Content and Format of Substantial Equivalence Reports; Food and Drug Administration Actions on Substantial Equivalence Reports

Federal RegisterOct 5, 2021

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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.

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

https://www.regulations.gov

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,

AskCTP@fda.hhs.gov

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

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

Abbreviation

What it means

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

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

Particulate Matter

PMTA

Premarket Tobacco Application

PRA

Paperwork Reduction Act of 1995

QRA

Quantitative Risk Assessment

RIA

Regulatory Impact Analysis

RYO

Roll-Your-Own

Substantial Equivalence

TPMF

Tobacco Product Master File

TSNA

Tobacco-Specific Nitrosamines

VOC

Volatile Organic Compound

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:

• Submission of a premarket tobacco application under section 910(b);

• 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

• submission of a request for an exemption under section 905(j)(3) (implemented at § 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

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.

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.

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

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 §§ 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 § 16.1(b)(2) (21 CFR 16.1(b)(2)) regarding rescission (as included in the proposed rule), and we are finalizing § 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.,

§ 1107.18(

)).

(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

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.,

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.,

§ 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

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 (§ 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 § 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 § 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 § 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.

A recent court decision,

Cigar Ass'n of Am., et al.

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.”

Under the terms of the court's order, a “premium” cigar is defined as a cigar that meets all of the following eight criteria:

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.

Cigar Ass'n of Am., et al.

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;

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 § 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

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 (§ 1107.18(

)). 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

https://www.federalregister.gov/documents/2011/07/05/2011-16766/tobacco-products-exemptions-from-substantial-equivalence-requirements

). Please note that additional information related to exemption requests may be found at

https://www.fda.gov/tobacco-products/market-and-distribute-tobacco-product/exemption-substantial-equivalence

; FDA also maintains information on exemption requests that FDA has granted at:

https://www.fda.gov/tobacco-products/exemption-substantial-equivalence/marketing-orders-exemption-se

2. Definitions (§ 1107.12)

Proposed § 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 § 1107.12. That definition is:

• “

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 § 1107.12 are to the following terms:

•

Brand

to add an “s” following “brand name” in the definition;

•

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”;

•

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;

•

Harmful and potentially harmful constituent

to add the phrase “including as an aerosol or any other emission” in paragraph (1);

•

Heating source

to change “a” to “the”;

•

Other features

to delete “and are necessary for review”; and

•

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.

• 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.

• 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

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.

• 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 (§ 1107.18(

)). 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.

• 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

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.

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

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.

• “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,”

which are discussed as follows.

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.

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.

Note that for the purposes of this final rule, “deemed tobacco products” are those tobacco products subject to the deeming final rule.

• 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.

• 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).

• 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

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.

• 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.

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.

• 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.

• 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 § 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.)

• 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.

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:

○ A change in product quantity between the new and predicate tobacco products;

○ a change in container closure system between the new and predicate non-moist tobacco products (

e.g.,

soft pack to hard pack of cigarettes);

○ 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;

○ 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;

○ 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;

○ a change in tipping paper color from plain to cork where the target specifications of the tipping paper are identical;

○ a change in adhesive in the non-combusted portion of a cigarette;

○ 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);

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.

○ 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;

○ 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);

○ 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;

○ 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;

○ 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;

○ 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);

○ a change in inert tip material (

e.g.,

replacing a wood tip with a plastic tip on a cigar);

○ a change from non-Fire Standard Compliant (FSC) paper to FSC paper (also known as low ignition propensity paper);

○ a change from one FSC paper to an alternate FSC paper; and

○ 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.,

§§ 1107.18(d) and 1107.19). However, we disagree with the

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 § 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 § 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.

(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 § 1107.18 but would not need to include the comparison information as set out in § 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:

https://www.fda.gov/media/124674/download

(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

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 § 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 § 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 § 1107.19, unlike modifications that fall under the different characteristics prong, which do require submission of the information in § 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

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

https://www.fda.gov/tobacco-products/substantial-equivalence/marketing-orders-se

). 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

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:

○ 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.

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.

○ 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.

○ 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.

○ The new tobacco product compared to the predicate has potentially higher abuse liability.

○ The new tobacco product has the potential to increase dependence.

