different questions of public health.
    [cir] The new tobacco product compared to the predicate has the
potential to affect use behavior such as an increase in initiation of
the product, especially among youth or other vulnerable populations; a
decrease in cessation; or use by different tobacco-use status groups.
    [cir] The new tobacco product compared to the predicate has
potentially higher abuse liability.
    [cir] The new tobacco product has the potential to increase
dependence.
    Based on these considerations, as well as other public health
considerations, FDA will determine whether the applicant has
demonstrated that any differences do not cause the new tobacco product
to raise different questions of public health.
    (Comment 41) Other comments request that FDA include a definition
of the phrase ``different questions of public health'' in the final
regulation. The comments assert that industry needs this information to
determine the appropriate pathway for its SE submission. Some comments
propose definitions of the phrase; for example, one comment proposes to
define the phase ``different questions of public health'' to mean when
``the new product as a whole raises questions of public health that are
significantly different in type and magnitude from those presented by
[Pre-Existing tobacco products] or other legally marketed tobacco
products.'' The comments contend that the analysis should look at
``different questions of public health'' as a whole rather than the
implications of the particular product as compared to another product.
One comment suggests that an applicant could satisfy the public health
analysis by providing HPHC data for both the new and predicate
products, and if none of the HPHCs for the new product are
statistically higher than the predicate product, then the new product
should pass the public health analysis. The comment suggests that
applicants could submit a quantitative risk assessment (QRA) (defined
by the comment as a magnitude of individual disease risk tool), and if
the new product is of no greater risk than the predicate product then
the new product should pass the public health analysis. This comment
also suggests that FDA should establish a QRA framework and ``identify
the number of product runs or batches necessary to generate HPHC
data,'' as well as publish this data so that manufacturers can generate
QRA category curves.
    (Response 41) We agree that changes in characteristics could cause
the new tobacco product to raise ``different questions of public
health'' where ``the new product as a whole raises questions of public
health that are significantly different in type and magnitude from
those presented by [Pre-Existing] or other legally marketed tobacco
products.'' However, instead of adopting a definition, we include
additional details in the preceding paragraphs on what we may consider
when determining if a new tobacco product raises different questions of
public health. The public health analysis of an SE Report involves the
evaluation of all toxicologically relevant changes, including HPHCs,
but also non-tobacco ingredient changes that may cause the new tobacco
product to raise different questions of public health. At this time, we
are not recommending the inclusion of QRA with SE Reports, as they are
not needed for the comparison of HPHCs from the new and corresponding
predicate tobacco products. If an applicant has scientific evidence
that a QRA would be supportive in evaluating the overall toxicological
comparison between a new and predicate tobacco product, we strongly
encourage the applicant to contact FDA and to justify the methodology
and applicability of a potential QRA before an applicant voluntarily
develops or submits a risk assessment, as the assessment may not

be needed or appropriate to support the SE Report.
    (Comment 42) Another comment asserts that a definition of different
questions of public health should include information that indicates a
product with a low usage rate will not impact public health.
    (Response 42) We disagree with the assertion that new tobacco
products with low usage rates would necessarily not impact public
health. Under section 905(j)(1)(A)(i) of the FD&C Act, the basis for
determining substantial equivalence is through the comparison of the
new tobacco product to the predicate tobacco product. Therefore,
providing prevalence of use (even if it indicates low usage) of the new
tobacco product without comparison to prevalence of use to a predicate
tobacco product is insufficient to determine if the new tobacco product
raises different questions of public health. In addition, differences
in the composition of users of the new and predicate tobacco products
may still raise DQPH even with low overall prevalence of use.
Furthermore, FDA's assessment of the product's impact on public health
goes beyond usage rate. For example, a new tobacco product that has a
low usage rate, but is found to be more toxic than the predicate
tobacco product (e.g., a tobacco product with higher HPHCs than the
predicate tobacco product) could raise different questions of public
health and be found not substantially equivalent. Moreover, prevalence
can change over time, and it can be difficult to predict the prevalence
of a new product before it is marketed.
 Tobacco Product
    We proposed to include the statutory definition of tobacco product
(section 201(rr) of the FD&C Act (21 U.S.C. 321(rr))). In the FD&C Act,
tobacco product is defined as any product made or derived from tobacco
that is intended for human consumption, including any component, part,
or accessory of a tobacco product (except for raw materials other than
tobacco used in manufacturing a component, part, or accessory of a
tobacco product). The term ``tobacco product'' does not mean an article
that under the FD&C Act is a drug (section 201(g)(1)), a device
(section 201(h)), or a combination product (section 503(g) (21 U.S.C.
353(g))). We discuss the comment related to this definition in the
following paragraphs, and we are including this definition in the final
rule without change.
    (Comment 43) At least one comment disagrees with FDA's
interpretation of tobacco product (i.e., as encompassing the whole
product and not limited to a single unit or portion) and argues that
FDA's interpretation is too broad, misinterprets the FD&C Act, and is
unnecessary.
    (Response 43) We disagree with these objections related to the
language included in the proposed rule's discussion of new tobacco
product and tobacco product. Rather, as noted in the proposed rule, and
supported by the Philip Morris decision, for purposes of determining
whether a tobacco product is new under section 910 of the FD&C Act, and
therefore requires premarket authorization prior to marketing, a
``tobacco product'' encompasses the whole product (e.g., a pack of
cigarettes or a tin of loose tobacco), and is not limited to a single
unit or portion of the whole product (e.g., a single cigarette or a
single snus pouch). (See Philip Morris, 202 F. Supp. 3d at 55-57.) If
an SE Report includes information on only a portion of a new tobacco
product, FDA would have an incomplete understanding of the tobacco
product (e.g., FDA may not get information on the container closure
system, which could impact the consumable product) and would not be
able to determine, for example, potential impacts on initiation and
cessation of tobacco use (information which may be needed for
determining whether there are DQPH).
 Tobacco Product Manufacturer
    We proposed to include the statutory definition of tobacco product
manufacturer in the rule (section 900(20) of the FD&C Act). The statute
defines tobacco product manufacturer as any person, including a
repacker or relabeler, who: (1) Manufactures, fabricates, assembles,
processes, or labels a tobacco product or (2) imports a finished
tobacco product for sale or distribution in the United States. In the
following paragraphs, we discuss the comments related to this
definition. We are including this definition without change in the
final rule.
    (Comment 44) One comment requests that FDA clarify that ``an entity
that contracts with another domestic entity to manufacture a tobacco
product'' is included in this definition.
    (Response 44) The rule includes the definition of tobacco product
manufacturer from the FD&C Act, stating that ``tobacco product
manufacturer'' includes any repacker or relabeler and any person who
manufactures, fabricates, assembles, processes, or labels a tobacco
product; or imports a finished tobacco product for sale or distribution
in the United States (this term and definition are included in the
final rule). Under this definition, contract entities engaged in the
activities described in the definition of a tobacco product
manufacturer would fall within the scope of the definition of tobacco
product manufacturer.

D. Comments on Subpart C--Substantial Equivalence Reports and FDA
Responses

1. Submission of an SE Report (Sec.  1107.16)
    Proposed Sec.  1107.16 would establish when an applicant should
submit an SE Report. We received no comments on this proposed section,
and we are finalizing this section without change.
2. Content and Format of an SE Report (Sec.  1107.18)
    Proposed Sec.  1107.18 set out the required content and format of
SE Reports. This proposed section included requirements related to: (a)
Overview; (b) format; (c) general information; (d) summary; (e) new
tobacco product description; (f) description of predicate tobacco
product; (g) comparison information; (h) comparative testing
information; (i) statement of compliance with applicable tobacco
product standards; (j) health information summary or statement
regarding availability of such information; (k) compliance with part 25
(21 CFR part 25); and (l) certification statement. Proposed Sec.
1107.18(b) and (c) also included requirements for the use of Form FDA
3964 (Tobacco Amendment and General Correspondence Report) and Form FDA
3965 (Tobacco Substantial Equivalence Report Submission) (Refs. 8 and
9).
    After considering the comments, we are revising Sec.  1107.18 in
several places for consistency with other changes to the rule and to
add clarity. Specifically, in Sec.  1107.18(a), we have revised
language that previously referred to ``grandfathered'' to reflect the
statutory language related to what types of tobacco product can serve
as predicate tobacco products. We also added in paragraph (a) a cross-
reference to Sec.  1105.10 to clarify that FDA generally intends to
refuse to accept an SE Report for review if it does not comply with
both Sec. Sec.  1105.10 and 1107.18 to help ensure applicants are aware
that the requirements of both sections must be satisfied. As we explain
further below, we have made modifications to Sec.  1107.18(g) and (h)
to clarify what information is needed for acceptance for further
review.
    We are also revising Sec.  1107.18(c)(4) to add ``voluntary'' as a
modifier to ``request'' to further emphasize that

seeking an FDA determination relating to a potential predicate tobacco
product is a voluntary process. We revised Sec.  1107.18(c)(5) and (6)
to add ``including email address'' as information the SE Report must
include to help ensure we have complete contact information.
    We revised Sec.  1107.18(c)(7)(iii) (product category, product
subcategory, and product properties table) to help ensure that we are
able to identify and evaluate each product more accurately and
efficiently for purposes of SE review. Under this revised taxonomy,
some tobacco products may fit under more than one category. For
example, the cigarette product category no longer lists noncombusted
cigarettes as a subcategory. Instead, for purposes of SE review, a
``heated tobacco product'' category has been added to the
identification tables. This SE 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 be used only 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. Sec.  1107.18(c)(7)(iii) and 1107.19(a)(21) under the heated
tobacco product category.\9\ FDA believes these product categorizations
will help ensure that applications include the most relevant
information for their product, which in turn will speed up FDA's review
and ability to reach an authorization decision.
---------------------------------------------------------------------------

    \9\ The categorization of HTPs as a separate category from
cigarettes in this rule, as demonstrated in Sec. Sec.
1107.18(c)(7)(iii) and 1107.19(a)(21), does not extend to other
legal requirements beyond those associated with the SE review
process.
---------------------------------------------------------------------------

    Other changes to Sec.  1107.18(c)(7)(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;
and 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; 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 SE Report pertains, as it can be described further
through identification of additional properties (e.g., fine cut, long
cut). However, for the purposes of determining whether characteristics
related to tobacco cut size cause the new tobacco product to raise
different questions of public health, information to determine tobacco
cut size is required under Sec.  1107.19 for the product categories
specified in that section.
    Across all product categories, the subcategory of ``co-package''
has been removed from Sec.  1107.18(c)(7)(iii). If an applicant submits
an SE Report for a co-packaged tobacco product, the unique
identification of this co-packaged product would include 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 RYO tobacco filler and rolling
papers.
    In Sec.  1107.18(d)(2), we have added ``any differences in
characteristics do not cause the new tobacco product to'' instead of
``does not'' to clarify that this part of the sentence refers to
differences in characteristics.
    In Sec.  1107.18(e), we are deleting ``including the fermentation
process, where applicable, with information on the type and quantity of
the microbial inoculum and/or fermentation solutions'' as the SE Report
does not need to include this as part of a concise overview of the
process used to manufacture the new tobacco product. The information
that would have been submitted under this proposed requirement would
also be duplicative of the fermentation information that will be
submitted as part of the SE Report under Sec.  1107.19.
    In Sec.  1107.18(f), for the reasons explained earlier in this
preamble, we have removed references to ``grandfathered'' and instead
use language that reflects the statutory definition of predicate
tobacco product. We are also deleting from Sec.  1107.18 proposed
paragraph (f)(2)(i), which would have required the predicate tobacco
product to be in the same product category and subcategory as the new
tobacco product and making corresponding renumbering edits to this
subsection. As we discuss in later paragraphs, we are removing this
requirement because although it will likely be difficult for an
applicant to demonstrate substantial equivalence in this situation
(where the new product is in a different category or subcategory as its
selected predicate), it may, in rare cases, be possible for an
applicant to make a showing of substantial equivalence. In Sec.
1107.18(f)(2)(iii) (formerly (f)(2)(iv)), we have changed ``rescission
order'' to ``rescission action,'' which is a more accurate description.
    In Sec.  1107.18(g), we have made some minor clarifying edits, and
in Sec.  1107.18(h) we have added ``that has been demonstrated to be
fully validated'' following comparative testing, which is needed to
ensure the method is fit for purpose and the measured values can be
accurately compared between a new and predicate tobacco product. FDA
considers full validation of a quantitative analytical procedure to
include: (1) Accuracy; precision (repeatability, intermediate
precision, and robustness); (2) selectivity; (3) sensitivity (limit of
detection and limit of quantification); (4) linearity; and (5) range.
The performance criteria typically include information such as the
target analyte, an approximation of the range of concentrations of the
analyte in the sample, the intended purpose of the procedure (e.g.,
qualitative, quantitative, major component, minor component, etc.), and
the number of samples to be analyzed.
    We have also corrected minor typographical errors in proposed Sec.
1107.18(g) and (k)(2). We have also removed the phrase ``as described
in Sec.  1107.19'' from Sec.  1107.18(g) and (h) to better reflect that
FDA's determination of acceptability for review is not intended to be
an exhaustive review of the SE Report but rather is intended to serve
as a check that the SE Report generally includes required information
before FDA accepts an SE Report and proceeds to substantive review. For
the same reason, we also moved the detailed requirements related to
comparative testing from proposed Sec.  1107.18(h) to Sec.  1107.19.
    Both ``same characteristics'' and ``different characteristics'' SE
Reports must provide the information required by Sec.  1107.18(g). As
explained in Sec.  1107.18(g), if the new tobacco product

