full text of such information in its PMTA. FDA is implementing this
restriction because cross-referencing information from other types of
applications (e.g., SE Reports, previously submitted PMTAs for
different products) can make review difficult and contribute to delays
in the review process.
    (Comment 19) One comment stated that FDA should amend the
application format requirements so that it allows PMTAs to include
information by cross-reference to parts of previously filed PMTAs for
different products that contain studies applicable to the new tobacco
product.
    (Response 19) The format requirements of Sec.  1114.7(b) permit an
applicant to cross-reference a tobacco product master file or a pending
MRTPA for the same tobacco product. FDA declines to revise Sec.
1114.7(b) to broadly allow an applicant to cross-reference information
contained in any previously filed PMTA because it could result in a
process in which FDA would have to pull information from a variety of
sources to have a complete PMTA for review, which would increase the
potential for error and decrease the efficiency of FDA's review.
Additionally, permitting an applicant to broadly cross-reference
information presented for different products would not necessarily
result in a more efficient review process. FDA is limiting the ability
of applicants to cross-reference content from previously reviewed PMTAs
to specific circumstances set forth in Sec. Sec.  1114.15 and 1114.17
where it would facilitate application review. Where an applicant
intends to submit the same information in multiple applications
submitted at different periods in time, FDA recommends establishing a
TPMF containing the information so that it could be included by cross-
reference in each application.
    An applicant may also submit a single premarket submission for
multiple products (i.e., a bundled PMTA) and a single, combined cover
letter and table of contents across all products; however, when FDA
receives a premarket submission that covers multiple new tobacco
products, we intend to consider information on each product as a
separate, individual PMTA and it is important to identify the content
that pertains to each product.
    (Comment 20) Multiple comments requested additional information
regarding how they should bundle multiple PMTAs for related or similar
tobacco products into a single submission. One comment requested that
FDA formally clarify whether e-liquid manufacturers and manufacturers
of closed-system devices may bundle applications for multiple flavors
of e-liquid that share common nicotine strengths, package sizes,
propylene glycol/vegetable glycerin ratios, or other characteristics.
Another comment requested information regarding how a manufacturer
should submit PMTAs for products that are used together but may be sold
separately (e.g., closed e-liquids, such as cartridges or pods that are
not intended to be refillable, and the e-cigarette with which the e-
liquids would be used).
    (Response 20) FDA recommends that an applicant group PMTAs for
products in the same subcategory (see Sec.  1114.7(c)) that are
produced by the same manufacturer into a single submission because they
will likely share a significant amount of application content. An
applicant grouping PMTAs together by subcategory would be required to
use Form FDA 4057b to identify the products that are contained in the
grouped submission. Additionally, FDA recommends an applicant group
PMTAs for a new tobacco product and its components or parts into a
single submission where an applicant seeks to sell the components or
parts separately. As discussed in section VIII.B.3., FDA generally
considers an open e-cigarette, also referred to as a refillable e-
cigarette, to be an e-cigarette that includes a reservoir that a user
can refill with an e-liquid of their choosing. A closed e-cigarette is
an e-cigarette that includes an e-liquid reservoir that is not
refillable, such as a disposable cigalike, or that uses e-liquid
contained in replaceable cartridges or pods that are not intended to be
refillable. For example, if a manufacturer wanted to sell a closed e-
cigarette and the closed e-liquids (e.g., nonrefillable cartridges or
pods) that could be used with the e-cigarette separately, it should
group a PMTA for the e-cigarette and PMTAs for each of the e-liquids
into a single submission. FDA does not recommend grouping open e-
liquids and open ENDS devices that will be sold separately in a single
submission except for instances where the applicant is seeking a
marketing granted order for the e-liquids that have been designed by
the manufacturer to be used solely in a particular open ENDS device.
FDA reminds applicants that we intend to consider information on each
product as a separate, individual PMTA, so it is important to identify
the content that pertains to each product. If an applicant does not
clearly identify the content in the submission that makes up the PMTA
for each product, FDA may refuse to accept or refuse to file the
submission.
3. General Information
    Section 1114.7(c), including table 1, lists the information that
must be included in the general information section of the PMTA. This
information consists of general administrative information that
includes the type of submission, the new tobacco product with unique
identifiers, and contact information. Specifically, table 1 to Sec.
1114.7(c)(3)(iii) provides for the information needed to help ensure
that we are able to identify and evaluate each product more accurately
and efficiently. This table includes, among other categories,
requirements to submit general information related to ENDS product
category and several subcategories of ENDS. FDA generally considers
ENDS to be electronic nicotine delivery systems that deliver
aerosolized e-liquid when inhaled. The term ``e-cigarette'' refers to
an electronic device that delivers e-liquid in aerosol form into the
mouth and lungs when inhaled; it is also sometimes referred to as an
aerosolizing apparatus. An open e-cigarette, also referred to as a
refillable e-cigarette, is an e-cigarette that includes a reservoir
that a user can refill with an e-liquid of their choosing. A closed e-
cigarette is an e-cigarette that includes an e-liquid reservoir that is
not refillable, such as a disposable cigalike, or that uses e-liquid
contained in replaceable cartridges or pods that are not intended to be
refillable. For additional information on ENDS, consult the ENDS PMTA
Guidance.
    In this final rule, we have revised table 1 to Sec.
1114.7(c)(3)(iii) to help ensure that FDA is able to identify and
evaluate each product more accurately and efficiently. For example, the
table includes a waterpipe head as a subcategory of waterpipe. A
waterpipe head is a container that is typically made of materials like
clay, marble, or glass and is used to contain coal and tobacco during a
waterpipe smoking session.
    Additionally, the cigarette product category no longer lists
noncombusted cigarettes as a subcategory. Instead, for purposes of PMTA
review, a ``heated tobacco product'' category has been added to the
identification tables. Under this revised taxonomy, some tobacco

products may fit under more than one category. This PMTA review
category should be used for (among others) tobacco products that meet
the definition of a cigarette but are not combusted (products that do
not exceed 350[deg] C). Heated tobacco products (HTP) can be used with
e-liquids, other types of tobacco filler, or consumable (e.g., wax,
oils). If, however, a tobacco product can only be used with e-liquids,
it should be captured under ``ENDS'' and not the HTP category. To
ensure we have all the information we need to efficiently and
effectively review your application, if the product that is the subject
of your application is a heated tobacco product and is not an ENDS
product, you should submit information under Sec.  1114.7(c)(3)(iii)
under the heated tobacco product category and comply with the design
parameter requirements for HTPs in table 22 to Sec.
1114.7(i)(2)(ii).\15\ FDA believes these product categorizations will
help ensure that applications include the most relevant information for
their product, which in turn will facilitate FDA's review and ability
to reach an authorization decision.
---------------------------------------------------------------------------

    \15\ Note that the purpose of the unique identification tables
in Sec.  1114.7(c)(3)(iii) is to explain what information we need to
identify and evaluate different types of products, and Sec.
1114.7(i)(2)(ii) explains the design parameters needed for product
characterization (see discussion below). The categorization of HTPs
in Sec.  1114.7(c)(3)(iii) and (i)(2)(ii) does not extend to other
legal requirements beyond those associated with unique
identification and product characterization for premarket review.
---------------------------------------------------------------------------

    Other changes to table 1 to Sec.  1114.7(c)(3)(iii) include FDA's
clarification under the ``cigar'' category to designate ``leaf-
wrapped'' cigars as unfiltered to more accurately describe the product
category, as ``leaf-wrapped'' cigars typically do not include filters;
under the ``waterpipe'' category, ``waterpipe'' diameter has been added
to distinguish between waterpipes of different sizes (width/diameter
and height) where all other uniquely identifying information is the
same; and under the ``pipe tobacco filler'' category, ``tobacco cut
style'' has been added to distinguish between different cut pipe
tobacco filler, e.g., standard cut, such as shag cut, bugler cut, loose
cut, etc.; or a pressed cut, such as flake, cube cut, roll cake, etc.
or a mixture. Additionally, FDA has removed the requirement to provide
tobacco cut size from the unique identification requirements for
smokeless tobacco and cigar tobacco filler. A specific numerical value
for this field is not necessary to uniquely identify the specific
product to which the PMTA pertains, as it can be described further
through identification of additional properties (e.g., fine cut, long
cut). However, to fully characterize the tobacco product and evaluate
its health effects, information to determine tobacco cut size is
required under Sec.  1114.7(i)(2)(ii) for the product categories
specified in that section.
    Additionally, across all product categories, the subcategory of
``co-package'' has been removed from Sec.  1114.7(c). If an applicant
submits a PMTA for a co-packaged tobacco product, the unique
identification of this co-packaged product would require the specific
items needed to identify each product within the co-package. For
example, if the co-package is a pouch of roll-your-own (RYO) tobacco
filler that contains rolling papers inside the pouch, the applicant
would identify the tobacco product as a co-packaged product and provide
the unique identification for both the RYO tobacco filler and the
rolling papers.
    The PMTA must contain the following information using the FDA-
provided form(s) (i.e., Form FDA 4057 (Ref. 10) and Form FDA 4057b
(Ref. 11)), as appropriate:
     Applicant name, address, and contact information;
     the name, address, and contact information for the
authorized representative or U.S. agent (for a foreign applicant). As
required by Sec.  1105.10(a)(5) for application acceptance, a foreign
applicant must identify a U.S. agent (i.e., an individual located in
the United States who is authorized to act on behalf of the applicant
for the submission) to help FDA ensure adequate notice is provided to
applicants for official Agency communications, assist FDA in
communicating with the foreign applicant, and help the Agency to
efficiently process applications and avoid delays; and
     information to uniquely identify the product. Providing
unique identifying information is important to aid in FDA's review
because it ensures FDA has information readily available to distinguish
the tobacco product from other tobacco products, including additional
new tobacco products in a bundled submission (i.e., more than one
application contained in a single submission), and assists FDA in
performing its acceptance and filing reviews. The required unique
identifying information includes:
    [cir] The manufacturer;
    [cir] product name(s), including the brand and subbrand (or other
commercial name(s) used in commercial distribution); and
    [cir] product category; product subcategory; and product
properties, as provided by the table in Sec.  1114.7(c). The applicant
must select and provide the appropriate category, subcategory, and
product properties for the new tobacco product. As discussed
previously, if an applicant submits a PMTA for a co-packaged tobacco
product, the unique identification of this co-packaged product must
include the specific items needed to identify each product within the
co-package. For example, if the co-package is a pouch of RYO tobacco
filler that contains rolling papers inside the pouch, the applicant
must identify the tobacco product as a co-packaged product and provide
the unique identification for both the RYO tobacco filler and the
rolling papers. This product-specific information is required under
sections 910(b)(1)(B) and (G) of the FD&C Act and this rule requires
its inclusion in the general information section of the submission to
help FDA quickly check whether the product is within CTP's purview and
identify the specific product that is the subject of the submission.
For more information regarding product properties and why specific
properties are a required part of an application, see the discussion of
Sec.  1114.7(i)(1) in section VIII.B.9. It is important to note that
for the characterizing flavor product property, the applicant must
state ``none'' if it does not consider the product to have a
characterizing flavor. FDA encourages applicants that have questions
regarding how to describe their product's characterizing flavor to
contact FDA prior to submission.
    For each type of tobacco product, the applicant should also include
any additional properties to fully identify the tobacco product, if
applicable. For example, use of product descriptors such as ``extra-
long'' should be identified. While failure to include such additional
properties to help uniquely identify the tobacco product would not
serve as the basis for FDA refusing to accept an application under
Sec.  1114.27(a)(1), it would likely slow down the substantive review
process.
    FDA received a few comments regarding Sec.  1114.7(c)(3), as
discussed below.
    (Comment 21) One comment stated that Sec.  1114.7(c)(3)(iii) should
be amended to require disclosure of all flavoring agents regardless of
whether they constitute characterizing flavors and all solvents rather
than just propylene glycol and glycerin in all new tobacco products.
    (Response 21) We decline to make this proposed edit, because such
information is already required as part of the full listing of all of
the product's ingredients, additives, and constituents

