Notice2025-21864
Monoclonal Antibodies: Streamlined Nonclinical Safety Studies; Draft Guidance for Industry; Availability
Primary source
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Published
December 3, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Monoclonal Antibodies: Streamlined Nonclinical Safety Studies." The draft guidance provides recommendations for streamlined approaches to assess long-term safety from monoclonal antibodies that recognize a single molecular target (referred to as monospecific antibodies); describes when general toxicology studies are not warranted or may be limited to a short-term study; and addresses reproductive, developmental, and juvenile toxicity assessments. When finalized, the guidance is intended to assist sponsors in avoiding unnecessary use of animals, particularly non-human primates (NHPs), in furtherance of the 3R principles of reducing, refining, and replacing the use of animal testing.
Full Text
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<title>Federal Register, Volume 90 Issue 230 (Wednesday, December 3, 2025)</title>
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[Federal Register Volume 90, Number 230 (Wednesday, December 3, 2025)]
[Notices]
[Pages 55742-55744]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-21864]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-D-4634]
Monoclonal Antibodies: Streamlined Nonclinical Safety Studies;
Draft Guidance for Industry; Availability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 or Agency) is announcing
the availability of a draft guidance for industry entitled ``Monoclonal
Antibodies: Streamlined Nonclinical Safety Studies.'' The draft
guidance provides recommendations for streamlined approaches to assess
long-term safety from monoclonal antibodies that recognize a single
molecular target (referred to as monospecific antibodies); describes
when general toxicology studies are not warranted or may be limited to
a short-term study; and addresses reproductive, developmental, and
juvenile toxicity assessments. When finalized, the guidance is intended
to assist sponsors in avoiding unnecessary use of animals, particularly
non-human primates (NHPs), in furtherance of the 3R principles of
reducing, refining, and replacing the use of animal testing.
DATES: Submit either electronic or written comments on the draft
guidance by February 2, 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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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
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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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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:
<bullet> 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.
<bullet> 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-4634 for ``Monoclonal Antibodies: Streamlined Nonclinical
Safety Studies.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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
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: Haleh Saber, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 2324, Silver Spring, MD 20993-0002, 301-
796-1410, <a href="/cdn-cgi/l/email-protection#4129202d24296f3220232433012725206f2929326f262e37"><span class="__cf_email__" data-cfemail="96fef7faf3feb8e5f7f4f3e4d6f0f2f7b8fefee5b8f1f9e0">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Monoclonal Antibodies: Streamlined Nonclinical Safety
Studies.'' This guidance, when finalized, is intended to assist
sponsors in implementing streamlined approaches for nonclinical safety
assessments of monoclonal antibodies that recognize a single molecular
target (monospecific antibodies). Most antibodies are pharmacologically
active in NHPs only and thus animal toxicology studies would include
testing in NHPs. This draft guidance is intended to facilitate drug
development for monospecific antibodies while avoiding unnecessary use
of animals, particularly NHPs, consistent with the 3R principles of
reducing, refining, and replacing animal testing. This draft guidance
provides recommendations for streamlined approaches to assess long-term
safety from monospecific antibodies; describes when general toxicology
studies are not warranted or may be limited to a short-term study; and
addresses reproductive, developmental, and juvenile toxicity
assessments. The draft guidance provides examples of when a 3-month or
longer animal toxicology study may not be warranted or when certain
safety studies could be replaced with a weight-of-evidence (WoE) risk
assessment and makes clear that a WoE risk assessment may include new
approach methodologies.
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 ``Monoclonal
Antibodies: Streamlined Nonclinical Safety Studies.'' 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 new 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 relating to the submission of nonclinical safety
studies in new drug applications have been approved under OMB control
number 0910-0001. The collections of information in 21 CFR part 312
relating to the submission of nonclinical safety studies in
investigational new drug applications have been approved under OMB
control number 0910-0014. The collections of information in section
351(a) of the PHS Act and 21 CFR part 601 relating to the submission of
nonclinical safety studies in biologics license applications have been
approved under OMB control number 0910-0338.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <a href="https://www.regulations.gov">https://www.regulations.gov</a>, https://www.fda.gov/drugs/guidance-
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compliance-regulatory-information/guidances-drugs, or <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>.
Lowell M. Zeta,
Acting Deputy Commissioner for Policy, Legislation, and International
Affairs.
[FR Doc. 2025-21864 Filed 12-2-25; 8:45 am]
BILLING CODE 4164-01-P
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