has limited changes to a characteristic(s) when compared to the
predicate tobacco product, and all other characteristics are identical
(e.g., a change to product quantity), the applicant must provide
comparison information related to any characteristic(s) that have
changed, but may certify that the other characteristics are identical
under Sec.  1107.18(l)(2).
    Where the new tobacco product has the same characteristics as the
predicate tobacco products, applicants need only explain that their SE
Report is a ``same characteristics'' report to satisfy the requirement
of Sec.  1107.18(h). Furthermore, as explained in Sec.  1107.18(h), an
applicant need not provide comparative testing information for any
characteristics that are identical between the new tobacco product and
the predicate tobacco product, and for which the applicant has
certified that the characteristics are identical under Sec.
1107.18(l)(2).
    The following paragraphs describe the comments we received on
proposed Sec.  1107.18 and our responses to those comments.
 Forms (Sec.  1107.18(b)-(c))
    Proposed Sec.  1107.18(b) and (c) included requirements that the
applicant use the forms that FDA provides when submitting an SE Report.
Following our consideration of the comments related to the forms, we
are finalizing these requirements without change. We describe the
comments to these subsections and our responses next.
    (Comment 45) At least one comment states that use of the FDA forms
should be optional rather than mandatory.
    (Response 45) We disagree. As explained in the proposed rule, the
requirements in this rule, including use of these forms, are intended
to provide clarity to applicants with respect to what they must submit
in an SE Report and to help ensure that an SE Report provides
information necessary for FDA to determine whether the new tobacco
product is substantially equivalent to a tobacco product commercially
marketed (other than for test marketing) in the United States as of
February 15, 2007. Additionally, use of a standardized form allows FDA
to receive information in a way that allows for faster processing and
uploading of the SE Report and its contents, thereby increasing
efficiency of the review process.
    (Comment 46) One comment believes FDA has underestimated the time
needed to complete the forms and did not explain how it arrived at
these estimates.
    (Response 46) FDA conducted a thorough analysis of the current
paperwork burden associated with the SE program and other similar
forms. After a further review of similar forms, we have adjusted Form
3965 to 45 minutes per response and Form 3964 to 10 minutes per
response. Using our knowledge of elements in an SE report FDA believe
we have applied the most accurate burden to the forms. Beyond entering
data into the form, we conclude that the burden for searching existing
data sources and gathering and maintaining the data needed, is
accounted for in the burden charts. FDA notes that the commenter did
not provide a recommendation for alternative estimates (see also
section IX of this final rule).
    (Comment 47) Another comment notes that although FDA appears to
recognize that the evidence required in an SE Report depends on whether
the new tobacco product has the ``same'' characteristics as the
predicate product or if the new tobacco product has ``different''
characteristics than the predicate product, this distinction is not
reflected in either the draft of Form FDA 3965 or the rule itself.
    (Response 47) The form has been revised to include a section where
the applicant would distinguish whether they are submitting a ``same
characteristics'' SE Report, or a ``different characteristics'' SE
Report. A ``same characteristics'' SE Report must describe the
modification(s) and include all of the other information required in
Sec.  1107.18. As described in previous paragraphs, however, an SE
Report submitted under the same characteristics prong would not be
required to provide the information described in Sec.  1107.19.
 General Information (Sec.  1107.18(c))
    Proposed Sec.  1107.18(c) listed the information that the SE Report
would be required to include. This information included general
administrative information specifying the type of submission (e.g., SE
Report or amendment to a report); unique identification of both the new
and the predicate tobacco products, as well as contact information.
Following our consideration of comments, we are finalizing Sec.
1107.18(c) with changes to reflect updates to Sec.  1107.18(c)(7)(iii)
(related to product category, product subcategory, and product
properties).
    (Comment 48) Several comments request clarity regarding the
proposed requirement that an SE Report include information about the
product's characterizing flavor. Specifically, the comments request FDA
to clarify the requirement or include a definition of the term, or seek
to understand if the purpose of the requirement is simply to see how
the applicant identifies the product (e.g., ``no characterizing
flavor'' or a ``particular flavor''). Some comments note that the only
information available is in an FDA memorandum, and they disagree with
how the memorandum explains that characterizing flavor should be
indicated by factors including chemical composition or olfactory
response (the comment cites an FDA document, entitled, ``Unique
Identification of Tobacco Products,'' November 2016, which is available
at: https://www.fda.gov/media/124658/download). Other comments request
that FDA consider only the toxicological effects rather than the effect
on user behavior, when considering the differences in characterizing
flavor between the new and predicate tobacco products.
    (Response 48) This final rule does not define characterizing
flavor. As part of uniquely identifying a new and predicate tobacco
product, the SE Report must include product property information on
whether the products have a characterizing flavor or not. The SE Report
may state, for example, that a new cigarette has ``none'' for the
product property of characterizing flavor. In addition, this
information is needed as part of fully characterizing a new tobacco
product to aid FDA during the review process and in making an SE
determination. When considering the differences in characterizing
flavor between the new and predicate tobacco products, FDA considers
both the toxicological effects and the effects on user behavior.
    (Comment 49) At least one comment indicates general disagreement
that a change in characterizing flavor should require submission of an
SE Report. The comment states that, if a new product includes a
different flavoring from the predicate, FDA should not require that an
SE Report be submitted for that new or different flavor but that, if an
SE Report is required, the product should not ``fail'' SE review
``unless the addition of flavor alters the chemistry of the product
such that it increases the inherent risks of tobacco-related diseases
in an individual user either through the introduction of new or greater
HPHCs.'' A comment also states FDA has not explained why a change in
characterizing flavor would require submission of an SE Report for a
product with different characteristics.
    (Response 49) We disagree that an SE Report should not be required
for a change in characterizing flavor. Section 910(a)(1) of the FD&C
Act establishes that any modification results in a new tobacco product.
A change to or

addition or deletion of ingredients that make up a characterizing
flavor renders a tobacco product ``new.'' For FDA to make an SE
finding, the SE Report must demonstrate that the new tobacco product is
substantially equivalent to the predicate tobacco product. As we
explain in previous paragraphs related to the definition of substantial
equivalence, at this time, an SE Report for the removal of a
characterizing flavor is likely to be able to come in as a same
characteristic SE Report as FDA has found such a change does not
require scientific data to show that the change does not cause the new
tobacco product to raise different questions of public health.
 New Tobacco Product Description (Sec.  1107.18(e))
    (Comment 50) Several comments object to requiring any manufacturing
information, such as the ``concise overview of the process used to
manufacture the tobacco product'' as provided in this subsection as
unnecessary in an SE review. These comments note that FDA should
address manufacturing procedures through manufacturing practice
regulations issued under section 906(e) of the FD&C Act (21 U.S.C.
387f). Another comment disagrees with these comments, stating that
information on manufacturing practices is important to ensure that
products are consistently produced.
    (Response 50) We agree with the comment suggesting that information
on manufacturing practices can be relevant to an SE determination.
Note, however, that a concise overview of the process used to
manufacture the new tobacco product is only needed where the
manufacturing process for the new tobacco product could affect the
characteristics of the new tobacco product beyond what is described
elsewhere in the SE Report. If the manufacturing process for the new
tobacco product does not affect the characteristics of the new tobacco
product beyond what is described elsewhere in the SE Report, an
applicant must state that to satisfy Sec.  1107.18(e)(3).
    As explained in the proposed rule, this overview would not need to
be an exhaustive discussion but enough information to enable FDA to
fully understand and compare the characteristics that can be affected
by the manufacturing process of the new tobacco product and the
predicate tobacco product. FDA has found during reviews of SE Reports
that changes in manufacturing may impact the characteristics of the
tobacco product, e.g., the quantities of nicotine (total and free), as
well as HPHCs such as TSNAs. Such changes could cause the new product
to raise different questions of public health, e.g., an increase in
TSNAs may increase the risk for certain types of cancer (Ref. 10).
    We disagree with the comments that suggest this information would
be more appropriately required through manufacturing practices
regulations issued under section 906 of the FD&C Act. Section 906
authorizes FDA to issue regulations requiring that the methods used in,
and the facilities and controls used for, the manufacture,
preproduction design validation (including a process to assess the
performance of a tobacco product), packing, and storage of a tobacco
product conform to current good manufacturing practice. Such
regulations could include comprehensive requirements on purchasing
controls, production and process controls, and requirements related to
acceptance activities and nonconforming products (see, e.g., 21 CFR
part 820). In comparison, Sec.  1107.18(e)(3) requires only a ``concise
overview'' of the process used to manufacture the new tobacco product''
to aid FDA in understanding in how the manufacturing process might
affect the characteristics (or, if the manufacturing process does not
affect the characteristics of the new tobacco product beyond what is
described elsewhere in an SE Report, an applicant may simply state
that). The requirement for a concise overview is vastly different from
the manufacturing information that may be required under a tobacco
products manufacturing practices regulation under section 906 of the
FD&C Act. Moreover, the purpose of the requirement in Sec.
1107.18(e)(3) is not for the purposes described in section 906 of the
FD&C Act but, rather, is to help ensure enough information to enable
FDA to fully understand and compare the characteristics that can be
affected by the manufacturing process of the new tobacco product and
the predicate tobacco product.
 Description of the Predicate Product (Sec.  1107.18(f))
    As described in an earlier paragraph in this section, we have made
changes to this subsection for consistency with changes that we made to
the definition of predicate tobacco product and other clarifying edits.
We also removed the requirement that a tobacco product to which a new
tobacco product is compared be in the same category and subcategory of
product as the new tobacco product. In the following paragraphs, we
describe the comments we received on this subsection and our responses.
    (Comment 51) Some comments object to the proposed requirement that
the new and predicate products be in the same category and subcategory.
The comments state, ``there is nothing in the statute to prohibit the
attempted use of cross-category comparisons in an SE submission'' and
also refer to the deeming final rule as suggesting such a comparison is
appropriate. The comments state that while cross-category comparisons
may be more burdensome or require more information, the comparison may
be appropriate and, therefore, applicants should be permitted to
attempt it.
    (Response 51) After careful review of the comments submitted and
our own experience, we agree and are no longer requiring that the new
and predicate products be in the same category and subcategory. We note
that it would likely be difficult for an applicant to demonstrate
substantial equivalence where the new product is in a different
category or subcategory as its selected predicate, but it may, in rare
cases, be possible for an applicant to make a showing of substantial
equivalence. For example, an applicant may be able to compare a new
snus tobacco product to a pouched moist snuff predicate tobacco
product.
    It continues to be critical, however, that an applicant select an
appropriate predicate tobacco product and provide the scientific
evidence demonstrating the new tobacco product is substantially
equivalent to that predicate. Even where there are differences in the
category or subcategory between the new and predicate tobacco products,
FDA could issue an SE order if the applicant provides scientific
evidence that demonstrates to FDA that differences between the new
product and the predicate product do not cause the new tobacco product
to raise different questions of public health. Comparison of a new and
predicate tobacco product is much easier, and more likely to result in
a finding of SE, if the new and predicate tobacco products are of the
same category and subcategory, as the basic characteristics of the
predicate and new products are likely to be more similar. For example,
manufacturers of ENDS may find it difficult to show that their product
is substantially equivalent to a combusted cigarette or a smokeless
tobacco product because of the differences in product properties.
    If an applicant chooses to compare a new and predicate tobacco
product that are not in the same category or subcategory, for FDA to be
able to conduct a review of the SE Report, the

