FDA’s emerging framework to reduce animal testing: Implications for drug development timelines, cost, and clinical strategy

In November 2025, the UK government introduced the national "Government Strategy and Roadmap" for phasing out animal testing.[1] The US Food and Drug Administration (FDA) has also issued a roadmap and draft guidance for reducing or eliminating animal testing for certain drugs.[2]^,[3]This isn’t just a policy change, it’s a fundamental re-thinking of how safety and efficacy are demonstrated before first-in-human trials. What should drug developers expect regarding non-clinical development plans in the coming years?

As the UK progresses towards an animal-free clinical trial setting, we must look to other markets and regions to assess their actions and progress and what this means globally. The FDA is entering a pivotal phase in reshaping non-clinical development, focusing on developing and adopting alternatives in the next three to five years.

A series of recent initiatives – including the Roadmap to Reducing Animal Testing in Preclinical Safety Studies and the draft Monoclonal Antibodies: Streamlined Nonclinical Safety Studies guidance – signals a strategic shift toward reducing reliance on non-human primates (NHPs) and other animal species. The move is grounded in the FDA’s commitment to the three Rs (reduce, refine, replace) and bolstered by significant scientific advances in human-relevant New Approach Methodologies (NAMs).

Collectively, these updates stand to reconfigure the economic, operational, and scientific landscape of preclinical safety assessment, with meaningful implications for drug development timelines, programme costs, and clinical trial strategy.

Why the FDA is accelerating away from animal testing

The FDA’s recent position reflects growing recognition of the limitations of animal models in predicting human outcomes. According to the Roadmap, more than 90% of drugs that perform well in animal studies fail in humans because safety and efficacy signals observed in animals often do not translate.[4] The new draft guidance places particular emphasis on refining non-clinical programmes for monoclonal antibodies (mAbs).The document emphasises that, for these antibodies, clinically relevant toxicities typically arise from exaggerated pharmacology, rather than off-target effects. This scientific reality provides the foundation for a more streamlined non-clinical framework moving forward.

The new FDA paradigm: Streamlined preclinical programmes for monospecific antibodies

The recently issued draft guidance proposes a major modernisation of non-clinical expectations for monospecific antibodies. Key FDA proposals include:

Limiting long-term (>3 months) toxicology in non-rodent species, provided sponsors conduct a robust weight-of-evidence (WoE) risk assessment incorporating mechanistic biology, short-term toxicology studies, pharmacokinetic (PK) data, literature assessments, other non-clinical data (including the use of NAMs), and any relevant clinical data.
Determining when 3-month toxicology studies are not warranted, such as when anti-drug antibodies confound interpretation, severe short-term toxicity precludes longer studies, mAbs do not bind targets in any relevant species, or extensive prior knowledge shows that animal data for the target has not been predictive of human toxicities.
Conducting general toxicology studies in a single rodent species when the mAb has similar pharmacological activity to humans in both rodent and non-rodent species.
Utilising a WoE to determine whether additional studies are warranted to address juvenile, reproductive, or development safety.

Importantly, the FDA emphasises early engagement and encourages sponsors to discuss NAM integration and reduction of animal studies in Type B meetings, signalling openness to case-by-case consideration with regard to non-clinical development plans.

The Roadmap: FDA’s vision to make animal studies the exception

The Roadmap outlines the FDA’s broader ambition: animal studies as the exception in non-clinical safety testing, rather than the default – within three to five years.

Short-term (1–3 year) actions include:

As discussed above, reducing 6-month toxicology studies in non-rodent species for mAbs to 3 months, when justified by short-term tox and NAM data – and, in some cases, foregoing 3-month toxicology studies.
Reduce toxicology testing timeframes for other drug categories based on relevant prior clinical information about the product or product class.
Encouraging parallel submission of NAM and animal data to accelerate validation.
Launching pilot cases where animal studies are waived in favour of NAMs.
Utilise pre-existing international data when applicable.
Building a comprehensive, open-access international toxicity database integrating animal and human data to train predictive models.

Longer-term (3–5 year) goals:

Establish NAMs as the regulatory default for toxicology evaluation.
Use animal testing only when NAMs cannot yet address a specific scientific question.

The FDA outlines specific steps and considerations for integrating NAMs into standard non-clinical development. These steps include support for developing NAMs, establishing validation and qualification plans, developing new guidance, ongoing training, communication, and evaluation. These efforts are strengthened through the FDA’s active coordination with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), National Institutes of Health (NIH) and the Department of Veterans Affairs (VA), and other federal research partners to standardise, validate, and compare NAMs across agencies to ensure best practices are implemented

Implications for drug development timelines and costs

Shortened toxicology study requirements, combined with NAM alternatives, have the potential to significantly shorten the preclinical phase. The new framework proposes a ≤3‑month tox studies for mAbs. In some cases, no NHP study is required when no pharmacologically relevant species exists. The NAMs (e.g., organs-on-chips, in silico tools, computational modelling) can provide faster turnaround and can be conducted in parallel. This could reduce the preclinical safety timelines significantly, depending on programme complexity. Some NAMs can be more human-predictive than animal studies and therefore can potentially identify human-specific risks earlier, reduce uncertainty around first-in-human dose selection, and support accelerated transitions into clinical dosing cohorts.