in Sec.  1114.7(i)(1)(ii). Section 1114.7(c)(3)(iii), entitled
``general information,'' is intended to allow FDA to quickly determine
whether the product is under CTP's jurisdiction and readily identify
the specific product that is the subject of the application. A complete
listing of all flavoring agents and solvents in this section would not
further the purpose of this section.
    (Comment 22) One comment requested that FDA amend Sec.
1114.7(c)(3)(iii) to remove the ``dissolvable'' tobacco product
subcategory and replace it with design parameters for an ``oral
tobacco-derived nicotine (OTDN)'' subcategory. The comment stated that
not only does ``dissolvable'' more appropriately describe a product
trait, dissolvable products are less prevalent on the market today than
OTDN products.
    (Response 22) FDA declines to remove the ``dissolvable'' tobacco
product subcategory and replace it with ``oral tobacco-derived nicotine
(OTDN).'' In 2009, the Family Smoking Prevention and Tobacco Control
Act authorized FDA to regulate, among other things, smokeless tobacco
products, the definition of which includes some dissolvables that
contain finely ground tobacco. While design parameters of the
dissolvable tobacco products may resemble those of OTDN, the OTDN
subcategory could imply that such products only contain nicotine that
is derived from tobacco, and not finely ground tobacco. This narrow
definition would exclude dissolvable tobacco products that contain
finely ground tobacco. As discussed in section VIII.B.3., applicants
are required to identify the product category and subcategory in a PMTA
to help FDA quickly check whether the product is within CTP's purview
and identify the specific product that is the subject of the
submission. Where an applicant believes its new tobacco product, such
as OTDN, does not fit within a product category set forth in the rule,
it should identify the product category as ``other.''
    (Comment 23) One comment stated that FDA should remove the
requirement to identify the category and subcategory of the tobacco
product in Sec.  1114.7(c)(3), because applications should compare
their products to all other tobacco products and product categories are
not contemplated under section 910(b) of the FD&C Act. The comment also
stated that there is no justification to support the potential for
users to switch between products within categories when real-world
evidence shows that current users may switch to products from different
categories.
    (Response 23) FDA declines to remove the requirement to identify a
product's category and subcategory. Not only does this information
allow FDA to identify the product, it provides important context for
information contained in the application, including but not limited to
health risks associated with product design and its constituents,
product and packaging design risks and misuse hazards, principles of
operation, and warning statement requirements. Specifically,
identifying a product's category and subcategory ensures that FDA is
able to distinguish between products that have the same brand and
subbrand, but a different category or subcategory, which may be
associated with different health risks, design risks or even have
different warning statement requirements. For example, if an applicant
submits a PMTA for a product that has the same brand and subbrand as
another product but has been identified as smokeless tobacco, FDA will
review the product labeling to ensure it complies with category
specific applicable requirements such as the Comprehensive Smokeless
Tobacco Health and Education Act. Additionally, understanding the
category will allow FDA to determine whether the application meets the
requirement in Sec.  1114.27(b)(1)(ii)(B) to compare the health risks
of the new tobacco product to the health risks of products in the same
product category and products in at least one different product
category.
    Section 1114.7(c) also includes the following requirements:
     The type of PMTA. The applicant is required to state the
type of PMTA the applicant is submitting (i.e., PMTA, supplemental
PMTA, or resubmission);
     whether the applicant requests that FDA refer the PMTA to
the Tobacco Products Scientific Advisory Committee (TPSAC). An
applicant should briefly describe its justification for a request to
refer the PMTA to TPSAC. FDA retains the discretion to refer an
application to TPSAC but will consider an applicant's request as part
of its determination;
     identifying information regarding any prior submissions
relating to the new tobacco product, including STNs, where applicable.
The types of prior submissions include premarket applications, such as
PMTAs, SE Reports, and exemption requests, as well as other submissions
to FDA including MRTPAs and submissions related to investigational
tobacco products. The regulatory history of a tobacco product can
provide useful context for FDA's review of a submission;
     dates and purpose of any prior meetings with FDA regarding
the new tobacco product;
     if the tobacco product has previously been commercially
marketed \16\ in the U.S., the dates during which the tobacco product
was marketed;
---------------------------------------------------------------------------

    \16\ As described in Section IV.B.4., this includes products
that were commercially marketed in test markets.
---------------------------------------------------------------------------

     address and the Facility Establishment Identifier (FEI)
number(s), if available, of the establishment(s) involved in the
manufacturer of the new tobacco product. This information will assist
the Agency with environmental impact considerations and determinations
under part 25 by helping FDA understand the location of manufacturing
and scale of products that would be manufactured. Additionally, it
helps FDA schedule and conduct facility inspections;
     a brief statement regarding how the PMTA satisfies the
content requirements of section 910(b)(1) of the FD&C Act. This could
consist of a table reproducing the section 910(b)(1) requirements and
listing the sections or page numbers of the PMTA that satisfy the
requirements. FDA is requiring this brief statement under authority of
sections 701(a) and 910(b)(1)(G) of the FD&C Act, which will allow FDA
to more quickly locate application content necessary to determine
whether a PMTA should be accepted and filed for further review under
Sec.  1114.27;
     a brief description of how permitting the marketing of the
new tobacco product is expected to be appropriate for the APPH. This
description should be no more than a sentence or two that highlights
the key product characteristics and study results the applicant
believes would make the marketing of the product APPH (e.g., the
product delivers significantly lower levels of a specific HPHCs to
users than the tobacco products they are currently consuming, which
studies indicate may result in decreased morbidity and mortality); and
     a list identifying all enclosures, labels, and labeling
being submitted with the application. This list will help FDA identify
application content and ensure a PMTA contains all the information the
applicant intended to submit.
    FDA received several comments regarding these requirements (Sec.
1114.7(c)(4) through (12)), as discussed below:
    (Comment 24) One comment stated that FDA should refer all PMTAs to

TPSAC and should make all PMTAs available for public comment. The
comment stated that if referring all applications to TPSAC is
unfeasible, FDA should at least refer applications from major tobacco
companies and representative applications from smaller companies.
    (Response 24) We decline to take the comment's suggestion. Under
section 910(b)(2) of the FD&C Act, FDA has the discretion, on its own
initiative or upon the request of an applicant, to refer a PMTA to
TPSAC for reference and for submission of a report and recommendation
respecting the application. Referring an application to TPSAC is a
lengthy process that requires extensive time and resources, including
the significant back-and-forth process with an applicant to redact
trade secrets and confidential commercial information in an application
before it can be made publicly available. Receiving and reviewing
public comments also requires significant time and resources. It would
not be feasible to redact all PMTAs, receive and consider public
comments, and receive and consider TPSAC's report and recommendations
prior to acting on the expected high volume of applications the comment
is suggesting go to TPSAC within the 180-day review period required by
section 910(c) of the FD&C Act.
    (Comment 25) Multiple comments stated that FDA should require
applicants to specify whether the new tobacco product is a deemed
tobacco product that has been on the market prior to the deadline for
submitting a PMTA and, if so, require the submission of information
regarding the marketing of the product prior to application submission,
including items such as prior sales, labeling, advertising, and
marketing strategy. One comment also requested that FDA require an
applicant describe whether the prior marketing of its product has been
APPH and deny applications where this has not been the case.
    (Response 25) FDA has amended the rule to require a PMTA to specify
the prior dates, if any, during which the tobacco product was initially
marketed. Additionally, the requirement in Sec.  1114.7(k) to submit
full reports of investigations that are published or known to, or which
should reasonably be known to, an applicant includes the time period
during which an applicant previously marketed a deemed tobacco product.
While information relating to the prior marketing of a tobacco product
may inform FDA review of a PMTA, FDA declines to require an applicant
to describe whether it believed its prior marketing of a product was
APPH, or necessarily deny an application where prior marketing was not
APPH. FDA will make its own determination as to whether permitting the
marketing of the new tobacco product is APPH based on all of the
contents of the application. In addition, FDA has authority to include
postmarket requirements to help ensure that marketing of the product
after authorization continues to be APPH.
4. Descriptive Information
    Section 1114.7(d) requires applicants to provide descriptive
information that outlines the major aspects of the new tobacco product,
which is required to be submitted under section 910(b)(1)(A), (D), and
(G) of the FD&C Act. This information includes:
     A concise description of the new tobacco product (e.g.,
the product is a portioned smokeless tobacco product made using a blend
of burley and bright tobacco);
     a statement identifying all tobacco product standards
issued under section 907 of the FD&C Act that are applicable to the new
tobacco product and a brief description of how the new tobacco product
fully meets the identified tobacco product standard(s). If the new
tobacco product deviates from such standard(s), if applicable, the rule
requires the application to include adequate information to identify
and justify those deviations;
     the product name(s) as designated on the product's label;
     a description of problems identified in prototypes that
are the subject of studies contained in the application, or previous or
similar versions of the new tobacco product that were marketed, if any.
This includes information regarding any health risks such as
overheating, fires, or explosions as well any information regarding
manufacturing issues related to the product, such as packaging defects
that could pose a health risk. If there are previous or similar
versions that were marketed or that are the subject of studies in the
application, the rule requires the applicant to include a bibliography
of all reports regarding the previous or similar version of the
product, whether adverse or supportive. FDA requires this information
under section 910(b)(1)(A) and (G) of the FD&C Act to assess whether
any known issues with a predecessor product that could affect the
health risks of the new tobacco product have been addressed; and
     any restrictions on the sale, distribution, advertising,
or promotion of the new tobacco product (as described in section
910(c)(1)(B) of the FD&C Act) that the applicant proposes to be
included as part of a marketing granted order, if issued. The applicant
may choose to propose restrictions on the sales and distribution of the
tobacco product to help support a showing that the marketing of the
product is appropriate for the protection of the public health (e.g., a
restriction that decreases the likelihood that those who do not
currently use tobacco products will initiate tobacco product use with
the new tobacco product). If an applicant does not wish to propose any
additional restrictions, it must explicitly state that it proposes no
restrictions. As described in Sec.  1114.31, FDA may consider these
proposed restrictions during its review of the PMTA and, where
appropriate, include applicant proposed restrictions in the marketing
granted order for the product together with any additional restrictions
FDA may require.
    FDA received many comments regarding the descriptive information
requirements, as discussed below.
    (Comment 26) Multiple comments requested that FDA revise the
requirement in Sec.  1114.7(d)(4). One comment stated that section
910(b)(1)(B) of the FD&C Act limits review to the new tobacco product
that is the subject of the application and does not permit review of
other products. The comments also stated that the terms ``previous or
similar version,'' ``prototype,'' and ``problem'' are so vague that
they would leave applicants guessing at what information must be
included. The comments concluded by stating that a product's effects on
public health should be determined based on data about the product in
its current form.
    (Response 26) FDA disagrees with the comments statement that FDA
cannot require this information or consider it during product review.
FDA is requiring the submission of information regarding prototypes and
previous or similar versions of the tobacco product to assess whether
an applicant has addressed any known issues with a predecessor product
that could affect the health risks of the new tobacco product. The
terms ``previous or similar version,'' or ``prototype,'' mean any
previous generation, model, or version of a tobacco product that has
undergone testing or was on the market in other countries, such as
first-generation ENDS products that underwent aerosols or battery
testing, and was subsequently modified as a result of testing, adverse
experiences, or other design concerns that could impact the public
health. Rather than using section 910(b)(1)(B) of the FD&C Act, as
cited by the comments as authority for this requirement, FDA

