Premarket Tobacco Product Applications and Recordkeeping Requirements
Federal RegisterSep 25, 2019
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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:
Proposed rule.
SUMMARY:
The Food and Drug Administration (FDA) is issuing a proposed rule that would set forth requirements for premarket tobacco product applications (PMTAs) and would require manufacturers to maintain records establishing that their tobacco products are legally marketed. The proposed rule would help to ensure that PMTAs contain sufficient information for FDA to determine whether a marketing order should be issued for a new tobacco product, including detailed information regarding the physical aspects of a tobacco product, as well as full reports of information to demonstrate the scope of, and details regarding, investigations that may show the potential health risks of the product. The proposed rule would codify the general procedures FDA would follow when evaluating PMTAs, including application acceptance, application filing, and inspections, and would also create postmarket reporting requirements for applicants that receive marketing orders. The proposed rule would allow for the submission of PMTAs in alternative formats in certain instances to reduce the burden of submitting a PMTA for modifications to a product that previously received a PMTA marketing order or resubmitting a PMTA to address deficiencies specified in a no marketing order. The proposed rule would also require tobacco product manufacturers to keep records regarding the legal marketing of certain tobacco products without a PMTA, such as documents showing that a tobacco product is not required to undergo premarket review or has received premarket authorization.
DATES:
Submit either electronic or written comments on the proposed rule by November 25, 2019.
ADDRESSES:
You may submit comments as follows:
Electronic Submissions
Submit electronic comments in the following way:
•
Federal eRulemaking Portal:
https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to
https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on
https://www.regulations.gov.
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).
Written/Paper Submissions
Submit written/paper submissions as follows:
•
Mail/Hand Delivery/Courier (for written/paper submissions):
Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”
Instructions:
All submissions received must include the Docket No. FDA-2019-N-2854 for “Premarket Tobacco Product Applications and Recordkeeping Requirements.” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at
https://www.regulations.gov
or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday.
• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on
https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at:
https://www.fda.gov/regulatory-information/dockets-management.
Docket:
For access to the docket to read background documents or the electronic and written/paper comments received, go to
https://www.regulations.gov
and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Submit comments on information collection issues to the Office of Management and Budget in the following ways: Fax to the Office of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, Fax: 202-395-7285, or email to
oira_submission@omb.eop.gov.
All comments should be identified with the title, “Premarket Tobacco Product Applications and Recordkeeping Requirements.”
FOR FURTHER INFORMATION CONTACT:
Paul Hart or Samantha Loh Collado at the 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. Proposed Regulations for the Maintenance of Records Demonstrating That a Tobacco Product Was Commercially Marketed in the United States as of February 15, 2007 (Part 1100, Proposed Subpart C)
A. Purpose and Scope (Proposed § 1100.200)
B. Definitions (Proposed § 1100.202)
C. Recordkeeping Requirements (Proposed § 1100.204)
IV. Proposed Regulations for the Maintenance of Records Relating to Exemptions From the Requirements of Demonstrating Substantial Equivalence (Proposed § 1107.3)
A. Definition
B. Record Maintenance
C. Record Quality
D. Record Retention
V. Proposed Regulations for Premarket Tobacco Product Applications (Proposed Part 1114)
VI. General (Proposed Part 1114, Subpart A)
A. Scope (Proposed § 1114.1)
B. Definitions (Proposed § 1114.3)
VII. Premarket Tobacco Product Applications (Proposed Part 1114, Subpart B)
A. Application Submission (Proposed § 1114.5)
B. Required Content and Format (Proposed § 1114.7)
C. Amendments (Proposed § 1114.9)
D. Withdrawal by Applicant (Proposed § 1114.11)
E. Change in Ownership of an Application (Proposed § 1114.13)
F. Supplemental Application Submission (Proposed § 1114.15)
G. Resubmissions (Proposed § 1114.17)
VIII. FDA Review (Proposed Part 1114, Subpart C)
A. Communications Between FDA and Applicants (Proposed § 1114.25)
B. Review Procedure (Proposed § 1114.27)
C. FDA Action on an Application (Proposed § 1114.29)
D. Issuance of a Marketing Order (Proposed § 1114.31)
E. Issuance of a No Marketing Order (Proposed § 1114.33)
F. Withdrawal of a Marketing Order (Proposed § 1114.35)
G. Temporary Suspension of a Marketing Order (Proposed § 1114.37)
IX. Postmarket Requirements (Proposed Part 1114, Subpart D)
A. Postmarket Changes (Proposed § 1114.39)
B. Reporting Requirements (Proposed § 1114.41)
X. Miscellaneous (Proposed Part 1114, Subpart E)
A. Record Retention (Proposed § 1114.45)
B. Confidentiality (Proposed § 1114.47)
C. Electronic Submission (Proposed § 1114.49)
XI. Paperwork Reduction Act of 1995
XII. Executive Order 13132: Federalism
XIII. Consultation and Coordination With Indian Tribal Governments
XIV. Analysis of Environmental Impact
XV. Preliminary Economic Analysis of Impacts
XVI. Proposed Effective Date
XVII. References
Executive Summary
A. Purpose of the Regulatory Action
This proposed rule would interpret and set forth requirements related to the content and format of PMTAs, the procedure by which FDA would review PMTAs, and the maintenance of records regarding the legal marketing of certain tobacco products without PMTAs. The proposed content and format requirements for PMTAs would assist FDA in completing initial, procedural reviews of applications, which include a determination of whether an application has sufficient information for FDA to initiate a substantive review of the PMTA. These content requirements would require 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 proposing to require 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.
FDA is basing this proposed rule on the experience the Agency has gained 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. FDA has received thousands of premarket applications that range widely in the level of detail they contain. For example, some have very little of the information that is necessary for FDA to complete its statutorily required review, while other applications are more detailed and provide the necessary sufficient supporting information. This experience has been helpful in developing the proposed rule, which describes the information FDA is proposing that an applicant must include in a PMTA for FDA to be able to complete a substantive review of an application.
Although FDA has conducted acceptance and filing reviews of hundreds of PMTAs, it is still gaining experience in applying the statutory authorization standard to PMTAs because few have contained sufficient information to reach substantive review. The main focus of the proposed rule's content requirements is the threshold amount of information necessary for application filing, rather than every piece of information necessary to receive a marketing order both because FDA is still gaining experience in applying the authorization standard to PMTAs and because at this time, FDA believes applicants have some flexibility in the types of scientific information they can submit in order to provide sufficient health risk information to meet the standard.
The proposed rule also addresses issues such as the procedures by which FDA will review a PMTA, the retention of records related to the PMTA, confidentiality of application information, electronic submission of the PMTA and amendments, and postmarket reporting requirements. The proposed rule would also create requirements for the maintenance of records demonstrating the legal marketing status of grandfathered tobacco products and products that are exempt from the requirements of demonstrating substantial equivalence.
B. Legal Authority
This proposed 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
The proposed rule would create requirements for tobacco product manufacturers to maintain records regarding the legal marketing of grandfathered tobacco products and products that are exempt from the requirements of demonstrating substantial equivalence. This proposed rule would also set forth content and format requirements for PMTAs. Under the proposed rule, a PMTA must contain information necessary for FDA to determine whether it should issue a marketing 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: There is a showing that marketing of the new tobacco product would be appropriate for the protection of the public health; 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)); the product labeling is not false or misleading in any particular; and 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 proposed rule would also allow applicants to submit a supplemental PMTA or a resubmission, which would reduce the burden of submitting and reviewing an application. A supplemental PMTA could 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 PMTA marketing order. A resubmission could be submitted to address application deficiencies following the issuance of a no marketing order. The proposed rule would also require the submission of postmarket reports by applicants that receive a PMTA marketing order.
In addition, the proposed rule would explain how an applicant could amend or withdraw a PMTA and how an applicant may transfer ownership of a PMTA to a new owner. The proposed rule also addresses FDA communications with applicants and identifies the actions that FDA may take after receipt of a PMTA. The proposed rule addresses when FDA may withdraw a PMTA marketing order and explains how long an applicant would be required to maintain the records related to the PMTA and postmarket reports. The proposed rule would also set forth FDA's disclosure procedures regarding PMTAs and require the electronic submission of PMTAs, unless the applicant requests and obtains a waiver.
D. Costs and Benefits
If finalized, the proposed rule would create cost savings for firms and for FDA by reducing the number of follow-on submissions for PMTAs (
i.e.,
additional PMTAs submitted for the same product(s) after FDA refuses to accept or file, or issues a no marketing order in response to, an initial PMTA). The proposed rule would also create cost savings for FDA by reducing the cost of review, reducing the number of deficiency letters we would issue during substantive scientific review, and eliminating the need to process unnecessary data. We estimate that average annualized benefits over 20 years would equal $5.54 million at a 7 percent discount rate and $5.44 million at a 3 percent discount rate.
If finalized, the proposed rule would create costs for firms and for FDA by increasing the number of complete PMTA submissions for deemed and originally regulated tobacco products. Moreover, because this is the first regulation to account for the costs of the PMTA requirements for originally regulated products, we also include the costs to submit and review PMTAs for these tobacco products; we already included the costs to submit and review PMTAs for deemed tobacco products in the final regulatory impact analysis for the final rule entitled “Deeming Tobacco Products To Be Subject to the Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations Restricting the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Product Packages and Advertisements” (Deeming Rule), which was published in the
Federal Register
of May 10, 2016 (81 FR 28973). Firms would incur costs to maintain and submit postmarket reports, and we would incur costs to review postmarket reports. Finally, firms would incur costs to read and understand the rule and costs to maintain records for some grandfathered products. We estimate that average annualized costs over 20 years would equal $7.05 million at a 7 percent discount rate and $6.76 million at a 3 percent discount rate.
Table of Abbreviations/Commonly Used Acronyms
Abbreviation/
acronym
What it means
FDA
Food and Drug Administration.
CTP
Center for Tobacco Products.
FD&C Act
Federal Food, Drug, and Cosmetic Act.
EA
Environmental assessment.
ENDS
Electronic nicotine delivery systems.
FEI
Facility Establishment Identifier.
APPH
Appropriate for the protection of public health.
CAS
Chemical Abstracts Service.
FOIA
Freedom of Information Act.
GLP
Good laboratory practice.
HPHC
Harmful and potentially harmful constituent.
IUPAC
International Union of Pure and Applied Chemistry.
ICH
International Council for Harmonization.
IRB
Institutional Review Board.
ISO
International Organization for Standardization.
MRTPA
Modified risk tobacco product application.
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.
PDU
Power delivery unit.
PG/VG
Propylene glycol/vegetable glycerin.
PMTA
Premarket tobacco product application.
PRIA
Preliminary regulatory impact analysis.
RYO
Roll-your-own.
SE
Substantial equivalence.
The Secretary
The Secretary of Health and Human Services.
STN
Submission tracking number.
TPMF
Tobacco product master file.
TSNA
Tobacco specific nitrosamine.
TPSAC
Tobacco products scientific advisory committee.
UNII
Unique Ingredients Identifier.