Based on these considerations, as well as other public health considerations, FDA will determine whether the applicant has demonstrated that any differences do not cause the new tobacco product to raise different questions of public health.

(Comment 41) Other comments request that FDA include a definition of the phrase “different questions of public health” in the final regulation. The comments assert that industry needs this information to determine the appropriate pathway for its SE submission. Some comments propose definitions of the phrase; for example, one comment proposes to define the phase “different questions of public health” to mean when “the new product as a whole raises questions of public health that are significantly different in type and magnitude from those presented by [Pre-Existing tobacco products] or other legally marketed tobacco products.” The comments contend that the analysis should look at “different questions of public health” as a whole rather than the implications of the particular product as compared to another product. One comment suggests that an applicant could satisfy the public health analysis by providing HPHC data for both the new and predicate products, and if none of the HPHCs for the new product are statistically higher than the predicate product, then the new product should pass the public health analysis. The comment suggests that applicants could submit a quantitative risk assessment (QRA) (defined by the comment as a magnitude of individual disease risk tool), and if the new product is of no greater risk than the predicate product then the new product should pass the public health analysis. This comment also suggests that FDA should establish a QRA framework and “identify the number of product runs or batches necessary to generate HPHC data,” as well as publish this data so that manufacturers can generate QRA category curves.

(Response 41) We agree that changes in characteristics could cause the new tobacco product to raise “different questions of public health” where “the new product as a whole raises questions of public health that are significantly different in type and magnitude from those presented by [Pre-Existing] or other legally marketed tobacco products.” However, instead of adopting a definition, we include additional details in the preceding paragraphs on what we may consider when determining if a new tobacco product raises different questions of public health. The public health analysis of an SE Report involves the evaluation of all toxicologically relevant changes, including HPHCs, but also non-tobacco ingredient changes that may cause the new tobacco product to raise different questions of public health. At this time, we are not recommending the inclusion of QRA with SE Reports, as they are not needed for the comparison of HPHCs from the new and corresponding predicate tobacco products. If an applicant has scientific evidence that a QRA would be supportive in evaluating the overall toxicological comparison between a new and predicate tobacco product, we strongly encourage the applicant to contact FDA and to justify the methodology and applicability of a potential QRA before an applicant voluntarily develops or submits a risk assessment, as the assessment may not

be needed or appropriate to support the SE Report.

(Comment 42) Another comment asserts that a definition of different questions of public health should include information that indicates a product with a low usage rate will not impact public health.

(Response 42) We disagree with the assertion that new tobacco products with low usage rates would necessarily not impact public health. Under section 905(j)(1)(A)(i) of the FD&C Act, the basis for determining substantial equivalence is through the comparison of the new tobacco product to the predicate tobacco product. Therefore, providing prevalence of use (even if it indicates low usage) of the new tobacco product without comparison to prevalence of use to a predicate tobacco product is insufficient to determine if the new tobacco product raises different questions of public health. In addition, differences in the composition of users of the new and predicate tobacco products may still raise DQPH even with low overall prevalence of use. Furthermore, FDA's assessment of the product's impact on public health goes beyond usage rate. For example, a new tobacco product that has a low usage rate, but is found to be more toxic than the predicate tobacco product (

e.g.,

a tobacco product with higher HPHCs than the predicate tobacco product) could raise different questions of public health and be found not substantially equivalent. Moreover, prevalence can change over time, and it can be difficult to predict the prevalence of a new product before it is marketed.

• Tobacco Product

We proposed to include the statutory definition of tobacco product (section 201(rr) of the FD&C Act (21 U.S.C. 321(rr))). In the FD&C Act, tobacco product is defined as any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part, or accessory of a tobacco product). The term “tobacco product” does not mean an article that under the FD&C Act is a drug (section 201(g)(1)), a device (section 201(h)), or a combination product (section 503(g) (21 U.S.C. 353(g))). We discuss the comment related to this definition in the following paragraphs, and we are including this definition in the final rule without change.

(Comment 43) At least one comment disagrees with FDA's interpretation of tobacco product (

i.e.,

as encompassing the whole product and not limited to a single unit or portion) and argues that FDA's interpretation is too broad, misinterprets the FD&C Act, and is unnecessary.

