Monoclonal Antibodies: Streamlined Nonclinical Safety Studies; Draft Guidance for Industry; Availability

<NOTICE> DEPARTMENT OF HEALTH AND HUMAN SERVICES <SUBAGY>Food and Drug Administration</SUBAGY> <DEPDOC>[Docket No. FDA-2025-D-4634]</DEPDOC> <SUBJECT>Monoclonal Antibodies: Streamlined Nonclinical Safety Studies; Draft Guidance for Industry; Availability</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Food and Drug Administration, HHS. <HD SOURCE="HED">ACTION:</HD> Notice of availability. <SUM> <HD SOURCE="HED">SUMMARY:</HD> The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Monoclonal Antibodies: Streamlined Nonclinical Safety Studies.” The draft guidance provides recommendations for streamlined approaches to assess long-term safety from monoclonal antibodies that recognize a single molecular target (referred to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. </SUM> <DATES> <HD SOURCE="HED">DATES:</HD> Submit either electronic or written comments on the draft guidance by February 2, 2026 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance. </DATES> <HD SOURCE="HED">ADDRESSES:</HD> You may submit comments on any guidance at any time as follows: <HD SOURCE="HD2">Electronic Submissions</HD> Submit electronic comments in the following way: • <E T="03">Federal eRulemaking Portal: https://www.regulations.gov.</E> Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to <E T="03">https://www.regulations.gov</E> 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 <E T="03">https://www.regulations.gov.</E> • 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”). <HD SOURCE="HD2">Written/Paper Submissions</HD> Submit written/paper submissions as follows: • <E T="03">Mail/Hand Delivery/Courier (for written/paper submissions):</E> 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.” <E T="03">Instructions:</E> 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 <E T="03">https://www.regulations.gov</E> 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 <E T="03">https://www.regulations.gov.</E> 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: <E T="03">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.</E> <E T="03">Docket:</E> For access to the docket to read background documents or the electronic and written/paper comments received, go to <E T="03">https://www.regulations.gov</E> 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 <E T="02">SUPPLEMENTARY INFORMATION</E> section for electronic access to the draft guidance document. <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> 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, <E T="03">haleh.saber@fda.hhs.gov.</E> </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> <HD SOURCE="HD1">I. Background</HD> 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. <HD SOURCE="HD1">II. Paperwork Reduction Act of 1995</HD> 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. <HD SOURCE="HD1">III. Electronic Access</HD> Persons with access to the internet may obtain the draft guidance at <E T="03"> https://www.regulations.gov, https://www.fda.gov/drugs/guidance- compliance-regulatory-information/guidances-drugs, </E> or <E T="03">https://www.fda.gov/regulatory-information/search-fda-guidance-documents.</E> <SIG> <NAME>Lowell M. Zeta,</NAME> Acting Deputy Commissioner for Policy, Legislation, and International Affairs. </SIG> </SUPLINF> <FRDOC>[FR Doc. 2025-21864 ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 10k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━