Preclinical research has traditionally utilized laboratory animals to elucidate the safety, tolerability, pharmacokinetics, and pharmacodynamics of new chemical entities prior to human trials. The use of animal models has been pivotal in advancing scientific knowledge and medical breakthroughs, contributing significantly to our understanding of the complex biological processes and human diseases. However, many promising treatments that have demonstrated efficacy in animal studies have failed to translate to human subjects during clinical trials. Consequently, animal testing faces ethical concerns and criticism regarding its predictive reliability for human responses. This has led to the development of 3R principles (Replacement, Reduction, Refinement), introduced in 1959, advocating for alternative methods and improved animal welfare in research. Furthermore, regulatory frameworks and recent legislation, such as the 2022 FDA Modernisation Act, emphasize modern scientific alternatives to traditional animal testing. Emerging approaches, known as the 3Cs-cell culture, computer simulation, and phase 0 clinical trials-offer promising nonanimal solutions that could accelerate drug development and address ethical concerns, potentially rendering preclinical research more humane and efficient.
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