Rule2021-21009
Content and Format of Substantial Equivalence Reports; Food and Drug Administration Actions on Substantial Equivalence Reports
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Published
October 5, 2021
Effective
November 4, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is issuing this final rule to provide additional information on the content and format of reports intended to demonstrate the substantial equivalence of a tobacco product (SE Reports). The final rule also establishes the general procedures FDA intends to follow when evaluating SE Reports, including procedures that address communications with the applicant and the confidentiality of data in an SE Report. The final rule will provide applicants with more certainty and clarity related to preparing and submitting SE Reports.
Full Text
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[Federal Register Volume 86, Number 190 (Tuesday, October 5, 2021)]
[Rules and Regulations]
[Pages 55224-55300]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-21009]
[[Page 55223]]
Vol. 86
Tuesday,
No. 190
October 5, 2021
Part III
Department of Health and Human Services
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Food and Drug Administration
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21 CFR Parts 16, 1100, 1107, et al.
Content and Format of Substantial Equivalence Reports; Food and Drug
Administration Actions on Substantial Equivalence Reports, and
Premarket Tobacco Product Applications and Recordkeeping Requirements;
Final Rules
Applications for Premarket Review of New Tobacco Products; Draft
Guidance for Industry; Withdrawal; Notice
Federal Register / Vol. 86, No. 190 / Tuesday, October 5, 2021 /
Rules and Regulations
[[Page 55224]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 16 and 1107
[Docket No. FDA-2016-N-3818]
RIN 0910-AH89
Content and Format of Substantial Equivalence Reports; Food and
Drug Administration Actions on Substantial Equivalence Reports
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
issuing this final rule to provide additional information on the
content and format of reports intended to demonstrate the substantial
equivalence of a tobacco product (SE Reports). The final rule also
establishes the general procedures FDA intends to follow when
evaluating SE Reports, including procedures that address communications
with the applicant and the confidentiality of data in an SE Report. The
final rule will provide applicants with more certainty and clarity
related to preparing and submitting SE Reports.
DATES: This rule is effective November 4, 2021.
ADDRESSES: For access to the docket to read background documents or
comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the
docket number found in brackets in the heading of this final rule into
the ``Search'' box and follow the prompts, and/or go to the Dockets
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852,
240-402-5700.
FOR FURTHER INFORMATION CONTACT: Daniel Gittleson or Nathan Mease,
Office of Regulations, Center for Tobacco Products, Food and Drug
Administration, Document Control Center, Bldg. 71, Rm. G335, 10903 New
Hampshire Ave., Silver Spring, MD 20993-0002, 877-287-1373,
<a href="/cdn-cgi/l/email-protection#d392a0b890878393b5b7b2fdbbbba0fdb4bca5"><span class="__cf_email__" data-cfemail="2667554d65727666404247084e4e5508414950">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose of the Final Rule
B. Summary of the Major Provisions of the Final Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
IV. Legal Authority
V. Description of the Final Regulation and Comments and Responses
A. Introduction
B. Description of General Comments and FDA Responses
C. Comments on Subpart B--General and FDA Responses
D. Comments on Subpart C--Substantial Equivalence Reports and
FDA Responses
E. Comments on Subpart D--FDA Review and FDA Responses
F. Comments on Subpart E--Miscellaneous Provisions and FDA
Responses
G. Comments on Other Issues for Consideration and FDA Responses
VI. Effective Date
VII. Economic Analysis of Impacts
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Congressional Review Act
XII. Consultation and Coordination With Indian Tribal Governments
XIII. References
I. Executive Summary
A. Purpose of the Final Rule
This final rule provides further information on the content and
format of SE Reports, including the information that SE Reports must
contain. FDA is finalizing this rule after reviewing comments to the
proposed rule (84 FR 12740, April 2, 2019), as well as the SE review
experience the Agency has gained since enactment of the Family Smoking
Prevention and Tobacco Control Act (Tobacco Control Act) (Pub. L. 111-
31). As explained in the proposed rule, the SE Reports that FDA has
seen to date range widely in the level of detail included, with some
reports including very little information on the comparison of the new
tobacco product with a predicate tobacco product and some including
much more. This final rule will provide applicants with a better
understanding of the level of detail that an SE Report must contain.
The final rule also addresses issues such as FDA communications with
the applicant, the retention of records that support the SE Report,
confidentiality of SE Reports, and electronic submission of the SE
Report and amendments.
B. Summary of the Major Provisions of the Final Rule
Under the final rule, an SE Report must provide information
comparing the new tobacco product to a predicate tobacco product,
including information that will enable FDA to uniquely identify the new
tobacco product and the predicate tobacco product, as well as
comparison information. The requirements will 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 (as required by section 910(a)(2)(A) of
the FD&C Act).
In addition, the rule explains how an applicant can amend or
withdraw an SE Report, and explains how an applicant may transfer
ownership of an SE Report to a new applicant. The rule also addresses
FDA communications with applicants on SE Reports and explains FDA
review cycles and FDA actions, including the issuance of orders and the
rescission of orders. The rule also establishes the length of time
records related to the SE Report must be maintained, describes FDA's
disclosure provisions, and requires electronic submission of SE
Reports, unless the applicant requests and is granted a waiver.
C. Legal Authority
This rule is being issued based upon FDA's authority to require
premarket review of new tobacco products under sections 905(j) and
910(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 387e(j) and 387j(a)), FDA's authority to require reports under
section 909(a) of the FD&C Act (21 U.S.C. 387i(a)), FDA's authorities
related to adulterated and misbranded tobacco products under sections
902 and 903 (21 U.S.C. 387b and 387c), as well as FDA's rulemaking and
inspection authorities under sections 701(a) and 704 of the FD&C Act
(21 U.S.C. 371(a) and 374).
D. Costs and Benefits
This final rule would impose incremental compliance costs on
affected entities to read and understand the rule, establish or revise
internal procedures, and fill out a form for SE Reports. We estimate
that the present value of industry compliance costs ranges from $0.4
million to $3.4 million, with a primary estimate of $1.9 million at a 3
percent discount rate, and from $0.4 million to $2.9 million, with a
primary estimate of $1.6 million at a 7 percent discount rate over 10
years. Annualized industry compliance costs over 10 years range from
$0.05 million to $0.39 million, with a primary estimate of $0.22
million at a 3 percent discount rate and from $0.06 million to $0.42
million, with a primary estimate of $0.23 million at a 7 percent
discount rate.
The incremental benefits of this final rule are potential time-
savings to industry and cost-savings to government. The final rule
clarifies when applicants may certify that certain
[[Page 55225]]
characteristics are identical in the new tobacco product and the
predicate tobacco product. Certifying may save applicants time in
preparing their SE Reports. We anticipate shorter review times for SE
Reports as a result of this final rule. In addition, based on our
experience with prior SE Reports, we believe this final rule will lead
to higher quality SE Reports, saving us time in review and requiring
fewer staff to review SE Reports, which will result in cost-savings. We
estimate that the present value of government cost-savings ranges from
$15.1 million to $150.6 million, with a primary estimate of $50.2
million at a 3 percent discount rate, and from $12.4 million to $124
million, with a primary estimate of $41.3 million at a 7 percent
discount rate over 10 years. Annualized government cost-savings over 10
years range from $1.8 million to $17.7 million, with a primary estimate
of $5.9 million at both 3 and 7 percent discount rates.
The qualitative benefits of this final rule include additional
clarity to industry about the requirements for the content and format
of SE Reports. The final rule would also establish the general
procedures we will follow in reviewing and communicating with
applicants. In addition, this final rule would make the SE pathway more
predictable.
II. Table of Abbreviations/Commonly Used Acronyms in This Document
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Abbreviation What it means
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ANPRM............................... Advance Notice of Proposed
Rulemaking
CCS................................. Container Closure System
CORESTA............................. Cooperation Centre for Scientific
Research Relative to Tobacco
CTP................................. Center for Tobacco Products
DQPH................................ Different Questions of Public
Health
ENDS................................ Electronic Nicotine Delivery
System
EA.................................. Environmental Assessment
E.O................................. Executive Order
FDA................................. Food and Drug Administration
FD&C Act............................ Federal Food, Drug, and Cosmetic
Act
FSC................................. Fire Standard Compliant
FOIA................................ Freedom of Information Act
GRAS................................ Generally Recognized as Safe
HPHC................................ Harmful and Potentially Harmful
Constituents
HTP................................. Heated Tobacco Products
MDSS................................ Manufacturing Data Sheet
Specification
NEPA................................ National Environmental Policy Act
of 1969
NSE................................. Not Substantially Equivalent
PDU................................. Power Delivery Unit
PM.................................. Particulate Matter
PMTA................................ Premarket Tobacco Application
PRA................................. Paperwork Reduction Act of 1995
QRA................................. Quantitative Risk Assessment
RIA................................. Regulatory Impact Analysis
RYO................................. Roll-Your-Own
SE.................................. Substantial Equivalence
TPMF................................ Tobacco Product Master File
TSNA................................ Tobacco-Specific Nitrosamines
VOC................................. Volatile Organic Compound
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III. Background
The FD&C Act, as amended by the Tobacco Control Act, generally
requires that before a new tobacco product may be introduced into
interstate commerce for commercial distribution in the United States,
the new tobacco product must undergo premarket review by FDA. Section
910(a)(1) of the FD&C Act defines a ``new tobacco product'' as: (1) Any
tobacco product (including those products in test markets) that was not
commercially marketed in the United States as of February 15, 2007, or
(2) any modification (including a change in design, any component, any
part, or any constituent, including a smoke constituent, or in the
content, delivery or form of nicotine, or any other additive or
ingredient) of a tobacco product where the modified product was
commercially marketed in the United States after February 15, 2007.
The FD&C Act establishes three premarket review pathways for a new
tobacco product:
<bullet> Submission of a premarket tobacco application under
section 910(b);
<bullet> submission of a report intended to demonstrate that the
new tobacco product is substantially equivalent to a predicate tobacco
product under section 905(j)(1)(A) (``SE Report''); and
<bullet> submission of a request for an exemption under section
905(j)(3) (implemented at Sec. 1107.1 (21 CFR 1107.1)).
Under section 910(a)(2)(B) of the FD&C Act, a manufacturer of a
tobacco product that was first introduced or delivered for introduction
into interstate commerce for commercial distribution after February 15,
2007, and prior to March 22, 2011, that submitted an SE Report \1\
prior to March 23, 2011, may continue to market the tobacco product
unless FDA issues an order that the tobacco product is not
substantially equivalent (``provisional'' tobacco products). For any
new tobacco product introduced or delivered for introduction into
interstate commerce for commercial distribution on or after March 22,
2011, or for which a substantial equivalence report was not submitted
prior to March 23, 2011, a manufacturer must first submit a premarket
application for the new tobacco product to FDA, and FDA must issue an
order authorizing the commercial distribution of the new tobacco
product or find the product exempt from the requirements of substantial
equivalence under section 910(a)(2)(A) of the FD&C Act, before the
product may be introduced into commercial distribution. If a new
tobacco product is marketed without an order or a finding of exemption
from substantial equivalence, it is adulterated under section 902 of
the FD&C Act and misbranded under section 903 of the FD&C Act and
subject to enforcement action.
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\1\ In this rule, FDA refers to ``SE applications'' as ``SE
Reports,'' but the terms both refer to a premarket submissions under
section 905(j)(1)(A) of the FD&C Act.
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Since the enactment of the Tobacco Control Act, FDA has received
thousands of SE Reports, many of which lacked the information necessary
for FDA to make a substantial equivalence determination. To assist
applicants in better preparing an SE Report, on April 2, 2019, FDA
issued a proposed rule to provide additional information regarding the
content and format of reports intended to establish the substantial
equivalence of a tobacco product. FDA received about 100 comments to
the docket for the proposed rule, including comments from tobacco
product manufacturers and trade organizations, retailers,
representatives of tribes/tribal organizations, public health groups,
individual consumers, and other submitters. We summarize and respond to
these comments in section V of this rule. After considering these
comments, FDA developed this final rule, which includes changes made in
response to the comments.
IV. Legal Authority
As described in the following paragraphs, FDA is issuing this rule
to address the content, form, and manner of reports intended to
demonstrate the substantial equivalence of a new tobacco product to a
predicate tobacco product. The rule also addresses record keeping,
reports, and the information essential to FDA's implementation of the
FD&C Act. In accordance with section 5 of the Tobacco Control Act, FDA
intends that the requirements established by this rule are severable
and that the invalidation of any provision of this rule would not
affect the validity of any other part of this rule.