(Response 43) We disagree with these objections related to the language included in the proposed rule's discussion of new tobacco product and tobacco product. Rather, as noted in the proposed rule, and supported by the

Philip Morris

decision, for purposes of determining whether a tobacco product is new under section 910 of the FD&C Act, and therefore requires premarket authorization prior to marketing, a “tobacco product” encompasses the whole product (

e.g.,

a pack of cigarettes or a tin of loose tobacco), and is not limited to a single unit or portion of the whole product (

e.g.,

a single cigarette or a single snus pouch). (

See Philip Morris,

202 F. Supp. 3d at 55-57.) If an SE Report includes information on only a portion of a new tobacco product, FDA would have an incomplete understanding of the tobacco product (

e.g.,

FDA may not get information on the container closure system, which could impact the consumable product) and would not be able to determine, for example, potential impacts on initiation and cessation of tobacco use (information which may be needed for determining whether there are DQPH).

• Tobacco Product Manufacturer

We proposed to include the statutory definition of tobacco product manufacturer in the rule (section 900(20) of the FD&C Act). The statute defines tobacco product manufacturer as any person, including a repacker or relabeler, who: (1) Manufactures, fabricates, assembles, processes, or labels a tobacco product or (2) imports a finished tobacco product for sale or distribution in the United States. In the following paragraphs, we discuss the comments related to this definition. We are including this definition without change in the final rule.

(Comment 44) One comment requests that FDA clarify that “an entity that contracts with another domestic entity to manufacture a tobacco product” is included in this definition.

(Response 44) The rule includes the definition of tobacco product manufacturer from the FD&C Act, stating that “tobacco product manufacturer” includes any repacker or relabeler and any person who manufactures, fabricates, assembles, processes, or labels a tobacco product; or imports a finished tobacco product for sale or distribution in the United States (this term and definition are included in the final rule). Under this definition, contract entities engaged in the activities described in the definition of a tobacco product manufacturer would fall within the scope of the definition of tobacco product manufacturer.

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

1. Submission of an SE Report (§ 1107.16)

Proposed § 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 (§ 1107.18)

Proposed § 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 (

) certification statement. Proposed § 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 § 1107.18 in several places for consistency with other changes to the rule and to add clarity. Specifically, in § 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 § 1105.10 to clarify that FDA generally intends to refuse to accept an SE Report for review if it does not comply with both §§ 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 § 1107.18(g) and (h) to clarify what information is needed for acceptance for further review.

We are also revising § 1107.18(c)(4) to add “voluntary” as a modifier to “request” to further emphasize that

seeking an FDA determination relating to a potential predicate tobacco product is a voluntary process. We revised § 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 § 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°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 §§ 1107.18(c)(7)(iii) and 1107.19(a)(21) under the heated tobacco product category.

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.

The categorization of HTPs as a separate category from cigarettes in this rule, as demonstrated in §§ 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 § 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 § 1107.19 for the product categories specified in that section.

Across all product categories, the subcategory of “co-package” has been removed from § 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 § 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 § 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 § 1107.19.

In § 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 § 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 § 1107.18(f)(2)(iii) (formerly (f)(2)(iv)), we have changed “rescission order” to “rescission action,” which is a more accurate description.

In § 1107.18(g), we have made some minor clarifying edits, and in § 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 § 1107.18(g) and (k)(2). We have also removed the phrase “as described in § 1107.19” from § 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 § 1107.18(h) to § 1107.19.

Both “same characteristics” and “different characteristics” SE Reports must provide the information required by § 1107.18(g). As explained in § 1107.18(g), if the new tobacco product

has limited changes to a characteristic(s) when compared to the predicate tobacco product, and all other characteristics are identical (

e.g.,

a change to product quantity), the applicant must provide comparison information related to any characteristic(s) that have changed, but may certify that the other characteristics are identical under § 1107.18(

)(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 § 1107.18(h). Furthermore, as explained in § 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 § 1107.18(

)(2).

The following paragraphs describe the comments we received on proposed § 1107.18 and our responses to those comments.

• Forms (§ 1107.18(b)-(c))

Proposed § 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 § 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 § 1107.19.

