The preclinical drug development process is inefficient at selecting drug candidates for human clinical trials, since only 11% of drug candidates selected for clinical trials exit with regulatory approval. Current technology is based on isolated human cells and animal surrogates. We believe that a “human” multiorgan model based on physiologically based pharmacokinetics-pharmacodynamic (PBPK-PD) models that house interconnected modules with tissue mimics of various organs. The system captures key aspects of human physiology that would potentially reduce drug attrition in clinical trials and decrease the cost of development. Integrated, multi-organ microphysiological systems (MPS) based on human tissues (also known as “body-on-a-chip”) could be important tools to improve the selection of drug candidates exiting preclinical trials for those drug most likely to earn regulatory approval from clinical trials. This methodology integrates microsystems fabrication technology and surface modifications with protein and cellular components, for initiating and maintaining self-assembly and growth into biologically, mechanically and electronically interactive functional multi-component systems. While systems can be sampled to measure the concentrations of drugs, metabolites, or biomarkers, they also can be interrogated in situ for functional responses such as electrical activity, force generation, or integrity of barrier function. Operation up to 28 days has been achieved allowing observation of both acute and chronic responses with serum free media. Most importantly these technical advances allow prediction of both a drug’s potential efficacy and toxicity (side-effects) in pre-clinical studies. This talk will also give results of six workshops held at NIH to explore what is needed for validation and qualification of these new systems.
Upon completion, participant will be able to understand how to construct and the function of human-on-a-chip system and their application to opioid research.
Upon completion, participant will be able to understand overdose models in a multi-organ system and evaluate the acute and chronic effects of overdose treatments such as Naloxone on overdose recovery, efficacy as well as off-target toxicity for cardiac, muscle, kidney and liver.
Upon completion, participant will be able to understand applications of human-on-a-chip systems for regulatory science and activity.