USA – Evaluating the Potential of Microengineered Human Cellular Systems to Predict Drug Effects in the Clinic

CDER researchers are developing systems that allow for replication of human physiology and better prediction of drug effects before the initiation of clinical trials. These systems have the potential to reduce costly clinical trial failures resulting from observed toxicities.

Our ability to detect drug toxicity before the clinical phase of drug evaluation is limited by physiological differences between animal models used in preclinical testing and human subjects in clinical trials, as well as differences between drug effects in patients and those observed in laboratory assays. These challenges mean that drug developers often conduct costly clinical trials of new drug compounds only to have them fail when toxic effects are observed.

Developing Systems for Improved Preclinical Prediction of Drug Effects in Humans

Microphysiological systems, organs-on-chip, organoids, and physiological cellular microsystems are different classes of microengineered cellular systems made possible by recent advances in microfabrication, which is the process of fabricating miniature structures at micrometer scales or smaller. In constructing these in vitro experimental platforms, researchers are attempting to replicate human physiology and allow observation of drug effects that may correspond more closely to those that would be seen in patients. In addition to detecting more liabilities before clinical trials are conducted, these tools have the potential to replace or supplement clinical trial data when more extensive trials are impractical (e.g., in evaluating drugs to treat rare diseases or developing medical countermeasures to emerging disease threats)…