applicant should provide a strong scientific justification for why a
product that may differ from the new tobacco product in even the most
basic of characteristics and parameters is an appropriate predicate and
how any differences in characteristics do not cause the new tobacco
product to raise different questions of public health. For example,
where the new and predicate tobacco products are not in the same
category or subcategory, an applicant could provide information to
demonstrate that users or likely users of the new product display very
similar tobacco product use behaviors (e.g., likelihood of initiation,
experimentation, switching, dual-use/polyuse, or cessation, as well as
actual use patterns, frequency and amount of use) in addition to
information on comparison of HPHCs exposure.
    (Comment 52) One comment agrees with the proposed requirement of
Sec.  1107.18(f) that an applicant include a single predicate product
for comparison and that a composite predicate tobacco product would be
inconsistent with the FD&C Act. Other comments disagree with FDA's
proposal to require manufacturers to identify a single predicate
product to compare to the new product. Several of these comments
contend that manufacturers should be able to use multiple predicates in
a single SE report, stating that permitting the use of multiple
predicates would be more consistent with statutory design and also
align with the substantial equivalence requirements for devices in
sections 510(k) and 513(g) of the FD&C Act. The comments state that we
have been inconsistent in our position regarding the use of predicate
products and contend that the one predicate approach described in the
proposed regulation would create problems for manufacturers because it
does not allow for product innovation. In support of this, some
comments refer to FDA webinars that suggest that use of two predicates
would be appropriate, an FDA decision to permit two predicates to be
used for a smokeless product, and an FDA policy memorandum that
acknowledges ``multiple predicate tobacco products are identified in an
SE Report'' (this comment referenced the FDA memorandum FDA, ``Use of
Surrogate Tobacco Products in SE Reports,'' September 2016. Available
at: https://www.fda.gov/media/124665/download). Some comments ask that,
if the final rule maintains the single predicate approach, applicants
be permitted to amend currently pending SE Reports to designate the
most appropriate predicate product.
    (Response 52) We disagree that the final rule should permit the use
of multiple predicate tobacco products in an SE Report. There is
nothing in the statutory language to support the assertion that the SE
comparison can be made to a range of predicate products, and doing so
would be inconsistent with the premise of SE review. Creating a new
tobacco product from a range of predicate tobacco products can raise
different questions of public health beyond those questions raised by
the individual predicates because of the way the various additives and
other features of a tobacco product interact to impact how chemicals
are handled by the body. Some of the ways chemicals can interact is to
alter how they are absorbed into the body, metabolized by the body, or
how they bind to receptors in the body.
    For example, acetaldehyde when present at a level that is below its
independent reinforcing effect could boost the reinforcing effect of
nicotine, the primary addictive substance in tobacco, beyond what it
would be without acetaldehyde present or the sum of the two independent
effects (Refs. 11 and 12). If a component from one predicate that
contains nicotine is mixed with a component from another predicate that
contains acetaldehyde, the synergistic effect of this mixture could
raise different questions of public health beyond the separate
predicates, because the addictiveness of the product could be greater
than either independently or the sum of the two predicate products
alone and may reduce cessation and increase initiation, thereby
impacting public health.
    Finally, the comments also cite instances where it appears that FDA
has suggested or permitted reference to two predicate tobacco products.
However, in the past, if an SE Report referenced multiple predicate
tobacco products, we generally have either broken this down into
multiple reports or have used a single predicate tobacco product for
comparison. This approach can result in delays in processing or
reviewing an SE Report, which the final rule seeks to prevent by
requiring use of single predicate tobacco product. With respect to the
comment that requests that FDA permit this for pending SE Reports, as
explained in previous paragraphs, this rule does not apply to pending
submissions.
    (Comment 53) Some comments suggest that requiring that predicate
tobacco products be ``fully characterized'' would be too restrictive
and have an anticompetitive impact. These comments state that the level
of detail required to fully characterize a predicate tobacco product
would necessarily limit each manufacturer to using its own products as
predicates and would become too difficult with the passage of time. The
comments also suggest there is no public health purpose to requiring
these data on predicates.
    (Response 53) We disagree. Demonstrating substantial equivalence
necessitates a comparison of physical characteristics between a new and
predicate tobacco product. In the absence of predicate product
characteristics, FDA is unable to conduct scientific review and fulfill
its statutory obligation. If an applicant does not have access to a
predicate product or wishes to use a predicate product they do not own,
one option is the use of a Tobacco Product Master File (TPMF) (see,
e.g., the guidance entitled ``Tobacco Product Master Files, which can
be accessed at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/tobacco-product-master-files). A TPMF is a file that
is voluntarily submitted to the Center for Tobacco Products (CTP) that
contains trade secret and/or confidential commercial information about
a tobacco product or component that the owner does not want to share
with other persons. TPMFs are a beneficial tool for manufacturers,
component suppliers, and ingredient suppliers, and can assist the
tobacco product submission process. Also, as discussed in the following
paragraph, if an applicant no longer manufacturers a predicate product,
it can be remanufactured and tested for the purposes of SE review, or a
surrogate may be appropriate for use in place of the actual predicate
tobacco product.
 Comparison Information (Sec.  1107.18(g)) (Surrogates)
    In the proposed rule, in the description of Sec.  1107.18(g), FDA
requested comment on the use of information from surrogate tobacco
products where there is inadequate data available for the new or
predicate tobacco product. FDA received several comments on the use of
information from surrogate tobacco products.
    (Comment 54) One comment states that manufacturers should not be
able to use a surrogate tobacco product in the place of a predicate
tobacco product. The comment argues that there is no statutory basis
for allowing this, and requests FDA to remove this from the final
regulation.
    (Response 54) Under the statute, applicants must submit an SE
Report that provides information to support that a new tobacco product
is

substantially equivalent to a predicate tobacco product. The use of
surrogate tobacco products in certain situations does not change those
statutory requirements. Although permitting use of a surrogate tobacco
product may provide an opportunity for applicants to provide stand-in
information in lieu of the precise predicate product itself, it is the
applicant's responsibility to provide FDA with adequate bridging
information for FDA to determine that it is appropriate to extrapolate
the data provided on the surrogate tobacco product to the actual
predicate product. Ultimately, FDA makes a determination as to whether
or not the new product is substantially equivalent to the selected,
valid predicate product.
    (Comment 55) Several comments request that FDA provide more
information regarding the use of surrogate tobacco products, including
whether these may be used for SE Reports for cigars. Some comments
request that FDA define a surrogate product in the final regulation or
that FDA clarify when and how surrogate data may be used, to ensure
that its use is applied consistently across applicants and FDA
reviewers. The comments on this topic request more clarity on the use
of surrogates to assist applicants in providing sufficient information
about the surrogate in their submissions.
    (Response 55) Although we are not adding a definition of
``surrogate tobacco product'' to this final rule, for the purposes of
an SE review, FDA considers a surrogate tobacco product to be a tobacco
product, other than the predicate or new tobacco product that is the
subject of the SE Report, for which data are available (or can be
generated) and may be scientifically bridged or extrapolated to the
predicate or new tobacco product. A surrogate tobacco product is not a
fictional tobacco product, but an actual product for which there are
empirical data.\10\ FDA believes that, when appropriate, applicants,
regardless of category of tobacco product, may use a surrogate tobacco
product but should clearly designate the specific parts of the SE
Report for which the surrogate tobacco product is to be used.\11\ Such
a surrogate tobacco product may be used, where appropriate, by an
applicant looking to demonstrate the substantial equivalence of a new
cigar product as compared to a valid predicate.
---------------------------------------------------------------------------

    \10\ Note that a predicate tobacco product that is no longer
being manufactured may be reproduced using the design parameters,
tobacco blend, structural materials, and ingredients that are
identical to those of the predicate tobacco previously produced,
and, in this case, FDA would consider the reproduced predicate
product to be the predicate product. But if the reproduced predicate
product differs from the predicate product in any characteristic,
FDA would consider the product to be a surrogate and the applicant
would have to supply appropriate bridging information to the
selected predicate product. For example, if the reproduced predicate
product has the same tobacco blend (percentage of tobacco type) and
tobacco curing process as the predicate product, FDA would consider
the reproduced predicate product to be the predicate product, even
if the crop years are different. If, however, there is any change in
the amount of ingredients, including grade and purity or in
materials or design parameters, including any change to a
manufacturing process that would affect design parameters, FDA would
consider the reproduced product to be a surrogate tobacco product.
    \11\ Surrogate products are not predicate tobacco products.
Evidence of commercial marketing for surrogate products is not
appropriate to determine whether the predicate tobacco product is a
tobacco product commercially marketed (other than for test
marketing) as of February 15, 2007.
---------------------------------------------------------------------------

    FDA believes it would only be appropriate to use a surrogate
tobacco product when the relevant data are not available for the new or
predicate tobacco product and the surrogate tobacco product data can be
scientifically bridged to the new or predicate product. Data for a
surrogate tobacco product may be provided in place of data for the new
or predicate tobacco products, but applicants should provide a
scientific justification for why it is reasonable to use the surrogate
data and then bridge between the surrogate data and the new or
predicate tobacco product. For example, if stability data for a
smokeless predicate product are not available, but there is a smokeless
surrogate product for which there is stability testing data that can be
bridged to the predicate (e.g., through data on the water content and
activity, tobacco (blend and format), ingredients, and container
closure), these data could be used for the missing predicate stability
data. Similarly, if smoking regimen data (intense and non-intense) for
the predicate tobacco product are not available, test data from a
surrogate tobacco product could be appropriate if the predicate and
surrogate tobacco products can be bridged through data (e.g.,
ventilation, paper, tobacco blend, filtration). However, surrogate
products should not be used for the purpose of extrapolating target
specifications and range limits from a surrogate product to a new
product (emphasis added). This is because target specifications and
range limits should be specified by the manufacturer for the new
tobacco product. If an applicant chooses to use a surrogate tobacco
product, we recommend an SE Report include the following information
related to the surrogate product:
    [cir] The tobacco product to which data on the surrogate product is
to be bridged (e.g., predicate product);
    [cir] A detailed description of the ingredients in the surrogate
product, noting any difference(s) in ingredients from the bridged
tobacco product (i.e., the new tobacco product or predicate tobacco
product);
    [cir] Design parameters of the surrogate product (e.g., cigarette
paper base paper porosity, ventilation, tobacco cut or particle size);
\12\
---------------------------------------------------------------------------

    \12\ For example, if an applicant submits HPHC data from a
surrogate combusted filtered cigarette in lieu of HPHC data from a
predicate combusted filtered cigarette, the applicant could explain
that the surrogate data are appropriate for FDA to consider because
the surrogate and predicate tobacco products are identical with the
exception of tobacco blend differences. The SE Report also should
include data that show those differences are not expected to cause
the surrogate tobacco product to yield significant differences in
HPHC when compared to the predicate product. Please note that this
is just one approach, and FDA expects that the scientific
justification for use of the surrogate tobacco product may vary from
case to case and depend on the type of differences (e.g., in tobacco
blend, design features) between the surrogate tobacco product and
the new or predicate tobacco product.
---------------------------------------------------------------------------

