June 5, 2018 TO

Memorandum Date: May 23, 2018

Order Date: June 5, 2018

TO: Lane County Board of Commissioners, Sitting as the Board of Health

DEPARTMENT: Health & Human Services

PRESENTED BY: Karen Gaffney, Director Jocelyn Warren, Public Health Manager

AGENDA ITEM TITLE: ORDER ______IN THE MATTER OF APPROVING SUBMISSION OF COMMENTS AND INPUT TO THE U.S. FOOD AND DRUG ADMINISTRATION FOR CONSIDERATION IN CONJUNCTION WITH PROPOSED RULEMAKING REGARDING NICOTINE LEVELS IN CIGARETTES, FLAVORED TOBACCO PRODUCTS AND THE REGULATION OF PREMIUM CIGARS

I. MOTION

In the Matter of Approving Submission of Comments and Input to the U.S. Food and Drug Administration for Consideration in Conjunction with Proposed Rulemaking Regarding the Nicotine Levels in Cigarettes, Flavored Tobacco Products and Regulation of Premium Cigars.

II. AGENDA ITEM SUMMARY

Health & Human Services (H&HS) is bringing forward an action item: requesting BCC/BoH concurrence with and authority to provide written comments and input to the U.S. Food and Drug Administration (FDA) regarding tobacco/nicotine products.

III. BACKGROUND/IMPLICATIONS OF ACTION

A. Board Action and Other History

BCC/BoH: The Community Health Improvement Plan (CHIP, 2016-2019) was adopted via BO 16-08-16-01 and identifies tobacco use reduction as a major priority. The CHIP includes objectives and policies designed to support the reduction of tobacco/nicotine use and to restrict tobacco/nicotine-initiation by youth.

FDA: In March, the federal Food & Drug Administration (FDA) solicited comments regarding tobacco/nicotine products, as follows:

1. On March 16, the FDA invited comments, stating that “because tobacco- related harms ultimately result from addiction” to nicotine, it is considering taking action to reduce the level of nicotine in products to protect the public’s health. 2. On March 21, the FDA requested comments related to the “role that flavors play in tobacco products”, noting that flavors may attract youth to initiate tobacco product use, but may also assist adult smokers to “reduce cigarette use and switch to potentially less harmful products.” 3. On March 26, the FDA noted that “premium cigars” have been excluded from regulation, but that there is “no appropriate public health justification to exclude premium cigars from regulation” and solicited comments regarding the appropriate regulatory status of premium cigars.

B. Policy Issues

The attached proposed letters are all in keeping with the priorities identified in the CHIP and approved by the Board.

C. Board Goals

The issuance of the proposed comments and input support Priority 1 – the promotion of a Safe and Healthy County.

D. Financial and/or Resource Considerations

There are no financial implications of submitting these letters.

E. Health Implications

The negative health impact of tobacco/nicotine use remains the leading cause of preventable death in Lane County and represents significant costs, both financial and personal, to all county employers and residents. Nicotine is highly addictive and its use is most commonly initiated among youth, not adults. Lane County has a high rate of smoking particularly among people living in poverty, resulting in high costs both to the individuals who are addicted as well higher medical and social costs to the larger community.

F. Analysis

The attached letters set forth the basis for commenting in response to each of these FDA proposals and in support of the objectives identified in the CHIP. A brief summary of each follows:

Nicotine Levels – the level directly impacts the addictiveness of the products. That addiction is what results in the daily exposure to toxicants and carcinogens, which is in addition to the negative impact of the act of smoking and the impact of the nicotine itself, which is both a stimulant and a sedative that rapidly impacts the brain, after every inhalation.

Flavored Products – flavors can mask the harshness and taste of tobacco, increasing the appeal of these products, particularly to youth. In Lane County, the 2014 Retail Assessment revealed that 99% of retailers sold at least one type of flavored product and that 85% sold flavored little cigars or cigarillos. Among e- cigarette retailers, 70% offered a flavored option.

Premium Cigars – all cigar smoking is harmful, for the same reasons that cigarette smoking is harmful. However, cigar smoking produces more secondhand smoke and cigars contain higher levels of some toxicants than do cigarettes.

G. Alternatives/Options

1. To approve submission of the attached letters regarding nicotine levels in cigarettes, flavored tobacco/nicotine products, and the regulation of premium cigars to the U.S. Food and Drug Administration via the online portal and to delegate authority to the BCC Chair to sign the letters.

2. To request revisions to one or more of the attached letters, approve submission of the letters regarding nicotine levels in cigarettes, flavored tobacco/nicotine products, and the regulation of premium cigars to the U.S. Food and Drug Administration via the online portal , and to delegate authority to the BCC Chair to sign the letters.

3. To approve submission of some of the letters and to delegate authority to the BCC chair to sign the approved letters.

4. To decline to submit comments and input at this time.

IV. RECOMMENDATION

To approve number 1, above.

V. TIMING/IMPLEMENTATION

Commentary may be uploaded electronically, if approved. The deadline for Comment submissions is June 14, 2018.

VI. FOLLOW-UP

H&HS will work with CAO staff to have the letters, with any requested revisions, signed by the BCC Chair and submitted in a timely manner.

VII. ATTACHMENT

Board Order Letter - nicotine levels in cigarettes Letter - flavored products Letter – regulatory status of premium cigars FDA-2017-N-6189-001 FDA-2017-N-6565-001 FDA-2017-N-6107-001

BEFORE THE BOARD OF COMMISSIONERS OF LANE COUNTY, OREGON SITTING AS THE LANE COUNTY BOARD OF HEALTH

ORDER NO: 16-05-24-XX IN THE MATTER OF APPROVING SUBMISSION OF COMMENTS AND INPUT TO THE U.S. FOOD AND DRUG ADMINISTRATION FOR CONSIDERATION IN CONJUNCTION WITH PROPOSED RULEMAKING REGARDING NICOTINE LEVELS IN CIGARETTES, FLAVORED TOBACCO PRODUCTS AND THE REGULATION OF PREMIUM CIGARS

WHEREAS, the Board of County Commissioners of Lane County has a stated interest in promoting the public’s health and in countering the negative impact of tobacco/nicotine on County residents; and

WHEREAS, the Board supports the objectives of the current Community Health Improvement Plan, which support submitting these comments;

NOW, THEREFORE, the Board of County Commissioners of Lane County ORDERS as follows:

1. That the Chair of the Board be delegated authority to sign the attached letter to the U.S. Food and Drug Administration regarding nicotine levels in cigarettes and Health & Human Services be authorized to submit the letter via the online portal; and 2. That the Chair of the Board be delegated authority to sign the attached letter to the U.S. Food and Drug Administration regarding flavored tobacco/nicotine products and Health & Human Services be authorized to submit the letter via the online portal; and 3. That the Chair of the Board be delegated authority to sign the attached letter to the U.S. Food and Drug Administration regarding the regulation of premium cigars and Health & Human Services be authorized to submit the letter via the online portal.

ADOPTED this ______day of June, 2018

Jay Bozievich, Chair APPROVED AS TO FORM Lane County Board of Commissioners Date

LANE COUNTY OFFICE OF LEGAL COUNSEL

June 5, 2018

Division of Dockets Management HFA-305 Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 Submitted electronically via the Federal eRulemaking Portal

RE: Docket No. FDA-2017-N-6189 Tobacco Product Standard for Nicotine Level of Certain Tobacco Products RIN 0910-AH86

To Whom It May Concern,

The Undersigned, acting as the Chair of and commenting on behalf of, the Lane County Board of Commissioners, sitting as the Lane County Board of Health, is pleased to submit the following comments in response to the FDA advance notice of proposed rulemaking regarding setting a maximum level of nicotine in cigarettes. We support the FDA in setting a maximum nicotine level that covers all combustible tobacco products such as: cigarettes, all cigars, so called “heat-not-burn” products, waterpipe tobacco, roll-your-own tobacco, and pipe tobacco. This should also include emerging products like heated cigarettes.

According to Apelberg, et al. (2018), if this policy is put in place by 2020, about 5 million additional adult smokers would quit smoking within just one year after implementation; and by the year 2100, only about 1.4 percent of the U.S. adult population would smoke in part because it would prevent more than 33 million people from becoming regular smokers, more than 134 million years of life would be gained among the U.S. population, and more than 8 million premature deaths from tobacco would be prevented. Given the millions of lives at stake, we urge the FDA to finalize this regulation as soon as possible.

Background

Lane County’s first priority in our Strategic Plan is to ensure a safe and healthy county, and a priority of our Community Health Improvement Plan (CHIP) is to address the main drivers of youth tobacco use. Lane County, with a population (362,895) that accounts for ten percent (10%) of the state’s population and a large, diverse geography that extends from the Cascade Mountains to the Pacific Ocean, faces many challenges and localized disparities in its efforts to protect the public’s health. For instance, the Cities of Florence and Oakridge, rural areas of the county, have much higher tobacco use rates (32% and 26%, respectively, compared to 19% in Eugene), including during pregnancy (30% and 31%, respectively, compared to 12% in Eugene), and subsequently carry a higher burden of tobacco-related diseases and deaths. The Lane County Board of Commissioners and Board of Health, as part of CHIP implementation, took a lead role in the state to prevent tobacco use among our youth by making Lane County the first county in Oregon to pass tobacco retail licensing (including no free samples, no self-service displays, no mobile vending, no new retailers within 1,000 feet of public schools, and posting of a health warning and Quit Line number in retailers) and increasing the minimum legal sales age of tobacco from 18 to 21 years of age.

Importance of Tobacco Prevention

• Tobacco use is the leading preventable cause of disease, disability, and death in Lane County, the cause of 1 in 4 deaths, killing over 700 people each year (2 per day) and costing Lane County nearly $260 million a year in medical costs and lost productivity due to early death. This burden of tobacco use costs Lane County about $1800 a year per household. • Over time, in Oregon, cigarette smoking prevalence has decreased by 22 percent among adults, 64 percent among 11th grade students, and 80 percent among 8th grade students. • However, since the introduction of e-cigarettes in Lane County, the percentage of youth smoking and using other tobacco products has increased.

Lane County supports:

• Reducing nicotine in cigarettes and other combustible tobacco products to non-addictive levels and implementing a standard for noncombustible products that lowers nicotine to non-addictive levels. o Tobacco-related harms ultimately result from addiction to the nicotine in the products, causing frequent, repetitive exposure to toxicants and carcinogens. Every day more youth are becoming addicted to tobacco products and acquiring a lifelong struggle with addiction that ends in death for most. Immediately reducing the nicotine in combustible tobacco products to non-addictive levels would prevent youth from becoming addicted and save millions of lives. o In Lane County, since the introduction of e-cigarettes, the percentage of youth smoking and using other tobacco products has increased. See Chart 1 below. From 2013 to 2017, youth use of all tobacco products (e-cigarettes, smokeless tobacco, all cigars, nonmenthol cigarettes), except hookah, has increased. At this rate, we would expect an increase in the percent of youth who become addicted to nicotine, and eventually, die from tobacco-related deaths. o The 2014 Lane County Retail Assessment and the Oregon State Police Inspections revealed that combustible tobacco products can be sweet (flavored), cheap, and easy to obtain for youth. In Lane County, 91% of tobacco retailers sell single little cigars or cigarillos. The average price for a single, flavored little cigar or cigarillo varied from $1.05 countywide to $0.69 in the rural City of Florence, making these products more accessible to youth in the rural area and contributing to the rural tobacco health inequities. It is also important to note that 77 percent of tobacco retailers in Lane County accept SNAP (i.e. food stamps, EBT), which means they are serving vulnerable populations. When these populations enter a tobacco retailer to purchase food, they are being subjected to tobacco advertising, which results in an increase in impulse purchases. When combustible tobacco products contain highly addictive levels of nicotine, all of these factors – flavors, cheap prices, easy access, and exposure – together, make youth more likely to initiate tobacco use and become addicted.

Current Tobacco Use Among 11th Graders in Lane County, 2013, 2017 25% 19.5 20% 17.2 18.0 14.9 15% 13.6 10.1 9.9 8.7 10% 7.4 6.5 7.1 6.4 5% 3.9 3.8

0% Any Tobacco Non-Cigarette Electronic Smokeless Large cigar, Cigarettes Hookah Product Use Tobacco nicotine tobacco little cigar or (non-menthol) tobacco Products delivery device (males) cigarillo

Note: 64.2% of 11th graders who used tobacco used 2013 flavored tobacco or vaping products 2017 Source: Oregon Healthy Teens Surveys, 2013 and 2017.

Chart 1. Use of tobacco products, especially non-cigarette products, increasing among 11th graders in Lane County.

o To be the most protective of public health, especially vulnerable populations, we urge the FDA to establish a maximum nicotine standard that is non-addictive. The existing evidence base strongly supports FDA action to reduce nicotine in combustible products. A product standard that maintains some addiction level, even minimally, will continue to contribute to the addiction of youth and the inequitable burden on vulnerable populations, and ultimately, not achieve the maximum benefit to public health. To be the most protective of public health, the FDA should quickly implement a standard to reduce nicotine to non-addictive levels in all combustible tobacco products, not just cigarettes, to prevent switching to other harmful products; and implement a standard for noncombustible tobacco products that gradually lowers nicotine to non-addictive levels. o It is important that the FDA not depend entirely on this proposal alone to reduce tobacco-related death and disease. According to the research, in addition to reducing nicotine in combustible tobacco products, the FDA should take other effective actions, such as considering requiring large, graphic health warnings covering at least half of cigarette packs; prohibiting menthol and other characterizing flavors in cigarettes and all other tobacco products; and supporting the development of innovative new products to help more smokers quit.

Conclusion

Lane County thanks the FDA for accepting and considering our comments to consider reducing nicotine to non-addictive levels in all combustible tobacco products. There is scientific evidence that limiting nicotine in cigarettes to minimally or non-addictive levels can help more smokers quit and prevent children from becoming addicted. Research shows that reducing nicotine content in cigarettes is technologically feasible and can be done without unintended consequences, such as causing smokers to compensate by smoking more cigarettes. Based on evidence from research and the field, we expect that reducing nicotine to non-addictive levels in all combustible tobacco products would lead to significant reductions in youth addiction and use of tobacco, a significant increase in addicted adults quitting tobacco, and a decrease in the number of people exposed to secondhand smoke. June 5, 2018

Division of Dockets Management HFA-305 Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 Submitted electronically via the Federal eRulemaking Portal

RE: Docket No. FDA-2017-N-6565 Regulation of Flavors in Tobacco Products RIN 0910-AH60

To Whom It May Concern,

The Undersigned, acting as the Chair of and commenting on behalf of, the Lane County Board of Commissioners, sitting as the Lane County Board of Health, is pleased to submit the following comments in response to the FDA advance notice of proposed rulemaking regarding the regulation of flavors in tobacco products and the initiation and pattern of tobacco product use, particularly among youth and young adults. We support the FDA in prohibiting menthol as a characterizing flavor and all other characterizing flavors in all tobacco products.

The Lane County Board of Commissioners and Board of Health, as part of CHIP implementation, took a lead role in the state to prevent tobacco use among our youth by making Lane County the first county in Oregon to pass tobacco retail licensing (including no free samples, no self-service displays, no mobile vending, no new retailers within 1,000 feet of public schools, and posting of a health warning and Quit Line number in retailers) and increasing the minimum legal sales age of tobacco from 18 to 21 years of age.

Importance of Tobacco Control

• Tobacco use is the leading preventable cause of disease, disability, and death in Lane County, the cause of 1 in 4 deaths, killing over 700 people each year (2 per day) and costing Lane County nearly $260 million a year in medical costs and lost productivity due to early death. This burden of tobacco use costs Lane County about $1800 a year per household. • Over time, in Oregon, cigarette smoking prevalence has decreased by 22 percent among adults, 64 percent among 11th grade students, and 80 percent among 8th grade students. • However, Lane County youth have increased their use of other tobacco products that tend to be flavored, such as cigars, cigarillos, smokeless tobacco, and e-cigarettes, threatening to offset declines in cigarette use.

Lane County supports:

• Prohibiting Flavored Tobacco Products o The federal policy prohibiting characterizing flavors in cigarettes should include menthol and be extended to all tobacco products. . Flavored nicotine products are a gateway to lifelong nicotine addiction. Flavors can mask the natural harshness and taste of tobacco, making flavored tobacco products easier to use and increasing their appeal among youth. The combination of nicotine and flavoring targets young people and should not be permitted. . Electronic cigarettes and cigarillos come in a wide variety of flavors, such peach, grape, pineapple, skittle, cracker jack, yummy gummy, scout cookie, juicy fruit, koolaid, tootsie pop, marshmallow, fruity pebble, bazooka, scooby snax, carnival cotton candy, and strawberry cupcake, all of which are found in retailers in Lane County. . The 2014 Lane County Retail Assessment revealed that 99 percent of retailers sold at least one type of flavored tobacco product, including menthol cigarettes, and 85 percent sold flavored little cigars or cigarillos. Of the retailers that sold e- cigarettes, 70 percent offered a flavored option. Of the retailers that sold smokeless tobacco, 76 percent offered a flavored option. A majority (61%) of tobacco retailers displayed products or advertising, including flavored products, in a way that appeals to children (near youth products or at a child’s eye level). See Photos 1-4 below for examples. The average price for a single, flavored little cigar or cigarillo varied from $1.05 countywide to $0.69 in the rural City of Florence, making these flavored products more accessible to youth in the rural area and contributing to the rural tobacco health inequities. It is also important to note that 77 percent of tobacco retailers in Lane County accept SNAP (i.e. food stamps, EBT), which means they are serving vulnerable populations. When these populations enter a tobacco retailer, nearly all of which sell flavored tobacco, to purchase food, they are being subjected to tobacco advertising. . The Oregon Healthy Teens survey reveals that youth smoking has decreased over time, while youth use of other tobacco products that tend to be flavored has increased. In 2017, 7 percent of Lane County 11th grade students smoked nonmenthol cigarettes, compared to 18 percent who used non-cigarette tobacco products. Among the 8th and 11th graders who used tobacco, a majority, (71 percent and 64 percent, respectively), used flavored tobacco or vaping products. In Lane County, from 2013 to 2017, there was a 450 percent increase in the percent of 11th grade students who used e-cigarettes. See Chart 1 below. Current Tobacco Use Among 11th Graders in Lane County, 2013, 2017 25% 19.5 20% 17.2 18.0 14.9 15% 13.6 10.1 9.9 8.7 10% 7.4 6.5 7.1 6.4 5% 3.9 3.8

0% Any Tobacco Non-Cigarette Electronic Smokeless Large cigar, Cigarettes Hookah Product Use Tobacco nicotine tobacco little cigar or (non-menthol) tobacco Products delivery (males) cigarillo device

Note: 64.2% of 11th graders who used tobacco used 2013 flavored tobacco or vaping products 2017 Source: Oregon Healthy Teens Surveys, 2013 and 2017.

Chart 1. Use of tobacco products, especially non-cigarette products, increasing among 11th graders in Lane County.

Photo 1. Flavored e-cigarettes, vape pens, and flavored e-liquid is placed next to candy on the counter in a Lane County retailer in the eye level of three to four year old children. Photo 2. Flavored smokeless tobacco (chew) ad placed Photo 3. Ad for cigarettes that can be squeezed to at the eye level of three to four year old children release menthol flavoring placed at the eye level of outside a retailer in Lane County. This is a very three to four year old children outside a retailer in Lane common practice. County. This is a very common practice.

Photo 4. Flavored smokeless tobacco (snus) ad placed next to candy on the counter at the eye level of three to four year

old children in a Lane

County retailer.

o The evidence on the public health impact of menthol in cigarettes is clear. The Tobacco Products Scientific Advisory Committee and the FDA’s own scientists have already concluded that the removal of menthol would benefit public health. The agency has already issued an ANPRM on this topic. There is an abundance of scientific evidence and every additional delay means lives lost. The FDA needs to act on menthol now. o If the FDA moves forward with a comprehensive nicotine standard while prohibiting flavors, there is no need to exempt any flavor or any class of products with a goal of incentivizing adult smokers to switch to less harmful products; the nicotine standard for combustible products creates a much greater incentive for smokers to stop using combustible products.

Community Support for Prohibiting Flavored Tobacco Products

Members of community coalitions in Lane County have expressed a strong desire to prohibit flavored tobacco products. For example, the Community Health Improvement Plan (CHIP) Tobacco Workgroup, whose purpose is to develop and implement a plan to reach the CHIP objective created to prevent and reduce tobacco use in Lane County, includes members from a variety of community partner agencies, such as PeaceHealth Hospitals, United Way of Lane County, Trillium Community Health Plan, and University of Oregon. CHIP Tobacco Workgroup members have proposed and recommended prohibiting flavored tobacco products multiple times, which is documented in the monthly meeting minutes.

The Lane County Tobacco Prevention & Education Program has had an increase of reports from local parents, educators, law enforcement, and youth about an increase of youth using the novel, popular flavored JUUL vaping devices at school and inside classrooms. JUUL devices are slim, high-tech devices, that look like flash drives, are charged through USB ports, and use nicotine cartridges, or ‘pods’, that come in a variety of flavors. Because of the novel product design that uses organic nicotine salts extracted from tobacco leaves, PAX Labs claims JUUL provides a nicotine concentration comparable to a traditional cigarette and delivers nicotine 1.25 to 2.7 times faster than other e-cigarettes. From the national data and local evidence, there has been a tremendous increase in the number of youth using the JUUL vaping devices. This is of special concern because they are flavored and always contain nicotine comparable to cigarettes.

School district leaders and youth from the City of Cottage Grove have mentioned how flavors are the main reason for youth use of tobacco and vaping products. The following video displays the testimony from a high school principal and one such youth: https://www.youtube.com/watch?v=Y7LA59Aw1Yc. See below for quotes from the video.

“If…the cigarette companies or the vape companies didn’t have the flavors, I don’t think kids would do them because cigarettes obviously taste pretty bad. And so I think just the flavors that they make promote it more for the younger audience.” – Tristan, Cottage Grove High School Senior, 2014

“Kids want stuff that tastes good, and it makes them feel good, so if it tastes good and it makes them feel good, it’s a lot easier for them to go back for more, and…then they get hooked because there’s that chemical dependency.” – Iton Udosenata, Cottage Grove High School Principal, 2014 The City of Cottage Grove Police Chief also talked about how flavors affect youth in his community and makes his job harder. Please see his video testimony at the following website and see a quote from the video below: https://www.youtube.com/watch?v=MQOs2rYy5qA.

“…children need the most protection. Flavored tobacco products are just an enticement for these kids and younger people to try them. It’s a selling point for them. It’s not going to be the same as smoking a cigarette. They’ll be smoking something and it’ll taste like a banana, for instance, or something like that, so it won’t be the harsh flavor, and they’ll enjoy it more. The tobacco industry can really make my job a little more difficult. They think it’s acceptable, and they’re just trying to reach these young, impressionable kids. That’s what they’re going to try to do – get them hooked on a habit that going to cost them a lot of money.” – Michael Grover, City of Cottage Grove Police Chief, 2015

Young children were shown products, which they didn’t know were tobacco, from a nearby store, and their reactions were recorded. The following Smokefree Oregon video reveals how young children are attracted to flavored tobacco products: https://www.youtube.com/watch?v=KRPhlAr50Hw.

More Youth Use Flavored Tobacco than Adults

A study of the Wave 1 data from the Population Assessment of Tobacco and Health (PATH) Study, collected in 2013 to 2014 revealed that current use of flavored tobacco, including menthol, was highest among youth (80% among ages 12-17 years) and young adults (73% among ages 18-24); while the lowest use of flavored tobacco was among older adults (29% among ages ≥65 years). Additionally, 81 percent of youth and 86 percent of young adults who had ever used tobacco reported that their first product was flavored, versus 54 percent of adults aged ≥25 years. Using a flavored tobacco product at first use makes youth and adults more likely to be a current tobacco user (Villanti et al, American Journal of Preventive Medicine, August 2017).

E-liquid Flavors Are Toxic

The use of flavored tobacco products is not safe for consumption. A new study published in the journal Frontiers in Physiology found that exposure to e-cigarette flavoring chemicals and liquids can cause a significant increase in inflammation to monocytes, which is a type of white blood cell active in the immune system. Many flavoring compounds are also toxic, with cinnamon, vanilla, and buttery flavors among the worst, and mixing e-liquid flavors causes the most toxicity to white blood cells (Muthumalage et al, Frontier Physiology, 11 January 2018).

Users of Flavored Tobacco Products are Less Likely to Quit

Flavored tobacco increases the likelihood that someone will continue using tobacco and decreases their likelihood of quitting. Research has shown that if someone first uses a flavored tobacco product, they are more likely to currently be a tobacco-user and to use multiple tobacco products. Users of only flavored non-cigarette tobacco products were less likely to report trying to quit using tobacco. Younger adults and Black, non-Hispanic adults were more likely to start using tobacco through flavored products and to currently be a tobacco user (Smith et al, Tobacco Control, 5 October 2016). This reveals a health inequity component to flavored tobacco.

Conclusion

Lane County thanks the FDA for accepting and considering our comments to consider further regulating flavors in tobacco products. Based on evidence from research and the field, we expect that including menthol in the prohibition of characterizing flavors in cigarettes and extending the prohibition to all tobacco products, including e-cigarettes, would lead to significant reductions in youth initiation of all tobacco product use, significant cessation by adult tobacco users, and would have an especially beneficial effect on vulnerable populations with high rates of tobacco use, especially menthol and other flavored products.

June 5, 2018

Division of Dockets Management HFA-305 Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 Submitted electronically via the Federal eRulemaking Portal

RE: Docket No. FDA-2017-N-6107 Regulation of Premium Cigars RIN 0910-AH88

To Whom It May Concern,

Importance of Tobacco Control

Lane County supports:

• Including all cigars, including premium cigars, in FDA regulation. o In 2016, the FDA issued the final deeming regulation and determined that the agency would regulate all cigars, including premium cigars. In that rule, the FDA concluded the following: “(1) All cigars pose serious negative health risks, (2) the available evidence does not provide a basis for FDA to conclude that the patterns of premium cigar use sufficiently reduce the health risks to warrant the exclusion, and (3) premium cigars are used by youth and young adults.” Because those findings remain accurate, the agency must continue to regulate premium cigars in a manner that is consistent with the evidence and best protects public health. o In 2014, Lane County Health & Human Services submitted comments in response to the FDA’s proposed rule to Deeming Tobacco Products to be Subject to the Federal Food, Drug, and cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products (Docket No. FDA-2014-N-0189, RIN 0910- AG38). Lane County’s comments remain the same and as follows on whether premium cigars should be regulated and if they should be regulated the same as other cigars. . All cigar smoking harms health. According to the National Cancer Institute and the U.S. Surgeon General, cigar smoking causes cancer, heart disease and chronic obstructive pulmonary disease (COPD). . Cigar smoke, like cigarette smoke, contains toxic and cancer causing chemicals that are harmful to both smokers and nonsmokers. In fact, cigars produce even more secondhand smoke than cigarettes and can contain higher levels of some toxins than cigarettes. . Lane County supports Option 1 of the proposal to bring all cigars, including premium, under the FDA’s authority. o Cigar smoking is not limited to adults. The 2016 National Youth Tobacco Survey found that high school boys now smoke cigars (i.e., large cigars, cigarillos and small cigars) at a slightly higher rate than cigarettes (9.9 percent to 9.1 percent). In Lane County, the 2017 Oregon Health Teens Survey revealed that cigar use is increasing among youth. More 11th graders (10%) used large cigars, little cigars or cigarillos than smoked nonmenthol cigarettes (7%) or hookah tobacco (4%), and about the same percent of males used smokeless tobacco (10%) as all 11th graders who smoked cigars. See Chart 1 below. In addition, cigars are sold in hundreds of flavors, including sweet flavors that appeal to kids. Research has found that flavors play a key role in youth use of tobacco products, including cigars. We urge the FDA to strengthening its rules, including prohibiting the sale of all flavored tobacco products, instead of weakening them. o The 2014 Lane County Retail Assessment and the Oregon State Police Inspections revealed that 91% of tobacco retailers sell single little cigars or cigarillos. The average price for a single, flavored little cigar or cigarillo varied from $1.05 countywide to $0.69 in the rural City of Florence, making these products more accessible to youth in the rural area and contributing to the rural tobacco health inequities. o It is important to note that the appeal of smoking cigars among a younger demographic is the result of marketing strategies aimed at youth by the tobacco industry. Research indicates that different brands of cigars are attractive to users with specific characteristics. For example the Black and Mild cigar is a brand that is preferred by urban minority youth. Another factor that contributes to the use of this particular brand is affordability. Black and Mild cigars are often sold individually and are priced well below one dollar (Soldz et al, Tobacco Control, 2003). The FDA needs to consider how tobacco companies are engaging in deliberate marketing to segments of the illegal youth market for cigars.

Current Tobacco Use Among 11th Graders in Lane County, 2013, 2017 25% 19.5 20% 17.2 18.0 14.9 15% 13.6 10.1 9.9 8.7 10% 7.4 6.5 7.1 6.4 5% 3.9 3.8

0% Any Tobacco Non-Cigarette Electronic Smokeless Large cigar, Cigarettes Hookah Product Use Tobacco nicotine tobacco little cigar or (non-menthol) tobacco Products delivery device (males) cigarillo

Note: 64.2% of 11th graders who used tobacco used 2013 flavored tobacco or vaping products 2017 Source: Oregon Healthy Teens Surveys, 2013 and 2017.

Chart 1. Use of tobacco products, including large cigars, little cigars and cigarillos, increasing among 11th graders in Lane County.

