SBA Member, 23.10.2018
Government research project to predict hepatic clearance of drugs in humans using Akura™ Flow system results in development partnerships with top pharma companies.
InSphero AG has successfully completed a collaborative project with the FHNW University in Switzerland to develop a 3D organ-on-a-chip assay for predicting metabolic stability of low clearance compounds in pharmaceutical drug development. The one-year project was funded by Innosuisse, the Swiss Innovation Agency.
Low intrinsic clearance, a pharmacokinetic measure of how efficiently or rapidly a compound is eliminated from the body, is a frequent goal of drug discovery projects that seek to reduce dose, enhance exposure, and prolong half-life of drug candidates. Generating accurate in vitro clearance data that reliably predicts drug clearance in humans, however, has proven challenging due to limitations of traditional 2D hepatocyte models and metabolic stability assays
FHNW Professor of Molecular Toxicology Dr. Laura Suter-Dick says, “2D hepatocyte models are not metabolically active long enough in culture to accurately predict intrinsic clearance of slowly metabolized compounds. With InSphero‘s 3D InSight™ Human Liver Microtissues, which are highly standardized, long-lived 3D in vitro models composed of the primary human liver cells necessary for core metabolic functions of the liver, we were able to develop an advanced in vitro assay for investigating and predicting hepatic clearance of drugs in humans.“ To optimize the performance of the assay, the collaborative project team applied InSphero’s novel Akura™ Flow microphysiological system, which allows for up to ten human liver microtissues to be loaded in a single channel to increase the cell-to-media ratio by up to ten fold.
InSphero Head of Technologies and Platforms Dr. Olivier Frey says, “This successful application of our Akura™ Flow platform underscores the importance of using proven, fit-for-purpose biological models in emerging organ-on-a-chip systems. It is an excellent example of how our enabling 3D technology and physiologically relevant models consistently deliver robust, reliable, and reproducible results.” Based on promising data from this innovation project, InSphero has partnered with top pharma companies in Europe and US to further evaluate and benchmark the assay and test low clearance characteristics of drugs under development. InSphero is optimistic this approach will establish a new standard for low clearance assessment.
The new 3D InSight™ Low Clearance Assay will be available as a InSphero in vitro toxicology drug metabolism service starting in early 2019.