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###### Department of Health and Human Services

###### Food and Drug Administration

          - [Docket No. FDA-2021-D-0756]

# AGENCY:

Food and Drug Administration, HHS

# ACTION:

Notice of availability.

# SUMMARY:

The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a final guidance for industry entitled “Validation and Verification of Analytical Testing Methods Used for Tobacco Products.” The guidance provides information and recommendations related to the validation and verification of analytical test methods, including analytical testing of tobacco product constituents, ingredients, and additives, as well as stability testing of tobacco products. This guidance is intended to help industry produce more consistent and reliable analytical data used to support regulatory submissions for finished tobacco products. This guidance finalizes the draft guidance of the same title issued in December 2021.

# DATES:

                        The announcement of the guidance is published in the                         **Federal Register**                         on January 7, 2025.                    

# ADDRESSES:

You may submit either electronic or written comments on Agency guidances at any time 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-2021-D-0756 for “Validation and Verification of Analytical Testing Methods Used for Tobacco Products.”                           ( print page 1160)                        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, 240-402-7500.                
      - 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.govinfo.gov/​content/​pkg/​FR-2015-09-18/​pdf/​2015-23389.pdf. 

*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, 240-402-7500.                

You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)).

                    Submit written requests for single copies of this guidance to the Center for Tobacco Products, Food and Drug Administration, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G335, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your request or include a Fax number to which the guidance document may be sent. See the                     **SUPPLEMENTARY INFORMATION**                     section for information on electronic access to the guidance.                

# FOR FURTHER INFORMATION CONTACT:

                        Robert Schwartz or Nathan Mease, Center for Tobacco Products, Food and Drug Administration, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G335, Silver Spring, MD 20993-0002, 1-877-287-1373, email:                         *CTPRegulations@fda.hhs.gov.*

# SUPPLEMENTARY INFORMATION:

## I. Background

FDA is announcing the availability of a guidance for industry entitled “Validation and Verification of Analytical Testing Methods Used for Tobacco Products.” This guidance provides information and recommendations on how tobacco product manufacturers can produce validation and verification data for the analytical procedures and methods used to support regulatory submissions for finished tobacco products including substantial equivalence (SE) reports, premarket tobacco product applications (PMTA), and modified risk tobacco product applications (MRTPA). Additionally, the principles in this guidance may be used for finished tobacco product testing and reporting of harmful and potentially harmful constituents (HPHCs) in tobacco products and tobacco smoke.

The Federal Food, Drug, and Cosmetic Act (FD&C Act) requires, among other things, premarket review for new tobacco products and modified risk tobacco products (see sections 910 and 911 of the FD&C Act (21 U.S.C. 387j and 21 U.S.C. 387k)) and reporting of harmful and potentially harmful constituents under section 904 of the FD&C Act (21 U.S.C. 387d). Regulatory submissions often contain data from analytical testing, such as data about ingredients, constituents, and additives. In standard practice, analytical testing is done through validation of the analytical test method. In these cases, the applicant will want to use analytical test methods that are sufficiently precise, accurate, selective, and sensitive. Validation involves documenting, using specific laboratory investigations, that the performance characteristics of the test method are suitable and reliable for the intended analytical applications, in terms of precision, accuracy, selectivity, and sensitivity. This guidance is intended to help industry produce more consistent and reliable analytical data used to support regulatory submissions for finished tobacco products, such as SE, PMTA, MRTPA submissions, and for finished tobacco product testing and reporting of HPHCs in tobacco products and tobacco smoke.

This guidance finalizes the draft guidance of the same title issued on December 22, 2021 (86 FR 72603). FDA considered comments received on the draft guidance and revised the final guidance as appropriate in response to the comments. Changes from the draft to the final guidance include:
    - Updates to the Background section reflecting statutory revisions to the term “tobacco product” to include non-tobacco (synthetic) nicotine (see Pub. L. 117-103 );
    - Acknowledgment that alternative validation procedures and recommendations may differ from those in this guidance;
    - Expression of the Agency's support for the use of national and international standard analytical test methods for the analysis of finished tobacco products;
    - The addition of definitions for several new terms and revisions to several existing definitions to improve clarity;
    - Updates reflecting PMTA rule and SE Report rule requirements for documenting laboratory accreditation;
    - Updates to citations supporting the replicate recommendations in the guidance and for alternative validation procedures;
    - Corrections, revisions, or clarifications to calculations, formulas or equations, or units of measure in the text and tables;
    - The addition of an equation as an approach to adjust for interference bias when determining selectivity;
    - Clarification of the Agency's thinking on the adequacy of linear regression (R 2                     ) for determining the linearity parameter as part of analytical test method validation;                
    - The addition of a spike and recovery approach for determining the limit of detection in order to provide flexibility in the analytical sampling procedure recommendations;
    - Expansion on the discussion of tobacco product reference standards; and
    - Editorial revisions to the text to improve clarity and consistency of terms used throughout the guidance.

                    This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the current thinking of FDA on “Validation and Verification of Analytical Testing Methods Used for Tobacco Products.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements                           ( print page 1161)                        of the applicable statutes and regulations.                

## II. Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of information found in FDA regulations. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The collections of information in section 910(c)(1)(A)(i) of the FD&C Act have been approved under OMB control number 0910-0768; the collections of information in section 905(j) of the FD&C Act (21 U.S.C. 387e(j)) have been approved under OMB control number 0910-0673; the collections of information in 21 CFR part 1107 have been approved under OMB control number 0910-0684; the collections of information in section 904(a)(3) of the FD&C Act have been approved under OMB control number 0910-0732, and the collections of information in 21 CFR part 1114 have been approved under OMB control number 0910-0879.

## III. Electronic Access

                    Persons with access to the internet may obtain an electronic version of the guidance at                     *https://www.fda.gov/​regulatory-information/​search-fda-guidance-documents, https://www.fda.gov/​tobacco-products/​rules-regulations-and-guidance-related-tobacco-products/​guidance-related-tobacco-products,*                     or                     *https://www.regulations.gov.*

Dated: December 26, 2024.

Kimberlee Trzeciak,

Deputy Commissioner for Policy, Legislation, and International Affairs.

[FR Doc. 2024-31541 Filed 1-6-25; 8:45 am]

BILLING CODE 4164-01-P