Statement from ICMRA on animal testing for human¹ medicines

This statement reflects the shared perspective of ICMRA members, highlights work already underway internationally and supports the continued movement toward the regulatory acceptance of non-animal-based methods or approaches for regulatory testing of human medicines. The key purpose of the document is to encourage the development and implementation of scientifically valid alternative methods where possible, in a manner that is globally consistent.

1    Introduction

Historically, the development and quality control testing of medicines has involved the use of live animals for proof-of-concept purposes and to assess their mechanism of action, safety, and quality. Some regions and countries are revising their regulatory frameworks to facilitate acceptance of scientifically justified methods which do not require in vivo testing, and in some regions, the use of animals is only permissible if there are no suitable alternatives (1). Similarly, international organisations such as the World Health Organization (WHO) are also updating their regulatory guidelines to promote the development and adoption, of non-animal methods for use in drug development studies and quality control/batch release testing. These alternatives to the use of live animals can include physicochemical or immunochemical methods, ex vivo, in vitro (e.g. simple (2D) or complex (3D) cell-based or microphysiological systems), and in silico (e.g. computer modelling, artificial intelligence-enabled analyses of large datasets) methods, and more use of human-derived data (e.g. through human microdose studies).

ICMRA notes that scientific developments in recent years suggest regulatory dependence on the use of animals in medicines testing can be reduced, provided that quality and patient safety are appropriately ensured (2,3).

ICMRA calls on developers of medicines, manufacturers, regulators and national control laboratories to continue to advance and implement alternative methods or approaches, wherever, and as soon as, possible. 

This call applies to all stages of a medicine’s life cycle: from initial candidate screening and early development, through the pre-clinical and non-clinical testing and into the licensing and marketing stages.

2.1    New medicines: from development to authorisation 

Internationally applicable guidance such as that provided by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use (ICH) sets out requirements to ensure the development and registration of safe, effective, and high-quality medicines. Such guidance can include recommendations on the use of animals (e.g. application of the 3Rs principles: Replacement, Reduction and Refinement) and provide considerations/criteria for non-animal-based methods (e.g. ICH S5) (4). In this way, harmonised guidance can contribute to a reduction in animal use while ensuring that expectations are aligned across regulatory regions and countries. There is an opportunity to further advance harmonisation through revisions of existing ICH guidelines and/or through the drafting of new guidelines, which more specifically outline expectations for adoption of novel approaches and non-animal methods. 
Regardless of whether animal-based or non-animal-based models are used, the method(s) supporting development of medicines and their clinical use must provide sufficient evidence on whether: 
(1) the product has an acceptable safety profile, and 
(2) there is credible scientific evidence that supports a claim that the therapeutic/prophylactic intervention could bring benefit to an identifiable set of patients.

It is already accepted in most regions and countries that, in general, there is no scientific justification for conducting studies in animals for certain classes of medicines such as generic drugs or follow-on biologics (biosimilars). This approach may also apply where the pharmacological effect cannot be meaningfully reproduced in any animal species, thereby limiting the relevance of animal data for human risk assessment. In these circumstances, the regulatory requirements are typically addressed by cellular or other in vitro assays, as well as kinetic modelling. Taken together, these established practices suggest that similar approaches could potentially be applied more broadly, including to products that are pharmacologically active in animals, where scientifically justified. 

ICMRA recognises that replacing studies in live animals with use of non-animal-based testing methods requires a cautious, measured approach. All non-animal methods should demonstrate scientific validity and, where used as evidence to support the proof-of-concept, mechanism of action, or safety of a medicine, they should also be assessed for their regulatory acceptability. This assessment can be via separate formal validation or qualification processes for broad applications, or within individual product-specific regulatory procedures. 

Ultimately, complete elimination of animal use in general toxicity, reproductive toxicity and carcinogenicity studies as well as for pharmacodynamic and pharmacokinetic studies, remains a long-term goal. This will be achieved through progressive, stepwise, and weight-of-evidence-based approaches, and will require open interaction between international regulators, medicines developers, and those developing alternative methodologies.

ICMRA calls on medicines developers to employ methods that do not involve the use of animals and that are acceptable in a regulatory context. International medicines regulators should support and facilitate these efforts insofar as possible.

2.2    Quality control testing for batch release

The greatest impact in reducing the use of animals to meet regulatory requirements would be achieved by the adoption of non-animal methods for batch release testing (2,5). ICMRA recognises an opportunity to implement appropriately validated non-animal methods for the purpose of routine batch release testing, and that these may, in some cases, be superior to current animal models due to their better precision and discriminative power. 

ICMRA calls on international regulators to encourage development, validation, and adoption of non-animal tests for batch release purposes, and to challenge instances where animal use for batch release testing is proposed. In vivo batch release testing should only be approved where it is supported by robust scientific justification that there is no equivalent or superior non-animal methodology available.

ICMRA also emphasises the need for international harmonisation of quality testing requirements across different regions and countries to avoid scenarios where some authorities continue to require the use of animal methods for certain batch release tests, when others have already accepted the use of valid non-animal replacements. 

ICMRA calls on regulatory authorities to review and amend as appropriate existing in vivo testing requirements for batch release.

3    Transition period and future opportunities

It is likely that different regions and countries will move at different paces to accept a transition towards drug development, licensing, and batch release without testing in animals. ICMRA encourages drug manufacturers, developers and regulators to work together to enable this progressive paradigm shift, and to support harmonised implementation insofar as possible, recognising that different regions and countries may rely on different regulatory mechanisms to promote implementation. To facilitate the use of non-animal-based methods, authorities should consider appropriate incentives where feasible. Some suggested incentives include expediting meeting requests with regulatory health authorities, and the waiving of fees associated with the provision of scientific advice method qualification (6,7). As animal testing will continue in this transition period, plurality will exist, that is, a manufacturer of a new drug could use one or other approach (i.e. development with or without (certain) animal testing). It is expected that accrued experience with non-animal-based methods may obviate the need for animal testing in the future. Continued global regulatory dialogue will be critical with a view towards alignment in assessment standards and acceptance criteria. 

Where animal-based methods cannot yet be replaced or removed, efforts should continue to be made to reduce or refine the use of such methods as far as scientifically justified.

¹ ICMRA notes these principles could, to an extent, also apply to veterinary medicinal products (VMPs). However, as safety for users of VMPs and consumers of VMP residues in food needs to be ensured, testing strategies might differ from those for human medicinal products.

References
1 Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Available at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32010L0063. Accessed February 2026. 
2 Lilley et al.; Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals: Responses from a survey of vaccines and biological therapeutics manufacturers. Biologicals 2023 Feb; 81:101660. doi: 10.1016/j.biologicals.2022.11.002. Accessed February 2026.
3 Beilmann et al., Application of new approach methodologies for nonclinical safety assessment of drug candidates, Nat Rev Drug Discov. 2025 May. doi.org/10.1038/s41573-025-01182-9. Accessed February 2026.
4 See https://www.ich.org/page/safety-guidelines. Accessed February 2026.
5 Review of animal use requirements in WHO biologics guidelines. NC3Rs, NC3Rs report to WHO ECBS. Accessed February 2026. 
6 EFPIA Recommendations on Phasing Out Animal Testing for Chemical Safety Assessments. EFPIA, efpia-recommendations-on-phasing-out-animal-testing-for-chemical-safety-assessments.pdf. Accessed February 2026.
7 Roadmap to Reducing Animal Testing in Preclinical Safety Studies. FDA, roadmap_to_reducing_animal_testing_in_preclinical_safety_studies.pdf. Accessed February 2026.