FDA Publishes New Draft Guidance on Reducing Animal Testing in Nonclinical Safety Studies
The U.S. Food and Drug Administration (FDA) on Dec. 2, 2025, issued its draft guidance on Monoclonal Antibodies: Streamlined Nonclinical Safety Studies Guidance for Industry, the agency's most recent step in reducing animal testing in nonclinical settings.
As Holland & Knight previously reported, the FDA Modernization Act 2.0, passed in late 2022, authorized the use of nonanimal alternatives for investigational new drug applications, paving the way for this transition. FDA also held a public workshop in July 2025 focusing on strategies to reduce animal testing. In addition, the reauthorization of the Over-the-Counter Monograph User Fee Act (OMUFA) recently enacted by Congress requires FDA to consider certain types of nonclinical tests or any other alternative to animal testing that the FDA secretary deems appropriate in the consideration of certain drugs intended for topical administration.
Under the FDA Modernization Act 2.0, the agency opened the door for sponsors to incorporate new approach methodologies (NAMs) in drug development. The draft guidance aims to assist drug sponsors in implementing these methods under "nonclinical safety assessments of monoclonal antibodies that recognize a single molecular target" and "facilitate drug development for monospecific antibodies while avoiding unnecessary use of animals," with the goal of reducing animal testing and facilitating "greater efficiencies in product development."
FDA released its "road map" outlining its strategy to reduce animal testing in April 2025. The road map described a plan to replace animal testing in preclinical safety studies with scientifically validated NAMs. The draft guidance marks the first step in implementing this plan, specifically for monoclonal antibodies, and reflects FDA's belief that "six-month nonhuman primate toxicity testing can be eliminated or reduced."
In addition, the draft guidance outlines two overarching recommendations: the first on "Chronic Toxicology Studies" and the second on "Other Considerations for Nonclinical Safety Studies." Under Chronic Toxicology Studies, FDA advises that studies exceeding three months in nonrodent species are generally unwarranted for evaluating toxicities from chronic administration of monospecific antibodies when such data is supplemented with a "weight-of-evidence" (WoE) risk assessment. This assessment may include mechanisms of action and pharmacology data generated with the monospecific antibody, a literature-based assessment of potential toxicities associated with the molecular target and other nonclinical data as scientifically justified such as NAMs, transgenic models or data using surrogates.
Under Other Considerations for Nonclinical Safety Studies, FDA emphasizes that animal toxicology studies should use pharmacologically relevant species and that assessment of reproductive and developmental toxicities should begin with a WoE risk assessment. Any safety concerns identified through a WoE risk assessment can be addressed in clinical studies of the investigational products.
Conclusion
FDA's draft guidance represents the next step in the agency's efforts to "modernize" nonclinical drug evaluation. However, questions remain about whether or how FDA will implement the guidance. FDA encourages sponsors to discuss their nonclinical programs with the agency and says it will evaluate whether the sponsor's approach adequately addresses product safety and meets nonclinical regulatory requirements.
Holland & Knight attorneys will continue to monitor changes at FDA to help companies stay up to date on regulatory developments. If you have questions, please contact one of the authors or another member of Holland & Knight's Healthcare Team.
Information contained in this alert is for the general education and knowledge of our readers. It is not designed to be, and should not be used as, the sole source of information when analyzing and resolving a legal problem, and it should not be substituted for legal advice, which relies on a specific factual analysis. Moreover, the laws of each jurisdiction are different and are constantly changing. This information is not intended to create, and receipt of it does not constitute, an attorney-client relationship. If you have specific questions regarding a particular fact situation, we urge you to consult the authors of this publication, your Holland & Knight representative or other competent legal counsel.