I. Background
The Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) 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 before a new tobacco product may be introduced or delivered for introduction into interstate commerce, it must undergo premarket review by FDA. Section 910(a)(1) of the FD&C Act defines a “new tobacco product” as: (1) Any tobacco product (including those products in test markets) that was not commercially marketed in the United States as of February 15, 2007; or (2) any modification (including a change in design, any component, any part, or any constituent, including a smoke constituent, or in the content, delivery or form of nicotine, or any other additive or ingredient) of a tobacco product where the modified product was commercially marketed in the United States after February 15, 2007 (21 U.S.C. 387j(a)(1)).
The FD&C Act establishes three premarket review pathways
1
for a new tobacco product:
1
As described in the Preliminary Economic Analysis of Impacts (Ref. 118), we expect that manufacturers will submit PMTAs primarily for ENDS and will generally submit SE Reports or exemption requests for cigars and other deemed products. We also expect that a number of cigars and pipe tobacco products are grandfathered tobacco products (see section III of this document) not subject to premarket review. This is consistent with FDA's experience so far in issuing SE marketing orders for cigars and determining cigars to be grandfathered tobacco products, and is also consistent with the regulatory impact analysis for the Deeming Rule (“Deeming Tobacco Products To Be Subject to the Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations Restricting the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Product Packages and Advertisements,” (81 FR 28973) (May 10, 2016)).
• Submission of a PMTA under section 910(b);
• Submission of an application 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);
2
and
2
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 an applicant 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 PMTA or SE marketing order or a finding of exemption from substantial equivalence, it is adulterated under section 902 of the FD&C Act and misbranded under section 903 of the FD&C Act and subject to enforcement action.
Since 2010, FDA has received thousands of premarket applications for tobacco products, hundreds of which have been PMTAs. Of these PMTAs, FDA has completed its full substantive review on two sets of bundled PMTAs, which are single submissions containing PMTAs for a number of similar or related tobacco products (totaling 12 applications), all of which received marketing orders. To assist manufacturers in preparing PMTAs, FDA has issued guidance, conducted webinars, met with manufacturers, hosted a public meeting regarding premarket submissions, and posted the technical project lead reviews (which describe the reviews completed on specific PMTAs) and marketing orders issued to date. If finalized, the proposed rule would interpret and set forth requirements related to the PMTA premarket pathway and outline the information needed for FDA to determine whether it will issue a marketing order under the pathway.
FDA has also processed hundreds of exemption requests and thousands of voluntarily-submitted grandfathered status reviews. The proposed rule would state the records that a company would be required to keep regarding the legal marketing of its tobacco product.
II. Legal Authority
As described in the following paragraphs, FDA is proposing 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 proposing recordkeeping requirements regarding the legal marketing of grandfathered 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 would be established by this proposed rule be severable and that the invalidation of any provision of this proposed 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 PMTA marketing 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.
3
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)-(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 marketing the 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.
3
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 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 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. In addition, section 701(a) of the FD&C Act gives FDA general rulemaking authority to issue regulations for the efficient enforcement of the FD&C Act and section 704 of the FD&C Act provides FDA with general inspection authority.
III. Proposed Regulations for the Maintenance of Records Demonstrating That a Tobacco Product Was Commercially Marketed in the United States as of February 15, 2007 (Part 1100, Proposed Subpart C)
The proposed rule would add subpart C regarding records to Part 1100 of subchapter K of title 21.
A. Purpose and Scope (Proposed § 1100.200)
Proposed § 1100.200 states that subpart C of part 1100 would establish requirements for the maintenance of records by tobacco product manufacturers who introduce a grandfathered tobacco product, or deliver it for introduction, into interstate commerce. FDA is proposing requirements for tobacco product manufacturers to maintain records regarding the legal marketing of their tobacco products under the authority of section 909 of the FD&C Act. 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). The records that would be required under this subpart would demonstrate that a tobacco product is grandfathered and therefore not required by section 910(a) to have premarket review and are not adulterated if marketed without an FDA order. FDA is basing these requirements on its experience gained by performing thousands of grandfathered status reviews conducted during its review of substantial equivalence reports and at manufacturers' voluntary requests. In the absence of these required records, manufacturers do not always maintain sufficient documentation to demonstrate whether their tobacco product is grandfathered. The records that would be required under this rule would allow FDA to more quickly and efficiently determine whether a tobacco product is grandfathered.
B. Definitions (Proposed § 1100.202)
Proposed § 1100.202 sets forth the meaning of terms as they apply to proposed part 1100 and includes the following definitions from the FD&C Act:
1. Tobacco Product
As defined in section 201(rr)(1) of the FD&C Act (21 U.S.C. 321(rr)(1)), the term “tobacco product” means any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product (except for raw materials other than the tobacco used in manufacturing a component, part, or accessory of a tobacco product). The term “tobacco product” does not mean an article that under the FD&C Act is a drug (section 201(g)(1)), a device (section 201(h)), or a combination product (section 503(g) (21 U.S.C. 353(g))).
2. Tobacco Product Manufacturer
As defined in section 900(20) of the FD&C Act (21 U.S.C. 387(20)), the term “tobacco product manufacturer” means any person, including a repacker or relabeler, who: (1) Manufacturers, 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. Manufacturing activities typically do not include the activities of de-stemming, drying, or packaging tobacco leaves; mechanically removing foreign material from tobacco leaves; and humidifying tobacco leaves with nothing other than potable water in the form of steam or mist. For the purposes of this definition “finished tobacco product” would mean a tobacco product, including all components and parts, sealed in final packaging (
e.g.,
filters or filter tubes sold separately to consumers or as part of kits).
In addition, FDA proposes the following definitions:
3. Commercially Marketed
FDA proposes to define “commercially marketed” to mean the offering of a tobacco product for sale to consumers in all or parts of the United States. Factors FDA may consider include advertising or other means used to communicate that the tobacco product is available for purchase. Tobacco products that are exclusively in a test market are not commercially marketed.
4. Grandfathered Tobacco Product
FDA proposes to define a “grandfathered tobacco product” to mean a tobacco product that was commercially marketed in the United States on February 15, 2007. This term does not include tobacco products exclusively marketed in a test market as of that date. FDA interprets the statutory phrase “as of February 15, 2007,” as meaning that the tobacco product was commercially marketed in the United States “on February 15, 2007,” and this interpretation is based on a plain language reading of the term “as of.” The proposed definition reflects this interpretation, which has been included as part of previously issued regulations and guidance.
4
This definition is also in the proposed rule, “Content and Format of Substantial Equivalence Reports; Food and Drug Administration Actions on Substantial Equivalence Reports” (SE Proposed Rule), which was published in the
Federal Register
of April 2, 2019 (84 FR 12740).
5
A grandfathered tobacco product is not subject to the premarket requirements of section 910 of the FD&C Act.
A tobacco product that the applicant test marketed after February 15, 2007, is not a grandfathered tobacco product because it was not commercially marketed in the United States as of February 15, 2007 and, therefore, it is a new tobacco product subject to premarket review under section 910(a) of the FD&C Act.
4
See the final rule “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 “Establishing That a Tobacco Product Was Commercially Marketed in the United States as of February 15, 2007” (Grandfathered Tobacco Product Guidance) (79 FR 58358, September 29, 2014), available at
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance.
5
FDA intends the PMTA provisions in this proposed rule to be consistent with the SE Proposed Rule wherever it is appropriate. FDA intends to harmonize any differences between definitions in these proposed rules when issuing final rules.
As described in the SE Proposed Rule and in the definition of “new tobacco product” proposed in 21 CFR part 1114 below, FDA is 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:
• Offered in a limited number of regions;
• Offered for a limited time; or
• Offered to a chosen set of the population or specific demographic group.
C. Recordkeeping Requirements (Proposed § 1100.204)
1. Required Records
Consistent with the authority to require recordkeeping under section 909 of the FD&C Act, proposed § 1100.204(a) would require any tobacco product manufacturer that introduces a grandfathered 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 proposed requirement would ensure that records are available to FDA during an inspection. The proposed rule would 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. These records may include items such as:
(1) Dated copies of advertisements;
(2) Dated catalog pages;
(3) Dated promotional material;
(4) Dated trade publications;
(5) Dated bills of lading;
(6) Dated freight bills;
(7) Dated waybills;
(8) Dated invoices;
(9) Dated purchase orders;
(10) Dated customer receipts;
(11) Dated manufacturing documents;
(12) Dated distributor or retailer inventory lists; or
(13) Any other dated document that demonstrates that the tobacco product was commercially marketed (not exclusively in test markets) in the United States as of February 15, 2007. For additional information on records related to grandfathered tobacco products, see the Grandfathered Tobacco Product Guidance.
2. Record Maintenance
Proposed § 1100.204(b) would require that all records required to be 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. FDA is also proposing 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.
3. Record Retention
Proposed § 1100.204(c) would require that the records and documents demonstrating that the tobacco product was commercially marketed be retained for a period of 4 years from the date that either FDA makes a grandfather 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 as a means to help ensure that the records would be available for at least one biennial FDA inspection under section 704 and 905(g) of the FD&C Act. FDA's biennial inspections under section 905(g) 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 would allow FDA to verify the grandfathered 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 would still need to retain the records to allow FDA to verify the grandfathered status of the product when they resume marketing the product. Additionally, manufacturers might also want to retain records for longer than 4 years to help establish their product is grandfathered for use as a predicate product in an SE Report.
IV. Proposed Regulations for the Maintenance of Records Relating to Exemptions From the Requirements of Demonstrating Substantial Equivalence (Proposed § 1107.3)
The proposed rule would add § 1107.3 to part 1107 of subchapter K of title 21. Proposed § 1107.3 would establish recordkeeping requirements related to tobacco products that are exempt from the requirements of demonstrating substantial equivalence 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, proposed § 1107.3 would require 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 proposed rule would require 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
Proposed § 1107.3(a) would define “grandfathered tobacco product” as a tobacco product that was commercially marketed in the United States on February 15, 2007. The term would not include a tobacco product exclusively in test markets as of that date. 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,” this interpretation is based on a plain language reading of the term “as of.”
6
6
Id.
B. Record Maintenance
The proposed rule would require applicants to maintain all documents that support their abbreviated report, which includes the documents listed in proposed § 1107.3(b)(1). The proposed rule would not require an applicant to create new or additional records; rather, it would require 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 an applicant would be required to create by other regulatory or statutory sections such as the submission of exemption requests under § 1107.1, PMTAs under section 910(b) of the FD&C Act (or proposed part 1114 when finalized), SE Reports under section 905(j) FD&C Act, and tobacco product manufacturing requirements issued under section 906(e) of the FD&C Act. The records an applicant would be 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 would include, for example, items such as the types of information described in proposed § 1114.7(i) as described in section VII.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 proposed § 1114.7(j) as described in section VII.B.;
• Product labeling. As defined in section 201(m) of the FD&C Act, “labeling” means all labels and other written, printed, or graphic matter upon any article or any of its containers or wrappers, or accompanying such article. This would include, for example, specimens of all labeling for the new tobacco product, including labels, inserts, onserts, instructions, and other accompanying information. The specimens of labeling would include all panels, reflect the actual size and color proposed to be used for the tobacco product, and include any warning label statements and other information required by regulation or statute, as applicable;
• 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 proposed § 1107.3(b)(1), proposed § 1107.3(b)(2) through (b)(4) would 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 would need to maintain records demonstrating that the modification is being made to either a grandfathered 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 grandfathered tobacco product, proposed § 1107.3(b)(2) would require 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 marketing order from FDA (
i.e.,
an order from FDA authorizing the marketing of the new tobacco product after review of an SE Report or PMTA), proposed § 1107.3(b)(3) would require applicants to maintain a copy of the exemption or marketing 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 consistent with section 910(a)(2)(B) of the FD&C Act for which FDA has not issued an SE marketing order, an applicant would be required to 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
Proposed § 1107.3(c) would require 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 is also proposing that documents that have been translated from another language into English must 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 would help FDA ensure that the English language translations of documents are complete and accurately reflect the content of the original documents.