Section 910(a)(2) of the FD&C Act requires a new tobacco product to
be the subject of a premarket tobacco product application (PMTA)
marketing order unless FDA has issued an SE order authorizing its
commercial distribution or the tobacco product is exempt from
substantial equivalence. To satisfy the requirement of premarket
review, a manufacturer may submit a report intended to demonstrate the
substantial
[[Page 55226]]
equivalence of a new tobacco product to a predicate tobacco product
under section 905(j) of the FD&C Act. Section 905(j) provides that FDA
may prescribe the form and manner of the substantial equivalence
report, and section 910(a)(4) of the FD&C Act requires that as part of
the 905(j) report, the manufacturer provide an adequate summary of any
health information related to the new tobacco product or state that
such information will be made available upon request.
Based on the information provided by the applicant, section
910(a)(3)(A) of the FD&C Act authorizes FDA to issue an order finding
substantial equivalence when FDA finds that the new tobacco product is
in compliance with the requirements of the FD&C Act and either: (1) Has
the same characteristics as the predicate tobacco product or (2) has
different characteristics and the information submitted contains
information, including clinical data if deemed necessary by FDA, that
demonstrates that it is not appropriate to regulate the product under
the PMTA provisions because the product does not raise different
questions of public health.
Section 909(a) of the FD&C Act authorizes FDA to issue regulations
requiring tobacco product manufacturers or importers to maintain such
records, make such reports, and provide such information as may be
reasonably required to assure that their tobacco products are not
adulterated or misbranded and to otherwise protect public health.
Under section 902(6)(A) of the FD&C Act, a tobacco product is
adulterated if it is required to have premarket review and does not
have an order in effect under section 910(c)(1)(A)(i) of the FD&C Act.
Under section 903(a)(6) of the FD&C Act, a tobacco product is
misbranded if a notice or other information respecting it was not
provided as required by section 905(j) of the FD&C Act. In addition, a
tobacco product is misbranded if there is a failure or refusal to
furnish any material or information required under section 909 (section
903(a)(10)(B) of the FD&C Act).
Section 701(a) of the FD&C Act gives FDA general rulemaking
authority to issue regulations for the efficient enforcement of the
FD&C Act, and section 704 of the FD&C Act provides FDA with general
inspection authority.
V. Description of the Final Regulation and Comments and Responses
A. Introduction
We received about 100 comments to the docket for the proposed rule.
In addition to the comments specific to this rulemaking that we address
in this section, we received many general comments expressing support
or opposition to the rule. These comments express broad policy views
and do not address specific points related to this rulemaking.
Therefore, these general comments do not require a response. In this
section, we have grouped similar comments together by the topics
discussed or the particular portions of the proposed rule or codified
language to which they refer. To make it easier to identify comments
and FDA's responses, the word ``Comment,'' in parenthesis, appears
before the comment's description, and the word, ``Response,'' in
parenthesis appears before FDA's response. Each comment is numbered to
help distinguish among different comments, and the number assigned is
purely for organizational purposes and does not signify value or
importance. Similar comments are grouped together under the same
comment number. In this section we also describe changes we made to the
final rule following our consideration of the comments and other
information.
As described in more detail in this section, following our
consideration of these comments, we have made changes to proposed
Sec. Sec. 1107.10, 1107.12, 1107.18, 1107.19, 1107.22, 1107.40,
1107.44, 1107.46, 1107.48, and 1107.50. The changes are largely
intended to clarify areas of confusion or address concerns raised by
the comments, and we describe in detail the changes made to each of
these provisions in the following paragraphs. Following our review of
the comments, we are not making changes to other sections included in
the proposed rule and are finalizing those sections without change. In
addition, we received no comments on the proposed change to add
language to Sec. 16.1(b)(2) (21 CFR 16.1(b)(2)) regarding rescission
(as included in the proposed rule), and we are finalizing Sec.
16.1(b)(2) without change.
B. Description of General Comments and FDA Responses
(Comment 1) Some comments object to the proposed rule, stating that
the rule violates the statute because the rule would not create a
viable pathway to market products that qualify for the SE pathway that
is more streamlined than the PMTA pathway. For example, one comment
objects to the proposed rule and states that FDA has ``exceeded
Congressional intent by over-complicating the [premarket] pathways,
ignoring the first prong of the SE standard and making the second prong
nearly as burdensome as the PMTA pathway.'' Another comment states that
regardless of whether an SE Report cites the first or second prong for
determining substantial equivalence, ``the SE pathway is intended to be
significantly less burdensome than the PMTA pathway,'' and the SE
pathway should ``require the least information and be the simplest to
implement while the PMTA pathway, with its focus on the `protection of
public health' would require the more extensive information and data.''
Other comments also object to the rule and state the SE pathway should
be much more like a ``notification'' process than the PMTA pathway.
(Response 1) We disagree with these comments. We have received
thousands of premarket applications, including SE Reports, and we
developed this rule based on our experience with those SE Reports and
the framework for substantial equivalence under sections 905(j) and 910
of the FD&C Act. The statutory requirements related to substantial
equivalence differ from the statutory framework and requirements for a
PMTA, and each pathway has different standards for authorization. The
rule will provide applicants with additional clarity and understanding
of the information needed in an SE Report for FDA to make a
determination under the statutory requirements related to substantial
equivalence (sections 905(j) and 910(a) of the FD&C Act). Notably,
under the SE pathway, the applicant must receive an order prior to
marketing the new tobacco product (unless it has received authorization
through a different premarket pathway or it is a provisional tobacco
product); the FD&C Act does not authorize a ``notification process'' as
an alternative to receiving an SE order. As appropriate, however, we
have developed mechanisms to lessen the burden for submitting data that
are more streamlined by allowing for certifications when the data
between the new and predicate tobacco products are identical (see,
e.g., Sec. 1107.18(l)).
(Comment 2) Some comments suggest FDA adopt an approach similar to
the substantial equivalence process FDA applies to devices under
sections 510(k) and 513(i) of the FD&C Act (21 U.S.C. 360(k) and
360c(i)), for example, by permitting a notification process. Other
comments reference guidance documents related to the 510(k) process for
devices as examples of how to
[[Page 55227]]
implement the SE pathway for tobacco products.
(Response 2) We disagree with these comments. FDA's interpretation
of SE with respect to medical devices is based on different statutory
sections from those applicable to tobacco products and, due to the
differences in the statutory provisions underlying the 510(k) premarket
pathway, it has limited utility as a model in considering SE for
tobacco products. As described in the preceding response and also in
section IV below, sections 905(j) and 910(a) of the FD&C Act set out
the substantial equivalence provisions that are specifically applicable
to tobacco products, and reflect the differences in these regulated
products. For example, the medical device provisions involve
considerations related to the safety and effectiveness of medical
devices. In comparison, the statutory provisions relating to SE for
tobacco products focus on the characteristics of the new tobacco
product, and where there are differences, whether such differences
cause the new tobacco product to raise different questions of public
health.
(Comment 3) Some comments object that the proposed rule would
require behavioral information in an SE Report that the FD&C Act
requires only for a new product subject to a PMTA. One comment notes
that because the ``SE process is an exception to PMTA requirements,
designed to determine whether the product should have to undergo the
full PMTA process, [r]equiring manufacturers to submit PMTA-level
evidence . . . is illogical.''
(Response 3) We disagree with the suggestion that behavioral
information, such as initiation and cessation information, can never be
relevant in the evaluation of an SE report. Congress broadly delegated
to FDA the authority to specify what should be included in an SE Report
and imposed no constraints of the type the comments suggest. (See
section 905 (j)(1) of the FD&C Act (``report to the Secretary [of
Health and Human Services] (in such form and manner as the Secretary
shall prescribe)'')). As many comments point out, where the new tobacco
product has different characteristics than the predicate tobacco
product, the information submitted in the SE application must ``contain
information, including clinical data if deemed necessary by [FDA], that
demonstrates . . . [that] the product does not raise different
questions of public health.'' (Section 910(a)(3)(A)(ii) of the FD&C
Act.) Congress included findings in the Tobacco Control Act that make
clear that one of the public health purposes of the legislation was to
reduce dependence on tobacco. For example, Congress stated that the
Tobacco Control Act's ``purposes'' include ensuring that FDA has the
authority to address issues of particular concern to public health
officials, especially the use of tobacco by young people and dependence
on tobacco and promoting cessation to reduce disease risk and the
social-costs associated with tobacco-related diseases. (see Tobacco
Control Act sections 3(2) and (9)). In addition, Congress defined
substantial equivalence to mean that the information submitted contains
information, including clinical data if deemed necessary by the
Secretary, that demonstrates that it is not appropriate to regulate the
product under this section because the product does not raise different
questions of public health. (See FD&C Act 910(a)(3)(A)(ii).) The
reference to ``this section'' is a reference to the PMTA pathway.
Because one of the bases for FDA finding that a product is appropriate
for the protection of public health (i.e., the PMTA ``standard'')
includes the increased or decreased likelihood that existing users will
stop using and new users will initiate use of such products, it is
reasonable to examine those same considerations under the SE standard
to determine whether the differences between the predicate and the new
product show that the product should be reviewed under the PMTA
pathway.
As a result, in determining whether a new tobacco product raises
different questions of public health, FDA considers potential impacts
on initiation and cessation of tobacco use. If the SE Report lacks this
information, then we may be unable to determine that the product is
substantially equivalent.
(Comment 4) A number of comments assert that the proposed
regulation does not provide enough specificity to adequately guide
industry. For example, one comment states that the proposed rule lacked
clarity regarding the scope, type, and amount of testing and other
information needed in SE Reports for smokeless tobacco products and the
comment requests that FDA include more specific requirements regarding
the content of SE Reports for smokeless tobacco products. Other
comments suggest the rule requires too much information or the wrong
information.
(Response 4) We disagree with these comments. The rule provides
content and format information that will be applicable across a range
of categories and subcategories of tobacco products, including
smokeless tobacco products (see, e.g., Sec. 1107.19). In addition,
after reviewing the comments received in response to our invitation to
comment on design parameters for cigars, Electronic Nicotine Delivery
Systems (ENDS), and other tobacco products, the final rule now includes
design parameter information for these products. Based on our
experience, we believe that the requirements in this rule are necessary
for FDA to determine whether a product is substantially equivalent.
(Comment 5) One comment suggests that FDA should apply the rule to
currently pending SE Reports.
(Response 5) As the proposed rule explained, the requirements
included in the rule apply only after the effective date of this rule.
Accordingly, the requirements do not apply to an SE Report for a
provisional tobacco product or to any SE Report submitted before the
effective date of this rule. This does not prevent applicants with
pending SE Reports or those preparing SE Reports from referring to this
rule for guidance on how to submit amendments to pending SE reports or
prepare their SE Report prior to the effective date of this rule.
Please note that we will continue to evaluate currently pending SE
Reports and those submitted prior to the effective date as we have
evaluated those thousands of SE Reports in the years since the Tobacco
Control Act was enacted. Importantly, our previous SE evaluation
experience helped aid in the development of this final rule. In
practical effect, this means that an applicant submitting an SE report
before this rule goes into effect has an opportunity to benefit from
its contents but FDA will not refuse to accept an application for
lacking information first required in this rule (i.e., information not
already required by regulation or statute). For example, for an
application received before this rule is in effect, FDA would not
retroactively refuse to accept an application that lacks information
required for acceptance under this rule that was not already required
by regulation or statute. Likewise, if an application submitted before
the effective date of this rule lacks information necessary to enable
FDA to determine whether or not the product meets the statutory
standard as articulated in this rule (e.g., lack of data to show that
the new product is SE), FDA would not rely on this rule to deny the
application--instead FDA generally intends to evaluate SE reports and
communicate with applicants consistent with its review process to date.
(Comment 6) At least one comment suggests that FDA revise or
withdraw SE-related guidance documents when the Agency issues the final
SE regulation to reduce confusion and because the guidance documents
would
[[Page 55228]]
no longer be warranted. Other comments suggest that FDA issue new
guidance, including guidance documents with decision trees (e.g.,
similar to 510(k) process for devices).
