Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 1157 

criticized FDA regulation of IGAs in 

animals for neglecting animal welfare. 

The remaining comments came from 

industry (companies that produce IGAs 

and trade associations), individual 

developers of IGAs in animals, 

academics, non-governmental 

organizations (consumer, 

environmental), and individual 

consumers. 

FDA has made changes in the final 

GFI #187B that include additional 

explanation or clarification about: (1) 

how FDA’s animal safety review 

includes animal health and well-being; 

(2) how compositional analysis relates 

to the food safety evaluation; (3) what 

FDA means by a ‘‘significant change’’ 

with respect to durability; (4) what can 

be included in a single IGA-related 

application; (5) what methods, 

including methods other than whole 

genome sequencing, may be most 

appropriate for molecular 

characterization of the lineage of 

animals with the IGA; (6) further 

clarification regarding data 

expectations, including what data 

constitutes a ‘‘full characterization’’ of 

the site of alteration and potential 

unintended alterations; and (7) more 

detailed information on review 

timelines. In addition, editorial changes 

were made to improve clarity. The 

guidance announced in this notice 

finalizes the draft guidance dated May 

2024. 

This level 1 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 ‘‘Heritable 

Intentional Genomic Alterations in 

Animals: The Approval Process.’’ 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 25 have been 

approved under OMB control number 

0910–0322; the collections of 

information in 21 CFR part 58 have been 

approved under OMB control number 

0910–0119; the collections of 

information in 21 CFR part 207 have 

been approved under OMB control 

number 0910–0045; the collections of 

information in 21 CFR part 211 have 

been approved under OMB control 

number 0910–0139; the collections of 

information in 21 CFR part 511 have 

been approved under OMB control 

number 0910–0117; the collections of 

information in 21 CFR part 514 have 

been approved under OMB control 

number 0910–0284; and the collections 

of information in 21 CFR 558.6(a)(4) 

have been approved under OMB control 

number 0910–0363. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at https://

www.fda.gov/animal-veterinary/ 

guidance-regulations/guidanceindustry, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, or https://

www.regulations.gov. 

Dated: December 27, 2024. 

Kimberlee Trzeciak, 

Deputy Commissioner for Policy, Legislation, 

and International Affairs. 

[FR Doc. 2024–31532 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–2024–D–4689] 

Considerations for the Use of Artificial 

Intelligence To Support Regulatory 

Decision-Making for Drug and 

Biological Products; Draft Guidance 

for Industry; Availability; Comment 

Request 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of a draft 

guidance for industry entitled 

‘‘Considerations for the Use of Artificial 

Intelligence To Support Regulatory 

Decision-Making for Drug and 

Biological Products.’’ In accordance 

with its mission of protecting, 

promoting, and advancing public 

health, FDA’s Center for Drug 

Evaluation and Research (CDER), in 

collaboration with the Center for 

Biologics Evaluation and Research 

(CBER), the Center for Devices and 

Radiological Health (CDRH), the Center 

for Veterinary Medicine (CVM), the 

Oncology Center of Excellence (OCE), 

the Office of Combination Products 

(OCP), and the Office of Inspections and 

Investigations (OII), is issuing this draft 

guidance to provide recommendations 

to industry on the use of artificial 

intelligence (AI) to produce information 

or data intended to support regulatory 

decision-making regarding the safety, 

effectiveness, or quality for drug and 

biological products. 

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. 

Submit electronic or written comments 

on the proposed collection of 

information in the draft guidance by 

April 7, 2025. 

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. 


ddrumheller on DSK120RN23PROD with NOTICES1
1158 Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 

FDA–2024–D–4689 for ‘‘Considerations 

for the Use of Artificial Intelligence To 

Support Regulatory Decision-Making for 

Drug and Biological Products; Guidance 

for Industry.’’ 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 draft guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, 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 draft guidance may be sent. 

See the SUPPLEMENTARY INFORMATION

section for information on electronic 

access to the draft guidance. 

