U.S. regulators have announced a major change in the requirements for preclinical testing in drug development. In April, the Food and Drug Administration (FDA) stated it will begin phasing out mandatory in vivo testing for monoclonal antibodies and intends to extend this policy to other biologics and small molecules as more data become available.
Traditionally, preclinical safety and efficacy testing has relied on nonhuman in vivo models. With the new FDA announcement, drug developers are expected to adjust their strategies. According to U.S. regulators, this shift aims to improve patient safety, promote animal welfare, make pipelines for new treatments more efficient, reduce research and development costs, accelerate time to market, and establish new standards for ethical scientific discovery.
The policy allows immediate use of advanced human-relevant testing platforms—including computational models, lab-grown organoids, and organ-on-a-chip systems—to support investigational new drug (IND) applications. These alternatives, known as new approach methodologies (NAMs), may offer better predictions of toxicities and side effects than traditional animal tests. They also enable testing drugs on patient-specific cells, which could advance personalized medicine.
Additionally, the FDA’s policy encourages using real-world safety data from international sources such as electronic health records and patient registries for drug assessments. However, questions remain about which jurisdictions’ data will be accepted and how applications will be managed across regions.
While there is optimism about faster and more ethical drug development through these changes, experts caution that careful validation is needed to ensure continued patient safety and reliable data during the transition.
Public support appears strong: a 2024 survey of over 2,000 U.S. adults found that more than 85% favor moving away from animal testing toward modern methods. Congress previously supported this direction with a 2022 act authorizing validated non-animal alternatives in FDA applications.
However, current NAMs still face significant limitations. For example, no validated in vitro assays exist for certain neurological assessments required by regulatory guidance documents like ICH S7A; established techniques such as functional observational batteries cannot yet be replicated outside live animal studies. While some computational approaches can assess cardiovascular toxicity in silico, neurotoxicity remains challenging without live models.
General toxicology studies often rely on physical examination of tissue samples—a process not easily replaced by current technologies. Experts note that combining various assessment methods provides a comprehensive view of toxicity but achieving similar rigor without animal tests remains uncertain.
Another challenge is validating NAMs themselves; protocols lack standardization across advanced computational models or organ-on-a-chip systems (OOCs), raising reproducibility concerns. Regulatory plans emphasize multisite validation studies comparing NAMs directly with animal results—an especially complex task when evaluating chronic toxicity or immune-related effects.
Internationally, adoption varies: while the FDA moves forward with alternatives to animal tests for drugs such as monoclonal antibodies (mAbs), agencies like the European Medicines Agency continue requiring animal data except in cosmetics regulation; China’s NMPA and Japan’s PMDA maintain similar mandates for mAbs and all IND submissions. This lack of harmonization may require companies seeking global approvals to conduct additional studies meeting each region's standards.
Industry readiness presents further hurdles—adopting NAMs involves cultural changes within organizations plus investment in technology platforms like OOCs that have yet to see widespread use due partly to cost concerns and uncertainty around regulatory acceptance. Some laboratory partners may also lack experience operating these systems or interpreting their outputs; extra diligence is recommended when selecting collaborators.
There are also issues regarding training: although the FDA launched an OOC pilot program this year aimed at assessing readiness for wider adoption of these technologies among regulators won’t begin until 2026.
According to implementation plans outlined by the FDA's pilot program on NAMs adoption:
- The agency will monitor how well NAMs predict clinical outcomes,
- Track reductions in animal use hours—with a goal of halving them by 2027,
- And compare timelines between successful IND submissions using NAMs versus traditional approaches.
The impact on trust within the scientific community—and whether setbacks might slow progress—remains uncertain.
Phasing out animal assays requires fundamental changes throughout preclinical research processes but could eventually yield higher quality medicines at lower costs while maintaining patient safety levels seen today if challenges are addressed collaboratively across industry sectors.
"Early investment in human-relevant models, robust validation and regulatory engagement will be critical to maintaining a competitive advantage and ensuring access to global markets," one expert stated. "Success will also depend on adapting to the challenges ahead and building the expertise to interpret and act on new data sources." They added: "Those who can achieve this will help shape a new regulatory reality."
