# Premarket Tobacco Product Applications and Recordkeeping Requirements

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URL: https://www.frixlaw.com/law-library/documents/fr%3A2021-21011

## Record

- **Collection:** Federal Register
- **Document type:** Rule
- **Published:** October 5, 2021
- **Citation:** 86 FR 55300

## Text

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 1100, 1107 and 1114
[Docket No. FDA-2019-N-2854]
RIN 0910-AH44
Premarket Tobacco Product Applications and Recordkeeping Requirements

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Final rule.

SUMMARY:

The Food and Drug Administration (FDA, the Agency, us, or we) is issuing a final rule that sets forth requirements for premarket tobacco product applications (PMTAs) and requires manufacturers to maintain records establishing that their tobacco products are legally marketed. The rule will help ensure that PMTAs contain sufficient information for FDA to determine whether a marketing granted order should be issued for a new tobacco product. The rule codifies the general procedures FDA will follow when evaluating PMTAs and creates postmarket reporting requirements for applicants that receive marketing granted orders. The rule also requires tobacco product manufacturers to keep records establishing that their tobacco products are legally marketed, such as documents showing that a tobacco product is not required to undergo premarket review or has received premarket authorization.

DATES:

This rule is effective November 4, 2021.

FOR FURTHER INFORMATION CONTACT:

Paul Hart, Office of Regulations, Center for Tobacco Products (CTP), Food and Drug Administration, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G335, Silver Spring, MD 20993, 877-287-1373,
AskCTP@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

Table of Contents

Executive Summary

A. Purpose of the Regulatory Action

B. Legal Authority

C. Summary of Major Provisions

D. Costs and Benefits

Table of Abbreviations/Commonly Used Acronyms

I. Background

II. Legal Authority

III. General Description of Comments on the Proposed Rule

IV. Description of the Final Regulations for, and the Comments on and FDA's Responses Regarding, the Maintenance of Records Demonstrating That a Tobacco Product Was Commercially Marketed in the United States as of February 15, 2007 (Part 1100, Subpart C)

A. Purpose and Scope (§ 1100.200)

B. Definitions (§ 1100.202)

C. Recordkeeping Requirements (§ 1100.204)

V. Description of the Final Regulations for, and the Comments and FDA's Responses Regarding, the Maintenance of Records Relating to Exemptions From the Requirements of Demonstrating Substantial Equivalence (§ 1107.3)

A. Definition

B. Record Maintenance

C. Record Quality

D. Record Retention

VI. Description of the Final Regulations for, and the Comments and FDA's Responses Regarding, Premarket Tobacco Product Applications (Part 1114)

VII. General (Part 1114, Subpart A)

A. Scope (§ 1114.1)

B. Definitions (§ 1114.3)

VIII. Premarket Tobacco Product Applications (Part 1114, Subpart B)

A. Application Submission (§ 1114.5)

B. Required Content and Format (§ 1114.7)

C. Amendments (§ 1114.9)

D. Withdrawal by Applicant (§ 1114.11)

E. Change in Ownership of an Application (§ 1114.13)

F. Supplemental Application Submission (§ 1114.15)

G. Resubmissions (§ 1114.17)

IX. FDA Review (Part 1114, Subpart C)

A. Communications Between FDA and Applicants (§ 1114.25)

B. Review Procedure (§ 1114.27)

C. FDA Action on an Application (§ 1114.29)

D. Issuance of a Marketing Granted Order (§ 1114.31)

E. Issuance of a Marketing Denial Order (§ 1114.33)

F. Withdrawal of a Marketing Granted Order (§ 1114.35)

G. Temporary Suspension of a Marketing Granted Order (§ 1114.37)

X. Postmarket Requirements (Part 1114, Subpart D)

A. Postmarket Changes (§ 1114.39)

B. Reporting Requirements (§ 1114.41)

C. Requirements for Periodic Reports

D. Serious and Unexpected Adverse Experience Reporting

E. Submission of Additional Information

XI. Miscellaneous (Part 1114, Subpart E)

A. Record Retention (§ 1114.45)

B. Confidentiality (§ 1114.47)

C. Electronic Submission (§ 1114.49)

XII. Paperwork Reduction Act of 1995

XIII. Federalism: Executive Order 13132

XIV. Congressional Review Act

XV. Consultation and Coordination with Indian Tribal Governments

XVI. Analysis of Environmental Impact

XVII. Economic Analysis of Impacts

A. Introduction

B. Summary of Costs and Benefits

XVIII. Effective Date

XIX. References

Executive Summary

A. Purpose of the Regulatory Action

FDA is issuing this final rule to improve the efficiency of the submission and review of PMTAs. We are finalizing this rule after reviewing comments to the proposed rule (84 FR 50566, September 25, 2019) (hereinafter referred to as the proposed rule) and are basing this rule on the experience the Agency has gained by reviewing several types of premarket applications submitted by industry, including substantial equivalence (SE) reports, requests for exemptions from the SE requirements, modified risk tobacco product applications (MRTPAs), and PMTAs. As described in the proposed rule, FDA has received thousands of premarket applications that range widely in the level of detail they contain. This rule describes and sets forth requirements related to the content and format of PMTAs and will provide applicants with a better understanding of the information a PMTA must contain. The rule requires an applicant to submit detailed information regarding the physical aspects of its new tobacco product and full reports of information regarding investigations that may show the health risks of the new tobacco product and whether it presents the same or different risks compared to other tobacco products. FDA is requiring the submission of these health risk investigations to ensure it understands the full scope of what is known about the potential health risks of a new tobacco product.

The rule also addresses issues such as the procedures by which FDA reviews a PMTA, retention of records related to a PMTA, confidentiality of application information, electronic submission of the PMTA and amendments, and postmarket reporting requirements. FDA will announce the withdrawal of its September 2011 draft guidance entitled “Applications for Premarket Review of New Tobacco Products” in the
Federal Register
. Additionally, FDA will update the guidance for industry entitled “Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems” (the ENDS PMTA Guidance)
1

to ensure the product-specific recommendations on preparing and submitting PMTAs for ENDS are consistent with the requirements of this rule.

1
Available at
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance.

Additionally, the rule creates requirements for the maintenance of records demonstrating the legal marketing status of Pre-Existing Tobacco Products (
i.e.,
tobacco products, including those products in test markets) that were commercially marketed in the United States as of February 15, 2007) and products that are exempt from the requirements of demonstrating substantial equivalence. These recordkeeping requirements will allow FDA to more efficiently determine the legal marketing status of a tobacco product.

B. Legal Authority

This rule is being issued under FDA's authority to require premarket review of new tobacco products under section 910 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 387j), FDA's authority to require records and 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).

C. Summary of Major Provisions

This rule describes and sets forth content and format requirements for PMTAs and includes FDA's interpretations of various provisions in section 910 of the FD&C Act. Under the rule, a PMTA must contain information necessary for FDA to determine whether it should issue a marketing granted order for a new tobacco product under section 910(c)(1)(A) of the FD&C Act. Specifically, the PMTA must enable FDA to find whether: (1) There is a showing that permitting the marketing of the new tobacco product would be appropriate for the protection of the public health; (2) the methods used in, or the facilities and controls used for, the manufacture, processing, or packing of the product conform to the requirements of section 906(e) of the FD&C Act (21 U.S.C. 387f(e)); (3) the product labeling is not false or misleading in any particular; and (4) the product complies with any applicable product standard in effect under section 907 of the FD&C Act (21 U.S.C. 387g) or there is adequate information to justify a deviation from such standard. The rule will also allow applicants to submit a supplemental PMTA or a resubmission, which will improve the efficiency of submitting and reviewing an application in certain instances. A supplemental PMTA can be submitted in situations where an applicant is seeking authorization for a new tobacco product that is a modified version of a tobacco product for which they have already received a marketing granted order. A resubmission can be submitted to address application deficiencies following the issuance of a marketing denial order.

In addition, the rule explains how an applicant can amend or withdraw a PMTA and how an applicant may transfer ownership of a PMTA to a new owner. The rule also addresses FDA communications with applicants and identifies the actions that FDA may take after receipt of a PMTA. Where an applicant receives a marketing granted order, the rule requires the submission of postmarket reports, addresses when FDA may withdraw a marketing granted order, and explains how long an applicant will be required to maintain the records related to the PMTA and postmarket reports. The rule also sets forth FDA's disclosure procedures regarding PMTAs and requires the electronic submission of PMTAs, unless the applicant requests and obtains a waiver. Additionally, the rule requires tobacco product manufacturers to maintain records related to the legal marketing of Pre-Existing Tobacco Products and products that are exempt from the requirements of demonstrating substantial equivalence.

D. Costs and Benefits

The final rule will require manufacturers of Pre-Existing Tobacco Products and manufacturers of products that are exempt from the requirements of demonstrating SE to maintain records to demonstrate that they can legally market their products. For products that receive a PMTA marketing granted

order, the final rule will require certain postmarket reporting, including periodic reporting and adverse experience reporting. The final rule will also implement and set forth requirements for the content and format of PMTAs and the general procedures we intend to follow in reviewing and communicating with applicants.

The final rule will make the review of PMTAs more efficient. As a result, the final rule will create cost savings for FDA related to the review of some PMTAs. The final rule will also create cost savings for FDA and for PMTA applicants by reducing the number of PMTAs submitted. We estimate that annualized benefits over 20 years will equal $2.04 million at a 7 percent discount rate, with a low estimate of $1.36 million and a high estimate of $2.85 million. We estimate that annualized benefits over 20 years will equal $2.08 million at a 3 percent discount rate, with a low estimate of $1.43 million and a high estimate of $2.84 million.

This is the first regulation to address the costs of PMTA requirements for new, originally regulated tobacco products. While we already included the costs to submit and review PMTAs for deemed tobacco products
2

in the final regulatory impact analysis (RIA) for the deeming final rule, no RIA includes the costs to submit and review PMTAs for originally regulated tobacco products. Therefore, we include the costs to prepare and review PMTAs for these tobacco products in this analysis.

