[Federal Register Volume 90, Number 4 (Tuesday, January 7, 2025)]
[Notices]
[Pages 1157-1159]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-31542]


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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Regulatory Decision-Making for Drug and Biological Products; Draft 
Guidance for Industry; Availability; Comment Request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.

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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the availability of a draft guidance for industry entitled 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Inspections and Investigations (OII), is issuing this draft guidance to 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DATES: Submit either electronic or written comments on the draft 
guidance by April 7, 2025 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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proposed collection of information in the draft guidance by April 7, 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.

[[Page 1158]]

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, [email protected]; 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, [email protected]; 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, [email protected].

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 decision-making 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,

[[Page 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-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, 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