FDA's plan to Phase Out Animal testing: Implications for Drug Development
In April 2025, the U.S. Food and Drug Administration (FDA) announced its intention to phase out animal testing requirements for monoclonal antibodies and other pharmaceuticals. While this milestone signals progress toward more ethical and innovative drug development approaches, its implications warrant careful examination.
Despite the FDA’s announcement, there remains a widespread misconception – particularly among organizations with limited drug development expertise – that animal testing is no longer necessary or can be significantly reduced to expedite clinical entry. Preclinical programs can be expensive, costing anywhere between $15M and $100M, so any opportunity to reduce costs and timelines is an attractive option.
However, nonclinical evaluations of safety, efficacy, and pharmacokinetics still rely on animal models, and a complete elimination of their use remains impractical in the short term.
The Current State of Non-Clinical Testing
While the pharmaceutical industry continues to pursue the Replacement, Reduction, and Refinement (3Rs) of animal use, existing nonclinical study frameworks remain largely unchanged. Several key considerations support this reality:
1. New Approach Methodologies (NAMs)
Although the term "NAMs" has gained prominence, many of these strategies—such as in-vitro assessments, organoids, organ-on-a-chip technologies, and AI-based in-silico modelling—have been explored for years. Despite their promise, most NAMs fail to fully replicate the complexity of in-vivo animal systems, and many lack sufficient validation, yielding low concordance when assessed with known toxicants. A notable example is zebrafish, once proposed as an alternative to mammalian models, yet rarely – if ever – featured in regulatory submissions.
2. Unchanged Regulatory Expectations
In a recent publication, one of Fortrea's non-clinical regulatory strategists, Prof. Paul Baldrick, examined the standard suite of non-clinical studies required for Phase 1 clinical entry. His findings underscore the enduring necessity of pharmacology, ADME, and toxicology studies – unchanged for over 35 years of drug development. Even within monoclonal antibody research, prior studies questioning the necessity of certain toxicology assessments in primates have failed to drive notable regulatory changes.
3. Limited Adoption of Alternative Methods
The FDA’s Modernization Act 2.0 (2022) introduced provisions for human-relevant nonclinical testing, including cell-based assays, microphysiological systems, bioprinted models, and computational approaches. However, there is little evidence of widespread adoption of these alternatives in recent regulatory submissions.
4. Regulatory Interpretation and Global Harmonisation
The news release does not appear to reflect substantive engagement with FDA’s pharmaceutical/toxicology assessors, who continue to request additional studies—even in instances where scientific justification suggests they are unnecessary. Additionally, since nonclinical guidelines are globally harmonized through the International Council for Harmonisation (ICH), any modifications to animal testing paradigms will take considerable time to implement. For reference, updating the carcinogenicity testing guideline to consider moving away from two-species testing took over 15 years, with minimal change to current practices.
The Road Ahead
Although efforts to reduce animal use in pharmaceutical development are ongoing, tangible regulatory shifts are likely to emerge gradually. The FDA’s recent announcement signals continued progress in refining nonclinical testing methodologies, yet widespread adoption of alternative approaches will depend on their rigorous validation and acceptance by global regulatory bodies.
Learn more: Fortrea Regulatory Strategy
References:
- FDA Announces Plan to Phase Out Animal Testing Requirement for Monoclonal Antibodies and Other Drugs | FDA
- The Staggering Cost of Drug Development: A Look at the Numbers – GreenField Chemical Inc.
- The 3Rs | NC3Rs
- Baldrick, P. (2025) Current non clinical testing paradigm to allow clinical entry for pharmaceutical drug candidates. Reg. Tox. Pharmacol. 159, 105809
- Baldrick, P. (2011) Safety evaluation of biological drugs: What are the toxicology studies in primates telling us? Reg. Tox. Pharmacol. 59, 227–236