2
Note that for the purposes of this final rule, “deemed tobacco products” are those tobacco products 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”)). These products include cigars, pipe tobacco, waterpipe tobacco, electronic nicotine delivery systems (ENDS), and other novel tobacco products.

The final rule will increase the cost for applicants to prepare a PMTA. As a result, the final rule will generate incremental costs related to the preparation of PMTAs for ENDS products. Firms will incur costs to maintain and submit postmarket reports and we will incur costs to review these reports. Finally, firms will incur costs to read and understand the rule and costs to maintain records for some Pre-Existing Tobacco Products. We estimate that annualized costs over 20 years will equal $4.73 million at a 7 percent discount rate, with a low estimate of $2.63 million and a high estimate of $7.45 million. We estimate that annualized costs over 20 years will equal $4.86 million at a 3 percent discount rate, with a low estimate of $2.50 million and a high estimate of $7.95 million.

Table of Abbreviations/Commonly Used Acronyms

Abbreviation acronym
What it means

APPH
Appropriate for the protection of public health

CAS
Chemical Abstracts Service

CCI
Confidential commercial information

CCS
Container Closure System

CGMP
Current good manufacturing practices

CORESTA
Cooperation Centre for Scientific Research Relative to Tobacco

CTP
Center for Tobacco Products

DPF
Denier per filament

EA
Environmental assessment

ENDS
Electronic nicotine delivery systems

FDA
Food and Drug Administration

FD&C Act
Federal Food, Drug, and Cosmetic Act

FEI
Facility Establishment Identifier

FOIA
Freedom of Information Act

GLP
Good laboratory practice

HACCP
Hazard analysis and critical control point

HCI
Health Canada Intense

HHS
Department of Health and Human Services

HPHC
Harmful or potentially harmful constituent

HTP
Heated tobacco products

IUPAC
International Union of Pure and Applied Chemistry

ICH
International Council for Harmonization

IRB
Institutional Review Board

ISO
International Organization for Standardization

MDSS
Manufacturing Data Sheet Specification

mL
Milliliters

mm
Minimum and maximum diameter

MRTP
Modified risk tobacco product

MRTPA
Modified risk tobacco product application

NCI
National Cancer Institute

NEPA
National Environmental Policy Act of 1969

NNK
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

NNN
N-nitrosonornicotine

NTRM
Nontobacco related material

NYTS
National Youth Tobacco Survey

OMB
Office of Management and Budget

OTDN
Oral tobacco-derived nicotine

OV
Oven volatiles

PDU
Power delivery unit

PK
Pharmacokinetic

PM
Particulate matter

PMTA
Premarket tobacco product application

RIA
Regulatory Impact Analysis

RTA
Refuse to accept

RTF
Refuse to file

RYO
Roll-your-own

SAS
Statistical Analysis Software

SE
Substantial equivalence

Secretary
Secretary of Health and Human Services

SES
Socioeconomic status

STN
Submission tracking number

TAMC
Total aerobic microbial count

TPMF
Tobacco product master file

TSNA
Tobacco specific nitrosamine

TYMC
Total yeast and mold count

TPSAC
Tobacco Products Scientific Advisory Committee

UNII
Unique ingredients identifier

a
w

Water activity

I. Background

The Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) (Pub. L. 111-31) provides FDA with the authority to regulate tobacco products under the FD&C Act. The FD&C Act, as amended by the Tobacco Control Act, generally requires that a new tobacco product undergo premarket review by FDA before it may be introduced or delivered for introduction into interstate commerce. 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 (21 U.S.C. 387j(a)(1)).

The FD&C Act establishes three premarket review pathways for a new tobacco product:

• Submission of a PMTA 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) (21 U.S.C. 387e(j)(1)(A)) (SE Report);
3

and

3
Additionally, section 910(a)(2)(B) of the FD&C Act also allows for the continued marketing of new tobacco products first introduced or delivered for introduction into interstate commerce for commercial distribution after February 15, 2007, and prior to March 22, 2011, for which a manufacturer submitted an SE Report prior to March 23, 2011 (“provisional tobacco products”), unless FDA issues an order that the tobacco product is not substantially equivalent.

• submission of a request for an exemption under section 905(j)(3) (implemented at 21 CFR 1107.1) (exemption request).

Generally, if a new tobacco product is marketed without either a marketing granted order (for PMTAs), a

substantially equivalent order (for SE reports), or a finding of exemption from SE (for exemption requests), 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.

Since 2010, FDA has received a large volume of premarket applications for tobacco products, thousands of which have been PMTAs. Of these PMTAs, FDA has completed its full substantive review and acted on several sets of bundled PMTAs, which are single submissions containing PMTAs for a number of similar or related tobacco products. To assist manufacturers in preparing PMTAs, FDA has issued guidance, conducted webinars, met with manufacturers, hosted public meetings regarding premarket submissions, and posted the technical project lead reviews (which describe the reviews completed on specific PMTAs) and marketing granted orders issued to date. FDA has also completed review and issued decisions on hundreds of exemption requests, thousands of SE reports, and thousands of voluntarily submitted requests for Pre-Existing Tobacco Product status review, which has provided FDA with information and experience to use when implementing the PMTA program and establishing recordkeeping requirements.

FDA issued the proposed rule on September 25, 2019, to set forth proposed requirements related to the PMTA premarket pathway and outline the information needed for FDA to determine whether it will issue a marketing granted order under the pathway. FDA received about 1,000 comments to the docket for the proposed rule, including comments from individuals, academia, healthcare professionals, consumer advocacy groups, industry, public health groups, and trade associations. We summarize and respond to these comments in section III of this rule. After considering these comments, FDA developed this final rule, which includes changes made in response to the comments.

II. Legal Authority

As described in the following paragraphs, FDA is describing and setting forth requirements for the content, format, submission, and review of PMTAs, as well as other requirements related to PMTAs, including recordkeeping requirements, and postmarket reporting. FDA is also creating recordkeeping requirements regarding the legal marketing of Pre-Existing Tobacco Products and products that are exempt from the requirements of demonstrating substantial equivalence. In accordance with section 5 of the Tobacco Control Act, FDA intends that the requirements that are established by this rule be 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 that a new tobacco product be the subject of a marketing granted order unless FDA has issued an order finding it to be substantially equivalent to a predicate product, or exempt from the requirements of demonstrating substantial equivalence.
4

A manufacturer may choose to submit a PMTA under section 910(b) of the FD&C Act to satisfy the requirements of premarket review. Section 910(b)(1) describes the required contents of a PMTA and, in addition to the items specified in section 910(b)(1)(A) through (F), allows FDA to require applicants to submit other information relevant to the subject matter of the application under section 910(b)(1)(G). Section 910(c)(2) of the FD&C Act requires FDA to issue an order denying a PMTA if it finds that the applicant has not made a showing that permitting the marketing of the new tobacco product would be appropriate for the protection of the public health; the methods used in, or the facilities or controls used for, the manufacture, processing, or packing of the product do not conform to the requirements of section 906(e) of the FD&C Act; the proposed labeling is false or misleading in any particular; or the product has not been shown to meet the requirements of a product standard in effect and there is a lack of adequate information to justify a deviation from the standard, if applicable.

4
See section I for a discussion of provisional tobacco products and their relation to the premarket review requirements.

Section 909(a) of the FD&C Act authorizes FDA to issue regulations requiring tobacco product manufacturers or importers to maintain records, make reports, and provide information as may be reasonably required to assure that their tobacco products are not adulterated or misbranded and to otherwise protect public health. Section 910(f) of the FD&C Act allows FDA to require that applicants who receive marketing granted orders establish and maintain records, and submit reports to enable FDA to determine, or facilitate a determination of, whether there are or may be grounds for withdrawing or temporarily suspending an order.

Section 910(d)(1) of the FD&C Act grants FDA authority to issue an order withdrawing a marketing granted order if FDA finds:

• That the continued marketing of such tobacco product no longer is appropriate for the protection of the public health;

• that the application contained or was accompanied by an untrue statement of a material fact;

• that the applicant:

○ Has failed to establish a system for maintaining records, or has repeatedly or deliberately failed to maintain records or to make reports, required by an applicable regulation under section 909 of the FD&C Act;

○ has refused to permit access to, or copying or verification of, such records as required by section 704 of the FD&C Act; or

○ has not complied with the requirements of section 905 of the FD&C Act;

• on the basis of new information before the Secretary of Health and Human Services (the Secretary) with respect to such tobacco product, evaluated together with the evidence before the Secretary when the application was reviewed, that the methods used in, or the facilities and controls used for, the manufacture, processing, packing, or installation of such tobacco product do not conform with the requirements of section 906(e) of the FD&C Act and were not brought into conformity with such requirements within a reasonable time after receipt of written notice from the Secretary of nonconformity;

• on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when the application was reviewed, that the labeling of such tobacco product, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary of such fact; or

• on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such order was issued, that such tobacco product is not shown to conform in all respects to a tobacco product standard which is in effect under section 907 of the FD&C Act, compliance with which was a condition to the issuance of an order relating to the application, and that there is a lack of adequate information to justify the deviation from such standard, if applicable.

Under section 902(6) 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), or if it is in violation of an order under section 910(c)(1)(A) 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 also 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.

III. General Description of Comments on the Proposed Rule

FDA received over 1,000 comments on the proposed rule. The comments came from individuals, academia, healthcare professionals, consumer advocacy groups, industry, public health groups, and trade associations. In addition to the comments specific to this rulemaking that we address in sections IV through XVIII, we received many general comments expressing support or opposition to the rule. Some of 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. Other comments addressed topics outside the scope of this rulemaking, such as requests for product standards under section 907 of the FD&C Act, recommendations regarding the compliance date for manufacturers of deemed tobacco products to submit premarket applications, statements that ENDS and pipes should not be regulated as tobacco products, and that pipes should not be subject to the requirements of premarket review.

