The tide is turning as the U.S. Food and Drug Administration (FDA) gives the strongest signal to date that the future of preclinical safety assessment in the U.S. will rely increasingly on human-specific research as animal testing is phased out. Their mission is clear: ‘to improve drug safety and accelerate the evaluation process, while reducing animal experimentation, lowering research and development (R&D) costs, and ultimately, drug prices.’
In this article, I digest the recent announcement and outline the key reasons for my optimism regarding the proposed roadmap. My thoughts / insights are marked in italics.
Note: This article uses the terms human-specific and human-focused to refer to research that focuses on the use of human cells, human tissue, and / or human data. When referencing the FDA’s roadmap, the article also refers to new approach methodologies (NAMs). This term refers to a range of approaches, including computational models and cell-based assays, which may incorporate animal data (e.g computational modelling based on animal toxicity data).
The Announcement
On Thursday 10th April 2025 the FDA announced an ambitious plan in a bid to modernise the drug development process. In an accompanying 11-page roadmap, the agency outlined its three-year strategy aimed at replacing animal testing with more effective, human-specific methods. The programme will initially focus on monoclonal antibodies (mAbs), before expanding to other biological molecules, and eventually new chemical entities. In the long term (3-5 years), the FDA aims to make animal testing the exception rather than the norm for preclinical safety and toxicity testing. This announcement marks a pivotal moment in U.S. regulatory science, ushering in a new era where human-specific research takes centre stage.
Focuses on Human-Specific Research
As discussed in a previous Insights article, the drug discovery and development process is becoming increasingly costly and inefficient. While the reasons behind this are multifactorial, a significant challenge lies in the continued overreliance on animals in preclinical studies. This is despite growing evidence questioning the value and relevance of animal research. However, recent advancements in human-focused technologies, capable of more accurately predicting human-relevant outcomes, are driving a shift in the field. As many in the research community consider adopting strategies that prioritise human-specific research, the FDA’s recent announcement and roadmap represent significant endorsements of this approach.
Although the FDA’s plans are not exclusively focused on human-specific research – certainly not in the short term – the analysis of human cells, human tissue, and human data lies at the core of its strategy. In a pivotal moment, the agency has announced that it will now consider human drug toxicity data from other countries where a compound has already received approval.
This marks a welcome shift away from the traditionally independent approach adopted by regulators and represents a promising step toward reducing unnecessary animal testing.
“For too long drug manufacturers have performed additional animal testing of drugs that have data in broad human use internationally. This initiative marks a paradigm shift in drug evaluation and holds promise to accelerate cures and meaningful treatments for Americans while reducing animal use.”
–Martin A. Makary, M.D., M.P.H. FDA Commissioner
Beyond the analysis of pre-existing human data, complex in vitro models, such as organ-on-chip, and AI-based computational models are highlighted as key approaches in the agency’s plan. Both have shown great potential in predicting clinical outcomes and could be formally adopted to replace specific animal tests once regulators have gained confidence in the approaches. In isolation, these techniques can provide useful supportive data but currently fall short of what is required from regulators. However, the FDA highlights that when used as part of a human-specific toolbox, these techniques have real potential to offer a suitable alternative to animal studies.
Strikes the Right Balance
Developing a roadmap is inherently challenging. If the goals are overly ambitious, the roadmap risks being dismissed as unrealistic. On the other hand, an overly cautious approach may be perceived as uninspiring or lacking vision. The FDA needed to strike the right balance to create something groundbreaking.
While the FDA’s ultimate vision is bold, to make NAMs the new standard for regulatory research, there is a recognition that the shift away from animal use requires a transition period. Change must be underpinned by robust, reliable, and reproducible scientific data, which will enable regulators to gain confidence in these comparatively new methods. Their roadmap ensures that different approaches, such as organ-on-chip and computational models, are sufficiently tested and validated before they are fully implemented.
As part of a phased strategy, the FDA will first work in collaboration with selected mAb developers to implement a predominantly non-animal-based testing strategy. This initial phase is intended to serve as a pilot programme, which will then be expanded.