Conclusion

Lane County thanks the FDA for accepting and considering our comments to not exempt premium cigars from FDA regulation. In the FDA’s 2016 final deeming rules, the FDA already concluded that all cigars are harmful, used by youth and young adults, and the evidence does not provide a basis for the exclusion of premium cigars. We urge the FDA to uphold these previous conclusions and not exempt premium cigars from FDA regulation. 11818 Federal Register / Vol. 83, No. 52 / Friday, March 16, 2018 / Proposed Rules

DEPARTMENT OF HEALTH AND ADDRESSES: You may submit comments manner (see ADDRESSES), will be placed HUMAN SERVICES as follows. Please note that late, in the docket and, except for those untimely filed comments will not be submitted as ‘‘Confidential Food and Drug Administration considered. Electronic comments must Submissions,’’ publicly viewable at be submitted on or before June 14, 2018. https://www.regulations.gov or at the 21 CFR Part 1130 The https://www.regulations.gov Dockets Management Staff between 9 [Docket No. FDA–2017–N–6189] electronic filing system will accept a.m. and 4 p.m., Monday through comments until midnight Eastern Time Friday. RIN 0910–AH86 at the end of June 14, 2018. Comments • Confidential Submissions—To received by mail/hand delivery/courier submit a comment with confidential Tobacco Product Standard for Nicotine (for written/paper submissions) will be information that you do not wish to be Level of Combusted Cigarettes considered timely if they are made publicly available, submit your AGENCY: Food and Drug Administration, postmarked or the delivery service comments only as a written/paper HHS. acceptance receipt is on or before that submission. You should submit two copies total. One copy will include the ACTION: Advance notice of proposed date. rulemaking. information you claim to be confidential Electronic Submissions with a heading or cover note that states SUMMARY: The Food and Drug Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS Administration (FDA) is issuing this following way: CONFIDENTIAL INFORMATION.’’ The advance notice of proposed rulemaking • Federal eRulemaking Portal: Agency will review this copy, including (ANPRM) to obtain information for https://www.regulations.gov. Follow the the claimed confidential information, in consideration in developing a tobacco instructions for submitting comments. its consideration of comments. The product standard to set the maximum Comments submitted electronically, second copy, which will have the nicotine level for cigarettes. Because including attachments, to https:// claimed confidential information tobacco-related harms ultimately result www.regulations.gov will be posted to redacted/blacked out, will be available from addiction to the nicotine in such the docket unchanged. Because your for public viewing and posted on products, causing repeated use and comment will be made public, you are https://www.regulations.gov. Submit exposure to toxicants, FDA is solely responsible for ensuring that your both copies to the Dockets Management considering taking this action to reduce comment does not include any Staff. If you do not wish your name and the level of nicotine in these products confidential information that you or a contact information to be made publicly so they are minimally addictive or third party may not wish to be posted, available, you can provide this nonaddictive, using the best available such as medical information, your or information on the cover sheet and not science to determine a level that is anyone else’s Social Security number, or in the body of your comments and you appropriate for the protection of the confidential business information, such must identify this information as public health. FDA is using the term as a manufacturing process. Please note ‘‘confidential.’’ Any information marked ‘‘nonaddictive’’ in this document that if you include your name, contact as ‘‘confidential’’ will not be disclosed specifically in the context of a information, or other information that except in accordance with 21 CFR 10.20 potentially nonaddictive cigarette. We identifies you in the body of your and other applicable disclosure law. For acknowledge the highly addictive comments, that information will be more information about FDA’s posting potential of nicotine itself depending posted on https://www.regulations.gov. of comments to public dockets, see 80 • upon the route of delivery. As discussed If you want to submit a comment FR 56469, September 18, 2015, or access elsewhere in this document, questions with confidential information that you the information at: https://www.gpo.gov/ remain with respect to the precise level do not wish to be made available to the fdsys/pkg/FR-2015-09-18/pdf/2015- of nicotine in cigarettes that might public, submit the comment as a 23389.pdf. render them either minimally addictive written/paper submission and in the Docket: For access to the docket to or nonaddictive for specific members or manner detailed (see ‘‘Written/Paper read background documents or the segments of the population. We Submissions’’ and ‘‘Instructions’’). electronic and written/paper comments received, go to https:// envision the potential circumstance Written/Paper Submissions where nicotine levels in cigarettes do www.regulations.gov and insert the not spur or sustain addiction for some Submit written/paper submissions as docket number, found in brackets in the portion of potential smokers. This could follows: heading of this document, into the • Mail/Hand delivery/Courier (for give addicted users the choice and ‘‘Search’’ box and follow the prompts written/paper submissions): Dockets ability to quit more easily, and it could and/or go to the Dockets Management Management Staff (HFA–305), Food and help to prevent experimenters (mainly Staff, 5630 Fishers Lane, Rm. 1061, Drug Administration, 5630 Fishers youth) from initiating regular use and Rockville, MD 20852. Lane, Rm. 1061, Rockville, MD 20852. becoming regular smokers. The scope of • FOR FURTHER INFORMATION CONTACT: For written/paper comments Gerie Voss, Center for Tobacco products covered by any potential submitted to the Dockets Management product standard will be one issue for Products, Food and Drug Staff, FDA will post your comment, as Administration, 10903 New Hampshire comment in the ANPRM. Any well as any attachments, except for additional scientific data and research Ave., Silver Spring, MD 20993, 1–877– information submitted, marked and CTP–1373, [email protected]. relevant to the empirical basis for identified, as confidential, if submitted SUPPLEMENTARY INFORMATION: regulatory decisions related to a as detailed in ‘‘Instructions.’’ nicotine tobacco product standard is Instructions: All submissions received Table of Contents another issue for comment in the must include the Docket No. FDA– ANPRM. I. Executive Summary 2017–N–6189 for ‘‘Tobacco Product A. Purpose of the ANPRM DATES: Submit either electronic or Standard for Nicotine Level of Certain B. Summary of the Major Issues Raised in written comments on the ANPRM by Tobacco Products.’’ Received the ANPRM June 14, 2018. comments, those filed in a timely II. Background

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A. Purpose minimally addictive or nonaddictive central nervous system effects B. Legal Authority (however that were achieved) could contributing to addiction may be lower’’ III. Health Consequences of Combusted help current users quit and prevent (Ref. 2). The study authors concluded Tobacco Products future users from becoming addicted that ‘‘[p]reventing children from A. Nicotine in Combusted Tobacco Products and Its Impact on Users and escalating to regular use. becom[ing] addicted smokers and giving people greater freedom to stop smoking B. Negative Health Effects of Combusted B. Summary of the Major Issues Raised when they decide to quit by reducing Tobacco Product Use in the ANPRM IV. Requests for Comments and Information the addictiveness of cigarettes is a A. Scope In this ANPRM, FDA is seeking policy that increasingly appears to be B. Maximum Nicotine Level information on a variety of issues feasible and warranted’’ (id.). We C. Implementation (Single Target vs. regarding the development of a tobacco specifically request comment regarding Stepped-Down Approach) product standard that would limit the this paper’s conclusions and the D. Analytical Testing Method amount of nicotine in cigarettes. E. Technical Achievability possible impact of higher or lower F. Possible Countervailing Effects Specifically, FDA is seeking your maximum nicotine levels in a potential G. Other Considerations comments, evidence, and other nicotine tobacco product standard. If V. Potential Public Health Benefits of information supporting your responses FDA were to pursue a nicotine tobacco Preventing Initiation to Regular Use and to questions on the following topics: product standard, it would be important • Increasing Cessation Scope—Cigarettes are the tobacco for FDA to consider what maximum A. Smoking Cessation Would Lead to product category that causes the greatest nicotine level for such standard would Substantial Public Health Benefits for burden of harm to public health given be appropriate, how this maximum People of All Ages the prevalence of cigarette use, nicotine level should be measured (e.g., B. A Nicotine Tobacco Product Standard including among youth, and the toxicity nicotine yield, nicotine in tobacco filler, Could Lead to Substantial Improvement and addictiveness of these products and in Public Health something else), and how the threshold VI. References the resulting tobacco-related disease and of nicotine addiction should be death across the population, including measured, using the best available I. Executive Summary among non-users. If FDA were to science to determine a level that is A. Purpose of the ANPRM establish a nicotine tobacco product appropriate for the protection of the standard that covered only cigarettes, public health. FDA seeks comment on a Tobacco use causes a tremendous toll some number of addicted smokers could potential maximum nicotine level that of death and disease every year, and migrate to other similar combusted would be appropriate for the protection these effects are ultimately the result of tobacco products to maintain their of the public health, in light of scientific addiction to the nicotine in combustible nicotine dose (or engage in dual use evidence about the addictive properties cigarettes which causes repeated use of with other combusted tobacco of nicotine in cigarettes. FDA is such products, thus repeatedly exposing products), potentially reducing the particularly interested in comments users and non-users to toxicants. This positive public health impact of such a about the merits of nicotine levels like nicotine addiction causes users to rule. Because the scope would impact 0.3, 0.4, and 0.5 mg nicotine/g of engage in compulsive tobacco use, the potential public health benefits of a tobacco filler, as well as other levels of makes quitting less likely, and, thus, nicotine tobacco product standard, FDA nicotine. FDA is also requesting any repeatedly exposes them to thousands of is seeking comment on whether the information on additional scientific data toxicants in combusted tobacco standard should cover any or all of the and research which would provide products. This is especially true with following products: Combusted information about specific groups respect to cigarette smoking. Through cigarettes (which FDA has previously within the general population which this ANPRM, FDA indicates that it is interpreted to include kreteks and may have an increased sensitivity to considering the issuance of a product bidis), cigarette tobacco, roll-your-own nicotine’s reinforcing effects, or who standard to set a maximum nicotine (RYO) tobacco, some or all cigars, pipe may have otherwise not been captured level in cigarettes so that they are tobacco, and waterpipe tobacco. FDA in the literature on VLNC cigarettes. In minimally addictive or nonaddictive, intends that any nicotine tobacco addition, FDA is considering and using the best available science to product standard would cover all requesting information on additional determine a level that is appropriate for brands in a particular product category scientific data and research relevant to the protection of the public health. The and, therefore, those products currently the empirical basis for regulatory Agency seeks information and comment on the market and any new tobacco decisions related to a potential nicotine on a number of issues associated with products would be expected to adhere product standard. such a potential product standard. to the standard. • Implementation—If FDA were to Greatly reducing or eliminating the • Maximum Nicotine Level—FDA has issue a product standard establishing a addictiveness of cigarettes would have considered the existing peer-reviewed maximum nicotine level for cigarettes, significant benefits for youth, young studies regarding very low nicotine such a standard could propose either a adults, and adults. More than half of content (VLNC) cigarettes and the likely single target (where the nicotine is adult cigarette smokers make a serious effects of reducing nicotine in reduced all at once) or a stepped-down quit attempt each year (quit for at least combusted tobacco products (i.e., approach (where the nicotine is reduced a day), many of whom do not succeed cigarettes, cigars, pipe tobacco, roll- gradually over time through a sequence due to the addictive nature of these your-own tobacco, and waterpipe of incremental levels and products (Ref. 1). The establishment of tobacco). A 2013 survey paper noted implementation dates) to reach the a maximum nicotine level in cigarettes that researchers initially estimated that desired maximum nicotine level. not only could increase the likelihood of reducing the total nicotine content of • Analytical Testing Method—As part successful quit attempts, but it also cigarettes to 0.5 milligrams (mg) per rod of its consideration regarding a potential could help prevent experimenters would minimize addictiveness and that nicotine tobacco product standard, FDA (mainly youth and young adults) from a ‘‘more recent analysis suggests that the is also considering whether such a initiating regular cigarette smoking. maximum allowable nicotine content product standard should specify a Therefore, rendering cigarettes per cigarette that minimizes the risk of method for manufacturers to use to

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detect the level of nicotine in their a nicotine tobacco product standard results, and other information regarding products. FDA believes that the results could turn to other combusted tobacco economic impacts of a potential of any test to measure the nicotine in products to maintain their nicotine nicotine tobacco product standard. such products should be comparable dependence, both in combination with Further, this ANPRM briefly describes across different accredited testing cigarettes (i.e., dual use) or in place of the potential public health benefits that facilities and products. It is critical that cigarettes (i.e., switching). Coverage of could result from the increased the results from the test method used other combusted tobacco products, as cessation from and decreased initiation demonstrate a high level of specificity, FDA is considering, is one way to to regular use of cigarettes that FDA accuracy, and precision in measuring a significantly limit this product expects could occur with a nicotine range of nicotine levels across a wide migration or transition to dual use with tobacco product standard. FDA variety of tobacco blends and products. other combusted tobacco products. references findings from a population- FDA is aware of a variety of methods Another possible countervailing effect based simulation model that projects the being developed that quantify nicotine is the potential for increased harm due potential public health impact of in tobacco or tobacco product filler for to continued VLNC smoking with enacting a regulation lowering nicotine various products. altered smoking behaviors (e.g., increase levels in cigarettes and certain other • Technical Achievability—If FDA in number of cigarettes smoked, combusted tobacco products to were to move forward in this area and increased depth of inhalation). Some minimally addictive levels, utilizing proceed to the next step of issuing a studies of VLNC cigarettes with nicotine inputs derived from empirical evidence proposed rule, section 907(b)(1) of the levels similar to what FDA may and expert opinion (eight subject matter Federal Food, Drug, and Cosmetic Act consider including in a nicotine tobacco experts provided quantitative estimates (the FD&C Act) (21 U.S.C. 387g(b)(1) product standard have not resulted in for the potential outcomes of the policy would require that FDA consider compensatory smoking and have on smoking cessation, initiation, information submitted in connection demonstrated reductions in cigarettes switching, and dual use rates). Based on with that proposed product standard smoked per day and in exposure to the experts’ determinations that the regarding technical achievability of harmful constituents (e.g., Ref. 3; Ref. 4; reduction in nicotine levels in compliance. FDA continues to analyze Ref. 5). combusted tobacco products would the technical achievability of a Another possible countervailing effect create substantial reductions in smoking maximum nicotine level for cigarettes as of setting a maximum nicotine level for prevalence due to increased smoking part of its broader assessment of how cigarettes could be users seeking to add cessation and reduced initiation of best to exercise its regulatory authority nicotine in liquid or other form to their regular smoking, the model calculates in this area. Significant nicotine combusted tobacco product. Therefore, that by the year 2100, more than 33 reductions in cigarettes and other FDA is considering whether any action million youth and young adults who combusted tobacco products can be it might take to reduce nicotine in would have otherwise initiated regular achieved principally through tobacco cigarettes should be paired with a smoking would not start as a result of blending and cross-breeding plants, provision that would prohibit the sale or a nicotine tobacco product standard. genetic engineering, and chemical distribution of any tobacco product The model also projected that extraction. Agricultural practices (e.g., designed for the purposes of approximately 5 million additional controlled growing conditions, supplementing the nicotine content of smokers would quit smoking 1 year after fertilization, and harvest) as well as the combusted tobacco product (or implementation of the product standard, more recent, novel techniques also can where the reasonably foreseeable use of compared to the baseline scenario, the product is for the purposes of help to reduce nicotine levels. FDA is which would increase to approximately supplementing the nicotine content). considering the feasibility of the current 13 million additional former smokers FDA is also considering other regulatory nicotine reduction techniques—for within 5 years after policy options to address this concern. cigarette and other combusted tobacco implementation. product manufacturers of all sizes—to FDA is also considering whether significantly reduce nicotine levels to illicit trade could occur as a result of a II. Background nicotine tobacco product standard and levels similar to those in existing VLNC A. Purpose cigarettes. FDA also is considering the how that could impact the marketplace. proper timeframe for implementation of In addition, FDA is considering how, if On July 28, 2017, FDA announced a a possible nicotine tobacco product FDA were to issue a nicotine tobacco comprehensive approach to the standard to allow adequate time for product standard that prompted an regulation of nicotine that includes the industry to comply. In addition, FDA is increase in the illicit market, Agency’s plan to begin a public dialogue seeking data and information regarding comprehensive interventions could about lowering nicotine levels in the potential costs, including possible reduce the size of the illicit tobacco combustible cigarettes to minimally costs to farmers, to implement such a market through enforcement addictive or nonaddictive levels through standard. mechanisms and collaborations across achievable product standards, including • Possible Countervailing Effects— jurisdictions. the issuance of an ANPRM to seek input There may be possible countervailing • Other Considerations—FDA also on the potential public health benefits effects that could diminish the recognizes that, if FDA were to proceed and any possible adverse effects of population health benefits expected as a to the stage of proposing a rule in this lowering nicotine in cigarettes. Tobacco result of a nicotine tobacco product area, potential costs and benefits from a use causes a tremendous toll of death standard. As part of any subsequent possible nicotine tobacco product and disease every year, and these effects rulemaking, FDA would need to assess standard would be estimated and are ultimately the result of addiction to these effects in comparison to the considered in an accompanying the nicotine contained in combustible expected benefits, including among preliminary impact analysis, including cigarettes, leading to repeated exposure population subgroups. One possible the potential impacts on growers of to toxicants from such cigarettes. This countervailing effect is continued tobacco and current users of potentially nicotine addiction causes users to combusted tobacco product use. Current regulated products. Thus, FDA is also engage in compulsive use, makes smokers of tobacco products subject to seeking comments, data, research quitting less likely and, therefore,

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repeatedly exposes them (and others) to 2014, the Surgeon General estimated (Ref. 15). FDA expects that making thousands of toxicants in combusted that, unless this trajectory is changed cigarettes minimally addictive or tobacco products. This is especially true dramatically, 5.6 million youth aged 0 nonaddictive (however that were with respect to cigarette smoking. to 17 years alive today will die achieved) may have significant benefits Researchers have found that the prematurely from a smoking-related for youth by reducing the risk that youth mortality rate from any cause of death disease (Ref. 7 at table 12.2.2). In 2009, experimenters progress to regular use of at any given age is 2 to 3 times higher Congress estimated that a 50 percent cigarettes as a result of nicotine among current cigarette smokers, reduction in youth smoking would also dependence. compared to individuals who never result in approximately $75 billion in The adolescent brain is more smoked (Ref. 6).1 Through this ANPRM, savings 4 attributable to reduced health vulnerable to developing nicotine FDA indicates that it is considering the care costs (see section 2(14) of the dependence than the adult brain; there issuance of a product standard to set a Family Smoking Prevention and are also data from animal studies that maximum nicotine level in cigarettes so Tobacco Control Act; 21 U.S.C. 387 indicate that brain changes induced by that they are minimally addictive or note). As further explained in this nicotine may have long-term nonaddictive, using the best available ANPRM, if cigarettes were minimally consequences (i.e., the long-term science to determine a level that is addictive or nonaddictive, it is expected physical changes, caused by the appropriate for the protection of the that many fewer youth and young adults adolescent nicotine exposure, prevent public health.2 The Agency seeks would be subjected to the impacts of the brain from reaching its full information and comment on a number nicotine (which has a significantly potential, which could result in of issues associated with such a stronger effect on the developing brains permanent deficiencies) (Refs. 8 and 9). potential product standard. Greatly of youth (e.g., Refs. 8 and 9)) from Adolescent tobacco users who initiated reducing the addictiveness of cigarettes cigarettes, nor would they suffer from tobacco use at earlier ages were more would have significant benefits for the health and mortality effects of likely than those initiating at older ages youth, young adults, and adults.3 More cigarette use. to report symptoms of tobacco than half of adult smokers make a Nicotine is powerfully addictive. The dependence, putting them at greater risk serious quit attempt each year (quit for Surgeon General has reported that 87 for maintaining tobacco product use at least a day), many of whom are not percent of adult smokers start smoking into adulthood (Ref. 15). Evidence from able to succeed due to the addictive before the age of 18 and half of adult animal studies indicate that exposure to nature of these products (Ref. 1). The smokers become addicted before the age substances such as nicotine can disrupt establishment of a maximum nicotine of 18, which is before the age at which brain development and have long-term level in cigarettes not only could they can legally buy a pack of cigarettes consequences for executive cognitive increase the likelihood of successful (Ref. 7). Nearly all smokers begin before function (such as task-switching and quit attempts, but it also could help the age of 25, which is the approximate planning) and for the risk of developing prevent experimenters (mainly youth) age at which the brain has completed a substance abuse disorder and various from initiating regular use. Therefore, development (Ref. 8). Generally, those mental health problems (particularly FDA hypothesizes that making who begin smoking before the age of 18 affective disorders such as anxiety and cigarettes minimally addictive or are not aware of the degree of depression) as an adult (Ref. 16). This nonaddictive, using the best available addictiveness and the full extent of the exposure to nicotine can also have long- science to determine a level that is consequences of smoking when they term effects, including decreased appropriate for the protection of the begin experimenting with tobacco use attention performance and increased public health, would significantly (see, e.g., Ref. 10). Although youth impulsivity, which could promote the reduce the morbidity and mortality generally believe they will be able to maintenance of nicotine use behavior caused by smoking. quit when they want, in actuality they (id.). Further, the 2010 Surgeon Preventing nonsmokers, particularly have low success rates when making a General’s Report noted that symptoms youth and young adults, from becoming quit attempt. For example, more than 60 of dependence could result from even a regular smokers due to nicotine percent of high school aged daily limited exposure to nicotine during addiction would allow them to avoid smokers have tried to quit but less than adolescence (Ref. 17). the severe adverse health consequences 13 percent were successful at quitting For all these reasons, FDA is of smoking and would result in for 30 days or more (Ref. 11). In considering limiting the addictiveness substantial public health benefits. In addition, one study found that 3 percent of cigarettes by setting a product of 12th grade daily smokers estimated standard establishing a maximum 1 The discussion of scientific data discussed in that they would ‘‘definitely’’ still be nicotine level of cigarettes, to help this ANPRM is not intended to cover all available smoking in 5 years, while in reality 63 prevent experimenters (who are mainly information on this subject matter. Rather, it is youth) from becoming addicted to intended to provide only a sampling of some of the percent of this population is still current research that could be relevant to smoking 7 to 9 years later (Ref. 12). tobacco and, thus, prevent them from consideration of a potential nicotine tobacco Another survey revealed that ‘‘nearly 60 initiating regular use and from product standard. increasing their risk of tobacco-related 2 The Family Smoking Prevention and Tobacco percent of adolescents believe that they could smoke for a few years and then death and disease. Control Act specifically prohibits the Agency from FDA is also considering this action ‘‘requiring the reduction of nicotine yields of a quit’’ (Ref. 13). because age restrictions on the sale of tobacco product to zero’’ but generally authorizes Because it is such a powerful FDA to issue a tobacco product standard setting a tobacco products, by themselves, are not addiction, addiction to nicotine is often maximum nicotine level. Section 907(C)(3)(B) of the entirely effective in preventing youth lifelong (Ref. 14). Among adolescent FD&C Act. from obtaining cigarettes or other 3 The definitions of ‘‘youth,’’ ‘‘young adults,’’ and tobacco users in 2012, over half (52.2 combusted tobacco products. Youth ‘‘adults’’ can vary in scientific studies. The term percent) reported experiencing at least ‘‘youth’’ generally refers to middle school and/or smokers get their cigarettes from a one symptom of tobacco dependence high school age students. ‘‘Young adults’’ generally variety of sources, including directly refers to individuals 18 to 24 years of age. In some studies, ‘‘adults’’ may encompass individuals age 4 Congress’ estimate of approximately $75 billion purchasing them from retailers, giving 18 to 24 but generally refers to those individual 24 in savings, if adjusted for inflation, would amount others money to buy them, obtaining to 65 years of age. to $83.63 billion in 2017. them from other youth or adults (with

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or without their knowledge), or using nicotine exposure and have been found that meet the statutory definition of illegal means (i.e., shoplifting or to be reinforcing without concomitant tobacco product. stealing) (Ref. 18). The 2015 National nicotine exposure in experienced users Among the authorities included in Youth Risk Behavior Surveillance (Ref. 27). Once tobacco users become chapter IX of the FD&C Act is the Survey (YRBS) of high school students addicted to nicotine, they require authority to establish tobacco product in grades 9 through 12 found that 12.6 nicotine to avoid certain withdrawal standards. The Act authorizes FDA to percent of current cigarette smokers symptoms. In the process of obtaining adopt a tobacco product standard under under age 18 had purchased their nicotine, users of combusted tobacco section 907 of the FD&C Act if the cigarettes directly from stores or gas products are exposed to an array of Secretary of Health and Human Services stations despite the Federal minimum toxicants in tobacco and tobacco smoke (HHS) finds that a tobacco product age requirements for cigarettes (Ref. 19). that lead to a substantially increased standard is appropriate for the While continued vigorous enforcement risk of morbidity and mortality (see, e.g., protection of the public health. In of youth access restrictions is critical to Ref. 10). Although most current U.S. making such a finding, the Secretary of protecting public health, FDA is smokers report that they want to quit HHS must consider scientific evidence considering taking this additional step smoking, have attempted to quit, and concerning: (1) The risks and benefits of to ensure that even if youth do obtain regret starting (see, e.g., Refs. 28 and 29), the proposed standard to the population access to cigarettes, they will be less many smokers find it difficult to break as a whole, including users and likely to: (1) Become addicted to these their addiction and quit. Because of nonusers of tobacco products; (2) the products; (2) initiate regular use; and (3) nicotine addiction, many smokers lack increased or decreased likelihood that increase their risk of the many diseases the ability to choose whether or not to existing users of tobacco products will caused by, and debilitating effects of, continue smoking these toxic stop using such products; and (3) the combusted tobacco product use (Ref. combusted products despite their stated increased or decreased likelihood that 20). desire to quit (see, e.g., Ref. 17). those who do not use tobacco products will start using such products (section Similarly, limiting the nicotine in Accordingly, FDA is considering cigarettes could have significant benefits 907(a)(3)(B)(i) of the FD&C Act). whether to issue a tobacco product for adult tobacco product users, a large Section 907(a)(4) of the FD&C Act standard to: (1) Give addicted users of majority of whom want to quit but are states that tobacco product standards cigarettes the choice and ability to quit unsuccessful because of the highly must include provisions that are more easily by reducing the nicotine to addictive nature of these products (see, appropriate for the protection of the a minimally addictive or nonaddictive e.g., Ref. 21). Data from the 2015 public health. Section 907(a)(4)(B)(i) level and (2) reduce the risk of National Health Interview Survey show provides that a product standard must progression to regular use and nicotine that 68 percent of current adult cigarette include, where appropriate for the dependence for persons who smokers in the United States wanted to protection of the public health, experiment with the tobacco products quit and 55.4 percent of adult cigarette provisions respecting the construction, smokers made a past-year quit attempt covered by the standard. FDA components, ingredients, additives, of at least 1 day (Ref. 22). In high- hypothesizes that making cigarettes constituents, including smoke income countries, about 7 of 10 adult minimally addictive or nonaddictive, constituents, and properties of the smokers say they regret initiating using the best available science to tobacco product. Further, section smoking and would like to stop (Ref. 23 determine a level that is appropriate for 907(a)(4)(A)(i) states that provisions in at p. 2). Decreasing the nicotine in the protection of the public health, tobacco product standards must cigarettes so that they are minimally could significantly reduce the morbidity include, where appropriate, provisions addictive or nonaddictive (using the and mortality caused by smoking. for nicotine yields. Section best available science to determine a B. Legal Authority 907(a)(4)(B)(ii) also provides that a level that is appropriate for the product standard must, where protection of the public health) could The Family Smoking Prevention and appropriate for the protection of public help users quit if they want to—as the Tobacco Control Act (Tobacco Control health, include ‘‘provisions for the large majority of users say they do (e.g., Act) was enacted on June 22, 2009, testing (on a sample basis or, if Ref. 21). amending the FD&C Act and providing necessary, on an individual basis) of the Although many factors contribute to FDA with the authority to regulate tobacco product.’’ In addition, section an individual’s initial experimentation tobacco products (Pub. L. 111–31). 907(a)(4)(B)(iv) provides that, where with tobacco products, the addictive Section 901 of the FD&C Act (21 U.S.C. appropriate for the protection of public nature of tobacco is the major reason 387a), as amended by the Tobacco health, a product standard must include people progress to regular use, and it is Control Act, granted FDA authority to provisions requiring that the results of the presence of nicotine that causes regulate the manufacture, marketing, the tests of the tobacco product required youth, young adults, and adult users to and distribution of cigarettes, cigarette under section 907(a)(4)(B)(ii) show that become addicted to, and to sustain, tobacco, RYO tobacco, and smokeless the product is in conformity with the tobacco use (see, e.g., Refs. 24 and 25). tobacco to protect the public health and portions of the standard for which the While nicotine is the primary addictive to reduce tobacco use by minors. The test(s) were required. Finally, section chemical in tobacco, sensorimotor Tobacco Control Act also gave FDA the 907(d)(3)(B) of the FD&C Act prohibits stimuli that are repeatedly paired with authority to issue a regulation deeming the Agency from issuing a regulation nicotine through the process of smoking other products that meet the statutory that would require the reduction of also develop into conditioned definition of tobacco product to be nicotine yields of a tobacco product to reinforcers that contribute to the subject to FDA’s tobacco product zero. persistent nature of nicotine authority under chapter IX of the FD&C The FD&C Act also provides FDA dependence (Ref. 26). In cigarette users, Act. On May 10, 2016, FDA issued the with authority to issue regulations the sensory aspects of smoking, such as deeming rule (81 FR 28973), extending establishing restrictions on the sale and taste and sensations of smoking (e.g., FDA’s tobacco product authority to all distribution of a tobacco product throat hit), are often reinforcing as they tobacco products, other than the (section 906(d)(1) of the FD&C Act (21 have been paired repeatedly with accessories of deemed tobacco products, U.S.C. 387f(d)(1))). These restrictions

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may include restrictions on the access General’s Report states that 5.6 million actions) regarding tobacco within 1 or 2 to, and the advertising and promotion youth currently 0 to 17 years of age are days of first inhaling from a cigarette of, the tobacco product, if the Secretary projected to die prematurely from (Refs. 41 and 42). Another study found of HHS determines such regulation smoking-related illnesses (Ref. 7 at pp. that 19.4 percent of adolescents who would be appropriate for the protection 666–667). Accordingly, using the best smoked weekly also were considered to of the public health. available science to determine a level be nicotine dependent (Ref. 43). In a FDA intends to use the information that is appropriate for the protection of study regarding nicotine dependence submitted in response to this ANPRM, the public health, making cigarettes among recent onset adolescent smokers, its independent scientific knowledge, minimally addictive or nonaddictive individuals who smoked cigarettes at and other appropriate information, to would limit the number of youth and the lowest levels (i.e., smoking on only further inform its thinking about young adults who progress from 1 to 3 days of the past 30 days) options, including the scope, for a experimentation to regular use and who, experienced nicotine dependence potential product standard that would thereby, increase their risk for symptoms such as loss of control over set a maximum nicotine level for dangerous smoking-related diseases. smoking (42 percent) and irritability cigarettes, and restrictions prohibiting Researchers have determined that after not smoking for a while (23 the sale and distribution of any product almost one-third of adolescents aged 11 percent) (Ref. 44). Researchers in a 4- that violates such a standard. to 18 (31 percent) are ‘‘early year study of sixth grade students also experimenters,’’ meaning that they have found that ‘‘[e]ach of the nicotine III. Health Consequences of Combusted tried smoking at least one puff of a Tobacco Products withdrawal symptoms appeared in some cigarette (but smoked no more than 25 subjects prior to daily smoking’’ (Ref. A. Nicotine in Combusted Tobacco cigarettes in their lifetime) (Ref. 37). The 42) (emphasis added). Ten percent of Products and Its Impact on Users Centers for Disease Control and the subjects showed signs of addiction Prevention (CDC) and other researchers to tobacco use within 1 or 2 days of first Tobacco products are addictive, have estimated that 30 percent or more primarily due to the presence of inhaling from a cigarette, and half had of experimenters become established done so by the time they were smoking nicotine, and the magnitude of public smokers (Ref. 37, citing Refs. 38 and 39). health harm caused by tobacco products seven cigarettes per month (Ref. 42). Given these past trends, if one applies It is clear that many adult cigarette is inextricably linked to their addictive the 30 percent estimate to the nature (Ref. 13 at p. xi). Cigarettes are smokers want to quit. Data from the adolescents who were early 2015 National Health Interview Survey the most widely used tobacco products experimenters in 2000, then 2.9 million show that 68 percent of current adult among adults and are responsible for at of these early experimenters have now smokers in the United States wanted to least 480,000 premature deaths in the or will become established smokers quit and 55.4 percent of adult smokers United States each year (Ref. 7). Other (Ref. 37). Based on the number of made a past-year quit attempt of at least combusted tobacco products that are persons aged 0 to 17 in 2012, the 1 day (Ref. 22). According to an analysis possible targets of product migration Surgeon General estimated that of this survey, only 7.4 percent of (i.e., switch candidates for smokers to 17,371,000 of that group will become former adult cigarette smokers had maintain their nicotine addiction) or future smokers and 5,557,000 will die recently quit (id.). dual use have similar adverse health from a smoking-related disease (Ref. 7 at effects and can cause nicotine T. 12.2.1). These high numbers speak to For adult smokers who report quit dependence (Refs. 30 and 31). For the extreme vulnerability of today’s attempts, many of these attempts are example, researchers have found that children and adolescents to the health unsuccessful. For example, among the current exclusive cigar smokers and harms of tobacco use resulting from 19 million adults who reported current exclusive pipe smokers have an addiction. attempting to quit in 2005, increased risk for lung cancer and Nicotine addiction is a critical factor epidemiologic data suggest that only 4 tobacco-related cancers overall, as in the transition of smokers from to 7 percent were successful (Ref. 28 at compared to those who reported never experimentation to sustained smoking p. 15). Similarly, the Institute of using any type of combusted tobacco and in the continuation of smoking for Medicine (IOM), considering data from product (Ref. 32). We note that there is those who want to quit (Ref. 7 at p. 113; 2004, found that although a dose-response relationship between Ref. 17). Intermittent smokers, even very approximately 40.5 percent of adult the number of cigars and pipes smoked infrequent smokers, can become smokers reported attempting to quit in and the risk of disease (i.e., the larger addicted to tobacco products (Ref. 40). that year, only between 3 and 5 percent the number of cigars or pipes smoked, Longitudinal research has shown that were successful (Ref. 13 at p. 82). Adult the higher the risk of disease) (Ref. 31 smoking typically begins with smokers may make as many as thirty or at 110), but cigar and pipe users are still experimental cigarette use and the more quit attempts before succeeding subject to the addictive effects of transition to regular smoking can occur (Ref. 45). FDA also notes that adults nicotine through nicotine absorption relatively quickly by smoking as few as with education levels at or below the (and to the health impacts of long-term 100 cigarettes (Ref. 8). Other research equivalent of a high school diploma use that may follow from regular use found that among the 3.9 million have the highest smoking prevalence due to addiction) even if they report that middle and high school students who levels but the lowest quit ratios (i.e., the they do not inhale (Refs. 33–35). reported current use of tobacco products ratio of persons who have smoked at The Surgeon General has reported (including cigarettes and cigars) in 2012, least 100 cigarettes during their lifetime that ‘‘most people begin to smoke in 2 million of those students reported at but do not currently smoke to persons adolescence and develop characteristic least one symptom of dependence (Ref. who report smoking at least 100 patterns of nicotine dependence before 15). cigarettes during their lifetime) (Ref. 46). adulthood’’ (Ref. 36 at p. 29). Although the majority of adolescent Nicotine addiction and associated Adolescents develop physical daily smokers meet the criteria for withdrawal symptoms make it difficult dependence and experience withdrawal nicotine dependence, one study found for smokers to quit without using symptoms when they try to quit that the most susceptible youth lose cessation counseling and/or cessation smoking (id.). The 2014 Surgeon autonomy (i.e., independence in their medications.