    [cir] An identification in a side-by-side list of the
specifications for ingredients and additives, and materials and design
parameters, that differ between the surrogate and the tobacco product
to which data (e.g., HPHC or stability) on the surrogate product is to
be bridged, including tobacco blend or other ingredients, design
parameters, and materials such as pouch, filter tow, or paper. To
facilitate review and reduce FDA requests for clarification, FDA
recommends that side-by-side comparisons of the surrogate and
corresponding predicate or new product be provided in tabular format.
Where any difference in the characteristics of the products has the
potential to impact the use of test data between the surrogate and
predicate or new tobacco product, a scientific justification that
explains how the surrogate data may be bridged to the predicate or new
product will help FDA evaluate whether the surrogate is appropriate. We
recommend that the SE Report include supporting information, e.g.,
publications to show that bridging is appropriate (this may be provided
in an appendix);
    [cir] Testing procedures used to measure and obtain data on the
surrogate tobacco product that may be used in lieu of data on the
predicate product;
    [cir] Surrogate tobacco HPHC yields or quantities (these would not
be needed when the new or predicate tobacco product is available for
testing);
    [cir] Method validation reports of analytical testing (e.g.,
accuracy,

repeatability, limit of detection, limit of quantification).
    (Comment 56) One comment asks whether one product could be a
surrogate for another product if the products contain an identical
blend, but one product is wrapped in cellophane and the other is not.
    (Response 56) While it may be possible to use a surrogate product
in this instance, because the answer to this comment depends on more
specific information than is provided, we recommend that for this or
any other specific question related to the use of surrogates, the
applicant contact the Agency.
    (Comment 57) A few comments reference the comparison requirements
(in Sec.  1107.19) stating these unreasonably restrict the use of
surrogate products and do not promote clarity and efficiency.
    (Response 57) As we discuss in detail in preceding paragraphs, FDA
is allowing the use of surrogate tobacco product data in specific
scenarios and has provided a more robust description on how a surrogate
can be utilized in an SE Report. Section 1107.19 does not place
limitations on the type of scientific data an applicant may provide
surrogate information for in lieu of the actual new or predicate
tobacco product.
 Statement of Compliance With Applicable Tobacco Product
Standards (Sec.  1107.18(i))
    In the proposed rule, we invited comment on how we should handle SE
Reports that are pending at the time a final product standard issues
with respect to the requirement that the SE Report include a statement
of compliance with any applicable standard. We received some comments
in response, which we discuss and respond to in the following
paragraphs.
    (Comment 58) One comment suggested that FDA should continue its
review of the SE Report through final determination, and, if the
product is determined to be substantially equivalent, FDA could
condition the marketing of that product on the manufacturer
establishing compliance with the product standard that went into effect
while the SE Report was under review. The comment also states that, as
part of issuing a standard, FDA should establish the process for
bringing legally marketed products into compliance with the standard.
Another comment suggests that applicants be permitted to modify their
prior statements regarding compliance, and that compliance with the
standard be considered during review of the pending SE Report.
    (Response 58) We appreciate the information provided in response to
our invitation to comment. FDA agrees with the comments that suggest
that this issue should be considered as part of issuing a standard
under section 907 of the FD&C Act (21 U.S.C. 387g). Additionally, the
regulatory process that FDA must follow to issue a product standard
under section 907 of the FD&C Act is lengthy and would provide
applicants with notice of proposed requirements well in advance of any
change becoming effective.
 Compliance With Part 25 (Sec.  1107.18(k))
    (Comment 59) Some comments urge FDA to either remove the
requirement that manufacturers include an environmental assessment (EA)
in their SE Reports or establish categorical exclusions for SE reports.
The comments find the EA process unnecessarily burdensome without
legitimate purpose. One comment objects that requiring EAs for deemed
tobacco products that are still on the market is inconsistent with
FDA's categorical exclusion for provisional SE Reports (those products
on the market as of February 15, 2007) (see 80 FR 57531, September 24,
2015). The comment asserts FDA's different treatment of these
categories of products is arbitrary and capricious. Other comments
state that EAs are burdensome, with some noting greater difficulty for
cigar manufacturers, and that FDA could alleviate some of these costs
by allowing multiple products to be addressed in one EA or allowing the
use of EA-specific master files for all products manufactured at the
same facility.
    (Response 59) We disagree with the assertion that the requirement
of EAs is unnecessarily burdensome. FDA is required to examine the
environmental impacts of issuing marketing orders under the National
Environmental Policy Act of 1969 (NEPA) (FDA's implementing regulations
are at title 21 CFR, part 25). Part 25 requires EAs as a means of
assessing the potential environmental impacts from tobacco products,
which may present environmental issues during manufacturing (e.g.,
release of chemicals), use (e.g., smoke and aerosol may impact air
quality), and disposal (e.g., litter, which persists in the environment
and is toxic to different organisms). Per Sec.  25.20, an EA is
normally required for the issuance of an SE order, except that
provisional SE reports that receive an SE order are categorially
excluded under Sec.  25.35(a). SE Reports for which an NSE is issued
are also categorically excluded from having an EA under Sec.  25.35;
however, that outcome is not known until review of an SE Report is
complete.
    FDA also disagrees with the assertion that the requirement of EAs
for deemed tobacco products still on the market is inconsistent,
arbitrary, or capricious in comparison to the requirements for
provisional products. In issuing the categorical exclusion for
provisional products, FDA provided an estimate of the environmental
impacts of all FDA-regulated tobacco products on the market, including
products marketed after February 15, 2007, and before March 22, 2011,
and pre-Existing tobacco products (tobacco products that were
commercially marketed in the United States as of February 15, 2007) (79
FR 3742 at 3746). FDA currently lacks the information to conduct such
an analysis for deemed tobacco products still on the market. Unlike
provisional products, deemed tobacco products include products whose
environmental impacts are largely unknown, with the potential to result
in greater or different impacts on the environment compared to other
tobacco products. Because there is no basis for such a categorical
exclusion at this time, NEPA and its implementing regulations require
FDA to examine the potential environmental impacts from the issuance of
an SE order; therefore, EAs are required for deemed tobacco products to
comply with NEPA.
    We disagree with the suggestions that a single EA be submitted for
multiple products or that an EA-specific master file be permitted.
Additionally, FDA is required by regulation to evaluate the
environmental impact individually from one proposed action (Sec.
25.40(a)). An aggregated impact from multiple products is not
sufficient under NEPA to determine whether the individual proposed
action has a significant impact on the human environment.
 Certification Statement (Sec.  1107.18(l))
    (Comment 60) Some comments assert that FDA has no authority to
impose the certification requirement or that it invites imprecision and
falsification particularly when certifying that characteristics are
identical without supporting test data. Other comments suggest there is
no need for this ``additional assurance.'' Two comments suggest that an
applicant should be permitted to submit a certification stating that
all characteristics of the new and predicate tobacco products are
identical except for those identified. Alternatively, other comments
support

the certification approach and request that we permit applicants of
currently pending SE Reports to submit such a certification without
waiting for the final rule to become effective. One comment states that
any certification that some or all characteristics are identical must
be fully supported by actual test data.
    (Response 60) We disagree that FDA does not have the authority to
impose the certification requirement, that it invites imprecision or
falsification, or is unnecessary. Section 905(j)(1) of the FD&C Act
authorizes FDA to issue regulations prescribing the form and manner of
SE Reports, and we have included this requirement based on that
authority. Notably, as some comments indicate, these certifications can
help minimize the burden on applicants by providing an opportunity to
certify when characteristics are identical (Sec.  1107.18(l)(2)). With
respect to the concern related to ensuring there is underlying support
for a certification, the certification is intended in part to ensure
that an applicant is prepared to support their SE Report with further
information, if needed (for example, the certification in Sec.
1107.18(l)(2) provides that the company ``will maintain records to
support the comparison information in Sec.  1107.19 that substantiate
the accuracy of this statement''). Moreover, after careful
consideration of this concern, we also have included in Sec.
1107.18(l)(2) a requirement that a justification for the certification
be included. Such a justification could include, for example, the type
of test data that was compared between the new and predicate tobacco
products and/or a description of the quality control checks that were
conducted, which demonstrate the characteristics being certified are
identical. The certification also is intended to provide FDA with
assurance that the applicant has fully considered the SE Report and its
contents, believes there is a basis for making the findings required by
section 910(a)(2) of the FD&C Act, and understands the potential
consequences of submitting false information to the U.S. Government.
    Thus, contrary to what some of the comments suggest, the
certification is an important, but also simple, means of helping ensure
that the authorized representative is aware of and understands the
recordkeeping requirements, that the submission is truthful and
accurate, and the representative is authorized to submit the SE Report
on behalf of the applicant. For a certification under Sec.
1107.18(l)(2), the certification also helps ensure that the authorized
representative is aware of and understands that, in lieu of providing
data for each characteristic of the new and predicate tobacco products,
the applicant is choosing to certify that the characteristics of the
products are identical and that records will be maintained to support
this determination. With respect to the comment that requests FDA
permit this for pending SE Reports, as explained in preceding
paragraphs, this rule does not apply to pending submissions.
3. Comparison Information (Sec.  1107.19)
    Proposed Sec.  1107.19 set out the comparison information that
would be required in an SE Report. It also set forth the manner in
which the comparison section of the SE Report would be required to be
organized, and explained that applicants who make a comparison of a new
product to a predicate product may also need to provide information to
demonstrate that the new tobacco product is substantially equivalent to
the original predicate tobacco product. Following our consideration of
the comments, which we describe and respond to in detail in this
section, we are clarifying in this preamble and in changes to the
codified that Sec.  1107.19 applies to ``different characteristics'' SE
Reports. ``Same characteristics'' SE Reports do not need to include the
information in this section. In reviewing an SE Report, FDA may request
additional information if needed to make an SE determination.
    On our own initiative, we have revised the introductory text in
Sec.  1107.19 so that it no longer states ``The comparison section of
the SE Report must be organized in the following manner'' as not all of
the subsections require information to be submitted in an SE Report,
and instead added ``as described in this section.'' Following our
consideration of comments and based on our increased experience
reviewing SE Reports, we are finalizing with changes Sec.  1107.19(a)
(comparison of product design). These changes include the addition of
design parameters for cigars, pipes, waterpipes, ENDS, and heated
tobacco products, as described in detail in the product design
paragraphs that follow.
    In addition, we have made clarifications in Sec.  1107.19(c)
(product composition), including replacing ``material'' with
``ingredient'' in paragraph (c)(2)(iv) due to a typographical error;
adding examples of the type of tobacco to be identified and striking
``grade and variety'' in paragraph (c)(3)(i) because tobacco grading is
not uniform throughout the industry, which reduces the utility of this
information in application review, and FDA does not need to
characterize the tobacco type to the level of detail of tobacco variety
for the purposes of an SE evaluation; adding a requirement that
information on the type of curing method be submitted as paragraph
(c)(3)(ii) because the curing method is known to influence the
formation of TSNAs and other select HPHCs and this information will
allow FDA to fully characterize the tobacco (Refs. 13 and 14); adding
``of each type'' following quantity in paragraph (c)(3)(iii), and
striking proposed paragraph (c)(3)(iii) to clarify we need this for
each type of tobacco since many tobacco products are made from blends
of different tobacco types.
    To Sec.  1107.19(d)(1)(ii)(F) we have added a requirement that full
validation reports for each analytical method be included because, as
noted in the earlier discussion in this rule, this information is
needed to ensure the method is fit for purpose and the measured values
can be accurately compared between a new and predicate tobacco product.
    In addition, we added that reference product datasets be included
(if applicable) in Sec.  1107.19(d)(1)(ii)(J). A reference product is a
product of known physical and chemical composition and is typically
accompanied by a Certificate of Analysis that states the attributes of
the reference product. A suitable reference product is one that is
compositionally and functionally representative of the test samples in
the study, and laboratories may use a reference product for proficiency
testing to demonstrate that the laboratory is capable of accurately
measuring tobacco chemicals of interest and as a control sample during
instrument calibration, method validation, and sample analysis. Thus,
reference product datasets are used to demonstrate that the test
results obtained from testing of tobacco products are reliable. Because
of the addition of reference product datasets to the final rule, we
have renumbered proposed Sec.  1107.19(d)(1)(ii)(J) to Sec.
1107.19(d)(1)(ii)(K). In the final rule, we also are adding to Sec.
1107.19(d)(1)(ii)(K) ``Test data for combusted or heated tobacco
products must reflect testing conducted using both intense and
nonintense smoking or aerosol-generating regimens, where established''
(Refs. 15 and 16). The proposed rule explained that for combusted
tobacco products constituent smoke yields from the new and predicate
tobacco products would need to be determined using intense and
nonintense smoking regimens, but the proposed codified did not
specifically reference these regimens (see 84 FR

12740 at 12763). Following our consideration of comments on this issue
(see later paragraphs in this section for a discussion of comments), we
added codified text to ensure the understanding that this is required
for these products. Because heated tobacco products present issues
similar to combusted tobacco products, the final rule also specifies
that test data for heated tobacco products reflect testing conducted
using both intense and nonintense smoking or aerosol-generating
regimens, where established. The final rule also now includes a Sec.
1107.19(d)(1)(ii)(L) that clarifies that the applicant must include in
the SE Report a complete description of any smoking or aerosol-
generating regimens used for analytical testing that are not
standardized or widely accepted by the scientific community, if
applicable.
    In addition, we have reorganized and modified proposed Sec.
1107.19(e) for clarity. We also added a requirement for information on
the heat treatment process (if applicable), which is a tobacco
processing method that could potentially reduce the microbial load of
the tobacco product and result in lower levels of carcinogenic TSNAs,
thereby altering product composition (i.e., product characteristics) in
Sec.  1107.19(e)(2) (Refs. 17 and 18). For better organization, we
moved the stability information in proposed Sec.  1107.19(e) to Sec.
1107.19(f); moved the testing information from proposed Sec.
1107.18(h) to Sec.  1107.19; and renumbered proposed Sec.  1107.19(f)
to Sec.  1107.19(g) and proposed Sec.  1107.19(g) to Sec.  1107.19(h)
in this final rule.
    Following our consideration of comments, we are finalizing the
stability testing in Sec.  1107.19(f) with some changes. First, we are
expanding the types of tobacco products that will need to submit
information on stability and shelf life. The proposed rule would only
have required stability testing information for smokeless tobacco
products and tobacco products that contained fermented tobacco,
including naturally fermented tobacco. As explained in the proposed
rule, stability information is a particular concern with smokeless
tobacco products and other tobacco products that contain fermented
tobacco because the characteristics of these products can be affected
by the manufacturing process, storage conditions, and length of time on
a shelf.
    Upon further consideration, the final rule will require information
on stability and shelf life for all tobacco products, except RYO
tobacco products and cigarettes that are not HTPs.\13\ Information
obtained through stability testing and shelf life is important for FDA
to consider during its review to ensure that the tobacco products are
microbiologically and chemically stable during storage and do not
result in different questions of public health. Fermentation of tobacco
(including natural fermentation) affects the microbial content, which
could potentially affect TSNA content and product stability (Refs. 19-
24). In addition, based on our experience, HTPs can contain high levels
of humectants, which can affect product stability; therefore shelf life
and stability information is required to support an SE report for HTPs.
Humectants function to keep a product moist, thereby impacting the
moisture content and water activity of the product, which in turn may
impact microbial growth and product stability (Ref. 25).
---------------------------------------------------------------------------

