Roadmap to Reduce Animal Testing – The EU Talks, the US Acts!

Published on April 30th, 2025

The European Union (EU) has long positioned itself as a global leader in ethical and innovative science, particularly regarding the reduction and eventual elimination of animal testing for chemical safety assessments. Prompted significantly by the European Citizens' Initiative "Save Cruelty-Free Cosmetics," which gathered over 1.2 million signatures from EU citizens, the European Commission (EC) embarked on the comprehensive task of developing a roadmap aimed at phasing out animal testing. This initiative has led to extensive consultations, multi-stakeholder roundtables, and numerous workshops aimed at refining the roadmap. While this process aims for thoroughness and discussion, the downside is a cautious progression characterized by lengthy deliberations and careful considerations. As a result, although discussions have been ongoing for years, finalization of the document is anticipated no earlier than early 2026 and concrete implementation are still vague, and somewhere in the future. The authors contributed to this discussion in this series [1]. This methodical approach, while commendable in principle, risks being outpaced by faster-moving counterparts globally and is at risk of reducing its effectiveness by not consulting with its counterparts in the USA.

Contrasting sharply with the EU’s protracted and consultative approach, the United States, through the Food and Drug Administration (FDA), on 10th of April under its new Commissioner Martin A. Makary [2] unveiled a clear, ambitious, and detailed roadmap aimed at rapidly reducing animal testing in preclinical safety assessments [3]. Notably, on the very same day that the FDA unveiled its new animal-testing reduction roadmap, EPA Administrator Lee Zeldin announced a revival of the Agency’s previous 30% reduction—and eventual phase-out—targets for vertebrate testing, recommitting the Agency to eliminating animal tests by 2035 [4]. The FDA’s strategy explicitly recognizes the significant limitations of animal models, underscored by compelling statistics indicating that more than 90% of drugs successful in animal tests ultimately fail in human trials due to unexpected efficacy and safety issues. This inefficiency has profound implications for public health, ethical considerations, and economic costs associated with drug development.

Central to the FDA's approach is the adoption of scientifically validated New Approach Methodologies (NAMs), including organoid / organ-on-a-chip technologies aka Microphysiological Systems (MPS) [5], computational modeling [6], and advanced human-based in vitro assays. These technologies not only promise enhanced predictability regarding human responses but also significantly mitigate the ethical dilemmas inherent in animal experimentation. Moreover, they offer considerable potential for cost savings, faster drug development timelines, and improved patient safety outcomes.

A critical advantage enjoyed by the FDA is its uniquely centralized regulatory role, effectively combining responsibilities that the EU distributes among several agencies, notably the European Chemicals Agency (ECHA), European Medicines Agency (EMA) and the European Food Safety Authority (EFSA). This consolidation within the FDA facilitates more streamlined decision-making processes, a unified regulatory framework, and accelerated integration of innovative scientific advancements into practical applications. Considerably stronger staffing and the combination with intramural research aids in-house competence and its global strategic role. Such efficiency contrasts with the EU’s fragmented structure, where coordination between different regulatory bodies on an EU level, not always optimal consultation with member states and an incoherent legal framework [7] inherently slow down the process. It is also evidenced in its internal lack of coordination between stated policy objectives of a sustainable chemical strategy, its delayed revision of its key chemicals legislation (Registration, Evaluation, Authorisation, and Restriction of Chemicals, REACH) and its stated goal to transition away from the use of animal testing whilst at the same time having the legal and regulatory potential to accommodate for more safety assessment using NAMs [8].