The FDA’s ambitious long-term aim to make animal studies the exception rather than the norm for pre-clinical safety / toxicity testing is well supported by a clear three-year strategy. This includes six key objectives and six scientific and technical steps that the agency is considering, such as bringing together different stakeholders to support validation and integration of human-focused technologies into the regulatory process.
It is pleasing to see that the steps outlined address some of the most widely recognised hurdles preventing the adoption of human-specific research (as highlighted in a previous Insights article), including the need for investment in the development of alternative technologies, the creation of regulatory guidance and standards, as well as the need for training. The FDA’s roadmap reflects a comprehensive, strategic, and realistic approach to phasing out regulatory animal testing. By combining a clear long-term vision with practical short-term steps, it appears that the agency is looking to lay a solid foundation on which to build.
Presents Clear Benefits
The success of the FDA’s plan will depend heavily on the cooperation and active involvement of a broad range of stakeholders, all of whom will need to be convinced of the value of this new direction. While ethical concerns regarding the use of animals in research remain a significant motivating factor for change, it is important to realise that other considerations, such as scientific validity, potential cost efficiencies, and implications for timelines, also play a crucial role in influencing decision-making for many. It is therefore encouraging to see that the FDA’s announcement recognises this, as it outlines a strategy that promises to benefit all stakeholders.
“By leveraging AI-based computational modelling, human organ model-based lab testing, and real-world human data, we can get safer treatments to patients faster and more reliably, while also reducing R&D costs and drug prices. It is a win-win for public health and ethics.”
–Martin A. Makary, M.D., M.P.H. FDA Commissioner
For drug developers and sponsors, the FDA’s announcement marks a significant step forward in the agency’s growing confidence in human-focused technologies as a viable alternative to animal testing. While the FDA Modernization Act 2.0 was hailed as a groundbreaking policy, uncertainty persisted regarding regulators’ willingness to accept non-animal data in lieu of traditional animal data. However, the FDA’s latest announcement and accompanying roadmap offer a much clearer vision for how these alternative approaches could be integrated over time into the regulatory framework.
For many, there is a realisation that something needs to change. Much like for other drugs, the current mAb development process is marked by significant costs, extended timelines, and a continued reliance on animal testing. As outlined in the FDA’s roadmap, existing preclinical animal studies often fail to accurately predict human responses, due to species differences, stress factors, and immune system variations. The mAb TGN1412 incident serves as a stark reminder of these limitations1. By incorporating more predictive, human-specific models, drug developers could potentially not only reduce reliance on animal testing but also lower development costs, enhance decision-making, and accelerate the delivery of safer, more effective therapies.
The complete removal of animal testing from preclinical research is not likely to happen immediately. It is therefore crucial to implement a strategic framework that supports a transition toward non-animal methods. A key component of this transition involves the parallel submission of data from human-focused approaches, such as human organ-on chip data, alongside traditional animal data. This dual submission allows regulatory agencies to gain familiarity with emerging techniques and build confidence in their reliability and relevance. One of the persistent challenges in regulatory science is the lack of submitted data from human-focused approaches, often stemming from a perception that regulatory bodies inherently favour animal studies. This assumption can contribute to a self- perpetuating cycle: in the absence of data, regulators are unable to evaluate and validate these alternatives, while developers may be hesitant to invest in or submit such data due to the lack of established regulatory precedent2. Breaking this cycle requires proactive collaboration among stakeholders to foster the adoption of more human-focused technologies in safety assessment.
The current FDA strategy recognises this barrier and is addressing it by encouraging and incentivising the submission of NAM data in parallel with animal studies, thereby creating a ‘repository of experience’. Although the European Medicines Agency (EMA) has previously proposed a similar strategy, the FDA’s approach may be particularly impactful as it is to be coupled with tangible regulatory incentives, such as requiring a reduced number of animal replicates, or expedited review processes3.
Whether this is enough of a carrot to engage drug developers remains to be seen.
The benefits to patients, animal welfare, and the FDA itself are clear. If successful, the agency’s approach could lead to lower drug prices which will benefit patients. For organisations pushing for an end to animal research it represents a monumental moment, which has the potential to lead to a significant reduction in animal testing for regulatory studies.
