[Federal Register Volume 83, Number 55 (Wednesday, March 21, 2018)]
[Proposed Rules]
[Pages 12294-12301]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-05655]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 1100, 1140, and 1143

[Docket No. FDA-2017-N-6565]
RIN 0910-AH60


Regulation of Flavors in Tobacco Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Advance notice of proposed rulemaking.

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SUMMARY: The Food and Drug Administration (FDA) is issuing this advance 
notice of proposed rulemaking (ANPRM) to obtain information related to 
the role that flavors play in tobacco products. Specifically, this 
ANPRM is seeking comments, data, research results, or other information 
about, among other things, how flavors attract youth to initiate 
tobacco product use and about whether and how certain flavors may help 
adult cigarette smokers reduce cigarette use and switch to potentially 
less harmful products. FDA is seeking this information to inform 
regulatory actions FDA might take with respect to tobacco products with 
flavors, under the Federal Food, Drug, and Cosmetic Act (FD&C Act), as 
amended by the Family Smoking Prevention and Tobacco Control Act 
(Tobacco Control Act). Potential regulatory actions include, but are 
not limited to, tobacco product standards and restrictions on sale and 
distribution of tobacco products with flavors.

DATES: Submit either electronic or written comments by June 19, 2018.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before June 19, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of June 19, 2018. Comments received by 
mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2017-N-6565 for ``Regulation of Flavors in Tobacco Products.'' 
Received comments, those filed in a timely manner (see ADDRESSES), will 
be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information

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redacted/blacked out, will be available for public viewing and posted 
on https://www.regulations.gov. Submit both copies to the Dockets 
Management Staff. If you do not wish your name and contact information 
to be made publicly available, you can provide this information on the 
cover sheet and not in the body of your comments and you must identify 
this information as ``confidential.'' Any information marked as 
``confidential'' will not be disclosed except in accordance with 21 CFR 
10.20 and other applicable disclosure law. For more information about 
FDA's posting of comments to public dockets, see 80 FR 56469, September 
18, 2015, or access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Laura Rich or Katherine Collins, 
Center for Tobacco Products, Food and Drug Administration, Document 
Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G335, Silver 
Spring, MD 20993, 1-877-CTP-1373, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

A. The Tobacco Control Act

    The Tobacco Control Act (Pub. L. 111-31) was enacted on June 22, 
2009, amending the FD&C Act and providing FDA with the authority to 
regulate tobacco products. Specifically, the Tobacco Control Act amends 
the FD&C Act by adding a new chapter that provides FDA with authority 
over tobacco products. Section 901(b) of the FD&C Act (21 U.S.C. 
387a(b)), as amended by the Tobacco Control Act, states that the new 
chapter in the FD&C Act (chapter IX--Tobacco Products) (21 U.S.C. 387 
through 387u) applies to all cigarettes, cigarette tobacco, roll-your-
own tobacco, smokeless tobacco, and any other tobacco products that the 
Secretary of Health and Human Services by regulation deems to be 
subject to chapter IX. In the Federal Register of May 10, 2016 (81 FR 
28973), FDA issued a final rule deeming all products that meet the 
statutory definition of ``tobacco product'' in section 201(rr) of the 
FD&C Act (21 U.S.C. 321(rr)), except accessories of deemed tobacco 
products, to be subject to FDA's tobacco product authority (the deeming 
rule). The products now subject to FDA's tobacco product authority 
include electronic nicotine delivery systems (ENDS), cigars, 
waterpipes, pipe tobacco, nicotine gels, dissolvables that were not 
already subject to chapter IX of the FD&C Act, and other products that 
meet the statutory definition of ``tobacco product'' (other than 
accessories) that may be developed in the future.

