EURL ECVAM recommendation on non-animal-derived antibodies

Antibodies are binding molecules (affinity reagents) that have a high specificity for their unique target (antigen) and are crucial tools for research, diagnostics, therapeutics and regulatory procedures. Animals are still used for the generation of monoclonal and polyclonal antibodies as well as other types of affinity reagents despite the availability of technologies for their development and production that do not entail the use of animals. The EU Directive 2010/63/EU on the protection of animals used for scientific purposes does not allow the use of animal-based methods when other methods not entailing the use of animals exist, which would allow obtaining the results sought (Articles 4 “Principle of replacement, reduction and refinement” and 13 “Choice of method”). The EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) avails of the scientific opinion of the EURL ECVAM Scientific Advisory Committee (ESAC) about specific issues related to alternative methods. In 1998, based on the available evidence, ESAC concluded that for all levels of monoclonal antibody production, scientifically acceptable in vitro methods (i.e. use of hybridomas) were practicably available and that these methods were either better than, or equal to, the in vivo (ascites) production method in terms of antibody quality. Thus, the ESAC stated in 1998 that in vivo production of monoclonal antibodies by the ascites method was no longer scientifically necessary, except in rare cases. Nevertheless, the recent statistical information published by the European Commission on the use of animals for scientific purposes in the EU show an increase by 65% in the use of animals for monoclonal antibody production by the mouse ascites method between 2015 (27333 animals used) and 2017 (45024 animals used). It is unclear from the non-technical project summaries how the ascites method could be justified and as a consequence, why such projects could still be authorised in EU countries.