We describe and respond to comments in the description of the final rule in sections IV through XVIII. To make it easier to identify comments and our responses, the word “Comment,” in parentheses, will appear before each comment, and the word “Response,” in parentheses, will appear before each response. We have numbered the comments to make it easier to distinguish between comments; the numbers are for organizational purposes only and do not reflect the order in which we received the comments or any value associated with the comment. We have combined similar comments, or comments on similar topics that can be addressed by a single response, under one numbered comment.

IV. Description of the Final Regulations for, and Comments and FDA's Responses Regarding, the Maintenance of Records Demonstrating That a Tobacco Product Was Commercially Marketed in the United States as of February 15, 2007 (Part 1100, Subpart C)

The rule adds subpart C regarding records to part 1100 of subchapter K of Title 21. Other than the comments and changes described in this section regarding the proposed definition of the term “grandfathered tobacco product,” (now referred to as a “Pre-Existing Tobacco Product”), FDA received no comments regarding proposed part 1100 and FDA is finalizing the requirements as proposed without additional changes.

A. Purpose and Scope (§ 1100.200)

Subpart C of part 1100 establishes requirements for the maintenance of records by tobacco product manufacturers who introduce a Pre-Existing Tobacco Product, or deliver it for introduction, into interstate commerce. These requirements are created under the authority of section 909 of the FD&C Act, which authorizes FDA to require tobacco product manufacturers to establish and maintain records to assure that a tobacco product is not adulterated or misbranded and to otherwise protect public health. Under section 902(6)(A), a tobacco product is adulterated if it is required by section 910(a) of the FD&C Act to have premarket review and does not have an order in effect under section 910(c)(1)(A)(i). In addition, 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. The records that are required under this subpart demonstrate that a tobacco product is a Pre-Existing Tobacco Product and, therefore, not required by section 910(a) to have premarket review and not adulterated or misbranded if marketed without an FDA order. FDA is basing these requirements on its experience gained by performing thousands of Pre-Existing Tobacco Product status reviews conducted during its review of SE reports and at manufacturers' voluntary requests. These requirements are needed because currently manufacturers do not always maintain sufficient documentation to demonstrate that their tobacco product is a Pre-Existing Tobacco Product. The records that are required under this rule will allow FDA to more quickly and efficiently determine whether a tobacco product is a Pre-Existing Tobacco Product.

B. Definitions (§ 1100.202)

Section 1100.202 sets forth the meaning of terms as they apply to part 1100:

1. Tobacco Product

The rule defines the term “tobacco product” consistent with section 201(rr)(1) of the FD&C Act (21 U.S.C. 321(rr)(1))

2. Tobacco Product Manufacturer

The rule defines the term “tobacco product manufacturer” consistent with section 900(20) of the FD&C Act (21 U.S.C. 387(20)). FDA interprets the phrase “manufactures, fabricates, assembles, processes, or labels” in the definition as including, but not being limited to: (1) Repackaging or otherwise changing the container, wrapper, or labeling of any tobacco product package; (2) reconstituting tobacco leaves; or (3) applying any chemical, additive, or substance to the tobacco leaf other than potable water in the form of steam or mist. For the purposes of the definition, “finished tobacco product” means a tobacco product, including all components and parts, sealed in final packaging (
e.g.,
filters or filter tubes sold to consumers separately or as part of kits) or in the final form in which it is intended to be sold to consumers.

3. Commercially Marketed

In the proposed rule, FDA proposed to define “commercially marketed” as “selling or offering a tobacco product for sale to consumers in all or in parts of the United States.”

(Comment 1) Several comments discussed specific changes to the proposed definition of the term “commercially marketed.” One comment stated that the proposed definition of commercially marketed departs from the plain meaning of the statutory language and FDA's historical approach to evaluating whether a product is a Pre-Existing Tobacco Product. Specifically, comments raised concerns that inclusion of “in all or in parts of the United States” seems to depart from the plain meaning of the statutory phrase “commercially marketed in the United States” and requires that firms demonstrate that a product was offered nationwide, in multiple regions, or even across State lines. The comments also argue that, for example, the statutory definition of “new tobacco product” does not state or imply that a product offered for sale within a particular State cannot qualify as “commercially marketed in the United States.” The comments state that FDA should define “commercially marketed” 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.” Another comment expressed similar concerns, stating that the definition seems to require the selling or marketing of products directly to consumers as well as offering it for sale nationwide.

(Response 1) 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. Given the wide variety of input we have received on this term as well as the dictionary definition, we do not believe that the term “commercially marketed” has a plain meaning. Instead, we have 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. This definition 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. 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 the following items listed in § 1100.204(a): 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.

(Comment 2) One comment requested clarification as to whether limited edition products would be considered test marketed products or commercially marketed products.

(Response 2) “Limited edition” products are considered commercially marketed if they were sold or offered for sale in the United States to consumers or to any person for the eventual purchase by consumers in the United States—regardless of whether they were solely sold or offered for sale in a test market. Therefore, if a “limited edition” product was commercially marketed—even if only in a test market—as of February 15, 2007, it would be a Pre-Existing Tobacco Product. We note that considering test marketed products to be commercially marketed is a change in FDA's interpretation of section 910(a)(1)(A) of the FD&C Act, which is discussed further in the response to comment 3. However, a product that was solely in a test market as of February 15, 2007, 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 determine the commercial viability of a product through the collection of consumer reaction data.

4. Pre-Existing Tobacco Product

In the proposed rule, we proposed to define the term “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. A grandfathered tobacco product is not subject to the premarket requirements of section 910 of the FD&C Act.” In the final rule, we have changed this 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 many comments regarding the definition of “Pre-Existing Tobacco Product,”
5

which are discussed as follows.

5
Although comments were submitted regarding the term “grandfathered tobacco product,” we describe them using the new term, “Pre-Existing Tobacco Product,” throughout this document for clarity.

(Comment 3) Multiple comments discussed the proposed definition of the term “commercially marketed” as well as the definition of the term “test marketing” set forth in the preamble of the proposed rule as used in, or to inform, the definitions of “Pre-Existing Tobacco Product” and “new tobacco product” in the proposed rule. Some comments argued that Congress was intentional in its use of test markets in the definition of new tobacco product and, as such, a product in test market as of February 15, 2007 (if not subsequently modified within the meaning of section 910(a)(1)(B)), of the FD&C Act is not a new tobacco product and is not subject to premarket review. These comments also stated that because section 905(j)(1)(A)(i) of the FD&C Act explicitly excludes test marketed products from the commercially marketed products that may serve as valid predicate products, it demonstrates that the term “commercially marketed” encompasses products that are test marketed (
i.e.,
if test marketed products did not constitute commercially marketed products, there would have been no need for Congress to exclude them from the types of commercially marketed products that may qualify for use as predicate products under the substantial equivalence premarket pathway). Some comments requested FDA include the definitions as they were defined in the proposed rule, including as they relate to the definition of the term “new tobacco product” in proposed part 1114 (21 CFR part 1114). Other comments stated that the proposed definitions should not be included in the final rule because they are unnecessary, confusing, conflicting, and not useful. Specifically, some comments argued that FDA did not provide a workable or rational basis to distinguish “test marketing” from “commercially marketed” and the proposed definitions do not reflect industry realities.

(Response 3) Following our consideration of these comments, we have revised the definitions related to “Pre-Existing Tobacco Product” to remove language related to “exclusively” test marketed.

Upon reviewing comments received, we reassessed our interpretation of section 910(a)(1)(A) of the FD&C Act, and 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 that section 905 of the FD&C Act provides additional context that supports this interpretation. Section 905(j)(1)(A)(i) of the FD&C Act 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 section 910(a)(3), is substantially equivalent. Here, Congress' inclusion of the parenthetical “(other than for test marketing)” supports a reading of the term “commercially marketed” as

including products that were test marketed; otherwise, there would not be the need to specifically carve out test marketed products from the commercially marketed products that can serve as valid predicate products.

In addition, 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 (84 FR 50566 at 50571).

We agree with the commenter that further discussion of the term, test marketing, is needed to more accurately capture the scope of this term; accordingly, we are not including a definition of test marketing in the final rule.

After reviewing these comments and for the purposes of consistency, FDA is finalizing the definition of “Pre-Existing Tobacco Product” with changes to better align with the statute, first, by adding “(including those products in test markets)”, and, second, by removing “and does not include a tobacco product exclusively in test markets as of that date.” Specifically, FDA defines a “Pre-Existing Tobacco Product” to mean a tobacco product (including those products in test markets) that was commercially marketed in the United States as of February 15, 2007. The definition of “Pre-Existing Tobacco Product” in this rule reflects FDA's interpretation that “as of” means “on”, which has been included as part of previously issued regulations and guidance.
6

For more information on this topic, see the response to comment 5 explaining FDA's interpretation that “as of” means “on.” A Pre-Existing Tobacco Product is not subject to the premarket review requirements of section 910 of the FD&C Act.

6
See the final rule entitled “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 28973 at 28978, May 10, 2016) and the 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). Available at
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance.

C. Recordkeeping Requirements (§ 1100.204)

1. Required Records

Consistent with the authority to require recordkeeping under section 909 of the FD&C Act, § 1100.204(a) requires any tobacco product manufacturer that introduces a Pre-Existing Tobacco Product, or delivers it for introduction, into interstate commerce to maintain records and information necessary to adequately demonstrate that the tobacco product was commercially marketed in the United States as of February 15, 2007. This requirement will ensure, among other things, that records are available to FDA during an inspection. The rule does not require tobacco product manufacturers to maintain records for all of the types of information listed in § 1100.204(a); rather, the list provides examples of the types of records that may be used to demonstrate that a tobacco product was commercially marketed in the United States as of February 15, 2007.