B. Flavors and Tobacco Product Standards

    Section 907 of the FD&C Act (21 U.S.C. 387g) gives FDA the 
authority to establish tobacco product standards. To establish a 
tobacco product standard, FDA must find that the standard is 
appropriate for the protection of the public health, taking into 
consideration scientific evidence concerning the risks and benefits to 
the population as a whole, including users and nonusers of tobacco 
products; the increased or decreased likelihood that existing users of 
tobacco products will stop using such products; and the increased or 
decreased likelihood that those who do not use tobacco products will 
start using such products (section 907(a)(3)(A) and (B) of the FD&C 
Act). Thus, under section 907, FDA may issue product standards 
respecting the construction, components, ingredients, additives, 
constituents, and properties of tobacco products (section 
907(a)(4)(B)(i)) and restricting their sale and distribution (section 
907(a)(4)(B)(v)).\1\
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    \1\ As set forth above, section 907(a)(4)(B)(v) provides that 
product standards ``shall, where appropriate for the protection of 
the public health, include--. . . (v) a provision requiring that the 
sale and distribution of the tobacco product be restricted but only 
to the extent that the sale and distribution of a tobacco product 
may be restricted under a regulation under section 906(d).'' Section 
906(d) gives FDA authority to require restrictions on the sale and 
distribution of tobacco products by regulation if the Agency 
determines that such regulations would be appropriate for the 
protection of the public health. See section 906(d)(1) of the FD&C 
Act.
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    The Tobacco Control Act includes a ``Special Rule for Cigarettes,'' 
which prohibits cigarettes from containing characterizing flavors other 
than tobacco or menthol (section 907(a)(1)(A)). The statute also 
authorizes the Agency to issue additional product standards, including 
to address flavors in tobacco products (see section 907(a)(3)) and 
preserves FDA's authority to act with respect to menthol (section 
907(e)(3)). The deeming rule did not include provisions relating to 
flavors in tobacco products. Nevertheless, FDA explained that it did 
intend to consider the issues surrounding the role of flavors in 
tobacco products, including the role flavors play in youth and young 
adult use, as well as the existence of preliminary data that some 
adults may use flavored noncombusted tobacco products to transition 
away from combusted tobacco use. See 81 FR 28973 at 29014 and 29055.

C. The Role of Flavors in Tobacco Products Use

    Adolescence (under 18, also referred to as youth) and young 
adulthood (age 18 through 24) represent a time of heightened 
vulnerability to both the initiation of tobacco product use and the 
development of nicotine dependence (Ref. 1). Furthermore, flavors in 
tobacco products increase the appeal of those tobacco products to 
youth, and promote youth initiation (Ref. 2). Thus, the availability of 
tobacco products with flavors at these developmental stages attracts 
youth to initiate use of tobacco products and may result in lifelong 
use (Ref. 2). Researchers examining the impact of the Special Rule for 
Cigarettes have concluded that, while the prohibition of characterizing 
flavors in cigarettes has reduced adolescent tobacco product use, the 
continued availability of menthol cigarettes and other flavored tobacco 
products likely diminish the effects (Ref. 3). Researchers estimated a 
6 percent reduction in the probability of using any tobacco product 
after implementation of the Tobacco Control Act (2009-2013), and 
observed the reductions to be significantly associated with the Special 
Rule for Cigarettes (Ref. 3).
    The adverse health effects associated with tobacco product use by 
youth have been well documented. Nicotine exposure and smoking during 
adolescence can have unique adverse consequences on brain development 
(Refs. 2 and 4). For example, smoking cigarettes during adolescence is 
associated with lasting cognitive and behavioral impairments, including 
effects on working memory in smoking teens (Ref. 5) and alterations in 
the prefrontal attentional network in young adult smokers (Ref. 6). 
Furthermore, the nonclinical data related to nicotine exposure and 
epidemiologic studies related to smoking cigarettes during adolescence 
taken together suggest an age-dependent susceptibility to nicotine 
(Ref. 1).
    Use of tobacco products, which is facilitated by nicotine exposure 
and dependence, puts youth and young adults at greater risk for future 
health issues, such as coronary artery disease, cancer, and other known 
tobacco-related diseases (Refs. 1 and 4). Youth and

[[Page 12296]]

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

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

[[Page 12298]]