    \13\ See the discussion in section V.D.2, about how products
should be categorized for purposes of SE review.
---------------------------------------------------------------------------

    Based on FDA's experience with cigarettes and RYO tobacco products
under the SE pathway and because the vast majority of cigarettes and
RYO tobacco products do not contain fermented tobacco, these products
do not have the same stability concerns. However, we lack similar
experience with more novel tobacco products, such as ENDS and HTPs, and
thus need stability information for these types of products to
determine whether there is a difference in microbial factors or HPHC
quantities over time. The proposed rule did not specify that this
information was needed for novel tobacco products because we did not
expect many substantial equivalence reports to be submitted for novel
tobacco products. In reviewing the PMTA rule and its stability
requirements, though, we recognized the possibility that a novel
product manufacturer may pursue authorization through the SE pathway
and we wanted to make sure that both the PMTA and SE regulations would
require applicants to provide the Agency with the necessary stability
information. FDA believes information regarding these products' shelf
life and stability over time is needed to ensure FDA fully understands
the microbial and chemical stability of the new and predicate tobacco
products throughout their stated shelf life, and will thus have the
needed information to make the SE determination.
    Second, stability testing requirements have been updated to remove
identification of microbiological organisms by genus and species and
remove testing for pH, moisture content, nitrate and nitrite levels,
and preservatives and microbial metabolic inhibitors. In addition, if a
tobacco product does not have a defined shelf life, stability data will
need to be provided over a specified amount of time with a
justification for why that time period is appropriate.
    Section 1107.19(f)(2) of the proposed rule (now Sec.
1107.19(g)(2)) stated that, when an applicant states that its new
tobacco product has different characteristics than the predicate
tobacco product, the applicant must also include an explanation as to
why a difference in any of the following characteristics do not cause
the new product to raise different questions of public health: Product
design (Sec.  1107.19(a)); heating source (Sec.  1107.19(b)); materials
and ingredients (Sec.  1107.19(c)); and other features (Sec.
1107.19(d)). In addition, to demonstrate that a new tobacco product
with different characteristics is substantially equivalent, an
applicant must also explain why any difference in the manufacturing
process between the new tobacco product and the predicate tobacco
product does not raise different questions of public health (Sec.
1107.18(e)). Similarly, for smokeless tobacco products, an applicant
must explain why any difference in stability between the new tobacco
product and the predicate tobacco product does not raise different
questions of public health (Sec.  1107.19(e)). In the final rule, we
have updated this subsection to remove repetitive language (i.e.,
``with different characteristics''), add clarifying language (``would
not change the characteristics of the new tobacco product such that the
new tobacco product could'' and ``cause the new tobacco product to''),
and after ``smokeless tobacco'' add ``and tobacco products that contain
fermented tobacco as these tobacco products have similar stability
considerations.''
    We have also updated Sec.  1107.19(i) to reflect the updated
definition of predicate tobacco product, as described in the
definitions section of this final rule.
 Product Design (Sec.  1107.19(a))
    In the following paragraphs, we describe in more detail the changes
to Sec.  1107.19(a)and we describe the comments submitted on Sec.
1107.19(a) and our responses to those comments.
    We have revised Sec.  1107.19(a) so that it does not require test
data, target specifications and range limits be submitted in all
instances, as the proposed rule would have required.

Instead, Sec.  1107.19(a) requires that SE Reports include test data
(including test protocols, quantitative acceptance criteria, data sets
(i.e., measured values), and a summary of the results) only when the
target specification or range limits of the new tobacco product differ
from the predicate tobacco product. We have also clarified that test
data would need to be submitted for both the new and predicate tobacco
products. Additionally, FDA has clarified that for tobacco cut size or
particle size, when target specifications and range limits are not
available, the following alternative information may be submitted in
place of this information: A description of the tobacco cutting process
(including a complete description of the milling, cutting, and sifting
process; the control parameters of the miller or cutter; and any sift
specifications) or the measured particle size distribution for the new
and predicate tobacco products. This alternative may be used, for
example, if an applicant does not set target specifications or range
limits for tobacco cut size. In this case, they could submit
information about the tobacco cutting process of the new and predicate
tobacco products to demonstrate that the products are substantially
equivalent.
    Applicants may also choose to submit the necessary design parameter
information using a Manufacturing Data Sheet Specification (MDSS)
document. The MDSS is a document typically maintained by manufacturers,
describing all the parameters that are controlled by the manufacturer
during manufacture of their tobacco products. However, there will be
cases where the design parameters on the MDSS will not directly
translate into one of the product-specific design parameters required
in Sec.  1107.19. In these cases, additional information would need to
be submitted to provide the complete characterization necessary.
Additionally, FDA will not require test data for all parameters for
which target and range are required. For example, for parameters that
are observational (e.g., number of waterpipe holes), FDA would not seek
test data on that parameter. Also, some design parameters are machine
settings (e.g., tobacco cut size), calculated (e.g., denier per
filament), provided by suppliers (e.g., Certificate of Analysis for
base paper porosity), or can be extrapolated from other design
parameter test data (e.g., filter pressure drop test data is more
informative than filter length test data). FDA has clarified
alternative terminology for ``porosity'' understanding that applicants
may refer to this term as ``permeability'' for several design
parameters, as well as adding units of measure for several design
parameters.
    Following our review of comments, we have revised the tables of
design parameters required for certain product categories as described
here:
    Cigarettes: As discussed in section V.D.2 above, tobacco products
that meet the definition of cigarette but are heated tobacco products
should be categorized as heated tobacco products (HTPs) for purposes of
SE review. Accordingly, this section discusses cigarettes that are not
HTPs. Section 1107.19(a) has changed certain proposed requirements
under target specification and range. These changes include: (1)
Removal of the proposed requirement for applicants to provide cigarette
draw resistance as FDA determined that requiring this as distinct
parameter was unnecessary and not as informative as filter pressure
drop because draw resistance could be modified by the user by puffing
more or less intensely; (2) removal of cigarette paper base paper basis
weight as it provides duplicative information that is already captured
by the submission of ingredient levels (e.g., a higher basis weight
might be due to the inclusion of more cellulose and more calcium
carbonate); (3) addition of tobacco cut size as this parameter has an
influence on the chemical concentration in the combusted portion of the
cigarette, combustion temperature, and affects the particle size and
distribution of particles; (4) FDA has clarified terminology for
cigarette paper band porosity, as applicants may refer to this term as
permeability, and also provide an alternative to providing cigarette
paper band porosity or permeability. Band diffusivity, while not
preferred, is an acceptable alternative if it is currently not part of
an applicant's practice to specify cigarette paper band porosity.
Regardless of whether porosity or diffusivity is specified, the same
parameter must be provided for both the new and predicate tobacco
products to conduct a meaningful comparison. While there are minor
differences (porosity is more relevant during active puffing, whereas
diffusivity is more relevant during smoldering), the addition of
diffusivity as an alternative parameter allows flexibility to
applicants who do not directly measure porosity or permeability while
still providing FDA with the information it needs to make the
substantial equivalence finding (Ref. 26).
    FDA has revised certain proposed parameters for test data which
include: (1) Removal of puff count as this was duplicative of
information that an applicant would submit with smoke constituent data
because puff count is determined in a smoking machine using either the
International Organization for Standardization or Health Canada Intense
smoking regimen or other applicable regimen (Refs. 27 and 28); (2)
removal of cigarette draw resistance as explained above; (3) removal of
cigarette paper base paper basis weight as explained above; (4)
addition of tobacco filler mass as this has a direct influence on smoke
constituents (Ref. 29); and (5) the option to provide oven volatiles
instead of moisture as this provides similar information to FDA (Ref.
30) \14\ and allows the applicant flexibility to provide either
parameter based on the specific manufacturing processes they employ.
---------------------------------------------------------------------------

    \14\ Please note that the term ``moisture,'' has widely varying
and conflicting definitions and terminology in use within the
tobacco industry. It is common for ``moisture'' or ``moisture
content'' to be used to refer to water content of a material but in
relation to the tobacco industry it is necessary to differentiate
between ``moisture'' as water content and ``moisture'' as oven
volatiles. https://www.coresta.org/sites/default/files/technical_documents/main/PTM-CTR_MoistureWaterOvenVolatiles_July2014%282%29.pdf.
---------------------------------------------------------------------------

    Smokeless Tobacco: Section 1107.19(a) has changed certain proposed
requirements under target specification and range. These changes
include: (1) Removal of portion thickness as it is an unnecessary
parameter because it is the pouch effective area that may result in an
increase of the release level of nicotine, unprotonated nicotine, and
could affect TSNA levels and the pouch effective area can be calculated
from other required design parameters, i.e., pouch length and pouch
width; (2) addition of pouch material thickness as this parameter
influences the release level of nicotine and can affect TSNA levels;
\15\ (3) addition of nicotine dissolution rate because it is a measure
of how much free nicotine a user could be exposed to and differences in
nicotine dissolution can have an impact on addiction and nicotine
uptake (Refs. 31, 32, 85); and (4) clarification of requiring certain
parameters ``if applicable'' for portioned product properties (i.e.,
portion length, portion width, and portion mass, ``if applicable'' has
been removed) because these parameters are needed for all portioned
smokeless products. However, not all portioned products are pouched, so
the pouch-specific

properties should only be reported if applicable, and thus FDA has
added ``if applicable'' to pouch material porosity or permeability and
pouch material basis weight.
---------------------------------------------------------------------------

    \15\ See, e.g., Gale, N., G. Errington, and K. McAdam, Group
Research & Development, British American Tobacco, ``Effects of
Product Format on Nicotine and TSNA Extraction from Snus Pouches,''
Presentation at the 67th Tobacco Science Research Conference,
Williamsburg, VA, September 15-18, 2013. Available at: https://www.researchgate.net/publication/299854728_Effects_of_Product_Format_on_Nicotine_and_TSNA_Extraction_from_Snus_Pouches.
---------------------------------------------------------------------------