• General Information (§ 1107.18(c))

Proposed § 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 § 1107.18(c) with changes to reflect updates to § 1107.18(c)(7)(iii) (related to product category, product subcategory, and product properties).

(Comment 48) Several comments request clarity regarding the proposed requirement that an SE Report include information about the product's characterizing flavor. Specifically, the comments request FDA to clarify the requirement or include a definition of the term, or seek to understand if the purpose of the requirement is simply to see how the applicant identifies the product (

e.g.,

“no characterizing flavor” or a “particular flavor”). Some comments note that the only information available is in an FDA memorandum, and they disagree with how the memorandum explains that characterizing flavor should be indicated by factors including chemical composition or olfactory response (the comment cites an FDA document, entitled, “Unique Identification of Tobacco Products,” November 2016, which is available at:

https://www.fda.gov/media/124658/download

). Other comments request that FDA consider only the toxicological effects rather than the effect on user behavior, when considering the differences in characterizing flavor between the new and predicate tobacco products.

(Response 48) This final rule does not define characterizing flavor. As part of uniquely identifying a new and predicate tobacco product, the SE Report must include product property information on whether the products have a characterizing flavor or not. The SE Report may state, for example, that a new cigarette has “none” for the product property of characterizing flavor. In addition, this information is needed as part of fully characterizing a new tobacco product to aid FDA during the review process and in making an SE determination. When considering the differences in characterizing flavor between the new and predicate tobacco products, FDA considers both the toxicological effects and the effects on user behavior.

(Comment 49) At least one comment indicates general disagreement that a change in characterizing flavor should require submission of an SE Report. The comment states that, if a new product includes a different flavoring from the predicate, FDA should not require that an SE Report be submitted for that new or different flavor but that, if an SE Report is required, the product should not “fail” SE review “unless the addition of flavor alters the chemistry of the product such that it increases the inherent risks of tobacco-related diseases in an individual user either through the introduction of new or greater HPHCs.” A comment also states FDA has not explained why a change in characterizing flavor would require submission of an SE Report for a product with different characteristics.

(Response 49) We disagree that an SE Report should not be required for a change in characterizing flavor. Section 910(a)(1) of the FD&C Act establishes that any modification results in a new tobacco product. A change to or

addition or deletion of ingredients that make up a characterizing flavor renders a tobacco product “new.” For FDA to make an SE finding, the SE Report must demonstrate that the new tobacco product is substantially equivalent to the predicate tobacco product. As we explain in previous paragraphs related to the definition of substantial equivalence, at this time, an SE Report for the removal of a characterizing flavor is likely to be able to come in as a same characteristic SE Report as FDA has found such a change does not require scientific data to show that the change does not cause the new tobacco product to raise different questions of public health.

• New Tobacco Product Description (§ 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 § 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, § 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 § 1107.18(e)(3) is not for the purposes described in section 906 of the FD&C Act but, rather, is to help ensure enough information to enable FDA to fully understand and compare the characteristics that can be affected by the manufacturing process of the new tobacco product and the predicate tobacco product.

• Description of the Predicate Product (§ 1107.18(f))

As described in an earlier paragraph in this section, we have made changes to this subsection for consistency with changes that we made to the definition of predicate tobacco product and other clarifying edits. We also removed the requirement that a tobacco product to which a new tobacco product is compared be in the same category and subcategory of product as the new tobacco product. In the following paragraphs, we describe the comments we received on this subsection and our responses.

(Comment 51) Some comments object to the proposed requirement that the new and predicate products be in the same category and subcategory. The comments state, “there is nothing in the statute to prohibit the attempted use of cross-category comparisons in an SE submission” and also refer to the deeming final rule as suggesting such a comparison is appropriate. The comments state that while cross-category comparisons may be more burdensome or require more information, the comparison may be appropriate and, therefore, applicants should be permitted to attempt it.

(Response 51) After careful review of the comments submitted and our own experience, we agree and are no longer requiring that the new and predicate products be in the same category and subcategory. We note that it would likely be difficult for an applicant to demonstrate substantial equivalence where the new product is in a different category or subcategory as its selected predicate, but it may, in rare cases, be possible for an applicant to make a showing of substantial equivalence. For example, an applicant may be able to compare a new snus tobacco product to a pouched moist snuff predicate tobacco product.