D. Record Retention
Proposed § 1107.3(d) would require the records described in § 1107.3 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 would be available for at least one biennial FDA inspection under section 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.
V. Proposed Regulations for Premarket Tobacco Product Applications (Proposed Part 1114)
The proposed rule would add part 1114 to subchapter K of Title 21. The requirements set forth in this proposed part would apply to PMTAs for new tobacco products. Proposed subpart A sets out the scope and definitions that apply to this proposed part. Proposed subpart B sets out the proposed 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. Proposed subpart C describes how FDA proposes to review and act on applications, including provisions for withdrawal and temporary suspension of orders. Proposed subpart D describes proposed postmarket restrictions, reporting requirements, and inactivation and reactivation of a marketing order. Proposed subpart E sets out proposed miscellaneous requirements such as record retention, confidentiality, and electronic submissions.
VI. General (Proposed Part 1114, Subpart A)
A. Scope (Proposed § 1114.1)
Proposed § 1114.1 describes the scope of proposed part 1114 and its application to the submission, review, and postmarket requirements related to PMTAs. Proposed § 1114.1 provides that proposed part 1114 would not apply to MRTPAs, except instances where a single application is submitted under section 911(l)(4) of the FD&C Act instead of a separate PMTA and MRTPA
for the product. Under the proposed rule, an applicant that submits a single application seeking both a PMTA marketing order and a modified risk order under section 911(g) would need to meet the requirements of both part 1114 and section 911 of the FD&C Act. This section also notes that references in the proposed rule to regulatory sections of the Code of Federal Regulations (CFR) are to chapter I of title 21, unless otherwise noted. This means that any CFR reference that begins with “part” 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).
B. Definitions (Proposed § 1114.3)
Proposed § 1114.3 sets forth the meaning of terms as they apply to proposed part 1114. Proposed § 1114.3 includes the following definitions from the FD&C Act:
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, 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 proposed § 1114.3.
4. Label
As defined in section 201(k) of the FD&C Act (21 U.S.C. 321(k)), “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.
Under the FD&C Act, and as reflected in the proposed 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, specifications that change characteristics (
e.g.,
a modification to a different tobacco cut size) would render a tobacco product new.
Manufacturers sometimes co-package tobacco products. 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. Examples include a carton of cigarette packs and a variety pack of three smokeless tins shrink-wrapped together where the cigarette packs and smokeless tins, respectively, could be legally marketed separately. However, if a manufacturer wishes to co-package two or more tobacco products (including their respective container closure systems), premarket review is required for any new tobacco product that the manufacturer intends to include in the co-package. An example includes shrink-wrapping grandfathered tobacco filler (in its unmodified container closure system) with new rolling papers; here premarket authorization would be required for the rolling papers. In addition, co-packaging two or more tobacco products within the same container closure system results in a new tobacco product, unless such co-packaged product is grandfathered. Examples include an RYO kit where rolling papers are placed inside the tin of tobacco filler, and shrink-wrapping together two soft-packs of cigarettes, neither of which had been individually shrink-wrapped prior to being co-packaged. FDA invites comment on approaches to its review of these types of PMTAs, including, where relevant, how co-packaging products impacts consumer use and behavior.
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” can be considered to encompass 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) (finding that a change in product quantity results in a new tobacco product under the Tobacco Control Act). Consequently, a change in product quantity (
e.g.,
decreasing the weight of a smokeless package from 24 grams to 15 grams) results in a new tobacco product subject to premarket review since such a modification “necessarily entails a change in the amount of the constituent ingredients and additives within the tobacco product, including nicotine” (id. at 56).
FDA also interprets section 910(a)(1)(A) of the FD&C Act to mean
that a tobacco product marketed exclusively in test markets on February 15, 2007, is a new tobacco product that is subject to premarket review by FDA. A tobacco product that the applicant test marketed after February 15, 2007, is also a new tobacco product subject to premarket review under section 910(a) of the FD&C Act because it was not commercially marketed in the United States as of February 15, 2007.
Because the terms “test marketing” and “commercially marketed” are not interchangeable, FDA is considering whether it would be useful to applicants for the rule to expand on or further define the terms “test marketing” and “commercially marketed.” Specifically, as set forth in the description of proposed part 1100 and described in the SE Proposed Rule, FDA is 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:
• Offered in a limited number of regions;
• Offered for a limited time; or
• Offered to a chosen set of the population or specific demographic group.
As set forth in the description of proposed part 1100, FDA is considering whether to define “commercially marketed” to mean offering a tobacco product for sale to consumers in all or in parts of the United States. Factors FDA may consider include advertising or other means used to communicate that the tobacco product was available for purchase, including dated advertisements, dated catalog pages, dated promotional material, dated trade publications, dated bills of lading, dated freight bills, dated waybills, dated invoices, dated purchase orders, dated manufacturing documents, inventory lists, or any other document that demonstrates that the product was commercially marketed (other than exclusively in test markets) in the United States as of February 15, 2007. FDA invites comment on what evidence would be sufficient to demonstrate that a product was commercially marketed (other than in test markets) as of February 15, 2007.
FDA is inviting comments on: (1) Whether the rule should further expand on the interpretation or include definitions of these terms, (2) the substance of the definitions, if included, and (3) whether or not the approach described is adequate to protect the public health.
7. Package or Packaging
As defined in section 900(13) of the FD&C Act, the term “package,” also referred to in the proposed 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 proposed 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 characteristics of the 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.
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. Manufacturing activities typically do not include the activities of de-stemming, drying, or packaging tobacco leaves; mechanically removing foreign material from tobacco leaves; and humidifying tobacco leaves with nothing other than potable water in the form of steam or mist. A proposed definition for the term “finished tobacco product” is also included in the proposed rule.
In addition, FDA proposes the following definitions:
10. Accessory
FDA proposes to define “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:
(1) Is not intended or reasonably expected to affect or alter the performance, composition, constituents, or characteristics of a tobacco product or
(2) is intended or reasonably expected to affect or maintain the performance, composition, constituents, or characteristics of a tobacco product, but:
(i) Solely controls moisture and/or temperature of a stored product or
(ii) 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 and contained in the SE Proposed Rule. 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 proposes to define “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.
12. Applicant
FDA proposes to define “applicant” as any person that submits a premarket tobacco product application to receive a marketing order for a new tobacco product.
13. Component or Part
FDA proposes to define “component or part” as any software or assembly of materials intended or reasonably expected: (1) To alter or affect the tobacco product's performance, composition, constituents, or characteristics; or (2) to be used with or for the human consumption of a tobacco product. Component or part excludes anything that is an accessory of a tobacco product. A container closure system (which is also defined in this proposed 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 proposed 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 proposed definition matches the definition in § 1100.3 and that was published in the SE Proposed Rule and FDA invites comments on this approach in the PMTA context.
14. Composition
FDA proposes to define “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. This proposed definition matches the definition published in the SE Proposed Rule.
15. Constituent
FDA proposes to define “constituent” as any chemical or chemical compound in a tobacco product or in tobacco smoke or emission that is or potentially is inhaled, ingested, or absorbed into the body. Examples of constituents include harmful or potentially harmful constituents, total particulate matter, nicotine-free dry particulate matter, and water. A constituent also could include any other chemical or chemical compound contained in or produced by a tobacco product under conditions of use. This proposed definition matches the definition that was published in the SE Proposed Rule.
16. Container Closure System
FDA proposes to define “container closure system” as any packaging materials that are a component or part of the tobacco product. This proposed definition matches the definition published in the SE Proposed Rule.
Examples of what is typically a container closure system include the blister pack around a dissolvable tablet (in this example, if there is a box around a blister pack, the box is not considered a container closure system if it is not intended or reasonably expected to alter or affect the dissolvable tablet), the can that contains and protects a moist snuff product, and the plastic-wrapped hard pack or soft pack used to contain and protect cigarettes. A container closure system is a component or part of a tobacco product because of its potential to alter or affect the performance, composition, constituents, or other physical characteristics of the product.
In addition, considering a distinct subset of packaging (
i.e.,
container closure system) to be a component or part is consistent with the FD&C Act. For example, section 903(a)(2) of the FD&C Act describes when, under certain conditions, a tobacco product “in package form” is misbranded, thereby recognizing that at least some portion of the package is subsumed within the “tobacco product” (and the components and parts thereof). Similarly, the definition of “additive” in section 900(1) of the FD&C Act 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, further evinces Congress's understanding that packaging is not entirely separable from the tobacco product. Finally, 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.
According to the proposed definition above, packaging constitutes the container closure system if it is intended or reasonably expected to affect or alter the performance, composition, constituents, or characteristics of a tobacco product, even if it is also used to protect or contain the tobacco product. For example, packaging materials constitute the 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 (Ref. 1). Another example of this is when menthol or other ingredients are applied to the inner foil to become incorporated into the consumed product (Ref. 2). Packaging materials may also be intended or reasonably expected to affect the characteristics of a tobacco product by impacting the rate of leaching into, and ultimately, the amount of substances found in, the consumable tobacco product. In fact, it has been demonstrated that compounds in packaging materials may also diffuse into snuff and affect its characteristics (Ref. 3). Thus, for example, packaging material that affects the characteristics of a tobacco product by impacting the moisture level or shelf life of a tobacco product is a container closure system (
e.g.,
a plastic versus a metal container of smokeless tobacco). A difference in tobacco moisture is reasonably expected to affect microbial growth in the product, extraction efficiency, and total exposure to nicotine or the carcinogens N-nitrosonornicotine (NNN) or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (Refs. 4 and 5).
Treating a distinct subset of packaging as a component or part thus furthers the fundamental purpose of the Tobacco Control Act to protect the public health. This interpretation is also consistent with the broad definition of “tobacco product,” as well the definition of “additive,” which includes substances that may be reasonably expected to result, directly or indirectly, in it becoming a component or otherwise affecting the characteristics of any tobacco product—and not just substances that do
in fact
have such effects. This shows that Congress did not intend for FDA to be required to show that the container closure system did in fact alter or affect the tobacco product's performance, composition, constituents, or other characteristics. Indeed, if FDA were to adopt a narrow
construction of “tobacco product” to exclude these materials, it would impede the Agency's ability to evaluate whether authorizing the marketing of the tobacco product would be appropriate for the protection of the public health, thereby leaving the Agency unable to fully execute its mission to protect the public health.
