Stem Cell–Derived Organoids as a Next‐Generation Platform for Drug Toxicity and Efficacy Testing: Toward Replacing Animal Models in Regulatory Science

Three-dimensional, self-organizing structures derived from stem cells, known as organoids, represent a groundbreaking advancement in preclinical drug development. Organoid-based platforms advance preclinical testing by providing an accurate representation of human tissue architecture and genetics, surpassing traditional two-dimensional cultures and animal models in testing both drug safety and efficacy. Researchers are shifting toward organoid-based systems as primary components of new approach methodologies, as global regulatory bodies increasingly acknowledge animal testing limitations. This review delivers an exhaustive examination of organoid technologies and their applications in drug testing. Our study explores current methods used to model toxic responses in different organs—such as the liver, kidney, and heart—while highlighting how personalized and disease-specific organoids can enhance the accuracy of efficacy testing. Our investigation also examines regulatory frameworks and outlines the path toward organoid platform standardization and validation before their integration into drug development processes. Complex neural organoids show great promise but continue to face significant challenges, including biological variability, a lack of universal standards, and ethical concerns. The combination of organoid technology with microengineering techniques, artificial intelligence–based analysis, and high-throughput screening methods represents a transformative change in translational medicine. Organoid-based systems represent both scientific breakthroughs and ethical necessities, as they provide human-specific data while reducing dependence on animal testing. If organoid development progresses with regulatory approval, it could fundamentally transform drug discovery and safety evaluation methods.