Human Microphysiological Systems: Organs-on-Chips for In Vitro Efficacy, Safety, and Toxicity Testing
Danilo Tagle,
Associate Director for Special Initiatives,
National Institutes of Health
Advances in basic and preclinical science continue to fuel the drug discovery pipeline, however only a small fraction of compounds meet criteria for approval by the US FDA. More than 30% of promising medications have failed in human clinical trials because they are determined to be toxic despite promising pre-clinical studies in animal models, and another 60% fail due to lack of efficacy. The challenge of accurately predicting drug toxicities and efficacies is in part due to inherent species differences in drug metabolizing enzyme activities and cell-type specific sensitivities to toxicants. To address this challenge in drug development and regulatory science, the US NIH has invested 75 million dollars over a 5-year period to launch in 2012 the Microphysiological Systems (MPS) or Organs-on-Chips Program to develop alternative approaches that would enable early indications and potentially more reliable readouts of toxicity or efficacy.
The MPS program is a partnership between the NIH, DARPA, and the FDA. The goal of the program is to develop bio-engineered microdevices that represent functional units of the 10 major human organ systems: circulatory, respiratory, integumentary, reproductive, endocrine, gastrointestinal, nervous, urinary, musculoskeletal, and immune. The opportunities for significant advancements in the prediction of human drug toxicities through the development of microphysiological systems, requires a multi-disciplinary approach that relies on an understanding of human physiology, stem cell biology, material sciences and bioengineering. This unique and novel in vitro platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the drug development process. These microfabricated devices are also useful for modeling human diseases and may prove to be sufficient alternatives to the use of animal models. At the end of the five year funding period it is anticipated that the av
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