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Adolescents also experience low from cigarettes no matter how they means through which it is delivered can success rates when attempting to quit. smoked them and eventually would either reduce or enhance a product’s As we have noted, most Americans who stop trying to do so) (e.g., Refs. 4, 5, and potential for abuse and physiological use tobacco products begin using when 53), making it potentially easier for effects (Ref. 17 at p. 113). Quicker they are under the age of 18 and become smokers to make more successful quit delivery, higher rate of absorption, and addicted before reaching the age of 18 attempts and likely leading to a higher resulting concentration of (Refs. 36 and 47). Although many potentially substantial reduction in the nicotine increase the potential for adolescents believe ‘‘they can quit rate of relapse compared to current addiction (id. at p. 113). The ultimate [smoking] at any time and therefore levels.5 Former smokers that choose to levels of nicotine absorbed into the avoid addiction,’’ nicotine dependence switch completely to a potentially less blood for different tobacco products can be rapidly established (Ref. 13 at p. harmful nicotine delivery product (e.g., (e.g., cigarettes and cigars) can be 89; see also Ref. 28 at p. 158). Research electronic nicotine delivery systems similar in magnitude even though has shown that some adolescents report (ENDS)) to maintain their nicotine dose individuals may smoke them differently symptoms of withdrawal and craving also would, to the extent that those and the rate of absorption may be within days or weeks of beginning to products result in less harm, different (Ref. 25). smoke (Ref. 48). As a result, many significantly reduce their risk of The significant negative health effects adolescents are nicotine dependent tobacco-related death and disease. from cigarettes are a consequence of despite their relatively short smoking Accordingly, rendering cigarettes long-term use. Children and adults histories (Ref. 11). An analysis of data minimally addictive or nonaddictive continue using cigarettes primarily as a from the 2015 YRBS found that, of those (however that were achieved) would be result of their addiction to nicotine (e.g., currently smoking cigarettes, 45.4 expected to address the principal reason Ref. 7). Almost all adult smokers started percent had tried to quit smoking that smokers are unable to quit smoking. smoking cigarettes as children or young cigarettes during the previous year (Ref. B. Negative Health Effects of Combusted adults, and half of adult smokers 19). Likewise, an analysis of the 2012 Tobacco Product Use became addicted before turning 18 (id.). National Youth Tobacco Survey (NYTS) Cigarettes are responsible for revealed that 51.5 percent of middle and Nicotine is a powerfully addictive hundreds of thousands of premature high school student smokers had sought chemical. The effects of nicotine on the deaths every year from many diseases, to quit all tobacco use in the previous central nervous system occur rapidly put a substantial burden on the U.S. year (Ref. 49). after absorption (Ref. 25 at p. 12). Users health care system, and cause massive Relapse is the principal limiting factor of combusted tobacco products absorb economic losses to society (Ref. 7 at pp. in the transition of smoking to nicotine readily from tobacco smoke 659–666; another perspective on this nonsmoking status (Ref. 17). Relapse through the lungs (id. at p. iii). Nicotine issue is provided by Sloan et al. (Ref. refers to the point after an attempt to introduced through the lungs is rapidly 55)). Cigarette smoking causes more stop smoking when tobacco use distributed to the brain (id. at p. 12). deaths each year than AIDS, alcohol, becomes ongoing and persistent (Ref. With regular use, nicotine levels illegal drug use, homicide, suicide, and 17, citing Ref. 50). Most smokers who accumulate in the body during the day motor vehicle crashes combined (Ref. ultimately relapse do so soon after their from the tobacco product use and then 47). Every year, cigarette smoking is the quit attempt (Ref. 17). One study found decrease overnight as the body clears primary causal factor for 163,700 deaths that 80 to 90 percent of those the nicotine (id. at p. iii). Mild nicotine from cancer, 160,600 deaths from individuals who were smoking at 6 intoxication even occurs in first-time cardiovascular and metabolic diseases, months following a quit attempt had smokers (Ref. 25 at pp. 15–16). and 131,100 deaths from pulmonary resumed smoking within 2 weeks Tolerance to the effects of nicotine diseases (Ref. 7 at p. 659). In the United following their quit attempt (Ref. 51). develops rapidly. States, about 87 percent of all lung Long-term studies of individuals trying The addiction potential of a nicotine cancer deaths, 32 percent of coronary delivery system varies as a function of to quit smoking reveal that 30 to 40 heart disease deaths, and 79 percent of its total nicotine dosing capability, the percent of those who quit smoking for all cases of chronic obstructive speed at which it can deliver nicotine, 1 year eventually relapsed (id.). In fact, pulmonary disease (COPD) are the palatability and sensory one study following 840 participants for attributable to cigarette smoking (id.). characteristics of the system, how easy more than 8 years found that The 2014 Surgeon General’s Report it is for the user to extract nicotine, and approximately one-half of smokers who states that 5.6 million youth currently 0 the cost of the delivery system (Ref. 54). stopped smoking for 1 year relapsed to to 17 years of age are projected to die A cigarette is an inexpensive and regular smoking within the subsequent prematurely from smoking-related extremely effective nicotine delivery 7 years (Ref. 52). Researchers have illnesses (id. at pp. 666–667). device, which maximizes the cigarette’s found that a higher frequency of Data from the CDC’s Smoking- addicting and toxic effects (id.). The smoking predicts more severe Attributable Mortality, Morbidity, and amount of nicotine delivered and the withdrawal symptoms and earlier Economic Costs system for 2005–2009 relapse after an attempt to quit smoking (the most recent years for which and is associated with early lapses after 5 As stated throughout the document, FDA expects that, to maintain their nicotine dose, some analyses are available) indicate that cessation (Ref. 17 at p. 119). FDA number of addicted cigarette smokers could migrate cigarette smoking and exposure to specifically requests comment as to to other similar, combusted products (or engage in cigarette smoke are responsible for at whether higher frequency smokers dual use with such products) after the standard least 480,000 premature deaths each would experience more severe went into effect, reducing the benefits of the product standard. Since the scope would impact the year (id. at p. 659). However, this withdrawal symptoms from the use of potential public health benefits of such a nicotine estimate does not include deaths caused VLNC cigarettes. tobacco product standard, FDA is seeking comment by other combusted forms of tobacco, FDA expects that, if cigarettes were on whether the standard should cover any or all of such as cigars and pipes (id. at 665).6 minimally addictive or nonaddictive, the following products: Combusted cigarettes the nicotine level in cigarettes would be (which FDA has previously interpreted to include kreteks and bidis), cigarette tobacco, roll-your-own 6 As discussed in Ref. 56, regular cigar smoking self-limiting (i.e., smokers would be tobacco, some or all cigars, waterpipe tobacco, and was responsible for approximately 9,000 premature unable to obtain their nicotine dose pipe tobacco. deaths and more than 140,000 years of potential life

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The three leading causes of smoking- disease and aortic aneurysm, with the successful quit attempts by the majority attributable death for current and former magnitude in risk a function of the of smokers seeking to quit smoking smokers were lung cancer, heart disease, amount smoked and depth of inhalation every year and potentially prevent and COPD (id. at p. 660). For every (Ref. 31 at 119–155). Research indicates experimenters from becoming regular person who dies from a smoking-related that most cigar smokers do inhale some smokers. However, if a standard were to disease, approximately 30 more people amount of smoke, even when they do apply to cigarettes only, it could be will suffer from at least one smoking- not intend to inhale, and are not aware substantially less effective. Specifically, related disease (Ref. 58). of doing so (Refs. 33 and 34). Even when FDA expects that, to maintain their Cigarettes also have deadly effects on cigar smokers do not breathe smoke into nicotine dose, some number of addicted nonsmokers. From 2005 to 2009, an their lungs, they are still subject to the cigarette smokers could migrate to other estimated 7,330 lung cancer and 33,950 addictive effects of nicotine through similar, combusted products (or begin to heart disease deaths were attributable to nicotine absorption (Refs. 33 and 35). engage in dual use with such other exposure to secondhand smoke (Ref. 7 This is because cigar smoke dissolves in products) after the standard went into at p. 660). It is also well established that saliva, allowing the smoker to absorb effect, reducing the benefits of the secondhand tobacco smoke causes sufficient nicotine to create dependence, product standard. Former smokers that premature death and disease in children even if the smoke is not inhaled (Refs. choose to switch completely to a and in adults who do not smoke (see, 35 and 62). potentially less harmful nicotine e.g., Ref. 59 at p. 11). According to the Regular cigar smoking (which, in this delivery product (e.g., ENDS) to Surgeon General’s Report, ‘‘50 Years of study, constituted use on at least 15 of maintain their nicotine dose also would, Progress: A Report of the Surgeon the past 30 days) was responsible for to the extent that those products result General, 2014,’’ which summarizes approximately 9,000 premature deaths in less harm, significantly reduce their thousands of peer-reviewed scientific and more than 140,000 years of risk of tobacco-related death and studies and is itself peer-reviewed, potential life lost among adults aged 35 disease. Since the scope would impact smoking remains the leading years or older in 2010 (Ref. 56). the potential public health benefits of preventable cause of disease and death Researchers also have found that the such a nicotine tobacco product in the United States, and cigarettes have risk of dying from tobacco-related standard, FDA is seeking comment on been shown to cause an ever-expanding cancers is higher from current exclusive whether the standard should cover any number of diseases and health pipe smokers and current exclusive or all of the following products: conditions (Ref. 7 at pp. 107–621). As cigar smokers than for those who Combusted cigarettes (which FDA has stated in the 2014 Report, ‘‘cigarette reported never using combusted tobacco previously interpreted to include smoking has been causally linked to products (Ref. 32). kreteks and bidis), cigarette tobacco, disease of nearly all organs of the body, IV. Requests for Comments and RYO tobacco, some or all cigars, pipe to diminished health status, and to harm Information tobacco, and waterpipe tobacco. FDA to the fetus . . . [and] the burden of intends that any nicotine tobacco death and disease from tobacco use in To aid in its consideration regarding product standard would cover all the United States is overwhelmingly development of a nicotine tobacco brands in a product category and, caused by cigarettes and other product standard, FDA is seeking therefore, those products currently on combusted tobacco products’’ (Ref. 7 at comments, data, research results, and the market and any new tobacco p. 7). other information related to questions products would be expected to adhere Other combusted tobacco products, under the following topics: Scope of to the standard. particularly those that could be cigarette products to be covered, maximum FDA is continuing to weigh several alternatives if users were unable to nicotine level for a nicotine tobacco factors as it considers the scope of continue smoking cigarettes, cause product standard, implementation, products that should be subject to any similar negative health effects. For analytical testing, technical potential nicotine tobacco product example, there is a long-standing body achievability, possible countervailing standard—including the strength and of research, including reports from the effects (including the potential for an breadth of the available data derived Surgeon General and National Cancer illicit market), and other considerations. from studies of VLNC cigarettes on the Institute (NCI), demonstrating that cigar We ask that commenters clearly identify likely effects of reducing nicotine 7 (as use can cause serious adverse health the section and question associated with discussed in section IV.B); current effects (Ref. 31 at 119–155; Refs. 60, 61, their responsive comments and prevalence and initiation rates for and 33). NCI’s Smoking and Tobacco information. different classes of tobacco products; the Control Monograph No. 9 (‘‘Cigars: A. Scope available data on the toxicity, Health Effects and Trends’’), which addictiveness, and appeal of the A tobacco product standard limiting provides a comprehensive, peer- products; the use topography of the the nicotine level in cigarettes could reviewed analysis of the trends in cigar products (including quantity, frequency, address one of our nation’s greatest smoking and potential public health and duration of use); and the potential public health challenges: The death and consequences, as well as other research, for migration to, and dual use of, disease caused by cigarette use. demonstrates that cigar smoking leads to different products. Current VLNC Approximately 480,000 people die an increased risk of oral, laryngeal, cigarette literature indicates that every year from smoking cigarettes (Ref. esophageal, pharyngeal, and lung reduction of nicotine in cigarettes 7). Cigarettes are the tobacco product cancers, as well as coronary heart would make it more likely for smokers category that causes the greatest burden (even those not currently expressing a lost among adults aged 35 years or older in 2010. of harm to public health as a result of desire to quit) to cease cigarette use The 2014 Surgeon General Report states that the the prevalence of cigarette use and the (e.g., Refs. 4, 5, 63, and 64). In light of methodology for estimating the current population toxicity and addictiveness of these these data, FDA also believes that burden for use of combusted tobacco products other products. FDA hypothesizes that a than cigarettes remains under discussion, but the reduction of nicotine could help prevent number of added deaths is expected to be in the tobacco product standard limiting the thousands per year (Ref. 7 at 665, 14 SG; citing Ref. nicotine level in cigarettes could 7 VLNC cigarettes do not contain uniform 57). significantly increase the number of amounts of nicotine.

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experimenters from becoming addicted or dual use candidates? If FDA were to products were marketed as low nicotine to tobacco, resulting in regular tobacco issue a nicotine tobacco product delivery or ‘‘light’’ cigarettes. However, use. standard that did not include waterpipe cigarette users could modify their use Based on these considerations, FDA is tobacco products within the scope, what behaviors to compensate for this seeking comment on whether any would be the likelihood that former increase in ventilation. For example, the nicotine tobacco product standard smokers would switch to waterpipe vent holes could be easily blocked by should cover any or all of the following tobacco to maintain their nicotine users’ fingers or mouths, and larger or products: addiction? What are the relative risk more frequent puffs could be taken by • Combusted cigarettes (which FDA consequences of switching to waterpipe consumers (Ref. 65). As a result, these has previously interpreted to include tobacco? products were designed to make them kreteks and bidis), ‘‘appear’’ light to the user but could • B. Maximum Nicotine Level Cigarette tobacco, deliver as much nicotine to the user as • RYO tobacco, As discussed throughout this • high nicotine delivery cigarettes. The Cigars (some or all categories; i.e., document, nicotine is addictive and is compensatory behaviors of the cigarette small cigars, large cigars, cigarillos, and/ the primary reason why many smokers user were able to overcome the changes or so-called premium cigars), who want to quit are unable to do so. in ventilation in these higher ventilated • Pipe tobacco, and Accordingly, FDA is considering products. • Waterpipe tobacco. developing a proposed product standard VLNC cigarettes, in contrast, have Please explain your responses and to make cigarettes minimally addictive provide any evidence or other relied on reducing nicotine content in or nonaddictive by setting a maximum the tobacco filler rather than information supporting your responses nicotine level, using the best available to the following questions: engineering changes to the cigarette. science to determine a level that is Patents reveal that more than 96 percent 1. If FDA were to propose a product appropriate for the protection of the standard setting a maximum nicotine of nicotine can be successfully extracted public health. FDA has considered while achieving a product that ‘‘was level, should such a standard cover several peer-reviewed studies regarding subjectively rated as average in smoking other combusted tobacco products in very low nicotine content (VLNC) characteristics’’ (Ref. 66) and that up to addition to cigarettes? If so, which other cigarettes 8 and the likely effects of a 75 percent reduction in the nicotine products? If FDA were to propose to reducing nicotine in combusted tobacco. contained in a tobacco leaf can be include additional categories of A 2013 survey paper noted that achieved with an ‘‘effective and combusted tobacco products in a researchers initially estimated that economical system for producing nicotine tobacco product standard, reducing the total nicotine content of tobacco products . . . while should the standard be tailored to reflect cigarettes to 0.5 mg per rod would maintaining other desirable ingredients differences in these products? What minimize addictiveness and that a for good taste and flavor’’ (Ref. 67). criteria should be used to determine ‘‘more recent analysis suggests that the whether, and which, products should be maximum allowable nicotine content In conventional cigarettes covered? per cigarette that minimizes the risk of manufactured in the United States, 2. Some suggest that large cigars and central nervous system effects nicotine accounts for approximately 1.5 those cigars typically referred to as contributing to addiction may be lower’’ percent of the cigarette weight, or 10–14 ‘‘premium’’ cigars should be regulated (Ref. 2). The study authors concluded mg of nicotine per cigarette (Refs. 68– differently from other cigars, asserting that ‘‘[p]reventing children from 71) and generally have nicotine yields that they are used primarily by adults becom[ing] addicted smokers and giving in the 1.1 mg to 1.7 mg (Ref. 31 at p. and their patterns of use are different people greater freedom to stop smoking 67). Certain VLNC cigarettes have much from those of regular cigars (81 FR when they decide to quit by reducing lower nicotine yields than conventional 28973 at 29024). FDA requests the addictiveness of cigarettes is a cigarettes—in the 0.02–0.07 mg information and data on whether large policy that increasingly appears to be nicotine/cigarette range—due to product and/or so-called premium cigars should feasible and warranted’’ (id.). We changes that the user cannot overcome be excluded from a possible nicotine specifically request comment regarding (Ref. 72). Reducing the nicotine in the tobacco product standard based on this paper’s conclusions and the finished tobacco product places an asserted different patterns of use, and possible impact of higher or lower absolute maximum limit on the amount whether large and/or so-called premium maximum nicotine levels in a potential of nicotine that can be extracted by the cigars would be migration (or dual use) nicotine tobacco product standard. user in a given cigarette, unlike candidates if FDA were to issue a Early ‘‘light’’ cigarettes achieved a modifications such as ventilation holes, nicotine tobacco product standard that reduction in machine-measured which affect nicotine yield in smoke but excluded premium cigars from its scope. nicotine yield through a variety of can be overcome through user behavior. FDA also requests data and information means, including through the use of See section IV.C of this document for a on whether and how there is a way that, ventilation holes (although the actual discussion of possible compensatory if FDA were to exclude premium cigars nicotine content was not low). This smoking under a single target approach from the scope of a nicotine tobacco increase in ventilation led to lower or a stepped down approach to nicotine product standard, FDA could define yields of nicotine in smoke as measured reduction. ‘‘premium cigar’’ to include only by smoking machines, and these 1. VLNC Cigarettes unlikely migration or dual use products and thereby minimize such 8 Scientific studies regarding VLNC cigarettes use The first VLNC cigarettes studied by consequences. both ‘‘yield’’ and ‘‘content’’ to describe the amount researchers were produced by Philip of nicotine in research cigarettes. ‘‘Yield’’ is the Morris and marketed under the brand 3. Should waterpipe tobacco International Organization for Standardization (ISO) products, which are different from machine-generated nicotine smoke yield, and name ‘‘Next,’’ which was reported to regular pipe tobacco, be included in ‘‘content’’ refers to the nicotine in the tobacco filler contain 0.4 mg nicotine/g of tobacco such a standard? Are there data showing of the entire finished product. ‘‘Yield’’ and filler (Ref. 73). Later, the National ‘‘content’’ are not interchangeable terms. If neither Institute for Drug Abuse (NIDA) different use topographies or that they ‘‘yield’’ nor ‘‘content’’ is used, the nicotine levels are not likely to be migration substitutes in these studies refer to content. contracted with the Ultratech/Lifetech

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Corporation 9 to produce VLNC reduced risk tobacco products, Century is acting as a vendor for RTI for cigarettes for research purposes (Ref. 74; companies like 22nd Century are using this contract manufacturing Spectrum Ref. 75). The two types of cigarettes genetic engineering and plant breeding cigarettes that contain 0.4 mg nicotine/ produced were: (1) 1.1 mg/cigarette (cig) to produce very low nicotine tobacco for gram (g) of tobacco filler (id). Finally, ISO smoke nicotine (7.2 mg nicotine/cig incorporation into cigarettes. In 2014, Philip Morris manufactured cigarettes in filler) and (2) 0.07 mg/cig ISO smoke the company was granted patents for its with varying nicotine levels for research nicotine (filler levels were reported as 0, process to virtually eliminate the only (Ref. 79). FDA requests data and but FDA has estimated these levels to be nicotine in tobacco plants (Ref. 77). information regarding the risks to between 0.4 and 0.5 mg/cig) (Ref. 74). Further, low-nicotine cigarettes are smokers from inhalation of VLNC Researchers also have used Quest produced and distributed for research cigarette smoke. cigarettes, produced by Vector Tobacco, purposes by Research Triangle Institute Table 1 includes a list of VLNC to study the impact of reduced nicotine (RTI), under a contract for the NIDA’s cigarettes used in research studies and (Ref. 76). To provide consumers with Drug Supply Program (Ref. 78). 22nd their reported nicotine levels.

TABLE 1—FILLER NICOTINE AND ISO NICOTINE DELIVERY FOR LOW AND VERY LOW (*) NICOTINE CIGARETTES MADE AVAILABLE EITHER COMMERCIALLY OR FOR RESEARCH

ISO Nicotine Type of cigarette Filler nicotine level delivery (mg/g or mg/cig) (mg/cig)

Quest 1 ...... 12.5 mg/g; 8.9 mg/cig ...... 0.6 Quest 2 ...... 6.4 mg/g; 5.1 mg/cig ...... 0.3 Quest 3 ...... 1.0 mg/g; 0.4 mg/cig ...... *0.5 Ultratech/Lifetech ...... 10.3 mg/g 1; 7.2 mg/cig ...... 1.1 Ultratech/Lifetech2 ...... 0.6–0.7 mg/g 1; 0.4–0.5 mg/cig ...... *<0.06 Next ...... 0.4 mg/g ...... *0.08 Spectrum high nicotine ...... 11.4–12.8 mg/g ...... 0.6–1.0 Spectrum intermediate nicotine ...... 5.7–5.8 mg/g ...... 0.3 Spectrum low nicotine ...... 0.4 mg/g ...... *<0.04 Philip Morris 12 mg (for research only) ...... 14.4 mg/g 1; 10.1 mg/cig ...... 0.9 Philip Morris 8 mg (for research only) ...... 10.6 mg/g 1; 7.4 mg/cig ...... 0.6 Philip Morris 4 mg (for research only) ...... 5 mg/g 1; 3.5 mg/cig ...... 0.3 Philip Morris 2 mg (for research only) ...... 2.1 mg/g 1; 1.5 mg/cig ...... 0.2 Philip Morris 1 mg (for research only) ...... 0.9 mg/g 1; 0.6 mg/cig ...... 0.1 1 mg/g or mg/cigarette (cig) was calculated based on an estimate of 0.7 g of tobacco per cigarette (Ref. 80). 2 Filler nicotine level was reported as 0 mg/cig, but FDA estimates the cigarette contained 0.4–0.5 mg/cig.

2. Estimate of Addiction Threshold addictiveness. The first type uses smokers (a group sometimes referred to Levels indirect estimates based on information as tobacco ‘‘chippers’’) (Ref. 81, citing in humans regarding nicotine intake in Ref. 82,). In the 1994 review, researchers In 1994, certain scientists proposed smokers who appear not to be addicted suggested that a threshold level of the idea of federal regulation of nicotine to nicotine to estimate a likely threshold nicotine per cigarette should be low content, which could result in lower level. A second type includes studies of enough to prevent or limit the intake of nicotine and a lower level of VLNC use by study participants that development of nicotine addiction in nicotine dependence (Ref. 81). However, have reported increased quit attempts most young people, while providing FDA acknowledges that there is and cessation even in smokers not enough nicotine for taste and sensory individual variability in dose sensitivity interested in quitting. A third type sensation (e.g., Ref. 81). These to all addictive substances, making it includes studies that have revealed researchers found that based on existing difficult to determine a single addiction reduced positive subjective effects and studies at the time, ‘‘an absolute limit of threshold which would apply across the increased negative effects in VLNC 0.4 to 0.5 mg of nicotine per cigarette population. A proposal to lower the smokers. The fourth type includes should be adequate to prevent or limit nicotine in conventional cigarettes, or studies measuring nicotine receptor the development of addiction in most any tobacco product, could merit binding, which indicate that use of young people. At the same time, it may consideration only if there were a VLNC cigarettes yields significantly provide enough nicotine for taste and threshold nicotine exposure level below lower nicotinic acetylcholine receptor sensory stimulation’’ (id.), which FDA which the nicotine did not produce (nAChR) occupancy and cerebral interprets to mean that there would be significant reinforcing effects or sustain response. enough nicotine for an experienced user addiction in a majority of the a. Indirect estimates of an addiction to tell that there is nicotine in the population. FDA continues to assess threshold. In 1994, researchers tobacco product. VLNC cigarette studies analyzing conducted a review to explore indirect In another study seeking to estimate a addiction threshold levels, as discussed estimates of an addiction threshold by reinforcement threshold, scientists in this section. focusing on the smoking habits of a reviewed several studies, including one Four primary study types speak to the small population of smokers who in which abstinent smokers received level of nicotine in tobacco that could demonstrate reduced nicotine intravenous nicotine injections by significantly reduce product dependence, as compared to other pulling a lever in a fixed ratio task (Ref.

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

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83). The authors found that studies decreases in nicotine content, but there smoke VLNC cigarettes experience some using intravenous nicotine was no effect on the biomarker 1- of the same subjective effects as those administration suggest that the nicotine hydroxpyrene (1–HOP) (Ref. 88). One individuals who smoke traditional, NNC reinforcement threshold (i.e., the limitation of these studies is that they cigarettes. For example, VLNC users minimum amount of nicotine intake were conducted in an unregulated report experiencing reductions in required to initiate or maintain self- environment in which smokers certain physiological withdrawal administration) is between 1.5 to 6.0 continued to have access to the normal symptoms (e.g., craving, anxiety, micrograms/kg in humans and 3 to 10 nicotine content (NNC) cigarettes. irritability, depression) but do not micrograms/kg in rats (Ref. 84). One of the more recent studies (Ref. experience other symptoms associated Although the study’s authors noted 85) on this issue was a double-blind, with full nicotine content cigarettes potential limitations (i.e., intravenous parallel, randomized clinical trial (e.g., relief of physical withdrawal delivery does not mimic inhalation, conducted between June 2013 and July symptoms, increased stimulation and administration of nicotine alone omits 2014 that evaluated 840 participants alertness, reduction in restlessness) other psychoactive constituents in (780 completed the 6-week study) who (Refs. 44, 72, 74, 75, 89–93). Exposure tobacco smoke, and other factors such as were not interested in quitting smoking. over multiple days generally leads to a age, sex, and genetic variations may During the sixth week of the study, the reduction in cigarettes smoked per day influence nicotine’s reinforcing average number of cigarettes smoked per (Ref. 87). Furthermore, physiological properties) (Ref. 84), the lowest dose in day was lower for participants randomly responses after VLNC cigarettes, such as the study overlaps with the upper limit assigned to cigarettes containing 2.4, the increase in heart rate that is of an addiction threshold estimated by 1.3, or 0.4 mg of nicotine per gram of typically observed following nicotine the 1994 study (Ref. 81). Despite the tobacco (16.5, 16.3, and 14.9 cigarettes administration, are less than those seen study limitations of both these per day, respectively) than for those with higher nicotine cigarettes and are estimates, they help provide a range on assigned to their usual cigarette brand or absent in some cases (Ref. 74, 94, and which to potentially base a nicotine those cigarettes containing 5.2 or 15.8 95). Thus, it appears that transitioning level threshold. mg per gram (22.2 and 21.3 cigarettes to VLNC cigarettes (from NNC b. Findings of increased cessation for per day, respectively) (Ref. 85). Those cigarettes) may result in some VLNC cigarettes. Several studies participants using cigarettes with the behavioral and physiological responses indicate that people using significantly lowest nicotine content (0.4 mg per commonly experienced when using reduced nicotine content cigarettes (as gram nicotine/gram of tobacco filler, standard NNC cigarettes (e.g., reduced low as 0.4 mg nicotine/g of tobacco demonstrated reduced dependence, and appetite, increased alertness). These filler) are more likely to consider use of reduced nicotine cigarettes, responses, where present, are lower cessation (i.e., consider reducing including the VLNC cigarettes, with than those seen with standard nicotine cigarette intake as a step towards minimal evidence of withdrawal-related cigarettes and get progressively lower cessation or consider fully ceasing discomfort or safety concerns (id.). The over time. cigarette intake), even if they had not authors concluded that this study d. Lower nAChR occupancy and previously considered quitting (see, e.g., provides ‘‘preliminary-short term data cerebral response from the use of VLNC Refs. 4, 5, 63, and 64). These studies . . . [that] suggest that if nicotine cigarettes. VLNC cigarettes contain were not investigating VLNC cigarettes content is adequately reduced, smokers some nicotine, albeit at very low levels. as cessation aids. may benefit by smoking fewer cigarettes Although there is enough nicotine in Some studies showed that switching and experiencing less nicotine VLNC cigarettes to bind to acetylcholine to VLNC cigarettes results in a reduced dependence, with few negative receptors in the brain, there is not number of cigarettes smoked per day consequences’’ (id.). enough to consistently produce the full (Ref. 4; Ref. 76), reduced nicotine While these results, taken together range of subjective responses (i.e., those dependence (Refs. 4, 84, and 85), and with other studies, are promising, FDA responses based on or influenced by minimal evidence of withdrawal acknowledges the inherent limitations individual, internal perceptions or distress and increased depression (Ref. of the available research on changes in experiences) observed following use of 64, Ben 12; Refs. 85–87). On the other smoking as a function of VLNC NNC cigarettes (Refs. 74, 92, 96, and 97). hand, other researchers have reported cigarettes use. As noted by the Therefore, VLNC cigarettes may not the use of VLNC cigarettes did not investigators of the 2015 double-blind, produce the full range of subjective change the number of cigarettes smoked parallel, randomized clinical trial, ‘‘no effects as NNC cigarettes. This supports per day (Refs. 86 and 88), but they did large-scale clinical trials of reduced the hypothesis that many subjective and observe reductions in cotinine and nicotine cigarettes have been conducted. physiological effects observed following carbon monoxide levels. For example, Furthermore, little is known about the exposure to smoke from VLNC cigarettes in the Benowitz et al. 2015 study (Ref. dose-related effects of reduced nicotine. could be due to repeated pairing of 86), where researchers progressively Data derived from trials assessing a nicotine with sensory and conditioned lowered nicotine content over 7 months, range of reduced-nicotine cigarettes are cues or to other psychoactive chemicals. the authors found that, after the 7 critical for providing an empirical basis Given that these subjective and months of VLNC cigarette use, nicotine for regulatory decisions pertaining to physiological effects have been directly intake remained below baseline (i.e., nicotine product standards’’ (Ref. 85). linked to nicotine, it is likely that they plasma cotinine at 149 ng/ml vs. 250 ng/ As a result, FDA requests submission of are learned responses through repeated ml). The Mercincavage et al. study (Ref. additional data that may be used to pairing with nicotine and not due to 88), a randomized study of smokers explore further the hypotheses other chemicals in the smoke. progressively decreasing nicotine presented in this ANPRM (e.g., Please explain your responses and content over three ten day periods, also extended duration studies) and supports provide any evidence or other yielded mixed results regarding harm the development of additional studies to information supporting your responses exposure. The researchers found that further analyze these conclusions. to the following questions: certain biomarkers of exposure to toxic c. Subjective effects and relief of 1. The Tobacco Control Act prohibits tobacco-related constituents (i.e., withdrawal symptoms associated with FDA from reducing nicotine yields in cotinine and NNAL) decreased with VLNC cigarettes. Individuals who any combusted tobacco product to zero

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(section 907(d)(3) of the FD&C Act). If would perceive these VLNC cigarettes as that VLNC cigarettes would not (e.g., FDA were to propose a maximum ‘‘safe’’—and how could youth and adult Refs. 64, 76, and 105).10 nicotine level for cigarettes, what risk perceptions of these cigarettes FDA is aware of several studies that should be the maximum level to ensure impact initiation, use, and cessation have demonstrated the impact of an that the product is minimally addictive habits of combusted tobacco products? immediate (e.g., Refs. 53, 106–108) or a or nonaddictive, using the best available stepped-down approach (Ref. 64) to science to determine a level that is C. Implementation (Single Target vs. nicotine reduction on smoking cessation appropriate for the protection of the Stepped-Down Approach) outcomes. Researchers have found that public health? Rather than establishing the single target approach may be If FDA were to issue a product a nicotine target to make products associated with better cessation ‘‘minimally addictive’’ or standard establishing a maximum outcomes. Data from the International ‘‘nonaddictive,’’ should FDA consider a nicotine level for cigarettes, such a Tobacco Control Policy Evaluation 4- different threshold (e.g., less addictive standard would need to either propose Country Survey, a telephone survey of than current products on the market)? a single target (where the nicotine is more than 8,000 adult smokers in the How should the maximum level be reduced all at once) or a stepped-down United States, the United Kingdom, measured (e.g., nicotine yield, nicotine approach (where the nicotine is Canada, and Australia, illustrates the in cigarette filler, something else)? What gradually reduced over time through a cessation benefits from abrupt would be the potential health impacts of sequence of incremental levels and abstinence from cigarettes (‘‘cold requiring a maximum nicotine level implementation dates) to reach the turkey’’) when compared to a gradual such as 0.4 mg nicotine/g of tobacco desired maximum nicotine level. Some reduction of smoking prior to complete filler? FDA is interested in public health have suggested that any maximum abstinence (‘‘cut down’’) (Ref. 109). impacts of requiring different maximum nicotine level should be established as While this differs from the approaches nicotine levels, such as 0.3, 0.4, and 0.5 a single target (rather than a stepped- considered in this ANPRM, it provides mg nicotine/gram of tobacco filler, as down approach) to limit exposure to helpful insight into the effects of a well as other maximum nicotine levels harmful tobacco while providing similar gradual vs. single change in nicotine and solicits comments about the cessation rates to those that could occur intake. Researchers concluded that potential health impacts of different with a stepped-down approach. Some immediate nicotine cessation was maximum levels. level of compensatory smoking behavior ‘‘clearly associated with more successful 2. FDA lists four types of studies to (i.e., smokers seeking to obtain the outcomes’’ (Ref. 109). Scientists also estimate the threshold of nicotine amount of nicotine they need to sustain found higher abstinence rates for those addiction (i.e., indirect estimates; their addiction by smoking more using the single target approach in findings of increased cessation for cigarettes per day, taking more and studies comparing two levels of VLNC cigarettes; subjective effects, deeper puffs, and/or puffing with a commercial low-yield nicotine craving, and withdrawal associated with faster draw rate) theoretically could cigarettes and nicotine lozenges (Ref. 4). VLNC cigarettes; and lower nAChR Nevertheless, some studies have occur under either a single target or occupancy and cerebral response from found that both reduction strategies stepped-down approach and could the use of VLNC cigarettes). Should increase a smoker’s probability of impact the public health benefits of a FDA rely on some or all of these types cessation. For example, in a study of of studies? Why or why not? Is there a possible nicotine tobacco product smokers with no strong preference for a different method that FDA should standard. According to studies quitting method who were randomly investigate or use to determine the involving VLNC cigarettes and other assigned to study arms requiring either threshold for nicotine addiction? reduced nicotine cigarettes, researchers that they quit immediately or gradually 3. In addition to nicotine, minor expect there could be very little or no reduce their cigarette consumption over tobacco alkaloids (including compensatory smoking with a single 2 weeks, both the immediate and nornicotine, cotinine, anabasine, target approach and that it would be gradual cessation methods produced anatabine, and myosamine) and tobacco self-limiting (i.e., smokers would be similar results (Ref. 110). Likewise, in a smoke aldehydes (such as acetaldehyde) unable to obtain their nicotine dose meta-analysis of 10 studies to determine are pharmacologically active and may from cigarettes no matter how they the impact of stepped reduction of contribute to addiction (see, e.g., Refs. smoke them and eventually would stop nicotine versus a single nicotine target 98 and 99). Researchers have trying to do so), which could maximize in participants interested in quitting investigated the abuse potential of the benefits of such a tobacco product smoking, scientists determined that a nornicotine, cotinine, anabasine, and standard (Refs. 3–5). If individuals were stepped reduction in nicotine ‘‘provides acetaldehyde in animals (Ref. 100). to engage in compensatory smoking similar quit rates to abrupt quitting with However, many of these compounds are with a single target approach, no evidence that one method is only present in tobacco smoke at low researchers find that any compensatory significantly superior to the other in levels and are likely less potent than smoking at the maximum nicotine levels adults trying to quit smoking’’ (Ref. 111 nicotine in mediating pharmacological that FDA is considering here could only at p. 13) and concluded that there were response and, therefore, reinforcement be minimal and transient (e.g., Refs. no additional cessation benefits for the (Refs. 101 and 102). In addition to 103, 104, 92, and 93). stepped-down approach (Ref. 111 at p. setting a maximum nicotine level, 2). In contrast, during a stepped-down should the product standard also set FDA understands the argument that a maximum levels of other constituents approach, tobacco users may attempt to stepped-down approach to limiting the (e.g., nornicotine, acetaldehyde, compensate for the loss of nicotine nicotine levels in tobacco products anabasine) that may have the potential during the early stages of a stepped- to produce dependence and be down approach by smoking additional 10 However, the IOM has cited one study showing addictive? If so, at what levels? tobacco products or by smoking more that when nicotine content is stepped down, 4. If FDA were to finalize a nicotine intensely, since the intermediate-stage smokers do not engage in compensatory smoking products could allow for extraction of when nicotine is extracted from tobacco and, tobacco product standard, what is the therefore, do not increase their toxic exposures (Ref. potential that adults and adolescents nicotine through such efforts in a way 13 at p. 349).