(Response 6) FDA agrees that revision or withdrawal of guidance
documents is appropriate if the recommendations are no longer relevant
or could be confusing. Following issuance of this final rule, we intend
to review SE-related guidance documents to determine whether to revise
or withdraw any guidance documents. More specifically, we intend to
consider whether the recommendations or information included in those
guidance documents are outdated due to this final rule, and we will
update or withdraw those guidance documents as appropriate. Similarly,
we will consider whether new guidance documents should be developed or
whether updates should be made to existing guidance documents. FDA will
make any changes or withdrawals or issue new guidance documents
promptly pursuant to the procedures in 21 CFR 10.115.
C. Comments on Subpart B--General and FDA Responses
1. Scope (Sec. 1107.10)
This part establishes the procedures and provides information for
the submission of an SE Report under sections 905 and 910 of the FD&C
Act, the basic criteria for establishing substantial equivalence, and
the general procedures FDA intends to follow when evaluating SE
Reports. We are finalizing Sec. 1107.10 (Scope) with one change from
the proposed rule to reflect that this part applies to new tobacco
products ``other than `premium' cigars as defined in Sec. 1107.12.''
In the following paragraphs, we discuss the comments related to this
section, including comments on the scope of products covered.
(Comment 7) Several comments on the proposed rule discuss
``premium'' cigars. These comments included requests that FDA exempt
``premium'' cigars from premarket requirements, create a different
premarket pathway for ``premium'' cigars, or delay the effective date
for submitting premarket applications for ``premium'' cigars. Other
comments flag concerns with specific requirements included in the
proposed rule, such as concerns related to co-packaging requirements
(the comments state that ``premium'' cigar packaging does not have the
potential to alter or affect the performance, composition, constituent,
or other physical characteristics of the product); concerns related to
the applicability of ``product quantity'' change for ``premium'' cigars
as these are sold individually; and concerns related to the
``significant natural and inherent variability'' in handmade
``premium'' cigar products (the comments state these products cannot be
manufactured by hand consistently enough to permit manufacturers to
``fully characterize'' them in any meaningful way to permit a
traditional SE comparison). Other comments raise issues related to the
applicability of proposed requirements in Sec. 1107.19 to ``premium''
cigars, such as the proposed requirement that information on ``[t]he
type of tobacco, including grade and variety'' be submitted in an SE
Report, that harmful and potentially harmful constituents (HPHC) data
be submitted, given the variety of cigars and lack of smoke testing
methodologies for ``premium'' cigars, costs of HPHC testing, and
insufficient lab capacity, or that stability information be provided
given the characteristics of the product. Many of these comments
describe differences between ``premium'' cigars and other cigars, e.g.,
mechanized versus handmade processes, and state that these differences
make it more difficult for ``premium'' cigars to comply with SE
requirements.
(Response 7) FDA received a range of comments related to
``premium'' cigars.\2\ A recent court decision, Cigar Ass'n of Am., et
al. v. Food and Drug Admin., et al., ``remand[ed] the [deeming final
rule] to the FDA to consider developing a streamlined substantial
equivalence process for premium cigars'' and ``enjoin[ed] the FDA from
enforcing the premarket review requirements against premium cigars . .
. until the agency has completed its review.'' \3\ Under the terms of
the court's order, a ``premium'' cigar is defined as a cigar that meets
all of the following eight criteria:
---------------------------------------------------------------------------
\2\ Cigars are subject to Chapter IX of the FD&C Act as a result
of regulations enacted by FDA (Deeming Tobacco Products To Be
Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by
the Family Smoking Prevention and Tobacco Control Act; Restrictions
on the Sale and Distribution of Tobacco Products and Required
Warning Statements for Tobacco Products, 81 FR 28974, May 10, 2016
(``deeming final rule'')). The deeming final rule extended FDA's
regulatory authority to all tobacco products (excluding accessories
of such products). These products include all cigars, pipe tobacco,
waterpipe tobacco, electronic nicotine delivery systems (ENDS), and
other novel tobacco products.
\3\ Cigar Ass'n of Am., et al. v. Food and Drug Admin., et al.,
Case No. 1:16-cv-01460 (APM), (D.D.C. Aug. 19, 2020), Dkt. No. 214
(Cigar Ass'n of Am.).
---------------------------------------------------------------------------
1. Is wrapped in whole tobacco leaf;
2. contains a 100 percent leaf tobacco binder;
3. contains at least 50 percent (of the filler by weight) long
filler tobacco (i.e., whole tobacco leaves that run the length of the
cigar);
4. is handmade or hand rolled; \4\
---------------------------------------------------------------------------
\4\ A product is ``handmade or hand rolled'' if no machinery was
used apart from simple tools, such as a scissors to cut the tobacco
prior to rolling.
---------------------------------------------------------------------------
5. has no filter, nontobacco tip, or nontobacco mouthpiece;
6. does not have a characterizing flavor other than tobacco;
7. contains only tobacco, water, and vegetable gum with no other
ingredients or additives; and
8. weighs more than 6 pounds per 1,000 units.
As directed by the court in the Cigar Ass'n of Am. decision, FDA is
further considering the comments submitted to the deeming rule docket
that requested FDA create a streamlined SE process for ``premium''
cigars. Additionally, FDA notes that a Committee of the National
Academies of Science, Engineering, and Medicine is conducting a study
on such products. FDA intends to review the findings of that Committee
as well as any additional research specific to ``premium'' cigars (as
defined in the preceding paragraph) and their health effects, patterns
of use (such as frequency of use and usage patterns among underage
persons), and other factors. All such information will inform the
Agency's regulatory policy with respect to premarket review of
``premium'' cigars.
Because these are ongoing efforts, at this time, FDA is not
finalizing the proposed SE rule with respect to ``premium'' cigars.
Rather, FDA will take appropriate action once it has further considered
the comments submitted to the deeming rule docket that suggested FDA
create a streamlined SE process for ``premium'' cigars, as well as the
results from additional research. As such, the codified language has
been revised to exclude ``premium'' cigars from the scope of this final
rule, and the Cigar Ass'n of Am. court's definition of ``premium''
cigars has been added to Sec. 1107.12.
(Comment 8) One comment suggests that FDA add a definition for pipe
tobacco and create a different SE premarket pathway for pipe tobacco,
for example, more aligned with the 510(k) process for medical devices.
(Response 8) We interpret this comment to be a request that FDA
consider streamlined options within the three premarket pathways
available to pipe tobacco seeking authorization: PMTA, SE, and
exemption from SE, as provided in sections 905 and 910 of the FD&C Act.
Generally speaking, within the construct of the SE premarket pathway,
there are options for more
[[Page 55229]]
streamlined submissions, that will still provide the agency with the
information we need to determine whether the new tobacco product is SE,
which this final rule reflects. For example, where appropriate, certain
requirements (e.g., design parameters) are tailored by type of product.
In addition, the rule generally provides options to certify that
certain characteristics are identical in lieu of providing data for
each characteristic of the new and predicate tobacco product (Sec.
1107.18(l)). This option may be helpful to applicants as a means of
minimizing the content to be submitted, when appropriate. Finally,
because we are still considering how best to define ``pipe'' tobacco,
we are not including a definition of the term, but intend to undertake
further actions to define the term, if needed, at a future time.
However, we do not think a formal definition of ``pipe'' tobacco is
needed to continue regulating the product or to conduct an SE review.
(Comment 9) Some comments request that FDA clarify which changes
may proceed through the SE exemption pathway and those which may not.
The comment requests that FDA define the term ``minor modification'' to
help manufacturers understand which changes would qualify for the SE
exemption pathway. For example, the comments request that changes to
maintain product consistency or changes made by suppliers to components
be considered as changes eligible for the SE exemption pathway.
(Response 9) Requests for information on which changes would
qualify under the SE exemption pathway or for further information on
the term ``minor modification,'' relate to 21 CFR 1107.1 (see <a href="https://www.federalregister.gov/documents/2011/07/05/2011-16766/tobacco-products-exemptions-from-substantial-equivalence-requirements">https://www.federalregister.gov/documents/2011/07/05/2011-16766/tobacco-products-exemptions-from-substantial-equivalence-requirements</a>). Please
note that additional information related to exemption requests may be
found at <a href="https://www.fda.gov/tobacco-products/market-and-distribute-tobacco-product/exemption-substantial-equivalence">https://www.fda.gov/tobacco-products/market-and-distribute-tobacco-product/exemption-substantial-equivalence</a>; FDA also maintains
information on exemption requests that FDA has granted at: <a href="https://www.fda.gov/tobacco-products/exemption-substantial-equivalence/marketing-orders-exemption-se">https://www.fda.gov/tobacco-products/exemption-substantial-equivalence/marketing-orders-exemption-se</a>.
2. Definitions (Sec. 1107.12)
Proposed Sec. 1107.12 listed terms and definitions used in the
proposed rule. In this final rule, we have added a definition of
``premium'' cigars, as well as updated several definitions on our own
initiative to clarify the meaning or to reflect current premarket
review processes or to help the definitions apply across product
categories.
As discussed in section V.C.1 of this final rule, we are adding the
Cigar Ass'n of Am. court's definition of ``premium'' cigars to Sec.
1107.12. That definition is:
<bullet> ``Premium'' cigars means a type of cigar that: (1) Is
wrapped in whole tobacco leaf; (2) contains a 100 percent leaf tobacco
binder; (3) contains at least 50 percent (of the filler by weight) long
filler tobacco (i.e., whole tobacco leaves that run the length of the
cigar); (4) is handmade or hand rolled (i.e., no machinery was used
apart from simple tools, such as scissors to cut the tobacco prior to
rolling); (5) has no filter, nontobacco tip, or nontobacco mouthpiece;
(6) does not have a characterizing flavor other than tobacco; (7)
contains only tobacco, water, and vegetable gum with no other
ingredients or additives; and (8) weighs more than 6 pounds per 1,000
units.
The updates to Sec. 1107.12 are to the following terms:
<bullet> Brand to add an ``s'' following ``brand name'' in the
definition;
<bullet> Constituent to add ``(e.g., smoke, aerosol, droplets),''
to delete ``or any chemical or chemical compound in mainstream or
sidestream tobacco smoke,'' to add ``or part'' following component, and
to replace ``smoke'' with ``emission'';
<bullet> Finished tobacco product to move ``separately'' to follow
``consumers'' and to add ``or in the final form in which it is intended
to be sold to consumers'' to better clarify what is meant by finished;
<bullet> Harmful and potentially harmful constituent to add the
phrase ``including as an aerosol or any other emission'' in paragraph
(1);
<bullet> Heating source to change ``a'' to ``the'';
<bullet> Other features to delete ``and are necessary for review'';
and
<bullet> Submission tracking number to add ``voluntary'' and to
more closely track the statutory language by substituting ``that a
tobacco product was commercially marketed in the United States as of
February 15, 2007'' for ``grandfathered.''
We also received comments on several definitions included in the
proposed rule, and we describe and respond to those comments in the
following paragraphs. Following consideration of these comments, we
have added a definition of ``commercially marketed.'' In addition, we
have made changes to the definition of commercial distribution and
predicate tobacco product, as well as removing the definition
``grandfathered tobacco product,'' as discussed in the following
paragraphs related to those terms. Please note that if there were no
comments on a definition included in the proposed rule, there is no
discussion related to that definition. We are finalizing all other
definitions without change from the proposed rule.
<bullet> Accessory
(Comment 10) One comment supports the definition of accessory,
noting that it reflects the definition included in the deeming final
rule.
(Response 10) We agree and note the final rule includes this
definition without change from the proposed rule.
<bullet> Commercial Distribution
We proposed to define commercial distribution as: To mean any
distribution of a tobacco product to consumers or to another person
through sale or otherwise, but does not include interplant transfers of
a tobacco product between registered establishments within the same
parent, subsidiary, and/or affiliate company, nor does it include
providing a tobacco product for product testing where such product is
not made available for consumption or resale. ``Commercial
distribution'' does not include the handing or transfer of a tobacco
product from one consumer to another for personal consumption. For
foreign establishments, the term ``commercial distribution'' has the
same meaning, except that it does not include distribution of a tobacco
product that is neither imported nor offered for import into the United
States.
In the following paragraphs, we discuss comments we received on the
proposed definition of commercial distribution. After considering the
comments related to this proposed definition, we have made several
changes to this definition that are included in the final rule.
Specifically, we are: (1) Adding ``whether domestic or imported'' to
clarify the distribution, (2) changing ``another,'' to ``any,'' (3)
deleting ``through sale or otherwise'' as unnecessary; (4) deleting
``registered'' as a modifier to ``establishment,'' (5) adding
``personal'' as a modifier to ``consumption,'' and (6) striking some of
the language related to what commercial distribution does not include
as other changes to the definition now clarify this point.