17. Design
FDA proposes to define “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 and matches the definition published in the SE Proposed Rule. Examples of design parameters include ventilation, paper porosity, filter efficiency, battery voltage and current operating range, and electrical heater coil resistance.
18. Finished Tobacco Product
FDA proposes to define “finished tobacco product” to mean a tobacco product, including all components and parts, sealed in final packaging (
e.g.,
filters or filter tubes sold separately to consumers or as part of kits, e-liquids sold separately or packaged with an e-cigarette). This proposed definition matches the definition published in the SE Proposed Rule.
19. Harmful or Potentially Harmful Constituent (HPHC)
FDA proposes to define “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 proposed definition matches the definition published in the SE Proposed Rule.
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 products such as ENDS. FDA will finalize the addition of these HPHCs to the established list, as appropriate, after reviewing public comment and general intends to make any future updates to the established list of HPHCs through a similar notice and comment process.
20. Heating Source
FDA proposes to define “heating source” as the source of energy used to burn or heat the tobacco product. This proposed definition matches the definition published in the SE Proposed Rule. Examples of a heating source include a flame or a rechargeable battery.
21. Ingredient
FDA proposes to define “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. This proposed definition matches the definition published in the SE Proposed Rule. 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.
• Products of acid-base reactions, such as removal of a proton from protonated nicotine to generate the basic form of nicotine (“free” nicotine).
22. Line Data
FDA proposes to define “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 proposing to require that an applicant submit line data rather than source data to allow for a more efficient review process. As described in proposed § 1114.45, applicants would be required to retain all source data in the event that FDA needs to inspect the data as part of its application review.
23. Material
FDA proposes to define “material” to mean an assembly of ingredients. Materials are assembled to form the tobacco product, or components or parts of tobacco product. This proposed definition matches the definition published in the SE Proposed Rule. For example, material would include 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.
24. Marketing Order
FDA proposes to define “marketing 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.
25. No Marketing Order
FDA proposes to define “no marketing 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.
26. Other Features
FDA proposes to define “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. This proposed definition matches the definition published in the SE Proposed Rule. The definition would include: (a) 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 (b) any other product characteristics that relate to the chemical, biological, or physical properties of the tobacco product. Other features also would encompass 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.
27. Premarket Tobacco Product Application or PMTA
FDA proposes to define “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.
28. Serious Adverse Experience
FDA proposes to define “serious adverse experience” to mean an adverse experience that results in any of the following outcomes:
(a) Death;
(b) a life-threatening condition or illness;
(c) inpatient hospitalization or prolongation of existing hospitalization;
(d) a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions (
e.g.,
seizures not that do not result in hospitalization, burns that result in damage to a limb or nerve damage);
(e) a congenital anomaly/birth defect; or
(f) 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.
29. Unexpected Adverse Experience
FDA proposes to define “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:
(a) 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;
(b) 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
(c) the results of nonclinical investigations.
VII. Premarket Tobacco Product Applications (Proposed Part 1114, Subpart B)
A. Application Submission (Proposed § 1114.5)
Proposed § 1114.5 explains that if an applicant seeks a marketing order under the PMTA pathway for its new tobacco product, it would be required to submit a PMTA to FDA and receive a marketing 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 proposed § 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 of proposed § 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 proposed § 1114.27 in section VIII.B, FDA may refuse to accept or file an incomplete application for review.
B. Required Content and Format (Proposed § 1114.7)
1. General
Proposed § 1114.7(a) would require 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)); and
• Certification statement (as described in § 1114.7(l)).
As described in the discussion of proposed § 1114.27(a)(1) 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. As described in section VIII.B on proposed § 1114.27(b)(1), 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.
2. Format
Proposed § 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 (Ref. 6). Proposed § 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 proposing 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 proposed § 1114.49, FDA is proposing that the PMTA and all supporting documents must 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 would be permitted to obtain a waiver from the electronic filing requirement, in accordance with § 1114.49. FDA has provided information on our website about technical specifications, including electronic formats that would allow FDA to process, review, and archive the
application.
7
FDA intends to update this information as needed to accommodate changes in technology.
7
For more information on electronic submission, including electronic submission file formats and specification, please visit FDA's web page at:
https://www.fda.gov/industry/fda-esubmitter/using-esubmitter-prepare-tobacco-product-submissions
.
FDA is proposing 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 proposed § 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 submissions have not been in a static format, and thus, the pages reformat, renumber, rebullet, or re-date each time the document is accessed. Receiving applications with these issues affects our ability to cross-reference, share (internally), and efficiently evaluate information. Lastly, because 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
), proposed § 1114.7(b) would ensure that these files can be managed, opened, and read by the Agency for the duration of the retention period.
Finally, proposed § 1114.7(b)(2) would 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 (21 U.S.C. 387k). 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 master files, please consult the guidance for industry “Tobacco Product Master Files.”
8
8
Available at:
https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/guidance
.
Applicants may also include content in a PMTA by cross-reference to a pending MRTPA for the same tobacco product.
9
FDA recommends that applicants seeking to market a new tobacco product that has not previously received marketing authorization as a modified risk tobacco product submit a single application under section 911(l)(4) of the FD&C Act (
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 only one application and include it in the other by cross-reference. This approach would prevent any transcription errors and would also 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.
9
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 an order 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. Such an approach would 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 the proposed rule, except as described in subpart B, FDA would 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 would be required to include the full text of such information in its PMTA. FDA is proposing 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. An applicant may also submit a single premarket submission for multiple products (
i.e.,
a bundled PMTA) and a single, combined cover letter and table of contents across all products; however, when FDA receives a premarket submission that covers multiple new tobacco products, we intend to consider information on each product as a separate, individual PMTA and it is important to identify the content that pertains to each product.
3. General Information
Proposed § 1114.7(c) lists the information that would be required to be included in the General Information section of the PMTA. This information consists of general administrative information that includes the type of submission, the new tobacco product with unique identifiers, and contact information. The table, as set forth in proposed § 1114.7(c), would include requirements to submit general information related to electronic nicotine delivery systems (ENDS) product category and several subcategories of ENDS. FDA generally considers ENDS to be electronic nicotine delivery systems that deliver aerosolized e-liquid when inhaled. The term “e-cigarette” refers to an electronic device that delivers e-liquid in aerosol form into the mouth and lungs when inhaled; it is also sometimes referred to as an aerosolizing apparatus. An open e-cigarette, also referred to as a refillable e-cigarette, is an e-cigarette that includes a reservoir that a user can refill with an e-liquid of their choosing. A closed e-cigarette is an e-cigarette that includes an e-liquid reservoir that is not refillable, such as a disposable cigalike, or that uses e-liquid contained in replaceable cartridges or pods that are not intended to be refillable. For additional information on ENDS, consult the guidance “Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems.”
The PMTA would be required to include the following information using the FDA-provided form (Ref. 6), as appropriate:
• Applicant name, address, and contact information;
• The name, address, and contact information for the authorized
representative or U.S. agent (for a foreign applicant). As required by § 1105.10(a)(5) for application acceptance, a foreign applicant must identify a U.S. agent (
i.e.,
an individual located in the United States who is authorized to act on behalf of the applicant for the submission) to help FDA ensure adequate notice is provided to applicants for official Agency communications, assist FDA in communicating with the foreign applicant, and help the Agency to efficiently process applications and avoid delays.
• Information to uniquely identify the product. Providing unique identifying information is important to aid in FDA's review because it ensures FDA has information readily available to distinguish the tobacco product from other tobacco products, including additional new tobacco products in a bundled submission (
i.e.,
more than one application contained in a single submission), and assists FDA in performing its acceptance and filing reviews. The required unique identifying information would include:
○ The manufacturer;
○ Product name(s), including the brand and subbrand (or other commercial name(s) used in commercial distribution);
○ Product category; product subcategory; and product properties, as provided by the tables in proposed § 1114.7(c). The applicant would select and provide the appropriate category, subcategory, and product properties for the new tobacco product. This product-specific information is required under sections 910(b)(1)(B) and (G) of the FD&C Act and the proposed rule would require its inclusion in the general information section to help FDA quickly check whether the product is within CTP's purview and identify the specific product that is the subject of the submission. For more information regarding product properties and why specific properties would be a required part of an application, see the discussion of proposed § 1114.7(i)(1) in section VII.B.9. It is important to note that for the characterizing flavor product property, the applicant would be required to state “none” if it does not consider the product to have a characterizing flavor. Applicants that have questions regarding how to describe their product's characterizing flavor are encouraged to contact FDA prior to submission.
For each type of tobacco product, the applicant should also include any additional properties to fully identify the tobacco product, if applicable. For example, use of product descriptors such as “extra-long” should be identified. While failure to include such additional properties to help uniquely identify the tobacco product would not serve as the basis for FDA refusing to accept an application under proposed § 1114.27(a)(1), it would likely slow down the substantive review process.
• The type of PMTA. The applicant would be required to state the type of PMTA the applicant is submitting (
i.e.,
PMTA, supplemental PMTA, or resubmission);
• Whether the applicant requests that FDA refer the PMTA to the Tobacco Products Scientific Advisory Committee (TPSAC). An applicant should briefly describe its justification for a request to refer the PMTA to TPSAC. FDA retains the discretion to refer an application to TPSAC, but will consider an applicant's request as part of its determination.
• Identifying information regarding any prior submissions relating to the new tobacco product, including submission tracking numbers (STNs), where applicable. The types of prior submissions may include premarket applications, such as PMTAs, SE Reports, and exemption requests, as well as other submissions to FDA including MRTPAs and submissions related to investigational tobacco products. The regulatory history of a tobacco product can provide useful context for FDA's review of a submission;
• Dates and purpose of any prior meetings with FDA regarding the new tobacco product;
• Address and the Facility Establishment Identifier (FEI) number(s) of the establishment(s) involved in the manufacturer of the new tobacco product. This information would assist the Agency with environmental impact considerations and determinations under part 25 by helping FDA understand the location of manufacturing and scale of products that would be manufactured. Additionally, it helps FDA schedule and conduct facility inspections;
• A brief statement regarding how the PMTA satisfies the content requirements of section 910(b)(1) of the FD&C Act. This could consist of a table reproducing the section 910(b)(1) requirements and listing the sections or page numbers of the PMTA that satisfy the requirements. FDA is requiring this brief statement under authority of sections 701(a) and 910(b)(1)(G) of the FD&C Act, which would allow FDA to more quickly locate application content necessary to determine whether a PMTA should be accepted and filed for further review under proposed § 1114.27;
• A brief description of how permitting the marketing of the new tobacco product is expected to be appropriate for the protection of the public health (APPH). This description should be no more than a sentence or two that highlights the key product characteristics and study results the applicant believes would make the marketing of the product APPH (
e.g.,
the product delivers significantly lower levels of a specific HPHCs to users than the tobacco products they are currently consuming, which studies indicate may result in decreased morbidity and mortality); and
• A list identifying all enclosures, labels, and labeling being submitted with the application. This list will help FDA identify application content and ensure a PMTA contains all the information the applicant intended to submit.
