[Federal Register Volume 91, Number 53 (Thursday, March 19, 2026)]
[Notices]
[Pages 13313-13314]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-05390]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2025-D-6131]


General Considerations for the Use of New Approach Methodologies 
in Drug Development; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing the availability of a draft guidance for industry entitled 
``General Considerations for the Use of New Approach Methodologies in 
Drug Development.'' The purpose of this draft guidance is to provide 
drug developers with a validation framework and general recommendations 
for using new approach methodologies (NAMs) in drug development. 
Although animal toxicity studies have proved to be a critical method to 
identify potential risks to human health, finding ways to improve human 
relevance while reducing the use of animals by developing reliable NAMs 
furthers an important Center for Drug Evaluation and Research (CDER) 
priority to move away from reliance on animal testing. The 
recommendations in this draft guidance are intended to highlight 
scientific principles of study design and reporting that can be applied 
broadly and flexibly in the validation of NAMs used in drug 
development. This draft guidance is not intended to address specific 
NAMs and does not address the use of NAMs in drug discovery; rather, it 
encourages the use of NAMs in regulatory submissions, especially when 
they improve the predictivity of nonclinical studies for increased 
safety in clinical trials.

DATES: Submit either electronic or written comments on the draft 
guidance by May 18, 2026 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2025-D-6131 for ``General Considerations for the Use of New 
Approach Methodologies.'' 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

[[Page 13314]]

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 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Nakissa Sadrieh, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Avenue, Bldg. 22, Rm. 6163, Silver Spring, MD 20993, 240-402-
2194.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``General Considerations for the Use of New Approach 
Methodologies.'' This guidance describes CDER's general recommendations 
to consider for validating NAMs when nonclinical NAMs data are provided 
in support of a drug application or regarding an order issued under 
section 505G of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for 
an OTC monograph. This includes OTC monograph orders issued under 
section 505G of the FD&C Act for nonprescription drugs intended for 
topical administration. Among other things, this guidance is issued in 
compliance with the requirement that FDA issue a new draft guidance on 
nonclinical testing alternatives to animal testing for OTC monograph 
drugs intended for topical administration under section 505G(r)(2)(B).
    As part of the Consolidated Appropriations Act, 2023 (Pub. L. 117-
328), the Food and Drug Omnibus Reform Act provided increased clarity 
to stakeholders regarding the potential use of new approach 
methodologies to support nonclinical data packages in investigational 
new drug applications. Specifically, section 3209(a) of the 
Consolidated Appropriations Act, 2023 amended section 505(i) of the 
FD&C Act to clarify that nonclinical tests can be used to support 
proposed clinical testing. Section 3209(a) further amends the FD&C Act 
by defining ``nonclinical test'' as ``a test conducted in vitro, in 
silico, or in chemico, or a nonhuman in vivo test, that occurs before 
or during the clinical trial phase of the investigation of the safety 
and effectiveness of a drug'' and provides examples, including cell-
based assays, organ chips and microphysiological systems, computer 
modeling, other nonhuman or human biology-based test methods (such as 
bioprinting), and animal tests.\1\
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    \1\ Section 505(z) of the FD&C Act (21 U.S.C. 355(z)).
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    FDA's current regulatory framework permits and encourages the use 
of NAMs, as described in existing regulations and guidance. CDER has 
developed this guidance document to further encourage the submission of 
NAM data.
    This guidance, when finalized, will provide key considerations 
related to the validation of NAM data, to help ensure data quality and 
reliability and to support regulatory decision-making by CDER. The 
considerations provided in this draft guidance reflect recent 
developments in validation frameworks for NAMs. FDA's goal in issuing 
this draft guidance is to help facilitate the development and use of 
validated NAMs that accurately predict risks to human health, while 
also decreasing usage of animal testing. This draft guidance includes 
general validation considerations for industry, focusing on context of 
use, human biological relevance, technical characterization, and how to 
demonstrate that a NAM is fit-for-purpose. This guidance is intended to 
encourage the submission of NAMs and early engagement with drug review 
divisions. This guidance is not intended to address specific NAMs and 
does not address the use of NAMs in drug discovery.
    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 ``General 
Considerations for the Use of New Approach Methodologies in Drug 
Development.'' 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.
    As we develop final guidance on this topic, FDA will consider 
comments on costs or cost savings the guidance may generate, relevant 
for Executive Order 14192.

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 314 pertaining to the submission of new drug 
applications have been approved under OMB control number 0910-0001. The 
collections of information in 21 CFR part 312 pertaining to the 
investigational new drug applications have been approved under OMB 
control number 0910-0014. The collections of information in 21 CFR part 
601 pertaining to the submission of biologics license applications have 
been approved under OMB control number 0910-0338. The collections of 
information in 21 CFR 58 pertaining to good laboratory practice for 
nonclinical laboratory studies have been approved under OMB control 
number 0910-0119.

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/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-05390 Filed 3-18-26; 8:45 am]
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