2. Record Maintenance

Section 1100.204(b) requires that all records maintained under this part be legible, in the English language, and available for inspection and copying by officers or employees duly designated by the Secretary. This section also requires documents that have been translated from another language into English to be accompanied by: (1) The original language version of the document; (2) a signed statement by an authorized representative of the manufacturer certifying that the English language translation is complete and accurate; and (3) a brief statement of the qualifications of the person who made the translation (
e.g.,
education and experience). This information will help FDA ensure that the English language translations of documents are complete and accurately reflect the content of the original documents.

3. Record Retention

Section 1100.204(c) requires that the records and documents demonstrating that the tobacco product was commercially marketed as of February 15, 2007, be retained for a period of at least 4 years from the date that either FDA makes a Pre-Existing Tobacco Product determination or the tobacco product manufacturer permanently ceases the introduction or delivery for introduction into interstate commerce of the tobacco product, whichever occurs sooner. FDA has selected 4 years to help ensure that the records will be available for at least one biennial FDA inspection under sections 704 and 905(g) of the FD&C Act. FDA's biennial inspections under section 905(g) of the FD&C Act are required to occur at least once in every 2-year period after a manufacturer registers an establishment with FDA, which could result in inspections occurring nearly 4 years apart. Retaining records for 4 years after a manufacturer permanently ceases introduction or delivery for introduction into interstate commerce of the tobacco product will allow FDA to verify the Pre-Existing Tobacco Product status of the product during the time period in which it is offered for sale to consumers. Manufacturers that only temporarily cease the introduction or delivery for introduction into interstate commerce of the tobacco product must retain the records to allow FDA to verify the Pre-Existing Tobacco Product status of the product when they resume marketing the product. Additionally, manufacturers might want to retain records for longer than 4 years to help establish their product is a Pre-Existing Tobacco Product and may be eligible as a predicate product in an SE Report if it was commercially marketed (other than for test marketing) in the United States as of February 15, 2007.

V. Description of the Final Regulations for, and the Comments and FDA's Responses Regarding, the Maintenance of Records Relating to Exemptions From the Requirements of Demonstrating Substantial Equivalence (§ 1107.3)

The rule adds § 1107.3 to part 1107 of subchapter K of Title 21. Other than the comments and changes described in this section regarding the proposed definition of the term “grandfathered tobacco product” (now referred to as a “Pre-Existing Tobacco Product”), FDA received no comments regarding proposed § 1107.3, FDA is finalizing the requirements as proposed with one other change; we have removed the proposed requirement to maintain product labeling a part of § 1107.3 because it is not necessary to support an abbreviated report.

Section 1107.3 establishes recordkeeping requirements related to tobacco products that are exempt from the requirements of demonstrating SE under section 910(a)(2)(A)(ii) of the FD&C Act. Consistent with the authority to require recordkeeping under section 909 of the FD&C Act, § 1107.3 requires applicants that submitted an abbreviated report under section 905(j)(1)(A)(ii) of the FD&C Act, and received a letter from FDA

acknowledging the receipt of an abbreviated report, to maintain all records necessary to support the exemption for at least 4 years from the date FDA issues an acknowledgement letter in response to an abbreviated report. The rule requires the applicant to maintain records that are legible, written in English, and available for inspection and copying by officers or employees designated by the Secretary. Applicants may want to retain the records for a longer period if, for example they intend to submit a subsequent exemption request for a modification to the tobacco product.

A. Definition

Section 1107.3(a) defines “Pre-Existing Tobacco Product”
7

as a tobacco product (including those products in test markets) that was commercially marketed in the United States as of February 15, 2007. FDA has considered the comments described in section IV and revised this term as described in the responses in that section. As described in section IV.B.4., FDA interprets the phrase “as of February 15, 2007,” as meaning that the tobacco product was commercially marketed in the United States “on February 15, 2007.” See the response to comment 5 explaining FDA's interpretation that “as of” means “on.”

7
As described in section IV.B, we have changed the term “grandfathered tobacco product” to “Pre-Existing Tobacco Product.”

B. Record Maintenance

The rule requires applicants to maintain all documents that support their abbreviated report, which includes the documents listed in § 1107.3(b)(1). The rule does not require an applicant to create new or additional records; rather, it requires an applicant to maintain the records it has, obtains, or creates (including those created on its behalf, such as by a contract research organization) that support its abbreviated report. This includes documents that an applicant creates under other regulatory or statutory sections such as the submission of exemption requests under § 1107.1, PMTAs under part 1114, SE Reports under section 905(j) of the FD&C Act, and tobacco product manufacturing practice requirements issued under section 906(e) of the FD&C Act. The records an applicant is required to maintain include, but are not limited to:

• A copy of the abbreviated report and, if applicable, the exemption request and all amendments thereto;

• a copy of the acknowledgement letter issued in response to an abbreviated report and, if applicable, a copy of the exemption order issued by FDA;

• documents related to formulation of product, product specifications, packaging, and related items. Product formulation includes, for example, items such as the types of information described in § 1114.7(i) as described in section VIII.B.;

• documents showing that design specifications are consistently met. This could include, for example, information about testing procedures that are carried out before the product is released to market, such as the information described in § 1114.7(j) as described in section VIII.B.;

• documents related to product packing and storage conditions;

• analytical test method records, including:

○ Performance criteria;

○ validation or verification documentation; and

○ reports/results from these test methods; and

• source data and related summaries.

In addition to the documents specified in § 1107.3(b)(1), paragraphs (b)(2) through (b)(4) require tobacco product manufacturers to maintain records that support a determination that their exemption request meets the requirements of section 905(j)(3)(A)(i) of the FD&C Act that the modification to a product additive described in the exemption request was a minor modification made to a tobacco product that can be sold under the FD&C Act. This means that applicants need to maintain records demonstrating that the modification is being made to either a Pre-Existing Tobacco Product or a new tobacco product that has satisfied the premarket review requirements of section 910(a)(2) of the FD&C Act. For abbreviated reports based on a modification to a Pre-Existing Tobacco Product, § 1107.3(b)(2) requires applicants to maintain the documentation in § 1100.204 to demonstrate that the product that is being modified is legally marketed. For abbreviated reports based on a modification to a tobacco product that has previously received an exemption order in response to a request under § 1107.1 (and for which the applicant has submitted an abbreviated report under 905(j)(1)(A)(ii)), or a substantially equivalent order or a marketing granted order from FDA, § 1107.3(b)(3) requires applicants to maintain a copy of the exemption order, substantially equivalent order, or marketing granted order to demonstrate the product being modified is legally marketed. For abbreviated reports based on a modification to a tobacco product that is being marketed pursuant to section 910(a)(2)(B) of the FD&C Act for which FDA has not issued a substantially equivalent order, an applicant must maintain all communications to and from FDA relating to the pending SE Report, such as a letter acknowledging receipt of the report.

C. Record Quality

Section 1107.3(c) requires the records to be legible, in the English language, and available for inspection and copying by officers or employees duly designated by the Secretary. FDA also requires documents that have been translated from another language into English be accompanied by: (1) The original language version of the document, (2) a signed statement by an authorized representative of the manufacturer certifying that the English language translation is complete and accurate, and (3) a brief statement of the qualifications of the person who made the translation (
e.g.,
education and experience). This information helps FDA ensure that the English language translations of documents are complete and accurately reflect the content of the original documents.

D. Record Retention

Section 1107.3(d) requires the records described in § 1107.3(b) to be maintained for a period of not less than 4 years from the date on which FDA issues an acknowledgement letter in response to an abbreviated report. FDA has selected 4 years as a means to help ensure that the records are available for at least one biennial FDA inspection under sections 704 and 905(g) of the FD&C Act. FDA's biennial inspections under section 905(g) of the FD&C Act are required to occur at least once in every 2-year period after a manufacturer registers an establishment with FDA, which could result in inspections occurring nearly 4 years apart.

VI. Description of the Final Regulations for, and the Comments and FDA's Responses Regarding, Premarket Tobacco Product Applications (Part 1114)

The rule adds part 1114 to subchapter K of Title 21. The requirements set forth in this part apply to PMTAs for new tobacco products. Subpart A sets out the scope and definitions that apply to this part. Subpart B sets out the criteria for PMTA submission, content and format of PMTAs, application amendments, withdrawal of an application by an applicant, supplemental PMTAs, resubmissions, and change in ownership or contact information for a

PMTA. Subpart C describes FDA review and actions on applications, including provisions for withdrawal and temporary suspension of orders. Subpart D describes postmarket restrictions and reporting requirements. Subpart E sets miscellaneous requirements such as record retention, confidentiality, and electronic submission.

VII. General (Part 1114, Subpart A)

A. Scope (§ 1114.1)

Section 1114.1 describes the scope of part 1114 and its applicability to the submission and review of, and postmarket requirements related to, PMTAs. Section 1114.1 provides that part 1114 does not apply to MRTPAs, except instances where a single application is submitted to seek both a marketing granted order and a modified risk order instead of a separate PMTA and MRTPA. Under the rule, a single application seeking both a marketing granted order and a modified risk order under section 911(g) of the FD&C Act needs to meet the content and format requirements of both part 1114 and section 911 of the FD&C Act (21 U.S.C. 387k) (and any implementing regulations). This section also notes that references in the rule to regulatory sections of the Code of Federal Regulations (CFR) are to chapter I of Title 21, unless otherwise noted. Therefore, any CFR reference that begins with “part,” “section,” or the section symbol (§ ) should be read as if it were preceded by “21 CFR” (
e.g.,
§ 1114.1 refers to 21 CFR 1114.1, part 58 refers to 21 CFR part 58), unless another source is cited (
e.g.,
the FD&C Act).