Furthermore, pharmaceutical safety plays a uniquely pivotal role in driving regulatory progress – the market size and time pressure in drug development make pharmaceutical industry the early adaptor of new methodologies. The role of the FDA in the US and beyond is underscored by its disproportionate influence in the global pharmaceutical market. The US, representing only approximately 4% of the world's population, commands about 53% of the global pharmaceutical market and an even more impressive 67% of the market for patented drugs [9]. This extraordinary market share not only places the FDA at the center of global pharmaceutical innovation but also positions it uniquely to drive substantial regulatory change. Consequently, developments and regulatory decisions made by the FDA inevitably resonate globally, influencing policies far beyond American borders and beyond the pharmaceutical sector. Given that FDA approvals influence over two-thirds of the global patented-drug market, these U.S. actions will ripple far beyond North America. Countries in the Global South—as importers of medicines and chemicals—will effectively be asked to align their safety assessments with NAM-based evidence, accelerating technology adoption but also posing capacity-building challenges. To ensure ethical practices do not become a Western-only concern, the implementation of the roadmap must emphasizes co-development of New Approach Methodologies (NAMs) with low- and middle-income countries. This includes shared training programs, technology transfer grants, and regional validation centers that respect local contexts while upholding global standards. Governments with limited budgets can leverage open-access guidance documents, public–private consortia, and tiered validation schemes. For instance, a ‘light-touch’ certification could recognize in silico models or low-cost organ-on-chip platforms, while international agencies provide technical assistance and pooled procurement for shared testing infrastructure. Initiating data sharing schemes between global north and global south partners would also lessen the regulatory and organizational burden, decrease the need for regulatory testing and increase mutual capacity building and monitoring of public health issues [10].

The FDA’s roadmap offers tangible, actionable steps designed for immediate impact. Key measures include a prompt reduction in animal testing durations, particularly for monoclonal antibody studies, the establishment of robust interagency collaborations (notably involving the NIH and ICCVAM), and clear incentives for industry and research organizations to adopt NAMs. Additionally, the roadmap delineates clear validation protocols, structured timelines, and concrete milestones, ensuring transparency and accountability in transitioning towards animal-free or animal-reduced testing methodologies.

The immediacy and practical orientation of the FDA's strategy clearly distinguish it from the EU’s cautious, deliberative process. While stakeholder engagement and thorough legislative scrutiny are undeniably essential components of any significant regulatory shift, the prolonged EU process poses substantial risks, particularly in terms of competitive disadvantages and delayed scientific advancements. As global momentum increasingly favors ethical, innovative methodologies that avoid or reduce animal usage, protracted debates and delayed implementation could compromise the EU's leadership and influence in setting global standards whilst compromising consumer safety and at the cost of animals’ lives.

Another pivotal component accelerating regulatory innovation in the US is the integration of artificial intelligence (AI). A recent publication co-authored by at the time FDA Commissioner Robert M. Califf emphasizes the critical role AI is already playing in regulatory science, highlighting its ability to significantly enhance regulatory efficiency and decision-making [11]. AI tools automate information retrieval and synthesis, perform systematic reviews efficiently, and provide more nuanced risk characterizations. Moreover, advanced AI models in predictive toxicology and drug safety hold potential to greatly reduce reliance on animal testing, offering more precise and scalable alternatives [12]. Commissioner Califf underscores the need for adaptable regulatory frameworks that can keep pace with AI advancements, advocating ongoing international dialogue and a trained workforce to maximize the technology's benefits while mitigating its risks.

Thus, the EU must recognize and learn from the urgency and effectiveness embodied by the FDA’s recent actions. Accelerating validation processes for NAMs [13-17], adopting explicit regulatory guidelines, and ensuring decisive implementation strategies could drastically expedite Europe's transition toward ethical and scientifically advanced chemical safety assessment methodologies. By reducing the complexity inherent in multi-agency interactions, a closer link to the validation body, and a more sustainable strategic development of NAMs as well as adopting a more streamlined decision-making framework, the EU could significantly enhance its regulatory agility and responsiveness. As part of the  NWA project “Accelerating the transition to animal-free NGRA: A transformative governance approach” [18] the SAFE consortium is using transformative governance [19] - the formal and informal rules, networks and decision-making processes at local, national and global scales—to deliberately steer deep, systemic change by integrating five complementary governance approaches:

1.          Integrative: aligning solutions across sectors, scales and issues;

2.          Inclusive: empowering traditionally marginalized actors and perspectives;

3.          Adaptive: embedding continuous learning, experimentation and feedback;

4.          Transdisciplinary: bridging diverse knowledge systems and disciplines;

5.          Anticipatory: applying precaution and foresight to manage uncertain futures.

By operationalizing these five approaches in concert and focusing on the underlying social, economic and normative drivers of a problem, transformative governance creates the enabling conditions for fundamental transitions—such as the move to animal-free safety assessment—across multiple levels. Using transformative governance as a blueprint would inform whether a governance framework would be able to steer towards technological, social and economic reorganization along new values, goals and paradigms – transformative change.

