Drug screening, oral bioavailability and regulatory aspects: a need for human organoids
This review examines the significant limitations of traditional preclinical testing systems for determining the oral bioavailability of drugs. Rodent models used in animal experiments differ substantially from humans in anatomy, enzyme expression, and gastrointestinal pH, resulting in poor translation of findings to human biology. Conventional human 2D cell lines also fail to adequately represent healthy human intestinal tissue because they lack important cell types and exhibit altered enzyme expression patterns. The authors explain why 3D intestinal organoids are scientifically superior to these systems, as they more accurately replicate the physiological diversity of the human intestinal epithelium. Combined with organ-on-a-chip technologies and in silico models, organoids enable precise drug screening under physiologically relevant conditions. In light of the global regulatory toward phasing out animal testing, human organoids offer the potential to identify unsuitable drug candidates at an early stage and to sustainably replace animal experiments in the regulatory evaluation of medicines.