percent), candy/chocolate/other sweet (26.5 percent), and menthol/mint 
(24.8 percent) (Ref. 54).
    Among adult e-cigarette users, a study with experienced exclusive 
e-cigarette and dual (e-cigarette and cigarette) users (aged 18 years 
or older) found that bitterness and harshness are negatively associated 
with liking e-cigarettes, while sweetness and ``coolness'' are 
positively associated with liking them (Ref. 55). In addition, 
sweetness appeared to have a greater impact than coolness on liking 
(Ref. 55).
7. Flavors May Contain or Form Toxic Compounds
    Evidence exists regarding the toxicity of flavors, specifically 
certain ingredients in those flavors that have been used in tobacco 
products. Of particular concern for combusted or heated tobacco 
products is that toxicity also may result from the chemicals formed 
when flavors are heated or burned (Refs. 56 through 60). Diacetyl and 
acetyl propionyl, which are flavor ingredients that have been found in 
e-liquids, are highly irritating volatile organic compounds (Refs. 56 
and 60). There is scientific evidence showing a link between repeated 
inhalation exposures to these flavor ingredients and adverse 
respiratory health outcomes in humans (Ref. 60). Finally, we note that 
certain substances may be authorized as a food additive or may be 
considered ``generally recognized as safe'' (GRAS) for certain uses in 
food. However, being authorized as a food additive or being considered 
GRAS, in and of itself, does not mean that the substances are safe when 
used in a tobacco product. The food additive approval or GRAS status of 
a substance applies only to specific intended uses in food, and are not 
supported by studies that account for inhalation toxicity. Importantly, 
exposure to chemicals via the inhalation route can have very different 
effects from oral exposure, and most tobacco products are inhaled (Ref. 
61). For example, direct ``portal of entry'' effects to the respiratory 
tract, which is relatively more sensitive than the gastrointestinal 
tract, can occur upon inhalation exposure. There are also important 
metabolic differences between the two routes of exposure: After oral 
ingestion, a substance can be detoxified through ``first-pass 
metabolism'' in the liver before reaching systemic circulation. By 
contrast, substances introduced into the body via inhalation go 
directly into systemic circulation without the same potential for 
detoxification (Ref. 61).

D. The Potential Role of Flavors in Facilitating Transition From 
Cigarettes to Tobacco Products That May Pose Less Risk

    FDA also is aware of self-reported information suggesting that the 
availability of flavors in some noncombusted tobacco products (e.g., 
ENDS) may help some adult users decrease their cigarette use and 
transition away from combusted products to potentially less harmful 
products (Refs. 62 and 63). Reports from a focus group of eleven e-
cigarette users, nine of whom switched to e-cigarettes from smoking a 
half-pack per day or more of cigarettes, suggest that the ability of 
consumers to personalize their e-liquids by mixing and matching flavors 
could contribute to e-cigarette appeal among cigarette smokers (Ref. 
62). In one survey using an online convenience sample (i.e., self-
selected respondents recruited from online vape forums), respondents 
indicated that flavor variety was ``very important'' in reducing or 
quitting smoking (Ref. 63). Almost half of the respondents in that 
survey indicated that a reduction in available flavors would ``increase 
craving[s] for tobacco cigarettes and would make reducing or completely 
substituting smoking less likely'' (Ref. 63).
    The issues surrounding the use of flavors in tobacco products 
involve various considerations. While data show significant youth 
appeal and continued growth in youth and young adult use of flavored 
tobacco products, which can lead to lifelong tobacco product use, self-
reported information from a study (Ref. 63) shows that some flavors in 
ENDS may play a positive role in helping some adults transition away 
from cigarettes to potentially less harmful products. In addition, we 
note that, currently, no ENDS have been approved as effective cessation 
aids. In the preamble to the deeming rule, FDA discussed the evidence 
available to date, and found that some systematic reviews found 
insufficient data to draw a conclusion about the efficacy of e-
cigarettes as cessation aids (81 FR 28973 at 29037). A recent 
systematic review by the National Academies of Sciences, Engineering, 
and Medicine found ``limited evidence that e-cigarettes may be 
effective aids to promote smoking cessation,'' and that ``there is 
moderate evidence from observational studies that more frequent use of 
e-cigarettes is associated with increased likelihood of cessation,'' 
thus, the evidence remains inconclusive (Ref. 64).

II. Requests for Comments and Information

    FDA is seeking comments (including comments on this document and 
the data presented), data, research results, and other information 
related to the following topics. Please explain your responses and 
provide any evidence or other information supporting them.
     For the purposes of the questions in this ANPRM, when 
seeking comments, data, research results, and other information on 
``flavors,'' FDA is seeking information relating to the following (as 
applicable): (1) Artificial or natural flavor additives, compounds, 
constituents, or ingredients or any other flavoring ingredient in a 
tobacco product, including its components or parts; (2) the 
multisensory experience of a flavor during use of tobacco products; (3) 
flavor representations (including descriptors), either explicit or 
implicit, in or on the labeling, advertising, and packaging of tobacco 
products; and (4) any other means that impart flavor or represent that 
tobacco products are flavored. The foregoing is intended only to 
provide guidance to commenters and is not intended to limit or restrict 
the information they may submit. Additionally, for purposes of the 
questions in the ANPRM:
     ``Youth'' means under age 18; and
     ``Young adult'' means ages 18 through 24.
    FDA intends to use the information submitted in response to this 
Federal Register document, its independent scientific knowledge, and 
other appropriate information to inform regulatory actions FDA might 
take with respect to flavors in tobacco products. When submitting 
information, provide evidence by product class (e.g., cigarettes, 
cigars, pipes) for each topic, when available. If it exists, discuss 
the influence of flavors by flavor type/category (e.g., fruit, candy, 
menthol) for each topic. Also, provide information regarding any 
positive or negative effects that may result from a regulatory action 
FDA might take with respect to flavors in tobacco products, including, 
but not limited to, health implications and economic impacts. We ask 
that commenters clearly identify the section and question number 
associated with their responsive comments and information.

