Abstract:

Laboratory animals are increasingly utilized as in vivo models for life sciences, medical research, and drug development, and the associated ethical and welfare issues have attracted increasing attention. The "3R" principle (replacement, reduction, refinement) is a globally recognized guideline for conducting animal experiments, providing direction for balancing scientific research with animal welfare. New approach methodologies refer to technologies that mimic human physiological systems and can replace or reduce traditional animal experiments, mainly including in vitro (e.g., organoids, organ-on-a-chip,3D bioprinting models), in chemico, and in silico tools. This review systematically examines the technical characteristics, development history, and applications of new approach methodologies in disease modeling, drug development, toxicological evaluation, etc., and focuses on the implementation path of the "3R" principle. New approach methodologies can replace some animal experiments through in vitro biomimetic models, reduce the number of experimental animals used through high-throughput screening and computational simulation, optimize experimental design and alleviate animal suffering through accurate dose prediction and early biomarker monitoring. New approach methodologies still face challenges such as the inability to fully recapitulate the complex human physiological system, insufficient standardization and reproducibility, and underdeveloped validation and acceptance pathways. With continuous technological innovation, rigorous scientific validation, proactive international cooperation, and sound policy support, new approach methodologies are expected to gradually reduce the use of traditional animal experiments and advance biomedical research toward the coordinated pursuit of scientific rigor, animal welfare, and cost-effectiveness.

Key words: New approach methodologies, "3R" principle, Organoids, Organ-on-a-chip, 3D bioprinting models, In silico tools, Laboratory animal ethics