Leveraging biomarkers and translational medicine for preclinical safety - Lessons for advancing the validation of alternatives to animal testing

Main Article Content

Thomas Hartung , Nicholas M. P. King, Nicole Kleinstreuer, Marcel Leist, Danilo A. Tagle
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Abstract

This article explores the potential of principles established in translational medicine for the use of bio­markers to advance the validation of alternatives to animal testing in preclinical safety assessment. It examines especially how such principles can enhance the predictive power, mechanistic under­standing, and human relevance of new approach methodologies (NAMs). Key concepts from translational medicine, such as fit-for-purpose validation, evidence-based approaches, and inte­grated testing strategies, are already being applied to the development and validation of NAMs. The article discusses challenges in implementing biomarker-based approaches, including standardi­zation, demonstration of relevance, regulatory acceptance, and addressing biological complexity. It also highlights opportunities for advancement through collaborative efforts, technological inno­vations, and regulatory evolution. Case studies demonstrate successful applications of biomarkers in preclinical safety, while future perspectives explore emerging trends like multi-omics integration, microphysiological systems, and artificial intelligence. The article emphasizes the potential of bio­markers and translational science approaches in creating more predictive, efficient, and ethical preclinical safety assessment paradigms in the use of NAMs. Use of biomarkers can enable the mechanistic validation of human-relevant models and provide a means to relate changes in NAMs to animal or clinical study results. By leveraging these tools, the field can work towards reducing reliance on animal testing while improving the accuracy and human relevance of safety predictions.


Plain language summary
This article examines how biomarkers and translational science principles can improve safety testing without using animals. Biomarkers are quantifiable indicators of biological processes. Some of these can predict disease progression or drug effects. Translational science aims to apply laboratory findings towards clinical benefits. The article explores how combining these approaches can create better, more human-relevant and validated alternatives to animal testing. It discusses challenges that the field faces, including standardization of methods and getting regulatory acceptance. It also highlights opportunities, like integration with emerging technologies and increased global collabo­ration. The ultimate goal is to improve human health by streamlining NAM validation processes, i.e., show that new safety tests are more accurate, efficient, and ethical than current animal-based methods.

Article Details

How to Cite
Hartung, T. (2024) “Leveraging biomarkers and translational medicine for preclinical safety - Lessons for advancing the validation of alternatives to animal testing”, ALTEX - Alternatives to animal experimentation, 41(4), pp. 545–566. doi: 10.14573/altex.2410011.
Section
Food for Thought ...
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