Presentation by Dr Andre Menache, AIA Chair and Scientific Consultant at Antidote Europe to the 6th annual meeting of the European Veterinary College of Behavioural Medicine and Animal Welfare in Paris on 3rd October 2024
The regulatory requirement that all new pharmaceutical drugs be tested on animals before proceeding to clinical trials can be traced back to the Doctors’ Trial in Nuremberg at the end of the Second World War (Greek, 2012). Subsequent recommendations and directives, including the Helsinki Declaration (World Medical Association weblink) relevant EU Directives (European Medicines Agency weblink) and the International Conference on Harmonisation continue to rely on the Nuremberg Codes with respect to animal use and regulatory toxicology (Ohno, 2002). However, it would appear that the laws have not kept up with scientific progress. As an example, human organ on a chip technology is now widely available and increasingly used by the pharmaceutical industry for the purposes of evaluating drug safety in preclinical screening. While ‘human on a chip’ technology is still under development, the human liver on a chip is probably the most significant innovation currently being used by industry and could be considered to have achieved ‘validation’ status based on a weight of evidence approach (Ewart, 2022). It is far more predictive than animal testing in terms of correctly identifying drug induced liver injury (DILI). As DILI is the leading cause of withdrawal of approved drugs from the market (Levner, 2023), it makes sense that the liver on a chip should be included in all new drug applications (NDA) as a matter of urgency and that the results obtained from animal tests be submitted to the relevant regulatory agencies and compared with the results obtained from the liver on a chip.
References :
- European Medicines Agency : ethical use of animals in medical testing. Available at : https://www.ema.europa.eu/en/human-regulatory-overview/research-development/ethical-use-animals-medicine-testing
- Ewart, L. Apostolou, A. Briggs, S. et al. (2022) « Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology », Nature Communications Medicine 2 : 154.
- Greek, R. Pippus, A. Hansen, L. (2012) « The Nuremberg Code subverts human health and safety by requiring animal modelling », BMC Med Ethics Jul 8:13:16.
- Levner, D. and Ewart, L. (2023) « Integrating Liver-Chip data into pharmaceutical decision-making processes », EXPERT OPINION ON DRUG DISCOVERY, 18 :2 :1313-1320.
- Ohno, Y. (2002) « ICH guidelines–implementation of the 3Rs (refinement, reduction, and replacement): incorporating best scientific practices into the regulatory process », ILAR J 43 Suppl:S95-8.
- WMA DECLARATION OF HELSINKI – ETHICAL PRINCIPLES FOR MEDICAL RESEARCH INVOLVING HUMAN SUBJECTS.
Available at : https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/
Animal Interfaith Alliance 