FDA issues draft guidance to reduce six-month nonhuman primate testing for monoclonal antibodies

On December 2, 2025, The US Food and Drug Administration issued draft guidance identifying specific types of monoclonal antibody products for which the agency believes six-month toxicity testing in non-human primates (NHPs) can be reduced or eliminated. According to the FDA, this move is part of a broader roadmap to modernize nonclinical drug evaluation and reduce animal testing by incorporating human-relevant methods and risk-based assessments.¹

“We are delivering on our roadmap commitment to eliminate animal testing requirements in drug evaluation and our promise to accelerate cures and meaningful treatments for Americans,” said FDA Commissioner Marty Makary, MD, MPH. “Modern science has given us far more effective and humane ways of evaluating drug safety than animal testing. This reform may reduce the amount of time it takes to bring a drug to market and lower research and development costs, which can translate into lower drug prices.¹”

Why this matters to veterinary professionals

According to the FDA release, NHPs (often macaques) have been widely used in preclinical safety packages for biologics. A typical monoclonal antibody program can involve more than 100 NHPs, with per-animal costs cited at roughly $50,000, a substantial ethical and financial burden for drug developers and research programs. Reducing or replacing these studies could lower development costs and reduce animal use.¹

Although the FDA’s guidance is framed within the context of monoclonal antibody development generally, with immediate relevance to human therapeutics, the agency also touches veterinary biologics and research practices. This means the guidance and its underlying science could have downstream implications for veterinary biologics, translational studies, and institutional animal care policies.¹

What the guidance recommends

The draft guidance outlines product types and a knowledge-based, risk-assessment approach under which six-month NHP toxicity testing may be unnecessary. Rather than overturning the principles of the existing framework, the draft guidance clarifies how those principles can be applied in a more targeted way.¹

Sponsors can use a knowledge-based, risk-assessment process to justify shorter or no six-month NHP studies for specified monoclonal antibody product types, provided there is sufficient mechanistic, toxicologic and human-relevant data to support safety decisions. In practice, the FDA encourages the use of alternative evidence streams such as computational toxicology, organoid or other in-vitro systems, and real-world human safety data as acceptable inputs to those product-specific risk assessments.^1-2

“By incorporating a knowledge-based risk assessment, we can make better informed decisions about drug safety while maintaining the rigorous safety standards that patients depend on,” said Richard Pazdur, MD, Director of the Center for Drug Evaluation and Research. “Risk assessments may leverage advanced methodologies. This evolution in our approach reflects both scientific progress and our responsibility to use the most effective tools for drug evaluation.¹”

What to expect next

The document is a draft guidance and the FDA is soliciting public input as it finalizes recommendations. Stakeholders, including academic researchers, industry sponsors, institutional animal care and use committees, and veterinary scientists, may want to review the draft and consider submitting comments.¹

The draft guidance can be viewed as part of a coordinated, cross-agency effort to validate and adopt “new approach methodologies” that reduce animal testing while preserving safety. The FDA convened an FDA-NIH workshop on July 7, 2025, that brought federal scientists, international regulators, industry, and academic experts together to discuss practical pathways for implementing organoids, computational models, organ-on-a-chip platforms, and other human-relevant tools in regulatory decision-making. That workshop, together with the draft guidance, appears to indicate institutional momentum with continued opportunities to comment, pilot nonanimal methods, and adapt internal study plans as the science and regulatory expectations evolve.^1,3

References

1. Food and Drug Administration. FDA releases draft guidance on reducing testing on non-human primates for monoclonal antibodies. FDA News Release. December 2, 2025. Accessed December 2, 2025. https://www.fda.gov/news-events/press-announcements/fda-releases-draft-guidance-reducing-testing-non-human-primates-monoclonal-antibodies.
2. Food and Drug Administration. S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals. Updated May 2012. Accessed December 2, 2025. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/s6r1-preclinical-safety-evaluation-biotechnology-derived-pharmaceuticals
3. FDA–NIH Workshop (Reducing Animal Testing)
   Food and Drug Administration. FDA–NIH Workshop: Reducing Animal Testing. July 7, 2025. Accessed December 2, 2025. https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/fda-nih-workshop-reducing-animal-testing-07072025