Microphysiological systems in absorption, distribution, metabolism, and elimination sciences.

The use of microphysiological systems (MPS) to support absorption, distribution, metabolism, and elimination (ADME) sciences has grown substantially in the last decade, in part driven by regulatory demands to move away from traditional animal-based safety assessment studies and industry desires to develop methodologies to efficiently screen and characterize drugs in the development pipeline. The past decade of MPS development has yielded great user-driven technological advances with the collective fine-tuning of cell culture techniques, fluid delivery systems, materials engineering, and performance enhancing modifications. The rapid advances in MPS technology have now made it feasible to evaluate critical ADME parameters within a stand-alone organ system or through interconnected organ systems. This review surveys current MPS developed for liver, kidney, and intestinal systems as stand-alone or interconnected organ systems, and evaluates each system for specific performance criteria recommended by regulatory authorities and MPS leaders that would render each system suitable for evaluating drug ADME. Whereas some systems are more suitable for ADME type research than others, not all system designs were intended to meet the recently published desired performance criteria and are reported as a summary of initial proof-of-concept studies.