(Comment 4) Some comments requested that “premium” cigars be exempt from the PMTA premarket pathway or that a different premarket pathway be created for them. Several comments describe the difference between “premium” cigars and other products, such as cigarettes or ENDS, and argue that these differences make it more difficult for “premium” cigars to comply with PMTA requirements. These comments request 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.

(Response 4) FDA received a range of comments related to “premium” cigars. A recent court decision “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.”
8

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

8

Cigar Ass'n of Am., et al.
v.
Food and Drug Admin., et al.,
Case No. 1:16-cv-01460 (APM), (D.D.C. August 19, 2020), Dkt. No. 214 (
Cigar Ass'n of Am.
).

• Is wrapped in whole tobacco leaf;

• contains a 100 percent leaf tobacco binder;

• 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);

• is handmade or hand rolled;
9

9
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.

• has no filter, nontobacco tip, or nontobacco mouthpiece;

• does not have a characterizing flavor other than tobacco;

• contains only tobacco, water, and vegetable gum with no other ingredients or additives; and

• 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 final 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 consider 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. Such information will inform the Agency's regulatory policy with respect to premarket review of “premium” cigars. Although the court opinion specifically discusses considering comments on the SE pathway, FDA's research efforts may also inform issues related to the review of applications for premium cigars under the PMTA pathway. Because these are ongoing efforts, at this time, FDA is not finalizing the proposed PMTA rule with respect to “premium” cigars. Rather, FDA will take appropriate action once it has further considered this matter, including 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 section § 1114.3.

B. Definitions (§ 1114.3)

Section 1114.3 provides the meaning of terms as they apply to part 1114:

1. Additive

As defined in section 900(1) of the FD&C Act, “additive” means 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 substances 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.

An additive can be a type of ingredient in a tobacco product; an example is methyl salicylate in smokeless tobacco, which can serve as an absorption enhancer and affect the characteristics of the tobacco product by changing the rate of absorption into the body. Tobacco is not an additive.

2. Brand

As defined in section 900(2) of the FD&C Act, “brand” means a variety of tobacco product distinguished by the tobacco used, tar content, nicotine content, flavoring used, size, filtration, packaging, logo, registered trademark, brand name(s), identifiable pattern of colors, or any combination of such attributes.

3. Characteristics

As defined in section 910(a)(3)(B) of the FD&C Act, “characteristics” means the materials, ingredients, design, composition, heating source, or other features of a tobacco product. The terms used in the definition of characteristic (materials, ingredients, design, etc.) are defined in § 1114.3.

4. Label

As defined in section 201(k) of the FD&C Act, “label” means a display of written, printed, or graphic matter upon the immediate container of any article; and a requirement made by or under authority of the FD&C Act that any word, statement, or other information appear on the label shall not be considered to be complied with unless such word, statement, or other information also appears on the outside container or wrapper, if any there be, of the retail package of such article, or is

easily legible through the outside container or wrapper.

5. Labeling

As defined in section 201(m) of the FD&C Act, “labeling” means all labels and other written, printed, or graphic matter: (1) Upon any article or any of its containers or wrappers or (2) accompanying such article.

6. New Tobacco Product

As defined in section 910(a)(1) of the FD&C Act, “new tobacco product” means: (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.

FDA received many comments regarding the proposed definition of “new tobacco product,” as discussed below.

(Comment 5) Multiple comments questioned FDA's interpretation of the phrase “as of February 15, 2007” as used in the definition of the terms “Pre-Existing Tobacco Product” and “new tobacco product” and stated that there is a lack of rationale for its interpretation. Comments argue that the plain meaning of the term “as of” support the interpretation that “as of” means “on or before” rather than “on”. As such, a tobacco product must qualify as a Pre-Existing Tobacco Product if it was commercially marketed in the United States at any time on or before February 15, 2007.

(Response 5) As previously stated, FDA's longstanding interpretation is that the statutory phrase “as of February 15, 2007,” 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 comments, the term “as of ” does not have a clear 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 (
e.g.,
compare “until” with “from”), the term is ambiguous. Even assuming “as of” could be interpreted as “at any time prior to and not necessarily including on the particular date” (in short referred to as the “on or before” 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 SE provision. It is reasonable to conclude that Congress did not intend to allow an immeasurable number of obsolete, abandoned, or discontinued products that were marketed before February 15, 2007, to return to the market without any premarket review or serve as predicates under the SE provision, but rather intended to confine this number to those products that were commercially marketed in the United States on February 15, 2007. Thus, we decline to adopt the interpretation the comments suggest.

Under section 910(a)(1) of the FD&C Act, and as reflected in the definition, 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 (21 U.S.C. 387j(a)(1)(B)). For example, modifications to cigarette paper, container closure systems (
e.g.,
change from glass to plastic e-liquid vials or from plastic to tin container closures), product quantity, or tobacco cut size would result in a new tobacco product.

(Comment 6) One comment stated that the term “co-packaging,” which is included in the discussion of the definition of the term “new tobacco product,” is confusing and does not provide a basis for regulating co-packaged products as part of premarket review.

(Response 6) Manufacturers sometimes co-package tobacco products, and FDA seeks to clarify what effect co-packaging tobacco products may have on whether those products are required to undergo premarket review. If there has been a change to the packaging of co-packaged tobacco products that is intended or reasonably expected to affect or alter the performance, composition, constituents, or characteristics of the tobacco product, then it is a change to the container closure system and, therefore, is a new 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 co-packaged together within a container closure system, it results in a new tobacco product requiring premarket authorization. However, 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.

In addition, 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 USA Inc.
v.
U.S. Food & Drug Admin.,
202 F. Supp. 3d 31, 55-57 (D.D.C. 2016). If a premarket application 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.

7. Package or Packaging

As defined in section 900(13) of the FD&C Act, the term “package,” also referred to in the rule as “packaging,” means 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. A subset of package is the container closure system (also defined in this rule). For example, the carton holding multiple soft packs of cigarettes is considered the package, and each soft

pack with surrounding cellophane is considered the container closure system. 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 consumable tobacco product), but 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.

8. Tobacco Product

As defined in section 201(rr) of the FD&C Act, the term “tobacco product” means any product that is 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 is a drug under section 201(g)(1), a device under section 201(h), or a combination product described in section 503(g) of the FD&C Act (21 U.S.C. 353(g)).

9. Tobacco Product Manufacturer

As defined in section 900(20) of the FD&C Act, the term “tobacco product manufacturer” means any person, including any 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. FDA interprets “manufactures, fabricates, assembles, processes, or labels” as including, but not being limited to, (1) repackaging or otherwise changing the container, wrapper, or labeling of any tobacco product package; (2) reconstituting tobacco leaves; or (3) applying any chemical, additive, or substance to the tobacco leaf other than potable water in the form of steam or mist. A definition for the term “finished tobacco product” is also included in the rule.

10. Accessory

FDA defines “accessory” as any product that is intended or reasonably expected to be used with or for the human consumption of a tobacco product; does not contain tobacco and is not made or derived from tobacco; and meets either of the following:

• Is not intended or reasonably expected to affect or alter the performance, composition, constituents, or characteristics of a tobacco product or

• is intended or reasonably expected to affect or maintain the performance, composition, constituents, or characteristics of a tobacco product, but:

○ Solely controls moisture and/or temperature of a stored product or

○ solely provides an external heat source to initiate but not maintain combustion of a tobacco product.

This matches the definition of accessory set forth in § 1100.3. Examples of accessories are ashtrays and spittoons because they do not contain tobacco, are not derived from tobacco, and do not affect or alter the performance, composition, constituents, or characteristics of a tobacco product. Examples of accessories also include humidors or refrigerators that solely control the moisture and/or temperature of a stored product and conventional matches and lighters that solely provide an external heat source to initiate but not maintain combustion of a tobacco product.

11. Adverse Experience

FDA defines “adverse experience” as any unfavorable physical or psychological effect in a person that is temporally associated with the use of or exposure to a tobacco product, whether or not the person uses the tobacco product, and whether or not the effect is considered to be related to the use of or exposure to the tobacco product. FDA received many comments regarding this definition, as discussed below.

(Comment 7) Multiple comments requested changes to the definition of what constitutes an adverse experience. One comment requested FDA amend the definition to explicitly include increased use by youth or young adults. Another comment stated that the definition of adverse experience is too broad and subjective, and should be revised to refer to a health-related event associated with the use of or exposure to (intended or incidental) a tobacco product.

(Response 7) FDA declines to change the definition of adverse experience because this widely understood definition is generally consistent with language used throughout the Agency and is designed to capture a broad swath of information related to health effects from FDA regulated products. Due to the fact that the experience may not relate to the individual user but could also affect the general public or bystander, it is FDA's intent that the definition remain broad to ensure we receive the potential wide variety of voluntary reports of adverse experiences involving tobacco products from investigators, consumers, healthcare professionals and concerned members of the public. Additionally, FDA declines to revise the definition to include use by youth and young adults because it constitutes a behavior, not a health effect related to an adverse experience. Increases in use by individuals under the minimum age of sale will be monitored through the review of periodic reports submitted under § 1114.41, among other means.

FDA notes that it is important to also include information regarding adverse experiences associated with use of or exposure to a product where the individual suffering the adverse experience did not use the product because it can help FDA determine health risks for nonusers, such as the effects of second-hand exposure or accidental exposure (
e.g.,
skin burns from accidental exposure to liquid nicotine, harmful effects resulting from a child drinking an e-liquid, respiratory difficulties from second-hand exposure to an e-cigarette). Additionally, reporting information regarding all adverse experiences that are temporally associated with the use of or exposure to the product will help the applicant avoid self-selection bias of what is reported to FDA and help identify harmful effects that are not obviously attributable to the product.

12. Applicant

FDA defines “applicant” as any person that submits a PMTA to receive a marketing granted order for a new tobacco product.

