NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Guidance

Replacement methods and approaches with potential regulatory applicability

Database to help identify opportunities to use alternative methods and approaches in regulatory safety assessment.

As part of the UK Government's 2025 Strategy on Replacing Animals in Science, the NC3Rs, with support from its expert Regulatory Sciences Forum, has developed a list of currently available replacement methods and approaches1 that may provide acceptable data sources to inform regulatory decision-making for safety assessments without the use of animals under UK medicines and chemicals regulations2.

List of replacement methods and approaches with potential regulatory applicability v1 October 2026.xlsx
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Further information

About the list

The first version of this list, published in October 2026, contains examples of replacement methods and approaches considered scientifically valid for use in testing strategies to potentially inform regulatory decision-making. The following criteria have been used to identify the methods and approaches for inclusion in the list:

  • The method or approach has been published as a validated standardised test method, such as those adopted by the Organisation for Economic Cooperation and Development (OECD).
  • The method or approach has been explicitly cited within relevant regulatory guidance or a regulatory scientific opinion as providing data that may be acceptable for decision-making.

The list includes guidance documents that can help organisations use these methods and approaches in practice. The replacement methods and approaches are categorised by the relevant toxicity area/endpoint they inform. The list is not exhaustive. Future versions of this list will provide further information on the contexts and conditions for which data from these methods and approaches may be considered under specific UK regulatory frameworks.

Considerations for applying the methods and approaches

Regulatory requirements may vary between agencies and the use of data from replacement methods and approaches is on a sector and regulation-dependent basis. Organisations should discuss the use of alternative methods and approaches with regulators at an early stage, where possible, to ensure the data generated will meet the relevant requirements.

It is important to note the design of a testing strategy should, depending on the regulatory regime, consider the availability and adequacy of existing data, whether adaptations to data requirements or waivers may be appropriate, and whether non-testing approaches such as read-across or computational modelling can provide the information needed to meet the relevant regulatory requirements.

Organisations are encouraged to include replacement methods and approaches in their testing strategies and provide data from these in regulatory submissions where appropriate. Depending on the regulatory context, this may be alongside data from animal studies. Increasing the inclusion of data from alternative methods and approaches in submissions will help build confidence in their use and support wider acceptance by regulators.

Open consultation (closes 22 January 2027)

If you have comments on the list (version one), please provide any feedback to natalie.burden@nc3rs.org.uk by 22 January 2027. 

The list is currently published as an Excel spreadsheet, and future versions will be published as an online database. Version two of the list will be published in 2027.

Notes

  1. Replacement of the use of animals that are protected under the UK’s Animals (Scientific Procedures) Act 1986 (ASPA) with scientifically robust alternatives in areas where animals otherwise would have been used. For the purposes of this list, this includes methods and approaches that are in vitro, in silico, in chemico, or ex vivo, and the use of organisms such as invertebrates and early-stage life forms of vertebrates that are not protected under the ASPA. 
  2. Medicines refer to both human and veterinary medicines including biological products such as vaccines. Chemicals encompass industrial chemicals, agrochemicals, biocides, cosmetic ingredients and consumer products. Hazard effects that may be considered as part of safety assessment processes across the relevant regulatory frameworks are listed below.  

    Human health  

    - Acute systemic toxicity 
    - Skin and eye irritation/corrosion 
    - Skin sensitisation 
    - Repeated-dose toxicity/specific target organ toxicity 
    - Genotoxicity/mutagenicity 
    - Carcinogenicity 
    - Reproductive toxicity 
    - Developmental toxicity 
    - Endocrine disruption 
    - Neurotoxicity 
    - Immunotoxicity 
    - Toxicokinetics/absorption, distribution, metabolism and excretion 
    - Mechanistic and emerging toxicology endpoints (e.g. through measurement of biomarkers or using omics approaches)

    Environmental protection of vertebrate wildlife species 

    - Acute effects: mortality/survival 
    - Chronic effects: mortality/survival, growth, development, reproduction 
    - Endocrine disruption 
    - Bioaccumulation/secondary poisoning
     
  3. This list has been developed with a specific focus on UK regulatory requirements. Other lists exist which provide information on replacement methods and approaches that may be accepted in other geographical regions, include (but not limited to): 

    - Alternative Methods Accepted by US Agencies 
    - CAMERA - Collection of Alternative Methods for Regulatory Application 
    - TSAR - Tracking System for Alternative methods towards Regulatory acceptance 
    - Test methods evaluated by the Japanese Centre for the Validation of Alternative Methods (JaCVAM) for regulatory uses 
    - US EPA List of Alternative Test Methods and Strategies (or New Approach Methodologies)
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