bases its authority for this provision on section 910(b)(1)(G) of the
FD&C Act, which requires applicants to submit other information
relevant to the subject matter of the application as the Secretary may
require.
    The information required in Sec.  1114.7(d)(4) will allow FDA to
review information regarding risks present in closely related products
and determine whether the applicant has addressed such risks in the
development of the product that is the subject of the PMTA. FDA
declines to adopt the comments' proposed approach that would require
FDA to ignore information about known problems and related health risks
that could be present in the tobacco product under review. We note that
information about known problems and related health risks (e.g.,
product class effects such as mouth ulcers in moist tobacco) would be
informative and could be used to bridge health effect information.
Specifically, this information could help FDA to determine the validity
and applicability of the studies that relied on a prototype.
5. Samples of New Tobacco Products and Components or Parts
    Section 910(b)(1)(E) of the FD&C Act requires an applicant to
submit samples of a tobacco product and its components as FDA may
reasonably require. After FDA accepts a submission, FDA will determine
whether it will require product samples and, if so, issue instructions
on how and where to submit the samples, and the number of samples that
are required. Section 1114.7(e) requires an applicant to submit samples
of the finished tobacco product and its components in accordance with
instructions issued to the applicant after a PMTA is accepted for
review, as well as to submit additional samples if required by FDA
during application review. FDA generally expects that product samples
will be a required part of a PMTA and that an applicant should be
prepared to submit them in accordance with FDA instructions within 30
days after submitting a PMTA. There may be situations in which sample
submission may not be necessary, including, in some circumstances,
PMTAs that are resubmitted for the same product after a marketing
denial order (such as resubmissions as described in Sec.  1114.17) or
PMTAs submitted for modifications to an authorized product where the
modifications do not require review of new samples as part of the PMTA
evaluation process. Presubmission meetings with FDA may help provide
additional information about whether product samples will need to be
included in a PMTA; however, in most situations, FDA will only be able
to determine the need for product samples after a PMTA is accepted for
review.
    FDA received many comments regarding product samples, as discussed
below.
    (Comment 27) One comment agreed that requesting samples after a
PMTA submission has been accepted makes sense; however, it stated that
providing information regarding the quantity and type of samples that
will be required for submission in advance is important to ensure that
the samples FDA requires are actually available at the time of request.
    (Response 27) As described in section VIII.B.5, FDA generally
expects that product samples will be a required part of a PMTA and that
an applicant should be prepared to submit them in accordance with FDA
instructions within 30 days after submitting a PMTA. Because the
quantity and type of samples need for testing may vary based upon a
number of factors including product category and specific product
characteristics, FDA intends to determine the quantity and type that
will be required after application acceptance. However, as noted in
section VIII.B.5., presubmission meetings with FDA may help provide
additional information about whether product samples will need to be
included in a PMTA.
    (Comment 28) We received multiple comments regarding FDA's proposal
to require an applicant to submit product samples only after an
application is accepted for review. One comment stated that the start
of FDA's 180-day review period should not be postponed until samples
are received and should instead begin at the time the application is
otherwise complete except for samples. Another comment requested that
FDA amend the rule to allow applicants to submit product samples as
part of its initial PMTA to avoid delays. The comment stated that the
costs of the delaying the start of substantive review outweigh any
minor savings gained by postponing inevitable product sample
submission. The comment also noted that under FDA's proposed approach,
FDA could indefinitely delay filing an application for review by not
requesting product samples after application acceptance.
    (Response 28) We decline to make the requested revisions. FDA will
have applicants submit samples (if required by FDA) after acceptance of
an application rather than as part of an initial submission. This
timing will help FDA to determine the need for samples, allow the
samples to be tracked and identified as part of the correct
application, and facilitate the submission of samples to testing
facilities that are adequately prepared to accept them (e.g., one that
has a refrigerated unit if the product needs to be stored at a certain
temperature). Additionally, by having applicants submit samples after
FDA accepts an application, applicants will be able to avoid the effort
and expense of submitting samples if the application is not accepted
for review or if samples are not required. It will also allow FDA to
avoid similar concerns with respect to storage and the return of
samples for applications where FDA refuses to accept a PMTA. As
described in Sec.  1114.27, if required by FDA, product samples will be
necessary for application filing and FDA intends to refuse to file a
PMTA for a lack of product samples if the applicant has not submitted
samples in accordance with FDA's instructions by the time FDA is
prepared to make its filing determination.
    FDA intends to notify an applicant if it determines after PMTA
acceptance that product samples are not required for PMTA filing;
however, even in such a situation, FDA may request product samples
during substantive review after an application is filed, as needed. FDA
generally expects that, where required, samples will be requested
within 30 days after application submission. Applicants may discuss the
need for product samples during a presubmission meeting with FDA, which
may speed up the sample submission process.
6. Labeling and Description of Marketing Plans
    Section 1114.7(f) of the rule requires that a PMTA contain
specimens of labeling and describe the applicant's marketing plans for
the new tobacco product.
    a. Labeling. Section 910(b)(1)(F) of the FD&C Act requires that a
PMTA contain specimens of the proposed labeling to be used for the
tobacco product. Section 1114.7(f)(1) elaborates on this requirement
and requires the application to contain specimens of all proposed
labeling for the new tobacco product, including labels, inserts,
onserts, instructions, and other accompanying information.
    FDA received comments regarding the submission of labeling, as
described below.
    (Comment 29) One comment stated that FDA's proposal to require
``specimens of all proposed labeling'' in Sec.  1114.7(f)(1) is outside
the scope of its authority under section 910 of the FD&C

Act and requested that FDA remove the word ``all'' from the
requirement. The comment stated that the statute requires the
submission of specimens proposed to be used, which connotes a typical
example of a larger whole and, as such, is not compatible with the
requirement to provide ``all'' proposed labeling.
    (Response 29) FDA disagrees with the assertion that Sec.
1114.7(f)(1) is outside of its authority and declines to interpret the
term ``specimens'' as used in section 910(b)(1)(F) of the FD&C Act to
mean a representative sample. FDA's interpretation of section
910(b)(1)(F) in Sec.  1114.7(f)(1) is consistent with how it interprets
similar statutory requirements to submit specimens of labeling for both
new drug applications and premarket approval applications for medical
devices.\17\ Not only did FDA's interpretation of these requirements
for drugs and devices exist when Congress enacted the same requirement
in the Tobacco Control Act, section 905(i)(1)(B) of the FD&C Act
demonstrates Congress understands how to require a representative
sample when it intends to do so. It did not do so here. Furthermore,
requiring specimens of all proposed labeling is important to FDA's
review of an application, because FDA must deny a PMTA under section
910(c)(2)(C) of the FD&C Act where it finds, based on a fair evaluation
of all material facts, the proposed labeling is false or misleading in
any particular. This requirement to deny a PMTA based upon any
particular of the proposed labeling is at odds with the comment's
suggestion that Congress intended FDA to review only a general
representation of what an applicant proposes to use.
---------------------------------------------------------------------------

    \17\ See the interpretation of section 505(b)(1)(F) of the FD&C
Act (21 U.S.C. 355(b)(1)) in 21 CFR 314.50(e)(2)(ii) (50 FR 7493,
February 22, 1985) for new drug application, and the interpretation
of 515(c)(1)(F) (21 U.S.C. 360e(c)(1)(F)) in 21 CFR 814.20(b)(10)
for premarket approval applications for medical devices.
---------------------------------------------------------------------------

    The labeling specimens are required to include all panels and
reflect the actual size and color proposed to be used for such tobacco
product. The labels must include any warning statements required by
statute or regulation, such as the Federal Cigarette Labeling and
Advertising Act, the Comprehensive Smokeless Tobacco Health and
Education Act, or the minimum required warning statements contained in
21 CFR part 1143. For products that are required to provide rotational
warning statements, the applicant should submit labeling with each of
the required warnings in the rotation.\18\
---------------------------------------------------------------------------

    \18\ For more information on rotational warning statement
requirements, see https://www.fda.gov/tobacco-products/products-guidance-regulations/labeling-and-warning-statements-tobacco-products.
---------------------------------------------------------------------------

    As described in Sec.  1114.33, product labeling is an important
part of FDA's review of an application, because FDA must deny a PMTA
under section 910(c)(2)(C) of the FD&C Act where it finds, based on a
fair evaluation of all material facts, the proposed labeling is false
or misleading in any particular. Additionally, product labeling can be
an important part of FDA's determination under section 910(c)(2)(A) of
the FD&C Act of whether there is a showing that permitting the
marketing of the product would be APPH because it can be used to help
show perception of the risks of the product and the ability of
individuals to understand the labeling, including any instructions for
use, as described in Sec.  1114.7(k)(1)(iv).
    b. Description of Marketing Plans.--i. General. In the proposed
rule, the marketing plans provision in proposed Sec.  1114.7(f)(2)
would have required an applicant to submit detailed information about
all plans it had developed to market its new tobacco product. In
response to comments and on FDA's own initiative, we have revised the
requirement to submit information concerning the applicant's plans to
market the new tobacco product. Rather than requiring all of the
detailed information required in proposed Sec.  1114.7(f)(2), FDA has
revised this section to require only a high-level description of
several key aspects of these plans that directly inform FDA's APPH
determination. FDA notes that, pursuant to Section 910(b)(1)(G) of the
FD&C Act, the Agency may require additional information related to
marketing plans on a case-by-case basis, if the agency determines
during review that additional information is needed to help determine
if a product is appropriate for the protection of the public health.
FDA's discussion of the comments is included below.
    (Comment 30) One comment stated that FDA should clarify the scope
of marketing information it expects to see in a PMTA and explain how it
plans to engage in a science-based review of labeling and marketing
plans, noting that the rule provides little detail as to what specific
marketing information the Agency expects to see. The comment stated
that it is unclear whether FDA is proposing to require submission of
information about top-line product messaging or specific pieces of the
advertising and marketing strategies for their use. The comment noted
that it is also unclear to what extent FDA expects to see results of
consumer research. In addition, the comment stated that it remains
unknown how the Agency plans to review labeling and marketing plans and
what specific considerations or methodologies will guide assessment of
consumer risk perception, comprehension, and use intentions.
    (Response 30) FDA has revised Sec.  1114.7(f)(2) to require only
high-level marketing plan information that it generally expects
applicants will have developed prior to seeking marketing authorization
for their products. The description of marketing plans now required by
Sec.  1114.7(f)(2)--including intended audience, how the applicant
would target the intended audience and what other groups would
foreseeably be exposed, and how exposure would be limited for
individuals below the minimum age of sale--seeks information necessary
for FDA to properly evaluate the extent of youth exposure to marketing
materials for the product and youth access to the product. Discussion
of these items will not require applicants to conduct consumer
research; however, where an applicant had undertaken such research, the
results of such research will be required by Sec.  1114.7(f)(2) or
(k)(1)(iv). As discussed in section VIII.B.6.b., this information will
allow FDA to consider whether an applicant has addressed potential
concerns about the marketing of its product, such as tobacco product
use initiation by individuals under the minimum age of sale, and will
help FDA to assess whether the plans to market the product are
consistent with the applicant's discussion of the likelihood of changes
in tobacco product use behavior in the application. These
considerations will help FDA to determine whether there is a showing
that permitting the tobacco product to be marketed is appropriate for
the protection of public health.
    (Comment 31) One comment stated that the marketing plan
requirements seem to be based on the premise that companies will have
developed marketing plans by the time of application submission, which
fails to account for the small vape shops that currently serve as both
retailers and manufacturers who are unlikely to have undertaken
consumer research. The comment requested that FDA edit the marketing
plan requirements to apply only ``as applicable'' to companies that
have conducted such research.
    (Response 31) The requirement to provide descriptions of marketing
plans does not require applicants to undertake market or consumer
research. Rather,