13. Commercially Marketed

In the proposed rule, FDA proposed to define “commercially marketed” as “selling or offering a tobacco product for sale to consumers in all or in parts of the United States.” After reviewing comments described in section IV, FDA has decided to finalize the definition of “commercially marketed” to mean 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. See discussion in section IV.B.3.

14. Component or Part

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. Component or part excludes anything that is an accessory of a tobacco product. A container closure system (which is also defined in this section) is considered a component or part. With respect to these definitions, FDA notes that “component” and “part” are separate and distinct terms within chapter IX of the FD&C Act. However, for purposes of this rule, FDA is using the terms “component” and “part” interchangeably and without emphasizing a distinction between the terms. FDA may clarify the distinctions between “component” and “part” in the future. This definition matches the definition in § 1100.3.

15. Composition

FDA defines “composition” as the materials in a tobacco product, including ingredients, additives, and biological organisms. The term includes the manner in which the materials, for example, ingredients, additives, and biological organisms, are arranged and integrated to produce a tobacco product. Composition refers primarily to the chemical and biological properties of a tobacco product, whereas design refers to the physical properties of a tobacco product. A biological organism refers to any living biological entity, such as an animal, plant, fungus, or bacterium.

16. Constituent

In this final rule, we have updated the definition of constituent on our own initiative to clarify the meaning. FDA defines “constituent” as any chemical or chemical compound in a tobacco product that is or potentially is inhaled, ingested, or absorbed into the body, any chemical or chemical compound in an emission (
e.g.,
smoke, aerosol, droplets) from a tobacco product, that either transfers from any component or part of the tobacco product to the emission or that is formed by the product, including through combustion or heating of tobacco, additives, or other components of the tobacco product.

17. Container Closure System

FDA defines “container closure system” as any packaging materials that are a component or part of a tobacco product. FDA received several comments regarding the proposed definition, as discussed below.

(Comment 8) A few comments suggested related revisions to both the definitions of the terms “container closure system” (CCS), “packaging,” and “component or part,” as well as what modifications to a CCS FDA considers to result in a new tobacco product. The comments requested that the definition of CCS be limited to only the product packaging that is designed or reasonably expected to alter the product characteristics after the time of manufacture. Comments stated that failure to make such a change would be inconsistent with the court's decision in
Philip Morris
v.
FDA,
202 F. Supp. 3d 31, 51 (D.D.C. 2016). Citing this case, which in the course of distinguishing between a product and its labeling, referenced “the physical attributes of the product itself, as distinct from its label or the package in which it is contained,” the comments argue that the law's requirements for new tobacco products apply only when there are changes in “the physical attributes of a tobacco product—not its labeling or packaging.”
Id.
Likewise, the comments stated that modifications to the CCS should result in a new tobacco product only if modifications are intended or reasonably expected to alter the characteristics of the product. The comments maintained that if the packaging's purpose is merely to maintain or preserve the characteristics of the product, it should only be considered packaging, not a CCS.

(Response 8) As described in the 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. Contrary to the commenter's assertion, 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. This is consistent with the holding of
Philip Morris,
202 F. Supp. at 51, as is its converse: Packaging that is not the container closure system and is not intended or reasonably expected to affect or alter the performance, composition, constituents, or characteristics of the tobacco product is, therefore, not a component or part of a tobacco product. As such, packaging that is, for example, the packaging around a blister pack is not part of the PMTA 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. However, where a change in the container closure system could affect the chemistry of the product, FDA requires the applicant, where it submits a PMTA, to demonstrate that permitting marketing of the product with the change in the container closure system is appropriate for the protection of public health.

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 diffuse into snuff and affect its characteristics (Ref. 2). Thus, 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 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 those that may reasonably be expected to have such effects. Similarly, if FDA were to adopt a narrow construction of “tobacco product” to exclude these materials, the Agency's ability to evaluate whether permitting the marketing of the new tobacco product was appropriate for the protection of public health (APPH) 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.

18. Design

FDA defines “design” to mean the form and structure concerning, and the manner in which components or parts, ingredients, software, and materials are integrated to produce a tobacco product. This term refers to the physical properties of a tobacco product. Examples of design parameters include ventilation, paper porosity, filter efficiency, battery voltage and current operating range, and electrical heater coil resistance. FDA received one comment on this definition, as discussed below.

(Comment 9) One comment stated that the definition of the term “design” does not take into account the inherent variability that can occur in tobacco crops over the years. The comment stated that such variability may require manufacturers to alter, in a limited capacity, certain characteristics of the product, in order to minimize variability of constituent levels in its final aerosol. The comment concluded that the proposed definition was rather narrow and did not allow for the control of emission levels through design adjustments. The comment recommended that the definition be amended to allow applicants to adjust design features for the sole purpose of accommodating natural variability of tobacco plants, without requiring the submission of a new PMTA or a supplemental PMTA.

(Response 9) FDA declines to make changes as a result of this comment. At this time, FDA does not intend to enforce the requirement of premarket review in section 910 for tobacco blending changes required to address the natural variation of tobacco (
e.g.,
blending changes due to variation in growing conditions) to maintain a consistent product.
10

Where an applicant changes other characteristics of a tobacco product (
i.e.,
characteristics other than tobacco blend) to minimize variability of the product, FDA intends to enforce the premarket authorization requirements, and the PMTA must contain all appropriate information for the distinct new tobacco product that would result from such changes.

10
For more information on FDA's enforcement of premarket review for tobacco blending changes, see the guidance entitled “Demonstrating the Substantial Equivalence of a New Tobacco Product: Responses to Frequently Asked Questions” available at
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance.

19. Finished Tobacco Product

FDA defines “finished tobacco product” to mean a tobacco product, including all components and parts, sealed in final packaging (
e.g.,
filters or filter tubes sold to consumers separately or as part of kits, or e-liquids sealed in final packaging sold to consumers either separately or as part of kits) or in the final form in which it is intended to be sold to consumers. FDA received one comment on this definition, as discussed below.

(Comment 10) One comment stated that the definition of the term “finished tobacco product” should conform to the definition previously used in the registration and listing guidance, which included the phrase “intended for consumer use.”

(Response 10) FDA has edited the definition of the term “finished tobacco product” to include the phrase “or in the final form in which it is intended to be sold to consumers” to help clarify the meaning of the term “finished.” We believe that by including products sold in the final form in which it is intended to be sold to consumers, we are capturing a variety of products including those intended for consumer use as requested by the commenter.

20. Harmful or Potentially Harmful Constituent (HPHC)

FDA defines “harmful or 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, including as an aerosol or any other emission and (2) causes or has the potential to cause direct or indirect harm to users or nonusers of tobacco products. This definition aligns with the definition provided for in the guidance for industry entitled “`Harmful and Potentially Harmful Constituents' in Tobacco Products as Used in Section 904(e) of the FD&C Act.”

The established list of HPHCs can be found on FDA's website at
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/harmful-and-potentially-harmful-constituents-tobacco-products-and-tobacco-smoke-established-list
(77 FR 20034, April 3, 2012). FDA issued a notice in the
Federal Register
of August 5, 2019 (84 FR 38032), seeking public comment on the proposed addition of 19 constituents to the established list of HPHCs. FDA is proposing these additions to reflect the range of tobacco products now subject to FDA's tobacco product authorities, including deemed tobacco products such as ENDS. FDA will finalize the addition of these HPHCs to the established list, as appropriate, after reviewing public comment and generally intends to make any future updates to the established list of HPHCs through a similar notice and comment process.

FDA received one comment on this definition, as discussed below.

(Comment 11) One comment stated that FDA should either change the definition of the term “harmful or potentially harmful constituent” (HPHC) to include a list of all HPHCs for which testing results must be submitted in a PMTA or include a list of all such HPHCs elsewhere in the rule.

(Response 11) FDA declines to revise the definition of HPHC. In defining this term, FDA is describing criteria for what constitutes an HPHC and is not attempting to identify specific constituents. In contrast, section 904 of the FD&C Act requires FDA to establish, and periodically revise, a list of HPHCs. More importantly for PMTA content, as discussed in section VIII.B.9.a.v., an application would not be required to contain testing for all HPHCs; rather, it would be required to contain testing for constituents, including HPHCs, that are contained within and can be delivered by the type of product and contain a description of why the HPHCs that were tested are appropriate for the type of product.

FDA similarly declines to set forth a list of constituents that must be tested because it would be overly broad as it pertains to most tobacco products. It is FDA's understanding that manufacturers have information concerning what constituents might be

emitted from their specific tobacco products. FDA believes that allowing applicants to use this knowledge in selecting the appropriate constituents for testing would result in a more efficient process for preparing PMTAs than requiring manufacturers to test for each constituent in a broad list, including HPHCs that might not pertain to the applicant's specific product.

21. Heating Source

FDA defines “heating source” as the source of energy used to burn or heat the tobacco product. Examples of a heating source include a flame or a rechargeable battery.

22. Ingredient

FDA defines “ingredient” as tobacco, substances, compounds, or additives 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. For example, an ingredient may be a single chemical substance, leaf tobacco, or the product of a reaction, such as a chemical reaction, in manufacturing. Examples of substances and compounds (ingredients) reasonably expected to be formed through a chemical reaction during tobacco product manufacturing include the following:

• The reaction of sugars with amines to form families of compounds with new carbon-nitrogen bonds, including Maillard reaction products and Amadori compounds;

• the reaction of sodium hydroxide with citric acid to form sodium citrate;

• the production of ethyl alcohol, a residual solvent, from ethyl acetate during production of tipping paper adhesive;

• products of thermolytic reactions, such as the production of carboxylic acids from sugar esters;

• products of enzymatically or nonenzymatically catalyzed reactions, such as the hydrolytic production of flavor or aroma precursors from nonvolatile glucosides; and

• products of acid-base reactions, such as removal of a proton from protonated nicotine to generate the basic form of nicotine (“free” nicotine).