(Comment 11) One comment states that the definition of commercial
distribution included in the proposed rule is overly broad and
unworkable. This comment notes that including the phrase ``any
distribution of a tobacco product to consumers or to another person
through sale or otherwise'' (emphasis in comment) renders the
definition open-ended and potentially
[[Page 55230]]
includes any movement of a finished product that does not fit within
one of the enumerated exclusions, even if the product is not available
for consumption or resale. The comment notes that if FDA is concerned
with distribution of tobacco products that may be used for sampling
purposes, then FDA should tailor the definition to specify sampling (or
to an activity that either is a sale or promotes the sale of a
product).
(Response 11) FDA agrees that the definition of commercial
distribution included in the proposed rule required additional
refinement. We have thus removed ``through sale or otherwise'' from the
definition to clarify that commercial distribution is not limited to
the sale of tobacco products to the consumer. However, ``any person''
is necessary to capture movement such as that between a manufacturer,
importer, and distributor. As described in the preceding paragraph,
however, FDA has made minor revisions to the definition for
clarification to help in understanding the scope of this term.
(Comment 12) At least one comment objects to the use of
``registered'' establishments in the definition of commercial
distribution, stating that FDA should not require that interplant
transfers be between registered establishments to be excluded from the
scope of commercial distribution. This comment also notes that because
only domestic establishments are currently required to register,
interplant transfers with a company's foreign manufacturing facilities
(that are not registered) would be considered commercial distribution
under the proposed definition.
(Response 12) We agree that ``registered'' should be deleted, and
we have updated the definition in this final rule to reflect this
deletion. Furthermore, as we previously noted in the proposed rule, the
term commercial distribution excludes the providing of a tobacco
product for product testing where such products are not made available
for personal consumption or resale. Additionally, FDA does not intend
this term to include the handing or transfer of a tobacco product from
one consumer to another for personal consumption (consumer to consumer
transfers).
(Comment 13) One comment requests that FDA use the same definition
for commercial distribution and commercial marketing and proposes that
the definition be revised to recognize that commercial marketing and
commercial distribution may occur from the time of sale from a foreign
manufacturer to a U.S. distributor. The comment suggests that this
approach would better reflect that many pipe tobaccos are sold as
private label items to a specific retailer with a limited geographical
footprint.
(Response 13) We decline to make a change to combine these
definitions because, although the terms have some overlap, they are
also distinct, as reflected in the statute. Thus, it would not be
appropriate to combine the terms. As we discuss in the paragraphs
related to the definition of ``new tobacco product,'' following our
review of comments, we have decided to include a definition of
commercially marketed in this final rule. In response to the comment
related to pipe tobacco sales, we note that with respect to the sale
from a foreign manufacturer to a U.S. distributor, the final rule's
definitions of commercially marketed and commercial distribution
include a sale from a foreign manufacturer to a U.S. distributor and
sale of tobacco products to a specific retailer with a limited
geographical footprint. Applicants or others who have questions as to
whether a specific activity falls within these terms should contact
FDA.
<bullet> Component or Part
We proposed to define component or part as ``any software or
assembly of materials intended or reasonably expected: (1) To alter or
affect the tobacco product's performance, composition, constituents, or
characteristics or (2) to be used with or for the human consumption of
a tobacco product. Component or part excludes anything that is an
accessory of a tobacco product.'' In the following paragraphs, we
summarize the comments we received on this proposed definition of
component and part, which we are finalizing without change. We also
received comments on the inclusion of ``container closure system'' as a
subset of component or part, and we address those comments in the
paragraphs related to the definition of container closure system.
(Comment 14) Some comments express concern about the definition of
component and part noting, for example, that using the terms
interchangeably can be confusing and that FDA should either define each
separately or settle on one term and use that term. Another comment
supports the definition of component and part noting that the term and
definition are consistent with language in the deeming final rule.
(Response 14) We agree that it is appropriate in this context to
remain consistent in defining terms across tobacco product regulations.
Thus, this final rule maintains the definition that was included in the
proposed rule and which reflects the definition included in the deeming
final rule (see, e.g., 21 CFR 1100.3). We disagree with comments
suggesting the definition is too broad or that we should break
``component or part'' into two definitions at this time. Although we
appreciate the concern about confusion, the rule makes clear that both
component and part share the same definition, and applicants can apply
the terms accordingly. Should FDA determine at some future point that a
distinction between the terms is necessary, we would undertake notice
and comment rulemaking on the issue before we would apply any changes.
(Comment 15) One comment requests that FDA exercise enforcement
discretion for the submission of SE Reports for smoking pipes. The
comment acknowledges that the deeming final rule states that smoking
pipes are components and parts of tobacco products (81 FR 28974 at
29042) but notes that FDA has exercised enforcement discretion for the
submission of ingredient reports for smoking pipes and suggests FDA do
the same for SE requirements.
(Response 15) As the comment states, FDA has established compliance
policies related to other FD&C Act requirements for smoking pipes. We
decline to extend or establish such a premarket compliance policy for
smoking pipes because pipes can impact the risk profile of the tobacco
product with which the pipe is used, e.g., by increasing HPHC exposure.
We note that the rule includes options to certify that certain
characteristics are identical in lieu of providing data for each
characteristic of the new and predicate tobacco product (Sec.
1107.18(l)). This option may be helpful to applicants as a means of
minimizing the content to be submitted, when appropriate. We also
encourage potential applicants to reach out to FDA to discuss questions
related to preparing an SE Report.
<bullet> Container Closure System (CCS)
We proposed to define ``container closure system'' as ``any
packaging materials that are a component or part of a tobacco
product.'' As described in the following paragraphs, we received
several comments related to the definition of container closure system
included in the proposed rule, as well as comments on the discussion of
co-packaging that was included in the proposed rule. After considering
the comments, we are finalizing this definition without change from the
proposed rule.
(Comment 16) Some comments object to the definition of container
closure
[[Page 55231]]
system as ``any packaging materials that are a component or part of a
tobacco product,'' stating it is inconsistent with the FD&C Act (as
amended by the Tobacco Control Act) and ``an impermissible back door
effort'' to subject packaging changes to SE review. One comment adds
that the definition transforms packaging into a ``component or part''
of a tobacco product contrary to a D.C. District Court decision (Philip
Morris USA Inc. v. FDA, 202 F. Supp 3d 31 (D.D.C. 2016)) (Philip Morris
decision). These comments also state that although the FD&C Act
provides FDA with authority to regulate packaging under sections 903(a)
and 905(i) of the FD&C Act, that authority does not provide FDA with
the ability to include packaging under the definition of component or
part and thereby subject packaging to premarket review.
(Response 16) FDA is not requiring that an applicant include
information on all aspects of the packaging, but the requirements of
the final rule do require information on the CCS as a component or part
of the tobacco product. As explained in the proposed rule, a container
closure system is a component or part of a tobacco product because of
its potential to alter or affect the performance, composition,
constituents, or other physical characteristics of the product. We are
including this requirement in the final rule because, as discussed in
the proposed rule, treating this distinct subset of packaging as a
component or part furthers the fundamental purpose of the Tobacco
Control Act to protect the public health. Some examples include CCS
where substances in the CCS are intended or reasonably expected to
affect product moisture, or when menthol is applied to inner foil to
become incorporated into the consumed product (Ref. 1). FDA can require
the applicant to demonstrate that the change in the container closure
system does not cause the new tobacco product to raise different
questions of public health where such information is needed to
demonstrate substantial equivalence.
(Comment 17) Other comments assert that the definition of container
closure system and the preamble discussion in the proposed rule
improperly provide that a container closure system ``is'' considered a
component or part ``categorically, without regard to whether the
container closure system somehow changes the tobacco product in any
way.'' The comments contend this approach is also contrary to the
Philip Morris decision and that the plain meaning of component and part
``pertains to something that is or can be expected to become
incorporated into the tobacco product itself, meaning a piece or
portion of a larger whole tobacco product.'' The comments state that
container closure systems are not components or parts because the
package is external to the tobacco product. The comments disagree with
the examples that FDA included in the preamble to the proposed rule,
such as the soft pack for cigarettes, stating these are examples of
packaging that are outside the scope of components and parts.
(Response 17) As described in detail in the proposed rule, FDA
defines ``component or part'' as any software or assembly of materials
intended or reasonably expected: (1) To alter or affect the tobacco
product's performance, composition, constituents, or characteristics or
(2) to be used with or for the human consumption of a tobacco product.
Packaging that constitutes the container closure system is intended or
reasonably expected to affect or alter the performance, composition,
constituents, or characteristics of the tobacco product (e.g., leaching
substances that are then incorporated into a tobacco product), and is
thus a component or part of a tobacco product. Where a change in the
container closure system could affect the chemistry of the product, FDA
could require the applicant to demonstrate that the change in the
container closure system does not cause the new tobacco product to
raise different questions of public health.
Packaging that is not the container closure system is not intended
or reasonably expected to affect or alter the performance, composition,
constituents, or characteristics of the tobacco product and is
therefore not a component or part of a tobacco product. As such,
packaging that is, for example, the box around a blister pack, is not a
CCS if it is not intended or reasonably expected to alter or affect the
performance, composition, constituents, or characteristics of the
tobacco product within the blister pack.
For example, packaging materials constitute a container closure
system if substances within that packaging are intended or reasonably
expected to affect product moisture, e.g., when the manufacturer
changes the package of a moist snuff from plastic to fiberboard, which
can affect microbial stability and tobacco-specific nitrosamine (TSNA)
formation during storage. Another example of this is when menthol or
other ingredients are applied to the inner foil to become incorporated
into the consumed product (Ref. 1). Packaging materials may also be
intended or reasonably expected to affect the characteristics of a
tobacco product by impacting the rate of leaching into, and ultimately,
the amount of substances found in, the consumable tobacco product. In
fact, it has been demonstrated that compounds in packaging materials
may also diffuse into snuff and affect its characteristics (Ref. 2).
Thus, for example, packaging material that affects the characteristics
of a tobacco product by impacting the moisture level or shelf life of a
tobacco product is a container closure system (e.g., a plastic versus a
metal container of smokeless tobacco). A difference in tobacco moisture
is reasonably expected to affect microbial growth in the product,
extraction efficiency, and total exposure to nicotine or the
carcinogens N-nitrosonornicotine (NNN) or 4-(methylnitrosamino)-1-(3-
pyridyl)-1-butanone (NNK) (Ref. 3).
Considering a distinct subset of packaging (i.e., container closure
system) to be a component or part is consistent with the FD&C Act and
furthers the fundamental purpose of the Tobacco Control Act to protect
the public health. For example, section 900(1) of the FD&C Act (21
U.S.C. 387(1)) defines an ``additive'' as any substance the intended
use of which results or may reasonably be expected to result, directly
or indirectly, in its becoming a component or otherwise affecting the
characteristic of any tobacco product (including any substance intended
for use as a flavoring or coloring or in producing, manufacturing,
packing, processing, preparing, treating, packaging, transporting, or
holding), except that such term does not include tobacco or a pesticide
chemical residue in or on raw tobacco or a pesticide chemical. Congress
specifically included a broad definition of additive that encompasses
not just substances that do in fact have such effects but also may
reasonably be expected to. Similarly, if FDA were to adopt a narrow
construction of ``tobacco product'' to exclude these materials, the
Agency's ability to evaluate whether the differences between the new
and predicate tobacco product cause the new tobacco product to raise
different questions of public health would be impeded, thereby leaving
the Agency unable to fully execute its mission to protect the public
health. The definition of ``package'' in section 900(13) of the FD&C
Act does not dictate a contrary result, and can be reasonably
interpreted to mean that a distinct subset of packaging is also a
component or part of a tobacco product.