A. The Role of Flavors (Other Than Tobacco) in Tobacco Products

    1. Provide studies or information regarding the role of flavors 
(other than tobacco) generally in tobacco products. If the response 
relies on research in other areas (e.g., consumer products),

[[Page 12299]]

discuss the appropriateness of extrapolating from such research to 
tobacco products.

B. Flavors (Other Than Tobacco) and Initiation and Patterns of Tobacco 
Product Use, Particularly Among Youth and Young Adults

    2. Provide studies or information regarding the role of flavors 
(other than tobacco) in initiation and/or patterns of use of combusted 
tobacco products, particularly among youth and young adults.
    3. Provide studies or information regarding the role of flavors 
(other than tobacco) in initiation and/or patterns of use of 
noncombusted tobacco products, particularly among youth and young 
adults.
    4. Provide studies or information regarding the role of flavors 
(other than tobacco) in noncombusted tobacco products on initiation of 
tobacco product use or progression to use of other tobacco products 
(for example, from noncombusted to combusted tobacco products), 
particularly among youth and young adults.

C. Flavors (Other Than Tobacco) and Cessation, Dual Use, and Relapse 
Among Current and Former Tobacco Product Users

    5. Provide studies or information regarding the role of flavors 
(other than tobacco) in helping adult cigarette smokers reduce 
cigarette use and/or switch to potentially less harmful tobacco 
products.
    6. Provide studies or information regarding the role of flavors 
(other than tobacco) in noncombusted tobacco products on the likelihood 
of: (1) Cessation of combusted tobacco products use, (2) cessation of 
all tobacco product use, and (3) uptake of dual use of combusted and 
noncombusted tobacco products among current and former tobacco product 
users. Include information from, and define, all populations: Youth, 
young adults, and adults (and any subgroup thereof, if applicable).
    7. Provide studies or information regarding the role of flavors 
(other than tobacco) in noncombusted products on the likelihood of: (1) 
Delayed or impeded cessation among users who would have otherwise quit 
combusted tobacco product use, or (2) delayed or impeded cessation 
among users who would have otherwise quit all tobacco product use. 
Include information from, and define, all populations: Youth, young 
adults, and adults (and any subgroup thereof, if applicable).
    8. Provide studies or information regarding the role of flavors 
(other than tobacco) in noncombusted tobacco products on the likelihood 
that former combusted tobacco product users relapse. Include 
information from, and define, all populations: Youth, young adults, and 
adults (and any subgroup thereof, if applicable).

D. Additional Public Health Considerations

    9. Provide studies or information regarding the potential toxicity 
or adverse health effects to the user or others from any flavors (e.g., 
flavor additives, compounds, or ingredients) in tobacco products. These 
adverse health outcomes may include, but are not limited to, cancer or 
adverse respiratory, cardiac, or reproductive/development effects. Of 
particular interest are studies or information on inhalation exposure 
to any flavor. Provide studies or information on what, if any, toxic 
chemicals might be formed from the heating or burning of tobacco 
products with flavors and the potential toxicity or health risks that 
might result from these formed chemicals.
    10. Provide studies or information on the impact, whether intended 
or unintended, of public health efforts by local jurisdictions, States, 
and members of the international community to impose restrictions on 
the manufacture, marketing, sale or distribution of all or a subset of 
tobacco products with flavors (other than tobacco), including but not 
limited to cigars, ENDS, menthol cigarettes, and smokeless tobacco 
products.
    11. Provide studies or information regarding consumer perceptions 
of the health risks of tobacco products with flavors (other than 
tobacco) when compared to other tobacco products, both with and without 
flavors. Include information from, and define, all populations: Youth, 
young adults, and adults (and any subgroup thereof, if applicable).
    12. Provide studies or information regarding consumer perceptions, 
if any, of the addictiveness of tobacco products with flavors (other 
than tobacco). Include information from, and define, all populations: 
Youth, young adults, and adults (and any subgroup thereof, if 
applicable).