23. Line Data

FDA defines “line data” to mean an analyzable dataset of observations for each individual study participant, laboratory animal, or test replicate. Line data typically provides information that is more useful to FDA's review of an application than data in its more “raw” forms because it allows information about time, people, and places involved in investigations to be organized and reviewed quickly, and it facilitates tracking of different categories of cases. FDA is requiring an applicant to submit line data rather than source data (also referred to as raw data) to allow for a more efficient review process. As described in § 1114.45, applicants are required to retain all source data in the event that FDA needs to inspect the data as part of its application review.

24. Material

FDA defines “material” to mean an assembly of ingredients. Materials are assembled to form a tobacco product, or components or parts of tobacco product. For example, material includes the glue or paper pulp for a cigarette where the paper pulp includes multiple ingredients (
e.g.,
multiple types of tobacco, water, and flavors) assembled into the paper (or pulp depending on the water content). Another example of a material is a plastic composed of chemical substances that houses electrical components.

25. Marketing Granted Order

FDA defines “marketing granted order” to mean the order described in section 910(c)(1)(A)(i) of the FD&C Act that authorizes the new tobacco product to be introduced or delivered for introduction into interstate commerce.

26. Marketing Denial Order

FDA defines “marketing denial order” to mean the order described in section 910(c)(1)(A)(ii) of the FD&C Act that the product may not be introduced or delivered for introduction into interstate commerce.

27. Other Features

FDA defines “other features” to mean any distinguishing qualities of a tobacco product similar to those specifically enumerated in section 910(a)(3)(B) of the FD&C Act. The definition includes: (1) HPHCs (the definition of new tobacco product includes any modification to any constituents, including smoke constituents; section 910(a)(1)(B) of the FD&C Act) and (2) any other product characteristics that relate to the chemical, biological, or physical properties of the tobacco product. The term “other features” also encompasses other product characteristics that relate to the chemical, biological, and physical properties of the product that would not be included as a material, ingredient, design, composition, or heating source.

28. Premarket Tobacco Product Application or PMTA

FDA defines “premarket tobacco product application” or “PMTA” to mean the application described in section 910(b) of the FD&C Act. This term includes the initial premarket tobacco product application and all subsequent amendments.

29. “Premium” Cigar

As discussed in section VI.A., we are adding the
Cigar Ass'n of Am.
court's definition of “premium” cigars to § 1114.3. “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.

30. Serious Adverse Experience

FDA defines “serious adverse experience” to mean an adverse experience that results in any of the following outcomes: (1) Death; (2) a life-threatening condition or illness; (3) inpatient hospitalization or prolongation of existing hospitalization; (4) a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions (
e.g.,
seizures that do not result in hospitalization, burns that result in damage to a limb or nerve damage); (5) a congenital anomaly/birth defect; or (6) any other adverse experience that, based upon appropriate medical judgment, may jeopardize the health of a person and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. This could include, for example, carbon monoxide poisoning, which if left untreated, could result in long term and possibly delayed brain damage or heart damage.

FDA received one comment on this definition, as discussed below.

(Comment 12) One comment stated that the definition of the term “serious adverse experience” needs to be clarified, recommending that it be aligned with a similar definition used by FDA for drugs. Specifically, the comment requested that FDA further

define the term “life-threatening condition or illness” in paragraph (b) of the definition to mean, as it does in the drug context, any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse experience as it occurred,
i.e.,
it does not include an adverse experience that, had it occurred in a more severe form, might have caused death. The comment also requested that FDA restrict the “catch-all” in paragraph (f) of the definition so that it focuses on “important medical events,” similar to the definition for drugs, rather than “adverse experiences” as the definition currently does.

(Response 12) FDA declines to revise the definition of serious adverse experience because it captures the events for which FDA would need prompt notification once a product is on the market. Through paragraph (b) of the definition of “serious adverse experience,” FDA is seeking information about adverse experiences carrying an immediate risk of death. In contrast, through paragraph (f) of the definition of “serious adverse experience,” FDA is interested in receiving prompt notification of a condition that could have delayed consequences, for example, one that that could cause death or severe organ damage if left untreated, or immediate death had it occurred in a more severe form so we can investigate whether the condition could occur in a more severe form and cause death in different individuals. We believe that having paragraph (f) focus on adverse experiences appropriately captures this scope. Applicants with questions regarding whether an adverse experience qualifies as a serious adverse experience are encouraged to promptly contact FDA.

31. Submission Tracking Number or STN

FDA defines “submission tracking number” or “STN” to mean the number that FDA assigns to submissions that are received from an applicant, such as a PMTA and a supplemental PMTA. FDA has added this definition to the final rule on its own initiative to help clarify requirements to specify submission tracking numbers.

32. Unexpected Adverse Experience

FDA defines “unexpected adverse experience” to mean an adverse experience occurring in one or more persons in which the nature, severity, or frequency of the experience is not consistent with: (1) The known or foreseeable risks associated with the use or exposure to the tobacco product as described in the PMTA (including the results of human subject investigations) and other relevant sources of information, such as the product labeling and postmarket reports; (2) the expected natural progression of any underlying disease, disorder, or condition of the persons(s) experiencing the adverse experience and the person's predisposing risk factor profile for the adverse experience; or (3) the results of nonclinical investigations.

FDA received one comment regarding this definition, as discussed below.

(Comment 13) One comment stated that the definition of unexpected adverse experience is unnecessarily complex and would likely lead to unduly burdensome reporting. The comment noted potential difficulties with assessing what constitutes a “foreseeable” risk and expressed a belief that the definition should be aligned with those found in other product groups that focus on unexpected adverse experiences being those that are not currently listed on product packaging and not previously observed.

(Response 13) FDA declines to revise the definition of unexpected adverse experience because it captures the events and information that should be disclosed. This information is important to FDA's ongoing monitoring of a tobacco product because it would alert the Agency to the potential scope and frequency for health risks that were not previously considered as part of application review and may inform a determination of whether the marketing granted order should be withdrawn or temporarily suspended. Foreseeable risks are harms that could reasonably be predicted based upon the content of the PMTA and other available sources of information and is largely based on mechanism of action or composition of the tobacco product.

33. Vulnerable populations

The proposed rule did not expressly discuss vulnerable populations. However, FDA received several comments regarding this issue, as discussed below.

(Comment 14) Multiple comments raised concerns related to the lack of reference to vulnerable populations in the proposed rule. One comment stated that the tobacco industry has a history of marketing its products to individuals with specific characteristics, including, but not limited to veterans, individuals with a low socioeconomic status (SES), and vulnerable populations. The comment requested that FDA require applicants to specify detailed demographic information in their marketing plans, including the targeting of its marketing by SES as part of a PMTA. Another comment stated that a definition of vulnerable populations should be included in the final rule. In addition, multiple comments requested FDA require PMTAs to contain a consideration of the effects of permitting the marketing of the new tobacco product on vulnerable or sensitive subpopulations (
e.g.,
individuals whose health has been compromised).

(Response 14) FDA agrees that consideration of vulnerable populations is an important part of determining whether permitting the marketing of a new tobacco product would be APPH. As discussed in section IX.D.1., FDA considers many factors when making its APPH determination, including the likelihood that existing users of tobacco products will stop using such products and the likelihood that nonusers of tobacco products will start using. This could include information regarding the marketing of a new tobacco product that may produce a positive effect for some subpopulations while producing differential effects for other subpopulations. For example, a non-combusted tobacco product that may help current adult smokers transition away from cigarettes may appeal to and lead to tobacco product initiation among youth and young adults who have never used tobacco products.

To ensure FDA understands the full health impact of the product, it is important for FDA to consider vulnerable populations and how the marketing of the new tobacco product can impact the likelihood that existing users of tobacco products will stop using such products and the likelihood that nonusers will start using the product. FDA has revised the rule to emphasize the importance of considering the effect of marketing a new tobacco product would have on vulnerable populations as well defined the term “vulnerable populations” in § 1114.3 to mean groups that are susceptible to tobacco product risk and harm due to disproportionate rates of tobacco product initiation, use, burden of tobacco-related diseases, or decreased cessation. Relevant vulnerable populations will vary depending on the type of tobacco product and may change over time, and can include, but are not limited to, youth and young adults, those who are of low SES, certain racial or ethnic populations, underserved rural populations, people with co-morbid mental health conditions or substance use disorders, military or veteran populations, people who are pregnant or are trying to become pregnant, and sexual or gender minorities (Refs. 4-9).

Also note that section VIII.B.6.b. includes SES as an example demographic characteristic to clarify the range of potential characteristics that may be included in descriptions of marketing plans.

VIII. Premarket Tobacco Product Applications (Part 1114, Subpart B)

A. Application Submission (§ 1114.5)

As described in § 1114.5, if an applicant seeks a marketing granted order under the PMTA pathway for its new tobacco product, it would be required to submit a PMTA to FDA and receive a marketing granted order before the tobacco product may be introduced or delivered for introduction into interstate commerce. An applicant submitting a PMTA to FDA should include all information required to be in a PMTA as part of its initial submission, including all sections specified in § 1114.7(a), except for product samples which, if required, must be submitted after a PMTA is accepted for review as described in the discussion § 1114.7(e) in section VII.B.5. Submitting a complete application as part of an initial submission is important because, as explained in the discussion of § 1114.27 in section VIII.B, FDA may refuse to accept or file an incomplete application for review.

FDA received several comments regarding the scope of products required to submit a PMTA.

(Comment 15) Some comments request that certain tobacco products, such as ENDS and oral tobacco derived nicotine, be exempt from the PMTA premarket pathway or that a different premarket pathway be created for them. The comments described certain products as significantly less harmful than other products, which they contended justifies either an exemption from the requirements of the PMTA pathway or a creation of a streamlined pathway under which products can be authorized based upon a few approaches, such as the submission of significantly less information that would be required under this rule. Other comments requested a similar streamlined pathway for small businesses due to the cost of preparing a PMTA.