Sec.  1114.7(f)(2) requires PMTAs to contain a discussion of several
key high-level aspects of the applicant's plans to market the product.
The discussion of these items will not require consumer research;
however, be aware that Sec.  1114.7(k)(1)(iv) requires applicants to
submit reports of all information published or known to, or which
should reasonably be known to, the applicant concerning investigations
regarding the impact of the product and its label, labeling, and
advertising, to the extent that advertising has been studied, on
individuals' perception of the product and use intentions. This will
include any consumer research that the applicant has undertaken or used
to develop the aspects of its marketing plan identified in Sec.
1114.7(f)(2).
    (Comment 32) One comment stated that FDA should amend the marketing
plan requirements in Sec.  1114.7(f)(2) to include specific language
about dual use because the reality is that most adult users of tobacco
products become dual users.
    (Response 32) We have edited Sec.  1114.7(f)(2) to include polyuse
as an example tobacco use behavior that descriptions of marketing plans
may address in describing target audiences. FDA requires descriptions
of marketing plans to inform our determination of whether the new
product is appropriate for the protection of public health. As part of
FDA's determination of the risks and benefits to the health of the
population as a whole (which includes youth, young adults, and other
vulnerable populations), FDA will consider the potential for long-term
dual use among current users. FDA reviews the descriptions of marketing
plans in conjunction with the other submitted information, which can
include tobacco product perception and use intention studies and actual
use studies to assess the likelihood that current users will switch
completely to the new product or become a dual or polyuser of tobacco
products. To the extent that the description of marketing plans
contains information about the target audience by psychographic
characteristics including tobacco use patterns, FDA will consider
whether dual use is likely given the description of the marketing plans
and the other submitted information.
    (Comment 33) One commenter stated that the marketing plan
requirements are outside of what the FD&C Act allows FDA to review as
part of a PMTA. The commenter stated that the structure of the FD&C Act
shows that Congress did not intend for FDA to review marketing plan
information as part of a PMTA because where Congress found such
information to be relevant to FDA's analysis, it expressly added such a
requirement to the statute (e.g., section 905(i)(1) of the FD&C Act).
The commenter stated that in contrast, in section 910 of the FD&C Act
Congress required that PMTAs must contain only ``specimens of the
proposed labeling to be used for [the] tobacco product.'' The commenter
concluded that the fact that Congress omitted a broader requirement for
advertisements in section 910 of the FD&C Act but included the
requirement for only ``specimens'' of labeling shows that Congress did
not consider broader information relevant to FDA's evaluation of a
PMTA. The commenter also states that FDA's claim of authority under
section 910(b)(1)(G) is ineffective because it does not grant FDA the
limitless authority to require content; rather, FDA only has the
authority to require information under 910(b)(1)(G) of the FD&C Act
that is reasonable and reasonably explained, which the commenter
maintains that FDA has failed to do here.
    (Response 33) As discussed in Response 30, FDA has revised Sec.
1114.7(f)(2) to require only high-level marketing plan information that
it generally expects applicants will have developed prior to seeking
marketing authorization for their products. But even so, we disagree
with the commenter's position that FDA lacks statutory authority to
require marketing plans as part of a PMTA. In describing the required
contents of a PMTA in section 910(b)(1)(G), Congress explicitly
authorized FDA to require ``such other information relevant to the
subject matter of the application.'' This provision demonstrates that
Congress intended for FDA to apply its expertise with respect to review
of scientific applications and the overall administration of the
Tobacco Control Act to determine what additional information would be
``relevant'' to whether the application meets the requirements to
receive marketing authorization.
    We have determined that the description of marketing plans required
by Sec.  1114.7(f)(2) is relevant to the subject matter of a PMTA. To
issue a marketing granted order for a new tobacco product, FDA must
determine that permitting such tobacco product to be marketed would be
APPH, which requires FDA to consider the likelihood that those who do
not use tobacco products, including youth, will start using them.
Determining the extent to which youth will be exposed to marketing
materials for the product is critical to that consideration. As
explained by Congress in enacting the Tobacco Control Act, tobacco
advertising, marketing, and promotion substantially contribute to youth
trial and uptake of tobacco use. See, e.g., Tobacco Control Act section
2(5) (tobacco advertising and marketing contribute significantly to the
use of tobacco products by adolescents.); id. section 2(15)
(advertising, marketing and promotion of tobacco products have resulted
in increased use of such products by youth.); id. section 2(20)
(children are exposed to substantial and unavoidable tobacco
advertising that increases the number of young people who begin to use
tobacco); id. section 2(22) (tobacco advertising expands the size of
the tobacco market by increasing consumption of tobacco products
including tobacco use by young people). Congress enacted the Tobacco
Control Act against the backdrop of years of litigation exposing
previous tobacco product marketing campaigns in which companies
successfully targeted and recruited new youth smokers. See, e.g.,
United States v. Philip Morris USA, Inc., 449 F. Supp. 2d 1, 616
(D.D.C. 2006) (``As the following evidence demonstrates, Defendants
have utilized the vast amount of research and tracking data they
accumulated on youth smoking initiation, tastes and preferences by
employing themes which resonate with youth in their marketing
campaigns. Defendants have focused their attention on young people
under the age of twenty-one in order to recruit replacement smokers and
have emphasized the popularity, physical attractiveness, and `coolness'
of their youth brands. Above all, Defendants have burnished the image
of their youth brands to convey rugged independence, rebelliousness,
love of life, adventurousness, confidence, self-assurance, and
belonging to the `in' crowd.'' (internal citation omitted)), aff'd in
part, rev'd in part on other grounds, 566 F.3d 1095 (D.C. Cir. 2009);
see also 449 F. Supp. 2d at 616-39.
    A well-established body of scientific evidence confirms the
continuing impact of tobacco product marketing on initiation and use by
individuals under the minimum age of sale. See, e.g., Dep't of Health &
Human Servs., E-Cigarette Use Among Youth and Young Adults: A Report of
the Surgeon General 170 (2016) (``An analysis of the 2011 National
Youth Tobacco Survey found that adolescents who reported frequent
exposure to protobacco advertising at the point of sale and on the
internet (e.g., seeing ads most of the time or always) had
significantly higher odds of ever using e-cigarettes, and there was a
dose-response association between the number of marketing channels to
which

they were exposed and ever use[.]''); Dep't of Health & Human Servs.,
Preventing Tobacco Use Among Youth and Young Adults: A Report of the
Surgeon General 598 (2012) (``[T]here is strong empirical evidence,
along with the tobacco industry's own internal documents and trial
testimony, as well as widely accepted principles of advertising and
marketing that support the conclusion that tobacco manufacturers'
advertising, marketing, and promotions recruit new users as youth and
continue to reinforce use among young adults[.]''). Companies marketing
newer forms of tobacco products have employed some of the same
techniques, as well as newer innovations, to attract the youth market.
For example, ENDS manufacturers have used social media, including
influencers, to help create an image for their products as being cool
and having sex appeal, sponsored music festivals, and created products
with youth-appealing cartoon images (see, e.g., Refs. 12 through 15).
    The descriptions of marketing plans required by Sec.
1114.7(f)(2)--including intended audience, how the applicant would
target the intended audience and what other groups would foreseeably be
exposed, and how exposure would be limited for individuals below the
minimum age of sale (e.g., avoiding online social media without access
restrictions)--seeks information necessary for FDA to properly evaluate
the extent of youth exposure to marketing materials for the product and
youth access to the product. Accordingly, this information is directly
relevant to the subject matter of a PMTA, including FDA's consideration
of the likelihood that youth will use the tobacco product and its
determination that permitting the product to be marketed would be APPH.
    Because Congress clearly and unambiguously authorized FDA to
require additional relevant information, that should be ``the end of
[the] analysis.'' Zuni Pub. Sch. Dist. No. 89 v. Dep't of Educ., 550
U.S. 81, 93 (2007) (citing Chevron, U.S.A., Inc. v. Natural Res. Def.
Council, Inc., 467 U.S. 837 (1984)). But even if Congress has not
``directly'' addressed ``the precise question at issue,'' FDA's
interpretation is a ``permissible construction of the statute,''
Chevron, 467 U.S. 837 at 843, on a matter where the Agency's expertise
plays a significant role in resolving important questions related to
the administration of the statute. Barnhart v. Walton, 535 U.S. 212,
222 (2002).
    In determining to require the submission of descriptions of
marketing plans as part of a PMTA, FDA considered the information it
needed to be able to evaluate whether the statutory requirements for
PMTA authorization are met, as well as the context and purpose of the
PMTA requirement. As discussed above, a well-established body of
historical and scientific evidence and Congress's own findings in
enacting the Tobacco Control Act support FDA's reasonable conclusion
that potential exposure to tobacco product advertising, marketing, and
promotion is relevant to, and indeed a critical factor in, FDA's
statutorily required determination of the likelihood that nonusers,
including youth, will use a new tobacco product. Moreover, based on
this evidence, as well as the expertise it has developed regarding
tobacco product marketing over more than a decade of administering the
Tobacco Control Act, FDA has rationally concluded that the required
descriptions of marketing plans will directly inform its assessment of
who may be exposed to the applicant's labeling, advertising, marketing,
and promotion and, as a result, its consideration of the potential
impact on youth initiation and use. FDA's assessment of who may be
exposed to tobacco product marketing materials and activities will
include individuals below the minimum age of sale, recently raised from
18 to 21 years. For example, information regarding how the applicant
will target the intended audience, such as the marketing channels and
tactics an applicant expects to use, will permit FDA to determine the
extent to which youth would be exposed to and influenced by marketing
for the product. (See, e.g., Refs. 13, 16, and 17) As another example,
a description of the ways in which an applicant would limit exposure to
tobacco product marketing materials and activities for individuals
below the minimum age of sale will inform FDA's assessment of the
potential for youth exposure to these materials and activities.
    Submission of descriptions of marketing plans also supports the
Tobacco Control Act's mandate that FDA protect youth from the dangers
of tobacco use. See, e.g., Tobacco Control Act section 3(2), (7)
(purposes of the Tobacco Control Act include to ensure that FDA has
authority to address issues of particular concern to public health
officials, especially the use of tobacco by young people, and to ensure
that tobacco products are not sold or accessible to underage
purchasers). In enacting the Tobacco Control Act and giving FDA this
mandate, Congress recognized the substantial impact of exposure to
tobacco product advertising, marketing, and promotion on youth tobacco
use. See, e.g., Tobacco Control Act section 2(15) (advertising,
marketing and promotion of tobacco products have resulted in increased
use of such products by youth.). Based on this context and the ample
scientific evidence supporting the powerful impact of marketing on
youth tobacco use, FDA reasonably concluded that determining the extent
to which youth may be exposed to marketing materials for a new tobacco
product is critical to its evaluation of the potential for youth to use
the new tobacco product and to its ability to fulfill its mandate to
protect youth from the dangers of tobacco use. To that end, the
requirement for descriptions of marketing plans seeks information that
directly informs FDA's assessment of the extent to which youth may be
exposed to marketing materials for the new tobacco product, as well as
information to help FDA determine whether any concerns about youth use
of the product and the corresponding increases in health risks would be
mitigated, such as information regarding the extent to which an
applicant would restrict access to the tobacco product for individuals
below the minimum age of sale.
    Contrary to the comment, Congress's inclusion of an advertising
requirement in non-PMTA-related sections of the FD&C Act, such as
section 905(i)(1), and omission of the requirement in section
910(b)(1)(F) of the FD&C Act, does not demonstrate Congress's intent to
exclude description of marketing plans from PMTAs. Congress's explicit
authorization in 910(b)(1)(G) of the FD&C Act that FDA may require
``such other information relevant to the subject matter of the
application'' defeats the commenter's inference by omission argument.
See Adirondack Med. Ctr. v. Sebelius, 740 F.3d 692, 697 (D.C. Cir.
2014) (the ``expressio unius canon'' is a ``poor indicator of Congress'
intent'' where there is a ``broad grant of authority'' to the Agency;
instead, `` `Congress is presumed to have left to reasonable agency
discretion questions that it has not directly resolved' '' (quoting
Cheney R.R. Co. v. I.C.C., 902 F.2d 66, 68-69 (D.C. Cir. 1990)).
Indeed, Congress did not ``omit'' an advertising requirement from
section 910(b)(1) but rather left its inclusion to FDA's discretion and
judgment. As explained above, FDA has reasonably exercised its
discretion in construing section 910(b)(1)(G) of the FD&C Act to
require descriptions of marketing plans based on the Tobacco Control
Act's context and purpose, ample scientific evidence,