4. Descriptive Information
Proposed § 1114.7(d) would require applicants to provide descriptive information in this section that outlines the major aspects of the new tobacco product, which is required to be submitted under sections 910(b)(1)(A), (D), and (G) of the FD&C Act. This information would include:
• A concise description of the new tobacco product (
e.g.,
the product is a portioned smokeless tobacco product made using a blend of burley and bright tobacco);
• A statement identifying all tobacco product standards issued under section 907 of the FD&C Act that are applicable to the new tobacco product and a brief description of how the new tobacco product fully meets the identified tobacco product standard(s). If the new tobacco product deviates from such standard(s), if applicable, the proposed rule would require the application to include adequate information to identify and justify those deviations;
• The product name(s) as designated on the product's label;
• A description of problems identified in prototypes that are the subject of studies contained in the application, or previous or similar versions of the new tobacco product that were marketed, if any. If there are previous or similar versions that are the subject of studies in the application or were marketed, the proposed rule would require the applicant to include a bibliography of all reports regarding the previous or similar version of the product, whether adverse or supportive. FDA would require this information under section 910(b)(1)(A) and (G) of the FD&C Act to assess whether any known issues with a predecessor product that
could affect the health risks of the new tobacco product have been addressed;
• Any restrictions on the sale, distribution, advertising, or promotion of the new tobacco product (as described in section 910(c)(1)(B) of the FD&C Act) that the applicant proposes to be included as part of a marketing order, if issued. The applicant may choose to propose restrictions on the sales and distribution of the tobacco product to help support a showing that the marketing of the product is appropriate for the protection of the public health (
e.g.,
a restriction that decreases the likelihood that those who do not currently use tobacco products will initiate tobacco product use with the new tobacco product). If an applicant does not wish to propose any additional restrictions, it would be required to explicitly state that it proposes no restrictions. As described in proposed § 1114.31, FDA will consider these proposed restrictions during its review of the PMTA and, where appropriate, include the restrictions in the marketing order for the product together with any additional restrictions FDA may require.
5. Samples of New Tobacco Products and Components or Parts
Section 910(b)(1)(E) of the FD&C Act requires an applicant to submit samples of a tobacco product and its components as FDA may reasonably require. After FDA accepts a submission, FDA will determine whether it will require product samples and, if so, issue instructions on how and where to submit the samples, and the number of samples that are required. Proposed § 1114.7(e) would require an applicant to submit samples of the finished tobacco product and its components in accordance with instructions issued to the applicant after a PMTA is accepted for review, as well as to submit additional samples if required by FDA during application review. FDA generally expects that product samples will be a required part of a PMTA and that an applicant should be prepared to submit them in accordance with FDA instructions within 30 days after submitting a PMTA. There may be situations in which sample submission may not be necessary, including, in some circumstances, PMTAs that are resubmitted for the same product after a no marketing order (such as resubmissions as described in § 1114.17) or PMTAs submitted for modifications to an authorized product where the modifications do not require review of new samples as part of the PMTA evaluation process. Presubmission meetings with FDA may help provide additional information about whether product samples will need to be included in a PMTA; however, in most situations, FDA will only be able to determine the need for product samples after a PMTA is accepted for review.
FDA is proposing to have applicants submit samples as required by FDA after acceptance of an application rather than as part of an initial submission. This would allow FDA to determine the need for samples, allow the samples to be tracked and identified as part of the correct application, and submitted to testing facilities that are adequately prepared to accept the samples (
e.g.,
one that has a refrigerated unit if the product needs to be stored at a certain temperature). Additionally, by having applicants submit samples after FDA accepts an application, applicants will be able to avoid the effort and expense of submitting samples if the application is not accepted for review or if samples are not required. As described in proposed § 1114.27, if required by FDA, product samples would be necessary for application filing and FDA intends to refuse to file a PMTA for a lack of product samples if the applicant has not submitted samples in accordance with FDA's instructions by the time FDA is prepared to make its filing determination. FDA intends to notify an applicant if it determines after PMTA acceptance that product samples are not required for PMTA filing; however, even in such a situation, FDA may request product samples during substantive review after an application is filed, as needed.
6. Labeling and Marketing Plans
Proposed § 1114.7(f) of the FD&C Act would require that a PMTA contain specimens of labeling and the applicant's marketing plans for the new tobacco product.
a.
Labeling.
Section 910(b)(1)(F) of the FD&C Act requires that a PMTA contain specimens of the proposed labeling to be used for the tobacco product. Proposed § 1114.7(f)(1) would elaborate on this requirement and require the application to contain specimens of all proposed labeling for the new tobacco product, including labels, inserts, onserts, instructions, and other accompanying information. The specimens of labeling would be required to include all panels and reflect the actual size and color proposed to be used for such tobacco product. The labels must include any warning statements required by statute or regulation such as the Federal Cigarette Labeling and Advertising Act, the Comprehensive Smokeless Tobacco Health and Education Act, or the minimum required warning statements contained in 21 CFR part 1143.
As described in proposed § 1114.33, product labeling is an important part of FDA's review of an application because FDA must deny a PMTA under section 910(c)(2)(C) of the FD&C Act where it finds, based on a fair evaluation of all material facts, the proposed labeling is false or misleading in any particular. Additionally, product labeling can be an important part of FDA's determination under section 910(c)(2)(A) of the FD&C Act of whether there is a showing that permitting the marketing of the product would be APPH because it can be used to help show perception of the risks of the product and the ability of individuals to understand the labeling, including any instructions for use, as described in proposed § 1114.7(k)(1)(iv).
b.
Marketing Plan.
Proposed § 1114.7(f)(2) would require a PMTA to contain a description of the applicant's marketing plans for the tobacco product that an applicant has developed by the time of submission and concerning at least the first year of marketing after an applicant receives a marketing order, including information relating to labeling, advertising, marketing, promotion, and sales and distribution of its new tobacco product. FDA is proposing to require the submission of marketing plans as part of a PMTA under its authority in section 910(b)(1)(G) of the FD&C Act to require other information relevant to the subject matter of the application because marketing plans can provide important information regarding whether permitting the marketing of the new tobacco product would be APPH. Specifically, marketing plans can inform FDA's consideration under section 910(c)(4) of the FD&C Act of the potential risks and benefits of the tobacco product to the population as a whole, including whether the marketing of the product would increase or decrease the likelihood that those who do not use tobacco products, including youth and young adults, will start using them.
FDA is proposing to require the submission of marketing plans to help it understand and prevent or minimize the potential harm that could be caused by the marketing of a new tobacco product. Consistent with its mission to protect the public health, FDA seeks to limit youth exposure to the labeling, advertising, marketing, or promotion of a new tobacco product in order to limit uptake of the new tobacco product by nonusers of tobacco products, especially youth. FDA must also assess potential uptake of the new tobacco product by current tobacco product users who
would have otherwise stopped using tobacco products and how use of the new tobacco product may affect poly use behaviors and subsequent tobacco use. Applicants may have information that allows them to carefully target the marketing for a particular product to reach only its intended consumers of legal age. In reviewing the marketing plans contained in a PMTA, FDA intends to consider how an applicant will target the marketing of its new tobacco product to reach its intended consumers of legal age and to assess potential effect on nonusers. FDA will also consider how the applicant intends to minimize the extent to which youth can access the product and are exposed to its marketing. Where FDA determines that restrictions on the sales and distribution of the new tobacco product (including access to, and the advertising and promotion of, the tobacco product) would be APPH, FDA can impose such restrictions under the terms of a marketing order as described in section VIII.D.
The applicant's marketing plans will help FDA determine whether permitting the marketing of the new tobacco product would be APPH because they will provide input that is critical to FDA's determination of the likelihood of changes in tobacco product use behavior, especially when considered in conjunction with other information contained in the application. FDA will review the marketing plan to evaluate potential youth access to, and youth exposure to the labeling, advertising, marketing, or promotion of, a new tobacco product. For example, heavy use of online social media to promote a tobacco product without access restrictions, as opposed to actions such as paper mailings directed only to current smokers of legal age, indicates the potential for youth to be exposed to the promotion of the product. This information would help FDA make its APPH determination by showing whether a PMTA fully or accurately accounts for the likelihood of changes in tobacco product use behavior that may occur as a result of marketing the new tobacco product. For example, if the PMTA does not address youth access to the product, youth exposure to the product's labeling, advertising, marketing, and promotion, and youth initiation, such as describing how it proposes to restrict the sale or distribution of its product to limit potential youth access to the product (
e.g.,
selling the tobacco product in adult-only establishments) or exposure to advertising (
e.g.,
using age verification controls for digital advertising), FDA may be unable to determine that the applicant has made a showing that permitting the marketing of the new tobacco product would be APPH. FDA expects that companies seeking authorization will have prepared plans for potential marketing that they expect to undertake during at least an initial period of marketing, such that providing these plans as part of the application would not require significant resources.
Additionally, as set forth in proposed § 1114.41, FDA would require each applicant that receives a marketing order to continue to report its marketing plans, along with items such as copies of the product's labeling, advertising, marketing, and promotion, and the results of the implementation of such plans. Continuing to monitor the marketing plans for the new tobacco product once on the market is important to help FDA evaluate both the potential for changes to tobacco product use behavior and the implementation of any restrictions in the marketing order. As described in section VIII.F., where FDA finds that the continued marketing of a new tobacco product is no longer APPH, such as where changes in the marketing of a new tobacco product result or are likely to result in a significant increase in youth initiation not foreseen in FDA's review of a PMTA, FDA would withdraw the marketing order for a product.
There is a well-established body of scientific evidence regarding the effect of advertising and marketing on tobacco product initiation (
see e.g.,
Refs. 7-10), which FDA must consider as part of its basis for determining whether permitting the marketing of a product would be appropriate for the protection of the public health under section 910(c)(4) of the FD&C Act. The impact of tobacco advertising and marketing on youth and young adult tobacco use behavior has been well documented. The 2012 Surgeon General's report,
Preventing Tobacco Use Among Youth and Young Adults,
synthesizes more than 30 years of research on the topic and states that the strong empirical evidence, along with the tobacco industry's own internal documents and trial testimony, as well as widely accepted principles of advertising and marketing, support the conclusion that tobacco manufacturers' advertising, marketing, and promotions recruit new users as youth and continue to reinforce use among young adults. (Ref. 12). The National Cancer Institute made a similar conclusion it its monograph,
The Role of the Media in Promoting and Reducing Tobacco Use,
that the total weight of evidence—from multiple types of studies, conducted by investigators from different disciplines, and using data from many countries—demonstrates a causal relationship between tobacco advertising and promotion and increased tobacco use. (Ref. 8). A variety of research has found that exposure to advertising is associated with susceptibility to use tobacco products and the actual use of tobacco products (
see e.g.,
Refs. 13-21). For example, research has found that the use of certain kinds of imagery, such as logos and cartoons, have an impact on youth tobacco initiation (
see, e.g.,
Refs. 22-24) and that a key tactic of tobacco companies seeking to attract and recruit youth users is to use advertising and marketing with aspirational imagery and themes known to resonate with younger audiences, such as independence, popularity, rebelliousness, attractiveness, and being cool (Ref. 12).
