Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 1159 

including postmarketing safety 

surveillance and reporting 

requirements, regardless of the 

technology utilized. 

The Agency also recognizes that 

sponsors may have questions about 

credibility assessment plans in 

connection with the postmarketing 

phase. Therefore, the Agency seeks 

feedback about whether development of 

additional guidance specific to the use 

of AI models in postmarketing 

pharmacovigilance would be helpful 

and, if so, the topics that would be most 

useful for the Agency to address. For 

general discussion about the use of AI 

models or other emerging technologies 

in pharmacovigilance, FDA has 

established the Emerging Drug Safety 

Technology Meeting (EDSTM) Program. 

The risk-based credibility assessment 

framework proposed within the draft 

guidance is informed by: (1) over 800 

comments received on the 2023 

discussion papers published by CDER 

entitled ‘‘Using Artificial Intelligence & 

Machine Learning in the Development 

of Drug & Biological Products’’ (https:// 

www.fda.gov/media/167973/download) 

and ‘‘Artificial Intelligence in Drug 

Manufacturing’’ (https://www.fda.gov/ 

media/165743/download); (2) FDA’s 

experience with reviewing over 300 

submissions with AI and machine 

learning components across all phases 

of the drug development process; and 

(3) current regulatory science research. 

However, FDA understands that this is 

a rapidly evolving field, involving 

multidisciplinary expertise. FDA 

requests public comment from industry 

and all other interested parties on the 

guidance, with emphasis on the 

following items: 

• How well the proposed risk-based 

credibility assessment framework aligns 

with industry’s experience; and 

• Whether the options available for 

sponsors and other interested parties to 

engage with FDA on AI are sufficient. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on the use of AI to support regulatory 

decision-making for drug and biological 

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 of the applicable statutes 

and regulations. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. The previously approved 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (PRA) (44 U.S.C. 

3501–3521). The collections of 

information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014; the collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001; the collections of 

information in 21 CFR part 601 have 

been approved under OMB control 

number 0910–0338. 

III. Electronic Access 

Persons with access to the internet 

may obtain an electronic version of the 

draft guidance at https://www.fda.gov/ 

drugs/guidance-compliance-regulatoryinformation/guidances-drugs, https://

www.fda.gov/vaccines-blood-biologics/ 

guidance-compliance-regulatoryinformation-biologics/biologicsguidances, https://www.fda.gov/ 

medical-devices/device-advicecomprehensive-regulatory-assistance/ 

guidance-documents-medical-devicesand-radiation-emitting-products, 

https://www.fda.gov/regulatoryinformation/search-fda-guidancedocuments, or https:// 

www.regulations.gov. 

Dated: December 27, 2024. 

Kimberlee Trzeciak, 

Deputy Commissioner for Policy, Legislation, 

and International Affairs. 

[FR Doc. 2024–31542 Filed 1–6–25; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–D–0756] 

Validation and Verification of 

Analytical Testing Methods Used for 

Tobacco Products; Guidance for 

Industry; Availability 

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.’’ 


ddrumheller on DSK120RN23PROD with NOTICES1
1160 Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 

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 nontobacco (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 (R2) 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 


ddrumheller on DSK120RN23PROD with NOTICES1
Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 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-fdaguidance-documents, https://

www.fda.gov/tobacco-products/rulesregulations-and-guidance-relatedtobacco-products/guidance-relatedtobacco-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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–D–5591] 

Evaluation of Sex-Specific and GenderSpecific Data in Medical Device 

Clinical Studies; Draft Guidance for 

Industry and Food and Drug 

Administration Staff; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of the draft 

guidance entitled ‘‘Evaluation of SexSpecific and Gender-Specific Data in 

Medical Device Clinical Studies.’’ This 

document provides guidance on the 

study and evaluation of sex- and/or 

gender-specific data in clinical 

investigations or research involving one 

or more subjects to determine the safety 

or effectiveness of a device. The purpose 

of this guidance is to encourage sciencedriven consideration of sex and/or 

gender, as appropriate for both the 

scientific question being addressed and 

the intended use of the device, when 

designing medical device clinical 

studies and reporting data from such 

studies in accordance with legal 

requirements. This draft guidance is not 

final nor is it for implementation at this 

time. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by April 7, 2025 to ensure that the 

Agency considers your comment on this 

draft guidance before it begins work on 

the final version of the guidance. 

ADDRESSES: You may submit comments 

on any guidance 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– 

2023–D–5591 for ‘‘Evaluation of SexSpecific and Gender-Specific Data in 

Medical Device Clinical Studies.’’ 

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)). 


ddrumheller on DSK120RN23PROD with NOTICES1