From Roadmap to Reality: Validating NAMs for FDA's Plan to Phase Out Animal Testing
By Yiguang Zhu | May 15th, 2025
The U.S. Food and Drug Administration (FDA) recently announced a groundbreaking plan to phase out its requirement for animal testing in the development of monoclonal antibody (mAb) therapies and other drugs. This move, outlined in its new roadmap, represents a paradigm shift from conventional animal experiments toward more effective, human-relevant New Approach Methodologies (NAMs)—a collective term for in vitro (e.g. cell assays, organoids), in silico (computational), and other non-animal approaches.
FDA’s announcement does not yet eliminate animal testing requirements outright but lays the groundwork for such a future. The agency will start by encouraging the use of NAMs data in Investigational New Drug (IND) applications, either with or as a replacement for animal data. To incentivize this, the agency will offer streamlined reviews for applications that include scientifically validated NAMs. Additionally, the agency will leverage pre-existing human safety data from international studies when appropriate. Over time, the roadmap envisions making animal studies the exception rather than the rule in preclinical drug development.
This is a welcome move. For decades, drug safety and efficacy testing relied heavily on animal experiments. Studies indicate that over 90% of drugs that appear safe and effective in animals fail during human clinical trials—often due to lack of efficacy or unforeseen toxicity. This high attrition rate represents not only a regulatory flaw but also a significant financial burden. The average development cost of mAbs is estimated at $650-$750 million. As Dr. Paul Locke said in an interview with CNN, “It’s really nice to see FDA make this step in the right direction... [it] will improve public health and get us much better medicines much more quickly with using fewer resources.” Dr. Locke, an expert in public health and policy, has long advocated for moving beyond animal models, especially when NAMs technology can offer human-specific insights.
From a public health perspective, using NAMs instead of animal testing offers multiple benefits: improved predictive accuracy, faster timelines, and lower R&D costs. From an ethical perspective, this move can save countless animals from unnecessary suffering. This progress is backed by a growing body of scientific evidence, the bipartisan support of the FDA Modernization Act 2.0, and a robust coalition of stakeholders ranging from NAMs developers to major pharmaceutical companies, to scientific communities and advocacy groups.
Yet, as much as we celebrate this shift, real progress hinges on establishing a robust validation framework to ensure the regulatory acceptance of these new technologies. This necessity brings us to the challenge and opportunity of validation.
NAMs validation involves demonstrating that these new methods reliably predict human response at least as effectively as—and ideally more effectively than—conventional animal methods. To address this challenge, FDA plans to collaborate with federal agencies including the National Institutes of Health and the Department of Veterans Affairs through the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). These collaborations are vital for standardizing validation protocols, reducing redundant efforts across agencies, establishing transparent data-sharing frameworks, and developing clear implementation guidance for NAMs. Such concerted efforts will build confidence among end-users and the public, thereby supporting the integration of NAMs into industrial and regulatory practice.
However, several key issues arising from the current NAM validation practices of federal agencies must be addressed. For instance, the accuracy of many computational models, such as physiologically-based pharmacokinetic (PBPK) simulations that show how a drug travels through and is processed by the body and AI tools that predict potential toxicity, relies heavily on high-quality, compatible human-derived data that highlights the need for continued investment in data management infrastructure. Furthermore, current validation strategies often require defining a narrow "context-of-use" early in the process. While intended to guide NAMs development and ensure scientific relevance, this approach may inadvertently limit the full potential of versatile platforms like organ-on-a-chip systems. Overly restricting the scope based on predefined contexts may hinder the broader acceptance and application of powerful NAMs.
To avoid that pitfall, NAM validation must demonstrate two things: first, that the NAM’s engineering is robust enough to deliver reliable, reproducible results in routine practice; and second, that its readout more faithfully reflects human biology and predicts clinical outcomes than legacy animal tests. Meeting these benchmarks will build the confidence needed for broader regulatory and industrial adoption. Existing programs like FDA’s Drug Development Tool (DDT) qualification programs, including the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program, serve as initial explorations in this direction. Yet, the slow pace is concerning. As of April 2025, the ISTAND pilot lists only eight NAMs accepted into the program. Of these, just one has advanced to the Qualification Plan phase (the second stage of the process). Further, only one tissue chip technology is listed, and it still resides in the initial Letter of Intent phase. This slow progress highlights the immense challenge and urgent need for accelerated development and wider implementation.
To make this transition meaningful and lasting, FDA must ensure that NAMs developers, policymakers, and end-users are aligned on what counts as "validated" and under what conditions validation is enough to justify replacing animal data. Clear guidance documents, transparent regulatory acceptance requirements, and proactive engagement with stakeholders are essential to building confidence in this new paradigm.
This is the FDA's moment to lead, and the path forward requires continued investment, interdisciplinary collaboration, and a scientifically rigorous, transparent validation framework. Ultimately, this is not only about transforming testing methodologies, but also an opportunity to foster a future that values ethics, efficiency, and enhanced human health outcomes.
The views expressed do not necessarily reflect the official policy or position of Johns Hopkins University or Johns Hopkins Bloomberg School of Public Health.