Contrary to one of the comments, the court's decision in Philip
Morris does
[[Page 55232]]
not necessitate a different interpretation than the one FDA has adopted
and described above. First, the court was presented with a challenge
relating to FDA's regulation of product labels and changes in product
quantities. It was not asked to decide on--and the Agency did not
brief--the validity of FDA's interpretation of container closure
system. Second, FDA is not seeking to incorporate into the SE
evaluation any packaging that is not intended nor reasonably expected
to affect or alter the performance, composition, constituents, or
characteristics of the product itself. As noted above, for example, the
packaging around a blister pack is not part of the SE review process if
it is not intended or reasonably expected to alter or affect the
performance, composition, constituents, or characteristics of the
tobacco product within the blister pack. The court's opinion in Philip
Morris emphasizes the importance of looking to whether the ``physical
attributes of the product itself'' have changed in determining whether
a tobacco product is new. Philip Morris, 202 F. Supp. 3d at 51. By
limiting our review to changes to the CCS, we are only looking at
packaging that is intended or reasonably expected to affect or alter
the performance composition, constituents, or characteristics of the
tobacco product--in other words, we are looking at changes that could
affect the ``physical attributes'' of the product. Such an
interpretation is consistent with the Philip Morris decision, and, as
explained above, consistent with the Tobacco Control Act's purpose and
treatment of other definitions within the FD&C Act.
(Comment 18) One comment states that a container closure system
should only qualify as a component or part of the product when it is
designed or reasonably expected to change the characteristics of the
tobacco product, and not when it is designed to maintain or preserve
the characteristics of the product. Other comments state that FDA
should not require an SE Report for a change to a CCS because a
product's packaging does not impact its characteristics.
(Response 18) If aspects of packaging of a tobacco product are
intended or reasonably expected to affect or alter the performance,
composition, constituents, or characteristics of the tobacco product,
we consider that packaging to be a CCS that is a component or part of
the product. A change to the CCS would require a premarket submission.
Packaging that is intended or reasonably expected to maintain or
preserve the characteristics of the product could be reasonably
expected to affect or alter the performance, composition, constituents,
or characteristics of the product. For example, as described in the
preceding response, packaging material that affects the characteristics
of a tobacco product, including cigars, by impacting the moisture level
or shelf life of a tobacco product is a container closure system (e.g.,
a plastic versus a metal container of smokeless tobacco) (Refs. 1-3).
(Comment 19) Some comments object to the discussion in the proposed
rule that stated that ``co-packaging two or more tobacco products
within the same container closure system results in a new tobacco
product.'' The comments assert that this ``new category of packaging''
created by the proposed rule has no basis in the FD&C Act and that it
is improper to regulate co-packaged tobacco products as part of SE
review. Accordingly, the comments request FDA to exclude co-packaged
tobacco products from the scope of new tobacco products. The comment
argues that as long as each separate product is legally marketed, co-
packaging of the products does not create a new tobacco product
requiring SE review. Other comments state that changes to the container
closure system of co-packaged products should only result in a new
product when they intend or reasonably expect to change the physical
characteristics of the product.
(Response 19) We agree that changing the packaging of co-packaged
tobacco products only results in a new tobacco product where such
packaging is intended or reasonably expected to affect or alter the
performance, composition, constituents, or characteristics of the
tobacco product. Under section 910(a)(1)(B) of the FD&C Act, new
tobacco products include those that are new because they have been
rendered new through any modification (including a change in design,
any component, any part, or any constituent, including a smoke
constituent, or in the content, delivery or form of nicotine, or any
other additive or ingredient) of a tobacco product where the modified
product was commercially marketed in the United States after February
15, 2007. Therefore, if two or more products are proposed to be co-
packaged together within a single container closure system, that
results in a new tobacco product requiring premarket authorization.
However, as explained in the proposed rule, co-packaging two or more
legally marketed tobacco products, where there are no changes,
including no change to the container closure system(s), does not result
in a new tobacco product.
<bullet> ``Grandfathered'' Tobacco Product
We proposed to include a definition of ``grandfathered tobacco
product'' as ``a tobacco product that was commercially marketed in the
United States as of February 15, 2007, and does not include a tobacco
product exclusively in test markets as of that date.'' Such a product
would not be subject to the premarket requirements of section 910 of
the FD&C Act. We received several comments on this definition, as well
as related comments on the definition of new tobacco product, and we
respond to those comments in the following paragraphs and in the
paragraphs related to ``new tobacco product.'' We are removing this
definition because the term is no longer used in the codified text. In
this preamble, we have changed the term from ``grandfathered tobacco
product'' to ``Pre-Existing tobacco product'' because it more
appropriately describes these products, by using the more precise
``Pre-Existing'' in place of ``grandfathered.'' FDA received several
comments regarding the definition of ``Pre-Existing tobacco product,''
\5\ which are discussed as follows.
---------------------------------------------------------------------------
\5\ While comments were submitted regarding the term
``grandfathered tobacco product,'' we describe them using the new
term, ``Pre-Existing tobacco product,'' throughout this document for
the sake of clarity.
---------------------------------------------------------------------------
(Comment 20) Several comments suggest that we consider alternative
dates to February 15, 2007, as the date after which premarket review
would be required for deemed tobacco products, such as the effective
date of the deeming final rule (i.e., August 8, 2016).
(Response 20) As indicated in the deeming final rule, FDA lacks the
authority to change the February 15, 2007, date for any tobacco
products, including deemed tobacco products.\6\ This date is explicitly
prescribed in the statute. Section 910(a)(1)(A) of the FD&C Act states,
in pertinent part, that the term ``new tobacco product'' means, in
part, any tobacco product (including those products in test markets)
that was not commercially marketed in the United States as of February
15, 2007. For purposes of the SE pathway, the statute also clearly
states that a predicate product must be commercially marketed (other
than for test marketing) in the United States on February 15, 2007, in
both section 910(a)(2)(A) and section 905(j)(1) of the FD&C Act.
---------------------------------------------------------------------------
\6\ Note that for the purposes of this final rule, ``deemed
tobacco products'' are those tobacco products subject to the deeming
final rule.
---------------------------------------------------------------------------
[[Page 55233]]
<bullet> Harmful and Potentially Harmful Constituent (HPHC)
We proposed to define ``harmful and potentially harmful
constituent'' as any chemical or chemical compound in a tobacco product
or tobacco smoke or emission that: (1) Is or potentially is inhaled,
ingested, or absorbed into the body and (2) causes or has the potential
to cause direct or indirect harm to users or nonusers of tobacco
products. We received comment on this definition, which we respond to
in the following paragraphs. We are finalizing this definition to
clarify that HPHCs include chemicals or chemical compounds that are
potentially inhaled, ingested, or absorbed into the body ``as an
aerosol or any other emission'' as described in the preamble to the
proposed rule.
(Comment 21) At least one comment supports the proposed definition,
noting it is consistent with the criteria applied in formulating the
HPHC list and includes both substances that are or potentially could be
inhaled, ingested, or absorbed into the body (77 FR 20034, April 3,
2012).
(Response 21) We agree with the comment and note the definition is
included in the final rule, with the change as noted, which we made to
ensure consistency with other regulatory documents.
<bullet> Ingredient
We proposed to define ``ingredient'' as tobacco, substances,
compounds, or additives contained within or added to the tobacco,
paper, filter, or any other component or part of a tobacco product,
including substances and compounds reasonably expected to be formed
through a chemical reaction during tobacco product manufacturing. We
received a comment on this definition, which we respond to in the
following paragraph. We are finalizing this definition without change.
(Comment 22) One comment disagrees with the proposed definition of
``ingredient,'' stating that ``compounds reasonably expected to be
formed through a chemical reaction during manufacturing are not
properly identified as ingredients'' and that the proposed definition
``is imprecise'' and will ``inevitably be subject to varying
interpretations.''
(Response 22) We disagree that this definition should not include
``compounds reasonably expected to be formed through a chemical
reaction'' as information on these ingredients is needed to aid FDA in
making an SE determination. However, we note that the phrase
``compounds reasonably expected to be formed through a chemical
reaction during tobacco product manufacturing'' should be interpreted
as compounds formed through well-known chemical reactions, for example,
reactions of sugars which could lead to the formation of related
alcohols, ketones, aldehydes, and esters (Refs. 4 and 5) and reactions
of nicotine which could lead to the formation of related N-nitrosamines
(Ref. 6).
<bullet> New Tobacco Product
In the proposed rule, we included the statutory definition of ``new
tobacco product,'' which is defined as: (1) Any tobacco product
(including those products in test markets) that was not commercially
marketed in the United States as of February 15, 2007, or (2) any
modification (including a change in design, any component, any part, or
any constituent, including a smoke constituent, or in the content,
delivery or form of nicotine, or any other additive or ingredient) of a
tobacco product where the modified product was commercially marketed in
the United States after February 15, 2007. (See section 910(a)(1) of
the FD&C Act.) The final rule continues to include this statutory
definition. In the following paragraphs, we respond to comments related
to the definition of ``new tobacco product'' generally.
In addition, FDA received many comments related to our invitation
to comment on the terms ``test marketing'' and ``commercially
marketed,'' which are terms included in the statutory definition of new
tobacco product. In subsequent paragraphs, we describe and respond to
these comments on test marketing and commercially marketed. Following
our consideration of these comments, we are adding a definition of
``commercially marketed,'' to the final rule, which states
``commercially marketed means selling or offering for sale a tobacco
product in the United States to consumers or to any person for the
eventual purchase by consumers in the United States.'' We also describe
this definition below.
(Comment 23) One comment requests that FDA clarify that, under the
definition of new tobacco product, a modification to an existing
product's label does not require an SE Report. This comment cites the
Philip Morris decision.
(Response 23) A modification to an existing product's label
standing alone does not require an SE Report.
(Comment 24) Some comments address FDA's interpretation that a
tobacco product exclusively test marketed as of February 15, 2007, is
considered a new tobacco product under section 910 of the FD&C Act.
Other comments indicate FDA's interpretation is correct, and one of
these comments also notes that a tobacco product that was test marketed
as of February 15, 2007, cannot serve as a predicate tobacco product
under section 905(j) of the FD&C Act.
(Response 24) Following our consideration of these comments, we
agree with the comment indicating that a tobacco product test marketed
in the United States as of February 15, 2007, is not a new tobacco
product. Section 910(a)(1)(A) defines a ``new tobacco product'' to
include ``any tobacco product (including those in test markets) that
was not commercially marketed in the United States as of February 15,
2007.'' The parenthetical ``including those in test markets'' in
section 910(a)(1)(A) of the FD&C Act modifies the phrase directly
before it--``any tobacco product''--and is intended to clarify that
tobacco products commercially marketed in test markets in the United
States as of February 15, 2007, should be treated the same way as any
other tobacco product that was commercially marketed as of February 15,
2007, i.e., they are not ``new tobacco products.'' We also agree with
the comment that states that under section 905(j) of the FD&C Act, a
tobacco product that was solely in a test market as of February 15,
2007, despite being a Pre-Existing tobacco product, cannot serve as a
predicate tobacco product, which is consistent with the position taken
in the proposed rule. Section 905(j)(1)(A)(i) describes products that
can serve as valid predicate tobacco products: A tobacco product
commercially marketed (other than for test marketing) in the United
States as of February 15, 2007, or a tobacco product that the Secretary
by delegation to FDA has previously determined, pursuant to subsection
(a)(3) of section 910, is substantially equivalent. Here, the
parenthetical ``other than for test marketing'' explains a product
solely sold in test markets as of February 15, 2007, cannot serve as a
valid predicate tobacco product. Therefore, a product cannot serve as a
predicate if it was exclusively sold in a test market as of February
15, 2007.
(Comment 25) Another comment disagrees with FDA's interpretation
that the phrase ``as of'' means ``on'' arguing that ``[i]f Congress has
intended that [Pre-Existing tobacco] products must have been
commercially marketed on the singular date of February 15, 2007, it
would have used the word `on' in the statute,'' but, instead,
``Congress used the phrase `as of,' which, in this context, plainly
communicates marketing on or before February 15, 2007'' (emphases
[[Page 55234]]
omitted). This comment references a dictionary definition of ``as of
now'' as meaning up to the present time and also notes that Congress
used the term ``on'' in other places in the Tobacco Control Act (e.g.,
section 904(c)(1) use of ``on June 22, 2009''). The comment argues that
``as of'' should be interpreted as ``on or before.''
