Keynote Presentation: The NIH Microphysiological Systems Program: Tissue on Chips for Safety, Efficacy, and Precision Medicine Studies with Live Q&A

Current methods used to predict safety and efficacy of candidate drugs accounts for as much as 90% failure rate. Approximately 30% of drugs have failed in human clinical trials due to adverse reactions, and another 60% fail due to lack of efficacy. A number of these failures can be attributed to poor predictability of human response from animal and 2D in vitro models currently being used in drug development. Recent systematic studies on the predictive value of animal models have demonstrated a poor correlation between animal data and human outcomes owing to substantial interspecies differences in key disease pathways and disease-induced changes in gene expression profiles, highlighting the critical need for alternative methods to model complex human-relevant conditions. To address this challenge, the NIH Tissue Chips or Microphysiological Systems (MPS) program https://ncats.nih.gov/tissuechip is developing better risk assessment tools that can provide more reliable readouts of toxicity and efficacy of candidate therapies. Tissue chips are bioengineered 3D microfluidic platforms utilizing chip technology and human-derived cells and tissues that are intended to mimic tissue cytoarchitecture and functional units of human organs and systems. In addition to drug development, these microfabricated devices are useful for modeling human diseases, and for studies in precision medicine and environmental exposures. By emulating human physiology, these chips have the potential to increase the predictive power of preclinical modeling, which in turn will move the pharmaceutical industry closer to its aspiration of clinically relevant and ultimately animal-free drug discovery. Tissue chips as novel preclinical modeling platforms offer improved clinical predictions of human response, provide a more efficient approach to mechanistic investigation, early safety liability screening and even more translationally relevant modeling of drug distribution and metabolism. Near term regulatory approval of these human-relevant platforms will fill gaps in current capabilities for assessing important properties of disposition, efficacy, and safety liabilities. The recent passage of the FDA Modernization Act 2.0 will only hasten this process. Towards this end, NCATS is also establishing Translational Centers for MPS to qualify tissue chips as drug development tools.

Learning Objectives:

1. Learn about what tissue chips/MPS are how they are being used as risk assessment tools for safety and efficacy studies.

2. Learn how Tissue chips/MPS are currently being used in industry, especially in drug development.

3. Learn about what it takes to get tissue chips/MPS into regulatory acceptance.