    Roll-your-own tobacco, rolling papers: Section 1107.19(a) has
changed a proposed requirement under target specification, range, and
test data. This change includes the option to provide diffusivity in
lieu of cigarette paper band porosity (also described as permeability)
for the reasons explained above under Cigarettes.
    Roll-your-own tobacco, non-filtered tubes: Section 1107.19(a) has
changed certain proposed requirements under target specification and
range. These changes include the addition of: (1) Clarification of
terminology changing ``total mass (mg)'' to ``tube mass (mg);'' (2) the
option to provide tube diameter as an alternative to tube circumference
as FDA is able to obtain the information necessary from other required
design parameters; and (3) the option for the applicant to provide
diffusivity in lieu of cigarette paper band porosity or permeability as
described above. This alternative is also provided under test data for
this product category.
    Roll-your-own tobacco, filtered tubes: Section 1107.19(a) has
changed certain proposed requirements under target specification and
range. These changes include the addition of: (1) Clarification of
terminology changing ``total mass (mg)'' to ``tube mass (mg);'' (2) the
option to provide tube diameter as an alternative to tube circumference
as FDA is able to obtain the information necessary from other required
design parameters; (3) the option for the applicant to provide filter
efficiency as an alternative to denier per filament, total denier, or
filter density (Ref. 33); and (4) the option for the applicant to
provide diffusivity in lieu of cigarette paper band porosity or
permeability as described above. These alternatives (filter efficiency
and diffusivity) are also provided under test data for this product
category.
    Roll-your-own tobacco: Section 1107.19(a) has changed certain
proposed requirements under target specification, range, and test data.
This change includes the removal of the requirement for the applicant
to provide filler mass as this is provided as part of unique
identification of the tobacco product under Sec.  1107.18.
    In addition, in the proposed rule, we invited comments and
information on the parameters that may be needed to support an SE
Report for tobacco products that were not specifically included in the
proposed rule, such as cigars and ENDS. Based on the comments and
information we received, we have added design parameters to Sec.
1107.19(a) for cigar tobacco products, pipe tobacco products, waterpipe
tobacco products, ENDS tobacco products, and heated tobacco products,
as described in the following paragraphs.
    Cigars. Cigarettes (outside the category of heated tobacco
products) and cigars are generally similar in design and principles of
operation as they are both cylinders filled with a blend of processed
tobacco that is generally smoked. Both are generally lit with a fire
source, which burns the tobacco as the user inhales at one end; thus,
they are consumed and deliver nicotine in a similar manner. A main
difference between cigarettes and cigars is that cigars are either
wrapped in a tobacco leaf (wrapper and binder) or a material containing
tobacco, whereas non-HTP cigarettes are wrapped in paper (cigarette
paper) or a material that does not contain tobacco. Additionally,
cigars come in a wider variety of sizes and may be thicker in diameter
and contain more tobacco filler than cigarettes. Despite these
differences, for both types of tobacco products, no matter the size,
air is pulled through the tobacco column, which aids in tobacco
combustion and nicotine delivery. Cigarette paper commonly has an
established porosity or permeability, that is set during manufacturing,
while cigar wrapper properties are based on the tobacco used as the
wrapper. Although cigars and cigarettes may be wrapped in different
materials, both cigar wrappers and binders, as well as cigarette
papers, have inherent permeabilities/porosities, which may affect smoke
constituent yields. Cigars may be filtered (containing filter tow or
other materials), unfiltered, or unfiltered with tips made of wood or
plastic, while most cigarettes have filters (containing filter tow) and
do not contain tips. If a cigar does contain a filter, it will be
similar to cigarette filters and contain tow. Based on FDA's experience
with cigarettes, many design parameters required to assess public
health impacts for cigarettes will also be needed to assess public
health impacts for cigars. The following paragraphs describe in more
detail the required parameters for each subcategory of cigars.
    Filtered, sheet-wrapped cigars: Section 1107.19(a) includes the
design parameters that must be contained in an SE Report to fully
characterize filtered, sheet-wrapped cigars and how changes to these
parameters may impact public health, as described next:
    [cir] Cigar mass reflects the amount of tobacco in a cigar, which
may affect smoke constituent yields (Ref. 34).
    [cir] Cigar puff count can directly affect smoke constituent yields
(Ref. 34).
    [cir] Cigar length and diameter can directly affect the amount of
tobacco that is burned and, in turn, affect smoke constituent yields
(Ref. 35).
    [cir] Tobacco filler mass may affect smoke constituent yields (Ref.
34).
    [cir] For cigarettes, the cigarette paper basis weight may affect
puff count and smoke constituents (Ref. 36). Similarly for cigars, the
cigar wrapper and binder basis weight may affect puff count and smoke
constituent yields (Refs. 36 and 37).
    [cir] For cigarettes, the paper length and width may affect puff
count and smoke constituents (Ref. 36). Similarly for cigars, the cigar
wrapper and binder width and wrapper length may directly influence the
area through which air is permitted to enter the tobacco column, which,
in turn, may affect puff count and smoke constituent yields.
    [cir] Cigar wrapper porosity may affect smoke constituent yields
(Refs. 37 and 38).
    [cir] For cigarettes, tobacco rod density may modify burn
properties and smoke constituent yields (Refs. 39 and 40). Similarly
for cigars, the tobacco rod density may modify burn properties and
smoke constituent yields.
    [cir] For cigarettes, the tobacco moisture or oven volatiles may
affect puff count (Ref. 41). Similarly for cigars, the tobacco moisture
or oven volatiles may affect puff count.
    [cir] For cigarettes, the tobacco cut size may result in more
particulate matter (Ref. 42). Similarly for cigars, the tobacco cut
size alters the size of the tobacco pieces, which may result in more
particulate matter.
    [cir] For cigarettes, the band porosity may affect smoke
constituent yields (Ref. 43). Similarly for cigars, the wrapper or
binder band porosity or permeability may affect smoke constituent
yields because band porosity allows for the overall assessment of the
weighted change in air flow through the paper during active puffing.
    [cir] For cigarettes, the band width may affect smoke yields (Ref.
44). Similarly for cigars, the wrapper band width and binder band width
may affect ventilation and, in turn, smoke constituent yields.
    [cir] For cigarettes, the band space may affect puff count (Ref.
45). Similarly for cigars, the wrapper band space and binder band space
may affect ignition propensity and, in turn, puff count.

    [cir] For cigarettes, the filter parameters can impact smoke yields
(Ref. 33). Similarly for cigars, the filter diameter, filter mass, and
filter tow crimping index, denier per filament, total denier, filter
density, and filter length may affect filter efficiency and, in turn,
smoke constituent yields.
    [cir] For cigarettes, the filter pressure drop affects smoke yields
(Ref. 46). Similarly for cigars, the filter pressure drop may affect
smoke constituent yields.
    [cir] For cigarettes, tipping paper length may affect smoke
constituent yields (Ref. 47). Similarly for cigars, the tipping paper
length may affect smoke constituent yields.
    [cir] Ventilation may affect smoke constituent yields (Ref. 34).
    [cir] For cigarettes, the diameter can affect the smoke yields
(Ref. 46). Similarly for cigars, the cigar maximum and minimum diameter
may affect rod density, which modifies the burn properties and smoke
yields; FDA needs this information to characterize the diameters as
shapes of cigars can differ with the tips being narrower than the
center of the cigar. This may result in multiple rod densities used to
test the smoke and influence smoke yields depending on what part of the
cigar is tested.
    [cir] For cigarettes, the paper porosity may affect smoke
constituents (Ref. 43). Similarly for cigars, the binder porosity may
affect or may further limit air flow into and out of the cigar which
may affect smoke yields.
    Unfiltered, sheet-wrapped cigars: Section 1107.19(a) includes the
design parameters that must be contained in an SE Report to fully
characterize unfiltered, sheet-wrapped cigars and how changes to these
parameters may impact public health, as described next:
    [cir] Cigar mass reflects the amount of tobacco in a cigar, which
may affect smoke constituent yields (Ref. 34).
    [cir] Cigar puff count can directly affect smoke constituent yields
(Ref. 34).
    [cir] Cigar length and diameter can directly affect the amount of
tobacco that is burned and, in turn, affect smoke constituent yields
(Ref. 35).
    [cir] Tobacco filler mass may affect smoke constituent yields (Ref.
34).
    [cir] For cigarettes, the cigarette paper basis weight may affect
puff count and smoke constituents (Ref. 36). Similarly for cigars, the
cigar wrapper and binder basis weight may affect puff count and smoke
constituent yields (Refs. 36 and 37).
    [cir] For cigarettes, the paper length and width may affect puff
count and smoke constituents (Ref. 36). Similarly for cigars, the cigar
wrapper and binder width and wrapper length may directly influence the
area through which air is permitted to enter the tobacco column, which,
in turn, may affect puff count and smoke constituent yields.
    [cir] Cigar wrapper porosity may affect smoke constituent yields
(Refs. 37 and 38).
    [cir] For cigarettes, tobacco rod density may modify burn
properties and smoke constituent yields (Refs. 39 and 40). Similarly
for cigars, the tobacco rod density may modify burn properties and
smoke constituent yields.
    [cir] For cigarettes, the tobacco moisture or oven volatiles may
affect puff count (Ref. 41). Similarly for cigars, the tobacco moisture
or oven volatiles may affect puff count.
    [cir] For cigarettes, the tobacco cut size may result in more
particulate matter (Ref. 42). Similarly for cigars, the tobacco cut
size alters the size of the tobacco pieces, which may result in more
particulate matter.
    [cir] For cigarettes, the band porosity may affect smoke
constituent yields (Ref. 43). Similarly for cigars, the wrapper or
binder band porosity or permeability may affect smoke constituent
yields because band porosity allows for the overall assessment of the
weighted change in air flow through the paper during active puffing.
    [cir] For cigarettes, the band width may affect smoke yields (Ref.
44). Similarly for cigars, the wrapper and binder band width may affect
ventilation and, in turn, smoke constituent yields.
    [cir] For cigarettes, the band space may affect puff count (Ref.
45). Similarly for cigars, the wrapper and binder band space may affect
ignition propensity and, in turn, puff count.
    [cir] Cigar tip mass, length, and inner diameter dimensions
directly influence the overall cigar draw resistance and in turn, puff
count (Ref. 48).
    [cir] For cigarettes, the diameter can affect the smoke yields
(Ref. 46). Similarly for cigars, the cigar maximum and minimum diameter
may affect rod density, which modifies the burn properties and smoke
yields; FDA needs this information to characterize the diameters as
shapes of cigars can differ with the tips being narrower than the
center of the cigar. This may result in multiple rod densities used to
test the smoke and influence smoke yields depending on what part of the
cigar is tested.
    [cir] For cigarettes, the paper porosity may affect smoke
constituents (Ref. 43). Similarly for cigars, the binder porosity may
affect or may further limit air flow into and out of the cigar which
may affect smoke yields.
    Unfiltered, leaf-wrapped cigars: Section 1107.19(a) includes the
design parameters that must be contained in an SE Report to fully
characterize unfiltered, leaf-wrapped cigars and how changes to these
parameters may impact public health, as described next:
    [cir] Cigar mass reflects the amount of tobacco in a cigar, which
may affect smoke constituent yields (Ref. 34).
    [cir] Cigar puff count can directly affect smoke constituent yields
(Ref. 34).
    [cir] For cigarettes, the paper length and width may affect puff
count and smoke constituents (Ref. 36). Similarly for cigars, the cigar
binder and wrapper length and wrapper width may directly influence the
area through which air is permitted to enter the tobacco column, which,
in turn, may affect puff count and smoke constituent yields.
    [cir] Cigar length and diameter can directly affect the amount of
tobacco that is burned and, in turn, affect smoke constituent yields
(Ref. 35).
    [cir] For cigarettes, the tobacco moisture or oven volatiles may
affect puff count (Ref. 41). Similarly for cigars, the tobacco moisture
or oven volatiles may affect puff count.
    [cir] For cigarettes, the cigarette paper basis weight may affect
puff count and smoke constituents (Ref. 36). Similarly for cigars, the
cigar wrapper and binder basis weight may affect puff count and smoke
constituent yields (Refs. 36 and 37).
    [cir] For cigarettes, tobacco rod density may modify burn
properties and smoke constituent yields (Refs. 39 and 40). Similarly
for cigars, the tobacco rod density may modify burn properties and
smoke constituent yields.
    [cir] For cigarettes, the tobacco cut size may result in more
particulate matter (Ref. 42). Similarly for cigars, the tobacco cut
size alters the size of the tobacco pieces, which may result in more
particulate matter.
    [cir] Tobacco filler mass may affect smoke constituent yields (Ref.
34).
    [cir] For cigarettes, the diameter can affect the smoke yields
(Ref. 46). Similarly for cigars, the cigar maximum and minimum diameter
may affect rod density, which modifies the burn properties and smoke
yields; FDA needs this information to characterize the diameters as
shapes of cigars can differ with the tips being narrower than the
center of the cigar. This may result in multiple rod densities used to
test the smoke and influence smoke yields depending on what part of the
cigar is tested.
    Cigar filler: \16\ Section 1107.19(a) describes the design
parameters that

must be contained in an SE Report to fully characterize cigar filler
and how changes to these parameters may impact public health, as
described next:
---------------------------------------------------------------------------

    \16\ These design parameters are for an SE Report where ``cigar
filler'' is the new tobacco product (not when cigar filler is a
component or part of a cigar or other tobacco product).
---------------------------------------------------------------------------

    [cir] For cigarettes, the tobacco cut size may result in more
particulate matter (Ref. 42). Similarly for cigars, the tobacco cut
size alters the size of the tobacco pieces, which may result in more
particulate matter.
    [cir] For cigarettes, the tobacco moisture or oven volatiles may
affect puff count (Ref. 41). Similarly for cigars, the tobacco moisture
or oven volatiles may affect puff count.
    Cigar component: \17\ Section 1107.19(a) includes the design
parameters that must be contained in an SE Report to fully characterize
a cigar component and how changes to these parameters may impact public
health, as described next:
---------------------------------------------------------------------------

    \17\ These design parameters are for an SE Report where a
``cigar component'' is the new tobacco product (not when the cigar
component is a component or part of a cigar or other tobacco
product).
---------------------------------------------------------------------------