and the Agency's own expertise developed over a decade of administering
the statute.
    (Comment 34) The commenter also stated that the marketing plans
requirement potentially limits speech, raising First Amendment
concerns. The commenter stated that the requirement places more than an
incidental burden on protected expression, and the government cannot
show it directly advances a substantial government interest that is
drawn narrowly to achieve that interest. In terms of the alleged
burden, the commenter stated that the requirement would distract and
deter manufacturers from the focused development and implementation of
robust marketing plans--ultimately burdening the right of consumers to
receive, and manufacturers to provide, information about products
determined by FDA to be appropriate for the protection of the public
health. Additionally, the commenter asserted that the requirement would
significantly chill protected speech due to the threat that FDA might
disclose information about applicants' marketing plans to TPSAC or the
public and thereby compromise an applicant's competitive strategy.
    The commenter also asserted that the proposed requirement for
manufacturers to report ``total dollar amount(s) of media buys and
marketing and promotional activities'' would have been particularly
burdensome and lacked justification. It stated that there was no
evidence in the record that reporting such information for truthful
advertising and marketing of a product with a PMTA order would directly
advance the government's interest. The commenter also asserted that
FDA's proposed request for marketing plans would not yield meaningful
information given the amount of time it could take for FDA to review an
application, the evolving tobacco product landscape, and the likelihood
that the applicant's marketing plans would change.
    In arguing that the government has not justified these burdens, the
commenter asserts that the marketing plans requirement is a content-
based burden on speech in that it applies only to applicants who wish
to engage in the marketing of tobacco products, and therefore the
government's justification is subject to strict scrutiny under Reed v.
Town of Gilbert, 135 S. Ct. 2218, 2226 (2015), or at least heightened
scrutiny under Sorrell v. IMS Health Inc., 564 U.S. 552 (2011). The
commenter states that FDA's required marketing disclosures are not
narrowly tailored nor do they directly advance a compelling government
interest, so they cannot meet the higher standard for content-based
restrictions.
    (Response 34) As discussed in Response 30, FDA has revised Sec.
1114.7(f)(2) to require only high-level marketing plan information that
it generally expects applicants will have developed prior to seeking
marketing authorization for their products. That noted, we do not agree
that the requirement for descriptions of marketing plans raises First
Amendment concerns for several reasons. First, we disagree that the
requirement to submit descriptions of marketing plans burdens speech.
Federal Agencies routinely require regulated industry to disclose
information to the government. The FD&C Act contains several premarket
authorization requirements, including for drugs and devices, which have
existed for decades, and whose constitutionality is not seriously
questioned. Indeed, in the proliferation of lawsuits challenging
various aspects of the Tobacco Control Act, there have been few direct
challenges to the PMTA requirements, and any related challenges have
been resolved in the government's favor. See Nicopure Labs., LLC v.
FDA, 266 F. Supp. 3d 360, 391-95, 409 (D.D.C. 2017) (upholding FDA's
decision to apply PMTA requirements to deemed tobacco products as
permissible under the Administrative Procedure Act, and upholding the
statutory PMTA requirement under the Due Process clause of the
Constitution), aff'd on other grounds, 944 F.3d 267 (D.C. Cir. 2019)
(PMTA rulings were not appealed); see also, e.g., Nicopure Labs., 944
F.3d at 284-90 (D.C. Cir. 2019) (rejecting First Amendment challenge to
the Tobacco Control Act requirement that manufacturers obtain premarket
review of MRTPs).
    To the extent that the commenter contends that the requirement to
provide a description of its marketing plans to FDA would impinge on an
applicant's ability to market its tobacco products, FDA is not aware of
any evidence to support that contention (and the commenter cites none).
The comment's assertion that the requirement would distract and deter
manufacturers from the focused development and implementation of robust
marketing plans strains credulity given tobacco manufacturers'
incentives to market their products and the significant resources
tobacco product manufacturers commit to marketing their products each
year. See Edenfield v. Fane, 507 U.S. 761, 766 (1993) (``A seller has a
strong financial incentive to educate the market and stimulate demand
for his product or service.''). The Federal Trade Commission reported
that advertising and promotional expenditures by major cigarette
manufacturers totaled $8.401 billion in 2018 (Ref. 18).
    FDA has considered the comment's position regarding the proposed
Sec.  1114.7(f)(2) requirement that applicants provide ``total dollar
amount(s) of media buys and marketing and promotional activities.'' FDA
has revised Sec.  1114.7(f)(2) to no longer require total dollar
amounts of media buys and marketing and promotional activities. In
addition, FDA has revised this section to require only high-level
information that it expects applicants will generally have developed
prior to seeking marketing authorization for their products. For
example, revised Sec.  1114.7(f)(2)(i) and (ii) require an applicant to
provide a discussion of the intended audience for the marketing
materials and activities for the tobacco product and how the applicant
would target those marketing materials and activities to the intended
audience. Based on its experience, FDA expects that an applicant will
generally have considered its intended audience and how it will target
its marketing materials and activities to that audience by the time it
submits its PMTA. Discussion of these items will not require applicants
to conduct consumer research; however, where an applicant has
undertaken such research, such as conducting tobacco product perception
and intention studies, it will be required to be included in the PMTA
as set forth in Sec.  1114.7(k)(1)(iii), where applicable. Applicants
will be required to provide the descriptions of marketing plans
identified in this section based on the plans they have developed as of
the time of submitting their PMTA, and where an applicant has not
developed plans relating to one or more items in Sec.  1114.7(f)(2),
they would be required to state that in their application.
    The comment's concern that commercial speech would be chilled due
to the perceived risk that FDA would disclose an applicant's
description of its marketing plans to TPSAC or the public and thereby
compromise confidential commercial information (CCI) in those marketing
plans is unwarranted. FDA generally may not make information in an
application publicly available to the extent that the information
constitutes trade secrets or CCI. See 5 U.S.C. 552(b)(4); 18 U.S.C.
1905; 21 U.S.C. 387f(c); 21 CFR 20.61(c); id. Sec.  1114.47(a) (FDA
will determine the public availability of any part of a PMTA under this
section and part 20 (21 CFR part 20)). The Tobacco Control Act does not
require FDA to refer PMTAs (or any

information contained therein) to TPSAC, instead committing that
decision to the Secretary's discretion. See 21 U.S.C. 387j(b)(2)
(providing that the Secretary ``may'' refer PMTAs to TPSAC ``on the
Secretary's own initiative; or . . . upon the request of an
applicant''). If the Secretary finds it appropriate to consult the
TPSAC on an issue that requires consideration of CCI contained in the
description of marketing plans, FDA may share that information only
with TPSAC members who are subject to the same restrictions with
respect to disclosure of CCI as any other FDA employee. See 21 CFR
20.84; id. 21 CFR 14.86(a)(2). Additionally, if the Secretary refers a
PMTA to TPSAC, Sec.  1114.47(b)(4) of this rule provides that CCI
contained in the application generally will not be available for public
disclosure. FDA may close a portion of a TPSAC meeting to allow
discussion of an applicant's CCI to take place without disclosing the
CCI to the public. See 21 CFR 14.27(b)(3) (allowing portions of an
advisory committee meeting to be closed if they concern the review of
trade secrets and CCI).
    FDA also disagrees with the commenter's assertion that FDA's
requirement for marketing plans as originally proposed would not yield
meaningful information given the amount of time it might take for FDA
to review an application, the evolving tobacco product landscape, and
the likelihood that the applicant's marketing plans would change.
Because we have revised Sec.  1114.7(f)(2) to require a discussion of
high-level items, rather than the submission of details that are more
subject to change (e.g., media buys, dollar amount, specific tactics),
we generally do not expect the information contained in the applicant's
description of marketing plans to change significantly after the
submission of the application. However, under Sec.  1114.9, FDA may
request, or an applicant may submit on its own initiative, an amendment
to its PMTA containing information that is necessary for FDA to
complete its review of the application, including information regarding
any alterations or updates to the required description of marketing
plans. As described in section VIII.C., so long as such an amendment
does not require significant review time, it will not be considered a
major amendment for which the review period will be extended by up to
180 days and even where such an amendment is major amendment, FDA
anticipates it would generally take less than 180 days to complete
review thereof.
    Second, even if the requirements of Sec.  1114.7(f)(2) restricted
speech, they would readily pass muster under the intermediate scrutiny
test for commercial speech articulated in Central Hudson Gas & Elec.
Corp. v. Pub. Serv. Comm'n, 447 U.S. 557 (1980). Under that test,
Agencies may regulate speech where the regulation advances a
substantial government interest and the regulation is no more extensive
than necessary to serve that interest.
    It is well established that FDA has a substantial interest in
protecting youth from tobacco products. See Lorillard Tobacco Co. v.
Reilly, 533 U.S. 525, 564-66 (2001); see also Discount Tobacco City &
Lottery, Inc. v. United States, 674 F.3d 509, 519-20, 541 (6th Cir.
2012). Youth are a significant population of concern for reasons that
have been extensively documented in scientific research and in the
Tobacco Control Act. For example, youth are especially susceptible to
addiction due to their ongoing and incomplete brain development. See
2012 Surgeon General's Report. In addition, most tobacco use is
established in adolescence and age of initiation plays a significant
role in the progression from tobacco experimentation to regular use.
See id.; see also, e.g., Tobacco Control Act section 2(1) (``The use of
tobacco products by the Nation's children is a pediatric disease of
considerable proportions that results in new generations of tobacco-
dependent children and adults.''); id. section 2(4) (``Virtually all
new users of tobacco products are under the minimum legal age to
purchase such products.''). FDA has a statutory mandate to protect
youth from these dangers of tobacco product use. See, e.g., Tobacco
Control Act section 3(2), (7) (purposes of the Tobacco Control Act
include to ensure that FDA has authority to address issues of
particular concern to public health officials, especially the use of
tobacco by young people, and to ensure that (tobacco products) are not
sold or accessible to underage purchasers).
    The requirement for applications to contain descriptions of
marketing plans clearly and directly advances FDA's substantial
interest in protecting youth from the dangers of tobacco product use.
As explained in section VIII.B.6.b, it is well established that
exposure to tobacco product labeling, advertising, marketing, and
promotion has a direct and powerful impact on youth trial and uptake of
tobacco product use. See, e.g., Tobacco Control Act section 2(5)
(``Tobacco advertising and marketing contribute significantly to the
use of nicotine-containing tobacco products by adolescents.''); 2016
Surgeon General's Report at 170 (``An analysis of the 2011 National
Youth Tobacco Survey found that adolescents who reported frequent
exposure to protobacco advertising at the point of sale and on the
internet (e.g., seeing ads most of the time or always) had
significantly higher odds of ever using e-cigarettes, and there was a
dose-response association between the number of marketing channels to
which they were exposed and ever use[.]''); 2012 Surgeon General's
Report at 598 (``[T]here is strong empirical evidence, along with the
tobacco industry's own internal documents and trial testimony, as well
as widely accepted principles of advertising and marketing that support
the conclusion that tobacco manufacturers' advertising, marketing, and
promotions recruit new users as youth and continue to reinforce use
among young adults[.]'').
    Accordingly, determining the extent to which youth may be exposed
to marketing materials for a new tobacco product is critical to FDA's
evaluation of the potential for youth use of the new tobacco product.
The requirement for descriptions of marketing plans seeks information
that directly informs the extent to which youth may be exposed to these
marketing materials, including information regarding the intended
audience for the materials, how the applicant plans to target the
materials to that audience and what other groups would foreseeably be
exposed to those materials, and how the applicant plans to limit youth
exposure to the materials. In addition, the requirement seeks
information to help FDA determine whether any concerns about youth use
of the product and the corresponding increases in health risks may be
mitigated, such as information regarding how the applicant plans to
limit youth access to the product. Moreover, the requirement for
descriptions of marketing plans is no more extensive than necessary to
permit FDA to make these determinations, as it requires minimal, high-
level information that FDA expects an applicant to have at the time of
submitting its application.
    In addition, the requirement for descriptions of marketing plans
clearly and directly advances FDA's substantial government interest in
ensuring that permitting the marketing of new tobacco products would be
APPH. Under section 910(c)(2)(4) of the FD&C Act, a key consideration
of the APPH determination is whether permitting the marketing of the
product would increase or decrease the likelihood that those who do not
use tobacco products, including youth, will start using them. Among
nonusers, youth are a significant population of concern for the reasons
already explained above. Determining the extent to which youth would be