(Response 25) As discussed in the proposed rule, FDA's longstanding
interpretation is that ``as of'' means that the tobacco product was
commercially marketed in the United States ``on February 15, 2007''
(see the final guidance entitled ``Establishing That a Tobacco Product
Was Commercially Marketed in the United States as of February 15,
2007'' (79 FR 58358, September 29, 2014)). Contrary to the comment, the
term ``as of'' does not have a plain meaning. The dictionary
definitions of ``as of'' include: ``on; at'' (Webster's II New
Riverside University Dictionary, 1988); ``beginning on; on and after''
(Webster's Unabridged Dictionary Random House 1997); ``from, at, or
until a given time'' (The American Heritage Dictionary of Idioms 2003);
``on, at, from--used to indicate a time or date at which something
begins or ends'' (Merriam Webster's Online Dictionary). As evidenced
from these varying definitions, the term is ambiguous. ``[A]s of''
could be interpreted either as ``at any time prior to and not
necessarily including on the particular date'' (in short referred to as
the ``on or before'' interpretation) or as ``at any time up to and
necessarily including on the particular date'' (in short referred to as
the ``on'' interpretation). Interpreting ``as of'' to mean ``on'' gives
a firm line of demarcation that provides clarity. Additionally, reading
``as of'' to mean ``on or before'' would mean that obsolete, abandoned,
or discontinued tobacco products could return to the market without any
premarket review and could serve as predicates under the substantial
equivalence provision. It is reasonable to conclude that Congress did
not intend to allow an immeasurable number of obsolete, abandoned, or
discontinued tobacco products that were marketed before February 15,
2007, to return to the market without any premarket review or serve as
predicates under the substantial equivalence provision, but rather
intended to confine this number to those tobacco products that were
commercially marketed in the United States on February 15, 2007. Thus,
we decline to change to the interpretation the comment suggests.
<bullet> Test Marketing and Commercially Marketed
In the preamble to the proposed rule, we explained that FDA was
considering whether to add the following definition of test marketing:
``test marketing'' means distributing or offering for sale (which may
be shown by advertisements, etc.) a tobacco product in the United
States for the purpose of determining consumer response or other
consumer reaction to the tobacco product, with or without the user
knowing it is a test product, in which any of the following criteria
apply: (1) Offered in a limited number of regions; (2) offered for a
limited time; or (3) offered to a chosen set of the population or
specific demographic group. In addition, the proposed rule stated we
were considering whether to add a definition of commercially marketed,
such as ``offering a tobacco product for sale to consumers in all or in
parts of the United States.''
After reviewing the comments we received in response to the
invitation to comment, we have determined that further discussion of
the scope of ``test marketing'' is needed before we issue a definition
of this term; however, following our consideration of comments, we have
decided to codify a definition of ``commercially marketed.'' The
proposed rule stated we were considering whether to add a definition of
commercially marketed, such as ``offering a tobacco product for sale to
consumers in all or in parts of the United States.'' The final rule now
includes a definition of ``commercially marketed'' as selling or
offering for sale a tobacco product in the United States to consumers
or to any person for the eventual purchase by consumers in the United
States. This addition clarifies that tobacco products that are not sold
or offered for sale in order to reach consumers within the United
States, such as tobacco products sold solely for export fall outside of
the definition of commercial marketing.
We describe the comments and our responses on these terms in the
following paragraphs.
(Comment 26) Several comments provide suggestions on how to define
commercially marketed and test marketed, and some comments request that
FDA not define these at all, finding the discussion in the proposed
rule confusing. One comment suggests that FDA define ``commercially
marketed'' and ``test marketing'' as meaning the same thing. Those
comments addressing test marketing indicate that manufacturers may
distribute and market tobacco product in limited regions for a set
period of time without test marketing the products. Some comments
suggest that ``test marketing'' should not be based on time or
geographical region, but rather should be based on manufacturer intent.
One comment suggests that consumer response is an inherent part of
marketing any product, for testing purposes or otherwise.
Comments addressing the term ``commercially marketed'' as discussed
in the proposed rule, suggest that if defined, it should be defined as
``offered for sale in the United States to any individual or entity by
advertising or by any other manner used to communicate that the tobacco
product is available for purchase.'' One comment states FDA has never
required firms to demonstrate that a product was offered for sale to
consumers, and, in fact, many manufacturers do not market or sell
directly to consumers, to establish that their tobacco product is a
Pre-Existing tobacco product. Other comments suggest either that a
product sold wholly within one state would be commercially marketed or
that anything other than a nationwide product launch could constitute
test marketing.
(Response 26) Following our consideration of the responses to the
proposed rule's invitation to comment on these terms, we agree that
further discussion and experience on the term test marking is needed in
order to more accurately capture the scope of this term. As we stated
previously, we are accordingly not including a definition of test
marketing in the final rule. However, after reviewing the comments
related to commercially marketed, we have added a definition of this
term to the final rule, which reflects the input we received.
Specifically, we added a definition stating that ``commercially
marketed'' means selling or offering for sale a tobacco product in the
United States to consumers or to any person for the eventual purchase
by consumers in the United States. Examples of products that may not be
covered by the definition of commercially marketed include
investigational tobacco products and free samples. Examples of
documentation of commercial marketing may include dated bills of
lading, dated freight bills, dated waybills, dated invoices, dated
purchase orders, dated advertisements, dated catalog pages, dated
promotional material, dated trade publications, dated manufacturing
documents, inventory lists, or any other document demonstrating that
the product was commercially marketed in the United States as of
February 15, 2007.
[[Page 55235]]
Importantly, as we explain in a preceding response, we also note
that although a ``solely'' test marketed product may not be considered
``new'' under section 910 of the FD&C Act, it cannot serve as a
predicate product under section 905(j) of the FD&C Act. Test marketed
products may include, for example, products that were sold or offered
for sale to consumers to determine the commercial viability of a
product through the collection of consumer reaction data.
(Comment 27) One comment requests that any definition of a test
marketed product include an alternative pathway for the test marketed
product to come to the market without having to file an SE Report. This
comment proposes a ``less cumbersome process by which products may be
test marketed, in order that companies may develop data on shelf-life,
HPHC changes, if any, over time, changes in nicotine content, etc.''
This comment proposes allowing the filing of a report advising FDA of a
manufacturer's desire to test market a product without the manufacturer
having to submit a premarket application.
(Response 27) This comment appears to provide suggestions more
closely concerned with research or investigational tobacco products.
Such products are outside of the scope of this rulemaking. In general,
any tobacco product (including products in test markets) that was not
commercially marketed in the United States as of February 15, 2007, is
considered a ``new tobacco product'' under section 910(a)(1) of the
FD&C Act. As such, manufacturers of test marketed products that were
not commercially marketed in the United States as of February 15, 2007,
are required to first submit to FDA a PMTA under section 910 for the
new tobacco product, and FDA must issue an order authorizing the
commercial distribution of the new tobacco product; or submit an SE
Report under section 905(j) of the FD&C Act, and FDA must issue an
order finding the product substantially equivalent to a predicate
tobacco product (section 910(a)(2)(A) of the FD&C Act); or FDA must
find the product exempt from the requirements of substantial
equivalence under section 910(a)(2)(A) of the FD&C Act, before the
product may be introduced into commercial distribution. If any new
tobacco product, including a test marketed product, enters into
interstate commerce for commercial distribution without an order or a
finding of exemption from substantial equivalence, it is adulterated
under section 902 of the FD&C Act and misbranded under section 903 of
the FD&C Act and subject to enforcement action.
<bullet> Package or Packaging
We proposed to define ``package or packaging'' as a pack, box,
carton, or container of any kind or, if no other container, any
wrapping (including cellophane), in which a tobacco product is offered
for sale, sold, or otherwise distributed to consumers. Although there
were no comments to the definition included in the proposed rule, there
were comments that discussed packaging in the context of CCS. We
address those comments in the discussion of the definition of CCS. We
are finalizing the definition of package or packaging without change.
<bullet> Predicate Tobacco Product
We proposed to define ``predicate tobacco product'' as a tobacco
product that is a Pre-existing Tobacco Product or a tobacco product
that FDA has previously found substantially equivalent under section
910(a)(2)(A)(i) of the FD&C Act. We received some comments related to
this term, which we discuss in the following paragraphs (see also
comments to Sec. 1107.18(f) for related discussion). We are finalizing
this definition with changes to more closely mirror the statutory
language. Thus, the definition in the final rule states that
``predicate tobacco product'' means a tobacco product that was
commercially marketed (other than for test marketing) in the United
States as of February 15, 2007, or a tobacco product that FDA has
previously found substantially equivalent under section 910(a)(2)(A)(i)
of the FD&C Act.
(Comment 28) Some comments request that FDA expand the definition
of predicate tobacco product to allow a product for which FDA issues a
marketing order under the PMTA pathway to serve as a predicate tobacco
product. Other comments suggest that tobacco products authorized
through the SE exemption pathway could serve as valid predicates.
(Response 28) The FD&C Act establishes which tobacco products may
serve as eligible predicate tobacco products for the SE premarket
pathway. These products are limited to tobacco products that were
commercially marketed (other than for test marketing) in the United
States as of February 15, 2007, and products that were previously found
SE by FDA. (See section 905(j)(1)(A) of the FD&C Act.)
<bullet> Substantial Equivalence
In the proposed rule, we proposed to include the statutory
definition of substantial equivalence, which states:
Substantially equivalent or substantial equivalence means, with
respect to a new tobacco product being compared to a predicate
tobacco product, that FDA by order has found that the new tobacco
product:
(1) Has the same characteristics as the predicate tobacco
product; or
(2) Has different characteristics and the information submitted
contains information, including clinical data if deemed necessary by
FDA, that demonstrates that it is not appropriate to require
premarket review under section 910(b) and (c) of the Federal Food,
Drug, and Cosmetic Act because the new tobacco product does not
raise different questions of public health.
(See section 910(a)(3) of the FD&C Act.)
In the proposed rule, we did not propose definitions of ``same
characteristics'' and ``different characteristics'' under section
910(a)(3)(A) of the FD&C Act. Rather, the proposed rule explained that
FDA is considering whether the ``same characteristics'' prong might be
appropriate for new tobacco products that are so similar to the
predicate product that FDA would not need scientific information to
determine whether the new product raises different questions of public
health. The proposed rule included four examples of changes between the
new and predicate products that might be appropriate to proceed through
the ``same characteristics'' prong, either individually or in
combination, and several examples where a new product would have
``different characteristics'' because the new product was dissimilar
enough from the predicate that FDA could not determine without
scientific information whether the new tobacco product raised different
questions of public health. We noted these examples were based on our
current thinking, relying on the current state of science and the
available evidence. We noted that, if evidence arises in a particular
case that requires more information from an applicant, we would
communicate to the applicant what information is needed to demonstrate
that the new tobacco product is substantially equivalent. The proposed
rule also included several factors that FDA might consider when
determining if a new product raised different questions of public
health. We invited comments on this discussion.
FDA received a number of comments related to this discussion.
Following our consideration of these comments, we have further refined
our thinking on these terms, particularly on changes that might be
appropriate to proceed through the same characteristics prong. This
includes adding other examples to this list. We describe our thinking
on these updates in the following paragraphs.
[[Page 55236]]
The final rule continues to include the statutory definition of
substantial equivalence, and does not include codified definitions of
``same characteristics'' or ``different characteristics.'' FDA intends
to further consider the scope of these terms and will undertake further
notice and comment rulemaking before moving to further define any of
these terms by regulation.
Following are examples of changes that are likely to be appropriate
to proceed as same characteristics at this time:
[cir] A change in product quantity between the new and predicate
tobacco products;
[cir] a change in container closure system between the new and
predicate non-moist tobacco products (e.g., soft pack to hard pack of
cigarettes);
[cir] a change in container closure system between the new and
predicate non-moist tobacco products where the same material is being
used (e.g., change from one plastic container to another plastic
container, change from one metal container to another metal container)
and there is no difference in flavors being added to the container
closure systems that would change the characterizing flavor;
[cir] for moist tobacco products, a change in container closure
system between the new and predicate tobacco products from one type of
plastic to another similar type of plastic where there is no difference
in flavors being added to the container closure systems that would
change the characterizing flavor and no difference in size of the
container closure system;
[cir] a change to a lower amount of total tobacco in the new
tobacco product without any corresponding changes in other ingredients
or characteristics in the new tobacco product;
[cir] a change in tipping paper color from plain to cork where the
target specifications of the tipping paper are identical;
[cir] a change in adhesive in the non-combusted portion of a
cigarette;
[cir] the replacement of one filter tow with an alternate filter
tow with identical target specifications (e.g., vendor specifications,
measured values for denier per filament, total denier); \7\
---------------------------------------------------------------------------
\7\ Note that the addition or removal of a filter between the
new and predicate tobacco products would not likely succeed through
the same characteristics prong because the addition or deletion of a
filter could impact product performance or HPHC yields and result in
different exposures to the consumer and population.