(Response 15) As described in detail throughout this rule, the information required by part 1114 is necessary to ensure FDA has sufficient information to consider, as required by section 910(c) of the FD&C Act, the potential risks and benefits of a new tobacco product to the health of the population as a whole in determining whether the marketing of that product would be appropriate for the protection of public health. FDA declines to create a streamlined pathway for certain tobacco product categories or manufacturers that permits the submission of significantly less information than required by this rule because it would result in FDA having insufficient information to make its statutorily required determinations under section 910(c) of the FD&C Act. Consistent with the deeming final rule,
11

we also decline the request to exempt products from the requirements of PMTA or from premarket review more broadly. Section 910 of the FD&C Act establishes the procedures that must be followed before a new tobacco product can be authorized for marketing and it applies to all new tobacco products.

11
See the deeming final rule (81 FR 28974) for responses to similar comments requesting alternative or abbreviated PMTA pathways and exemptions from the requirements of premarket review.

B. Required Content and Format (§ 1114.7)

1. General

As explained in § 1114.7(a), the rule requires each PMTA to contain sufficient information necessary for FDA to determine whether the grounds for denial of an application listed in section 910(c)(2) of the FD&C Act apply to the PMTA, which includes the following sections:

• General information (as described in § 1114.7(c));

• descriptive information (as described in § 1114.7(d));

• product samples (as described in § 1114.7(e));

• labeling (as described in § 1114.7(f));

• statement of compliance with part 25 (21 CFR part 25) (as described in § 1114.7(g));

• summary (as described in § 1114.7(h));

• product formulation (as described in § 1114.7(i));

• manufacturing (as described in § 1114.7(j));

• health risk investigations (as described in § 1114.7(k));

• the effect on the population as a whole (as described in § 1114.7(l)); and

• certification statement (as described in § 1114.7(m)).

As described in section VIII.B, if the application does not appear to contain these sections and the information required therein (except for product samples), the Agency may refuse to accept the application for review under § 1114.27(a)(1). As described in section VIII.B, if a PMTA does not contain sufficient information required by these sections to permit a substantive review, including substantive information regarding broad areas of scientific information noted where appropriate in this document, FDA may refuse to file the application under § 1114.27(b)(1).

2. Format

Section 1114.7(b) provides the general requirements for the format of the application and would require the applicant to submit the application with the appropriate FDA form(s) (
i.e.,
Form FDA 4057 (Ref. 10) and Form FDA 4057b (Ref. 11)). Section § 1114.7(b)(1) would require the application and any amendments to contain a comprehensive index and table of contents and be well organized, legible, and written in the English language. The comprehensive index would include the listing of files and data associated with those files (
e.g.,
for an application that is electronically submitted, the comprehensive index would include the listing of files and associated metadata). FDA is also requiring that documents that have been translated from another language into English must be accompanied by the original language version of the document, a signed statement by an authorized representative of the manufacturer certifying that the English language translation is complete and accurate, and a brief statement of the qualifications of the person who made the translation (
e.g.,
education and experience). This information would help FDA ensure that the English language translations of documents are complete and accurately reflect the content of the original documents.

As described in § 1114.49, FDA is requiring that the PMTA and all supporting documents be submitted to FDA in an electronic format that the Agency can process, review, and archive, unless the Agency has previously granted a waiver from these requirements. An application would not be considered received until CTP's Document Control Center has received an application that the Agency can process, review, and archive. Applicants that are unable to submit their applications in electronic format may seek a waiver from the electronic filing requirement, in accordance with § 1114.49.

FDA received several comments regarding PMTA format, as discussed below.

(Comment 16) One comment stated that FDA must address inconsistencies between the ENDS PMTA Guidance and the PMTA Proposed Rule, citing

differences such as marketing plans and application organization.

(Response 16) FDA will update the ENDS PMTA Guidance to ensure it is consistent with the requirements and recommendations in this rulemaking. When updated, the ENDS PMTA Guidance will provide updated important product-specific recommendations for applicants submitting PMTAs for ENDS. In addition, if applicants wish to discuss the development of a PMTA, the applicant may request a meeting as set forth in the guidance for industry and investigators entitled “Meetings with Industry and Investigators on the Research and Development of Tobacco Products.”
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Available at
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance

(Comment 17) One commenter stated that while the proposed rule notes FDA's intent to provide information regarding acceptable technical specifications for electronic submissions, it was not aware of FDA having done so and requested that the final rule contain clear and consistent expectations for electronic submissions so that industry can properly plan and prepare applications in advance of submission.

(Response 17) Applicants can visit FDA's web page for more information on electronic submission, including electronic submission file formats and specifications. As of the date of the publication of this rule, this information is located at:
https://www.fda.gov/industry/fda-esubmitter/using-esubmitter-prepare-tobacco-product-submissions.
This web page also contains a link to the document “Electronic Submission File Formats and Specifications,” which provides additional helpful information. As mentioned in the proposed rule, FDA intends to update this information as needed to accommodate changes in technology.

FDA has created these format requirements using its authority under sections 701 and 910 of the FD&C Act to efficiently enforce premarket review requirements. The requirements in § 1114.7(b) are intended to address some of the problems we have seen with applications to date. For example, some applications have been submitted to FDA in a proprietary or password protected format without providing FDA access or password information. Following up with an applicant to obtain access or password information takes time and contributes to delays. In addition, some electronic submission files have not been of a static format, and thus, the pages reformat, repaginate, rebullet, or redate each time the document is accessed. For example, Microsoft Word files can change upon opening by FDA reviewers, while PDF files remain as the applicant intended. Receiving applications with these issues affects our ability to cross-reference, share (internally), and efficiently evaluate information. Also, FDA is required under regulations governing Federal records to maintain many files long-term, and in a “sustainable” format (for more information on sustainable formats, please refer to National Archives and Records Administration Bulletin 2014-04,
https://www.archives.gov/records-mgmt/bulletins/2014/2014-04.html
), § 1114.7(b) will ensure that these files can be managed, opened, and read by the Agency for the duration of the retention period.

Finally, § 1114.7(b)(2) will allow an applicant to include content in a PMTA by cross-reference to a tobacco product master file (TPMF) or a pending MRTPA for the same tobacco product submitted under section 911 of the FD&C Act. A TPMF is a file that is voluntarily submitted to CTP that contains trade secret and/or confidential commercial information about a tobacco product or component that the owner does not want to share with other persons. TPMFs are a beneficial tool for manufacturers, component suppliers, and ingredient suppliers, and can assist the tobacco product submission process. TPMFs allow individuals to rely on the information contained in a TPMF in a submission to FDA without the TPMF owner having to disclose the information to those individuals. TPMFs are typically used to prevent the disclosure of information that contains trade secrets or confidential commercial information. One situation in which TPMFs might be useful in submitting a PMTA is where an applicant is seeking marketing authorization for a new tobacco product that is made using a component or part, or ingredient that is purchased from another tobacco product manufacturer (
e.g.,
blended tobacco or an e-liquid). Applicants must demonstrate they have the right to reference the TPMF to be able to include content by cross-reference, such as by having the master file holder provide a letter of authorization. Applicants must specify the master file number and clearly identify the specific content that it is incorporating into its PMTA. For FDA's current thinking on the use of TPMFs, please consult the guidance for industry entitled “Tobacco Product Master Files.”
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Available at:
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance.

(Comment 18) A number of comments submitted similar concerns about the lack of data standardization, stating that FDA should standardize the data required to be submitted and allow companies to rely on the same pool of standardized data where it applies to similar aspects of their new tobacco product, such as submitting the same ingredients, to improve the efficiency for both application submission and review.

(Response 18) When companies want to rely on the same pool of data, FDA encourages the use of shared resources, such as tobacco product master files, where appropriate.

Applicants may also include content in a PMTA by cross-reference to a pending MRTPA for the same tobacco product.
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FDA recommends that applicants seeking to market a new tobacco product that has not previously received marketing authorization as a modified risk tobacco product (MRTP) submit a single application to seek both a marketing granted order and a modified risk granted order (
i.e.,
a combined PMTA and MRTPA); however, where an applicant chooses to submit a separate PMTA and MRTPA, FDA recommends that an applicant submit the full text of any common content (
e.g.,
the manufacturing or product formulation sections) in a PMTA and include it in the MRTPA by cross-reference. This approach would prevent any transcription errors and would allow for a more effective review by FDA because the content would only need to be reviewed once to be considered as part of both applications.

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FDA has not included MRTPAs that resulted in a modified risk order in the list of documents that an applicant may cross-reference as part of a PMTA. Because a new tobacco product must receive premarket authorization under section 910 of the FD&C to be introduced or delivered for introduction into interstate commerce, FDA does not intend to act on a MRTPA unless the product has a pending application seeking, or has already received, marketing authorization under section 910, or is a Pre-Existing Tobacco Product. Such an approach will allow FDA to efficiently enforce section 911 of the FD&C Act by focusing its efforts on only those applications that could potentially result in a tobacco product being introduced to the market.

Under this rule, except as described in subpart B, FDA will not consider content included by cross-reference to any other sources of information outside of a submission. An applicant may use internal cross-references for any content that would need to be referenced in multiple sections of a PMTA (
i.e.,
include the full text of the content in one section and use cross-references to

the content in other sections), rather than including the full text of the same information multiple times. If an applicant wishes to include information it has previously submitted to FDA other than a master file or a pending MRTPA (
e.g.,
portions of an SE Report or previously submitted PMTA for a different product), the applicant must include the full text of such information in its PMTA. FDA is implementing this restriction because cross-referencing information from other types of applications (
e.g.,
SE Reports, previously submitted PMTAs for different products) can make review difficult and contribute to delays in the review process.

(Comment 19) One comment stated that FDA should amend the application format requirements so that it allows PMTAs to include information by cross-reference to part

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Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/fr%3A2021-21011. Public record. Not legal advice.