exposed to marketing materials for the product is therefore critical to
FDA's evaluation of the likelihood that youth will initiate tobacco use
with the new tobacco product. Accordingly, by providing FDA with
certain high-level information necessary to help determine potential
youth exposure to marketing materials for a new tobacco product, the
requirement for descriptions of marketing plans directly advances and
is reasonably tailored to FDA's substantial interest in ensuring that
permitting the marketing of the new tobacco product is APPH.
    Finally, we disagree with the commenter's assertion that Sec.
1114.7(f)(2)'s disclosure requirements are subject to strict scrutiny
under Reed v. Town of Gilbert, 135 S. Ct. 2218, 2226 (2015), or at
least heightened scrutiny under Sorrell v. IMS Health Inc., 564 U.S.
552 (2011). In Reed v. Town of Gilbert, the Court applied strict
scrutiny to content-based restrictions on noncommercial speech in
public fora. Reed had nothing to do with commercial speech doctrines,
see 135 S. Ct. at 2224-25, and it has not been understood to alter the
applicability of Central Hudson. Likewise, Sorrell ``did not mark a
fundamental departure from Central Hudson's four-factor test, and
Central Hudson continues to apply'' to regulations of commercial
speech, regardless of whether they are content based. Retail Digital
Network, LLC v. Prieto, 861 F.3d 839, 846 (9th Cir. 2017) (en banc);
accord Vugo, Inc. v. City of New York, 931 F.3d 42, 50 (2d Cir. 2019),
cert. denied, 140 S. Ct. 2717 (2020) (``No Court of Appeals has
concluded that Sorrell overturned Central Hudson. We agree with our
sister circuits that have held that Sorrell leaves the Central Hudson
regime in place, and accordingly we assess the constitutionality of the
City's ban under the Central Hudson standard.''); Missouri Broad. Ass'n
v. Lacy, 846 F.3d 295, 300 n.5 (8th Cir. 2017) (``The upshot [of
Sorrell] is that when a court determines commercial speech restrictions
are content- or speaker-based, it should then assess their
constitutionality under Central Hudson.'') (quotation marks omitted;
alteration in original); Nicopure Labs., LLC v. FDA, 266 F. Supp. 3d
360, 411 (D.D.C. 2017) (``[T]he Sorrell opinion did not alter or
replace the Central Hudson intermediate scrutiny standard to be applied
to commercial speech.''), aff'd, 944 F.3d 267, 290 (D.C. Cir. 2019)
(``Sorrell's concerns about suppression of advertising messages in the
marketplace of ideas are inapposite here.'').
    (Comment 35) Multiple comments expressed concerns about the
difficulty of creating marketing plans for the first year of product
marketing given that the time it has taken FDA to review PMTAs to date
has been unpredictable. Specifically, comments stated that the
requirement for marketing plans in proposed Sec.  1114.7(f)(2) did not
take into account the considerable external variables that inform
marketing plan decisions including competitor activities, FDA actions
and State or Federal legislation. Comments noted that FDA's evaluation
of the IQOS PMTA, for example, stretched over 2 years. The comments
requested more flexibility in their marketing plans, including the
potential to amend their plans during application review, to avoid
being locked into outdated plans that do not account for the use of new
technology or to allow for adjustment.
    (Response 35) FDA has revised and narrowed the scope of Sec.
1114.7(f)(2) to require an applicant's description of its marketing
plans to discuss certain key, high-level aspects of its plans to market
the product for the first year after receiving a marketing granted
order. FDA notes that the applicant's description of its marketing
plans does not by itself create rigid requirements regarding the way in
which an applicant must market its new tobacco product; however, where
an applicant proposes a specific restriction on its marketing of the
new tobacco product to support an APPH finding as part of its
description of its marketing plans (e.g., avoiding online social media
without access restrictions), FDA might incorporate such proposals into
the restrictions on the sales and distribution of a new tobacco product
in a marketing granted order as set forth in Sec.  1114.31(b).
Additionally, FDA will monitor an applicant's implementation of its
marketing plans as described in the application to ensure the marketing
of the new tobacco product continues to be APPH. Applicants are
required to report information about the marketing of their product
under Sec.  1114.41(a)(1)(xi), and FDA may require submission of
marketing plan changes in advance of implementation under Sec.
1114.31(b)(3).
    An applicant may alter or update its description of its marketing
plans during the course of application review by submitting an
amendment; however, as described in the response to comment 34, we
generally do not expect an applicant's approach to the high-level items
in Sec.  1114.7(f)(2) to change significantly after the submission of
an application. As described in section VIII.C., where such an
amendment requires significant review time (e.g., significant changes
to the intended audience(s) and how the marketing material and tactics
would be targeted thereto), it will be considered a major amendment for
which the review period will be extended by up to 180 days; however,
FDA will review such amendments promptly and generally expects review
of such changes will require fewer than 180 days.
    ii. Requirements for description of marketing plans. Section
1114.7(f)(2) requires a PMTA to contain a description of the
applicant's plans to market the new tobacco product, for at least the
first year the product would be marketed after receiving a marketing
granted order, in a way that permits FDA to determine whether this
information is consistent with the applicant's discussion of the
increased or decreased likelihood of changes in tobacco product use
behavior, including switching (i.e., complete transition to a different
tobacco product), initiation, cessation, and polyuse (i.e., using the
new tobacco product in conjunction with one or more other tobacco
products), under Sec.  1114.7(l), and whether permitting the new
tobacco product to be marketed would be APPH. This section requires
descriptions of actions to market the new tobacco product that would be
taken by the applicant, on behalf of the applicant, or at the
applicant's direction, and of any restrictions on the sales and
distribution of the new tobacco product that the applicant is proposing
to be included in the marketing granted order under section
910(c)(1)(B) of the FD&C Act. As set forth below, the description of an
applicant's plans to market a product will contain information that is
important to FDA's consideration of the likelihood of changes in
tobacco product use behavior (including initiation and cessation) under
section 910(c)(4) of the FD&C Act. The described changes in tobacco
product use behavior, when considered as part of FDA's determination of
the risks and benefits of the new tobacco product to the population as
a whole under section 910(c)(4) of the FD&C Act, form part of the basis
upon which FDA must make its finding of whether there is a showing that
permitting the marketing of the new tobacco product would be APPH under
section 910(c)(2)(A) of the FD&C Act. While the criteria for FDA to
accept and file the application in Sec.  1114.27 can be satisfied with
only some discussion of the four items in Sec.  1114.7(f)(2)(i) through
(iv), FDA encourages applicants to provide more detailed information to
help inform FDA's substantive APPH determination.

    An understanding of how an applicant plans to market a new tobacco
product for at least an initial period of time will help FDA determine
the potential for increases in health risks related to marketing of the
new tobacco product, such as the potential for youth initiation. If FDA
determines that the potential increases in health risks outweigh the
potential benefits, FDA would not be able to determine that the
marketing of the new tobacco product would be APPH and would issue a
marketing denial order.
    Section 1114.7(f)(2)(i) requires a PMTA to contain a description of
the specific group(s) to which the labeling, advertising, marketing,
promotion, and other consumer-directed activities for the new tobacco
product would be targeted (i.e., the intended audience(s)). As used in
Sec.  1114.7(f)(2), the term ``other consumer-directed activities''
includes any other types of action regarding the new tobacco product
taken by the applicant, on behalf of the applicant, or at the
applicant's direction that may directly or indirectly impact
information about the tobacco product that reaches consumers (e.g., use
of third parties or social media influencers to reach consumers).
Additionally, the labeling, advertising, marketing, promotion, and
other consumer-directed activities for a new tobacco product are
collectively referred to as ``marketing materials and activities'' in
this document for ease of reference. An applicant would need to provide
the characteristics it has used to identify the specific group(s) to
which its marketing materials and activities would be targeted, such as
age-range(s) (including young adult audiences ages 21 to 24 years, if
applicable) and other demographic characteristics, details of tobacco
use behaviors (e.g., dual use), and psychographic characteristics.
Examples of other demographic characteristics include, but are not
limited to, race, ethnicity, socioeconomic status and geographic
location (e.g., urban, rural). Such information will be informative to
FDA in identifying potential impacts of marketing on specific
populations, including vulnerable populations. Examples of types of
psychographic characteristics include, but are not limited to, hobbies,
interests, risk-taking behaviors, purchase behaviors, and online search
behaviors. Based on our experience, FDA generally expects that
applicants will have conducted or otherwise obtained market or consumer
research to determine its intended audience(s). Where an applicant has
conducted such research and has used the results to determine its
intended audience, FDA recommends an applicant discuss such information
in this section.
    As a general example, the description of the intended audience(s)
could include, for example, a statement that the applicant would target
its marketing materials and activities for the new tobacco product to
all current adult cigarette smokers, with a focus on cigarette smokers
aged 26 to 54 years who are seeking alternatives to combustible
cigarettes.
    Section 1114.7(f)(2)(ii) requires the applicant's description of
its marketing plans to contain a discussion of the ways in which the
applicant would target its marketing materials and activities for the
new tobacco product to reach the intended audience(s) described in
paragraph (i) and what other group(s) would foreseeably be exposed to
the marketing materials and activities as a result. A discussion of
these aspects of the plans can provide information that is important to
FDA's evaluation of the increased or decreased likelihood of changes in
tobacco product use behavior under section 910(c)(4) of the FD&C Act.
Describing how an applicant would target the marketing materials and
activities for the new tobacco product to intended audiences could help
FDA determine whether the applicant's descriptions of its marketing
plans are consistent with information in the application regarding the
likelihood of changes in tobacco product use behaviors, such as current
tobacco product users switching to the new tobacco product.
    A discussion of the ways in which the applicant would target the
marketing materials and activities for a new tobacco product to reach
the intended audience(s) can include items such as: how the applicant
would use key insights about its intended audience(s) to tailor its
marketing approach; the types and sources of data, technologies, and
methodologies the applicant would use to develop, implement, and track
targeted paid media plans (e.g., first and second-party age-verified
data, public records, industry-standard syndicated research services,
and embedded tracking pixels in digital advertising); and the marketing
channels and tactics an applicant expects to use.
    Additionally, this information will help FDA determine whether the
identified audiences and not other audiences, such as individuals below
the minimum age of sale, would be exposed to the marketing materials
and activities for the new tobacco product. Describing the other groups
that would foreseeably be exposed to the marketing materials and
activities for the new tobacco product will help FDA understand the
potential for other groups to be affected by the plans to market the
new tobacco product. For example, where an applicant's plans to target
its marketing materials and activities to an intended audience of adult
consumers has the potential to reach individuals below the minimum age
of sale, an applicant would have to note that potential and describe
whether the potential would be limited under paragraph (iii). FDA is
requiring a discussion of an applicant's plans to target its marketing
materials and activities to the intended audience(s) and the other
groups that could foreseeably be exposed to those materials as a result
of such targeting because, as discussed in the following paragraphs,
there is a well-established body of scientific evidence regarding the
effect of advertising and marketing on tobacco product behavior (see
e.g., Refs. 19-22).
    Section 1114.7(f)(2)(iii) requires the applicant's description of
its marketing plans to contain a discussion of the ways in which, for
individuals below the minimum age of sale, access to the new tobacco
product would be restricted and exposure to the marketing materials and
activities for the new tobacco product would be limited. Describing the
ways in which an applicant would restrict access to the new tobacco
product by individuals below the minimum age of sale would be an
important part of FDA's consideration under section 910(c)(4) of the
FD&C Act regarding the increased or decreased likelihood that persons
who do not use tobacco products will start using the tobacco product
that is the subject of the application. Limiting the potential for
youth to access the new tobacco product is one way to help mitigate the
potential for youth initiation with the new tobacco product (Refs. 23
and 24). For example, an applicant could propose to restrict the sale
and distribution of its new tobacco product to adult-only facilities
and limit the quantity of its product that an adult customer (other
than scientific researchers or research institutions) may purchase
within a given period of time to limit the potential for resale to
youth.
    Describing the ways in which an applicant would plan to limit the
exposure of individuals below the minimum age of sale to the marketing
materials and activities for the new tobacco product would also help
FDA assess the potential for initiation with the new tobacco product by
this group. Examples of how applicants could limit the exposure of
individuals below the

