Abstract

Organs-on-a-Chip: Challenges and Opportunities to Improve Safety Assessment During Drug Development

Cristina Bertinetti-Lapatki, Senior Scientist Mechanistic Safety, Roche Pharma Research & Early Development, F. Hoffmann-La Roche Ltd

In spite of the recent technological advances and the use of more sophisticated in vitro assay read outs which aid to improve the selection of drug candidates early on, drug-induced pre-clinical and clinical toxicities remain one of the leading causes of attrition for the pharmaceutical industry. Up to date, drug safety assessment is carried out on animal models and in vitro single-cell line monolayers or short-lived primary cell cultures. However, the in vivo models fail to fully resemble human physiology and oversimplified in vitro approaches do not accurately reflect the complex physiology of a target organ and often are not predictive of in vivo toxicities. In recent years, the development of advanced cellular models growing in 3 dimensions, displaying improved physiology, involving multiple cell types and the use of platforms incorporating flow and sheer forces has raised hopes for improving the prediction of drug induced adverse effects in human relevant systems. The challenges and opportunities of using such novel in vitro models for the assessment and understanding of the mechanisms of potential drug toxicities will be discussed highlighting case studies that demonstrate the advantage of these platforms to de-risk safety liabilities during drug development.