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could undermine the public health goals demonstrate a high level of specificity, coupled with flame ionization detection of such a standard by allowing for accuracy, and precision in measuring a (Ref. 115). prolonged exposure to tobacco-related range of nicotine levels across a wide CORESTA Method No. 62 is a toxicants during the step-down period. variety of tobacco blends and products. standard method used to analyze Although both approaches likely would A variety of methods have been in nicotine in tobacco filler and smokeless result in comparable quit rates development that allows nicotine in tobacco products (Ref. 116). This eventually, some studies have indicated tobacco or tobacco product filler to be method describes extraction of nicotine a greater likelihood of cessation success quantified for various products. For in solid tobacco in basified extraction with the use of a single target. In example, two Cooperation Centre for solution (using sodium hydroxide to addition, preliminary studies show that Scientific Research Relative to Tobacco deprotonate the nicotine in solution) of a single target approach could limit (CORESTA) methods have undergone either hexane containing n-heptadecane further exposure to harmful tobacco round-robin method validation studies or quinaldine internal standards or (when compared with the stepped-down in accordance with ISO 5725–1 through basified extraction solution (using approach to limiting nicotine levels). ISO 5725–2: (1) Continuous flow sodium hydroxide) of methyl-t-butyl FDA continues to weigh these factors, analysis (CFA) and (2) gas ether solution containing quinoline and will consider the information chromatography-flame ionization internal standard (id.). submitted in response to this ANPRM, detector (GC–FID). The CFA method FDA is also aware of other methods as it decides the appropriate approach measured a nicotine range of 0.69–3.30 that have been used to analyze nicotine for a potential nicotine tobacco product percent (or 6.9–33 mg/g) in burley and levels. Such methods include GC standard. flue-cured tobaccos and exhibited a combined with various detectors, GC– Please explain your responses and repeatability range of 0.03–0.17 and a MS with solid-phase microextraction as provide any evidence or other reproducibility range of 0.12–0.67, a preconcentration step for low information supporting your responses dependent on the mean (Ref. 112). A detection, other formats of GC–FID, to the following questions: GC–FID method for determining capillary electrophoresis combined with 1. What data are available to nicotine in fermented extractions from either ultraviolet (UV) or demonstrate that a single target tobacco leaves was validated in electrochemical detection, and approach to reach a maximum nicotine accordance with FDA and International alternative chromatography techniques level would or would not result in any Council for Harmonization of Technical including supercritical fluid unintended consequences? Requirements for Registration of chromatography-ion mobility detection 2. In the alternative, what data are Pharmaceuticals for Human Use (Ref. 117), reversed phase ion-pair available to demonstrate that a stepped- specifications, including specificity, liquid chromatographic extraction (Ref. down approach involving a sequence of linearity, precision, accuracy, and 118), and high-pressure liquid incremental levels and implementation robustness (Ref. 113). Gas chromatography with UV detection (Ref. dates to reach a proposed nicotine level chromatography-mass spectrometry 119). would or would not result in any (GC–MS) was used as the confirmation Please explain your responses and unintended consequences? technique in this study, in which a 3. If FDA were to select a stepped- provide any evidence or other recovery of 117.8 percent was achieved; down approach for a nicotine tobacco information supporting your responses recovery was within FDA guidelines product standard, what scientific to the following questions: (<120 percent) (Ref. 113). Nicotine evidence exists to support particular 1. If FDA were to issue a product content of 0.43 percent (4.3 mg/g) in the interim nicotine levels and the standard, should the Agency require a extract was reliably measured and appropriate number of steps that would standard method of product testing to stability testing on this same extract was be needed to reach the target level? analyze the nicotine levels in products 4. Would a single target and a conducted for 360 days (id.). In subject to the standard? If so, what stepped-down approach for addition, the WHO’s Tobacco method or methods should FDA use? implementation result in comparable Laboratory Network (TobLabNet) has 2. Should the Agency require quit rates or reduced initiation rates? developed a standard operating manufacturers to sample their products 5. What would be the likely procedure for determination of nicotine in a specific manner to ensure that implementation differences, including in cigarette tobacco filler using gas products do not contain excess levels of implementation timelines and transition chromatography (Ref. 114). The WHO’s nicotine? Should manufacturers be costs, between a single target approach TobLabNet determined that this method required to test each manufactured or a stepped-down approach involving a is suitable for the quantitative batch to ensure compliance with a sequence of incremental levels and determination of nicotine in cigarette product standard limiting nicotine implementation dates? tobacco filler by gas chromatography levels? What criteria should be used to (GC) (id.). determine if a batch passes or fails D. Analytical Testing Method We also note that ISO 10315 and testing? As part of its consideration regarding CORESTA Method No. 62 have been E. Technical Achievability a potential nicotine tobacco product used in substantial equivalence reports standard, FDA is also considering submitted to the Agency. ISO 10315 is FDA continues to analyze the whether such a product standard should a method for analyzing nicotine in technical achievability of a maximum specify a method for manufacturers to smoke. With this method, conditioned nicotine level for cigarettes as part of its use to detect the level of nicotine in cigarettes are smoked under ISO 4387 overall assessment of how best to their tobacco products. FDA believes conditions and smoke is captured on a implement this authority and is seeking that the results of any test method to Cambridge filter pad and extracted in comments from interested parties measure the nicotine in combusted propan-2-ol containing internal regarding this issue, including with tobacco products should be comparable standard such as n-heptadecane or respect to the technical achievability of across different accredited testing quinaldine (carvone or n-octadecane are such a standard for small cigarette and/ facilities and products. It is critical that other alternatives to internal standards) or small combusted tobacco product the results from the test method and analyzed immediately using GC manufacturers.

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The industry and consumer product cured, burley, oriental), geographical cured tobacco leaves harvested from the companies have developed versions of origin, year, and grade of the tobacco lowest stalk position may contain from denicotinized cigarettes and a range of (Ref. 128). Blend differences can 0.08 to 0.65 percent nicotine, whereas brands with differing nicotine levels. By produce significant variations in leaves from the highest positions may blending tobaccos based on nicotine nicotine concentration in the tobacco contain between 0.13 and 4.18 percent levels, tobacco companies have rod, leading to differences in smoke nicotine (Ref. 126, citing Ref. 134). manufactured their products to composition and yield (Ref. 120 at p. Therefore, substituting leaves found specifications that ensure the final 469). Grading, which is used to evaluate lower on the plants could reduce the product will have precise levels of and identify differences within tobacco nicotine content of tobacco products nicotine and have ensured that nicotine types and is a function of both plant (Ref. 131). levels vary only minimally within position (i.e., higher or lower on the A number of internal tobacco industry cigarette packs and from pack to pack stalk) and of quality (i.e., ripeness), and documents describe the use of leaf (60 FR 41453 at 41505, 41509, August segregation of grades by nicotine blending and tobacco selection to 11, 1995). In fact, the tobacco industry content, already has become common control the nicotine content of cigarettes has had programs in place since the practice (Ref. 128 at p. 2–3). (Ref. 128 at p. 3). For example, one 1960s to obtain ‘‘any level of nicotine Many tobacco lines are available, company project determined that low desired’’ (Ref. 120, citing Ref. 121). The including approximately 1,000 different nicotine cigarettes can be made by industry also has recognized that the tobacco varieties (Ref. 126). The tobacco selecting grades of tobacco with low techniques it has used to increase industry has used breeding and nicotine content (Ref. 128 at p. 3, citing nicotine levels can be used to reduce cultivation practices to develop high Ref. 135). Another observed that the nicotine levels as well (60 FR 41453 at nicotine tobacco plants to give demand for low nicotine tobacco has 41722). manufacturers greater flexibility in increased worldwide and necessitated a As previously described, VLNC blending and in controlling the amount shift in purchasing standards (Ref. 128 cigarettes have been produced since the of nicotine to be delivered (60 FR 41453 at p. 3, citing Ref. 136). 1970s. During this time, NCI contracted at 41694). These practices could be used for production of a line of cigarettes to develop low nicotine plants as well. 2. Chemical Extraction with widely varying nicotine In fact, tobacco industry documents Nicotine also can be removed from concentrations (Ref. 122, 81 SG). In the show that in the 1960s, tobacco tobacco via chemical extraction late 1980s, a major cigarette companies recognized the increasing technology. By the 1970s, tobacco manufacturer had plans to develop demand for low nicotine tobacco and manufacturers regularly practiced VLNC cigarettes with a reduction in began instituting projects that found nicotine extraction as a method to mainstream nicotine yields of greater that low nicotine cigarettes can be made control nicotine delivery (Ref. 128, than 95 percent (Ref. 123). More by selecting grades of tobacco with low citing Ref. 137; Refs. 138 and 139). recently, 22nd Century, acting as vendor nicotine content (Ref. 128; citing Ref. Extraction methods include water for RTI’s contract with NIDA, has 129; Ref. 130). extraction (coupled with steam or oven developed cigarettes, not currently Because the nicotine content of drying), solvent extraction, and commercially available, that are similar tobacco plants varies, manufacturers extractions of nicotine without usable in many sensory characteristics to could replace more commonly used leaf (Ref. 128). Supercritical fluid conventional cigarettes but with nicotine-rich varieties like Nicotiana extremely low nicotine levels (Refs. 54, rustica with lower nicotine varieties extraction also yielded success in the 124, and 125). (Ref. 131). Oriental Turkish-type 1990s, allowing for optimum extraction Significant reductions of nicotine in cigarettes also deliver substantially less times and the elimination of more time- combusted tobacco products can be nicotine than cigarettes that contain air- consuming steps (Refs. 140 and 141). achieved principally through tobacco cured Burley tobacco (Ref. 120; citing FDA notes that there are existing patents blending and cross-breeding plants, Ref. 132). In addition, manufacturers for chemical extraction of nicotine in genetic engineering, and chemical could select specific tobacco seedlings tobacco, which reveal that more than 96 extraction. Agricultural practices (e.g., that are low in nicotine and plant only percent of nicotine can be successfully controlled growing conditions, those low nicotine seedlings (Ref. 133). extracted while achieving a product that fertilization, harvest) as well as more Even without this selective breeding, ‘‘was subjectively rated as average in recent, novel techniques also can help manufacturers could use careful tobacco nicotine characteristics’’ (Refs. 142 and to reduce nicotine levels. One or a leaf purchasing plans to control the 66). combination of these processes could be nicotine content in their products (60 In addition, a major tobacco used to achieve the nicotine levels that FR 41453 at 41694). By maintaining manufacturer has used a high-pressure FDA is considering for a nicotine awareness of the differences and carbon dioxide process similar to the tobacco product standard. monitoring the levels in purchased process used to decaffeinate coffee. In tobacco, companies could produce this process, tobacco leaf is treated with 1. Tobacco Blending/Cross Breeding cigarettes with nicotine deliveries ammonium salt, then treated with Most of the cigarettes sold in the consistent to one-tenth of one percent carbon dioxide/water vapor, which has United States are blended cigarettes (despite variations of up to 25 percent achieved a 95 to 98 percent reduction in (Ref. 126). A tobacco industry executive in the nicotine content of the raw nicotine (Ref. 133, citing Ref. 143) previously testified that the main material grown in the same area, from Although some manufacturers believe component of a cigarette that year to year) (60 FR 41453 at 41694). that previous water extraction practices contributes to nicotine delivery is the The position of leaves on the plant may have rendered the tobacco tobacco blend and that year-to-year crop stalk also affects nicotine levels; tobacco ‘‘unsuitable for use,’’ other water variation does not determine the leaves located near the top of the plant extraction projects yielded suitable nicotine content in a cigarette (Ref. 127). can contain higher concentrations of smoking material with sizeable nicotine The term ‘‘leaf blending’’ describes the nicotine and lower stalk leaves reductions (80 to 85 percent reduction selection of tobaccos to be used in a generally contain lower nicotine levels in leaf nicotine) (Ref. 128, citing Ref. product by tobacco type (e.g., flue- (Ref. 114; Ref. 120). For example, flue- 144; Refs. 145 and 146).

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3. Genetic Engineering plant density (id., citing Ref. 162). In non-cigarette combusted tobacco Tobacco industry scientists have long other cases, chemical agents were products (e.g., cigarette tobacco, RYO recognized the potential for genetic observed to reduce nicotine content tobacco, little cigars, large cigars, engineering to control nicotine content (Ref. 128 citing Refs. 163–165). cigarillos, pipe tobacco, and waterpipe After growers harvest tobacco, it is (Ref. 147). The first practical application tobacco) that FDA is considering cured and aged before use in tobacco of biotechnology by a major tobacco covering under a nicotine tobacco products. The aging process naturally manufacturer was the development of product standard? changes the chemistry of the tobacco, 4. If FDA were to propose a tobacco low nicotine tobacco in the 1980s, including some reduction in nicotine product standard setting a maximum which led to the receipt of a patent for content (Ref. 128). At least one nicotine level, how, if at all, would such biotechnology for altering nicotine in manufacturer has explored efforts to a product standard impact tobacco tobacco plants (Refs. 133 and 148). speed up the process of aging tobacco, farmers’ growing and/or curing Other tobacco researchers and major in part to alter or limit the changes in practices? If FDA were to finalize a manufacturers also recognized the value chemistry that naturally occur (id., nicotine tobacco product standard, what of biotechnology for developing low citing Ref. 166). Other approaches to would be the costs and benefits for nicotine tobacco for cigarettes, curing and fermenting tobacco were tobacco farmers and tobacco processors, including for use as part of a smoking explored as a method for altering particularly regarding how any such cessation program (Ref. 149). nicotine content (Ref. 128). For rulemaking might affect them in light of Several American and international example, in one manufacturer’s report, new technologies and business tobacco companies genetically researchers observed that the properties opportunities that are foreseeable, but engineered low nicotine varietals in the of tobacco, including nicotine content, not now in place? In addition, if FDA 1960s and 1970s, including a strain with could be altered without the need for were to finalize a nicotine tobacco nicotine levels as low as 0.15 percent nontobacco additives by modifying product standard, what would be the (Ref. 128; citing Refs. 150–155). During curing practices (id., citing Ref. 167). In costs for farmers in light of such a that time period, the Kentucky Tobacco addition, manufacturers have explored standard? Research Board worked on genetic approaches to identify microbial 5. Section 907(d)(2) of the FD&C Act strains of low nicotine tobacco (with a bacteria that actively degraded nicotine provides that a tobacco product nicotine content of 0.2 percent) to be while leaving other components of the standard must set forth the effective used for experimental studies on the leaf intact (Ref. 128, citing Refs. 168 and date of the standard, which may not be role of nicotine in smoking behavior 169). Consumer product testing showed less than 1 year after publication of a (Ref. 128, citing Refs. 156–159). In that the ‘‘product acceptability’’ of that final rule unless FDA determines that an addition, Canadian researchers tobacco was equal to that of untreated earlier effective date is necessary for the examined low nicotine strains of tobacco (Ref. 128, citing Ref. 170). protection of the public health (and that tobacco, particularly in association with Researchers have developed novel such effective date be established ‘‘to efforts to develop a strain of flue-cured approaches to reducing the nicotine in minimize, consistent with the public or air-cured tobacco that would be tobacco products in recent years. For health, economic loss to, and disruption suitable as the base material for example, a salivary excretion produced or dislocation of, domestic and reconstituted tobacco (Ref. 128, citing by a caterpillar (containing the enzyme international trade’’). This section also Refs. 151 and 160). In 2003, Vector glucose oxidase) is applied to tobacco provides that the effective date be a Tobacco began marketing the Quest plant leaves and can reduce the nicotine minimum of 2 years after publication of cigarette, which was produced from in tobacco leaf by up to 75 percent and a final rule if the tobacco standard can genetically modified tobacco and provide an ‘‘effective and economical be met only by requiring ‘‘substantial contained only trace amounts of system for producing tobacco products changes to the methods of farming the nicotine (Ref. 133) (this product is no which contain about 0.01 mg nicotine domestically grown tobacco used by the longer on the market). Genetic per cigarette or less . . . while manufacturer.’’ Therefore, if FDA were engineering has resulted in reductions maintaining the other desirable to propose a product standard setting a of nicotine levels in the range of 80 to ingredients for good taste and flavor’’ maximum nicotine level, when should 98 percent (id.). In 2014, the U.S. Patent (Ref. 67). this standard become effective? What and Trademark Office granted two Please explain your responses and implementation timeframe would allow patents for two genes that may be provide any evidence or other adequate time for industry to comply? suppressed to achieve a substantial information supporting your responses Should the same timeframe be required decrease in nicotine in tobacco plants to the following questions: for all tobacco product manufacturers, (Ref. 161). 1. What methods are tobacco product regardless of their number of employees manufacturers currently using to 11 4. Other Practices and/or annual revenues? Given the maintain consistency of the nicotine in currently available processes to reduce Industry studies have shown that their products, given the variability of the nicotine in tobacco products (e.g., changes to growing and harvesting nicotine levels over growing seasons chemical processes, genetic practices affect the development of and crop type? How could these engineering), what do manufacturers tobacco chemistry, including nicotine methods be adapted to ensure that content (Ref. 128). Some manufacturers certain combusted tobacco products 11 The Tobacco Control Act defines ‘‘small have revised their agricultural practices meet a potential nicotine tobacco tobacco product manufacturer’’ to be a tobacco specifically to meet new product product standard? product manufacturer that employs fewer than 350 employees (21 U.S.C. 387(16)). In the preamble to development goals, such as the 2. What is the feasibility of using the the deeming rule, FDA defined ‘‘small-scale tobacco production of low nicotine tobacco (id.). techniques discussed in this section, or product manufacturers’’ to be a manufacturer of any For example, one manufacturer other nicotine reduction techniques, to regulated tobacco product with 150 employees or evaluated various experimental reduce the nicotine in cigarettes? fewer and annual total revenues of $5 million or 3. What is the feasibility of using the less (81 FR 28973 at 28980). If you are providing agricultural practices that could affect comments or information relevant to these the tobacco’s chemistry, including bulk- techniques discussed in this section, or definitions or a different definition, please note that curing, once-over harvesting, and high other nicotine reduction techniques, for definition in your comments.

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and others with relevant expertise define ‘‘premium cigar’’ to minimize ‘‘modest’’ (Ref. 172). The IOM suggests consider an appropriate timeframe to such consequences. that demand would be limited, because implement a product standard to reduce While FDA believes that some some smokers may quit and other will nicotine? Would a 2-year, 4-year, or 6- consumers would be satisfied with use modified products or seek legal year timeframe be appropriate? VLNC cigarettes, the Agency expects alternatives (id.). Although some 6. Should the standard include that there would be a subset of smokers may seek to purchase illicit provisions that would allow consumers uninterested in switching to products if available and accessible, the manufacturers, distributors, or retailers VLNC cigarettes or quitting tobacco IOM finds that this ‘‘would require to sell off existing nonconforming products altogether. This subset of established distribution networks and inventory of manufactured combusted consumers may seek to obtain illicit new sources of product (which would tobacco products? If so, what would be tobacco products after a standard either have to be smuggled from other a reasonable sell-off period? becomes effective (see FDA’s Draft countries or produced illegally) to create 7. What are the potential outcomes of Concept Paper). As a result, FDA is a supply of cigarettes with prohibited implementing methods to reduce considering whether an increase in features’’ (id.). Given that individuals nicotine content in cigarettes in terms of illicit trade might occur as a result of a have utilized distribution networks to impact on characteristics of cigarettes nicotine tobacco product standard and smuggle cigarettes and avoid higher (flavor, taste, aroma, etc.) and user how that could impact the marketplace taxes, FDA is considering whether there experience? and public health. The analysis of might be additional incentive to create possible illicit trade includes or obtain the prohibited cigarettes that F. Possible Countervailing Effects considerations regarding the sources of are not available elsewhere in the Section IV. B discusses some of the tobacco, how illicit tobacco products United States. In addition, the report potential benefits that FDA expects might be manufactured, possible explains that comprehensive could occur as a result of one possible workarounds (such as adding nicotine interventions by several countries show nicotine tobacco product standard. in liquid or other form to a product with that it is possible to reduce the size of There may be possible countervailing minimally addictive or nonaddictive the illicit tobacco market through nicotine levels), the ability to distribute effects that could diminish the enforcement mechanisms and illicit products, the development of population health benefits expected as a collaborations across jurisdictions (id.). consumer awareness, and how illicit If a nicotine tobacco product standard result of a nicotine tobacco product trade sales might take place (id.). The were to prompt the development of an standard. As part of any subsequent capacity to produce illicit tobacco illicit market, FDA would have the rulemaking FDA would need to assess products would depend upon a variety authority to take enforcement actions these effects in comparison to the of factors, including the ease of regarding the sale and distribution of expected benefits, including among acquiring the raw materials (particularly illicit tobacco products. The FD&C Act population subgroups. tobacco), the sophistication required to provides FDA with several tools that it One possible countervailing effect is construct the desired product, and the may use against noncompliant parties. continued combusted tobacco product purpose (whether it is for an For example, FDA could issue a use. Current smokers of tobacco individual’s personal use, or for wider Warning Letter, an advisory action in products covered by a nicotine tobacco distribution and sale). Large, which FDA notifies a regulated entity product standard could turn to other commercial, tobacco product that FDA has found evidence that the tobacco products to maintain their manufacturers have the resources, party violated the law. A Warning Letter nicotine dependence, both in sophistication, and ability to is used to achieve prompt voluntary combination with cigarettes (i.e., dual manufacture illicit tobacco products compliance. In a Warning Letter, FDA use) or in place of cigarettes (i.e., (id.). Illicit tobacco products also may informs the regulated entity that failure switching). For those users seeking to be smuggled and sold through the to comply with the requirements of the switch to a potentially less hazardous internet. It is unclear, however, to what FD&C Act and its implementing tobacco product (e.g., electronic extent such companies would be willing regulations may result in FDA nicotine delivery systems), FDA expects to risk their businesses (and resulting enforcement action. These actions may that the increase in consumer demand profits) to manufacture illicit tobacco include initiating administrative actions for such other products likely would be products (id.). Tribal manufacturers are or referring cases to the Department of met by the tobacco industry, which has an additional source of tobacco Justice for initiation of judicial action. a history of being responsive to market products, having relatively high FDA may seek to initiate an shifts (see FDA’s Draft Concept Paper sophistication and machinery in some administrative legal action against a published elsewhere in this issue of the instances, but they are also subject to regulated entity that can result in the Federal Register). For example, the same disincentives as large imposition of a fine or civil money traditional cigarette manufacturers manufacturers and generally lack penalty. Possible judicial actions may began to expand into the smokeless widespread distribution and sales include seizures, injunctions, and market when restrictions on where capabilities (id.). criminal prosecution. smokers were allowed to smoke were in The IOM has explored the issue of Another possible countervailing effect enacted in the 1980s, 1990s, and early possible illicit trade if FDA were to is the potential for increased harm due 2000s (id., citing Ref. 171). FDA also issue a tobacco product standard to continued VLNC smoking with wishes to better understand whether limiting the levels of nicotine in altered smoking behaviors. Some users would switch to premium cigars if cigarettes. The IOM found that although studies of VLNC cigarettes with nicotine these products were excluded from the there is insufficient evidence to draw levels similar to what FDA is scope of a nicotine tobacco product firm conclusions regarding how the U.S. considering have not found standard. FDA has requested data and illicit tobacco market would respond to compensatory smoking behavior and information on whether large and/or so- regulations requiring a reduction in the have found reductions in the number of called premium cigars would be nicotine content of cigarettes, limited cigarettes smoked per day and, migration or dual use candidates, or evidence suggests that the demand for consequently, decreased exposure to whether and how there is a way to illicit conventional cigarettes would be harmful constituents (as discussed in

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section IV.B of this document). If FDA tobacco product standard would be self- their relevant characteristics, such as decides to pursue a proposed nicotine limiting (i.e., smokers would be unable nicotine levels? How can available product standard, FDA will continue to to obtain their nicotine dose from sources of information, such as consider this potential countervailing cigarettes no matter how they smoke manufacturer registrations and/or effect. them and eventually would stop trying product listings with FDA, be used in Another possible countervailing effect to do so). Do any peer-reviewed studies this assessment? of setting a maximum nicotine level for demonstrate that lowering the nicotine 2. How should potential consumer cigarettes could be that users would content of cigarettes to minimally surplus or utility loss from the removal seek to add nicotine in liquid or other addictive levels might encourage of nicotine in cigarettes be considered, form to their combusted tobacco consumers to smoke more VLNC given the availability of other sources of products. Therefore, FDA is considering cigarettes to achieve the higher nicotine nicotine such as ENDS and the whether any action it might take to doses currently delivered by NNC continued availability of combustible reduce nicotine in combusted tobacco cigarettes? tobacco products? products should be paired with a 5. If a nicotine tobacco product 3. What sources of information could provision that would prohibit the sale or standard were in effect, the following be used to estimate the change in distribution of any tobacco product outcomes could occur: (1) Smokers demand for VLNC cigarettes? What designed for the purposes of could continue to smoke but use the low factors should we consider in estimating supplementing the nicotine content of a nicotine products; (2) smokers could the changes in demand for other tobacco combusted tobacco product (or any completely switch to, or dual use low products? product where the reasonably nicotine products with, other legal 4. What factors should be considered foreseeable use is for the purposes of tobacco or nicotine products; (3) in estimating changes in supplementing this nicotine content). smokers could quit using any nicotine experimentation and initiation that may FDA is also considering what other or tobacco product; or (4) smokers could occur as a result of a potential nicotine regulatory options may be available to seek to buy illegal cigarettes in an illicit tobacco product standard? address this concern and requests market. Are there data that would 5. In what ways might a change in comments on such options. provide information on which of these nicotine levels in cigarettes spur Please explain your responses and outcomes is most likely? Is there some innovation in the market for both provide any evidence or other other outcome that could occur? combusted and noncombusted tobacco information supporting your responses 6. If an illicit market developed, what products? to the following questions: percentage of current smokers would 6. What factors should be considered 1. In addition to a nicotine tobacco switch to illicit conventional cigarettes in estimating the impacts of product standard, should FDA consider rather than quitting or switching to externalities that might exist for VLNC any additional regulatory action to other legal products? How would this cigarettes, such as secondhand smoke, address the possibility of migration to, change if illicit conventional cigarettes litter, and pollution? How could the or dual use with, other tobacco were more expensive and/or harder to impact of externalities for VLNC products? obtain? How would this change with the cigarettes be compared to the impacts 2. If FDA were to issue a product implementation of improved monitoring from NNC cigarettes? standard setting a maximum nicotine and enhanced enforcement by FDA and 7. What factors should we consider in content for cigarettes, would smokers its partners? estimating the impact of changes in seek to add liquid nicotine to their 7. If a nicotine tobacco product demand for other tobacco products? VLNC cigarettes? Therefore, should standard prompted growth of an illicit 8. If FDA were to finalize a nicotine such a regulation include provisions market, how long would it likely last? tobacco product standard, what might prohibiting the sale or distribution of Would demand likely decrease over be the costs to current smokers? any tobacco product designed for the time, stay the same, or increase? 9. Are there any other relevant purposes of supplementing the nicotine 8. If a nicotine tobacco product comments or information that would be content of a combusted tobacco product standard prompted growth of an illicit helpful for FDA to consider in analyzing (or any product where the reasonably market, what effect, if any, would this the economic impacts of a proposed foreseeable use is to supplement this have on the market for illegal drugs? Are nicotine tobacco product standard? nicotine content)? How could such a there data showing a relationship V. Potential Public Health Benefits of provision be structured to efficiently between illicit tobacco use and illegal Preventing Initiation to Regular Use and effectively achieve this purpose? drug use? and Increasing Cessation Should FDA consider other means to 9. What mechanisms may be used to prevent supplementing the nicotine prevent, control, or contain illicit If FDA were to issue a proposed content of a combusted tobacco product markets in conventional cigarettes that tobacco product standard setting a subject to a nicotine tobacco product may develop if FDA establishes a maximum nicotine level, FDA would standard? product standard? What State and provide an analysis explaining how the 3. Would a nicotine tobacco product Federal entities may be responsible for proposed rule would be appropriate for standard affect the current illicit trade these mechanisms, and how much the protection of the public health market, and, if so, to what extent? How would they cost? (section 907(a)(3)(A) of the FD&C Act). would users obtain their sources of For the purposes of this ANPRM, this tobacco in an illicit market? How would G. Other Considerations section briefly describes the potential manufacturers distribute their illicit To aid in its consideration regarding public health benefits FDA believes products and develop consumer development of a nicotine tobacco could result from the increased awareness of such products? How product standard, FDA is seeking data, cessation and decreased initiation to would such sales take place? research results, and other information regular use that FDA expects could 4. FDA hypothesizes that, based on regarding the following: occur if cigarettes and possibly some currently available research, nicotine 1. What data may be helpful to assess other combusted tobacco products were levels like those levels that FDA would the universe of tobacco products that are minimally addictive or nonaddictive. It consider with a possible nicotine currently available to consumers and also references findings from a

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population-based simulation model that alleviate those complications as well tobacco products is highly addictive, quantified the potential public health (Ref. 17). and addiction to nicotine is the impact of enacting a regulation lowering Youth and young adults would ‘‘fundamental reason that individuals nicotine levels in cigarettes and some experience the greatest benefits from a persist in using tobacco products’’ (Ref. other combusted tobacco products to nicotine tobacco product standard, 17 at p. 105). Although nicotine itself is minimally addictive levels, utilizing because many of them may not progress not the direct cause of most tobacco- inputs derived from empirical evidence beyond experimentation and, therefore, attributable disease, addiction to the and expert opinion. We are seeking may not experience dangerous and nicotine in tobacco products is the public comment regarding the inputs deadly tobacco-related health effects. proximate cause of these conditions that should be used for modeling the Fetuses and children also would benefit because it sustains tobacco use (Refs. 54 impact of a nicotine tobacco product if their parents quit smoking, given the and 179). Addiction caused by nicotine standard. negative health consequences to the in tobacco is critical in the transition of fetus of a smoking mother and the smokers from experimentation to A. Smoking Cessation Would Lead to dangers of secondhand smoke. In sustained smoking and in the Substantial Public Health Benefits for addition, children of parents who maintenance of smoking for those who People of All Ages smoke, when compared with children of want to quit (Ref. 7 at p. 113; Ref. 17). Significant declines in the deaths nonsmoking parents, have an increased As a result, FDA expects that making caused by the use of combusted tobacco frequency of respiratory infections like cigarettes minimally addictive or products can be achieved by reducing pneumonia and bronchitis (Ref. 173). nonaddictive would reduce tobacco- the prevalence of smoking cigarettes and Smoking cessation reduces the rates of related harms by promoting smoking other combusted tobacco products. these respiratory symptoms and of cessation or complete migration to Smoking cessation has major and respiratory infections (Ref. 176 at p. alternative, potentially less harmful immediate health benefits for men and 467). Children exposed to tobacco noncombusted products and by women of all ages, regardless of health smoke in the home also are more likely reducing initiation. In this section, we status (Ref. 173 at p. i). Smoking to develop acute otitis media (middle summarize the approach used to cessation decreases the risk of the health ear infections) and persistent middle ear describe the possible impact of a consequences of smoking, and former effusions (thick or sticky fluid behind potential nicotine tobacco product smokers live longer than continuing the eardrum) (Ref. 173). If parents were standard to the population as a whole smokers. For example, persons who quit more able to quit because these products and present the findings of this analysis. become minimally addictive or smoking before age 50 have one-half the As discussed elsewhere in this nonaddictive, youth would experience risk of dying in the next 15 years document, FDA is considering the scope these health problems much less compared with continuing smokers (id. of a potential product standard, and has at p. v). frequently. Although the health benefits are asked for public comment. To assess the Smoking cessation reduces the risk of greater for people who stop smoking at impact of one potential option that cancers throughout the body (Ref. 173). earlier ages (Refs. 173 and 176), might maximize the potential public For example, although the risk of dying researchers estimate that smokers can health impact, it may be appropriate to from lung cancer is 22 times higher for gain years of additional life expectancy consider the Apelberg et al. 2018 male smokers than male nonsmokers no matter when they quit (Ref. 177). In publication, which presented (and 12 times higher for female smokers addition, scientists using data from the simulation modeling of a policy than female nonsmokers), the risk of Cancer Prevention Study (CPS–II), but scenario in which the scope of a lung cancer after 10 years of abstinence accounting for bias caused by smoking potential product standard restricted the is 30 to 50 percent that of continuing cessation after baseline, found that even nicotine level in cigarettes, cigarette smokers (id.; Refs. 174 and 175). smokers who quit at age 65 had an tobacco, RYO tobacco, cigars (including Smoking cessation also reduces the expected life expectancy increase of 2 little cigars, large cigars, and cigarillos, risk of other life-threatening illnesses years for men and 3.7 years for women but not so-called ‘‘premium’’ cigars), that occur in smokers. In addition to (Ref. 178). and pipe tobacco (other than waterpipe/ reducing the risk of cancers and the The benefits continue for those who hookah tobacco). As part of a formal mortality rates of smoking-related remain smoke free. At year one, an expert elicitation process (this process diseases, smoking cessation individual’s added risk of coronary centered around three online substantially reduces the risk of other heart disease becomes half that of a conferencing sessions held during dangerous diseases that can lead to smoker’s (Ref. 175). Between 2 and 5 January and February 2015, following a death or disability and cause a financial years after cessation, an individual’s written protocol designed to elicit strain on health care resources. For stroke risk is reduced to that of a opinions using a structured, example, smoking cessation nonsmoker (id.). In addition, a former standardized approach (see Ref. 181 for substantially reduces risk of peripheral smoker’s risk of cancers of the mouth, more details)), eight subject matter artery occlusive disease (which can throat, esophagus, and bladder is halved experts were asked to provide their cause complications that lead to loss of within five years (id.). By 10-years post individual estimates of the anticipated limbs) (Ref. 173). Former smokers also cessation, an individual’s risk of cancers impacts of a hypothetical policy (setting have half the excess risk of experiencing of the kidney and pancreas decreases a ‘‘maximum limit on the amount of an abdominal aortic aneurysm (id). The risk of coronary heart disease nicotine in cigarette tobacco filler’’ for compared to current smokers (id.). becomes that of a nonsmoker after 15 the purpose of reducing nicotine in Cigarette smoking also complicates years of abstinence (id.). cigarettes ‘‘to minimally addictive many diseases (e.g., smokers with levels’’) and to develop subjective diabetes have higher risk of B. A Nicotine Tobacco Product probability distributions for parameters complications, including heart and Standard Could Lead to Substantial of interest. kidney disease, poor blood flow in the Improvement in Public Health A more detailed description of the legs and feet, retinopathy and peripheral As stated throughout this document, methodology, data sources and inputs, neuropathy), and smoking cessation can nicotine at levels currently found in and results from this analysis can be