Complimenting this framework could be the policy arrangement approach (PAA) [20] which sees policy arrangements along four dimensions, 1.actors and their coalitions, 2. Resource division between these actors and the power imbalances this causes, 3. The formal and informal “rules of the game” in any given organisation and 4. The actor’s discourses - norms, values and problem definitions which shape actors’ problem definitions. These four dimensions are in constant dynamic interaction, such that a change in one will inexorably affect the others. Policy arrangements may be more or less unstable and subject to change depending on its constituent parts.

The convergence of mounting evidence on animal‐model failures, mature NAM toolboxes, mounting evidence of poor human predictivity and high attrition rates in animal studies has crystallized regulatory and public pressure against the use of animal-testing. This tension between a hitherto less responsive regulatory arrangement and the mounting pressure to change has created an incongruence in the policy arrangement on animal testing. This can be seen as gradual change in the discourse on safety assessment from one based on animal testing to one which embraces NAMs, effectively changing the problem- framing of how to adapt regulatory agencies.

The recent change in leadership changes at FDA (under Makary) and EPA (under Zeldin), together with bipartisan support earlier for the FDA Modernization Act 2.0, and the major investment of NIH into the Complement-ARIE program, have aligned actor coalitions and funding priorities (resources) on the USA side. This, along with a turbulent political climate domestically whereby the rules dimension can be seen as being a state of flux allows for a narrow opportunity for the EU to engage with the newly established regulatory leadership to exercise its mandate to provide a modern safety assessment system through the use of NAMs.

Most notably, the US National Institute of Health followed suite on 29 April announcing to prioritize human-based research technologies [21]. By developing and using cutting-edge alternative nonanimal research models, they align with the FDA’s recent initiative. NIH intends to establish the Office of Research Innovation, Validation, and Application (ORIVA). ORIVA shall expand funding and training in non-animal approaches and awareness of their value in translational success: “In addition, grant review staff will participate in mitigation training to address any possible bias towards animal studies and integrate experts on alternative methods into study sections. NIH will also publicly report on research spending annually to measure progress toward reduction of funding for animal studies and an increase in funding for human-based approaches.” This reorientation promises to leverage resources of NIH to make the FDA and EPA vision a reality [22].

Ultimately, the EU’s long-standing commitment to ethical scientific practice remains robust and clear. However, maintaining this position demands swift, decisive actions that go beyond discussions and consensus-building alone. Given the strategic importance of pharmaceutical safety and the disproportionate global influence of the US pharmaceutical market, it is imperative that the EU matches the proactive stance of the FDA. This is even more important while a global Human Exposome Project in the USA is emerging [23], which aims to transition toxicology from the ‘art of poisoning rats’ to the exposure side of disease [24]. A draft from the European parliament study [25] would see a potential counterpart with a European Human Exposome Initiative (EHEI). Adopting clear goals and coordination internally, and with its counterparts in the USA, the EU has a golden opportunity to transform its safety assessment systems. Doing so, will not only preserve the EU’s historical leadership role in ethical and innovative science but also align its policies more closely with contemporary scientific capabilities and societal obligations.

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[2] https://www.fda.gov/news-events/press-announcements/martin-makary-md-mph-sworn-fda-commissioner

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[18] Dutch Research Agenda (NWA) thematic programme Theme  Safety assessment via animal-free models: Accelerating the transition to animal-free NGRA: A transformative

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[19] Visseren-Hamakers, Ingrid J., and Marcel T. J. Kok, eds. 2022. Transforming Biodiversity Governance. Cambridge, United Kingdom ; New York, NY: Cambridge University Press.

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[21] https://www.nih.gov/news-events/news-releases/nih-prioritize-human-based-research-technologies

[22] Hartung T. The Turning Point: April 2025 Marks Historic Shift in US Animal Testing Policy, in press. Available at: https://www.altex.org/index.php/altex/article/view/2980/version/3042

[23] https://exposomemoonshot.org           

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[25] https://www.europarl.europa.eu/cmsdata/293792/04.1.%20EPRS_STOA_STUD_765.791_HumanExposomeResearch_DraftPanel.pdf?mc_cid=690f98bc9c

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