    [cir] For cigarettes, the paper length and width may affect puff
count and smoke constituents (Ref. 36). Similarly for cigars, the cigar
wrapper length and width may directly influence the area through which
air is permitted to enter the tobacco column, which, in turn, may
affect puff count and smoke constituent yields.
    [cir] For cigarettes, the cigarette paper basis weight may affect
puff count and smoke constituents (Ref. 36). Similarly for cigars, the
cigar wrapper basis weight may affect puff count and smoke constituent
yields (Refs. 36 and 37).
    [cir] Cigar wrapper porosity may affect smoke constituent yields
(Refs. 37 and 38).
    Pipe. Cigarette tobacco and pipe tobacco are similar, as they are
both processed tobacco that is cut, milled, and sifted before
ingredients are added to control for tobacco moisture and taste.
Therefore, tobacco parameters for a cigarette can be extrapolated to
tobacco parameters for a pipe. Additionally, the filter in a pipe is
similar to a filter in a cigarette, as they both contain tow and the
length of the filter can determine the amount of suction a smoker needs
to apply to the tobacco product to draw smoke through (filter pressure
drop). Furthermore, the filter in a pipe can affect the filter
efficiency just as a cigarette filter would. Therefore, filter pressure
drop and filter parameters for a cigarette can be extrapolated to the
filter parameters for a pipe. Based on FDA's experience with
cigarettes, many design parameters required to assess public health
impacts for cigarettes will also be needed to assess public health
impacts for pipes. The following paragraphs describe in more detail the
required parameters for each subcategory of pipes.
    Section 1107.19(a) includes the design parameters that must be
contained in an SE Report to fully characterize a pipe and how changes
to these parameters impact public health, as described next:
    [cir] The bowl chamber inner and outer diameters allow FDA to
calculate the chamber wall thickness. A thicker wall will lead to a
cooler smoke and makes it less likely the user will burn themselves
when holding the chamber. Additionally, the chamber inner diameter will
affect temperature and tobacco capacity, meaning the greater the pipe
surface area, the more leaf can be burned at once, and with increased
temperature, as we have learned from our experience with other types of
tobacco products (e.g., cigarettes), this will affect smoke
constituents.
    [cir] The bowl chamber hole shape is important to characterize the
pipe as this may affect the airflow and tobacco temperatures, which, as
we have learned from our experience with other types of tobacco
products (e.g., cigarettes), affects the burn rate and smoke
constituents delivered.
    [cir] The bowl chamber volume affects the burn rate and
temperature, which, as we have learned from our experience with other
types of tobacco products (e.g., cigarettes), dictates the smoke
constituents delivered to users.
    [cir] The draught hole allows the user to pull air through the
tobacco to their mouth. The diameter of the draught hole affects the
resistance to draw which, as we have learned from our experience with
other types of tobacco products (e.g., cigarettes), can impact nicotine
and other toxicant delivery to the user.
    [cir] The draught hole dimensions and geometry may affect the
airflow and oxygen available at the burning tobacco for the chemical
reaction and, as we have learned from our experience with other types
of tobacco products (e.g., cigarettes), can affect smoke constituent
yields.
    [cir] The location of the draught hole can affect airflow and
tobacco temperatures, which, as we have learned from our experience
with other types of tobacco products (e.g., cigarettes), affects the
burn rate and smoke constituents delivered.
    [cir] The stem of a pipe delivers smoke from the bowl to the user's
mouth. The length of the stem may affect the smoke temperature, which
may affect how the product is consumed, while the width of the stem may
affect resistance to draw which, as we have learned from our experience
with other types of tobacco products (e.g., cigarettes), can impact
toxicant delivery to the user.
    [cir] The shank of a pipe similarly may affect the smoke
temperature (length) and resistance to draw (diameter), which, as we
have learned from our experience with other types of tobacco products
(e.g., cigarettes), can impact nicotine and other toxicant delivery to
the user.
    [cir] For cigarettes, the filter pressure drop affects smoke yields
(Ref. 46). Similarly for pipes, the pressure drop through the air valve
can affect nicotine and other toxicant delivery to the user. Air flow
through an air valve can affect tobacco burn rate and tobacco
temperatures which in turn, may affect smoke constituent delivery to
the user.
    [cir] Some pipes may come with a filter. For cigarettes, filter
diameter, denier per filament, total denier, filter density, and filter
length may affect filter efficiency and, in turn, smoke constituent
yields (Ref. 33). Similarly for pipes, the filter efficiency, filter
pressure drop, and filter length may affect smoke constituent yields.
    Pipe tobacco. Section 1107.19(a) includes the design parameters
that must be contained in an SE Report to fully characterize pipe
tobacco and how changes to these parameters may impact public health:
    [cir] For cigarettes, the tobacco cut size may result in more
particulate matter (Ref. 42). Similarly for pipes, the tobacco cut size
alters the size of the tobacco pieces, which may result in more
particulate matter.
    [cir] For cigarettes, the tobacco moisture or oven volatiles may
affect puff count (Ref. 41). Similarly for pipes, the tobacco moisture
or oven volatiles may affect puff count.
    Waterpipes: Cigarette tobacco and waterpipe tobacco are similar, as
they are both processed tobacco that is cut, milled, and sifted before
ingredients are added to control for tobacco moisture and taste.
Therefore, tobacco parameters for a cigarette can be extrapolated to
tobacco parameters for a waterpipe. Additionally, the length of the
waterpipe stem affects the pressure drop in the waterpipe in a similar
way as the length of the filter and filter tow causes a filter pressure
drop in a cigarette: Both determine the amount of suction a smoker
needs to apply to the tobacco product to draw smoke through. Therefore,
filter pressure drop for a cigarette can be extrapolated to the
pressure drop of a waterpipe. Based on FDA's experience with
cigarettes, many design parameters required to assess

public health impacts for cigarettes will also be needed to assess
public health impacts for waterpipes. The following paragraphs describe
in more detail the required parameters for each subcategory of
waterpipes.
    Section 1107.19(a) includes the design parameters that must be
contained in an SE Report to fully characterize waterpipes and how
changes to these parameters may impact public health, as described
next:
    [cir] Hose dimensions (length and diameter) are directly
proportional to air infiltration and affects toxicant yields (Ref. 49).
    [cir] Hose material may affect hose permeability, which may affect
smoke constituent yields (Ref. 49).
    [cir] Water filtering efficiency is directly proportional to
mainstream smoke and can increase exposure to HPHCs (Ref. 50).
    [cir] For cigarettes, the filter pressure drop affects smoke yields
(Ref. 46). Similarly for waterpipes, the pressure drop may result in
differences in the difficulty of pulling air through the waterpipe and,
in turn, affect smoke constituent yields.
    [cir] Waterpipe components or parts, including stem, bowl,
windscreen (foil), and purge valve, impact puffing behavior and
toxicant exposure; therefore, the foil dimensions and ventilation may
affect smoke constituent yields (Ref. 51).
    [cir] The shape and size (diameter and volume) of the base can
affect the pressure drop or difficulty of pulling air through the
waterpipe hose (Ref. 51).
    [cir] The head dimensions (height, top diameter, bottom diameter,
volume, and number of holes) affect how long a smoke session lasts by
controlling how much tobacco can be used during a session. Head
dimensions can also affect airflow beneath and through the tobacco to
make heat transfer more effective, prolonging smoking sessions (Ref.
51).
    [cir] The head materials could aid in heat transfer, prolonging the
heating of the tobacco and causing the tobacco to reach temperatures
that affect smoke yields (Ref. 52).
    Waterpipe heating source: Section 1107.19(a) includes the design
parameters that must be contained in an SE Report to fully characterize
a waterpipe heating source and how changes to these parameters may
impact public health, as described next:
    [cir] When combusted, heating sources such as charcoal or wood
cinders expose the user to high yields of toxicants such as carbon
monoxide and polycyclic aromatic hydrocarbons. Therefore, the heating
source mass, density, and temperature may affect smoke constituent
yields (Ref. 53).
    Waterpipe filler: Section 1107.19(a) includes the design parameters
that must be contained in an SE Report to fully characterize waterpipe
filler and how changes to these parameters may impact public health, as
described next:
    [cir] For cigarettes, the tobacco cut size may result in more
particulate matter (Refs. 41 and 42). Similarly for waterpipe filler,
the tobacco cut size alters the size of the tobacco pieces, which may
result in more particulate matter. Finer tobacco cut size may result in
a decrease in filling power and in turn, a larger amount of tobacco in
the bowl.
    [cir] For cigarettes, the tobacco moisture or oven volatiles may
affect puff count (Ref. 41). Similarly for waterpipe filler, the
tobacco moisture or oven volatiles may affect puff count. Moisture
contributes to packing density, thus decreasing void volume.
    Waterpipe foil: Section 1107.19(a) includes the design parameters
that must be contained in an SE Report to fully characterize waterpipe
foil and changes to these parameters may impact public health, as
described next:
    [cir] Waterpipe components or parts, including the windscreen
(foil) impact smoke's puffing behavior and toxicant exposure.
Therefore, the foil dimensions such as length, width, diameter, and
foil thickness may affect smoke constituent yields (Ref. 51).
    [cir] The aluminum foil perforation pattern (diameter and number of
holes) impacts the path of hot gases through the tobacco mixture, which
may affect smoke constituent yields (Ref. 51).
    Waterpipe head: Section 1107.19(a) includes the design parameters
that must be contained in an SE Report to fully characterize a
waterpipe head and how changes to these parameters may impact public
health, as described next:
    [cir] Waterpipe components or parts, including stem, bowl,
windscreen (foil), and purge valve, impact puffing behavior and
toxicant exposure; therefore, the foil dimensions and ventilation may
affect smoke constituent yields (Ref. 51).
    ENDS: Section 1107.19(a) includes the design parameters that must
be contained in an SE Report to fully characterize ENDS and how changes
to these parameters may impact public health, as described next:
    [cir] The air flow rate of the ENDS can affect the coil/heating
element temperature, e-liquid consumption, and aerosol characteristics
such as particle number concentration, count median diameter, and
particulate matter (PM)2.5, which impact aerosol exposure (Ref. 54).
    [cir] Coil/heating element resistance may affect overall heating
element resistance, thereby influencing heating element temperature.
The coil/heating element's resistance, material and the voltage \18\
determine the current flow and heating element temperature. Because the
coil/heating element temperature is not constant, coil/heating element
resistance can be used to characterize the coil temperature over time.
The heating element temperature and temperature duration may affect
toxicant emissions and nicotine delivery (Refs. 55-59).
---------------------------------------------------------------------------

    \18\ Voltage, current, and resistance are used to ensure the
battery and the ENDS are operating within the ``normal operating
range.'' The battery manufacturer sets the normal range of the
voltage and current. Understanding the resistance allows FDA to
assess whether the coil is drawing more current than the battery is
designed for.
---------------------------------------------------------------------------

