Experts say FDA’s plan to reduce animal testing is already seeing success at 1 year, but challenges remain
The US Food and Drug Administration (FDA) roadmap to reduce animal testing as a requirement for drug development has already made an impact after its first year, but the initiative faces future challenges in scaling and international harmonization, a group of experts wrote in a recent paper published in Stem Cell Research & Therapy.
Last year, the agency sought to reduce, refine, and replace reliance on animal testing requirements for monoclonal antibodies and other drugs. In an announcement, the agency said companies could instead use real-world safety data from other countries with comparable regulatory standards and new approach methodologies (NAMs) for their investigational new drug applications. The agency released a draft guidance on the topic in March 2026 that requires NAMs to have context of use (COU), human biological relevance, technical characterization, and be fit-for-purpose (RELATED: FDA drafts guidance on animal testing alternatives, Regulatory Focus 18 March 2026; FDA seeks to reduce animal testing requirements for mAbs, other drugs, Regulatory Focus 11 April 2025).
This requirement in the draft guidance makes NAMs “the conceptual default in regulatory decision‑making,” Yiting Lei, of the department of biomedical engineering at The Chinese University of Hong Kong, and colleagues wrote. “This subtle but profound shift legitimizes integrated, multi‑modal evidence packages as scientifically superior to single animal studies, rather than treating them as discretionary concessions to animal welfare.”
The initiative is “already saving lives—both human and animal,” according to the FDA’s progress report for the first year of the program. The report attributes that success to the elimination of requirements for six-month primate studies in the development of monoclonal antibodies, allowing use of weight-of-evidence approaches to replace animal requirements in carcinogenicity studies, the development of an artificial intelligence (AI) drug development tool, the creation of a database containing acceptable uses of alternative methods, efforts to harmonize international regulatory requirements, and the creation of the Innovative Science and Technology Approaches for New Drugs (ISTAND) program for accepting products that have used novel approaches to drug development.
Liu and colleagues said FDA’s report shows the initiative “represents a measurable and significant departure from long-standing regulatory reliance on animal models, advancing a human‑centric, technology‑integrated framework that reshapes the standards of evidence, efficiency, and ethical conduct in drug development.
“The institutional infrastructure, regulatory frameworks, and global partnerships established in the first year provide a resilient foundation for continued advancement, reducing uncertainty for industry, standardizing evaluation for regulators, and accelerating the translation of innovative technologies into routine practice,” they wrote.
Challenges, future directions
Liu and colleagues noted that several scientific, structural, and cultural challenges remain that may affect the program's long-term success. The first is that validated NAMs are not evenly distributed in toxicology endpoints, with limited options in areas such as developmental and reproductive toxicity, chronic carcinogenicity, and long‑term organ damage. Factors such as inconsistent data formats and a lack of consensus on governance structures and international data‑sharing agreements also limit the creation of an open‑access global toxicity data repository.
“This fragmented validation landscape forces continued animal use for critical safety assessments, constraining the overall scope of reduction,” the authors said. “Without a unified, interoperable database, redundant testing continues, and the full evidentiary value of existing studies remains underutilized, perpetuating inefficiency and unnecessary animal use.”
There are also cultural, financial, and technical barriers that hinder the adoption of NAMs and the reduction of animal testing. Researchers have relied on animal models for testing for decades, and may not have specialized NAM training. Specialized expertise is also needed for developing weight-of-evidence frameworks to evaluate diverse data streams. In addition, it may be difficult for small biotechnology companies and academic laboratories to invest in NAM validation and standardization because of the upfront costs.
“These challenges are not failures of policy implementation but reflections of the systemic nature of the transition; replacing a century‑old testing paradigm requires more than regulatory updates—it demands sustained investment in workforce expertise, technical infrastructure, and targeted incentives to ensure equitable participation across the innovation landscape,” the authors said.
Liu and colleagues said FDA needs to use “deliberate expansion and institutional deepening” to build on its success in the first year. They pointed to the streamlined testing frameworks for monoclonal antibodies as a potential scalable model that could be applied to other biologics, small molecules, gene therapies, cell therapies, and in other areas such as medical countermeasures. The agency should prioritize validation efforts for endpoints with less coverage, including developmental toxicity and chronic carcinogenicity, they said.
“Implementation of quantitative animal‑use tracking systems will strengthen accountability, enabling data‑driven priority adjustment and transparent public reporting of progress,” Liu and colleagues wrote. “Completion of the global toxicity data repository, supported by standardized data formats and binding international agreements, will eliminate redundant testing and strengthen the collective evidence base that supports regulatory decisions.”
Greater international harmonization is also needed, particularly as NAMs become more specialized to different contexts, they added. “Continued collaboration among global regulatory bodies will prevent divergent standards from eroding gains and ensure that animal reduction delivers consistent benefits across global markets,” Liu and colleagues said.
To address cultural barriers to adoption, the authors recommended an approach that uses broader cultural transformation with expanded training programs to integrate NAMs into academic and professional settings. “Targeted incentives, including research grants, priority review vouchers, and public‑private partnerships, will democratize access to NAM technologies, ensuring that small developers and academic researchers can contribute to and benefit from the transition without being priced out by upfront costs,” they said.
Success in reducing animal testing can be measured through the number of animals spared as well as in reducing clinical trial attrition, quicker access to therapies for patients, and the creation of a regulatory environment where “animal studies are truly the exception rather than the rule,” the authors said.
“In the years ahead, the FDA’s framework is poised to serve as a global model, demonstrating that scientific advancement, regulatory rigor, and ethical stewardship are not competing priorities but complementary pillars of a modern, effective drug development ecosystem,” Liu and colleagues concluded.