“For animal welfare, it represents a major step toward ending the use of laboratory animals in drug testing. Thousands of animals, including dogs and primates, could eventually be spared each year as these new methods take root.”
– Martin A. Makary, M.D., M.P.H. FDA Commissioner
For the FDA, it has been an opportunity to show itself as a leader in driving innovation within regulatory science with a comprehensive strategy. The FDA plans to leverage its influence to drive global change, proposing revisions to ICH guidelines and collaborating with other regulatory bodies on qualification projects.
The announcement is likely to bring renewed pressure on other regulatory agencies to update their own frameworks and accelerate the shift toward human-specific research methods. The European Commission (EC) is currently developing a roadmap to phase out animal testing for chemical safety assessments (including pharmaceutical safety assessment), with an expected release in early 2026. Although the details of the roadmap are yet to be published, it is anticipated that the EC’s approach will align closely with that of the FDA, addressing many of the same key points4. This can only be a good thing, as the harmonisation of global regulatory strategies and enhanced international collaboration could catalyse the transition to more human-specific research in regulatory studies.
Recognises the Importance of Collaboration and Shows a Willingness to Adapt
Achieving this ambitious shift will be no small feat. However, two notable aspects of the FDA’s approach, both of which are worth highlighting, provide encouraging signs that it is set up for success: a strong emphasis on collaboration and a willingness to adapt in response to outcomes and feedback.
In its roadmap, the FDA has highlighted several critical partners who can help drive innovation and validation of NAMs. Through the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), which offers a strong platform for collaboration, the FDA plans to work closely with other federal agencies, such as the National Institutes of Health (NIH) to boost investment in NAM development. Additionally, the FDA aims to collaborate with the National Toxicology Program (NTP) to expand and validate the Tox21 programme, creating an extensive open-access database of international toxicity data.
Some of these collaborations already appear to be well established. With the FDA’s announcement still fresh, the NIH has unveiled a bold new initiative to reduce animal use in federally funded research, explicitly aligning itself with the FDA’s strategy. Each announcement is a major milestone on its own, but taken together, they represent something far more significant: the beginning of a concerted effort to change how medical research is conducted in the U.S.
Central to the FDA’s initiative is a strong commitment to data-driven decision-making. The agency has shown a desire to be flexible, adapting as it moves forward. The roadmap includes steps to monitor outcomes and track changes in toxicity testing over time, enabling real-time adjustments based on the latest data. The agency also intends to maintain an open dialogue with industry, academia, and NGOs throughout the process. Public meetings and advisory committee discussions will track progress and enable expert feedback. Initially, the FDA is seeking input from all stakeholders, with a public workshop scheduled later this year.
This is certainly one to keep an eye out for.
Overall Impression
The FDA’s recent announcement marks a major turning point in regulatory science. By embracing human-specific research, the agency is taking meaningful steps to modernise a system that has, for too long, relied on animal models that often fail to accurately predict human outcomes. The FDA’s plan is ambitious, but in my opinion, appropriately so. It strikes a commendable balance between vision and practicality, offering both immediate steps and long-term goals with a flexibility that enables it to adapt in response to the latest findings. If successfully implemented, this initiative could accelerate access to safer and more affordable treatments, reduce reliance on animal testing, and reshape the regulatory landscape, not just in the U.S., but worldwide.
References
- Attarwala, H. TGN1412: From Discovery to Disaster. J. Young Pharm. JYP 2, 332–336 (2010).
- Sewell, F. et al. New Approach Methodologies (NAMs): Identifying and Overcoming Hurdles to Accelerated Adoption. Toxicol. Res. 13, (2024).
- European Medicines Agency. Guideline on the Principles of Regulatory Acceptance of 3Rs (Replacement, Reduction, Refinement) Testing Approaches. (2016).
- Walder, L. et al. EU Roadmap for Phasing Out Animal Testing for Chemical Safety Assessments: Recommendations From a Multi-Stakeholder Roundtable. ALTEX – Altern. Anim. Exp. (2025).