusive cigar smoking and $1.5 billion attributed to poly tobacco use (

i.e.,

use of multiple tobacco products) involving cigar smoking plus cigarette or smokeless tobacco use (Ref. 167). In addition, overall mortality rates for all people who smoked cigars (

i.e.,

those who report inhaling as well as those who report not inhaling cigar smoke) are higher than rates for those who have never smoked, although they are generally lower than the rates observed for people who smoke cigarettes (Ref. 53 at p. 112). In an analysis of National Longitudinal Mortality Study (NLMS) data, researchers also found that the risk of dying from tobacco-related cancers is higher for people who currently exclusively use pipe tobacco and those who currently exclusively smoke cigars than for those who reported never using combusted tobacco products (Ref. 168). Another similar analysis using the restricted-use National Health Interview Survey-Linked Mortality Files (NHIS-LMF), following participants for mortality from 2000 through 2015, observed that people who currently smoked cigars daily had elevated risk of all-cause mortality compared to those who had never used tobacco (Ref. 169). In addition, researchers studying people who smoke cigars in 2009 and 2010 found that the average person who smokes cigars or pipes loses approximately 15 life years (Ref. 134).

Disparities in cigar-related health outcomes have also been observed by gender and race/ethnicity. Likely due to the greater prevalence of cigar use among men versus women, one analysis observed a significantly greater number of years of potential life lost for men than women (117,440 for men; 22,284 for women) associated with cigar use, as well as disparate monetary losses associated with cigar use ($19.5 billion

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+),

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).

Throughout this document, FDA uses the term “LGBTQI+” broadly when referring to lesbian, gay, bisexual, transgender, queer, and intersex communities. When we describe findings from the published literature, we refer specifically to the groups that are studied. For example, some authors examine tobacco-related outcomes for members who identify as lesbian, gay, bisexual, or transgender only; as such, the data are limited to those who identify as LGBT, and authors interpret the findings for those specific groups.

Industry marketing tactics have also included the incorporation of culture-specific imagery, traditional practices, and events that target specific racial and ethnic groups. For instance, tobacco companies have sponsored cultural events such as Cinco de Mayo celebrations, Chinese New Year celebrations, and activities related to Black History Month (Refs. 173 and 194) and have used the cultural significance of traditional tobacco to validate the authenticity of commercially available cigarettes, exploiting the traditions of Native people to encourage cigarette use (Ref. 195). Tobacco industry documents show that tobacco companies have strategically marketed their products to women with lower income, particularly Black and Hispanic women, (Ref. 196), people experiencing homelessness and people with mental illness (Refs. 197 and 198), and the LGBTQI+ community (Refs. 199 to 201). Research also demonstrates that since at least the 1960s, the tobacco industry has made strategic donations to organizations representing and affiliated with these communities (Refs. 120, 202 to 205). Internal industry documents reveal that at least one tobacco company considered such donations to be a “quid pro quo,” because they could result in the normalization of tobacco use, development of brand loyalty, and opposition to health-protective tobacco control policies (Ref. 206).

The industry's practices have resulted in long-term consequences for communities. Tobacco marketing influences social norms around tobacco use, making it more socially acceptable and increasing the likelihood of use (Refs. 207 to 209). In communities where the tobacco industry has disproportionately marketed to historically marginalized populations over decades, these social norms are transferred through peers and family generations, perpetuating the use of harmful combusted tobacco products, and contributing to present-day tobacco-related health disparities in these populations (Refs. 207, 210, and 211). Moreover, recent scientific evidence indicates that tobacco companies continue to target populations that experience tobacco-related health disparities with tobacco marketing (Refs. 178, 180, 191, 207, 212 to 226).

Although targeted marketing is only one factor in the development and perpetuation of combusted tobacco product use and related harms, it contributes to disparities that affect public health and are of great concern to FDA. Advancing health equity is a policy priority and an important component of fulfilling FDA's mission to protect and promote public health. FDA and the Federal Government recognize the advancement of health equity as “both a moral imperative and pragmatic policy,” as Executive Order 13995 states. Considerations related to health equity helped inform FDA's decision to prioritize this proposed product standard.

F. Consumer Knowledge, Attitudes, Beliefs, and Perceptions About Nicotine

The science on consumer knowledge, attitudes, beliefs, and perceptions about nicotine demonstrates that a majority of consumers correctly understand that nicotine is the substance in cigarettes that causes addiction. Nationally representative studies that examined nicotine addiction beliefs in the general population reported that the belief that nicotine is addictive was endorsed by approximately 85.8 percent of the population, and the belief that nicotine is responsible for driving continued cigarette use was endorsed by approximately 82.9 percent of the population (Refs. 227 to 233). A nationally representative survey found that 88 percent of people who currently smoke cigarettes and 91 percent of people who use e-cigarettes agreed that nicotine makes people want to smoke (Ref. 227). A nationally representative study of youth suggests that about 77.1 percent of respondents believe that nicotine definitely or probably causes addiction (Ref. 234).

