3Rs advice for project licence applicants: replacement

Replacement refers to the use of technologies or approaches that replace or avoid the use of animals in studies. This includes full replacement which avoids the use of any animals (e.g. human volunteers, computer and mathematical modelling, or established cell lines in place of animals) and partial replacement. Partial replacement generally falls into one of three categories: either the animal species used is not protected by law (e.g. invertebrates such as Drosophila or nematode worms), or is used at a life stage prior to it becoming protected (e.g. mammals, birds and reptiles before the last third of their gestation or incubation period; fish and amphibians before they can feed independently), or cells and tissues are used from animals that have not undergone any procedures other than killing by a permitted ‘Schedule 1’ method). Within the project licence application these full or partial replacements are often referred to as in silico, in vitro and ex vivo methods.

Project licence applicants are asked to detail which non-animal alternatives they have considered for the proposed work and explain why these are not suitable for the research objectives. Including this information in the application helps to demonstrate a thorough understanding of the research field. Applicants should conduct a thorough, well-designed search of the scientific literature, using appropriate keywords. In addition, a number of searchable databases are available which provide detailed information about alternative approaches and the scientific research they can help support.

Resources on searching for alternatives

  • The EURL ECVAM Search Guide has been developed to help users find information on alternative strategies and methods to animal-based research.
  • The Animal Welfare Information Centre has tips for searching for alternatives, as well as links to relevant databases.
  • Duke University Library also provides advice on how to search for non-animal alternatives and links to a number of freely available databases, most of which are specifically designed to search for alternative approaches.
  • NORECOPA has a series of databases, including alternatives to the use of animals in education and training.

To discover more about the utility of different invertebrate models such as Drosophila visit FlyBase, an online database of Drosophila genes and genomes. Additionally, Wormbase provides information about the genetics and biology of Caenorhabditis elegans and related nematodes. For information on using Galleria mellonella (wax moth larvae) in place of mammals for infection studies visit BioSystems Technology.

Human tissue

Human cells or tissue can help to replace the use of animal models and may provide more translational testing strategies. Visit our human tissue resource hub to understand what types of cells and tissue can be used and where they can be obtained. The UK Clinical Research Consortium has a Tissue Directory with sample collections covering multiple diseases, searchable by age, gender, disease classification, sample type, etc. For those interested in human brain tissue, see information from the UK Brain Banks Network. More information on the regulation of human tissue use can be found in guidance published by the Human Tissue Authority and the MRC

In vitro / in silico / ex vivo research

Applicants are often using in vitro, in silico and/or ex vivo approaches alongside their in vivo work; or have used these approaches during earlier stages of the research to inform project direction. Relevant examples should be given within the project licence application, including those where animals have been replaced during certain steps (e.g. during early screening) or where ex vivo samples have been obtained following a Schedule 1 method of killing (i.e. animals have not undergone regulated scientific procedures).

More information about in vitro models can be found on the websites of the Institute for In Vitro Sciences, In Vitro Toxicology Society and European Society of Toxicology In Vitro. Further information and guidance about organ-on-a-chip approaches can be found at the Organ on a Chip Technologies Network, while the 3DbioNet is a UKRI-funded network providing information and funding for 3D cell culture models. 

Page last updated: 6 July 2020