New Draft Guidance Highlights FDA Push Toward Human-Relevant Safety Models

On Dec. 2, 2025, FDA published new draft guidance that identifies monoclonal antibody (mAb) product types for which six-month, non-human primate toxicity studies may no longer be necessary. The move signals a shift in how regulators evaluate therapeutic safety and reflects a broader effort to modernize nonclinical assessment while reducing reliance on animal models (1).

According to an FDA press release, the draft guidance marks the agency’s continued progress in updating its approach to drug development, where alternative methodologies are beginning to play a larger role (1). In recent years, interest has grown across biopharmaceutical and pharmaceutical sectors in tools that can generate more human-relevant safety insights earlier in development. These evolving tools include organoid systems derived from human cells, real-world safety information from clinical settings, and computational toxicology models (1). Their increasing adoption, if ultimately reflected in formal policy, may influence how companies plan preclinical programs and allocate research resources (2).

“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, in the press release (1). “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.”

Why is FDA shifting its approach to mAb safety testing?

mAb development has traditionally required extensive nonclinical work, often involving large numbers of non-human primates such as macaques, FDA noted in the release, stating that a typical program may include more than 100 animals and can reach an estimated cost of $50,000 per animal (1). Many products that pass animal studies, however, ultimately fail to secure approval due to safety or efficacy issues that emerge only in human testing.

According to the agency, this discrepancy has underscored the limitations of traditional models and prompted calls for regulatory pathways that rely more heavily on human-centered scientific evidence. The new draft guidance outlines how risk-based strategies may replace, reduce, or refine animal testing expectations for certain product categories, FDA emphasized (1).

“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 FDA’s Center for Drug Evaluation and Research, in the release (1) (see infographic). “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.”

What broader implications may this guidance have for regulatory science and industry practice?

The draft guidance is linked to a wider roadmap that emphasizes new approach methodologies. FDA stated that the guidance’s implementation will involve coordination among federal bodies such as the National Institutes of Health and the Interagency Coordinating Committee on the Validation of Alternative Methods, as well as engagement with international regulatory partners (1). These collaborations are expected to help validate the scientific basis of non-animal approaches and guide future global regulatory alignment.

When finalized, the draft document will supplement the agency’s existing guidance on the nonclinical safety evaluation of biotechnology-derived pharmaceuticals, last updated in 2012 (3). The updated framework continues to support product-specific evaluation and flexible study designs that match the scientific needs of individual therapeutics, according to FDA (1).

The agency also convened a public workshop in July 2025, where sponsors, researchers, and patient advocates discussed strategies for reducing animal use while maintaining safety standards. Input from this workshop is said to be shaping the direction of emerging policy, and the finalized version of this new draft guidance may further influence how companies design early-stage development plans, forecast timelines, and consider investment in alternative testing platforms (1,4).

References

1. FDA. FDA Releases Draft Guidance on Reducing Testing on Non-Human Primates for Monoclonal Antibodies. Press Release. Dec. 2, 2025.
2. Luce, E.; Duclos-Vallee, J. C. Stem Cells and Organoids: A Paradigm Shift in Preclinical Models Toward Personalized Medicine. Pharmaceuticals (Basel) 2025, 18 (7), 992. DOI: 10.3390/ph18070992
3. FDA. Guidance for Industry, S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (CDER, May 2012).
4. FDA. FDA-NIH Workshop: Reducing Animal Testing. FDA.gov. July 7, 2025.