However, in contrast to high rates of correct beliefs about the addictiveness of nicotine, there are high rates of incorrect beliefs about the harms of nicotine. Studies that examined nicotine harm beliefs in the general population reported that the belief that nicotine causes cancer was endorsed by 40 to 78 percent of adult participants (Refs. 227, 228, 232, 233, 235 to 245). Additionally, a nationally representative study of youth suggests that about 74.7 percent believe that nicotine definitely or probably causes cancer (Ref. 234). Multiple nationally representative studies that examined nicotine harm perceptions by tobacco use status found that 52 to 61 percent of people who currently use cigarettes and up to 84 percent of people who do not use cigarettes endorsed the belief that nicotine itself causes cancer or that nicotine is the major contributing constituent in cigarettes that causes cancer (Refs. 228, 241, and 245). A more recent qualitative study of people who currently use little cigars and cigarillos suggests that the misperception that nicotine has significant adverse health

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)

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.

As previously noted in footnote 7, the term VLNC should not be confused with the cigarette brand name “VLN;” “VLN” refers to cigarette products authorized for marketing by FDA in 2019. See

https://www.fda.gov/media/133633/download?attachment

and

https://www.fda.gov/media/133635/download?attachment.

Some of the earliest VLNC cigarettes studied by academic researchers were produced by Philip Morris and marketed under the brand name “Next,” which was reported to contain 0.4 mg nicotine per gram of total tobacco (Ref. 248). Later, the National Institute on Drug Abuse (NIDA) contracted with the Ultratech/Lifetech Corporation

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).

Both Ultratech and Lifetech have been reported as being the company through which NIDA manufactured research cigarettes.

Commercially available Quest cigarettes were produced and marketed by Vector Tobacco in the early 2000s and utilized genetically engineered tobacco to create cigarettes with three distinct nicotine content levels (

i.e.,

Quest 1 (12.7 mg/g), Quest 2 (7.3 mg/g), Quest 3 (0.9 mg/g)) (table 1). These cigarettes were used in much of the VLNC research conducted prior to the development of SPECTRUM Nicotine Research Cigarettes; they are no longer on the market. Philip Morris also manufactured cigarettes with varying nicotine levels for research only (Ref. 251). In a public statement issued on July, 2018, 22nd Century Group, Inc. stated that they were already using genetic engineering and plant breeding to produce VLNC tobacco for cigarettes (Ref. 252). In 2014, the company was granted patents for its process to dramatically reduce the nicotine in tobacco plants (Ref. 253). This tobacco has been used to generate low nicotine content research cigarettes, produced and distributed by RTI International, under a contract with the NIDA Drug Supply Program (Ref. 254). 22nd Century Group, Inc. acts as a vendor for RTI for this contract, manufacturing SPECTRUM Nicotine Research Cigarettes that were reported to contain 0.4 mg nicotine per gram of tobacco (Ref. 254), and they also manufacture cigarettes with other reduced levels of nicotine. These SPECTRUM Nicotine Research Cigarettes are similar in many sensory characteristics to NNC cigarettes, but with VLNC (Refs. 255 and 256).

In 2019, 22nd Century Group, Inc. received FDA marketing authorization and, in 2021, received exposure modification orders for their VLNC cigarettes under the names VLN King and VLN Menthol King. VLN cigarettes are currently being marketed and sold to consumers in select U.S. markets as cigarettes with 95 percent less nicotine than conventional cigarettes. From January 1, 2023, to November 22, 2024, 22nd Century VLN cigarette dollar sales accounted for less than 0.001 percent of total cigarette dollar sales in any 4week period. Menthol flavored 22nd Century VLN cigarettes over the same time accounted for less than 0.001percent of any 4-week menthol flavored cigarette dollar sales.

FDA's own analyses, calculations and conclusions informed in part by the NielsenIQ Retail Measurement Service (RMS) data through NielsenIQ's RMS for the tobacco product category “Cigarettes” for the time period January 1, 2023 through November 2, 2024 for Total US Expanded All Outlets Combined (xAOC) and convenience stores are those of FDA and do not reflect the views of NielsenIQ. NielsenIQ is not responsible for, had no role in, and was not involved in analyzing and preparing the results reported herein, or in developing, reviewing, or confirming the research approaches used in connection with this report. NielsenIQ RMS data consist of weekly purchase and pricing data generated from participating retail store point-of-sale systems in all U.S. markets. See

https://NielsenIQ.com/global/en/

for more information.

Currently, these are the only authorized VLNC cigarettes. As we discuss in other parts of this document (see section VII.E), we believe the scientific evidence supports the technical achievability of the proposed standard; additionally, the tobacco industry and consumer product companies have developed a range of brands with differing nicotine levels. Thus, it appears there would be opportunities for any manufacturer who chooses to enter the market for products covered by thi

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