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found in two peer-reviewed The methodology implemented in this experts prior to the conference sessions. publications (Refs. 180 and 181). analysis has been detailed elsewhere Experts were asked to identify any other (Refs. 180 and 181). Briefly, the relevant information to share with the 1. Approach to Estimating Impacts to simulation begins with an initial the Population as a Whole panel. Detailed written questionnaires population that reflects the sex, age, and were completed by each expert as As described in this document, FDA tobacco use distribution (i.e., never, independent take-home exercises. To expects that making cigarettes current, and former use of cigarettes and maintain the independence of the minimally addictive or nonaddictive noncombusted products) of the U.S. experts and encourage open discussion, (however that were achieved) would population in 2015, based on U.S. involvement of FDA staff was limited. impact currently addicted smokers by Census Bureau estimates. The analysis increasing their ability to quit smoking projects population changes for 2016– To explore the potential impact of a and affect nonsmokers by reducing the 2100 in 1-year increments, while product standard that would maximally likelihood that they would become accounting for births, net migration benefit population health, the experts established and addicted smokers. (which accounts for immigration and were asked to assume that combusted Apelberg et al. 2018 updated a emigration) and deaths, the last of tobacco products that could be viewed previously published discrete system which is a function of age, sex, and as highly likely to serve as substitutes dynamic population model to compare tobacco use status. Baseline estimates for traditional cigarettes (i.e., RYO projected outcomes for a status-quo for tobacco use status (combinations of tobacco, pipe tobacco, nonpremium scenario (in which no maximum current, former, and never use for cigars) would be included in the policy, nicotine level is implemented) with cigarettes and noncombusted products) while other tobacco products (i.e., outcomes for a policy scenario in which by sex, age, and time since cessation (for premium cigars, waterpipe/hookah, a hypothetical regulation lowering cigarettes only) were obtained from the ENDS, smokeless tobacco) would be nicotine in cigarettes, and selected other 2015 National Health Interview Survey excluded.13 The eight experts were combusted tobacco products, to (NHIS) for adults (Ref. 1) and the 2015 asked to predict and quantify the minimally addictive was NYTS for youth (Ref. 182). Mortality anticipated impact of the policy on the implemented 12 (Ref. 181). rates and relative risks by tobacco use following model parameters: (1) The model incorporated, based on status were obtained from U.S. vital Cigarette smoking cessation rates; (2) estimates of subject matter experts, the statistics data, NHIS data linked for switching from cigarette smoking to following tobacco use transitions to mortality followup (for never smoker other tobacco products excluded from estimate the impact of the policy: (1) mortality rates and cigarette smoking the hypothetical policy scenario; (3) Cigarette smoking cessation; (2) cigarette relative risks), and the CPS–II (for dual use rates; (4) cigarette smoking smokers switching to noncombusted smokeless tobacco product relative initiation rates; and (5) initiation rates tobacco products (e.g., smokeless risks). In the absence of data on the for other tobacco products excluded tobacco and/or electronic cigarettes) long-term health risks of ENDS, from the hypothetical policy scenario. rather than quitting tobacco use entirely; Apelberg et al. assumed that the ENDS Each of the eight experts was asked to (3) continuing smokers becoming dual products carried the same risks provide his or her best estimate of the users of cigarettes and noncombusted associated with traditional smokeless parameters’ true value, estimates of the tobacco products; (4) nonsmokers tobacco (see Ref. 181 for more detail). minimum and maximum plausible initiating regular cigarette smoking; and Quantitative inputs for rates of post- values, and estimates of the 5th, 25th, (5) nonsmokers who have been policy smoking cessation, switching, 75th and 95th percentile values. Experts dissuaded from smoking cigarettes and and dual use in the hypothetical policy were asked first about impacts in the certain other combusted tobacco scenario were obtained through a formal first year immediately following the products, who may instead initiate use expert elicitation process. The potential product standard’s of a noncombusted tobacco product. methodology used to identify experts, implementation and then about the The model, based on input parameters develop the protocol, conduct the impacts in the years following the first derived from expert estimates, projected elicitation, and summarize the findings full year of implementation. Experts had the impact of the policy on four main has been described in detail elsewhere outcomes: (1) Prevalence of cigarette the option of providing separate (Ref. 181 at Appendix). Briefly, estimates of impacts for males and smoking and noncombusted tobacco elicitation candidates with expertise in product use; (2) the number of females for the initial and subsequent tobacco science and policy were years. For each question, experts were individuals dissuaded from cigarette identified, ranked, and recruited in smoking; (3) cumulative number of asked to provide the factors they accordance with a pre-specified considered pertinent to answering the tobacco-attributable deaths avoided; and protocol, based on publication history (4) cumulative life years gained as a question, including the studies and and accounting for potential conflicts of research findings most influential to result of a regulation setting a maximum interest. Candidates were required to nicotine level. informing their views, and to rate their self-certify that they were free of any familiarity with the relevant literature. actual, apparent, or potential conflicts of 12 The elicitation process provided the The policy scenario presented in Apelberg et al. interests. The elicitation process 2018 (Ref. 181) did not define a specific level of experts with opportunities to interact centered around three online nicotine as minimally addictive. Rather, the policy and discuss divergent views, from scenario simulated implementation of a conferencing sessions held during hypothetical standard in which cigarettes and January and February 2015, following a certain other combusted tobacco products were 13 While the policy scenario presented in made minimally addictive, informed by a formal written protocol designed to elicit Apelberg et al., 2018 (Ref. 181) is based on expert elicitation process (Ref. 181), used to opinions using a structured, reduction in nicotine level in cigarettes, cigarette estimate the impact of decreasing the addictiveness standardized approach (see Ref. 181 for tobacco, RYO tobacco, certain cigars and pipe of cigarettes on certain tobacco use behaviors. Given more details). Briefing books with key tobacco, the estimated population impact is based the lack of specificity in the hypothetical scenario papers on the topics of interest as well on reductions in cigarette smoking. FDA notes that posed in the Apelberg et al. study, caution is not accounting for reductions in the use of other warranted in extrapolating its results to the as background data on tobacco use and combusted tobacco products may underestimate the assessment of a particular policy. policy were provided to a panel of eight overall impact of this policy scenario.

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which each expert generated his/her subsequent years, the simulation model would quit smoking after initial and final estimates. projects that the difference in cigarette implementation of the policy, The eight experts’ judgments about smoking prevalence between the approximately 5 million additional the potential values of these parameters scenarios continues to grow due to the smokers are estimated to quit smoking are published in Apelberg et al. 2018 experts’ estimates of sustained increases within one year after implementation of (Ref. 181). While parameter estimates in cessation and decreases in initiation the product standard (5th and 95th and their probability distributions in the policy scenario. The projected percentile projections range from varied somewhat between participants, smoking prevalence drops to a median 110,000 to 19.7 million), compared to most experts had the view that making value of 1.4 percent (5th and 95th the baseline scenario. The number of cigarettes and certain other combusted percentile projections range from 0.2 additional smokers quitting would tobacco products minimally addictive percent to 5.9 percent) under the policy increase by approximately 13 million would lead to substantial initial and scenario by 2060 compared to 7.9 within 5 years after policy long-term increases in smoking percent under the baseline. Smoking implementation (5th and 95th percentile cessation among cigarette smokers and prevalence estimates for the year 2100 projections range from 430,000 to 30.5 decreased initiation among nonsmokers. are comparable to those for 2060. million), compared to the baseline Distributions provided by the eight Concurrent with a projected reduction scenario. experts’ parameter estimates were in cigarette smoking is a projected substantially broad in range. For increase in noncombusted product use. example, for both male and female non- TABLE 2—PROJECTED NUMBER OF IN- Adult noncombusted tobacco product DIVIDUALS WHO WOULD NOT INI- smokers, the median minimum and use is higher in the hypothetical policy TIATE REGULAR SMOKING AS A RE- maximum estimates from the eight scenario compared to the baseline experts on the ‘‘percent of reduction in scenario within the first year of SULT OF A NICOTINE TOBACCO annual smoking initiation rates’’ after implementation of the potential product PRODUCT STANDARD IMPLEMENTED the first year in response to the policy standard (Ref. 181 at Figure 1), due to IN 2020 ranged from 10 percent to 90 percent. estimated increases in switching from For both male and female smokers, the cigarette smoking and transitions to Cumulative new smoking initiates median minimum and maximum avoided dual cigarette and noncombusted (in millions) estimates from the eight experts on the product use as a result of the Year ‘‘percent of current smokers who quit hypothetical policy scenario. The 5th Median 95th smoking as a result of the policy’’ prevalence of noncombusted tobacco percentile percentile within the first year after policy product use remains higher in the implementation ranged from 4 percent policy scenario over time due to the 2040 .. 2.0 8.1 15.6 to 50 percent. experts’ predictions that there would be 2060 .. 3.9 16.0 31.0 To account for uncertainty associated 2080 .. 5.9 24.4 47.2 both increased uptake among smokers with the expected impact of the policy 2100 .. 8.0 33.1 64.1 (through either complete switching or scenario, Apelberg et al. 2018 used the dual use) and increased initiation due to distributions of the experts’ estimates in some dissuaded cigarette initiators Table 3 presents the estimated a Monte Carlo simulation. A Latin cumulative number of tobacco- Hypercube sampling with 1,000 sample taking up noncombusted products instead. attributable deaths potentially avoided values was performed for each of the and life years gained due to the experts’ expert’s response distributions. For each Table 2 provides a projection of the number of individuals who would not determinations that smoking rates simulation, the policy scenario was would decrease as a result of the compared to the baseline scenario to become cigarette smokers over time as a hypothetical policy scenario. By 2060, it estimate changes in the outcomes result of the hypothetical policy is estimated that a median value of described above. A summary of scenario. Since it is assumed, based on almost 3 million deaths due to tobacco distribution responses are provided in expert input, that there would be a would be avoided (5th and 95th Apelberg et al. 2018. sustained decrease in cigarette smoking initiation rates, the model projects that percentile projections range from 0.7 2. Projected Impacts to Users, Nonusers, the cumulative number of dissuaded million to 4.3 million), rising to 8.5 and the Population as a Whole smoking initiates continues to increase million by the end of the century (5th As illustrated in Figure 1 (Ref. 181), over time. By 2100, the median estimate and 95th percentile projections range using the experts’ input estimates for from the model, based on the experts’ from 2.2 million to 11.2 million). The the parameters described previously, estimates of potential initiation rates as reduction in premature deaths and assuming that the policy is a result of the policy, is that more than attributable to the hypothetical policy implemented in 2020, the simulation 33 million youth and young adults who scenario would result in approximately model projected that cigarette smoking would have otherwise initiated regular 33 million life years gained by 2060 (5th prevalence declines substantially in the smoking would not start as a result of and 95th percentile projections range policy scenario within the first year of the hypothetical policy scenario (5th from 7.8 million to 53.9 million) and implementation of the hypothetical and 95th percentile projections range over 134 million life years gained by policy scenario to a median value of from 8.0 million to 64.1 million). 2100 (5th and 95th percentile 10.8 percent compared with 12.8 Using the eight experts’ estimates for projections range from 31.6 million to percent in the baseline scenario. In the percent of current smokers who 183.0 million).

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TABLE 3—PROJECTED NUMBER OF TOBACCO-ATTRIBUTABLE DEATHS AVOIDED AND LIFE YEARS GAINED DUE TO REDUCED SMOKING AS A RESULT OF A NICOTINE TOBACCO PRODUCT STANDARD IMPLEMENTED IN 2020

Cumulative tobacco attributable deaths avoided Cumulative life years gained (millions) (millions) Year 5th 95th 5th 95th percentile Median percentile percentile Median percentile

2040 ...... 0.3 0.9 1.4 2.5 6.8 11.5 2060 ...... 0.7 2.8 4.3 7.8 33.1 53.9 2080 ...... 1.3 5.6 7.9 16.5 79.6 118.0 2100 ...... 2.2 8.5 11.2 31.6 134.4 183.0

3. Request for Comments • Percent of dissuaded smoking electronically at https:// Based on the experts’ judgments that initiates who initiate noncombusted www.regulations.gov. FDA has verified reducing nicotine levels in combusted tobacco product use instead. the website addresses, as of the date this tobacco products would increase Please include your assumptions about document publishes in the Federal smoking cessation and decrease the scope of the standard and data that Register, but websites are subject to smoking initiation, and calculations supports your estimates. change over time. from the simulation model describing 4. Additional Public Health Benefits 1. National Center for Health Statistics, the potential impact of reducing National Health Interview Survey nicotine to minimally addictive levels While the projections from the website, available at https:// in cigarettes and selected other simulation model calculating the www.cdc.gov/nchs/nhis/data- combusted tobacco products, FDA potential impact from reducing nicotine questionnaires-documentation.htm. 2. Benowitz, N.L., and J.E. Henningfield, anticipates a significant public health to minimally addictive levels in cigarettes suggest a significant public ‘‘Reducing the Nicotine Content to Make benefit to the United States. This Cigarettes Less Addictive,’’ Tobacco hypothesis is based on the assumption health benefit to the United States Control, 22(Suppl 1):i14-i17, 2013. that the reduction in nicotine levels in resulting from substantial reductions in 3. Hatsukami, D.K., S.J. Heishman, R.I. Vogel, combusted tobacco products would smoking prevalence (based on the et al., ‘‘Dose-Response Effects of create substantial reductions in smoking model’s inputs, which reflect the Spectrum Research Cigarettes,’’ Nicotine prevalence due to increased smoking experts’ assessments that the reduction & Tobacco Research, 15(6):1113–1121, cessation and reduced initiation of in nicotine levels in combusted tobacco 2013, available at http://ntr.oxford regular smoking. Given that research products would create substantial journals.org/content/15/6/1113.long#T4. studies cannot easily replicate the increases in smoking cessation and 4. Hatsukami, D., M. Kotlyar, L.A. reductions in initiation of regular Hertsgaard, et al., ‘‘Reduced Nicotine condition of a nationally enforced Content Cigarettes: Effects on Toxic restriction on nicotine to minimally smoking), the analysis does not address Exposure, Dependence, and Cessation,’’ addictive levels in cigarettes, FDA certain potential added benefits. First, Addiction, 105(2):343–355, 2010. sought expert opinion through an the model does not account for 5. Benowitz, N.L., S.M. Hall, S. Stewart, et established elicitation process to increased quality of life from decreased al., ‘‘Nicotine and Carcinogen Exposure provide the best estimates for the tobacco-related morbidity, nor does it With Smoking of Progressively Reduced potential values and associated ranges account for cost savings from medical Nicotine Content Cigarettes,’’ Cancer of the likely impact of a hypothetical care averted. Second, the analysis does Epidemiology Biomarkers & Prevention, reduction in cigarettes’ nicotine content not account for the impacts of 16(11):2479–2485, 2007. secondhand smoke exposure on public 6. Carter B.D., C.C. Abnet, D. Fesankich, et (to be achieved by a potential product al., ‘‘Smoking and Mortality—Beyond standard) on tobacco use behaviors. health in the United States. Third, the Established Causes,’’ New England FDA requests data, evidence, and other analysis does not account for reductions Journal of Medicine, 372:7, 631–640, information regarding the potential in harms caused by smoking-related 2015. public health benefits (or risks) if FDA fires. Fourth, the potential impact 7. U.S. Department of Health and Human were to move forward in this area. described does not account for the Services, ‘‘The Health Consequences of Specifically, FDA is seeking data, potential impact on population health Smoking—50 Years of Progress: A Report evidence, and other information that from use of the other combusted of the Surgeon General’’; 2014. could inform the following five products (e.g., cigars, pipes) if the 8. U.S. Department of Health and Human assumed rule were to cover such Services, ‘‘Preventing Tobacco Use parameter inputs that would be helpful Among Youth and Young Adults,’’ A in determining the public health impact products. Finally, these projections do Report of the Surgeon General; 2012. of a nicotine tobacco product standard: not assess whether there could be 9. Poorthuis, R.B., N.A. Goriounova, J.J. • Percent of current cigarette smokers potential health benefits associated with Couey, et al., ‘‘Nicotinic Actions on who would quit cigarette smoking as a smokers cutting down on the number of Neuronal Networks for Cognition: result of a standard restricting nicotine cigarettes smoked as a result of the General Principles and Long-Term to minimally addictive levels. standard. Consequences,’’ Biochemical • Percent of quitters switching to Pharmacology, 78(7):668–676, 2009. VI. References other combusted or noncombusted 10. Slovic, P., Smoking: Risk Perception, & Policy, II.6 ‘‘Cigarette Smokers: Rational tobacco products. The following references are on • Actors or Rational Fools?’’ Thousand Percent of continuing smokers who display in the Dockets Management Oaks, CA: Sage Publications, 2001. become dual product users of cigarettes Staff (see ADDRESSES) and are available 11. Centers for Disease Control and and noncombusted tobacco products. for viewing by interested persons Prevention, ‘‘High School Students Who • Percent reduction in annual between 9 a.m. and 4 p.m. Monday Tried to Quit Smoking Cigarettes— smoking initiation rates. through Friday; they are also available United States, 2007,’’ Morbidity and

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Mortality Weekly Report, 58(16); 428– Smoking: Nicotine and Addiction,’’ A Progress to Established Smoking in the 431, May 1, 2009. Report of the Surgeon General; 1988. United States,’’ American Journal of 12. Johnston L.D., O’Malley P.M., Bachman 26. Palmatier, M.I., X. Liu, G.L. Matteson, et Preventive Medicine, 13(5):385–391, J.G., & Schulenberg J.E., ‘‘Monitoring the al., ‘‘Conditioned Reinforcement in Rats 1997. Future National Survey Results on Drug Established with Self-Administered 39. Centers for Disease Control and Use, 1975–2004,’’ Volume I, Secondary Nicotine and Enhanced by Prevention. ‘‘Selected Cigarette Smoking school students (NIH Publication NO. Noncontingent Nicotine,’’ Initiation and Quitting Behaviors Among 05–5727), Bethesda, MD: National Psychopharmacology (Berl), 195(2), 235– High School Students—US, 1997,’’ Institute on Drug Abuse. 243. 2007, doi:10.1007/s00213–007– Morbidity and, Mortality Weekly Report, 13. Institute of Medicine of the National 0897–6. 47(19):386–389, 1998. Academies, ‘‘Ending the Tobacco 27. Rose, J.E., A. Salley, F.M. Behm, et al., 40. Shiffman, S., S.G. Ferguson, M.S. Dunbar, Problem: A Blueprint for the Nation,’’ ‘‘Reinforcing Effects of Nicotine and et al., ‘‘Tobacco Dependence Among 2007, available at http://national Non-Nicotine Components of Cigarette Intermittent Smokers,’’ Nicotine & academies.org/hmd/reports/2007/ Smoke,’’ Psychopharmacology (Berl) Tobacco Research, 14(11):1372–1381, ending-the-tobacco-problem-a-blueprint- 2010 May; 210(1):1–12. 2012. for-the-nation.aspx. 28. Fiore, M.C., C.R. Jaen, T.B. Baker, et al., 41. Kandel, D., C. Schaffran, P. Griesler, et 14. Levin, E.D., S. Lawrence, A. Petro, et al., ‘‘Treating Tobacco Use and Dependence: al., ‘‘On the Measurement of Nicotine ‘‘Adolescent vs. Adult-Onset Nicotine 2008 Update,’’ U.S. Department of Dependence in Adolescence: Self-Administration in Male Rats: Health and Human Services, 2008, Comparisons of the mFTQ and a DSM– Duration of Effect and Differential available at https://www.surgeongeneral. IV-Based Scale,’’ Journal of Pediatric Nicotinic Receptor Correlates,’’ gov/tobacco/treating_tobacco_use08.pdf. Psychology, 30(4):319–332, 2005. Neurotoxicology and Teratology, 29. Fong, G.T., D. Hammond, F.L. Laux, et 42. DiFranza, J.R., J.A. Sarageau, N.A. Rigotti, 29(4):458–465, 2007. al., ‘‘The Near-Universal Experience of et al., ‘‘Symptoms of Tobacco 15. Apelberg B.J., C.G. Corey, A.C. Hoffman, Regret Among Smokers in Four Dependence After Brief Intermittent et al., ‘‘Symptoms of Tobacco Countries: Findings From the Use,’’ Archives of Pediatrics & Dependence Among Middle and High International Tobacco Control Policy Adolescent Medicine, 161(7):704–710, School Tobacco Users,’’ American Evaluation Survey,’’ Nicotine & Tobacco 2007. Journal of Preventive Medicine, Research, 6:S341–S351, 2004. 43. O’Loughlin, J., J. DiFranza, R.F. Tyndale, 47(2S1):S4–S14, 2014. 30. Huh, J., and D.S. Timberlake, ‘‘Do et al., ‘‘Nicotine-Dependence Symptoms 16. Counotte, D.S., A.B. Smit, T. Battij, et al., Smokers of Specialty and Conventional are Associated with Smoking Frequency ‘‘Development of the Motivational Cigarettes Differ in Their Dependence on in Adolescents,’’ American Journal of System During Adolescence, and Its Nicotine?’’ Addictive Behaviors, Preventive Medicine, 25(3):219–225, Sensitivity to Disruption by Nicotine,’’ 34(2):204–211, 2009. 2003. Developmental Cognitive Neuroscience, 31. National Cancer Institute, ‘‘Cigars: Health 44. Rose, J.S., L.C. Dierker, E. Donny, 1(4):430–443, 2011. Effects and Trends,’’ NCI Smoking and ‘‘Nicotine Dependence Symptoms 17. U.S. Department of Health and Human Tobacco Control Monograph 9, 1998, Among Recent Onset Adolescent Services, ‘‘How Tobacco Smoke Causes available at https://cancercontrol. Smokers,’’ Drug and Alcohol Disease: The Biology and Behavioral cancer.gov/tcrb/monographs/9/m9_ Dependence, 106(2–3):126–132, 2010. Basis for Smoking-Attributable Disease,’’ 45. Chaiton, M., L. Diemert, J.E. Cohen, et al., A Report of the Surgeon General; 2010. complete.PDF. 18. Lenk, K.M., T.L. Toomey, Q. Shi, et al., 32. Christensen, C.H., B. Rostron, C. ‘‘Estimating the number of quit attempts ‘‘Do Sources of Cigarettes Among Cosgrove, et al., ‘‘Mortality Risks for U.S. it takes to quit smoking successfully in Adolescents Vary by Age Over Time?’’ Combustible Tobacco Users—Results a longitudinal cohort of smokers,’’ BMJ Journal of Child & Adolescent Substance from the Expanded National Open, 6:e011045, 2016. Abuse, 23:137–143, 2014. Longitudinal Mortality Study,’’ JAMA 46. Centers for Disease Control and 19. Kann, L., T. McManus, W.A. Harris, et al., Internal Medicine, 2018, available at Prevention, ‘‘Cigarette Smoking Among ‘‘Youth Risk Behavior Surveillance— https://jamanetwork.com/journals/ Adults and Trends in Smoking United States, 2015,’’ Morbidity and jamainternalmedicine/fullarticle/ Cessation—United States, 2008,’’ Mortality Weekly Report, 65(6); June 10, 2672576. Morbidity and Mortality Weekly Report, 2016. 33. Rodriguez, J., et al., ‘‘The Association of 58(44); 1227–1232, November 13, 2009, 20. Grucza, R.A., A.D. Plunk, P.R. Hipp, et Pipe and Cigar Use With Cotinine Levels, available at https://www.cdc.gov/mmwr/ al., ‘‘Long-Term Effects of Laws Lung Function, and Airflow preview/mmwrhtml/mm5844a2.htm. Governing Youth Access to Tobacco,’’ Obstruction,’’ Annals of Internal 47. Centers for Disease Control and American Journal of Public Health, Medicine, 152(4); 201, 2010. Prevention, ‘‘Surveillance for Cancers 103(8); 1493–1499, 2013. 34. McDonald, I.J., R.S. Bhatia, P.D. Hollett, Associated with Tobacco Use—United 21. Centers for Disease Control and ‘‘Deposition of Cigar Smoke Particles in States, 1999–2004,’’ Morbidity and Prevention, ‘‘Quitting Smoking Among the Lung: Evaluation with Ventilation Mortality Weekly Report, 57(SS08); 1–33, Adults—United States, 2001–2010,’’ Scan Using (99m)Tc-Labeled Sulfur September 5, 2008, available at https:// Morbidity and Mortality Weekly Report, Colloid Particles,’’ Journal of Nuclear www.cdc.gov/mmwr/preview/ 60(44); November 11, 2011. Medicine, 43(12):1591–1595, 2002. mmwrhtml/ss5708a1.htm. 22. Babb, S., A. Malarcher, G. Schauer, et al., 35. Weglicki, L.S., ‘‘Tobacco Use Assessment: 48. DiFranza, J., et al., ‘‘Initial Symptoms of ‘‘Quitting Smoking Among Adults— What Exactly Is Your Patient Using and Nicotine Dependence in Adolescents,’’ United States, 2000–2015,’’ Morbidity Why Is It Important to Know?’’ Ethnicity Tobacco Control, 9(3):313–319, 2000. and Mortality Weekly Report, 65(52): & Disease, 18(3 Supp. 3):s3–1–s3–6, 49. Tworek, C., G.L. Schaeur, C.C. Wu, et al., January 6, 2017. 2008. ‘‘Youth Tobacco Cessation; Quitting 23. Prabbhat, J. and F. Chaloupka, ‘‘Curbing 36. U.S. Department of Health and Human Intentions and Past-Year Quit the Epidemic: Governments and the Services, ‘‘Youth & Tobacco; Preventing Intentions,’’ American Journal of Economics of Tobacco Control,’’ The Tobacco Use Among Young People,’’ A Preventive Medicine, 014;47(2S1):S15– World Bank, 1999, available at http:// Report of the Surgeon General; 1994, S27, 2014. www.usaid.gov/policy/ads/200/ available at https://www.surgeongeneral. 50. Brandon, T.H., S.T. Tiffany, T.B. Baker, tobacco.pdf. gov/library/reports/. ‘‘The Process of Smoking Relapse’’ in 24. Institute of Medicine of the National 37. Mowery, P.D., M.C. Farrelly, et al., Relapse and Recovery in Drug Abuse. Academies, ‘‘Clearing the Smoke: ‘‘Progression to Established Smoking Edited by F.M. Tims, C.G. Leukefeld. Assessing the Science Base for Tobacco Among US Youths,’’ American Journal of NIDA Research Monograph 72, Rockville Harm Reduction,’’ 2001. Public Health, 94(2):331–337, 2004. (MD): National Institute of Drug Abuse, 25. U.S. Department of Health and Human 38. Choi W.S., J.P. Pierce, E.A. Gilpin, et al., 1986:104–17. DHHS Publication No. Services, ‘‘The Health Consequences of ‘‘Which Adolescent Experimenters (ADM) 90–1473.

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51. Kenford, S.L., M.C. Fiore, D.E. Jorenby, et 65. Scherer, G., ‘‘Smoking Behaviour and Smoked With Three Machine-Smoking al., ‘‘Predicting Smoking Cessation: Who Compensation: A Review of the Conditions,’’ Regulatory Toxicology and Will Quit With and Without the Nicotine Literature. Psychopharmacology, Pharmacology, 41(3):185–227, 2005. Patch,’’ The Journal of the American 145(1):1–20, 1999. 81. Benowitz, N.L., and J.E. Henningfield, Medical Association, 271(8):589–594, 66. Grubbs et al., ‘‘Process for Removal of ‘‘Establishing a Nicotine Threshold for 1994. Basic Materials,’’ Patent No. 5,018,540, Addiction. The Implications for Tobacco 52. Yudkin, P., ‘‘Abstinence from Smoking May 28, 1991. Regulation,’’ The New England Journal Eight Years After Participation in 67. Berger, ‘‘Methods of Reducing the of Medicine, 331(2):123–125, 1994. Randomized Controlled Trial of Nicotine Nicotine Content of Tobacco Plants and 82. Shiffman, S., ‘‘Tobacco ‘chippers’— Patch,’’ British Medical Journal, 327:28, Tobacco Plants Obtained Thereby,’’ Individual Differences in Tobacco 2003. Patent No. US 7,538,071 B2, May 26, Dependence,’’ Psychopharmacology 53. Hatsukami, D.K., L.A, Hertsgaard, R.I. 2009. (Berl.), 97:539–547, 1989. Vogel, et al., ‘‘Reduced Nicotine Content 68. Hukkanen, J., Jacob III, P., Benowitz, N.L., 83. Sofuoglu, M., S. Yoo, K.P. Hill, et al., Cigarettes and Nicotine Patch,’’ Cancer ‘‘Metabolism and Disposition Kinetics of ‘‘Self-Administration of Intravenous Epidemiology Biomarkers & Prevention, Nicotine,’’ Pharmacological Reviews, 57, Nicotine in Male and Female Cigarette 22(6):1015–1024, 2013. 79–115, 2005. Smokers,’’ Neuropsychopharmacology, 54. Henningfield, J.E., N.L. Benowitz, J. 69. Benowitz, N.L., S.M. Hall, R.L. Herning, 33(4):715–20, 2008. Slade, et al., ‘‘Reducing the et al., ‘‘Smokers of Low-Yield Cigarettes 84. Sofuoglu, M., and M.G. Lesage, ‘‘The Addictiveness of Cigarettes,’’ Tobacco do Not Consume Less Nicotine,’’ New Reinforcement Threshold for Nicotine as Control, 7(3):281–293, 1998. England Journal of Medicine, 309, 139– a Target for Tobacco Control,’’ Drug and 55. Sloan, F.A., J. Ostermann, C. Conover, et 142, 1983. Alcohol Dependence, 125(1–2):1–7, al. The Price of Smoking. MIT Press, 70. Kozlowski, L.T., N.Y. Mehta, C.T. 2012. Cambridge, MA, 2004. Sweeney, et al., ‘‘Filter ventilation and 85. Donny, E.C., R.L. Denlinger, J.W. Tidey, 56. Nonnemaker J., B. Rostron, P. Hall, et al., nicotine content of tobacco in cigarettes et al., ‘‘Randomized Trial of Reduced- ‘‘Mortality and Economic Costs From from Canada, the United Kingdom, and Nicotine Standards for Cigarettes,’’ The Regular Cigar Use in the United States, the United States,’’ Tobacco Control, 7, New England Journal of Medicine, 2010,’’ American Journal of Public 369–375, 1998. 373(14):1340–1349, 2015. Health, 104(9):e86–e91, 2014. 71. Jacob, P., L. Yu, A.T. Shulgin, et al., 86. Benowitz, N.L., N. Nardone, K.M. Daines, 57. Shapiro, J.A., E.J. Jacobs, and M.J. Thun, ‘‘Minor tobacco alkaloids as biomarkers et al., ‘‘Effect of reducing the nicotine ‘‘Cigar Smoking in Men and Risk of for tobacco use: Comparison of users of content of cigarettes on cigarette smoking Death From Tobacco-Related Cancers,’’ cigarettes, smokeless tobacco, cigars, and behavior and tobacco smoke toxicant Journal of the National Cancer Institute, pipes,’’ American Journal of Public exposure: 2-year follow up,’’ Addiction, 92(4):333–337, 2000. Health, 89, 731–736, 1999. 110(10); 1667–1665, 2015. 58. Alberg, A.J., D.R. Shopland, K.M. 72. Dallery, J., E.J. Houtsmuller, W.B. 87. Hatsukami, D.K., S.J. Heishman, R.I. Cummings, ‘‘The 2014 Surgeon General’s Pickworth, et al., ‘‘Effects of Cigarette Vogel, et al., ‘‘Dose-Response Effects of Report: Commemorating the 50th Nicotine Content and Smoking Pace on Spectrum Research Cigarettes,’’ Nicotine Anniversary of the 1964 Report of the Subsequent Craving and Smoking,’’ & Tobacco Research, 15(6):1113–1121, Advisory Committee to the U.S. Surgeon Psychopharmacology, 165(2):172–180, 2013. General and Updating the Evidence on 88. Mercincavage M., V. Souprountchouk, the Health Consequences of Cigarette 2003. Smoking,’’ American Journal of 73. Djordjevic et al at the CORESTA K.Z. Tang, et al., ‘‘A randomized Epidemiology, 179(4):403–412, 2014. Symposium, Kallithea, Greece, 1990— controlled trial of progressively reduced 59. U.S. Department of Health and Human paper # S04. nicotine content cigarettes on smoking Services, ‘‘The Health Consequences of 74. Pickworth, W.B., R.V. Fant, R.A. Nelson, behaviors, biomarkers of exposure, and Involuntary Exposure to Tobacco et al., ‘‘Pharmacodynamic Effects of New subjective ratings,’’ Cancer Smoke,’’ A Report of the Surgeon De-Nicotinized Cigarettes,’’ Nicotine & Epidemiology, Biomarkers & Prevention, General; 2006, available at https:// Tobacco Research, 1(4):357–364, 1999. doi: 10.1158/1055–9965.EPI–15–1088, www.surgeongeneral.gov/library/ 75. Buchhalter, A.R., M.C. Acosta, SE Evans, 2016. secondhandsmoke/report/. et al., ‘‘Tobacco Abstinence Symptom 89. Barrett, S.P., ‘‘The Effects of Nicotine, 60. U.S. Department of Health and Human Suppression: The Role Played by the Denicotinized Tobacco, and Nicotine- Services, ‘‘Reducing the Health Smoking-Related Stimuli That Are Containing Tobacco on Cigarette Consequences of Smoking—25 Years of Delivered by Denicotinized Cigarettes,’’ Craving, Withdrawal, and Self- Progress,’’ A Report of the Surgeon Addiction, 100(4):550–559, 2005. Administration in Male and Female General; 1989, available at https://www. 76. Becker, K.M., J.E. Rose, A.P. Albino, ‘‘A Smokers,’’ Behavioural Pharmacology, surgeongeneral.gov/library/reports/. Randomized Trial of Nicotine 21(2)144–152, 2010. 61. Henley, S.J., M.J. Thun, A. Chao, et al., Replacement Therapy in Combination 90. Eid, N.C., R.V. Fant, E.T. Moolchan, et al., ‘‘Association Between Exclusive Pipe with Reduced-Nicotine Cigarettes for ‘‘Placebo Cigarettes in a Spaced Smoking Smoking and Mortality from Cancer and Smoking Cessation,’’ Nicotine & Tobacco Paradigm,’’ Pharmacology Biochemistry Other Diseases,’’ Journal of the National Research, 10(7):1139–1148, 2008. and Behavior, 81(1):158–164, 2005. Cancer Institute, 96(11); 853, 2004. 77. Reducing Levels of Nicotinic Alkaloids in 91. Rose, J.E., F.M. Behm, E.C. Westman, et 62. Baker, F., S.R. Ainsworth, J.T. Dye, et al., Plants, available at https://www.lens.org/ al., ‘‘Dissociating Nicotine and ‘‘Health Risks Associated With Cigar lens/patent/US_8791329_B2. Nonnicotine Components of Cigarette Smoking,’’ Journal of the American 78. Notice of Availability of Nicotine Smoking,’’ Pharmacology Biochemistry Medical Association, 284(6):735–740, Research Cigarettes Through NIDA’s and Behavior, 67(1):71–81, 2000. 2000. Drug Supply Program, Notice NOT–DA– 92. Brody, A.L., M.A. Mandelkern, M.R. 63. Fiore, M., and T. Baker, ‘‘Reduced- 14–004, available at https://grants. Costello, et al., ‘‘Brain Nicotinic Nicotine Cigarettes—A Promising nih.gov/grants/guide/notice-files/NOT- Acetylcholine Receptor Occupancy: Regulatory Pathway,’’ The New England DA-14-004.html. Effect of Smoking a Denicotinized Journal of Medicine, 373(14):1289–1291, 79. Philip Morris, Alkaloid Reduced Tobacco Cigarette,’’ International Journal of 2015. (ART) Program, available at http://www. Neuropsychopharmacology, 12(3):305– 64. Benowitz, N.L., K.M. Dains, S.M. Hall, et xxiicentury.com/home/files/PM%20 316, 2009. al., ‘‘Smoking Behavior and Exposure to Alkaloid%20Reduced%20Tobacco 93. Perkins, K.A., M. Ciccocioppo, C.A. Tobacco Toxicants During 6 Months of %20Program.pdf. Conklin, et al., ‘‘Mood Influences on Smoking Progressively Reduced Nicotine 80. Counts, M.E., M.J. Morton, SW Laffoon, Acute Smoking Responses Are Content Cigarettes,’’ Cancer et al., ‘‘Smoke Composition and Independent of Nicotine Intake and Dose Epidemiology Biomarkers & Prevention, Predicting Relationships for Expectancy,’’ Journal of Abnormal 21(5):761–769, 2012. International Commercial Cigarettes Psychology, 117(1):79–93, 2008.