minimum age of sale to the marketing materials and activities could
include actions such as utilizing services that compare consumer
information against independent, competent, and reliable data sources,
such as public records, before granting users access to the applicant's
tobacco product website(s), using only first- or second-party age-
verified data to target paid digital advertising, and limiting sales to
adult-only stores. Applicants could also restrict or avoid the use of
marketing practices that are not or cannot be targeted in ways that
would limit exposure of individuals below the minimum age of sale and
choose tactics more narrowly targeted to current adult users of tobacco
products, such as avoiding online social media without access
restrictions to promote the tobacco product and, instead, choose
actions such as paper or electronic mail directed only to current
smokers at or above the minimum age of sale.
    FDA is requiring the description of an applicant's plans to market
the new tobacco product to contain a discussion of an applicant's plans
to target the marketing materials and activities to reach the intended
audience(s) and limit the exposure of individuals below the minimum age
of sale to such materials and activities, because there is a well-
established body of scientific evidence regarding their effect on
tobacco product use behavior (see e.g., Refs. 19-22). The impact of
tobacco marketing tactics on youth and young adult tobacco use behavior
in particular has been well documented. The 2012 Surgeon General's
report entitled ``Preventing Tobacco Use Among Youth and Young
Adults,'' (the 2012 SGR) synthesizes more than 30 years of research on
the topic and outlines the findings demonstrating that product
labeling, advertising, marketing, and promotion influence youth tobacco
use by shaping attitudes, beliefs, and risk perceptions, and promoting
pro-tobacco social and cultural norms (Ref. 9). The 2012 SGR states
that the strong empirical evidence, along with the tobacco industry's
own internal documents and trial testimony, as well as widely accepted
principles of advertising and marketing, support the conclusion that
tobacco manufacturers' advertising, marketing, and promotions recruit
new users as youth and continue to reinforce use among young adults
(Ref. 9). The 2012 SGR states that this evidence is sufficient to
conclude that marketing efforts and promotion by tobacco companies show
a consistent dose-response relationship in the initiation and
progression of tobacco use among young people (Ref. 9). The 2012 SGR
also states that research conducted by the tobacco industry
consistently demonstrates that the brand imagery portrayed on packages
is particularly influential during youth and young adulthood--the
period in which smoking behavior and brand preferences develop. The
2016 Surgeon General's report entitled, ``E-Cigarette Use Among Youth
and Young Adults,'' similarly synthesizes research on e-cigarettes and
concluded that e-cigarette manufacturers used tactics similar to those
used to market conventional cigarettes to youth and young adults (Ref.
15).
    The National Cancer Institute (NCI) made a similar conclusion in
its monograph, ``The Role of the Media in Promoting and Reducing
Tobacco Use,'' that the total weight of evidence--from multiple types
of studies, conducted by investigators from different disciplines, and
using data from many countries--demonstrates a causal relationship
between tobacco advertising and promotion and increased tobacco use
(Ref. 20). As such, the direct role of tobacco product marketing and
related activities in increasing tobacco use in the United States,
especially among youth, and the high rates of youth-exposure to tobacco
marketing due to its ubiquity, are two key rationales cited by NCI for
restricting tobacco product marketing and related activities (Ref. 20).
A variety of research has found that exposure to advertising is
associated with susceptibility to use tobacco products and the actual
use of tobacco products (see e.g., Refs. 25-33). For example, research
has found that the use of certain kinds of imagery, such as logos and
cartoons, have an impact on youth tobacco initiation (see, e.g., Refs.
34-36) and that a key tactic of tobacco companies seeking to attract
and recruit youth users is to use advertising and marketing with
aspirational imagery and themes known to resonate with younger
audiences, such as independence, popularity, rebelliousness,
attractiveness, and being cool (Ref. 9).
    An analysis of the 2011 National Youth Tobacco Survey (NYTS) found
that adolescents who reported frequent exposure to tobacco advertising
at the point of sale and on the internet had significantly higher odds
of ever using e-cigarettes and that there was a dose-response
association between the number of marketing channels to which they were
exposed and whether they used tobacco products (Refs. 15 and 33). An
analysis of 2014 NYTS data assessing exposure to e-cigarette
advertising in different channels (i.e., internet, print, television
and movies, retail stores) found that as the number of channels of e-
cigarette marketing exposure increased, the likelihood of use and
susceptibility also increased (Refs. 15, 37, and 38). Thus, providing
information regarding the ways in which an applicant would target the
marketing materials and activities for the new tobacco product to reach
the intended audience(s) and limit the exposure of individuals below
the minimum age of sale to such items can provide valuable insight into
the potential that youth would initiate tobacco product use.
    Finally, Sec.  1114.7(f)(2)(iv) requires the description of an
applicant's marketing plans to contain a concluding summary discussing
how the applicant's plans for marketing the new tobacco product are
consistent with the applicant's discussion regarding the increased or
decreased likelihood of changes in tobacco product use behavior
(including switching, initiation, cessation, and polyuse) under Sec.
1114.7(l) and permits FDA to determine whether permitting the marketing
of the new tobacco product would be APPH. This section requires an
application to contain a discussion of how each of the items in Sec.
1114.7(f)(2)(i) through (iii) are consistent with the applicant's
discussion regarding the increased or decreased likelihood of changes
in tobacco product use behavior by both current users and nonusers of
tobacco products. This includes, but is not limited to: How the planned
targeting of intended audience(s) is consistent with discussions
regarding the likelihood of changes in tobacco product use behavior
such as by current adult users, including switching, quitting, and
polyuse; and how, for individuals below the minimum age of sale,
restrictions on access to the new tobacco product and limitations on
exposure to the marketing materials and activities for the new tobacco
product are consistent with discussions regarding the likelihood of
tobacco product use initiation, including among youth. For example,
where an applicant expects current adult cigarette smokers to use its
new tobacco product, the applicant would be required to explain its
basis for concluding that its planned marketing is consistent with that
expectation, such as providing an explanation of how the applicant
determined its selected marketing channels and tactics would reasonably
reach its intended users. Similarly, if an applicant claims its
marketing plans would adequately prevent or reduce youth initiation,
the applicant would be required to explain its basis for such a
conclusion by

providing explanations of any measures or controls the applicant would
use to restrict youth access to the product (e.g., selling the product
only in brick-mortar retail locations), using competent and reliable
third-party services to verify the age and identity of product
purchasers, implementing purchase quantity limits) and limit youth
exposure to the product's marketing materials and activities (e.g.,
restricting its marketing to channels and tactics where it is possible
to target delivery of advertising to only age-verified adults).
    An applicant can use this portion of the summary as an opportunity
to help show the description of its marketing plans are consistent with
its expectations for the potential initiation by current nonusers of
tobacco products. For example, where conclusions drawn from tobacco
product perception and use intention studies contained in a PMTA show
the potential for current nonusers to initiate tobacco product use with
the new tobacco product, an applicant could discuss how its plans to
market the tobacco product, such as advertising at only point-of-sale
locations for tobacco products or sending direct mail marketing to
individuals of legal purchasing age who have opted-in to such
communications, would mitigate the potential for initiation by nonusers
and aligns with the applicant's discussion of such potential under
Sec.  1114.7(l).
    In addition to the basic requirements of Sec.  1114.7(f)(2), to
help inform FDA's APPH determination, applicants may develop and submit
more detailed plans to implement specific marketing campaigns. Not only
would this provide an applicant the opportunity to further address any
concerns about the potential for youth to initiate tobacco product use
with the new tobacco product, it would be an opportunity for an
applicant to more concretely show how it would target its marketing
materials and activities to reach the intended audience(s).
    The types of more detailed marketing plan information an applicant
could develop and submit as part of a PMTA include materials such as
strategic creative briefs, media and distribution channels, specific
tactics, and the intended scope of each marketing activity (e.g.,
information such as the expected reach and frequency of audience
exposures to the marketing, and timing and duration of the marketing
activities), and the information described in the items listed below.
These details, if provided, should be provided as part of the
appropriate discussion under Sec.  1114.7(f)(2) (if applicable) and can
include:
     A description of specific insights about the intended
audience(s) (e.g., findings from consumer research) that have informed
the applicant's marketing plans, including its strategic approach, key
messages and themes, creative direction, and potential tactics or
marketing channels. This could include product-specific insights (e.g.,
an audience's impressions of one product being just as harmful as
another, preference of a certain brand), as well as other beliefs,
interests, motivations, or behaviors that can be used to tailor an
applicant's approach to marketing the product. This could also include
information regarding where the intended audience(s) tends to consume
marketing and advertising (e.g., television programs the intended
audience(s) watches, social media influencers the intended audience(s)
follows, websites and retail locations the intended audience(s)
frequents) that can be used to tailor an applicant's approach, select
relevant marketing tactics, and use relevant marketing channels. The
applicant should describe such insights in either paragraph (i) or
(ii), as appropriate, and state the source of such data;
     plans to use owned, earned, shared, or paid media to
create labeling for, advertise, market, or promote the tobacco product.
While media categories overlap, owned media typically consists of a
company's own media properties and content they control, such as the
company's product-branded website or mobile application. Earned media
typically consists of unpaid media publicity or coverage of a company's
brand or product that the company did not commission or pay for, such
as a news article about the product or an influencer talking about a
company's product without compensation. Examples of plans to use earned
media can include, but are not limited to, pitching articles to news
outlets, using unsolicited consumer reviews or testimonials to promote
the product, and inviting influencers or reporters to attend a product
launch event. Shared media typically consists of social media
properties, such as a company's social media accounts and content,
including interactions with other social media users and their content,
such as comments, ``likes,'' and responses to comments. Paid media
typically consists of content that a company pays to place and promote
in media properties it does not own, such as advertising appearing on
television and radio, in and around retail stores, and in digital
media, including content shared by a celebrity who a company pays to
promote the tobacco product;
     plans to use (or not use) partners, influencers (e.g.,
celebrities, cultural icons, individuals with substantial followers on
social media), bloggers, or brand ambassadors to create labeling for,
advertise, market, or promote the tobacco product;
     plans to conduct (or not conduct) consumer engagements,
including events at which the tobacco product will be demonstrated; and
     plans to use public relations or other communications
outreach to promote the tobacco product. Public relations could consist
of actions such as using a public relations firm to promote the tobacco
product. Other communications to promote the product could consist of
actions such as direct mail to consumers.
7. Statement of Compliance With Part 25
    A PMTA must contain an environmental assessment (EA) prepared in
accordance with Sec.  25.40 or a valid claim of a categorical
exclusion, if applicable. Pursuant to Sec.  25.15(a), all submissions
requesting FDA action require the submission of either a claim of
categorical exclusion or an EA. In accordance with Sec.  25.40(a), an
EA must include, at a minimum, brief discussions of: The need for the
proposed action; alternatives to the proposed action as required by
section 102(2)(E) of the National Environmental Policy Act of 1969
(NEPA); the environmental impacts of the proposed action and
alternatives; the Agencies and persons consulted during the preparation
of the EA; and the relevant environmental issues relating to the use
and disposal of the tobacco product. Although applicants may wish to
review the categorical exclusions specific to tobacco product
applications at Sec.  25.35, the only categorical exclusion currently
available for a marketing order is for provisional SE reports that
receive an SE order in the SE premarket pathway, not for PMTAs. If the
applicant believes the action would qualify for an available
categorical exclusion, the applicant must state under Sec.  25.15(a)
and (d) that the action qualifies for a categorical exclusion, cite to
the claimed exclusion, and state that to the applicant's knowledge no
extraordinary circumstances exist under Sec.  25.21.
    Failure to include an EA in a PMTA is grounds for FDA to refuse to
accept an application and failure to include an adequate EA is
sufficient grounds under Sec.  25.15 for FDA to refuse to file the PMTA
or refuse to issue a marketing