Marketing plans would provide information about the ways and frequency with which consumers would be exposed to tobacco product advertising, marketing, promotion, and other communication activities. This information can provide valuable insight into the likelihood that nonusers, particularly youth, would initiate tobacco product use. An analysis of the 2011 National Youth Tobacco Survey (NYTS) found that adolescents who reported frequent exposure to tobacco advertising at the point of sale and on the internet had significantly higher odds of ever using e-cigarettes and that there was a dose-response association between the number of marketing channels to which they were exposed and whether they used tobacco products. (Refs. 21 and 25). An analysis of 2014 NYTS data assessing exposure to e-cigarette advertising in different channels (
i.e.,
internet, print, television and movies, retail stores) found that as the number of channels of e-cigarette marketing exposure increased, the likelihood of use and susceptibility also increased. (Refs. 25-27).
Proposed § 1114.7(f)(2) would require, as part of the description of the marketing plans, that the PMTA specify information such as the intended target audience(s), media and distribution channels, specific tactics, total dollar amount(s) of media buys and marketing and promotional activities, and timing for the activities, including, but not limited to, information describing the items listed below. As used in proposed § 1114.7(f)(2), other consumer-directed activities include any other types of action regarding the new tobacco product that may reach consumers, such as communications that are intended to
inform retailers' communications with consumers. If an applicant does not intend to use any advertising, marketing, promotion, or other communication activities directed at consumers regarding its new tobacco product, or the applicants has not developed marketing plans by the time of filing, the PMTA must contain a statement to that effect in this section of the application. The types of information that the marketing plan section would be required to contain include, but are not limited to:
• Any plans to use competent and reliable data sources, tools, technologies, and methodologies to establish, maintain, and monitor highly targeted marketing plans and media buys. This could include, for example, use of and sources of first and second-party age-verified data, public records, industry-standard syndicated research services, and embedded tracking pixels in digital advertising;
• A description of the target adult audiences by age-range(s) (including young adult audiences ages 18-24) and other demographic and psychographic characteristics. Examples of demographic characteristics include, but are not limited to race, ethnicity, and geographic location (
e.g.,
urban, rural). Examples of types of psychographic characteristics include, but are not limited to hobbies, interests, risk-taking behaviors, tobacco use behaviors, purchase behaviors, and online search behaviors;
• A description of the target audience insights (
e.g.,
demographics, psychographics, findings from consumer research) the applicant is using to inform its marketing plans, including its strategic approach, key messages and themes, creative direction, and potential tactics or marketing channels. FDA generally expects that applicants will have conducted market or consumer research to determine, and gain information regarding, its target audience. This could include product-specific insights (
e.g.,
target audience impressions of one product being just as harmful as another, preference of a certain brand), as well as other beliefs, interests, motivations, or behaviors that can be used to tailor a manufacturers approach to marketing the product. This could also include information regarding where the target audience tends to consume marketing and advertising (
e.g.,
television programs the target audience watches, social media influencers the target audience follows, websites and retail locations the target audience frequents) that can be used to tailor its approach, select relevant marketing tactics, and use relevant marketing channels. The applicant should describe such insights in this section of the application;
• Any means by which youth-access to the tobacco product or youth-exposure to the tobacco product labeling, advertising, marketing, and promotion would be limited. FDA expects that applications will contain information regarding how the applicant intends to prevent sales or distribution to individuals below the legal purchasing age. Such information could include, for example, whether and how the company intends to: utilize independent, third-party age and identity-verification software on its website(s); distribute its product only to age-restricted locations; and limit the quantity of its product that an adult customer may purchase within a given period of time;
• Plans to use owned, earned, shared, or paid social media to advertise or promote the tobacco product. While media categories often overlap, owned media typically consists of a company's own media properties they control, such as the company's product-branded website. Earned media typically consists of unpaid media publicity, consumer interest or pick up of advertising or promotion, such as a news article about the product or a social media influencer talking about a company's product or sharing's a company's social media post without payment. Shared media typically consists of a company's social media properties, such as a company's social media accounts and content. Paid media consists of advertising and promotion that a company pays for, such as advertising appearing on television and radio, in and around retail stores, and in digital media, including content shared by a social media influencer who a company pays to promote to the tobacco product;
• Plans to use partners, sponsors, influencers (
e.g.,
celebrities, cultural icons, individuals with substantial followers on social media), bloggers, or brand ambassadors to create labeling for, market, advertise or promote the tobacco product;
• Plans to conduct in-person consumer engagements, including events at which the tobacco product will be demonstrated or sampled. Applicants planning to conduct in-person engagements should include a description of how access would be restricted to individuals at or above the Federal minimum age of purchase; and
• Plans to use earned media, public relations, or other communications outreach to promote the tobacco product. Earned media could consist of actions such as plans to pitch stories about the new tobacco product to newspapers without compensation. Public relations could consist of actions such as using a public-relations firm to promote the tobacco product. Other communications to promote the product could consist of actions such as direct mail to consumers.
FDA invites comment on the specific information in the proposed marketing plans section, and whether FDA should require additional information related to marketing plans and the basis for any such additional provisions.
At this time, FDA is not proposing to require the submission of advertising for application filing, except where used as stimuli in studies (
e.g.,
stimuli in perception studies). Specifically, in addition to the marketing plan requirements in this section, proposed § 1114.7(k)(1)(iv) would require a PMTA to contain full reports of information concerning investigations that are published, known to, or should be known to, the applicant regarding the impact of the tobacco product's label, labeling, and advertising on perceptions of the product and tobacco product use intentions.
7. Statement of Compliance With Part 25
A PMTA must contain an environmental assessment (EA) prepared in accordance with § 25.40 or a valid claim of a categorical exclusion, if applicable. Pursuant to § 25.15(a), all submissions requesting FDA action require the submission of either a claim of categorical exclusion or an EA. In accordance with § 25.40(a), an environmental assessment must include, at a minimum, brief discussions of: The need for the proposed action; alternatives to the proposed action as required by section 102(2)(E) of the National Environmental Policy Act of 1969 (NEPA); the environmental impacts of the proposed action and alternatives; the agencies and persons consulted during the preparation of the EA, and the relevant environmental issues relating to the use and disposal of the tobacco product. Although applicants may wish to review the categorical exclusions specific to tobacco product applications at § 25.35, the only categorical exclusion currently available for a marketing order is for the substantial equivalence premarket pathway, not for PMTAs. If the applicant believes the action would qualify for an available categorical exclusion, the applicant would be required to state under § 25.15(a) and (d) that the action qualifies for a categorical exclusion, cite to the claimed exclusion, and state that to the applicant's
knowledge no extraordinary circumstances exist under § 25.21.
If the new tobacco product resulted from modification(s) to a legally marketed predecessor product (
i.e.,
a grandfathered tobacco product or a product that has received marketing authorization from FDA), the environmental assessment also would be required to include a statement indicating whether the new tobacco product is intended to: (1) Replace the predecessor tobacco product once the new tobacco product receives market authorization and is commercially marketed; (2) be a line extension of the predecessor tobacco product; (3) be marketed along with the predecessor product by the same manufacturer; and/or (4) be marketed along with the predecessor tobacco product by a different manufacturer (
e.g.,
by a manufacturer other than the manufacturer of the predecessor tobacco product). The change in what is available in the marketplace is a factor FDA considers in determining whether the issuance of a marketing order may significantly affect the quality of the human environment as part of its NEPA review,
e.g.,
the new product may present different disposal issues if more product remains after consumer use or if the materials that the new product is composed of degrade differently.
Failure to include an EA in a PMTA is grounds for FDA to refuse to accept an application and failure to include an adequate EA is sufficient grounds under § 25.15 for FDA to refuse to file the PMTA or refuse to issue a marketing order. (See the discussion of proposed §§ 1114.27 and 1114.29 in section VIII.)
8. Summary
Proposed § 1114.7(h) would require the application to contain a summary of the application contents in sufficient detail to provide FDA with an adequate understanding of the data and information in the application. FDA is proposing to require the summary under authority of sections 701(a) and 910(b)(1)(G) of the FD&C Act because it will provide FDA with an understanding of the information contained in the PMTA and allow FDA to plan and conduct a more efficient review of the detailed technical information the summary describes. The summary would also help reviewers understand the product and the accompanying scientific data more quickly and would allow applicants to highlight information they believe demonstrates their product should receive a marketing order. The summary should discuss all aspects of the PMTA and synthesize the application into a well-structured, unified document. The summary should serve as a briefing document that highlights the most important aspects of the application, with each section consisting of a page or two focused on information that the applicant believes contributes to a finding that permitting the marketing of the product would be APPH. The applicant would be required to summarize the content included in the PMTA in a manner that describes the operation of the product, the health risks of the new tobacco product, the product's effect on tobacco use behavior of current users, the product's effect on tobacco use initiation by nonusers, and the product's effect on the population as a whole. The summary section would be required to contain a discussion of the following items, where applicable, and explicitly identify areas in which there is a lack of information, if any:
• A summary of the product formulation section of the application. This section should provide a high-level description of the product formulation section of the application, highlighting information such as key ingredients, constituent levels, and design aspects of the product. See the discussion of proposed § 1114.7(i) in section VII.B.9;
• A summary of the manufacturing section of the application. This section should provide an overview of the manufacturing section of the application, including activities at each facility, and highlighting information such as major aspects of the manufacturing and controls, especially those that the applicant believes contribute to a finding that permitting the marketing of the product would be APPH (
e.g.,
an aspect of the manufacturing process that results in lower levels of HPHCs than other tobacco products in the same category). See the discussion of proposed § 1114.7(j) in section VII.B.12.;
• A summary of the health risk investigations section of the application. This section should briefly describe and synthesize the findings of each investigation describing:
○ The health risks of the tobacco product to both users and nonusers of the product and whether the tobacco product presents less health risk than other tobacco products, such as the risk of cancers (
e.g.,
lung, mouth, pancreatic), heart disease, stroke, or lung disease, compared to other categories of tobacco products and other tobacco products within the category, if known. See the discussion of proposed § 1114.7(k)(1)(i) in section VII.B.13.a.i.;
○ The impact the product and its marketing will have on the likelihood of changes in tobacco use behavior of tobacco product users, including cessation, switching (
i.e.,
to a different tobacco product), and poly use (
i.e.,
using the new tobacco product in conjunction with one or more other tobacco products). See the discussion of proposed § 1114.7(k)(1)(ii) in section VII.B.13.a.ii.;
○ The impact the product and its marketing will have on the likelihood of tobacco use initiation by tobacco products nonusers, especially youth and young adults, including among never users and former users, and the likelihood of poly use and switching behaviors. See the discussion of proposed § 1114.7(k)(1)(iii) in section VII.B.13.a.iii.;
○ How users and nonusers perceive the tobacco product and its label, labeling, and advertising, how the label, labeling, and advertising affect use intentions, and whether users are able to understand the labeling and instructions for use and use the product in accordance with those instructions. See the discussion of proposed § 1114.7(k)(1)(iv) in section VII.B.13.a.iv.; and
○ The impact of human factors on the health risks to product users and nonusers including, for example, how various use and misuse scenarios may impact the health risks posed by the product. See the discussion of proposed § 1114.7(k)(1)(v)) in section VII.B.13.a.v.