FOR FURTHER INFORMATION CONTACT: Tala 

Fakhouri, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 6330, Silver Spring, 

MD 20993–0002, 301–837–7407, 

Tala.Fakhouri@fda.hhs.gov; James 

Myers, Center for Biologics Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 71, Rm. 7301, Silver Spring, 

MD 20993–0002, 240–402–7911, 

James.Myers@fda.hhs.gov; or Sonja 

Fulmer, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 5530, Silver Spring, 

MD 20993–0002, 240–402–5979, 

Sonja.Fulmer@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance entitled 

‘‘Considerations for the Use of Artificial 

Intelligence To Support Regulatory 

Decision-Making for Drug and 

Biological Products.’’ This draft 

guidance, when finalized, will provide 

recommendations to industry on the use 

of AI to produce information or data 

intended to support regulatory decisionmaking regarding safety, effectiveness, 

or quality for drugs. Specifically, this 

guidance proposes a risk-based 

credibility assessment framework that 

may be used for establishing and 

evaluating the credibility of an AI model 

for a particular context of use (COU). 

For the purposes of this guidance, 

credibility refers to trust, established 

through the collection of credibility 

evidence, in the performance of an AI 

model for a particular COU. Credibility 

evidence is any evidence that could 

support the credibility of an AI model 

output for a specific COU. The COU 

defines the specific role and scope of 

the AI model used to address a question 

of interest. This guidance does not 

endorse the use of any specific AI 

approach or technique. 

This draft guidance discusses the use 

of AI models in the nonclinical, clinical, 

postmarketing, and manufacturing 

phases of the drug product life cycle, 

where the specific use of the AI model 

is to produce information or data to 

support regulatory decision-making 

regarding safety, effectiveness, or 

quality for drugs. This draft guidance 

does not address the use of AI models: 

(1) in drug discovery or (2) when used 

for operational efficiencies (e.g., internal 

workflows, resource allocation, drafting/ 

writing a regulatory submission) that do 

not impact patient safety, drug quality, 

or the reliability of results from a 

nonclinical or clinical study. We 

encourage sponsors to engage with FDA 

early if they are uncertain about 

whether or not their use of AI is within 

the scope of this guidance. 

The Agency recognizes that the use of 

AI in drug development is broad and 

rapidly evolving. This draft guidance, 

when finalized, is expected to help 

ensure that AI models used to support 

regulatory decision-making are 

sufficiently credible for the COU. The 

risk-based credibility assessment 

framework proposed in this draft 

guidance is intended to help sponsors 

and other interested parties plan, gather, 

organize, and document information to 

establish the credibility of AI model 

outputs. As described in this guidance, 

the proposed recommendations, 

considerations, and assessment 

activities (e.g., the level of oversight, the 

stringency of the credibility assessments 

and the performance acceptance criteria, 

the risk mitigation strategy, and the 

amount of documentation and detail 

associated with AI use) that can be used 

to establish model credibility will 

generally be tailored to the specific COU 

and will depend on model risk. 

This draft guidance also describes 

different options by which industry may 

engage with the Agency on issues 

related to AI model development. The 

draft guidance emphasizes the 

importance of early engagement with 

the Agency to help: (1) set expectations 

regarding the appropriate credibility 

assessment activities for the proposed 

model based on model risk and COU 

and (2) identify potential challenges and 

how such challenges may be addressed. 

The Agency recognizes, however, that 

certain uses of AI occur outside of the 

product development and marketing 

application processes with established 

meeting options. Specifically, in the 

context of postmarketing 

pharmacovigilance, certain 

documentation (e.g., processes and 

procedures) is not generally submitted 

to the Agency but is maintained 

according to the sponsor’s standard 

operating procedures and made 

available to the Agency upon request 

(e.g., during an inspection). In such 

cases, sponsors may choose to complete 

all the steps outlined in the draft 

guidance without seeking early 

engagement with the Agency. Sponsors 

remain responsible for compliance with 

statutory and regulatory requirements, 


ddrumheller on DSK120RN23PROD with NOTICES1
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