Center for Alternatives to Animal Testing (CAAT), Doerenkamp-Zbinden-Chair for Evidence-based Toxicology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
CAAT-Europe, University of Konstanz, Germany.
ALTEX. 2024;41(4):545-566. doi: 10.14573/altex.2410011.
This article explores the potential of principles established in translational medicine for the use of bio-markers 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 under-standing, and human relevance of new approach methodologies (NAMs). Key concepts from translational medicine, such as fit-for-purpose validation, evidence-based approaches, and inte-grated testing strategies, are already being applied to the development and validation of NAMs. The article discusses challenges in implementing biomarker-based approaches, including standardi-zation, demonstration of relevance, regulatory acceptance, and addressing biological complexity. It also highlights opportunities for advancement through collaborative efforts, technological inno-vations, 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 bio-markers 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.
本文探讨了转化医学中确立的原则在利用生物标志物方面的潜力，以推进替代动物测试在临床前安全性评估中的验证。本文特别研究了这些原则如何增强新方法（NAMs）的预测能力、机制理解和与人类的相关性。转化医学中的关键概念，如针对性验证、基于证据的方法和综合测试策略，已经应用于 NAMs 的开发和验证中。本文讨论了实施基于生物标志物的方法所面临的挑战，包括标准化、相关性证明、监管部门的接受程度以及解决生物学复杂性问题。它还强调了通过协作努力、技术创新和监管演变来实现进步的机会。案例研究展示了生物标志物在临床前安全性中的成功应用，而未来的展望则探讨了多组学整合、微生理系统和人工智能等新兴趋势。本文强调了生物标志物和转化科学方法在利用 NAMs 创建更具预测性、更有效和更符合伦理的临床前安全性评估范例方面的潜力。生物标志物的使用可以实现与人类相关模型的机制验证，并提供一种将 NAMs 的变化与动物或临床研究结果联系起来的方法。通过利用这些工具，该领域可以努力减少对动物测试的依赖，同时提高安全性预测的准确性和与人类的相关性。