The proposed rule also would require the summary to contain a concluding discussion demonstrating how the data and information contained in the PMTA both constitute valid scientific evidence and establish that permitting the marketing of the new tobacco product would be APPH, as determined with respect to the risks and benefits to the population as a whole, including users and nonusers of the tobacco product. FDA recommends that this discussion include estimates of the effect that the new tobacco product may have on the health of the population as a whole, such as effects on tobacco use initiation switching and cessation, and reductions in premature mortality, or increases in life-years lived. The estimates should integrate all of the information in the PMTA regarding the product and its potential effects on health, including, but not limited to adverse experiences, tobacco use behavior, and tobacco use initiation to provide an overall assessment of the potential effect that the product's marketing has or may have on overall tobacco-related morbidity and mortality. 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. As an illustration, an applicant may make an overall assessment of whether the product will have a net benefit on population health by accounting for potential reductions in disease risk (compared to other tobacco products) and the potential for current tobacco users to switch to the new tobacco product, and weighing that against the potential for nontobacco users to use the tobacco product and the accompanying potential increases in disease risks among those new tobacco product users. An applicant should provide quantitative assessments in the concluding discussion wherever possible; however, an applicant may provide qualitative assessments where appropriate for the type of investigation(s) on which the assessment is based (
e.g.,
focus group or interview-type studies).
The summary's concluding discussion must also briefly describe why the data and scientific information on which the applicant relies in concluding that permitting the marketing of the product would be APPH constitute valid scientific evidence. Section 910(c)(5)(A) of the FD&C Act requires FDA to make its determination of whether the marketing of a new tobacco product is APPH, where appropriate, on the basis of well-controlled investigations; however, under section 910(c)(5)(B) of the FD&C Act, where FDA determines that there exists valid scientific evidence other than well-controlled investigations that is sufficient to evaluate the product, FDA may use such evidence. As discussed in more detail in section VIII.D. regarding proposed § 1114.31, FDA considers valid scientific evidence to be evidence gathered using well-established or standardized methodologies from which it can be concluded by qualified experts that there is reasonable assurance of the reliability of its findings. Thus, if an application contains information regarding another tobacco product (
e.g.,
published literature, marketing information) with appropriate bridging studies and describes the relationship to the product that is the subject of the application, FDA will review that information to determine whether it is valid scientific evidence sufficient to demonstrate that permitting the marketing of a product would be APPH.
9. Product Formulation
Section 910(b)(1)(B) of the FD&C Act requires that a PMTA contain a full statement of the components, ingredients, additives, and properties, and of the principle or principles of operation, of such tobacco product. Proposed § 1114.7(i) would implement FDA's interpretation of this statutory requirement, together with its authority under section 910(b)(1)(G) of the FD&C Act, by requiring a PMTA to contain the following information:
a. Components or parts, materials, ingredients, constituents, and additives. Under the proposed rule, the application would be required to contain a full statement (
i.e.,
a listing) of the product components or parts, materials, ingredients other than tobacco, tobacco ingredients, HPHCs, and the container closure system.
i. Components or parts.
Proposed § 1114.7(i)(1)(i) would require the application to state the quantity, function, and purpose of, and where applicable, target specifications of each component or part in the product. This information should also include an explanation of how each component or part is, or can be, integrated into the product design, and the purpose and function of each component or part. Where the tobacco product contains software components, the rule would require:
• A description of the software or technology (
e.g.,
Bluetooth);
• A description of the purpose of the software or technology, such as monitoring where the tobacco product is located, activated, or used;
• A description of the data collected by the software and how this information will be used by the applicant.
This information is especially important as it may not be readily apparent from the component or part's identity what function and purpose it may serve. For example, software used in or with a product may have functions and purposed that are not immediately clear, such as use monitoring and location tracking functions, and may be able to function in conjunction with other electronic devices, such as a smart phone.
ii. Materials.
Proposed § 1114.7(i)(1)(ii) would require that the application include the following information for each material in the product because materials can affect the performance of the product. For example, in portioned smokeless tobacco products, the materials used in the pouch can affect the rate at which nicotine is released and specifications such as pouch fabric air permeability can provide information about how quickly nicotine can be delivered to the consumer. For ENDS, the material used in the construction of an electrical heater coil influences its resistance and the temperature reached by the coil, which in turn may affect the type and amount of HPHCs produced in aerosol. The rule would require:
• The material name and common name (if applicable);
• The component or part where it is located;
• The subcomponent or subpart where it is located (if applicable);
• The function of the material;
• Quantities (including ranges or means and acceptance limits);
• Specifications (including quality, grades, and suppliers) used for the new tobacco product (including any specification variations, if applicable); and
• Any other material properties that fully characterize the new tobacco product, such as pouch material porosity or air permeability for portioned smokeless products. While failure to include additional material properties to fully characterize the tobacco product would not serve as the basis for FDA refusing to accept or file an application under proposed § 1114.27(a)(1), it may slow down the substantive review process.
iii. Ingredients other than tobacco.
Proposed § 1114.7(i)(1)(iii) would require that the application contain information on ingredients other than tobacco (information on tobacco ingredients is addressed in proposed § 1114.7 (i)(1)(iv)). The required information would include:
• International Union of Pure and Applied Chemistry (IUPAC) chemical name and common name (if applicable);
• Chemical Abstracts Service (CAS) number or FDA Unique Ingredients Identifier (UNII). Both the IUPAC and CAS or UNII would be required to ensure FDA has the relevant information associated with each identifier and to allow FDA to efficiently differentiate between similar ingredients;
• The function of the ingredient;
• The quantity of the ingredient, with the unit of measure (including ranges or means, and acceptance limits);
• The specifications (including purity or grade and supplier); and
• For complex purchased ingredients, each single chemical substance would be required to be reported separately.
Additionally, FDA recommends that an application contain any other ingredient information to fully characterize the new tobacco product, as applicable. While failure to include other ingredient information to fully characterize the tobacco product would not serve as the basis for FDA refusing to accept or file an application under proposed § 1114.27(a)(1), it may slow down the substantive review process.
iv. Tobacco ingredients.
Proposed § 1114.7(i)(1)(iv) would require information regarding tobacco ingredients, including:
• The type(s) of tobacco, including grade(s) and variety or varieties. This information is important to determining the public health impact of the products because different grades and varieties have different constituent profiles. The application would also need to contain information on the applicant's grading system so that FDA understands the meaning of the grade;
• The quantity, with the unit of measure (including ranges or means, and acceptance limits), of each tobacco ingredient in the new tobacco product;
• The specification(s) of tobacco used for the new tobacco product (with any specification variation, if applicable); and
• A description of any genetic engineering that impacts characteristics, such as the constituent profile.
Additionally, FDA recommends a PMTA also contain any other information about tobacco ingredients to fully characterize the new tobacco product, as applicable, such as country of origin, which can affect constituent levels (Ref. 28). While failure to include other information about tobacco ingredients to fully characterize the tobacco product would not serve as the basis for FDA refusing to accept or file an application under proposed § 1114.27(a)(1), it may slow down the substantive review process.
If the new tobacco product does not contain tobacco (
e.g.,
rolling paper or tipping paper), this section of the application would be required to specifically state that the product does not contain tobacco.
FDA is proposing in § 1114.7(i)(1) that ingredient quantities be reported as mass per gram of tobacco for nonportioned tobacco products and as mass per portion for portioned tobacco products. These specific measurements provide consistent, complete information that would allow FDA to understand the ingredient quantities. In contrast, if ingredient quantities were reported as percentages, FDA would have to make assumptions about the denominator used to calculate the percentage. For example, if xylitol were reported as 10 percent of a portioned moist snuff, FDA would not able to determine if xylitol was 10 percent of the mass of the tobacco filler or of the entire product (containing filler, paper, etc.). For more information on uniquely identifying components, ingredients, and additives and reporting their quantities, please refer to FDA's guidance for industry “Listing of Ingredients in Tobacco Products.”
v. Constituents.
Proposed § 1114.7(i)(1)(v) would require a full statement of the constituents, including HPHCs and other constituents, contained within, or emitted from (including its smoke or aerosol), the product, including any reaction products from leaching or aging. FDA considers constituents to be properties of the new tobacco product, a full statement of which is required to be in a PMTA by section 910(b)(1)(B) of the FD&C Act. The constituents contained within, and delivered from, the product can be detected through constituent testing on the product. The constituent testing should reflect the various conditions under which consumers may use the product (
e.g.,
light use, typical use, and heavy use) and the types of products that consumers are likely to use in conjunction with the product. For example, an open (refillable) e-cigarette should be tested with a variety of e-liquids that consumers are likely to consume using the e-cigarette. The reports of constituent testing must be conducted in the manner required by, and include all information that is specified in, proposed § 1114.7(i)(1)(v), including the full test data.
FDA published an initial list of the constituents that it has identified as HPHCs in the
Federal Register
of April 3, 2012, which it intends to update periodically by providing the public with notice and the opportunity to submit comments. FDA is currently seeking public comment on its proposal to add 19 constituents to the established list of HPHCs.
10
An application would not be required to contain testing for all HPHCs on the initial list; rather, it would be required to contain testing for 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. The HPHC list can be helpful to applicants in preparing a description of why the HPHCs for which it tested are appropriate for the product type, including, where appropriate, why an applicant did not test for certain HPHCs. For example, a PMTA for a smokeless tobacco product would not be required to contain testing results for HPHCs that are a byproduct of combustion (
e.g.,
carbon monoxide) where the product does not contain or deliver such constituents. However, a PMTA for a tobacco product that an applicant claims aerosolizes a substance but does not combust it, such as an e-cigarette or heated tobacco product, should provide evidence, such as testing for HPHCs that result from complete or incomplete combustion, to demonstrate that the product is not combusted. For recommendations on constituent testing for ENDS products, please see the “Guidance for Industry, Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems.” Constituent testing data FDA is proposing that a PMTA contain for all products includes:
10
84 FR 38032 (August 5, 2019).
• The constituent names in alphabetical order;
• The common name(s);
• The CAS number;
• The mean quantity and variance with unit of measure;
• The number of samples and measurement replicates for each sample. As stated in proposed § 1114.7(i)(4)(iv), the testing would be required to be conducted using a sufficient sample size and number of replicates to substantiate the results of the type of testing conducted;
• A description of method procedure, method validation information and rationale for selecting each test method (as would be required by § 1114.7(i)(4)(v));
• The name and location of the testing laboratory or laboratories and documentation showing that the laboratory or laboratories is (or are) accredited by a nationally or internationally recognized external accreditation organization (as would be required by § 1114.7(i)(4)(i));
• The length of time between dates of manufacture and date(s) of testing (as would be required by § 1114.7(i)(4)(ii));
• Storage conditions of the tobacco product before it was tested. It is important for FDA to understand the storage conditions before testing because they could affect the quantity of volatile organic compounds or promote microbial growth in the tobacco product
(as would be required by § 1114.7(i)(4)(iii));
• Reports of constituent testing that include test protocols, any deviation(s) from the test protocols, quantitative acceptance criteria, line data, and a summary of the results, for each applicable parameter (as would be required by § 1114.7(i)(4)(vi); and
• Complete descriptions of any smoking or aerosol-generating regimens used for analytical testing that are not standardized or widely accepted by the scientific community, if applicable (as would be required by § 1114.7(i)(4)(vii).
