FDA announces plan to phase out requirement for animal testing for monoclonal antibodies and other drugs
2025-04-12
The US Food and Drug Administration has published a Roadmap to Reducing Animal Testing in Preclinical Safety Studies. The roadmap describes how FDA plans to reduce animal testing in preclinical safety studies with new approach methodologies (NAMs) such as organ-on-a-chip systems, computational modeling, and advanced in vitro assays. FDA aims to accelerate the validation and adoption of these methods in collaboration with federal agencies like National Institutes of Health (NIH) and Department of Veteran Affairs (VA) through ICCVAM, the Interagency Coordinating Committee on the Validation of Alternative Methods.
The initial focus of the program for reducing animal use will be preclinical safety testing of monoclonal antibodies (mAbs), and then will expand to include other biological molecules, new chemical entities and medical countermeasures. Current FDA requirements for mAbs mandate repeat-dose toxicity studies, pharmacokinetics and safety pharmacology, and involve the use of non-human primates. Testing human mAbs in animals is problematic as animals often produce antibodies against human mAbs, a response that is not predictive of human immunogenicity. Also, some human safety risks may not be detected in animal tests – an example was the mAB TGN1412, which caused a life-threatening cytokine release syndrome in human volunteers despite appearing safe in non-human primate studies.
The FDA’s 3-year implementation plan includes
- exploring pre-existing international data on human use in countries where the compound has been approved;
- encouraging sponsors to submit NAM data in parallel with animal data to build a repository of experience;
- developing an open-access repository with a collection of international drug toxicity data from animals and humans;
- reducing the routine 6-month primate toxicology testing for mAbs that show no concern in 1-month studies plus NAM tests to three months;
- reducing animal toxicity testing timeframes for other drug categories
- tracking and quantifying changes in toxicity testing costs and timelines
In the longer term, FDA aims to make animal studies the exception rather than the norm for pre-clinical safety/toxicity testing for mAbs safety, and eventually all drugs/therapeutics