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94. Gross, J., J. Lee, M.L. Stitzer, ‘‘Nicotine- Cancer Epidemiology Biomarkers & Chromatographic Determination of Containing Versus De-Nicotinized Prevention, 23(10):2032–2040, 2014. Nicotine in Commercial Tobacco Cigarettes: Effects on Craving and 106. Hatsukami, D.K., M. Kotylar, L.A. Products,’’ Journal of Agricultural and Withdrawal,’’ Pharmacology Hertsgaard, et al., ‘‘Reduced Nicotine Food Chemistry, 47(9):3713–3717, 1999. Biochemistry and Behavior, 57(1–2):159– Content Cigarettes: Effects on Toxicant 119. Svob Troje, Z., Z. Frobe, D. Perovic, 165, 1997. Exposure, Dependence and Cessation,’’ ‘‘Analysis of Selected Alkaloids and 95. Baldinger, B., M. Hasenfratz, K. Battig, Addiction, 105(2):343–355, 2010. Sugars in Tobacco Extract,’’ Journal of ‘‘Effects of Smoking Abstinence and 107. Rose, J.E., F.M. Behm, E.C. Westman, et Chromatography A, 775(1–2):101–107, Nicotine Abstinence on Heart-Rate, al., ‘‘Precessation Treatment with 1997. Activity and Cigarette Craving Under Nicotine Skin Patch Facilitates Smoking 120. Wayne, G.F., and C.M Carpenter, Field Conditions,’’ Human Cessation,’’ Nicotine & Tobacco ‘‘Tobacco Industry Manipulation of Psychopharmacology-Clinical and Research, 8(1):89–101, 2006. Nicotine Dosing,’’ Nicotine Experimental, 10(2):127–136, 1995. 108. Walker, N., C. Howe, C. Bullen, et al, Psychopharmacology, Handbook of 96. Domino, E.F., L.S. Ni, J.S. Domino, et al., ‘‘The Combined Effect of Very Low Experimental Pharmacology, (192):457– ‘‘Denicotinized Versus Average Nicotine Nicotine Content Cigarettes, Used as an 485, 2009. Tobacco Cigarette Smoking Differentially Adjunct to Usual Quitline Care (Nicotine 121. Griffith, R.B., ‘‘[Re: Information on Releases Striatal Dopamine,’’ Nicotine & Replacement Therapy and Behavioural Nicotine and Sugar in Tobacco for Neil Tobacco Research, 15(1):11–21, 2013. Support), on Smoking Cessation: A Gilliam’s Presentation at Chelwood],’’ 97. Pickworth, W.B., E.D. O’Hare, R.V. Fant, Randomized Controlled Trial,’’ Brown & Williamson. Bates: 102630333– et al., ‘‘EEG Effects of Conventional and Addiction, 107(10):1857–1867, 2012. 102630336 Exhibit 10. http://tobacco Denicotinized Cigarettes in a Spaced 109. Cheong, Y., H. Yong, R. Borland, ‘‘Does documents.org/youth/NcPdBWC Smoking Paradigm,’’ Brain and How You Quit Affect Success? A 19630918.Lt.html, 18 September 1963. Cognition, 53(1):75–81, 2003. Comparison of Abrupt and Gradual 122. U.S. Department of Health and Human 98. Clements, K.J., S. Caille, L. Stinus, et al., Methods Using Data from the Services, ‘‘The Health Consequences of ‘‘The Addition of Five Minor Tobacco International Tobacco Control Policy Smoking: The Changing Cigarette,’’ A Alkaloids Increases Nicotine-Induced Evaluation Study,’’ Nicotine & Tobacco Report of the Surgeon General; 1981. Hyperactivity, Sensitization and Research, 9(8):801–810, 2007. 123. Nicotine Reduction Program, April 24, Intravenous Self-Administration in 110. Etter, J., ‘‘Comparing Abrupt and 1989, available at: https://legacy.library. Rats,’’ International Journal of Gradual Smoking Cessation: A ucsf.edu/tid/srm73d00;jsessionid= Neuropsychopharmacology, Randomized Trial,’’ Drug and Alcohol FB8DABDE8C48ECC41CA7589B1E 12(10):1355–1366, 2009. Dependence, 118(2–3):360–365, 2011. 4A842E. 111. Lindson, N., P. Aveyard, J.R. Hughes, 99. Wu, W., D.L. Ashley, C.H. Watson, 124. Richter, P., R.S. Pappas, R. Bravo, et al., ‘‘Reduction Versus Abrupt Cessation in ‘‘Determination of Nicotine and Other ‘‘Characterization of Spectrum Variable Smokers Who Want to Quit,’’ Cochrane Minor Alkaloids in International Nicotine Research Cigarettes,’’ Tobacco Database of Systematic Reviews, 2010. Cigarettes by Solid-Phase Reg. Sci., 2(2):94–105, 2016. 112. Arrecis, J.J., and M. McLeod, ‘‘Food and 125. Ding, Y.S., P. Richter, B. Hearn, et al., Microextraction and Gas Drug Administration, Quantification of ‘‘Chemical Characterization of Chromatography/Mass Spectrometry,’’ Low Level Nicotine in Combustible Mainstream Smoke from Spectrum Analytical Chemistry, 74(19):4878–4884, Tobacco Products,’’ LIB #4550. 2002. 113. Millet, A., F. Stintzing, I. Merfort, Variable Nicotine Research Cigarettes,’’ 100. Hoffman, A.C., and SE Evans, ‘‘Abuse ‘‘Validation of a GC–FID Method for Tobacco Reg. Sci., 3(1):81–94, 2017. Potential of Non-Nicotine Tobacco Rapid Quantification of Nicotine in 126. National Cancer Institute, ‘‘The FTC Smoke Components: Acetaldehyde, Fermented Extracts Prepared from Cigarette Test Method for Determining Nornicotine, Cotinine, and Anabasine,’’ Nicotiana Tabacum Fresh Leaves and Tar, Nicotine, and Carbon Monoxide Nicotine & Tobacco Research, 15(3):622– Studies of Nicotine Metabolites,’’ Journal Yields of U.S. Cigarettes.’’ Smoking and 632, 2013. of Pharmaceutical and Biomedical Tobacco Control Monograph 7. 101. Dwoskin, L.P., L. Teng, S.T. Buxton, et Analysis, 49(5):1166–1171, 2009. 127. U.S. District Court for the District of al., ‘‘(S)-(-)-Cotinine, the Major Brain 114. World Health Organization, ‘‘Standard Columbia United States of America, Metabolite of Nicotine, Stimulates operating procedure for determination of Plaintiff, versus Philip Morris, USA, et Nicotinic Receptors to Evoke nicotine in cigarette tobacco filler,’’ al., defendants. Civil Action ANo. 99– [3H]dopamine Release From Rat Striatal WHO TobLabNet Official Method SOP 2496(GK). United States’ Written Direct Slices in a Calcium-Dependent Manner,’’ 04, 2014, available at: http://www.who. Examination of William A. Farone, Ph.D. Journal of Pharmacology and int/tobacco/publications/prod_ Submitted Pursuant to Order #471. Experimental Therapeutics, 288(3):905– regulation/789241503907/en/. 128. Wayne, G.F., ‘‘Tobacco Industry 911, 1999. 115. ISO 10315:2013; ‘‘Cigarettes— Research on Modification of Nicotine 102. Dwoskin, L.P., L.H. Teng, P.A. Crooks, Determination of Nicotine in Smoke Content in Tobacco (1960–1980),’’ Final ‘‘Nornicotine, a Nicotine Metabolite and Condensates—Gas-Chromatographic Report, Prepared for Health Canada, Tobacco Alkaloid: Desensitization of Method,’’ International Organization for Submission date: December 21, 2012. Nicotinic Receptor-Stimulated Dopamine Standardization, available at: https:// 129. Harwood, E.H., ‘‘Monthly Project Release From Rat Striatum,’’ European www.iso.org/standard/56744.html. Development Report’’, May 20, 19966, Journal of Pharmacology, 428(1):69–79, 116. Cooperation Centre for Scientific available at http://legacy.library.ucsf. 2001. Research Relative to Tobacco edu/tid/aqu29d00. 103. Benowitz, N.L., P. Jacob, B. Herrera, (CORESTA), Determination of Nicotine 130. ‘‘Unnamed Report,’’ 1967, available at ‘‘Nicotine Intake and Dose Response in Tobacco and Tobacco Products by Gas http://legacy.library.ucsf.edu/tid/ When Smoking Reduced-Nicotine Chromatographic Analysis, Method No. fqx81b00. Content Cigarettes,’’ Clinical 62, February 2005, available at: https:// 131. Tengs, T.O., S. Ahmad, J.M. Savage, et Pharmacology & Therapeutics, www.coresta.org/determination-nicotine- al., ‘‘The AMA Proposal to Mandate 80(6):703–714, 2006. tobacco-and-tobacco-products-gas- Nicotine Reduction in Cigarettes: A 104. Donny, E.C., and M. Jones, ‘‘Prolonged chromatographic-analysis-29185.html. Simulation of the Population Health Exposure to Denicotinized Cigarettes 117. Wu, C., W.F. Siems, J. Hill, et al., Impacts,’’ Preventive Medicine, With or Without Transdermal Nicotine,’’ ‘‘Analytical Determination of Nicotine in 40(2):170–180, 2005. Drug and Alcohol Dependence, 104(1– Tobacco by Supercritical Fluid 132. Bernasek, P.F., O.P. Furin, and G.R. 2):23–33, 2009. Chromatography-Ion Mobility Shelar, ‘‘Sugar/Nicotine Study,’’ R.J. 105. Hammond, D., and R.J. O’Connor, Detection,’’ Journal of Chromatography Reynolds. Bates: 510697389–510697410, ‘‘Reduced Nicotine Cigarettes: Smoking A, 811(1–2):157–161, 1998. July 29, 1992, available at https:// Behavior and Biomarkers of Exposure 118. Ciolino, L.A., D.B. Fraser, T.Y. Yi, et al., www.industrydocumentslibrary. Among Smokers Not Intending to Quit,’’ ‘‘Reversed Phase Ion-Pair Liquid ucsf.edu/tobacco/docs/#id=sljb0079.

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133. Dunsby, J. and L. Bero, ‘‘A Nicotine Collection, Bates No. 515600200/ Bacteria,’’ December 29, 1972, available Delivery Device Without the Nicotine? 515600203, available at http://legacy. at http://legacy.library.ucsf.edu/tid/ Tobacco Industry Development of Low library.ucsf.edu/tid/wyr92d00. jlw84a99. Nicotine Cigarettes,’’ Tobacco Control, 150. Rothmans of Pall Mall Canada Ltd., 169. Geiss, V.L., ‘‘Bw Process VI: Metabolism 13(4):362–369, 2004. ‘‘Minutes of Meeting on May 6, 1971,’’ of Nicotine and Other Biochemistry of 134. Tso, T.C., ‘‘The Potential for Producing May 13, 1971, available at http://legacy. the Bw Process,’’ January 2, 1975, Safer Cigarette Tobacco,’’ Agriculture library.ucsf.edu/tid/rng84a99. available at http://legacy.library.ucsf. Science Review, 10(3):1–10, 1972. 151. Boswall, G.W., ‘‘Project T–6534: edu/tid/gpx86a99. 135. Monthly Product Development Report, Tobacco for Reconstitution,’’ June 29, 170. Gravely, L.E., R.P. Newton, V.L. Geiss, Tobacco Products Development, MPRD– 1971, available at http://legacy. ‘‘Bw Process: IV Evaluation of Low T, (660000) November 5, 1966, May 20, library.ucsf.edu/tid/ung84a99. Nicotine Cigarettes Use for Consumer 1966, available at http://legacy.library. 152. Evans, L.M., ‘‘Low Nicotine Tobacco,’’ Product Testing,’’ June 24, 1973, ucsf.edu/tid/aqu29d00. August 2, 1971, available at http:// available at http://legacy.library. 136. Final Report 14-Day Single Dose legacy.library.ucsf.edu/tid/smu97e00. ucsf.edu/tid/zso05a99. Subacute Toxicity Study in the Rat With 153. Meyer, L.F., ‘‘Low Nicotine Cigarettes, 171. Carpenter, C.M., G.N. Connolly, O.A. A–7 Borriston Project No. 1564(2); March Smoking & Health Study Meeting,’’ Ayo-Yusuf, et al., ‘‘Developing smokeless 30, 1984, available at http://legacy. November 15, 1971, available at http:// tobacco products for smokers: an library.ucsf.edu/tid/fgx81b00. legacy.library.ucsf.edu/tid/zpn64e00. examination of tobacco industry 137. Ashburn, G., ‘‘Vapor-Phase Removal of 154. British American Tobacco, ‘‘Research documents,’’ Tobacco Control, 18, 54– Nicotine From Tobacco,’’ December 6, and Development Department: Progress 59, 2009. 1961, available at http://legacy.library. in 1972—Plans for 1973,’’ available at 172. Institute of Medicine of the National ucsf.edu/tid/cyo59d00. http://legacy.library.ucsf.edu/tid/ Academies, ‘‘Understanding the U.S. 138. Philip Morris, ‘‘Untitled Chart,’’ qdb84a99. Illicit Tobacco Market,’’ 2015, available available at http://legacy.library.ucsf. 155. Smith, T.E., ‘‘Report Number 72–18 at https://www.nap.edu/catalog/19016/ edu/tid/fgn84e00. Tobacco and Smoke Characteristics of understanding-the-us-illicit-tobacco- 139. Crouse, W.E., ‘‘Communication with Low Nicotine Strains of Burley,’’ June market-characteristics-policy-context- Michael Ogden, RJR, Bowman Gray 28, 1972, available at http://legacy. and. Development Center,’’ February 10, library.ucsf.edu/tid/gqq00f00. 173. U.S. Department of Health and Human 1987, available at http://legacy.library. 156. ‘‘Kentucky Tobacco Research Board— Services, ‘‘The Health Benefits of ucsf.edu/tid/zit31e00. 1977 Annual Review,’’ 1977, available at Smoking Cessation,’’ A Report of the 140. Ruiz-Rodriguez, A., M–R Bronze, M. http://legacy.library.ucsf.edu/tid/ Surgeon General; 1990, available at Nunes de Ponte, ‘‘Supercritical Fluid omd76b00. https://www.surgeongeneral.gov/library/ Extraction of Tobacco Leaves: A 157. Johnson, D.P., ‘‘Low Nicotine Tobacco,’’ reports/. Preliminary Study on the Extraction of March 29, 1977, available at http:// 174. World Health Organization, Fact Sheet Solanesol,’’ Journal of Supercritical legacy.library.ucsf.edu/tid/xsk53d00. About Health Benefits of Smoking Fluids, 45(2):171–176, 2008. 158. Neumann, C.L., ‘‘Low Nicotine Tobacco Cessation, available at http:// 141. Fischer, M., and T.M. Jeffries, Samples,’’ November 2, 1977, available www.who.int/tobacco/quitting/en_tfi_ ‘‘Optimization of Nicotine Extraction at http://legacy.library.ucsf.edu/tid/ quitting_fact_sheet.pdf. From Tobacco Using Supercritical Fluid eia65d00. 175. Centers for Disease Control and Technology With Dynamic Extraction 159. Hudson, A.B., ‘‘Organoleptic Evaluation Prevention, Benefits of Quitting, Modeling,’’ Journal of Agricultural and of Low Alkaloid Sample 8059,’’ available at https://wwws.cdc.gov/ Food Chemistry, 44(5):1258–1264, 1996. September 10, 1973, available at http:// tobacco/quit_smoking/how_to_quit/ 142. Roselius et al., ‘‘Process for the legacy.library.ucsf.edu/tid/ehf51e00. benefits/. Extraction of Nicotine From Tobacco,’’ 160. Cohen, N., ‘‘Minutes of Meeting on May 176. U.S. Department of Health and Human Patent No. 4,153,063, May 8, 1979. 6, 1971,’’ May 13, 1971, available at Services, ‘‘The Health Consequences of 143. ‘‘The ‘Denicotinized’ Cigarette,’’ N.D., http://legacy.library.ucsf.edu/tid/ Smoking,’’ A Report of the Surgeon Philip Morris Collection, Bates No. rng84a99. General; 2004, available at https://www. 2083480351, 1999, available at http:// 161. Hashimoto et al., ‘‘Reducing Levels of surgeongeneral.gov/library/smoking legacy.library.ucsf.edu/tid/rsy55c00. Nicotine Alkaloids in Plants,’’ U.S. consequences/index.html. 144. Crouse, W.E., ‘‘Nicotine Extraction Patent No. 8,791,329, July 29, 2014. 177. Jha, P., C. Ramasundarahettige, V. Preliminary Study of Methods for High 162. RJR, ‘‘MBO Evaluation Summary,’’ Landsman, et al., ‘‘21st-Century Hazards Nicotine Leaf Extraction,’’ June 20, 1976, November 30, 1976, available at http:// of Smoking and Benefits of Cessation in available at http://legacy.library.ucsf. legacy.library.ucsf.edu/tid/vrk59d00. the United States,’’ New England Journal edu/tid/zjt31e00. 163. Imperial Tobacco Company, ‘‘Report of Medicine, 368(4):341–350, 2013. 145. Groome, J.W., ‘‘Product Development Regarding Test on Quality of Final Flue- 178. Taylor Jr., D.H., V. Hasselblad, J. Henley, Committee: Meeting Report #60,’’ July Cured Product,’’ April 24, 1969, et al., ‘‘Benefits of Smoking Cessation for 20, 1972, available at http://legacy. available at http://legacy.library. Longevity,’’ American Journal of Public library.ucsf.edu/tid/hdz54a99. ucsf.edu/tid/rnr94a99. Health, 92(6):990–996, 2002. 146. Reid, J.R., ‘‘Investigation Into Extraction 164. Passey, M., Imperial Tobacco Company, 179. Benowitz, N.L., ‘‘Nicotine Addiction,’’ of Nicotine from Tobacco,’’ February 7, ‘‘Canadian Sucker Control Studies The New England Journal of Medicine, 1977, available at http://legacy.library. 630000 Crop,’’ December 18, 1964, 362(24):2295, 2010. ucsf.edu/tid/hgq09c00. available at http://legacy.library. 180. Vugrin, E.D., B.L. Rostron, S.J. Verzi, et 147. Hempfling, W., Philip Morris, ‘‘Philip ucsf.edu/tid/bjx60f00. al., ‘‘Modeling the Potential Effects of Morris and the ‘New Biotechnology,’ ’’ 165. ‘‘800000 D.R.S. Ridomil Experiment,’’ New Tobacco Products and Policies: A Philip Morris Collection, Bates No. 1980, available at http://legacy.library. Dynamic Population Model for Multiple 2024837696/202.4837704, October 9, ucsf.edu/tid/ucg52i00. Product Use and Harm,’’ PLOS One, 1987, available at http://legacy.library. 166. ‘‘Table XIII, Summary of Flue-Cured 2015, available at: https://doi.org/ ucsf.edu/tid/pgo68e00. Aging Study, Forced Aging,’’ December 10.1371/journal.pone.0121008. 148. Venable, M.B., Phillip Morris 31, 1991, available at http:// 181. Apelberg, B.J., S.P. Feirman, E. Salazar, Management Corporation, ‘‘Notification legacy.library.ucsf.edu/tid/uvu54f00. et al., ‘‘Potential Public Health Effects of of Issuance of US Patent,’’ Philip Morris 167. Mitchell, T.G., ‘‘PRT and Tobacco Lowering Nicotine in Cigarettes in the Collection, Bates No. 2060531727, Biomodification,’’ January 15, 1973, US,’’ The New England Journal of November 26, 1997, available at http:// available at http://legacy.library. Medicine, 2018, available at doi: legacy.library.ucsf.edu/tid/zel13e00. ucsf.edu/tid/rum47a99. 10.1056/NEJMsr1714617. 149. ‘‘Sensa Business Plan Executive 168. Geiss, V.L., ‘‘Bw Process I: Reductions 182. Centers for Disease Control and Summary,’’ April 4, 1992, R.J. Reynolds of Tobacco Nicotine Using Selected Prevention, National Youth Tobacco

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Survey website, available at https:// Dated: March 12, 2018. www.cdc.gov/tobacco/data_statistics/ Leslie Kux, surveys/nyts/index.htm. Associate Commissioner for Policy. [FR Doc. 2018–05345 Filed 3–15–18; 8:45 am] BILLING CODE 4164–01–P

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on ‘‘Postmarket Safety Reporting for DEPARTMENT OF HEALTH AND including attachments, to https:// Combination Products.’’ It does not HUMAN SERVICES www.regulations.gov will be posted to establish any rights for any person and the docket unchanged. Because your is not binding on FDA or the public. Food and Drug Administration comment will be made public, you are You can use an alternative approach if solely responsible for ensuring that your it satisfies the requirements of the 21 CFR Parts 1100, 1140, and 1143 comment does not include any applicable statutes and regulations. This [Docket No. FDA–2017–N–6565] confidential information that you or a guidance is not subject to Executive third party may not wish to be posted, RIN 0910–AH60 Order 12866. such as medical information, your or anyone else’s Social Security number, or IV. Paperwork Reduction Act of 1995 Regulation of Flavors in Tobacco confidential business information, such Products as a manufacturing process. Please note This guidance refers to previously AGENCY: Food and Drug Administration, that if you include your name, contact approved collections of information HHS. information, or other information that found in FDA regulations. These identifies you in the body of your ACTION: Advance notice of proposed collections of information are subject to comments, that information will be rulemaking. review by the Office of Management and posted on https://www.regulations.gov. • Budget (OMB) under the Paperwork SUMMARY: The Food and Drug If you want to submit a comment Reduction Act of 1995 (44 U.S.C. 3501– Administration (FDA) is issuing this with confidential information that you 3520). The collections of information in advance notice of proposed rulemaking do not wish to be made available to the 21 CFR 314.80(c) and (e), as well as for (ANPRM) to obtain information related public, submit the comment as a 21 CFR 314.81(b) are approved under to the role that flavors play in tobacco written/paper submission and in the OMB control numbers 0910–0001, products. Specifically, this ANPRM is manner detailed (see ‘‘Written/Paper 0910–0230, and 0910–0291. The seeking comments, data, research Submissions’’ and ‘‘Instructions’’). information collection provisions for 21 results, or other information about, Written/Paper Submissions among other things, how flavors attract CFR 600.80 and 600.81 are approved Submit written/paper submissions as youth to initiate tobacco product use under OMB control number 0910–0308. follows: Those for 21 CFR 606.170 are approved and about whether and how certain • Mail/Hand delivery/Courier (for under OMB control number 0910–0116. flavors may help adult cigarette smokers written/paper submissions): Dockets Those for 21 CFR 606.171 are approved reduce cigarette use and switch to Management Staff (HFA–305), Food and under OMB control number 0910–0458. potentially less harmful products. FDA Drug Administration, 5630 Fishers The information collection provisions is seeking this information to inform Lane, Rm. 1061, Rockville, MD 20852. for 21 CFR 803.50, 803.53, and 803.56 regulatory actions FDA might take with • For written/paper comments respect to tobacco products with flavors, are approved under OMB control submitted to the Dockets Management under the Federal Food, Drug, and numbers 0910–0291 and 0910–0437. Staff, FDA will post your comment, as Cosmetic Act (FD&C Act), as amended The information collection provisions well as any attachments, except for by the Family Smoking Prevention and information submitted, marked and for 21 CFR 806.10 and 806.20 are Tobacco Control Act (Tobacco Control approved under OMB control number identified, as confidential, if submitted Act). Potential regulatory actions as detailed in ‘‘Instructions.’’ 0910–0359. The information collection include, but are not limited to, tobacco provisions for 21 CFR 4.102, 4.103, and Instructions: All submissions received product standards and restrictions on must include the Docket No. FDA– 4.105 are approved under OMB control sale and distribution of tobacco 2017–N–6565 for ‘‘Regulation of Flavors number 0910–0834. products with flavors. in Tobacco Products.’’ Received V. Electronic Access DATES: Submit either electronic or comments, those filed in a timely written comments by June 19, 2018. manner (see ADDRESSES), will be placed Persons with access to the internet ADDRESSES: You may submit comments in the docket and, except for those may obtain the draft guidance at either as follows. Please note that late, submitted as ‘‘Confidential https://www.fda.gov/Combination untimely filed comments will not be Submissions,’’ publicly viewable at Products/GuidanceRegulatory considered. Electronic comments must https://www.regulations.gov or at the Information/ucm109110.htm or https:// be submitted on or before June 19, 2018. Dockets Management Staff between 9 www.regulations.gov. The https://www.regulations.gov a.m. and 4 p.m., Monday through Dated: March 15, 2018. electronic filing system will accept Friday. comments until midnight Eastern Time • Confidential Submissions—To Leslie Kux, at the end of June 19, 2018. Comments submit a comment with confidential Associate Commissioner for Policy. received by mail/hand delivery/courier information that you do not wish to be [FR Doc. 2018–05687 Filed 3–20–18; 8:45 am] (for written/paper submissions) will be made publicly available, submit your BILLING CODE 4164–01–P considered timely if they are comments only as a written/paper postmarked or the delivery service submission. You should submit two acceptance receipt is on or before that copies total. One copy will include the date. information you claim to be confidential with a heading or cover note that states Electronic Submissions ‘‘THIS DOCUMENT CONTAINS Submit electronic comments in the CONFIDENTIAL INFORMATION.’’ The following way: Agency will review this copy, including • Federal eRulemaking Portal: the claimed confidential information, in https://www.regulations.gov. Follow the its consideration of comments. The instructions for submitting comments. second copy, which will have the Comments submitted electronically, claimed confidential information

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redacted/blacked out, will be available accessories of deemed tobacco products, surrounding the role of flavors in for public viewing and posted on to be subject to FDA’s tobacco product tobacco products, including the role https://www.regulations.gov. Submit authority (the deeming rule). The flavors play in youth and young adult both copies to the Dockets Management products now subject to FDA’s tobacco use, as well as the existence of Staff. If you do not wish your name and product authority include electronic preliminary data that some adults may contact information to be made publicly nicotine delivery systems (ENDS), use flavored noncombusted tobacco available, you can provide this cigars, waterpipes, pipe tobacco, products to transition away from information on the cover sheet and not nicotine gels, dissolvables that were not combusted tobacco use. See 81 FR in the body of your comments and you already subject to chapter IX of the 28973 at 29014 and 29055. must identify this information as FD&C Act, and other products that meet C. The Role of Flavors in Tobacco ‘‘confidential.’’ Any information marked the statutory definition of ‘‘tobacco Products Use as ‘‘confidential’’ will not be disclosed product’’ (other than accessories) that except in accordance with 21 CFR 10.20 may be developed in the future. Adolescence (under 18, also referred and other applicable disclosure law. For to as youth) and young adulthood (age more information about FDA’s posting B. Flavors and Tobacco Product 18 through 24) represent a time of of comments to public dockets, see 80 Standards heightened vulnerability to both the FR 56469, September 18, 2015, or access Section 907 of the FD&C Act (21 initiation of tobacco product use and the the information at: https://www.gpo.gov/ U.S.C. 387g) gives FDA the authority to development of nicotine dependence fdsys/pkg/FR-2015-09-18/pdf/2015- establish tobacco product standards. To (Ref. 1). Furthermore, flavors in tobacco 23389.pdf. establish a tobacco product standard, products increase the appeal of those Docket: For access to the docket to FDA must find that the standard is tobacco products to youth, and promote read background documents or the appropriate for the protection of the youth initiation (Ref. 2). Thus, the electronic and written/paper comments public health, taking into consideration availability of tobacco products with received, go to https:// scientific evidence concerning the risks flavors at these developmental stages www.regulations.gov and insert the and benefits to the population as a attracts youth to initiate use of tobacco docket number, found in brackets in the whole, including users and nonusers of products and may result in lifelong use heading of this document, into the tobacco products; the increased or (Ref. 2). Researchers examining the ‘‘Search’’ box and follow the prompts decreased likelihood that existing users impact of the Special Rule for Cigarettes and/or go to the Dockets Management of tobacco products will stop using such have concluded that, while the Staff, 5630 Fishers Lane, Rm. 1061, products; and the increased or prohibition of characterizing flavors in Rockville, MD 20852. decreased likelihood that those who do cigarettes has reduced adolescent FOR FURTHER INFORMATION CONTACT: not use tobacco products will start using tobacco product use, the continued Laura Rich or Katherine Collins, Center such products (section 907(a)(3)(A) and availability of menthol cigarettes and for Tobacco Products, Food and Drug (B) of the FD&C Act). Thus, under other flavored tobacco products likely Administration, Document Control section 907, FDA may issue product diminish the effects (Ref. 3). Researchers Center, 10903 New Hampshire Ave., standards respecting the construction, estimated a 6 percent reduction in the Bldg. 71, Rm. G335, Silver Spring, MD components, ingredients, additives, probability of using any tobacco product 20993, 1–877–CTP–1373, constituents, and properties of tobacco after implementation of the Tobacco [email protected]. products (section 907(a)(4)(B)(i)) and Control Act (2009–2013), and observed the reductions to be significantly SUPPLEMENTARY INFORMATION: restricting their sale and distribution associated with the Special Rule for (section 907(a)(4)(B)(v)).1 I. Background Cigarettes (Ref. 3). The Tobacco Control Act includes a The adverse health effects associated A. The Tobacco Control Act ‘‘Special Rule for Cigarettes,’’ which with tobacco product use by youth have The Tobacco Control Act (Pub. L. prohibits cigarettes from containing been well documented. Nicotine 111–31) was enacted on June 22, 2009, characterizing flavors other than tobacco exposure and smoking during amending the FD&C Act and providing or menthol (section 907(a)(1)(A)). The adolescence can have unique adverse FDA with the authority to regulate statute also authorizes the Agency to consequences on brain development tobacco products. Specifically, the issue additional product standards, (Refs. 2 and 4). For example, smoking Tobacco Control Act amends the FD&C including to address flavors in tobacco cigarettes during adolescence is Act by adding a new chapter that products (see section 907(a)(3)) and associated with lasting cognitive and provides FDA with authority over preserves FDA’s authority to act with behavioral impairments, including tobacco products. Section 901(b) of the respect to menthol (section 907(e)(3)). effects on working memory in smoking FD&C Act (21 U.S.C. 387a(b)), as The deeming rule did not include teens (Ref. 5) and alterations in the amended by the Tobacco Control Act, provisions relating to flavors in tobacco prefrontal attentional network in young states that the new chapter in the FD&C products. Nevertheless, FDA explained adult smokers (Ref. 6). Furthermore, the Act (chapter IX—Tobacco Products) (21 that it did intend to consider the issues nonclinical data related to nicotine U.S.C. 387 through 387u) applies to all exposure and epidemiologic studies 1 As set forth above, section 907(a)(4)(B)(v) cigarettes, cigarette tobacco, roll-your- provides that product standards ‘‘shall, where related to smoking cigarettes during own tobacco, smokeless tobacco, and appropriate for the protection of the public health, adolescence taken together suggest an any other tobacco products that the include—. . . (v) a provision requiring that the sale age-dependent susceptibility to nicotine Secretary of Health and Human Services and distribution of the tobacco product be restricted (Ref. 1). but only to the extent that the sale and distribution by regulation deems to be subject to of a tobacco product may be restricted under a Use of tobacco products, which is chapter IX. In the Federal Register of regulation under section 906(d).’’ Section 906(d) facilitated by nicotine exposure and May 10, 2016 (81 FR 28973), FDA gives FDA authority to require restrictions on the dependence, puts youth and young issued a final rule deeming all products sale and distribution of tobacco products by adults at greater risk for future health regulation if the Agency determines that such that meet the statutory definition of regulations would be appropriate for the protection issues, such as coronary artery disease, ‘‘tobacco product’’ in section 201(rr) of of the public health. See section 906(d)(1) of the cancer, and other known tobacco-related the FD&C Act (21 U.S.C. 321(rr)), except FD&C Act. diseases (Refs. 1 and 4). Youth and