    [cir] Coil/heating element resistance and battery output voltage
determine power delivery unit (PDU) wattage. PDU wattage determines the
amount of heat produced by the atomizer. PDU wattage or wattage
operating range may affect the heating element temperature, thereby
affecting toxicant emissions (Refs. 57 and 59).
    [cir] An increase in battery capacity (mAh rating) can increase the
number of puffs the e-cigarette can deliver per vaping session. Longer
vaping sessions may lead to greater exposure to toxicant emissions
(Ref. 58).
    [cir] The temperature of the coil/heating element can affect the
chemical and physical characteristics of the aerosol delivered to the
user. An increase in coil/heating element temperature can increase HPHC
levels in the aerosol, therefore, maximum coil/heating element
temperature and temperature control deviation from this maximum coil/
heating element temperature can affect toxicant emissions and nicotine
delivery (Refs. 56-59).
    [cir] Number of coils/heating element present can affect overall
atomizer resistance and distribution of heat dissipation (Ref. 60).
    [cir] The position of the coil/heating element can increase the
possibility of dry puff conditions and subsequent increased toxicant
emissions (Ref. 57).
    [cir] Atomizer and cartridge components of e-cigarettes may be
heated repeatedly and aerosolized and can contribute to increased
toxicant emissions (Ref. 55).
    [cir] Puff count can differ depending on other puff topography
(e.g., puff duration and puff flow rate), e-cigarette and atomizer
design, and e-liquid parameters. Puff count can also affect total puff
volume, which in turn can

affect total toxicant emissions (Ref. 61). In addition, information on
the puff count of ENDS helps FDA assess how the product compares with
other products.
    [cir] E-liquid capacity of the atomizer tank/cartridge can affect
total puff volume, which in turn can affect total toxicant emissions
(Refs. 61 and 62).
    [cir] Battery/PDU voltage or voltage operating range may affect the
heating element temperature, thereby affecting toxicant emissions and
nicotine delivery (Refs. 56-59).
    [cir] Battery wattage or wattage operating range may affect the
heating element temperature, thereby affecting toxicant emissions
(Refs. 57 and 59).
    [cir] Coil/heating element resistance and battery output voltage
determine PDU wattage. PDU wattage determines the amount of heat
produced by the atomizer. PDU wattage or wattage operating range may
affect the heating element temperature, thereby affecting toxicant
emissions (Refs. 57 and 59).
    [cir] PDU wattage operating range may affect the heating element
temperature, thereby affecting toxicant emissions (Refs. 57 and 59).
    [cir] The temperature of the coil/heating element can affect the
chemical and physical characteristics of the aerosol delivered to the
user. An increase in coil/heating element temperature can increase HPHC
levels in the aerosol, therefore, maximum coil/heating element
temperature and temperature control deviation from this maximum coil/
heating element temperature can affect toxicant emissions and nicotine
delivery (Refs. 56-59).
    [cir] Coil/heating element resistance, number of coils/heating
element, coil/heating element gauge, and coil/heating element
configuration may affect overall heating element resistance, thereby
influencing heating element temperature. The heating element
temperature may affect toxicant emissions and nicotine delivery (Refs.
55-59).
    [cir] Battery type, battery current operating range, battery
failure safety features, battery conformance to standards, and PDU
current operating range are necessary for evaluating battery and PDU
safety. Risks of e-cigarette battery explosion, leakage, fire, or
overheating are a safety concern (Refs. 55 and 63).
    [cir] Battery power impacts the delivery of nicotine and the total
emissions of volatile aldehydes (Refs. 64 and 65).
    [cir] Battery and PDU voltage impacts the amount of e-liquid
consumed, the vapor temperature, and the total emissions of volatile
aldehydes (Ref. 65).
    [cir] The draw resistance of the ENDS impacts the ease of drawing
air into the ENDS to produce aerosol, which can affect nicotine and
other toxicant delivery to the user (Ref. 66). For cigarettes, we
evaluate filter pressure drop since it is more informative than draw
resistance; however, for ENDS, there is no filter pressure drop or
other similar parameter that could be used in place of draw resistance.
    [cir] PDU current cutoff is an electrical cutoff and a safety
feature, that interrupts electric current when a specific condition is
met (temperature, current, etc.) to protect the user. (Refs. 55 and
63).
    [cir] Inhaled aerosol temperatures can be damaging or uncomfortable
to users who inhale aerosol above a certain temperature (Ref. 67).
    E-liquid. Section 1107.19(a) includes the design parameters that
must be contained in an SE Report to fully characterize e-liquids and
how changes to these parameters may impact public health, as described
next:
    [cir] The e-liquid volume can affect the delivery of nicotine and
other toxicants to the user (Refs. 61 and 62).
    [cir] Aerosol parameters such as particle number concentration,
count median diameter, and PM2.5 are used to characterize
the amount and size of particles to which the user is exposed.
Epidemiological and clinical studies have shown that exposure to large
amounts of small particles can impair lung function and is correlated
with cardiovascular disease (Refs. 68 and 69).
    [cir] E-liquid viscosity and boiling point impact the proportion of
nicotine that is aerosolized (Ref. 70). E-liquid viscosity can also
affect the e-liquid absorbency through the wick and wicking rate,
possibly leading to dry puff conditions and increased toxicant
emissions. Also, the e-liquid viscosity can affect the electronic
cigarette nicotine and other toxicant delivery to the user (Refs. 60
and 61).
    [cir] The e-liquid volume can affect the delivery of nicotine and
other toxicants to the user (Refs. 61 and 62).
    Heated tobacco products (HTP): HTPs currently sold in global
markets can function in ways that are similar to products in other
product categories. For example, some HTPs can function like ENDS
products by aerosolizing e-liquids or using a battery and PDU to power
the product. Other HTPs can contain tobacco filler, like a non-HTP
cigarette or cigar, but are heated instead of combusted. For these
reasons, the properties of HTPs vary widely but are comparable to the
properties of other tobacco product categories. Based on FDA's
experience with other similarly characterized tobacco products, many
design parameters required to assess public health impacts for those
products will also be needed to assess public health impacts for HTPs.
The following paragraphs describe in more detail the required
parameters for each subcategory of HTPs.
    Section 1107.19(a) includes the design parameters that must be
contained in an SE Report to fully characterize HTPs and changes to how
these parameters may impact public health, as described next.
    [cir] For cigars, the length, diameter, and mass can affect smoke
constituent yields (Ref. 35). Similarly for HTPs, dimensions (mass,
length, width, height, and diameter) can directly affect the amount of
tobacco that is heated and, in turn, affect smoke constituent yields.
    [cir] For ENDS products, the draw resistance can affect nicotine
and other toxicant delivery to the user (Ref. 66). Similarly for HTPs,
the draw resistance can impact the ease of drawing air into the product
to produce aerosol, which can affect smoke constituent yields.
    [cir] For ENDS, puff count can affect total toxicants emissions
(Ref. 61). Similarly for HTPs, the puff count can affect puff volume,
which in turn can affect total toxicant emissions.
    [cir] For ENDS, e-liquid capacity of the atomizer tank/cartridge
can affect total toxicant emissions (Refs. 61 and 62). Similarly for
HTPs, the product volume (capacity of the cartridge) can affect total
puff volume, which, in turn, can affect total toxicant emissions.
    [cir] For ENDS, airflow rate can impact aerosol exposure (Ref. 54).
Similarly for HTPs, the airflow rate allows air to flow from the
heating element to the user's mouth; some products allow the user to
manually change the airflow while others have a minimum airflow that
activates the product. Overall, airflow rate will impact aerosol
exposure.
    [cir] For cigars, ventilation may affect smoke constituents yields
(Ref. 34). Similarly for HTPs, ventilation may affect smoke constituent
yields.
    [cir] For ENDS, the battery and PDU voltage can impact volatile
aldehydes emission (Ref. 65). Similarly for HTPs, the battery and PDU
voltage impact the amount of e-liquid consumed, the vapor temperature,
and the total emissions of volatile aldehydes.
    [cir] For ENDS, the battery type, failure safety features, and
battery conformance to standards are necessary for evaluating battery
and PDU safety. Risks of e-cigarette battery explosion, leakage, fire,
or overheating are a safety concern (Refs. 55 and 63). Similarly for
HTPs the temperature sensor is a safety feature that allows the product
power to be cut

off to ensure the product does not get too hot, causing the battery to
vent or harm the user.
    [cir] For cigarettes, the paper length and width may affect puff
count and smoke constituents (Ref. 36). Similarly for HTPs, the
material wrapper length and width may directly influence the area
through which the air is permitted to enter the tobacco column, which,
in turn, may affect puff count and smoke constituent yields.
    [cir] For cigarettes, the cigarette paper basis weight may affect
puff count and smoke constituents (Ref. 36). Similarly for HTPs, the
material wrapper basis weight may affect puff count and smoke
constituent yields.
    [cir] For cigars, the cigar wrapper porosity may affect smoke
constituent yields (Refs. 37 and 38). Similarly for HTPs, the material
porosity may affect smoke constituent yields.
    [cir] For ENDS, the heating element configuration and the
temperature it reaches based on the type of heating element and its
configuration, can affect the chemical and physical characteristics of
the aerosol delivered to the user (Refs. 56-59). Similarly, for HTPs,
different heating element sources, such as coils, can reach different
temperatures, which affects the chemical and physical characteristics
of the aerosol delivered to the user.
    [cir] For ENDS, the temperature of the heating element can affect
the chemical and physical characteristics of the aerosol delivered to
the user (Refs. 56-59). Similarly for HTPs, the temperature of the
heating element (heating element temperature range, operational
temperature, maximum temperature) can affect the chemical and physical
characteristics of the aerosol delivered to the user. An increase in
heating element temperature can increase HPHC levels in the aerosol;
therefore, maximum heating element temperature and temperature control
deviation from this maximum heating element temperature can affect
toxicant emissions and nicotine delivery.
    [cir] For ENDS, the heating element temperature may affect toxicant
emissions and nicotine delivery (Ref. 59). Similarly for HTPs, the
heating element can have a direct effect on the heat transfer to the e-
liquid or tobacco, and in turn, affect the smoke constituent yields.
    [cir] For ENDS, the heating element configuration may affect
toxicant emissions and nicotine delivery (Refs. 55-59). Similarly for
HTPs, the heating element configuration may affect overall heating
element resistance, thereby influencing heating element temperature.
The heating element temperature may affect toxicant emissions and
nicotine delivery.
    [cir] For ENDS, the heating element dimensions may affect toxicant
emissions and nicotine delivery (Refs. 55-59). Similarly for HTPs, the
heating element dimensions, such as length, influence the overall
surface area, which affects heating element resistance, which
influences the heating element temperature.
    [cir] For ENDS, the heating element mass may affect toxicant
emissions and nicotine delivery (Refs. 55-59). Similarly for HTPs, the
heating element mass influences the power delivery of the battery, and
in turn, the heat applied to the e-liquid or tobacco, which affects the
smoke constituent yields and in turn, affects the smoke constituent
yields.
    [cir] For ENDS, the heating element location may affect toxicant
emissions and nicotine delivery (Refs. 55-59). Similarly for HTPs, the
heating element location can affect nicotine emissions.
    [cir] For ENDS, the number of heating elements may influence the
heating element temperature thereby affecting toxicant exposure and
nicotine delivery (Ref. 60). Similarly for HTPs, the number of coils/
heating elements present can affect overall resistance and distribution
of heat dissipation.
    [cir] For ENDS, the heating element diameter or gauge may affect
toxicant emissions and nicotine delivery (Refs. 55-59). Similarly for
HTPs, the larger the diameter of the heating element, the lower its
resistance, and vice versa. Heating element resistance may influence
heating element temperature. The heating element temperature may affect
toxicant emissions and nicotine delivery.
    [cir] For ENDS, the heating element resistance may affect toxicant
emissions and nicotine delivery (Refs. 55-59). Similarly for HTPs, the
heating element resistance may affect overall heating element
resistance, thereby influencing heating element temperature. The
heating element temperature may affect toxicant emissions and nicotine
delivery.
    [cir] For cigars, tobacco filler mass may affect smoke constituent
yields (Ref. 34). Similarly for HTPs, the tobacco filler mass may
affect smoke constituent yields.
    [cir] For cigarettes, tobacco rod density may modify burn
properties and smoke constituent yields (Refs. 39 and 40). Similarly
for HTPs, the tobacco rod density may modify burn properties and smoke
constituent yields.
    [cir] For cigarettes, the tobacco moisture or oven volatiles may
affect puff count (Ref. 41). Similarly for HTPs, tobacco moisture or
oven volatiles may affect puff count.
    [cir] For cigarettes, tobacco cut size alters the size of the
tobacco pieces, which may result in more particulate matter (Ref. 42).
Similarly for HTPs, tobacco filler manufacturing and processing as well
as tobacco cut size alters the size of the tobacco pieces, which may
result in more particulate matter.
    [cir] For e-liquids, the e-liquid volume can affect the delivery of
nicotine and other toxicants to the user (Refs. 61 and 62). Similarly
for HTPs, the e-liquid volume can affect the delivery of nicotine and
other toxicants to the user.
    [cir] For e-liquids, the e-liquid viscosity can affect the
electronic cigarette nicotine and other toxicant delivery to the user
(Refs. 60, 61, and 70). Similarly for HTPs, the e-liquid viscosity and
boiling point impact the proportion of nicotine that is aerosolized
(Ref. 70). The e-liquid viscosity can affect the nicotine and other
toxicant delivery to the user.
    [cir] For ENDS, an increase in battery capacity (mAh rating) can
increase the number of puffs the e-cigarette can deliver per vaping
session. Longer vaping sessions may lead to greater exposure to
toxicant emissions (Ref. 58). Similarly for HTPs the battery capacity
is a measure of the charge stored by the battery. The higher the mAh
rating, the higher the capacity of the battery and the longer it will
last between charges. The longer the battery lasts, the more the user
can inhale smoke constituents.
    [cir] For ENDS the battery and PDU voltage operating range and
wattage effects volatile aldehydes emission (Ref. 65). Similarly for
HTPs, the battery and PDU voltage operating range or wattage impact the
amount of e-liquid consumed, the vapor temperature, and the total
emissions of volatile aldehydes.
    [cir] For ENDS, the battery type, battery current operating range,
battery failure safety features, battery conformance to standards, and
PDU current operating range are necessary for evaluating battery and