There are of course huge cost-saving implications with the current recommendations, especially for mAbs. Reducing a single six-month NHP toxicology study can eliminate tens of animals, reduce costs by millions, and relieve timeline uncertainty linked to NHP supply constraints. NAM platforms can require upfront investment, but offer faster, more scalable, and reusable systems. There is evidence that the use of NAM platforms can decrease GLP facility costs, provide higher predictive power and reduce late-stage failure costs. Human-relevant NAM data also leads to improved R&D efficiency and portfolio management.

Clinical development strategy: What sponsors should expect

The FDA’s WoE approach explicitly includes phase 1–2 clinical safety and PK data when assessing whether long-term toxicology studies are necessary. As a result, sponsors may see faster approval for extended dosing in first-in-human trials and greater flexibility in adaptive designs where clinical and NAM data jointly support dose escalation or cohort expansion. Because NAMs may capture human-relevant physiology, this could lead to the identification of mechanism-based biomarkers to monitor in early trials.

Additionally, as NAM reliability grows, sponsors may be able to delay, shorten, or waive certain reproductive or juvenile animal studies. And those willing to integrate robust NAM packages may benefit from reduced animal requirements, fewer studies, and strategic positioning as early adopters in a shifting regulatory landscape.

Strategic recommendations for sponsors

Incorporating NAMs early in development can significantly strengthen the rationale for reducing or abbreviating animal testing. Sponsors can present a compelling case for alternative testing methods by combining target biology, NAM data, clinical comparators, and translatable biomarkers into a unified evidence package aligned with the FDA’s weight-of-evidence framework. Strategic use of Type B meetings offers opportunities to propose NAM-based substitutions, request waivers, and clarify how species binding and target biology inform relevance.

The FDA’s Roadmap underscores the value of leveraging international human data, where available, to avoid unnecessary duplication of studies. Long-term toxicology strategies should be revisited across portfolios, particularly for monoclonal antibodies lacking a relevant animal model, programmes where anti-drug antibodies limit interpretability and targets backed by extensive prior human or clinical-class experience. Taken together, these approaches not only streamline development, but also advance more ethical, efficient, and scientifically robust pathways to regulatory approval.

A transformative moment in preclinical development

The FDA’s emerging framework represents more than a regulatory update; it is a paradigm shift toward human-relevant, science-forward drug development. By reducing reliance on animal models and embracing NAMs, the FDA aims to improve patient safety, accelerate timelines, reduce costs, and align regulation with modern biomedical science.

For sponsors, this transformation presents an opportunity: those who adapt early will be best positioned to benefit from shorter development cycles, lower costs, and greater predictability in bringing innovative therapies to patients.

References

[1] Gov.uk. Policy Paper. Replacing animals in science strategy,GOV.UK. Available at: https://www.gov.uk/government/publications/replacing-animals-in-science-strategy. Accessed December 2025.

[2] U.S. Food and Drugs Administration. 2025. FDA Announces Plan to Phase Out Animal Testing Requirement for Monoclonal Antibodies and Other Drugs, U.S. Food and Drug Administration. Available at: https://www.fda.gov/news-events/press-announcements/fda-announces-plan-phase-out-animal-testing-requirement-monoclonal-antibodies-and-other-drugs?.‌ Accessed December 2025.

[3] U.S. Food and Drugs Administration. 2025 Monoclonal Antibodies: Streamlined Nonclinical Safety Studies, U.S. Food and Drug Administration. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/monoclonal-antibodies-streamlined-nonclinical-safety-studies Accessed December 2025.

[4] Scientists highlight failures of animal testing in drug development | Cruelty Free International (2023) crueltyfreeinternational.org. Available at: https://crueltyfreeinternational.org/latest-news-and-updates/scientists-highlight-failures-animal-testing-drug-development. Accessed December 2025.

About the author

Jennifer Burke is a senior principal consultant in regulatory strategy at Lumanity. She has 30+ years of experience in drug development and spent her early career managing a laboratory animal facility and lab animal science team conducting oncology, infectious disease, and autoimmune research. Burke has spent the last 15 years in regulatory affairs, leveraging experience on both the sponsor side and as a consultant to navigate complex regulatory challenges. At Lumanity, she spearheads innovative regulatory strategies and drives timelines to optimise development pathways for clients, managing complex regulatory plans and submissions while collaborating with cross functional teams to drive business objectives. She guides teams through critical interactions with health authorities to ensure alignment of regulatory and development plans. Burke has extensive regulatory experience in the development of therapeutics in oncology, immuno-oncology, liver disease, weight management, and various rare diseases.