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young adult tobacco product users, feelings of pain or discomfort (Refs. 22 participated in the Population particularly cigarette smokers, also are and 23), or increase sensations of Assessment of Tobacco and Health at increased risk for future marijuana respiration ease (Refs. 22 through 26). (PATH) Study in 2013–2014, 88.7 and illicit drug use, developmental and Documents from the tobacco industry percent of youth who have ever used mental health disorders, reduced lung show that food flavors, such as fruit and (i.e., ever tried even one or two times) growth and impaired function, candy, were used to attract new users, waterpipe tobacco, 81 percent of e- increased risk of asthma, and early primarily youth (Ref. 1). Laboratory cigarette ever-users, and 65.4 percent of abdominal aortic atherosclerosis (Ref. research has confirmed that tobacco cigar ever-users reported that the first 1). products contain flavor chemicals at the product they used in these categories Nicotine is highly addictive. The use same level per serving as defined by the was flavored (Ref. 36). Similarly, 79.8 of nicotine can lead to nicotine studies, or higher than, popular candy percent of youth who reported being dependence, and makes quitting tobacco and drink products (Refs. 27 and 28). current tobacco product users in the products very difficult (Ref. 1). Flavors in food products can trigger PATH Study reported using a flavored Achieving tobacco cessation after reward pathways in the brain and tobacco product in the past 30 days, nicotine addiction is a long and difficult influence decision-making (Ref. 29). including 89 percent of waterpipe users, process. Smokers may try quitting 30 or Flavors in tobacco products can also 85.3 percent of e-cigarette users, and more times before succeeding (Ref. 7). trigger reward pathways in the brain 71.7 percent of cigar smokers (Ref. 36). According to data from the 2015 and additionally enhance the rewards of Data regarding use of flavored little National Health Interview Survey, 68 nicotine (Refs. 30 and 31). filtered cigars also demonstrate appeal percent of adult smokers in the United to youth and young adults. For example, States wanted to quit smoking and 55.4 2. Tobacco Product Use Patterns by 2017 Monitoring the Future data show percent made at least one quit attempt Youth that among 8th, 10th, and 12th grade in the past year; however, only 7.4 a. Overall tobacco product use. students, 60 percent of current little percent actually quit within the 6 to 12 According to National Youth Tobacco cigar users reported using flavored little months preceding the survey (Ref. 8). Survey (NYTS) data, the current use of cigars (Ref. 40). In addition, data from 1. The Appeal of Flavors Generally and e-cigarettes among U.S. youth increased the PATH Study show that among in Tobacco Products Specifically significantly between 2011 and 2015 current filtered cigar users, 79.3 percent (Ref. 32). While use dropped in 2016, e- of young adults aged 18–24 years and Flavor is a multisensory perception cigarettes remain the most commonly 56.2 percent of adults aged 25 years and consisting of taste, aroma, and used tobacco product by youth (Refs. 33 older report current flavored use (Ref. chemesthetic (e.g., cooling, burning) and 34). Current use of waterpipes 37). Moreover, both youth and young sensations in the mouth and throat (Ref. among U.S. youth increased adults identified flavors as a major 9). A robust body of literature in food significantly between 2011 and 2014, reason for their e-cigarette use (Refs. 36 consumer science demonstrates that but declined in 2015 and 2016 (Ref. 33). through 38). In addition, youth flavors impact the appeal of consumable The use of cigarettes, cigars, and consistently reported product flavoring products (Refs. 10 and 11), and that smokeless tobacco has generally as a reason for using waterpipes, cigars, flavor preferences drive food selection declined among youth in recent years, and smokeless tobacco (including snus and vary across age groups (Refs. 12 and although these products remain popular products) (Refs. 36 and 37). 13). Certain flavors are particularly among certain youth subpopulations While the prevalence of cigarette appealing to children and youth; for (Refs. 1, 33, and 35). smoking among youth generally has example, youth have a heightened b. Use of tobacco products with declined, rates of menthol smoking preference for sweet food tastes and flavors. Data regarding use of menthol among youth remained stable between greater rejection of bitter food tastes. cigarettes and non-cigarette tobacco 2004 and 2014 (Ref. 41). Youth and These preferences generally diminish products among youth from 2013–2014 young adult smokers are with age (Refs. 14 through 17). Flavor show widespread appeal of flavored disproportionately more likely to smoke compounds, such as sugar, are used to tobacco products 2 (Refs. 36 through 38). menthol than nonmenthol cigarettes, as enhance flavor or mask undesirable Results from the 2014 NYTS on flavored compared to older adult smokers; in tastes (e.g., bitter) in food. (Ref. 18). tobacco product use in the past 30 days 2014, 52.4 percent of youth smokers Research on the appeal of flavors in among middle and high school students aged 12–17 years, 50.5 percent of young food informs the understanding of the show that an estimated 3.26 million adult smokers aged 18–25 years, and appeal and the public health impact of youth tobacco product users (12 percent 36.3 percent of adult smokers aged 26 flavors in tobacco products. In fact, of all youth) reported using a flavored years or older, reported smoking many of the same compounds that are tobacco product in the past 30 days (Ref. menthol cigarettes (Ref. 42). Multiple added to food are also added to tobacco 39). By product, an estimated 1.58 studies show a greater use of menthol products to enhance flavor or mask million reported using a flavored e- cigarettes by younger smokers and less undesirable tastes (Refs. 19, 27, and 28). cigarette, 1.02 million reported using usage among older smokers (Refs. 42 As with food products, flavors are flavored waterpipe tobacco, 910,000 through 45). added to tobacco products to, among reported using flavored cigars, 900,000 other things, improve flavor and taste, 3. Flavors and Perceptions of Harm and reported using menthol cigarettes, such as by reducing the harshness, Likelihood of Tobacco Product Use 690,000 reported using flavored bitterness, and astringency of tobacco Perceptions about tobacco harm (i.e., smokeless tobacco (defined as chewing during inhalation (Refs. 19 and 20). beliefs about the health risks of tobacco) tobacco, snuff, dip, snus, or Studies involving cigarettes have shown can influence tobacco product use dissolvables), and 120,000 reported that the addition of sweet flavors behavior as research suggests that using flavored pipe tobacco (Ref. 39). increases the appeal of these products, adolescents who perceive lower harms Among youth (12–17 years) who especially to youth (Refs. 19 to 21). In from using tobacco products are more addition, the sensory qualities of 2 For the purposes of this ANPRM, the terms likely to initiate use (Ref. 46). Two menthol flavor produce an analgesic or ‘‘flavored tobacco product’’ and ‘‘flavors in tobacco systematic reviews report findings from ‘‘cooling’’ effect, which can reduce products’’ are used interchangeably. studies assessing participants’

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(including youth, young adults, and flavors, 56.8 percent reported preferring 6. Adults’ Use of Flavors in Tobacco adults) harm perceptions of flavored sweet flavors, while 8.7 percent Products tobacco products. Some findings show preferred menthol e-cigarettes (Ref. 50). Cross-sectional data from Wave 1 of that each age group perceived flavored Additional results from the same the PATH Study (Ref. 37) indicate that tobacco products as less harmful than research found that the top three adult (25 years or older) established unflavored products (Refs. 47 and 48). reasons for e-cigarette experimentation tobacco product users also often use 4. Flavors and Progression to Regular among ever e-cigarette users, regardless flavored products (44.8 percent). Use of cigarette smoking status and school Specifically, 35.6 percent of cigarette level, were curiosity (54.4 percent), the smokers (menthol), 63.2 percent of The association between initiation availability of appealing flavors (43.8 ENDS users, 47.8 percent of cigar with flavored tobacco products and smokers, 68.7 percent of waterpipe current tobacco product use was percent), and friends’ influence (31.6 users, and 48.7 percent of smokeless examined in Wave 1 of the PATH Study percent) (Ref. 51). Another cross- data, which indicated that 81 percent of sectional study, in which 1,567 young tobacco product users reported use of youth (12–17 years of age) and 86 adults (18–34 years) were recruited flavored products at Wave 1 (2013– percent of young adult (18–24 years of through Facebook ads, reported that the 2014). Among established users of age) ever tobacco users (i.e., those who most commonly used flavors among cigarettes and other tobacco products have used a tobacco product even once current e-cigarette users were fruit (66.9 (polyusers), 68.9 percent use at least one or twice in their lifetimes) reported that percent), candy (35.1 percent), and flavored product. The 2013–2014 NATS study data the first tobacco product they used was caramel/vanilla/chocolate/cream (33.3 (among adults aged 18 years or older) flavored, compared to 54 percent of percent) (Ref. 38). E-cigarette flavor adults aged 25 years and older (Ref. 37). preferences also varied by cigarette suggested that the tendency to use Controlling for other factors associated smoking status with former or never flavored e-cigarettes and flavored cigars differed by cigarette smoking status. with tobacco product use, youth ever cigarette smokers preferring flavors Never cigarette smokers tended to use tobacco users who reported their first more frequently than current cigarette flavored e-cigarettes more than other tobacco product was flavored had a 13 smokers (Ref. 38). percent higher prevalence of current groups. Specifically, findings indicated Qualitative findings reveal differences tobacco product use compared to youth that, among users of non-cigarette in e-cigarette flavor preferences as well. whose first product was not flavored. tobacco products, never-cigarette Research from a 2016 laboratory study Adult ever users reporting that the first smokers had the highest proportion of tobacco product they used was flavored of young adult cigarette smokers who flavored e-cigarette use (84.8 percent), had a 32 percent higher prevalence of used e-cigarettes for the study reported followed by 78.1 percent of recent current established tobacco product use fruit flavored (green apple) and dessert quitters and 63.2 percent of current (Ref. 37). flavored (chocolate) e-cigarettes were cigarette smokers. The study also In addition, a longitudinal more satisfying and rewarding than indicated, among users of non-cigarette examination of youth indicated that unflavored e-cigarettes (Ref. 52). tobacco products, that 43.8 percent of youth who initiate smoking with Furthermore, participants puffed current cigarette smokers reported menthol cigarettes may be at greater risk flavored e-cigarettes approximately 40 smoking flavored cigars, with 30.8 for progression from experimentation to times compared with approximately 23 percent of never smokers and 38.9 established smoking and nicotine times for unflavored e-cigarettes (Ref. percent of recent former smokers dependence than youth who initiate 52). Similarly, other research has shown reporting smoking flavored cigars (Ref. with nonmenthol cigarettes (Ref. 49). that sweet-flavored e-cigarettes produce 54). The 2013–2014 NATS study also higher appeal ratings among youth than reported flavor types used by product 5. Youth and Young Adult Flavor non-sweet and flavorless e-cigarettes among adults aged 18 and over. Users of Preferences (Ref. 53). flavored smokeless tobacco reported As mentioned in section I.C.1. of this using menthol/mint (76.9 percent), For cigars/cigarillos/little cigars, document, youth generally prefer sweet clove/spice/herb (12.3 percent), fruit waterpipe, and smokeless tobacco flavors (Refs. 14 through 17). (10.8 percent), and candy/chocolate/ products, limited evidence exists that Researchers reviewed the flavor other sweet (4.5 percent) (Ref. 54). differentiates types of flavors preferred chemicals and levels in several brands Flavored waterpipe users reported using (e.g., menthol, fruit) among young of candy and Kool-Aid drink mix and fruit (74 percent), menthol/mint (18.9 concluded that the chemicals used in adults. Among young adults (18–24 percent), candy/chocolate/other sweet these products largely overlapped with years of age), the 2013–2014 National (17.4 percent), clove/spice/herb (4.3 those in similarly labeled ‘‘cherry,’’ Adult Tobacco Survey (NATS) reported percent), alcohol (3.2 percent), and ‘‘grape,’’ ‘‘apple,’’ ‘‘peach,’’ and ‘‘berry’’ the top three flavor types used by other flavored (3 percent). Flavored e- tobacco products (Ref. 27). product. Young adult flavored cigarette users reported using fruit (44.9 Results from studies show that smokeless tobacco product users percent), menthol/mint (43.9 percent), flavored e-cigarettes appeal to youth and reported using menthol/mint (80.6 candy/chocolate/other sweet (25.7 young adults; however, these data may percent), fruit (13.9 percent), and clove/ percent), clove/spice/herb (7 percent), not reflect the flavor preferences among spice/herb (7.7 percent) (Ref. 54). Young other flavored (6.1 percent), and alcohol all U.S. youth and adults. In a survey adult flavored waterpipe users reported flavors (4 percent) (Ref. 54). Flavored conducted in four high schools and two using fruit (73.5 percent), menthol/mint cigar, cigarillo, and little cigar users middle schools in Connecticut in 2013, (18 percent), and candy/chocolate/other reported using fruit (52.4 percent), 70.7 percent of the lifetime e-cigarette sweet (17.3 percent). Young adult candy/chocolate/other sweet (22 users (adolescents who had tried an e- flavored cigar/cigarillo/little cigar users percent), alcohol (14.5 percent), cigarette) interviewed reported having reported using fruit (61.4 percent), menthol/mint (12.9 percent), clove/ used sweet flavors and 22.1 percent alcohol (21.9 percent), and candy/ spice/herb (8.1 percent) and other reported having used menthol-flavored chocolate/other sweet (20.8 percent) flavors (2.9 percent). Flavored pipe e-cigarettes. In terms of preferred (Ref. 54). smokers reported using fruit (56.6

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percent), candy/chocolate/other sweet D. The Potential Role of Flavors in II. Requests for Comments and (26.5 percent), and menthol/mint (24.8 Facilitating Transition From Cigarettes Information percent) (Ref. 54). to Tobacco Products That May Pose Less FDA is seeking comments (including Among adult e-cigarette users, a study Risk comments on this document and the with experienced exclusive e-cigarette FDA also is aware of self-reported data presented), data, research results, and dual (e-cigarette and cigarette) users information suggesting that the and other information related to the following topics. Please explain your (aged 18 years or older) found that availability of flavors in some responses and provide any evidence or bitterness and harshness are negatively noncombusted tobacco products (e.g., associated with liking e-cigarettes, while other information supporting them. ENDS) may help some adult users sweetness and ‘‘coolness’’ are positively • For the purposes of the questions in decrease their cigarette use and associated with liking them (Ref. 55). In this ANPRM, when seeking comments, transition away from combusted addition, sweetness appeared to have a data, research results, and other products to potentially less harmful greater impact than coolness on liking information on ‘‘flavors,’’ FDA is products (Refs. 62 and 63). Reports from (Ref. 55). seeking information relating to the a focus group of eleven e-cigarette users, following (as applicable): (1) Artificial 7. Flavors May Contain or Form Toxic nine of whom switched to e-cigarettes or natural flavor additives, compounds, Compounds from smoking a half-pack per day or constituents, or ingredients or any other more of cigarettes, suggest that the flavoring ingredient in a tobacco Evidence exists regarding the toxicity ability of consumers to personalize their of flavors, specifically certain product, including its components or e-liquids by mixing and matching parts; (2) the multisensory experience of ingredients in those flavors that have flavors could contribute to e-cigarette been used in tobacco products. Of a flavor during use of tobacco products; appeal among cigarette smokers (Ref. (3) flavor representations (including particular concern for combusted or 62). In one survey using an online descriptors), either explicit or implicit, heated tobacco products is that toxicity convenience sample (i.e., self-selected in or on the labeling, advertising, and also may result from the chemicals respondents recruited from online vape packaging of tobacco products; and (4) formed when flavors are heated or forums), respondents indicated that any other means that impart flavor or burned (Refs. 56 through 60). Diacetyl flavor variety was ‘‘very important’’ in represent that tobacco products are and acetyl propionyl, which are flavor reducing or quitting smoking (Ref. 63). flavored. The foregoing is intended only ingredients that have been found in e- Almost half of the respondents in that to provide guidance to commenters and liquids, are highly irritating volatile survey indicated that a reduction in is not intended to limit or restrict the organic compounds (Refs. 56 and 60). available flavors would ‘‘increase information they may submit. There is scientific evidence showing a craving[s] for tobacco cigarettes and Additionally, for purposes of the link between repeated inhalation would make reducing or completely questions in the ANPRM: exposures to these flavor ingredients substituting smoking less likely’’ (Ref. • ‘‘Youth’’ means under age 18; and and adverse respiratory health outcomes 63). • ‘‘Young adult’’ means ages 18 in humans (Ref. 60). Finally, we note through 24. that certain substances may be The issues surrounding the use of flavors in tobacco products involve FDA intends to use the information authorized as a food additive or may be submitted in response to this Federal considered ‘‘generally recognized as various considerations. While data show significant youth appeal and continued Register document, its independent safe’’ (GRAS) for certain uses in food. scientific knowledge, and other growth in youth and young adult use of However, being authorized as a food appropriate information to inform flavored tobacco products, which can additive or being considered GRAS, in regulatory actions FDA might take with lead to lifelong tobacco product use, and of itself, does not mean that the respect to flavors in tobacco products. self-reported information from a study substances are safe when used in a When submitting information, provide (Ref. 63) shows that some flavors in tobacco product. The food additive evidence by product class (e.g., approval or GRAS status of a substance ENDS may play a positive role in cigarettes, cigars, pipes) for each topic, applies only to specific intended uses in helping some adults transition away when available. If it exists, discuss the food, and are not supported by studies from cigarettes to potentially less influence of flavors by flavor type/ that account for inhalation toxicity. harmful products. In addition, we note category (e.g., fruit, candy, menthol) for Importantly, exposure to chemicals via that, currently, no ENDS have been each topic. Also, provide information the inhalation route can have very approved as effective cessation aids. In regarding any positive or negative different effects from oral exposure, and the preamble to the deeming rule, FDA effects that may result from a regulatory most tobacco products are inhaled (Ref. discussed the evidence available to date, action FDA might take with respect to 61). For example, direct ‘‘portal of and found that some systematic reviews flavors in tobacco products, including, entry’’ effects to the respiratory tract, found insufficient data to draw a but not limited to, health implications which is relatively more sensitive than conclusion about the efficacy of e- and economic impacts. We ask that the gastrointestinal tract, can occur cigarettes as cessation aids (81 FR 28973 commenters clearly identify the section upon inhalation exposure. There are at 29037). A recent systematic review by and question number associated with also important metabolic differences the National Academies of Sciences, their responsive comments and between the two routes of exposure: Engineering, and Medicine found information. After oral ingestion, a substance can be ‘‘limited evidence that e-cigarettes may detoxified through ‘‘first-pass be effective aids to promote smoking A. The Role of Flavors (Other Than metabolism’’ in the liver before reaching cessation,’’ and that ‘‘there is moderate Tobacco) in Tobacco Products systemic circulation. By contrast, evidence from observational studies that 1. Provide studies or information substances introduced into the body via more frequent use of e-cigarettes is regarding the role of flavors (other than inhalation go directly into systemic associated with increased likelihood of tobacco) generally in tobacco products. circulation without the same potential cessation,’’ thus, the evidence remains If the response relies on research in for detoxification (Ref. 61). inconclusive (Ref. 64). other areas (e.g., consumer products),

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discuss the appropriateness of tobacco) in noncombusted tobacco should FDA establish to protect the extrapolating from such research to products on the likelihood that former public health, and why? tobacco products. combusted tobacco product users 14. If FDA were to establish a tobacco relapse. Include information from, and product standard prohibiting or B. Flavors (Other Than Tobacco) and define, all populations: Youth, young restricting flavors, to which types of Initiation and Patterns of Tobacco adults, and adults (and any subgroup tobacco products should the standard Product Use, Particularly Among Youth thereof, if applicable). apply (e.g., combusted, noncombusted, and Young Adults both), and why? 2. Provide studies or information D. Additional Public Health 15. Menthol Flavor: regarding the role of flavors (other than Considerations a. FDA has carefully reviewed the tobacco) in initiation and/or patterns of 9. Provide studies or information data it received in response to the 2013 use of combusted tobacco products, regarding the potential toxicity or ANPRM on menthol in cigarettes (78 FR particularly among youth and young adverse health effects to the user or 44484, July 24, 2013). Provide any adults. others from any flavors (e.g., flavor additional data or information about the 3. Provide studies or information additives, compounds, or ingredients) in role of menthol in cigarettes, regarding the role of flavors (other than tobacco products. These adverse health particularly regarding the role menthol tobacco) in initiation and/or patterns of outcomes may include, but are not plays in smoking initiation and in the use of noncombusted tobacco products, limited to, cancer or adverse respiratory, likelihood of smoking cessation for all particularly among youth and young cardiac, or reproductive/development populations (youth, young adult, adult). adults. effects. Of particular interest are studies b. What additional evidence exists on 4. Provide studies or information or information on inhalation exposure the likelihood that smokers would regarding the role of flavors (other than to any flavor. Provide studies or completely switch to another tobacco tobacco) in noncombusted tobacco information on what, if any, toxic product, or start dual use with another products on initiation of tobacco chemicals might be formed from the product, in the event of a tobacco product use or progression to use of heating or burning of tobacco products product standard prohibiting or limiting other tobacco products (for example, with flavors and the potential toxicity or menthol in cigarettes? from noncombusted to combusted health risks that might result from these c. What is the role, if any, that tobacco products), particularly among formed chemicals. menthol plays in use of tobacco youth and young adults. 10. Provide studies or information on products other than cigarettes, including, but not limited to, cigars and C. Flavors (Other Than Tobacco) and the impact, whether intended or ENDS? Cessation, Dual Use, and Relapse unintended, of public health efforts by Among Current and Former Tobacco local jurisdictions, States, and members F. Sale or Distribution Restrictions Product Users of the international community to impose restrictions on the manufacture, 16. FDA may consider restrictions on 5. Provide studies or information marketing, sale or distribution of all or the sale and distribution of flavored regarding the role of flavors (other than a subset of tobacco products with tobacco products. Possible restrictions tobacco) in helping adult cigarette flavors (other than tobacco), including could include restrictions on the smokers reduce cigarette use and/or but not limited to cigars, ENDS, menthol advertising and promotion of tobacco switch to potentially less harmful cigarettes, and smokeless tobacco products with flavors; on access to tobacco products. products. tobacco products with flavors; and/or on 6. Provide studies or information 11. Provide studies or information the label, labeling, and/or packaging of regarding the role of flavors (other than regarding consumer perceptions of the tobacco products with flavors. These tobacco) in noncombusted tobacco health risks of tobacco products with restrictions could include requirements products on the likelihood of: (1) flavors (other than tobacco) when to bear warnings or disclosure Cessation of combusted tobacco compared to other tobacco products, statements. What such restrictions, if products use, (2) cessation of all tobacco both with and without flavors. Include any, should FDA consider and why? product use, and (3) uptake of dual use information from, and define, all G. Other Actions and Considerations of combusted and noncombusted populations: Youth, young adults, and tobacco products among current and adults (and any subgroup thereof, if 17. To the extent that flavors may former tobacco product users. Include applicable). pose both (1) potential benefits to adult information from, and define, all 12. Provide studies or information smokers who might consider switching populations: Youth, young adults, and regarding consumer perceptions, if any, to a noncombusted flavored tobacco adults (and any subgroup thereof, if of the addictiveness of tobacco products product with lower individual risk and applicable). with flavors (other than tobacco). (2) potential risks to nonusers who 7. Provide studies or information Include information from, and define, might initiate use of tobacco products regarding the role of flavors (other than all populations: Youth, young adults, through flavored tobacco products or to tobacco) in noncombusted products on and adults (and any subgroup thereof, if current users who might progress to the likelihood of: (1) Delayed or applicable). flavored tobacco products with higher impeded cessation among users who individual risks, how should FDA would have otherwise quit combusted E. Tobacco Product Standards assess and balance these benefits and tobacco product use, or (2) delayed or 13. All Flavors: risks? impeded cessation among users who a. Are there any specific flavors for 18. Provide studies or information on would have otherwise quit all tobacco which FDA should establish a tobacco the role of tobacco flavor in tobacco product use. Include information from, product standard? If so, which flavors products in initiation, patterns of use of and define, all populations: Youth, (e.g., flavor additives, compounds, or tobacco products (particularly with young adults, and adults (and any ingredients) and why? respect to progression from non- subgroup thereof, if applicable). b. With respect to your response to combusted to combusted tobacco 8. Provide studies or information the previous question, what level (e.g., products or from combusted to non- regarding the role of flavors (other than maximum, minimum, prohibition) combusted), reduction in use of

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combustible tobacco products and www.regulations.gov. FDA has verified Preferences in Humans,’’ Physiology and cessation of tobacco products. Include the website addresses, as of the date this Behavior, 39(5):639–641, 1987. information from, and define, all document publishes in the Federal 16. Enns, M.P., T.B. Van Itallie, and J.A. populations: Youth, young adults, and Register, but websites are subject to Grinker, ‘‘Contributions of Age, Sex and Degree of Fatness on Preferences and adults (and any subgroup thereof, if change over time. Magnitude Estimations for Sucrose in applicable). 1. U.S. Department of Health and Human Humans,’’ Physiology and Behavior, 19. Provide information on whether Services, ‘‘Preventing Tobacco Use 22(5):999–1003, 1979. manufacturing process(es) affect Among Youth and Young Adults: A 17. De Graaf, C. and E.H. Zandstra, product flavor. Describe any such Report of the Surgeon General, 2012.’’ ‘‘Sweetness Intensity and Pleasantness in manufacturing process(es), including 2. U.S. Department of Health and Human Children, Adolescents, and Adults,’’ the specific products that use the Services, ‘‘E-cigarette Use Among Youth Physiology and Behavior, 67(4):513–520, process(es), as well as specific flavors and Young Adults: A Report of the 1999. used in the process(es). Surgeon General, 2016.’’ 18. Hayes, J.E. and S. Johnson, ‘‘Sensory 3. Courtemanche, C.J., M.K. Palmer, and M.F. 20. Provide analyses regarding any Aspects of Bitter and Sweet Tastes Pesko, ‘‘Influence of the Flavored During Early Childhood,’’ Nutrition other tobacco product standard, Cigarette Ban on Adolescent Tobacco Today, 52(2):S41–S51, 2017. regulatory action, or other action that Use,’’ American Journal of Preventive 19. Carpenter, C.M., G.F. Wayne, J.L. Pauly, FDA could implement that you believe Medicine, 52(5):e139–e146, 2017. et al., ‘‘New Cigarette Brands With would more effectively reduce the 4. U.S. Department of Health and Human Flavors That Appeal to Youth: Tobacco harms caused by flavors in tobacco Services, ‘‘The Health Consequences of Marketing Strategies,’’ Health Affairs, products to better protect the public Smoking—50 Years of Progress: A Report 24(6):1601–1610, 2005. health than the tobacco product of the Surgeon General, 2014.’’ 20. Cummings, K.M., C.P. Morley, J.K. Horan, 5. Jacobsen, L.K., J.H. Krystal, W.E. Mencl, et standards or other regulatory actions et al., ‘‘Marketing to America’s Youth: al., ‘‘Effects of Smoking and Smoking Evidence From Corporate Documents,’’ discussed in the preceding questions. Abstinence on Cognition in Adolescent Tobacco Control, 11 Suppl 1(suppl 21. Discuss any other tobacco product Tobacco Smokers,’’ Biological 1):15–17, 2002. standard, regulatory action, or other Psychiatry, 57(1):56–66, 2005. 21. Manning, K.C., K.J. Kelly, and M.L. activity that FDA could pursue that 6. Musso, F., F. Bettermann, G. Vucurevic, et Comello, ‘‘Flavoured Cigarettes, would complement or increase the al., ‘‘Smoking Impacts on Prefrontal Sensation Seeking and Adolescents’ effectiveness of the potential tobacco Attentional Network Function in Young Perceptions of Cigarette Brands,’’ product standards or other regulatory Adult Brains,’’ Psychopharmacology Tobacco Control, 18(6):459–465, 2009. (Berl), 191(1):159–169, 2007. 22. Harris, B., ‘‘Menthol: A Review of Its actions discussed in the preceding 7. Chaiton, M., L. Diemert, J.E. Cohen, et al., questions. Thermoreceptor Interactions and Their ‘‘Estimating the Number of Quit Therapeutic Applications,’’ International 22. Are there any flavors that Attempts It Takes to Quit Smoking especially appeal to youth, young Journal of Aromatherapy, 16(3–4):117– Successfully in a Longitudinal Cohort of 131, 2006. Smokers,’’ BMJ Open, 6(6):e011045, adults, or other specific age group? If so, 23. Galeotti, N., L. Di Cesare Mannelli, G. 2016. how are such flavors distinguished from Mazzanti, et al., ‘‘Menthol: A Natural 8. Babb, S., A. Malarcher, G. Schauer, et al., other flavors? Analgesic Compound,’’ Neuroscience ‘‘Quitting Smoking Among Adults— 23. To the extent that you have Letters, 322(3):145–148, 2002. United States, 2000–2015,’’ Morbidity identified a tobacco product standard or and Mortality Weekly Report, 24. Nishino, T., Y. Tagaito, and Y. Sakurai, other regulatory action in response to 65(52):1457–1464, 2017. ‘‘Nasal Inhalation of L-Menthol Reduces the prior questions, provide additional 9. Small, D.M. and B.G. Green, ‘‘A Proposed Respiratory Discomfort Associated With information and comments on: (1) The Model of a Flavor Modality.’’ In: M.M. Loaded Breathing,’’ American Journal of technical achievability of compliance Murray and M.T. Wallace, M.T. (Eds.), Respiratory and Critical Care Medicine, 156(1):309–313, 1997. with the tobacco product standard or The Neural Bases of Multisensory Processes, Chapter 36. Boca Raton FL: 25. Lawrence, D., B. Cadman, and A.C. other regulatory action you identified; Hoffman, ‘‘Sensory Properties of and (2) how FDA could maximize CRC Press/Taylor & Francis, 2012. 10. Piqueras-Fiszman, B. and C. Spence Menthol and Smoking Topography,’’ compliance and public health benefits. (Eds.), Multisensory Flavor Perception: Tobacco Induced Diseases, 9 Suppl 24. If FDA were to establish a tobacco From Fundamental Neuroscience 1(Suppl 1):S3, 2011. product standard prohibiting or Through to the Marketplace. Cambridge: 26. Garten, S. and R.V. Falkner, ‘‘Continual restricting flavors in tobacco products, Woodhead Publishing, 2016. Smoking of Mentholated Cigarettes May what evidence is there, if any, that 11. Etie´vant, P., E. Guichard, C. Salles, et al., Mask the Early Warning Symptoms of consumers would start to flavor their (Eds.), Flavor: From Food to Behaviors, Respiratory Disease,’’ Preventive own tobacco products? Wellbeing and Health. Philadelphia: Medicine, 37(4):291–296, 2003. 25. What data may be used to assess Elsevier Science, 2016. 27. Brown, J.E., W. Luo, L.M. Isabelle, et al., 12. Beauchamp, G.K. and J.A. Mennella, ‘‘Candy Flavorings in Tobacco,’’ New and analyze the range and variety of England Journal of Medicine, flavored tobacco products that are ‘‘Flavor Perception in Human Infants: Development and Functional 370(23):2250–2252, 2014. currently available to consumers? How Significance,’’ Digestion, 83 Suppl 1:1–6, 28. Chen, C., L.M. Isabelle, W.B. Pickworth, can available sources of information, 2011. et al., ‘‘Levels of Mint and Wintergreen such as manufacturer registrations and/ 13. Cowart, B., G. Beauchamp, and J. Flavorants: Smokeless Tobacco Products or product listings with FDA, be used in Mennella, ‘‘Development of Taste and vs. Confectionery Products,’’ Food and this assessment? Smell in the Neonate.’’ In: R. Polin and Chemical Toxicology: An International S. Abman, (Eds.), Fetal and Neonatal Journal Published for the British III. References Physiology, pp.1899–1907. Philadelphia: Industrial Biological Research The following references are on Elsevier Saunders, 2011. Association, 48(2):755–763, 2010. display in the Dockets Management 14. Mennella, J.A., M.Y. Pepino, and D.R. 29. Rolls, E.T., ‘‘Flavor: Brain Processing.’’ In: Reed, ‘‘Genetic and Environmental P. Etievant, E. Guichard, C. Salles, et al., Staff (see ADDRESSES) and are available Determinants of Bitter Perception and (Eds.), Flavor: From Food to Behaviors, for viewing by interested persons Sweet Preferences,’’ Pediatrics, Wellbeing and Health, pp. 143–160. between 9 a.m. and 4 p.m., Monday 115(2):e216-e222, 2005. Philadelphia: Elsevier Science, 2016. through Friday; they are also available 15. Desor, J.A. and G.K. Beauchamp, 30. Touzani, K., R.J. Bodnar, and A. Sclafani, electronically at https:// ‘‘Longitudinal Changes in Sweet ‘‘Neuropharmacology of Learned Flavor