---------------------------------------------------------------------------
[cir] the removal of a dye or ink from the non-combusted portion of
a tobacco product or removal of printed monogram ink from the barrel of
a cigarette;
[cir] a change to replace a lower grade version of an ingredient
with an equal quantity of a higher grade version of the same ingredient
(e.g., replacing nicotine with USP grade nicotine);
[cir] a change to remove a single flavor ingredient, including a
complex ingredient, in the new tobacco product compared to the
predicate or removing an ingredient in the predicate tobacco product
and replacing that ingredient with an equal quantity of water in the
new tobacco product;
[cir] for combusted tobacco products, a change in the pattern of
non-ink watermark on papers or wrappers, provided the papers or
wrappers have identical target specifications and the change does not
alter or affect the design parameters of the paper/wrapper;
[cir] for combusted tobacco products, a change from one paper or
wrapper to a similar paper or wrapper from an alternate supplier that
do not impact HPHC yields;
[cir] a change between a new and predicate tobacco product that
results in a removal of characterizing flavor (e.g., removal of menthol
from cigarettes, or removal of cherry flavor in smokeless tobacco), as
well as removal of a flavor from a component of a finished tobacco
product (e.g., removal of vanilla flavored adhesive in cigars and
replacement with a non-flavored adhesive);
[cir] a change in inert tip material (e.g., replacing a wood tip
with a plastic tip on a cigar);
[cir] a change from non-Fire Standard Compliant (FSC) paper to FSC
paper (also known as low ignition propensity paper);
[cir] a change from one FSC paper to an alternate FSC paper; and
[cir] an absolute increase or decrease in ventilation of 11 percent
or less between the new and predicate tobacco product (Ref. 7).
(Comment 29) Some comments note that the Philip Morris decision is
instructive on the meaning of the term ``same characteristics.'' One
comment discussing the district court decision in the Philip Morris
(Philip Morris, 202 F.Supp. 3d at 54) case stated that ``same
characteristics means the product has more than minor modifications to
a predicate product, but less than significant modifications''. The
comments state that the district court rejected FDA's interpretation
that same characteristics meant that the new and predicate products had
identical characteristics. Other comments note the language in the
decision stating that ``the `same characteristics' prong may encompass
similar, but not necessarily identical, products, while the `different
characteristics' prong may cover significantly different products.''
(Response 29) We agree that the district court rejected FDA's
interpretation that same characteristics meant that the new and
predicate products had identical characteristics. As explained in the
proposed rule, we view the same characteristics prong to encompass new
tobacco products that are so similar to the predicate product that FDA
would not need scientific information beyond identification of the
changes to determine whether the new product raises different questions
of public health. The examples provided in the preceding paragraphs are
intended to further illustrate the changes that might be appropriate to
proceed through the same characteristics prong.
(Comment 30) One comment states that FDA should limit any finding
that a new tobacco product has the ``same characteristics'' as a
predicate product where the characteristics are not identical and an
applicant ``demonstrate[s] that the differences, both individually and
collectively, cannot plausibly have an effect on individual health or
population-level health.'' This comment states that at a minimum the
applicant should explain all the differences in characteristics and
demonstrate that the differences cannot plausibly increase the
potential harm to an individual or to the population as a whole. Other
comments view as inappropriate FDA's statement that the same
characteristics prong would be appropriate for new tobacco products
that are ``so similar'' to the predicate that FDA would not need
scientific information to determine whether the new product raises
different questions of public health. The comments maintain that a
public health analysis should not be part of the same characteristics
analysis.
(Response 30) Under the same characteristics prong, an applicant
need not demonstrate that any modifications to the new product do not
cause the new product to raise different questions of public health.
The ``different questions of public health'' analysis arises under the
different characteristics prong. An SE review is structured as a
tobacco product to tobacco product comparison, which does not account
for population standards. We agree, and the rule requires, that the
applicant provide information on the similarities and differences in
characteristics between the new and predicate tobacco products (see,
e.g., Sec. Sec. 1107.18(d) and 1107.19). However, we disagree with the
[[Page 55237]]
comments that suggest that public health considerations generally
should not be considered as part of an SE review under either prong.
Rather, under the SE pathway, FDA protects the public health by
authorizing only new tobacco products that are substantially equivalent
to a predicate tobacco product.
(Comment 31) Some comments request additional clarity on the same
characteristics prong and suggest that the lack of distinct definitions
for ``same characteristic'' and ``different characteristic'' creates
unclear pathways for manufacturers to follow. For example, one comment
finds circular FDA's suggestion that ``the `same characteristics'
analysis might be appropriate for new tobacco products that are so
similar to the predicate product that FDA would not need scientific
information to determine different questions of public health'' while
``different characteristics' [is] if a product were dissimilar enough
from the predicate product that FDA could not determine without
scientific information whether the new product raised different
questions of public health.'' This comment notes that FDA should
determine whether two products have the ``same characteristics,'' and,
if so, find the new product substantially equivalent, and, if not, then
move to the second prong to determine ``whether the new product as a
whole raises different questions of public health relative to products
in the same category that were on the market as of February 15, 2007.''
Similarly, another comment suggests that the ``function of the
`same characteristics' prong is to determine whether any difference in
characteristics between a new product and its predicate are materially
different,'' stating that materiality is determined by whether such
differences raise questions of public health. The comment further
argues that if the differences are not material, then the products have
the same characteristics. This comment suggests that under the
different characteristics prong, a product should be substantially
equivalent if requiring authorization under the more demanding PMTA
pathway is not appropriate because the product does not raise different
questions of public health.
Other comments suggest FDA define ``same characteristics'' to mean
the products being compared have similar, but not identical, materials,
ingredients, design, composition, heating source or other features, and
the differences are not material to a public health assessment of the
new product. The comment proposes FDA might define ``different
characteristics'' to mean the products being compared have material
differences in materials, ingredients, design, composition, heating
source or other features, such that there is a potential to raise
different questions of public health.
(Response 31) The initial decision of whether to submit a change
under the same characteristics or different characteristics prong in an
SE Report rests with the applicant who is best positioned to understand
their new tobacco product, as well as how it compares with the
predicate tobacco product. However, it is possible that FDA may
determine that an SE Report submitted under the different
characteristics prong has the same characteristics, or that FDA may
determine that an SE Report submitted under the same characteristics
prong has different characteristics. Note that an applicant's failure
to properly identify the type of report will not prevent further review
of the SE Report. In addition, although we agree that characteristics
that have material differences are likely to fall under the different
characteristics prong, we do not agree that a determination as to
whether any differences are ``materially different'' is necessarily a
function of the same characteristics prong or that using that term adds
much clarity. As noted, we view the same characteristics prong to
encompass new tobacco products that are so similar to the predicate
product that FDA would not need scientific information beyond
identification of the changes to determine whether the new product
raises different questions of public health.
The range and scope of comments received on this topic illustrate
that codifying definitions that will appropriately address the spectrum
of tobacco product and changes that an SE Report might include could be
premature and result in inflexibility. Thus, as we discussed earlier in
this section, although this final rule continues to include examples of
changes that might proceed as same characteristics, we have determined
at this time not to proceed with codifying definitions of same
characteristics and different characteristics.
(Comment 32) Several comments address whether there are some
classes of changes that would not require scientific information to
determine whether the new product raises different questions of public
health. Some comments note that several examples included in the
proposed rule as examples of changes that could proceed as same
characteristics in an SE Report should be eligible for the SE Exemption
pathway. For example, some comments state that product quantity changes
should be exempt from premarket review, although one comment states FDA
should not allow a product quantity change to fall under the same
characteristics prong of SE. Other comments request that we include
additional examples of changes that might proceed as same
characteristics in an SE Report, such as changes to low ignition
propensity cigarette paper, tipping paper, and tipping paper adhesives,
or that we provide a decision-tree.
(Response 32) FDA agrees that certain changes could proceed through
either the same characteristics prong or through the SE exemptions
pathway, and we disagree with the comment that suggests that product
quantity changes are not appropriate for a ``same characteristics'' SE
Report. At this time, based on the currently available evidence
regarding consumer perception and use, changes in product quantity
between a new and predicate tobacco product do not cause new tobacco
products to raise different questions of public health. As explained
earlier in this section of the final rule, we have added examples of
changes that are likely to be able to proceed as same characteristics
in an SE Report, including a change in tipping paper color from plain
to cork where the tipping paper target specifications are identical, a
change in adhesive, the removal of a dye or ink, or replacing filter
tow with an alternate filter tow with identical target specifications.
In addition, as we note above, with more review experience we intend to
provide further information and clarification about the Agency's
thinking about what kinds of modifications could proceed through the
same characteristics prong, different characteristics prong, and/or an
exemption request under section 905(j)(3) of the FD&C Act (as
implemented at Sec. 1107.1).
(Comment 33) One comment suggests that a change submitted as a same
characteristics SE Report could contain all the general information
outlined in proposed Sec. 1107.18(c), a certification that all
characteristics are identical between the predicate and new tobacco
product except for listed changes, a side-by-side design and ingredient
comparison, a health information summary statement, and a statement of
compliance with any applicable product standards. The comment notes
that a same characteristics SE Report should not contain comparative
testing data, HPHC testing, or stability testing.
[[Page 55238]]
(Response 33) FDA expects that SE Reports submitted under the same
characteristics prong will be for new tobacco products that are so
similar to the predicate product that FDA would not need scientific
information to determine whether the new product raises different
questions of public health. An SE Report submitted under the same
characteristics prong must contain the applicable required information
set out in Sec. 1107.18 but would not need to include the comparison
information as set out in Sec. 1107.19. If an applicant submitting an
SE Report under the same characteristics prong is not able to show that
the new tobacco product is eligible for the same characteristics prong,
the applicant should proceed under the different characteristics prong
which requires the submission of further information, such as
comparison of HPHCs data.
(Comment 34) Several comments also state that requiring SE
submissions for product quantity changes conflicts with an FDA
memorandum that the comments suggest show that FDA has no scientific or
other basis to require SE Reports for product quantity changes (this
comment references the FDA memorandum, ``Product Quantity Changes in
Substantial Equivalence Reports (SE Reports) for Statutorily Regulated
Tobacco Products.'' December 2017, available at: <a href="https://www.fda.gov/media/124674/download">https://www.fda.gov/media/124674/download</a>).
(Response 34) We disagree that product quantity changes for tobacco
products do not require premarket review. Section 910(a)(1) of the FD&C
Act defines a ``new tobacco product'' as: (1) Any tobacco product
(including those products in test markets) that was not commercially
marketed in the United States as of February 15, 2007, or (2) any
modification (including a change in design, any component, any part, or
any constituent, including a smoke constituent, or in the content,
delivery or form of nicotine, or any other additive or ingredient) of a
tobacco product where the modified product was commercially marketed in
the United States after February 15, 2007. As explained in Philip
Morris v. FDA, a change in product quantity results in a new tobacco
product requiring premarket authorization. Philip Morris, 202 F.Supp.
3d at 55-56.
We also disagree that product quantity changes can proceed through
the exemption pathway under section 905(j)(3) of the FD&C Act. The FD&C
Act establishes when a modification might be exempt from substantial
equivalence, stating that FDA may exempt from the requirements of
section 905(j) relating to the demonstration that a tobacco product is
substantially equivalent within the meaning of section 910 of the FD&C
Act, tobacco products that are modified by adding or deleting a tobacco
additive, or increasing or decreasing the quantity of an existing
tobacco additive (section 905(j)(3) of the FD&C Act; see also Sec.
1107.1). The statute limits the eligible modifications to changes to
additives. Therefore, a change in product quantity is not eligible to
use the exemption premarket pathway because a change in product
quantity, even if combined with a change in additives, is not only a
change in additives.
(Comment 35) Another comment requests that FDA extend the product
quantity change ``streamlined approach'' to other modifications and
suggests as examples ingredient changes within 5 percent of the target
and the replacement of non-Generally Recognized as Safe (GRAS) to GRAS
ingredients in smokeless tobacco.
(Response 35) FDA agrees in part with this comment. We agree that
other types of modifications can be submitted as a ``streamlined'' SE
Report. FDA has received numerous successful applications where the
manufacturer described any modification(s) between the new and
predicate tobacco product, and provided a certification statement that
all other characteristics are identical. For these SE Reports, FDA
expects the applicant to provide adequate data to support that the new
tobacco product is substantially equivalent to the predicate (which,
for a different characteristics report, would include data to support
that the proposed modification between the new and predicate tobacco
product does not cause the new tobacco product to raise different
questions of public health). A change in ingredient amount within 5
percent of the target specifications of the predicate tobacco product
may be found substantially equivalent. This is a case-by-case
determination. For example, a change of 5 percent could raise different
questions of public health if there is toxicity associated with that
ingredient; therefore, scientific data would be needed to ensure that
any increase in toxicity does not cause the new tobacco product to
raise different questions of public health. Also, if there are
ingredient changes within 5 percent of the target specifications for a
large number of ingredients (e.g., 30 ingredients), the totality of all
modifications may raise different questions of public health.
