FDA Releases Draft Guidance on Phasing Out Animal Testing

In April 2025, the FDA released its Roadmap to Reducing Animal Testing in Preclinical Safety Studies. The initial guidance from the Agency noted its initial focus would be on monoclonal antibodies (mAbs), but while this gained considerable interest from sponsors, as examined in a previous blog, limited actionable guidance for product development was provided.  

This week, the FDA released a draft guidance, “Monoclonal Antibodies: Streamlined Nonclinical Safety Studies,” as the next step in the eventual phasing out of animal models for preclinical programs, providing key inputs sponsors should consider in their product development.  

The draft guidance, which has a 60-day comment period, once finalized, will supplement several other FDA guidance documents, including S6(R1), S11, S5(R3), and ICH M3(R2). The FDA states the guidance at this stage is specific to monospecific antibodies, noting the guidance does not apply to multispecific antibodies, conjugated antibodies, and antibody constructs. As the FDA continues to collect additional data and examples from the reduction of animal studies, it will be interesting to see how this guidance is expanded to these excluded types of monoclonal antibodies or other product modalities.  

The actionable content of the draft guidance is broken into considerations for chronic toxicology studies and considerations for other nonclinical safety studies. Under ICH M3(R2) for clinical studies between two weeks and six months, the expectation was a preclinical study of the same duration. For a six-month clinical study, a six-month preclinical study was expected. In the draft guidance, FDA states based on data from previous monoclonal antibody programs, for clinical studies longer than three months, a preclinical study of three months, with supportive weight-of-evidence, is sufficient. This means in most situations the longest preclinical study duration for a monospecific mAb is 3 months. This would represent a significant decrease in the duration of the potential Good Laboratory Practice (GLP) toxicology studies to support first-in-human clinical trials whose dosing duration is greater than 3 months.  

Additionally, the FDA further details examples where even the three-month toxicology study may not be warranted due to properties of the monoclonal antibody, including formation of neutralizing or clearing anti-drug antibodies, requirement of severe immune suppression, lack of binding to any nonclinical species, or when there is substantial previous animal data against the specific molecular target, where data have not been predictive. It is noteworthy; this new approach may put additional emphasis and attention on the sponsor’s chemistry, manufacturing, and controls (CMC) timelines to align with the shortened preclinical timelines. 

For sponsors developing monospecific mAb, an FDA Meeting question to gain FDA feedback on the design of in vivo animal studies in the nonclinical program, following the principles outlined in this draft guidance, should be asked. Sponsors whose programs meet these criteria will want to get agreement with the Agency before removing the “standard” toxicology study from their program. The guidance also details how the weight-of-evidence argument may impact the need for additional studies for pediatric studies or the need for reproductive and developmental toxicity studies. The impact of the weight-of-evidence argument highlights a new consideration for sponsors to address during an FDA meeting, for example, a Pre-IND meeting, to align with the Agency. Sponsors may also want to consider pursuing a Type D or an INTERACT meeting with the FDA early on to align their product development planning.  

The draft guidance provides unique opportunities for sponsors developing monoclonal antibody products, yet it also introduces new considerations that must be considered at the Pre-IND stage. Sponsors of monospecific mAbs programs should engage the FDA to ensure alignment and best set the stage for their overall program development.  

We are available to discuss our experience and offer strategic advice to best de-risk your development program and position you for success. Contact us.