granted order. (See the discussion of Sec. Sec.  1114.27 and 1114.29 in
section IX.)
8. Summary
    Section 1114.7(h) requires the application to contain a summary of
the application contents in sufficient detail to provide FDA with an
adequate understanding of the data and information in the application.
FDA requires the summary under authority of sections 701(a) and
910(b)(1)(G) of the FD&C Act because it provides FDA with an
understanding of the information contained in the PMTA and allows FDA
to plan and conduct a more efficient review of the detailed technical
information the summary describes. The summary also helps reviewers
understand the product and the accompanying scientific data more
quickly and allows applicants to highlight information they believe
demonstrates their product should receive a marketing granted order.
    The summary should discuss all aspects of the PMTA and synthesize
the application in a well-structured, unified manner. The summary
should serve as a briefing document that highlights the most important
aspects of the application, with each section of the summary consisting
of a brief explanation of information that the applicant believes
contributes to a finding that permitting the marketing of the product
would be APPH. The applicant must summarize the content included in the
PMTA in a manner that describes the operation of the product, the
health risks of the new tobacco product, the product's effect on
tobacco use behavior of current users, the product's effect on tobacco
use initiation by nonusers, and the product's effect on the population
as a whole. The summary must describe the new tobacco product's
potential effects on youth, young adults, and other relevant vulnerable
populations. After reviewing comments on the proposed rule, FDA has
added vulnerable populations to this requirement in the final rule to
ensure the summary specifically accounts for those groups that may be
disproportionately affected or more likely to use the new tobacco
product. The summary must contain the following items, where
applicable:
     A summary of the product formulation section of the
application. This section should provide a high-level description of
the product formulation section of the application, highlighting
information such as key ingredients, constituent levels, and design
aspects of the product. See the discussion of Sec.  1114.7(i) in
section VIII.B.9;
     a summary of the manufacturing section of the application.
This section should provide an overview of the manufacturing section of
the application, including activities at each facility, and highlight
information such as major aspects of the manufacturing and controls,
especially those that the applicant believes contribute to a finding
that permitting the marketing of the product would be APPH (e.g., an
aspect of the manufacturing process that results in lower levels of
HPHCs than other tobacco products in the same category). See the
discussion of Sec.  1114.7(j) in section VIII.B.12;
     a summary of the health risk investigations section of the
application. This section should briefly describe and synthesize the
findings of each investigation describing the following items, and
explicitly identify areas in which there is a lack of information, if
any:
    [cir] The health risks of the tobacco product to both users and
nonusers of the product (including youth, young adults, and other
relevant vulnerable populations) and whether the tobacco product
presents less health risk than other tobacco products, such as the risk
of cancers (e.g., lung, mouth, pancreatic), heart disease, stroke, or
lung disease, compared to other categories of tobacco products and
other tobacco products within the category, if known. See the
discussion of Sec.  1114.7(k)(1)(i) in section VIII.B.13.a.iii.;
    [cir] The impact the product and its marketing will have on the
likelihood of changes in tobacco use behavior of tobacco product users
(including youth, young adults, and other relevant vulnerable
populations), including cessation, switching (i.e., to a different
tobacco product), and polyuse (i.e., using the new tobacco product in
conjunction with one or more other tobacco products). See the
discussion of Sec.  1114.7(k)(1)(ii) in section VIII.B.13.a.iv.;
    [cir] the impact the product and its marketing will have on the
likelihood of tobacco use initiation by tobacco products nonusers,
especially youth, young adults, and other relevant vulnerable
populations, including among never users and former users, and the
likelihood of polyuse and switching behaviors. See the discussion of
Sec.  1114.7(k)(1)(iii) in section VIII.B.13.a.v.;
    [cir] How users and nonusers perceive the risk of the tobacco
product based upon label, labeling, and advertising (if any has been
studied). This includes how the label, labeling, and advertising affect
use intentions. See the discussion of Sec.  1114.7(k)(1)(iv) in section
VIII.B.13.a.vi.;
    [cir] whether users are able to understand the labeling and
instructions for use, and use the product in accordance with those
instructions. See the discussion of Sec.  1114.7(k)(1)(iv) in section
VIII.B.13.a.vi.; and
    [cir] the impact of human factors on the health risks to product
users and nonusers including, for example, how various use and misuse
scenarios may impact the health risks posed by the product. See the
discussion of Sec.  1114.7(k)(1)(v)) in section VIII.B.13.a.vii..
    The rule also requires the summary to contain a concluding
discussion demonstrating how the data and information contained in the
PMTA both constitute valid scientific evidence and establish that
permitting the marketing of the new tobacco product would be APPH as
determined with respect to the risks and benefits to the population as
a whole, including users and nonusers of the tobacco product. The rule
also requires the summary to identify any key or pivotal studies on
which an applicant is relying to establish that permitting the
marketing of the new tobacco product would be APPH. FDA recommends that
this discussion include estimates of the effect that the new tobacco
product may have on the health of the population as a whole, such as
effects on tobacco use initiation switching and cessation, and
reductions in premature mortality, or increases in life-years lived.
The estimates should integrate all of the information in the PMTA
regarding the product and its potential effects on health, including,
but not limited to adverse experiences, tobacco use behavior, and
tobacco use initiation to provide an overall assessment of the
potential effect that permitting the product to be marketed has or may
have on overall tobacco-related morbidity and mortality.
    As an illustration, an applicant may make an overall assessment of
whether the product will likely have a net benefit on population health
by accounting for potential reductions in disease risk (compared to
other tobacco products) and the potential for current tobacco users to
switch to the new tobacco product, and weighing that against the
potential for nontobacco users to use the tobacco product and the
accompanying potential increases in disease risks among those new
tobacco product users. An applicant should provide quantitative
assessments in the concluding discussion wherever possible; however, an
applicant may provide qualitative assessments where

appropriate for the type of investigation(s) on which the assessment is
based (e.g., focus group or interview-type studies).
    The summary's concluding discussion must also briefly describe why
the data and scientific information on which the applicant relies in
concluding that permitting the marketing of the product would be APPH
constitute valid scientific evidence. Section 910(c)(5)(A) of the FD&C
Act requires FDA to make its determination of whether permitting the
marketing of a new tobacco product would be APPH, where appropriate, on
the basis of well-controlled investigations; however, under section
910(c)(5)(B) of the FD&C Act, where FDA determines that there exists
valid scientific evidence other than well-controlled investigations
that is sufficient to evaluate the product, FDA may use such evidence.
As discussed in more detail in section IX.D regarding Sec.  1114.31,
FDA considers valid scientific evidence to be evidence gathered using
well-established or standardized methodologies from which it can be
concluded by qualified experts that there is reasonable assurance of
the reliability of its findings. Thus, if an application contains
information regarding another tobacco product (e.g., published
literature, marketing information) with appropriate bridging studies
and describes the relationship to the product that is the subject of
the application, FDA will review that information to determine whether
it is valid scientific evidence sufficient to demonstrate that
permitting the marketing of a product would be APPH.
9. Product Formulation
    Section 910(b)(1)(B) of the FD&C Act requires that a PMTA contain a
full statement of the components, ingredients, additives, and
properties, and of the principle or principles of operation, of such
tobacco product. Section 1114.7(i) implements FDA's interpretation of
this statutory requirement, together with its authority under section
910(b)(1)(G) of the FD&C Act, by requiring a PMTA to contain the
following information:
    a. Components or parts, materials, ingredients, additives, and
constituents. Under the rule, the application is required to contain a
full statement (i.e., a listing) of the product components or parts,
materials, ingredients other than tobacco, tobacco ingredients, HPHCs,
and the container closure system.
    i. Components or parts. Section 1114.7(i)(1)(i) requires the
application to state the quantity, function, and purpose of, and where
applicable, target specifications of each component or part in the
product. This information should also include an explanation of how
each component or part is, or can be, integrated into the product
design, and the purpose and function of each component or part. Where
the tobacco product contains software components, the rule requires:
     A description of the software or technology (e.g.,
Bluetooth);
     a description of the purpose of the software or
technology, such as monitoring where the tobacco product is located,
activated, or used;
     a description of the data collected by the software and
how this information will be used by the applicant.
    FDA received comments regarding this section, as discussed below.
    (Comment 36) One comment stated that the rule should be amended to
state that FDA will issue a marketing denial order if the application
does not include specific assurances and evidence that there will be no
communication between the device and any external source, and that the
software would not be programmed to increase consumption.
    (Response 36) We agree that understanding how any software in a
product may function is important to the review of an application. For
example, software used in or with some consumer products may have
functions and purposes that are not immediately clear, such as use
monitoring and location tracking functions, and may be able to function
in conjunction with other electronic devices, such as a smart phone. We
decline to prohibit all communication between a new tobacco product and
external sources as part of this rulemaking because product standards
are outside the scope of this rulemaking; however, we will consider
information regarding software (if applicable) as part of substantive
review. For example, if the product has software features that could
help prevent youth use of the tobacco product, FDA would review this
information as part of the determination of whether permitting the
marketing of the new tobacco product would be APPH. This information is
especially important as it may not be readily apparent from a component
or part's identity what function and purpose it may serve.
    (Comment 37) One comment stated that FDA should amend Sec.
1114.7(i)(3)(ii) to also require specification of software or other
controls in an e-cigarette to limit the intensity of use, including
minimum inter-puff interval and maximum number of puffs per hour that
the device will deliver because, unlike with combusted cigarettes,
there are no obvious indicators for consumers of how quickly they are
consuming the product.
    (Response 37) As discussed in section VIII.B.10., FDA requires the
PMTA to contain a full narrative description of the way in which a
typical consumer will use the new tobacco product. This includes, for
example, a description of how a consumer operates the product, where
applicable, whether and how a consumer can change the product design
and add or subtract ingredients, the length of time it takes for a user
to consume a single unit of the product, and whether the product
incorporates a heating source and, if it does, a description of the
heating source. As described above, the presence of software or other
controls in an e-cigarette to limit the intensity of use would be
relevant to FDA's review of an application and a required part of a
PMTA submission under Sec.  1114.7.(i)(1)(i); however, FDA declines to
require such controls in all e-cigarettes as part of this rule because
it would constitute a product standard that is outside the scope of
this rule.
    ii. Materials. Section 1114.7(i)(1)(ii) requires the application to
contain information for each material in the product because materials
can affect the performance of the product. FDA considers materials to
be part of ``components'' under section 910(b)(1)(B) and the required
materials information is relevant to the subject matter of a PMTA under
section 910(b)(1)(G) because it is needed to fully characterize the
tobacco product and understand its health risks. For example, in
portioned smokeless tobacco products, the materials used in the pouch
can affect the rate at which nicotine is released and specifications
such as pouch fabric air permeability can provide information about how
quickly nicotine can be delivered to the consumer. For ENDS, the
material used in the construction of an electrical heater coil
influences its resistance and the temperature reached by the coil,
which in turn may affect the type and amount of HPHCs produced in
aerosol. The rule requires a PMTA to contain:
     The material name and common name (if applicable);
     the component or part of the tobacco product where the
material is located;
     the subcomponent or subpart where the material is located
(if applicable);
     the function of the material;
     quantities (including ranges or means and acceptance
limits) of the materials(s) in the new tobacco product;

     specifications (including quality, grades, and suppliers)
of the materials used for the new tobacco product (including any
specification variations, if applicable); and
     any other material properties that fully characterize the
new tobacco product, such as pouch material porosity or air
permeability for portioned smokeless products. While failure to include
additional material properties to fully characterize the tobacco
product would not serve as the basis for FDA refusing to accept or file
an application under Sec.  1114.27(a)(1), it may slow down the
substantive review process.
    FDA received comments regarding this section, as described below.
    (Comment 38) One comment requested that FDA clarify the scope of
the materials that an applicant would have to describe in a PMTA,
specifically requesting that FDA require PMTAs for e-cigarettes to
contain information on only those materials that are reasonably
expected to have contact with the e-liquid and not materials found in
items such as the exterior plastic casing, electronic circuitry, and
batteries. The comment stated that this would align with FDA's current
approach set forth in the guidance entitled ``Listing of Ingredients in
Tobacco Products.'' \19\
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    \19\ Available at https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance.
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    (Response 38) FDA declines to limit the scope of the materials in
an ENDS for which an applicant would have to provide information in a
PMTA to only those materials that are reasonably expected to have
contact with the e-liquid. As discussed in section Sec.  1114.3, FDA
defines material to mean an assembly of ingredients. Materials are
assembled to form the tobacco product, or components or parts of the
tobacco product. This includes both those materials that are in contact
with the e-liquid as well as any other materials in the product, such
as those used in the exterior plastic casing, electronic circuitry, and
batteries. FDA declines to limit the scope of materials for ENDS
because they are components or parts with the potential to introduce,
diffuse, leach or extract to become part of the e-liquid formulation or
constituents during storage and use. For example, batteries and solder
joints of the product have been shown to be the potential source of
metals contamination in e-liquid or aerosol (Ref. 39). Furthermore,
defective or damaged batteries on their own may lead to battery failure
or overheating, resulting in thermal runaway; thermal runaway has been
identified as an immediate threat in e-cigarettes, particularly due to
the metal enclosure of the e-cigarette batteries that allow the
dangerous build-up of gasses (Ref. 40). In addition, the guidance for
industry, entitled ``Listing of Ingredients in Tobacco Products,''
discusses FDA's current enforcement policy for ingredient listing
submission requirements under section 904(a)(1) of the FD&C Act. While
FDA does not intend to enforce ingredient listing requirements for
component and parts such as electrical components, batteries, and
electronic circuitry, FDA recognizes that the ingredients of these
other components and parts can also be important in determining the
public health impact of tobacco products. As the guidance states, FDA
will receive ingredient information for these other components and
parts during our premarket review of new tobacco products. This is
consistent with the rule's requirement to include information on
materials in a PMTA.
    iii. Ingredients other than tobacco. Section 1114.7(i)(1)(iii)
requires that the application contain information on ingredients other
than tobacco (tobacco ingredients are addressed in Sec.
1114.7(i)(1)(iv)). The application must contain:
     International Union of Pure and Applied Chemistry (IUPAC)
chemical name and common name (if applicable);
     Chemical Abstracts Service (CAS) number or FDA Unique
Ingredients Identifier (UNII). Both the IUPAC and CAS or UNII are
required to ensure FDA has the relevant information associated with
each identifier and to allow FDA to efficiently differentiate between
similar ingredients;
     the function of the ingredient;
     the quantity of the ingredient in the tobacco product,
with the unit of measure (including ranges or means, and acceptance
limits) reported as mass per gram of tobacco for nonportioned tobacco
products and as mass per portion for portioned tobacco products (with
any specification variation, if applicable);
     the specifications (including purity or grade and
supplier); and
     for complex purchased ingredients, each single chemical
substance reported separately.
    Additionally, FDA recommends that an application contain any other
ingredient information to fully characterize the new tobacco product,
as applicable. While failure to include other ingredient information to
fully characterize the tobacco product would not serve as the basis for
FDA refusing to accept or file an application under Sec.