For combusted or inhaled tobacco products, constituent smoke or aerosol yields from the new product would be required to be determined using intense and nonintense smoking or aerosol-generating regimens, where established. Two smoking or aerosol-generating regimens are required, where established, in order to understand the way that constituent yields delivered by a tobacco product can change over a range of different smoking conditions. If constituent yields were only reported from a single smoking or aerosol-generating regimen, FDA would have limited and potentially misleading information about constituent yields produced by a given tobacco product. Many studies demonstrate that different smoking regimens result in different constituent yields from the same product (Ref. 29-30). By requiring both an intense and a nonintense smoking or aerosol generating regimen, where established, FDA would have a better understanding of quantities of each constituent that may be produced by the tobacco product when used under different conditions. If an alternative to the established smoking regimens (
e.g.,
International Organization for Standardization (ISO) and Health Canada Intense (HCI) regimens for cigarettes) is used, such as where intense and nonintense smoking or aerosol generating regimens have not been established, the applicant would be required to provide an explanation of why the alternative provides comparable results to the intense and nonintense smoking regimens.
vi. Container closure system.
Proposed § 1114.7(i)(1)(vi) would require that the application contain a description of the container closure system for the new tobacco product, if applicable, including information describing how the container closure system protects and preserves the product from damage during transport, environmental contaminants, and leaching and migration of constituents into the new tobacco product. The description would also need to describe design features developed to prevent the risk of accidental exposure, if any (
e.g.,
child resistant packaging for e-liquids). These descriptions are important to FDA's review of the product because they will help demonstrate that the product used by consumers is in the same condition as that described in the application and manufactured by the applicant, and also provide information regarding whether the container closure system has any features that could prevent accidental exposure (
e.g.,
a feature that prevents e-liquid from being accidentally ingested by children). Additionally, evidence demonstrates that the container closure system used can change the characteristics of the product. Packaging materials constitute the container closure system if substances within that packaging are intended or reasonably expected to affect product moisture,
e.g.,
when the manufacturer changes the container closure system of a moist snuff from plastic to fiberboard, which can affect microbial stability and 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. 2). The container closure system 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 the container closure system may also diffuse into snuff and affect its characteristics (Ref. 3). Thus, for example, packaging material that affects the characteristics of a tobacco product by impacting the moisture level or shelf life of a tobacco product is a container closure system (
e.g.,
a plastic versus a metal container of smokeless tobacco) because 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 NNN or NNK. For additional examples of container closure systems that may support a finding that permitting an ENDS to be marketed would be APPH, see the “Guidance for Industry, Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems.”
vii. Statement of tobacco blending, reconstitution, manipulation.
Finally, the proposed rule would require a full statement of the tobacco blending, reconstitution, or manipulation, where applicable. This may include manufacturer specifications, and tobacco types, quantities, and tobacco grading systems. This information is important because it helps FDA understand the characteristics of the tobacco product. Information on tobacco grades and grading systems used by an applicant (where applicable) will help FDA understand the quality of tobacco used, which can provide important information since the specified tobacco grades may impact the tobacco chemistry (
e.g.,
the nicotine content) and, thereby, the chemical composition of the tobacco product (Ref. 31).
b. Other properties.
Proposed section § 1114.7(i)(2) describes additional parts of FDA's interpretation of the requirement in section 910(b)(1)(B) of the FD&C Act to provide a full statement of the product properties and, together with FDA's authority under section 910(b)(1)(G), would require the applicant to provide a full description of the properties of the tobacco product that includes:
i. Product dimensions and construction.
The product dimensions and the overall construction of the product using a diagram or schematic drawing that clearly depicts the finished product and its components with dimensions, operating parameters, and materials. Under the proposed definition for finished tobacco product (which includes all components and parts, sealed in final packaging), the dimensions and schematic drawings would be required to include the final packaging. The diagram or schematic is an annotated graphical representation that will help FDA understand the applicant's nomenclature, how the components and parts function together, and the overall principles of operation of the finished tobacco product.
ii. Design parameters and test data.
All design parameters of the product and test data, specifying nominal values or the explicit range of values as well as the design tolerance (
i.e.,
upper and lower range limits), where appropriate. Design parameters can change the health impact of the tobacco product by affecting the level of constituents that reach the user or nonuser and are also necessary to fully characterize a tobacco product. Tables 1 through 20 in proposed § 1114.7(i)(2)(ii)(B) provide the parameters that would be required for different categories of tobacco products. As part of the full description of the properties of the tobacco product, the proposed rule would also require, as included in the tables, a quantitative description of the performance criteria, including test protocols, line data, and a summary of the results, for each applicable design parameter and manufacturing step. The test data is a
required part of the PMTA to demonstrate the product consistently meets the nominal values or range of values as well as the design tolerance. The proposed parameters and their importance to understanding their impact on public health are described below.
Note that in addition to the parameters listed in tables 8 to 20 of the draft codified, FDA is also providing additional design parameters that it recommends including in a PMTA for certain types of deemed tobacco products in just the preamble. FDA is considering whether it should require the submission of these additional design parameters as part of the final rule and is requesting public comment regarding whether FDA should include these parameters as requirements in the final rule, whether FDA should recommend or require additional design parameters, and, if so, the basis for including additional design parameters.
Table 1 in proposed § 1114.7(i)(2)(ii)(B) describes the design parameters and information on performance criteria to be provided for cigarettes. These parameters are a necessary part of the application because they are needed to fully characterize the product and changes in these parameters may affect the cigarette's impact on the public health, as described below:
• Cigarette mass may affect smoke constituent yields (Ref. 32).
• Cigarette length may alter tobacco biomarker levels (Ref. 33).
• Cigarette diameter may affect filter efficiency and, in turn, smoke constituent yields (Ref. 34).
• Puff count can directly affect smoke constituent yields (Ref. 35).
• Cigarette draw resistance may result in differences in the difficulty of pulling air through the tobacco rod and, in turn, affect smoke constituent yields (Ref. 36).
• Tobacco rod length may alter tobacco biomarker levels (Ref. 33).
• Tobacco filler mass may affect smoke constituent yields (Ref. 32).
• Tobacco rod density may modify burn properties and smoke constituent yields (Refs. 37 and 38).
• Tobacco cut size alters the size of the tobacco pieces, which may result in more particulate matter (Ref. 39).
• Tobacco moisture may affect puff count (Ref. 40).
• Cigarette paper length and cigarette paper width may affect smoke constituent yields (Ref. 32).
• Cigarette paper base paper basis weight may affect puff count and smoke constituent yields (Ref. 41).
• Cigarette paper base paper porosity may affect smoke constituent yields (Ref. 41).
• Cigarette paper band porosity may affect smoke constituent yields because band porosity allows for the overall assessment of the weighted change in air flow through the cigarette paper during active puffing (Ref. 42).
• Cigarette paper band diffusivity may affect smoke constituent yields because it mimics air flow during smoldering (Ref. 43).
• Cigarette paper band width may affect ventilation and, in turn, smoke constituent yields (Ref. 44).
• Cigarette paper band space may affect ignition propensity and, in turn, puff count (Ref. 45).
• Filter efficiency may affect smoke constituent yields (Ref. 44).
• Filter diameter, filter mass, filter tow crimping index, denier per filament, total denier, filter density, and filter length may affect filter efficiency and, in turn, smoke constituent yields (Ref. 46).
• Filter pressure drop may affect smoke constituent yields (Ref. 47).
• Plug wrap, including length, width, basis weight, porosity, and caliper, contributes to the overall ventilation (Ref. 44).
• Tipping paper, including length, width, and basis weight, may affect smoke constituent yields (Ref. 48).
• Filter ventilation, including location and number of holes and rows, may affect smoke constituent yields (Ref. 34).
Table 2 in proposed § 1114.7(i)(2)(ii)(B) describes the design parameters and information on performance criteria to be provided for new portioned and non-portioned smokeless tobacco products. These parameters are a necessary part of the applications because they are needed to fully characterize the product and changes in these parameters may affect the smokeless tobacco product's impact on public health, as described below:
• Tobacco cut size may alter the particle surface area and accessibility of saliva to get to the surfaces of the tobacco, thereby affecting the amount and rate of constituents released from the product (Ref. 49).
• Tobacco moisture may affect microbial growth in the product, extraction efficiency, and total exposure to nicotine, NNN, and NNK (Refs. 4 and 5).
• Portion mass may affect user exposure to a tobacco product and, in turn, HPHCs contained in each portion (Ref. 50).
• Portion length may affect the constituents in each portion (Ref. 50).
• Portion width may result in a surface area difference, which is proportional to the amount and rate of constituents released from the product (Ref. 51).
• Portion thickness may result in a surface area difference, which is directly proportional to the amount and rate of constituents released from the product (Ref. 51).
• Pouch material basis weight, pouch material air permeability, and pouch material caliper influences the interactions between the tobacco and oral cavity, thereby potentially affecting the amount and rate of constituents released from the product (Ref. 52).
• Pouch material nicotine dissolution rate is a function of tobacco cut size and pouch materials, thereby potentially affecting the amount and rate of constituents released from the product (Ref. 53).
• Pouch material nicotine dissolution extent is a function of the initial release and duration of the ongoing release, thereby potentially affecting the amount and rate of constituents released from the product (Refs. 52 and 54).
Table 3 in proposed § 1114.7(i)(2)(ii)(B) describes the design parameters and information on performance criteria to be provided for new roll-your-own (RYO) tobacco rolling paper products. These parameters are a necessary part of the application because they are needed to fully characterize the product and changes in these parameters may affect the rolling paper's impact on public health, as described below:
• RYO paper length and RYO paper width may alter the surface area that is available for tobacco packing, thereby affecting the smoke constituent yields (Ref. 47).
• RYO paper mass may be a result of a surface area or basis weight difference and, in turn, may affect puff count and smoke constituent yields (Refs. 41 and 47).
• RYO paper base paper basis weight may affect puff count and smoke constituent yields (Ref. 41).
• RYO paper base paper porosity may affect smoke constituent yields (Ref. 41).
• RYO paper band porosity may affect smoke constituent yields because band porosity allows for the overall assessment of the weighted change in air flow through the cigarette paper during active puffing (Ref. 42).
• RYO paper band diffusivity may affect smoke constituent yields because it mimics air flow during smoldering (Ref. 43).
• RYO paper band width may affect ventilat
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