As with any ingredient change between a new and predicate tobacco
product, the applicant must provide adequate information to demonstrate
the new tobacco product meets the standard for authorization through
the SE pathway.
FDA has received SE Reports that have included a change from non-
GRAS to GRAS ingredients. Any ingredient change where the ingredients
involved are (1) chemically identical; (2) have the same or nearly the
same specifications; and (3) are present in identical or lower
quantities, are not expected to raise HPHC quantities. Ingredient
changes from non-GRAS to GRAS meet this type of change and therefore
are not expected to raise HPHC quantities. In this scenario, FDA agrees
no data would be needed beyond that required to identify this change
under Sec. 1107.18(g). FDA notes that GRAS designation pertains to
foods and is not determinative with respect to the substantial
equivalence standard, although in some cases, a GRAS determination and
data underlying that determination may be appropriately bridged to
tobacco products. As indicated above, changes from one ingredient to a
higher grade of that ingredient can qualify as a same characteristics
SE Report (e.g., a change from non-USP to USP grade nicotine).
(Comment 36) Several comments generally object to FDA's approach to
the ``different'' characteristics prong stating, for example, that FDA
treats every SE Report as a different characteristics SE Report. One
comment states that FDA is requiring the same or similar information
for both prongs, and that all SE reports in essence would have to
submit under the ``different'' characteristics prong to show the new
tobacco product has the same characteristics. The comments state that
the approach in the proposed rule is in conflict with Congressional
intent.
(Response 36) We disagree with this comment. Both the proposed rule
and this final rule illustrate modifications that are likely to be able
to fall under the same characteristics prong and thus would not require
submission of the information required under Sec. 1107.19, unlike
modifications that fall under the different characteristics prong,
which do require submission of the information in Sec. 1107.19.
(Comment 37) Some comments state that the different characteristics
prong does not make reference to a predicate tobacco product at all and
suggest that the different questions of public health determination
should be without reference to a predicate and instead be determined by
a comparison to all tobacco products in the marketplace. For example,
one comment suggests that FDA ``look only to the risks to the public
that are of a different type or
[[Page 55239]]
magnitude from the risks present in the market for the particular
category of tobacco product at issue as of the baseline date of
February 15, 2007.'' Similarly, some comments state that because the
FD&C Act does not include ``predicate product'' in the ``different
characteristics'' prong, FDA must evaluate products by comparing the
attributes of the product to a broader range of other marketed products
(beyond the referenced predicate). These comments generally state that
the different questions of public health language included in the
second prong is intended to route to the PMTA process those new tobacco
products that raise different questions of public health beyond those
already recognized, i.e., to identify products that have risks distinct
in type or magnitude from the existing, known risks prevalent in the
market as of February 15, 2007, and that this should be a ``heavy
lift'' before FDA can conclude that a new product raises different
questions of public health.
(Response 37) We disagree with the comment's assertion that the
analysis of different characteristics should include consideration of
all tobacco products in the marketplace as of February 15, 2007. Both
the same characteristics and different characteristics prongs are
specific to the comparison between a new tobacco product and its
predicate. A marketplace range of products, or multiple predicates, as
suggested by the commenter, would be inconsistent with the statutory
framework Congress provided for authorization through the SE pathway.
Nowhere in section 910(a)(3)(A) or 905(j) of the FD&C Act does the
statute state--either explicitly or implicitly--that the SE comparison
should be made to the market as a whole as of February 15, 2007. On the
contrary, there are numerous references to a single predicate product
throughout the sections of the FD&C Act which discuss SE. See, e.g.,
section 905(j)(1)(A)(i) of the FD&C Act (person seeking to introduce
new tobacco product via SE pathway must provide its basis for
determination that the new tobacco product is substantially equivalent,
within the meaning of section 910, to a tobacco product commercially
marketed as of February 15, 2007); section 910(a)(2)(A) of the FD&C Act
(a PMTA order is required unless FDA has issued an order that the new
tobacco product--is substantially equivalent to a tobacco product
commercially marketed as of February 15, 2007); section 910(a)(3)(A)
(``substantial equivalence'' means, with respect to the tobacco product
being compared to the predicate tobacco product); section 910(a)(3)(C)
(a new tobacco product may not be found to be substantially equivalent
to a predicate tobacco product that has been removed from the market or
that has been determined by a judicial order to be misbranded or
adulterated). There are no references in the FD&C Act that discuss any
SE finding in connection with the marketplace or a marketplace range of
products. In addition to being inconsistent with the FD&C Act, a
comparison to all tobacco products in the ``marketplace'' would make it
difficult and impractical to compare each characteristic between the
new and predicate tobacco products. This approach also raises questions
as to what should be considered the ``marketplace,'' such as which
tobacco products should be used in determining the marketplace and
whether the understanding of marketplace shifts over time.
This is in contrast to the evaluation FDA must make to authorize a
product through the PMTA pathway. In order to receive authorization
through the PMTA pathway, FDA must find that permitting the new tobacco
product to be marketed would be ``appropriate for the protection of the
public health.'' (See section 910(c)(2) of the FD&C Act.) In making
this determination, FDA must evaluate the risks and benefits to the
population as a whole, including users and nonusers of the tobacco
product, and taking into account the increased or decreased likelihood
that existing users of tobacco products will stop using such products;
and the increased or decreased likelihood that those who do not use
tobacco products will start using such products. (See section 910(a)(4)
of the FD&C Act.) This is a much different standard and inquiry than
that which is undertaken under the different questions of public health
analysis under SE.
(Comment 38) One comment states that FDA's intent to judge
differences in characteristics individually and in the aggregate under
the different characteristics prong ``place[s] undue and unreasonable
importance on every individual change to a specific ingredient,
material, or characteristic, no matter how minor or unrelated to public
health, and without any explanation of how FDA will weigh the
differences.'' This comment argues that if true, FDA will be unlikely
to determine that any new product is substantially equivalent.
(Response 38) We disagree with the assertion that we will be unable
to determine that any new tobacco product is substantially equivalent.
FDA has issued a high number of SE orders and a large ratio of such
orders relative to not substantially equivalent (NSE) orders. As of
December 31, 2019, of the orders issued for regular SE Reports, 80
percent were for an SE finding (a total of 1,009 SE orders versus a
total of 209 NSE orders) (information on marketing orders related to
substantial equivalence for tobacco products can be found at <a href="https://www.fda.gov/tobacco-products/substantial-equivalence/marketing-orders-se">https://www.fda.gov/tobacco-products/substantial-equivalence/marketing-orders-se</a>). Additionally, as of December 31, 2019, FDA had closed 96% of all
regular SE Reports accepted. FDA evaluates SE Reports on a case-by-case
basis based on the content of the SE Report. Certain changes between
the new and predicate tobacco product may affect additional
characteristics or impact HPHCs in a way that would cause a new tobacco
product to raise different questions of public health. For example,
certain changes in design parameters can lead to an increase HPHCs. We
also want to note, in response to the concern that FDA's approach
places ``unreasonable importance on every individual change'', ``no
matter how minor'' the change, that for changes that are minor
modification to tobacco additives, the exemption from substantial
equivalence pathway is available. SE Reports that include changes that
FDA believes limited or no information is needed may be eligible to
proceed as a ``same characteristics'' SE Report, as explained in the
examples above, or via a streamlined SE Report containing limited
information sufficient to demonstrate the changes subject of that SE
Report do not cause the new tobacco product to raise different
questions of public health.
(Comment 39) At least one comment states that the considerations
included in the proposed rule related to different characteristics and
different questions of public health exceed the physical
characteristics of the product itself (e.g., that FDA is requiring that
applicants examine the potential to increase initiation, increase abuse
liability, or decrease cessation). The comment further argues that, if
FDA is requiring applicants to address whether every change has the
potential to affect any of these outcomes, it is requiring
manufacturers to meet a subjective, unmeasurable standard contrary to
law, i.e., FDA appears to want manufacturers to prove a negative.
(Response 39) We disagree that these considerations do not relate
to the physical characteristics of a tobacco product. Rather, a
modification to a tobacco product may cause the new tobacco product to
have different characteristics from the predicate
[[Page 55240]]
tobacco product. When a new product has different characteristics, FDA
evaluates whether the totality of difference(s) in characteristics do
not cause the new product to raise different question of public health.
Congress stated that the Tobacco Control Act's ``purposes'' include
ensuring that the FDA has the authority to address issues of particular
concern to public health officials, especially the use of tobacco by
young people and dependence on tobacco and promoting cessation to
reduce disease risk and the social-costs associated with tobacco-
related diseases (Tobacco Control Act sections 3(2) and (9)). In
addition, as explained above, Congress defined substantial equivalence
to mean that the information submitted contains information, including
clinical data if deemed necessary by the Secretary, that demonstrates
that it is not appropriate to regulate the product under this section
because the product does not raise different questions of public
health. (See section 910(a)(3)(A)(ii) of the FD&C Act.) The reference
to ``this section'' is a reference to the PMTA pathway. Because one of
the bases for FDA finding that a product is appropriate for the
protection of public health (i.e., the PMTA ``standard'') includes the
increased or decreased likelihood that existing users will stop using
and new users will initiate use of such products, it is reasonable to
examine those same considerations under the SE standard to determine
whether the differences between the predicate and the new product show
that the product should be reviewed under the PMTA pathway. Thus, as
part of making the ``different questions of public health''
determination, FDA typically considers whether the new product has
potentially higher HPHC yields, toxicity, initiation, abuse liability,
or dependence relative to the predicate product.
(Comment 40) Some comments disagree with the proposed rule's
discussion of the phrase ``different questions of public health''
(DQPH) and state that FDA's thinking is incorrect. Other comments note
that the six identified factors included in the proposed rule for
determining if a new tobacco product raises different questions of
public health seem optional, non-exhaustive, and vague.
(Response 40) We agree that additional information may assist
applicants in understanding DQPH. Thus, in the following paragraphs FDA
is providing further information on our thinking related to this
phrase. Specifically, in evaluating whether an applicant has
demonstrated that a difference in characteristic does not cause the new
product to raise different questions of public health, FDA may
consider, among other public health considerations, whether:
[cir] The new tobacco product has higher HPHC yields compared to
the predicate tobacco product, and the difference in HPHC yields is
greater than the analytical variability of the method used to detect
it.\8\
---------------------------------------------------------------------------
\8\ In determining whether an applicant has demonstrated that
any differences in characteristics do not cause the new product to
raise different questions of public health, FDA will consider
whether increases in certain HPHCs are offset by decreases of other
HPHCs.
---------------------------------------------------------------------------
[cir] The new tobacco product has potentially higher toxicity due
to an appreciable increase in an ingredient associated with adverse
health effects, compared to the predicate tobacco product. For example,
the evaluation of the available toxicology information may show that an
increase in an ingredient between the new and predicate tobacco
products demonstrates an increase in cancer risk or non-cancer hazard
for users of the new tobacco product compared to those of the predicate
tobacco product, and thus causes the new tobacco product to raise
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
[[Page 55241]]
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.
<bullet> 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).
<bullet> 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
[[Page 55242]]
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
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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.
<bullet> 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.
<bullet> 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: <a href="https://www.fda.gov/media/124658/download">https://www.fda.gov/media/124658/download</a>). 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
[[Page 55244]]
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.
<bullet> 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.
<bullet> 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
[[Page 55245]]
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: <a href="https://www.fda.gov/media/124665/download">https://www.fda.gov/media/124665/download</a>). 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: <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/tobacco-product-master-files">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/tobacco-product-master-files</a>). 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.
<bullet> 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
[[Page 55246]]
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,
[[Page 55247]]
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.
<bullet> 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.
<bullet> 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.
<bullet> 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
[[Page 55248]]
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
[[Page 55249]]
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).
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\13\ See the discussion in section V.D.2, about how products
should be categorized for purposes of SE review.
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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 P
[…truncated; see source link]Indexed from Federal Register on October 5, 2021.
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