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Preferences,’’ Pharmacology, Possible Public Health Effects of Menthol 57. Hutzler, C., M. Paschke, S. Kruschinski, Biochemistry, and Behavior, 97(1):55–62, Versus Nonmenthol Cigarettes,’’ 2013. et al., ‘‘Chemical Hazards Present in 2010. 44. Fernander, A., M.K. Rayens, M. Zhang, et Liquids and Vapors of Electronic 31. Palmatier, M.I., J.E. Lantz, L.C. O’Brien, al., ‘‘Are Age of Smoking Initiation and Cigarettes,’’ Archives of Toxicology, and S.P. Metz, ‘‘Effects of Nicotine on Purchasing Patterns Associated With 88(7):1295–1308, 2014. Olfactogustatory Incentives: Preference, Menthol Smoking?’’ Addiction, 105 58. Tierney, P.A., C.D. Karpinski, J.E. Brown, Palatability, and Operant Choice Tests,’’ Suppl 1(s1):39–45, 2010. et al., ‘‘Flavour Chemicals in Electronic Nicotine & Tobacco Research, 45. Hersey, J.C., SW Ng, J.M. Nonnemaker, et Cigarette Fluids,’’ Tobacco Control, 15(9):1545–1554, 2013. al., ‘‘Are Menthol Cigarettes a Starter 25(e1):e10-e15, 2016. 32. Singh, T., R.A. Arrazola, C.G. Corey, et Product for Youth?’’ Nicotine & Tobacco 59. Farsalinos, K.E., K.A. Kistler, G. Gillman, al., ‘‘Tobacco Use Among Middle and Research, 8(3):403–413, 2006. et al., ‘‘Evaluation of Electronic Cigarette High School Students—United States, 46. Song, A.V., H.E. Morrell, J.L. Cornell, et Liquids and Aerosol for the Presence of 2011–2015,’’ Morbidity and Mortality al., ‘‘Perceptions of Smoking-Related Selected Inhalation Toxins,’’ Nicotine & Weekly Report, 65(14):361–367, 2016. Risks and Benefits as Predictors of Tobacco Research, 17(2):168–174, 2015. 33. Jamal, A., A. Gentzke, S.S. Hu, et al., Adolescent Smoking Initiation,’’ 60. National Institute for Occupational Safety ‘‘Tobacco Use Among Middle and High American Journal of Public Health, and Health, Criteria for a Recommended School Students—United States, 2011– 99(3):487–492, 2009. Standard: Occupational Exposure to 2016,’’ Morbidity and Mortality Weekly 47. Huang, L.-L., H.M. Baker, C. Meernik, et Diacetyl and 2,3-Pentanedione. Report, 66(23):597–603, 2017. al., ‘‘Impact of Non-menthol Flavours in Cincinnati, OH: U.S. Department of 34. Miech, R.A., L.D. Johnston, P.M. Tobacco Products on Perceptions and Health and Human Services, Centers for O’Malley, et al., Monitoring the Future, Use Among Youth, Young Adults and Disease Control and Prevention, National National Survey Results on Drug Use, Adults: A Systematic Review,’’ Tobacco Institute for Occupational Safety and 1975–2016: Overview, Key Findings on Control, 26(6):709–719, 2017. Health, 2016. Adolescent Drug Use. Ann Arbor: 48. Kowitt, S.D., C. Meernik, H.M. Baker, et 61. Klaassen, C.D., Casarett & Doull’s Institute for Social Research, The al., ‘‘Perceptions and Experiences With Toxicology: The Basic Science of University of Michigan, 2017. Flavored Non-Menthol Tobacco Poisons, Eighth Edition. McGraw-Hill 35. Couch, E.T., E. Darius, M.M. Walsh, et al., Products: A Systematic Review of Education, 2013. ‘‘Smokeless Tobacco Decision-Making Qualitative Studies,’’ International Among Rural Adolescent Males in 62. Barbeau, A.M., J. Burda, and M. Siegel, Journal of Environmental Research and ‘‘Perceived Efficacy of E-cigarettes California,’’ Journal of Community Public Health, 14(4):338, 2017. Health, 42(3):544–550, 2017. Versus Nicotine Replacement Therapy 49. Nonnemaker, J., J. Hersey, G. Homsi, et Among Successful E-cigarette Users: A 36. Ambrose, B.K., H.R. Day, B. Rostron, et al., ‘‘Initiation With Menthol Cigarettes al., ‘‘Flavored Tobacco Product Use Qualitative Approach,’’ Addiction and Youth Smoking Uptake,’’ Addiction, Among US Youth Aged 12–17 Years, Science & Clinical Practice, 8(1):5, 2013. 108(1):171–178, 2013. 2013–2014,’’ Journal of the American 63. Farsalinos, K.E., G. Romagna, D. Tsiapras, 50. Krishnan-Sarin, S., M.E. Morean, D.R. Medical Association, 314(17):1871–1873, et al., ‘‘Impact of Flavour Variability on Camenga, et al., ‘‘E-cigarette Use Among 2015. Electronic Cigarette Use Experience: An High School and Middle School 37. Villanti, A.C., A.L. Johnson, B.K. Internet Survey,’’ International Journal Adolescents in Connecticut,’’ Nicotine & Ambrose, et al., ‘‘Flavored Tobacco of Environmental Research and Public Product Use in Youth and Adults: Tobacco Research, 17(7):810–818, 2015. Health, 10(12):7272–7282, 2013, Findings From the First Wave of the 51. Kong, G., M. E. Morean, D. A. Cavallo, et available at https:// PATH Study (2013–2014),’’ American al., ‘‘Reasons for Electronic Cigarette www.ncbi.nlm.nih.gov/pmc/articles/ Journal of Preventive Medicine, Experimentation and Discontinuation PMC3881166/. 53(2):139–151, 2017. among Adolescents and Young Adults,’’ 64. Stratton, K., Y. Kwan, and D. L. Eaton 38. Berg, C.J., ‘‘Preferred Flavors and Reasons Nicotine & Tobacco Research, 2015 (Eds.), Public Health Consequences of E- for E-cigarette Use and Discontinued Use Jul;17(7):847–54. Cigarettes, National Academies of Among Never, Current, and Former 52. Audrain-McGovern, J., A.A. Strasser, and Sciences, Engineering, and Medicine, Smokers,’’ International Journal of E.P. Wileyto, ‘‘The Impact of Flavoring Washington DC: The National Public Health, 61(2):225–236, 2016. on the Rewarding and Reinforcing Value Academies Press, 2018. Doi: https:// 39. Corey, C.G., B.K. Ambrose, B.J. Apelberg, of E-cigarettes With Nicotine Among doi.org/10.17226/24952 (prepublication et al., ‘‘Flavored Tobacco Product Use Young Adult Smokers,’’ Drug and copy.) Alcohol Dependence, 166:263–267, 2016. Among Middle and High School Dated: March 15, 2018. Students—United States, 2014,’’ 53. Goldenson, N.I., M.G. Kirkpatrick, J.L. Morbidity and Mortality Weekly Report, Barrington-Trimis, et al., ‘‘Effects of Leslie Kux, 64(38):1066–1070, 2015. Sweet Flavorings and Nicotine on the Associate Commissioner for Policy. 40. Miech, R.A., J. E. Schulenburg, L.D. Appeal and Sensory Properties of E- [FR Doc. 2018–05655 Filed 3–20–18; 8:45 am] cigarettes Among Young Adult Vapers: Johnston, et al., ‘‘National Adolescent BILLING CODE 4164–01–P Drug Trends in 2017: Findings Application of a Novel Methodology,’’ Released.’’ Monitoring the Future: Ann Drug and Alcohol Dependence, 168:176– Arbor, MI, 2017, available at http:// 180, 2016. www.monitoringthefuture.org. 54. Bonhomme, M.G., E. Holder-Hayes, B.K. DEPARTMENT OF THE INTERIOR 41. Villanti, A.C., P.D. Mowery, C.D. Ambrose, et al., ‘‘Flavoured Non- Delnevo, et al., ‘‘Changes in the Cigarette Tobacco Product Use Among Bureau of Indian Affairs Prevalence and Correlates of Menthol US Adults: 2013–2014,’’ Tobacco Control, 25(Suppl 2):ii4-ii13, 2016. [189D0102DR/DS5A300000/ Cigarette Use in the USA, 2004–2014,’’ DR.5A311.IA000118] Tobacco Control, 25(Suppl 2):ii14-ii20, 55. Kim, H., J. Lim, S.S. Buehler, et al., ‘‘Role of Sweet and Other Flavours in Liking 2016. 25 CFR Part 273 42. Substance Abuse and Mental Health and Disliking of Electronic Cigarettes,’’ Services Administration, ‘‘Behavioral Tobacco Control, 25(Suppl 2):ii55-ii61, RIN 1076–AF24 Health Trends in the United States: 2016. Results from the 2014 National Survey 56. Allen, J.G., S.S. Flanigan, M. LeBlanc, et Education Contracts Under Johnson- on Drug Use and Health,’’ available at al., ‘‘Flavoring Chemicals in E-cigarettes: O’Malley Act https://www.samhsa.gov/data/sites/ Diacetyl, 2, 3-Pentanedione, and Acetoin default/files/NSDUH-FRR1-2014/ in a Sample of 51 Products, Including AGENCY: Bureau of Indian Affairs, NSDUH-FRR1-2014.pdf. Fruit-, Candy-, and Cocktail-Flavored E- Interior. cigarettes,’’ Environmental Health 43. Food and Drug Administration, ACTION: Proposed rule. ‘‘Preliminary Scientific Evaluation of the Perspectives, 124(6):733–739, 2016.

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(2) Its one-part rates that include fixed chapter as indicated in the instructions under the Federal Food, Drug, and costs, by set out in the form and Implementation Cosmetic Act (FD&C Act), as amended (3) The percentage calculated Guide, and must be properly completed by the Family Smoking Prevention and consistent with the instructions to FERC and verified. Each natural gas company Tobacco Control Act (Tobacco Control Form No. 501–G prescribed by § 260.402 must file FERC Form No. 501–G Act), and regulations regarding the sale of this chapter. according to the schedule set forth in and distribution of tobacco products. (d) Timing. Any natural gas company the Implementation Guide set out in Specifically, this ANPRM is seeking filing to reduce its rates pursuant to this that form. Each report must be prepared comments, data, research results, or section must do so no later than the date in conformance with the Commission’s other information that may inform that it files its FERC Form No. 501–G form and guidance posted and available regulatory actions FDA might take with pursuant to § 260.402. for downloading from the FERC website respect to premium cigars. (e) Hearing Issues. (1) The only issues (http://www.ferc.gov). One copy of the DATES: Submit either electronic or that may be raised by Commission staff report must be retained by the written comments by June 25, 2018. or any intervenor under the procedures respondent in its files. ADDRESSES: You may submit comments established in this section are: as follows. Please note that late, (i) Whether or not the natural gas PART 284—CERTAIN SALES AND untimely filed comments will not be company may file under this section. TRANSPORTATION OF NATURAL GAS considered. Electronic comments must (ii) Whether or not the percentage UNDER THE NATURAL GAS POLICY reduction permitted in § 154.402(c)(iii) be submitted on or before June 25, 2018. ACT OF 1978 AND RELATED The https://www.regulations.gov has been properly applied, and AUTHORITIES (iii) Whether or not the correct electronic filing system will accept information was used in that ■ 5. The authority citation for part 284 comments until midnight Eastern Time calculation. continues to read as follows: at the end of June 25, 2018. Comments (2) Any other issue raised will be received by mail/hand delivery/courier Authority: 15 U.S.C. 717–717z, 3301–3432; (for written/paper submissions) will be severed from the proceeding and 42 U.S.C. 7101–7352; 43 U.S.C. 1331–1356. dismissed without prejudice. considered timely if they are ■ 6. In § 284.123, add paragraph (i) to postmarked or the delivery service PART 260—STATEMENTS AND read as follows: acceptance receipt is on or before that REPORTS (SCHEDULES) date. § 284.123 Rates and charges. ■ 3. The authority citation for part 260 * * * * * Electronic Submissions continues to read as follows: (i) If an intrastate pipeline’s rates on Submit electronic comments in the Authority: 15 U.S.C. 717–717w, 3301– file with the appropriate state regulatory following way: 3432; 42 U.S.C. 7101–7352. agency are reduced to reflect the • Federal eRulemaking Portal: ■ 4. Add § 260.402 to read as follows: reduced income tax rates adopted in the https://www.regulations.gov. Follow the Tax Cuts and Jobs Act of 2017, the instructions for submitting comments. § 260.402 FERC Form No. 501–G. One-time intrastate pipeline must file a new rate Comments submitted electronically, Report on Rate Effect of the Tax Cuts and election pursuant to paragraph (b) of including attachments, to https:// Jobs Act. this section not later than 30 days after www.regulations.gov will be posted to (a) Prescription. The form for the One- the reduced intrastate rate becomes the docket unchanged. Because your time Report on Rate Effect of the Tax effective. This requirement applies comment will be made public, you are Cuts and Jobs Act of 2017, designated regardless of whether the intrastate solely responsible for ensuring that your herein as FERC Form No. 501–G is pipeline’s existing interstate rates are comment does not include any prescribed. based on § 284.123(b)(1) or (2). confidential information that you or a (b) Filing requirement. (1) Who must third party may not wish to be posted, [FR Doc. 2018–05669 Filed 3–23–18; 8:45 am] file. (i) Except as provided in paragraph such as medical information, your or (b)(1)(ii) of this section, every natural BILLING CODE 6717–01–P anyone else’s Social Security number, or gas company that is required under this confidential business information, such part to file a Form No. 2 or 2A for 2017 as a manufacturing process. Please note and has cost-based rates for service DEPARTMENT OF HEALTH AND that if you include your name, contact under any rate schedule that were filed HUMAN SERVICES information, or other information that electronically pursuant to part 154 of Food and Drug Administration identifies you in the body of your this chapter, must prepare and file with comments, that information will be the Commission a FERC Form No. 501– 21 CFR Parts 1100, 1140, and 1143 posted on https://www.regulations.gov. G pursuant to the definitions and • If you want to submit a comment instructions set forth in that form and [Docket No. FDA–2017–N–6107] with confidential information that you the Implementation Guide. RIN 0910–AH88 do not wish to be made available to the (ii) A natural gas company whose public, submit the comment as a rates are being examined in a general Regulation of Premium Cigars written/paper submission and in the rate case under section 4 of the Natural manner detailed (see ‘‘Written/Paper Gas Act or in an investigation under AGENCY: Food and Drug Administration, Submissions’’ and ‘‘Instructions’’). section 5 of the Natural Gas Act need HHS. Written/Paper Submissions not file FERC Form No. 501–G. In ACTION: Advance notice of proposed addition, a natural gas company that rulemaking. Submit written/paper submissions as files an uncontested settlement of its follows: rates pursuant to § 385.207(a)(5) of this SUMMARY: The Food and Drug • Mail/Hand Delivery/Courier (for chapter after March 26, 2018 need not Administration (FDA) is issuing this written/paper submissions): Dockets file FERC Form No. 501–G. advance notice of proposed rulemaking Management Staff (HFA–305), Food and (2) FERC Form No. 501–G must be (ANPRM) to obtain information related Drug Administration, 5630 Fishers filed as prescribed in § 385.2011 of this to the regulation of premium cigars Lane, Rm. 1061, Rockville, MD 20852.

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• For written/paper comments for Tobacco Products, Food and Drug additional products meeting the submitted to the Dockets Management Administration, 10903 New Hampshire statutory definition of ‘‘tobacco Staff, FDA will post your comment, as Ave., Silver Spring, MD 20993, 1–877– product’’ in section 201(rr) of the FD&C well as any attachments, except for 287–1373, [email protected]. Act (21 U.S.C. 321(rr)), except information submitted, marked and SUPPLEMENTARY INFORMATION: accessories to those products, to be identified, as confidential, if submitted subject to chapter IX of the FD&C Act as detailed in ‘‘Instructions.’’ I. Background (the proposed deeming rule). In that Instructions: All submissions received On July 28, 2017, FDA announced a proposed rule, FDA proposed two, must include the Docket No. FDA– new comprehensive plan for tobacco alternative, options: Option 1 proposed 2017–N–6107 for ‘‘Regulation of and nicotine regulation that will serve to extend the Agency’s tobacco product Premium Cigars.’’ Received comments, as a multi-year roadmap to better protect authorities to all products that meet the those filed in a timely manner (see children and significantly reduce definition of ‘‘tobacco product’’ in the ADDRESSES), will be placed in the docket tobacco-related disease and death. As FD&C Act, except accessories of newly and, except for those submitted as part of that announcement, FDA stated deemed tobacco products, while Option ‘‘Confidential Submissions,’’ publicly that it would solicit additional 2 proposed to extend the Agency’s viewable at https://www.regulations.gov comments and scientific data related to tobacco product authorities to all or at the Dockets Management Staff the patterns of use and resulting public tobacco products set forth in Option 1, between 9 a.m. and 4 p.m., Monday health impacts from premium cigars and except so-called premium cigars (79 FR through Friday. consider the appropriate regulatory 23142 at 23150 through 23152). After • Confidential Submissions—To status of premium cigars. The goal is to carefully considering the public submit a comment with confidential ensure that FDA has a broad scientific comments on the rule, the Agency information that you do not wish to be and regulatory foundation to efficiently decided to adopt Option 1, concluding made publicly available, submit your and effectively implement the Tobacco that there was no appropriate public comments only as a written/paper Control Act. Moreover, the regulatory health justification to exclude premium submission. You should submit two considerations with respect to premium cigars from regulation. Specifically, copies total. One copy will include the cigars, their use, and related public FDA concluded that: (1) All cigars pose information you claim to be confidential health issues continue to be of serious negative health risks, (2) the with a heading or cover note that states significant interest to some available evidence does not provide a ‘‘THIS DOCUMENT CONTAINS stakeholders, as well as a topic of basis for FDA to conclude that the CONFIDENTIAL INFORMATION.’’ The ongoing and emerging research. Given patterns of premium cigar use Agency will review this copy, including the ongoing interest from many parties sufficiently reduce the health risks to the claimed confidential information, in and sectors, such as industry and warrant exclusion, and (3) premium its consideration of comments. The Members of Congress, in the regulatory cigars are used by youth and young second copy, which will have the status of premium cigars, FDA is issuing adults. FDA noted that, although some claimed confidential information this ANPRM to request relevant new premium cigar smokers might smoke redacted/blacked out, will be available and different information, data, and these products infrequently or report for public viewing and posted on analysis not submitted in response to that they do not inhale, these behaviors https://www.regulations.gov. Submit FDA’s proposed deeming rule (79 FR do not negate the adverse health effects both copies to the Dockets Management 23142, discussed below) that could of tobacco smoke or demonstrate that Staff. If you do not wish your name and inform FDA’s regulation of premium cigars do not cause secondhand smoke- contact information to be made publicly cigars. related disease in others. Consequently, available, you can provide this The Tobacco Control Act was enacted premium cigars were included in the information on the cover sheet and not on June 22, 2009, amending the FD&C scope of the final deeming rule in the body of your comments and you Act and providing FDA with the published on May 10, 2016 (81 FR must identify this information as authority to regulate tobacco products 28974 at 29020) to more effectively ‘‘confidential.’’ Any information marked (Pub. L. 111–31). Specifically, section protect the public health. We received numerous comments on as ‘‘confidential’’ will not be disclosed 101(b) of the Tobacco Control Act the deeming proposed rule with respect except in accordance with 21 CFR 10.20 amends the FD&C Act by adding a new to premium cigars, both in favor of and chapter that provides FDA with and other applicable disclosure law. For against regulating these products. authority over tobacco products. Section more information about FDA’s posting However, the comments against 901 of the FD&C Act (21 U.S.C. 387a), of comments to public dockets, see 80 regulation provided little data to as amended by the Tobacco Control Act, FR 56469, September 18, 2015, or access support the opinions expressed and, states that the new chapter in the FD&C the information at: https://www.gpo.gov/ where studies were submitted, provided Act (chapter IX—Tobacco Products) (21 fdsys/pkg/FR-2015-09-18/pdf/2015- little information about the studies U.S.C. 387 through 387u) 1 applies to all 23389.pdf. cited. Docket: For access to the docket to cigarettes, cigarette tobacco, roll-your- FDA is seeking comments, evidence, read background documents or the own tobacco, smokeless tobacco, and information, data, and analysis that electronic and written/paper comments any other tobacco products that the were not submitted in response to the received, go to https:// Secretary of Health and Human Services proposed deeming rule, or that may www.regulations.gov and insert the by regulation deems to be subject to the have become available since then, that docket number, found in brackets in the chapter. could further inform FDA’s thinking heading of this document, into the In the Federal Register of April 25, about the regulation of premium cigars. ‘‘Search’’ box and follow the prompts 2014 (79 FR 23142), FDA published a One example of the type of information and/or go to the Dockets Management proposed rule seeking to deem that would be responsive to this request Staff, 5630 Fishers Lane, Rm. 1061, is a recent publication that assessed use Rockville, MD 20852. 1 In the U.S. Code, the tobacco control provisions constitute a new Subchapter IX of Chapter 9, which patterns and related behaviors of FOR FURTHER INFORMATION CONTACT: constitutes the Federal Food, Drug, and Cosmetic smokers of ‘‘premium’’ and other cigar Nathan Mease or Deirdre Jurand, Center Act. types (Ref. 1). This paper, the PATH

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Study Paper, analyzed findings from the A. Definition of Premium Cigars cigars, along with the information’s 2013–2014 Population Assessment of 1. Explain what data may be used to source and the definition of ‘‘premium Tobacco and Health (PATH) Study with assess (a) the universe of cigar products cigar’’ used in the data provided. a focus on smokers of filtered cigars, that are currently available to B. Use Patterns of Premium Cigars cigarillos, and traditional cigars, which consumers and (b) their relevant were further classified by study authors If available to you, provide the characteristics, including ‘‘premium’’ following information related to the use as either ‘‘premium’’ or ‘‘non- status. How can available sources of premium.’’ 2 With respect to this group patterns of premium cigars generally information, such as manufacturer and among youth and young adults of smokers, the PATH Study Paper registrations and/or product listings described similarities and differences in specifically: with FDA, be used in this assessment? 1. Studies or information regarding user characteristics, tobacco use 2. Explain what you believe to be the patterns, and purchasing behaviors the potential role of premium cigars on particular defining characteristics of tobacco initiation and progression to use according to cigar type. Among the premium cigars. These characteristics findings stated in this PATH Study of other tobacco products, especially could include, but not be limited to: compared and contrasted against the Paper were that those who smoked a. Size (e.g., length, ring gauge, total ‘‘premium’’ cigars tended to report potential roles of other cigars. weight). 2. Studies or information regarding smoking them on fewer days compared b. Tobacco filler type and minimum with smokers of the other cigar types behavioral data related to dual use of required percentages of each filler per premium cigars and other tobacco and reported consuming fewer cigars cigar. per day, on average, compared with products, especially compared and c. Fermentation type. contrasted against dual use of other smokers of other cigar types. In its d. Wrapper and binder composition conclusion, the PATH Study Paper cigars. (e.g., whole leaf, reconstituted or 3. Studies or information regarding highlighted the importance of homogenized tobacco leaf). adequately describing the cigar type the frequency and intensity (e.g., e. Where the tobacco used for number of cigars smoked per day, depth studied and, where appropriate, premium cigar filler or wrappers is differentiating results by cigar type. of smoke inhalation, number of days grown, and whether differences in smoking during a particular time When reviewing the PATH Study growing practices for that tobacco, as period) of premium cigar use, especially Paper and any other studies concerning compared to tobacco used in other compared and contrasted against other cigars, it should be noted that tobacco cigars, result in different health impacts. cigars. research studies have not used a single, f. Presence or absence of a filter. 4. Studies or information regarding consistent definition of ‘‘premium’’ g. Presence or absence of a the proportion of premium cigar cigars. As demonstrated by FDA’s mouthpiece. smokers showing symptoms of request for definitional information in h. Manufacturing and assembly dependence, especially compared and this document, FDA considers it process (e.g., including any production contrasted against other cigars. important to understand what by hand or by machine). 5. Studies or information regarding definitions of premium cigar are used i. Rate of production (e.g., ‘‘produced the abuse liability of premium cigars when analyzing and comparing results at no more than [insert number] units compared with other tobacco products, across studies and papers. per minute’’). especially compared and contrasted For the purposes of the questions in j. Presence or absence of flavor against other cigars. this ANPRM, ‘‘cigar’’ means a tobacco imparting compounds, flavor additives, 6. Studies or information regarding product that: (1) Is not a cigarette and or characterizing flavors other than the impact of premium cigar labeling, (2) is a roll of tobacco wrapped in leaf tobacco. advertising, and marketing efforts on tobacco or any substance containing k. Presence or absence of any patterns of use, especially compared tobacco (see 21 CFR 1143.1). additives other than cigar glue. and contrasted against other cigars. l. Nicotine content. 7. Information on the extent to which II. Requests for Comments and m. Tar delivery amounts (and how users of other tobacco products might Information this should be defined and measured). switch to premium cigars if FDA were FDA is seeking comments, data, n. Carbon monoxide delivery amounts to exempt premium cigars from research results, and other information (and how this should be defined and regulation or to regulate premium cigars related to the following topics: measured). differently from other cigars, and the o. Retail price. measures that could be taken to prevent • Definition of premium cigars p. Frequency with which price this from occurring. Where you discuss • Use patterns of premium cigars changes are initiated by particular levels the potential effects of FDA regulating • Public health considerations in the distribution chain (retailers, premium cigars differently from other associated with premium cigars manufacturers, importers, and/or cigars, please describe the specific distributors). different treatment that you envision. Please provide any evidence or other q. Packaging quantity and size. information supporting your comments. r. Any action directed to consumers, C. Public Health Considerations Also, provide the definition of by a retailer or manufacturer, such as If available to you, provide the ‘‘premium cigar,’’ ‘‘youth,’’ and ‘‘young through labeling, advertising, or following information related to public adult’’ used for the studies, information, marketing, which would reasonably be health considerations: or views provided in your responses. expected to result in consumers 1. Studies or information on any believing that the tobacco product is a applicable manufacturing, marketing, 2 While authors of the PATH Study Paper premium cigar. sale, distribution, advertising, labeling, included FDA employees, the definition of 3. If available to you, provide annual and/or packaging requirements and premium cigars reported in the PATH Study Paper restrictions in the FD&C Act and its was used for research purposes only, and does not sales data, including market size and necessarily reflect FDA’s current thinking on volume, for products that you believe implementing regulations, and whether regulatory policy. should be categorized as premium they should be applied differently to

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premium cigars compared to other 1143.5(a)(1)). Comment on whether any ACTION: Request for information; tobacco products, including other additional or alternative warning reopening of the rulemaking record for cigars. statements would be appropriate and public comments. 2. Studies or information regarding provide your suggested language and nicotine concentrations for premium any relevant studies or information. SUMMARY: In response to requests from cigars compared to other tobacco a. WARNING: Cigar smoking can the public, the Mine Safety and Health products, including other cigars. cause cancers of the mouth and throat, Administration (MSHA) is reopening 3. Studies or information regarding even if you do not inhale. the rulemaking record for public the risk of oral cancer, esophageal b. WARNING: Cigar smoking can comments on the Agency’s request for cancer, laryngeal cancer, lung cancer, or cause lung cancer and heart disease. information on Exposure of any other form of cancer associated with c. WARNING: Cigars are not a safe Underground Miners to Diesel Exhaust. premium cigars, especially compared alternative to cigarettes. DATES: The comment period for the and contrasted with risks for other d. WARNING: Tobacco smoke request for information, published on cigars. increases the risk of lung cancer and June 8, 2016 (81 FR 36826), which 4. Studies or information regarding heart disease, even in nonsmokers. closed on January 9, 2018 (82 FR 2284), the risk of heart disease associated with e. WARNING: Cigar use while is reopened. Comments must be premium cigars, especially compared pregnant can harm you and your baby; received on or before midnight Eastern and contrasted with risks for other or SURGEON GENERAL WARNING: Standard Time on March 26, 2019. cigars. Tobacco Use Increases the Risk of ADDRESSES: Submit comments and 5. Studies or information regarding Infertility, Stillbirth and Low Birth informational materials for the the risk of aortic aneurysm associated Weight. rulemaking record, identified by RIN with premium cigars, especially f. WARNING: This product contains 1219–AB86 or Docket No. MSHA–2014– compared and contrasted with risks for nicotine. Nicotine is an addictive 0031, by one of the following methods: • other cigars. chemical. Federal E-Rulemaking Portal: 6. Studies or information regarding http://www.regulations.gov. Follow the the risk of periodontal disease III. Reference on-line instructions for submitting associated with premium cigars, The following reference is on display comments. especially compared and contrasted in the Dockets Management Staff (see • Email: zzMSHA-comments@ with risks for other cigars. ADDRESSES) and is available for viewing dol.gov. • 7. Studies or information regarding by interested persons between 9 a.m. Mail: MSHA, Office of Standards, the risk of stroke associated with and 4 p.m., Monday through Friday; it Regulations, and Variances, 201 12th premium cigars, especially compared is also available electronically at https:// Street South, Suite 4E401, Arlington, and contrasted with risks for other Virginia 22202–5452. www.regulations.gov. FDA has verified • cigars. the website address, as of the date this Hand Delivery or Courier: 201 12th 8. Studies or information regarding document publishes in the Federal Street South, Suite 4E401, Arlington, the risk of chronic obstructive Register, but websites are subject to Virginia, between 9:00 a.m. and 5:00 pulmonary disease associated with change over time. p.m. Monday through Friday, except premium cigars, especially compared Federal holidays. Sign in at the and contrasted with risks for other 1. Corey, C.G., E. Holder-Hayes, A.B. Nguyen, receptionist’s desk on the 4th floor East, cigars. et al. ‘‘U.S. Adult Cigar Smoking Suite 4E401. Patterns, Purchasing Behaviors, and 9. Studies or information regarding • Fax: 202–693–9441. Reasons for Use According to Cigar Instructions: All submissions must risk of cancers of the mouth and throat Type: Findings From the Population for premium cigar users who do not Assessment of Tobacco and Health include ‘‘RIN 1219–AB86’’ or ‘‘Docket inhale or who report that they do not (PATH) Study, 2013–2014’’, Nicotine & No. MSHA–2014–0031.’’ Do not include inhale, especially compared and Tobacco Research, September 15, 2017, personal information that you do not contrasted with risks for other cigars. available at https://academic.oup.com/ want publicly disclosed; MSHA will 10. Studies or information on the ntr/article/4159211/U-S-adult-cigar- post all comments without change to impact of premium cigar use on other smoking-patterns-purchasing. http://www.regulations.gov and http:// public health endpoints, including users Dated: March 21, 2018. arlweb.msha.gov/currentcomments.asp, and non-users, especially compared and Leslie Kux, including any personal information contrasted with the impact of other Associate Commissioner for Policy. provided. Docket: For access to the docket to cigars. [FR Doc. 2018–06047 Filed 3–23–18; 8:45 am] 11. Studies or information regarding read comments received, go to http:// the addictiveness of premium cigars. BILLING CODE 4164–01–P www.regulations.gov or http:// 12. Studies or information regarding arlweb.msha.gov/currentcomments.asp. consumer perceptions of the health risks To read background documents, go to of premium cigars when compared to DEPARTMENT OF LABOR http://www.regulations.gov. Review the other tobacco products, including other docket in person at MSHA, Office of Mine Safety and Health Administration cigars. Standards, Regulations, and Variances, 13. Studies or information regarding 201 12th Street South, Arlington, 30 CFR Parts 57, 70, 72, and 75 consumer perceptions of the Virginia, between 9:00 a.m. and 5:00 addictiveness of premium cigars, [Docket No. MSHA–2014–0031] p.m. Monday through Friday, except especially compared and contrasted Federal Holidays. Sign in at the RIN 1219–AB86 with perceptions for other cigars. receptionist’s desk in Suite 4E401. 14. Studies or information on the Exposure of Underground Miners to Email Notification: To subscribe to required warning statements, shown Diesel Exhaust receive an email notification when below and which will be required to MSHA publishes rules in the Federal appear on cigar packaging and AGENCY: Mine Safety and Health Register, go to http://www.msha.gov/ advertising in the near future (21 CFR Administration, Labor. subscriptions.

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