It continues to be critical, however, that an applicant select an appropriate predicate tobacco product and provide the scientific evidence demonstrating the new tobacco product is substantially equivalent to that predicate. Even where there are differences in the category or subcategory between the new and predicate tobacco products, FDA could issue an SE order if the applicant provides scientific evidence that demonstrates to FDA that differences between the new product and the predicate product do not cause the new tobacco product to raise different questions of public health. Comparison of a new and predicate tobacco product is much easier, and more likely to result in a finding of SE, if the new and predicate tobacco products are of the same category and subcategory, as the basic characteristics of the predicate and new products are likely to be more similar. For example, manufacturers of ENDS may find it difficult to show that their product is substantially equivalent to a combusted cigarette or a smokeless tobacco product because of the differences in product properties.

If an applicant chooses to compare a new and predicate tobacco product that are not in the same category or subcategory, for FDA to be able to conduct a review of the SE Report, the

applicant should provide a strong scientific justification for why a product that may differ from the new tobacco product in even the most basic of characteristics and parameters is an appropriate predicate and how any differences in characteristics do not cause the new tobacco product to raise different questions of public health. For example, where the new and predicate tobacco products are not in the same category or subcategory, an applicant could provide information to demonstrate that users or likely users of the new product display very similar tobacco product use behaviors (

e.g.,

likelihood of initiation, experimentation, switching, dual-use/polyuse, or cessation, as well as actual use patterns, frequency and amount of use) in addition to information on comparison of HPHCs exposure.

(Comment 52) One comment agrees with the proposed requirement of § 1107.18(f) that an applicant include a single predicate product for comparison and that a composite predicate tobacco product would be inconsistent with the FD&C Act. Other comments disagree with FDA's proposal to require manufacturers to identify a single predicate product to compare to the new product. Several of these comments contend that manufacturers should be able to use multiple predicates in a single SE report, stating that permitting the use of multiple predicates would be more consistent with statutory design and also align with the substantial equivalence requirements for devices in sections 510(k) and 513(g) of the FD&C Act. The comments state that we have been inconsistent in our position regarding the use of predicate products and contend that the one predicate approach described in the proposed regulation would create problems for manufacturers because it does not allow for product innovation. In support of this, some comments refer to FDA webinars that suggest that use of two predicates would be appropriate, an FDA decision to permit two predicates to be used for a smokeless product, and an FDA policy memorandum that acknowledges “multiple predicate tobacco products are identified in an SE Report” (this comment referenced the FDA memorandum FDA, “Use of Surrogate Tobacco Products in SE Reports,” September 2016. Available at:

https://www.fda.gov/media/124665/download

). Some comments ask that, if the final rule maintains the single predicate approach, applicants be permitted to amend currently pending SE Reports to designate the most appropriate predicate product.

(Response 52) We disagree that the final rule should permit the use of multiple predicate tobacco products in an SE Report. There is nothing in the statutory language to support the assertion that the SE comparison can be made to a range of predicate products, and doing so would be inconsistent with the premise of SE review. Creating a new tobacco product from a range of predicate tobacco products can raise different questions of public health beyond those questions raised by the individual predicates because of the way the various additives and other features of a tobacco product interact to impact how chemicals are handled by the body. Some of the ways chemicals can interact is to alter how they are absorbed into the body, metabolized by the body, or how they bind to receptors in the body.

For example, acetaldehyde when present at a level that is below its independent reinforcing effect could boost the reinforcing effect of nicotine, the primary addictive substance in tobacco, beyond what it would be without acetaldehyde present or the sum of the two independent effects (Refs. 11 and 12). If a component from one predicate that contains nicotine is mixed with a component from another predicate that contains acetaldehyde, the synergistic effect of this mixture could raise different questions of public health beyond the separate predicates, because the addictiveness of the product could be greater than either independently or the sum of the two predicate products alone and may reduce cessation and increase initiation, thereby impacting public health.

Finally, the comments also cite instances where it appears that FDA has suggested or permitted reference to two predicate tobacco products. However, in

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