E. Tobacco Product Standards

    13. All Flavors:
    a. Are there any specific flavors for which FDA should establish a 
tobacco product standard? If so, which flavors (e.g., flavor additives, 
compounds, or ingredients) and why?
    b. With respect to your response to the previous question, what 
level (e.g., maximum, minimum, prohibition) should FDA establish to 
protect the public health, and why?
    14. If FDA were to establish a tobacco product standard prohibiting 
or restricting flavors, to which types of tobacco products should the 
standard apply (e.g., combusted, noncombusted, both), and why?
    15. Menthol Flavor:
    a. FDA has carefully reviewed the data it received in response to 
the 2013 ANPRM on menthol in cigarettes (78 FR 44484, July 24, 2013). 
Provide any additional data or information about the role of menthol in 
cigarettes, particularly regarding the role menthol plays in smoking 
initiation and in the likelihood of smoking cessation for all 
populations (youth, young adult, adult).
    b. What additional evidence exists on the likelihood that smokers 
would completely switch to another tobacco product, or start dual use 
with another product, in the event of a tobacco product standard 
prohibiting or limiting menthol in cigarettes?
    c. What is the role, if any, that menthol plays in use of tobacco 
products other than cigarettes, including, but not limited to, cigars 
and ENDS?

F. Sale or Distribution Restrictions

    16. FDA may consider restrictions on the sale and distribution of 
flavored tobacco products. Possible restrictions could include 
restrictions on the advertising and promotion of tobacco products with 
flavors; on access to tobacco products with flavors; and/or on the 
label, labeling, and/or packaging of tobacco products with flavors. 
These restrictions could include requirements to bear warnings or 
disclosure statements. What such restrictions, if any, should FDA 
consider and why?

G. Other Actions and Considerations

    17. To the extent that flavors may pose both (1) potential benefits 
to adult smokers who might consider switching to a noncombusted 
flavored tobacco product with lower individual risk and (2) potential 
risks to nonusers who might initiate use of tobacco products through 
flavored tobacco products or to current users who might progress to 
flavored tobacco products with higher individual risks, how should FDA 
assess and balance these benefits and risks?
    18. Provide studies or information on the role of tobacco flavor in 
tobacco products in initiation, patterns of use of tobacco products 
(particularly with respect to progression from non-combusted to 
combusted tobacco products or from combusted to non-combusted), 
reduction in use of

[[Page 12300]]

combustible tobacco products and cessation of tobacco products. Include 
information from, and define, all populations: Youth, young adults, and 
adults (and any subgroup thereof, if applicable).
    19. Provide information on whether manufacturing process(es) affect 
product flavor. Describe any such manufacturing process(es), including 
the specific products that use the process(es), as well as specific 
flavors used in the process(es).
    20. Provide analyses regarding any other tobacco product standard, 
regulatory action, or other action that FDA could implement that you 
believe would more effectively reduce the harms caused by flavors in 
tobacco products to better protect the public health than the tobacco 
product standards or other regulatory actions discussed in the 
preceding questions.
    21. Discuss any other tobacco product standard, regulatory action, 
or other activity that FDA could pursue that would complement or 
increase the effectiveness of the potential tobacco product standards 
or other regulatory actions discussed in the preceding questions.
    22. Are there any flavors that especially appeal to youth, young 
adults, or other specific age group? If so, how are such flavors 
distinguished from other flavors?
    23. To the extent that you have identified a tobacco product 
standard or other regulatory action in response to the prior questions, 
provide additional information and comments on: (1) The technical 
achievability of compliance with the tobacco product standard or other 
regulatory action you identified; and (2) how FDA could maximize 
compliance and public health benefits.
    24. If FDA were to establish a tobacco product standard prohibiting 
or restricting flavors in tobacco products, what evidence is there, if 
any, that consumers would start to flavor their own tobacco products?
    25. What data may be used to assess and analyze the range and 
variety of flavored tobacco products that are currently available to 
consumers? How can available sources of information, such as 
manufacturer registrations and/or product listings with FDA, be used in 
this assessment?

III. References

    The following references are on display in the Dockets Management 
Staff (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at https://www.regulations.gov. FDA has 
verified the website addresses, as of the date this document publishes 
in the Federal Register, but websites are subject to change over time.

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copy.)

    Dated: March 15, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-05655 Filed 3-20-18; 8:45 am]
BILLING CODE 4164-01-P