Aim of the project is the development of an automated in vitro screening system for cardiac safety pharmacology with respect to the 3R concept. In the long term the system will replace a significant proportion of the animal experiments performed in cardiac safety pharmacology (Replacement). Besides direct replacement of animal experiments, the system allows for significant reduction of required experiments in safety pharmacology, as the high throughput system permits accomplishment of the mandatory tests already at early time points (Reduction). Compared to existing in vitro assays, this novel development promises a higher validity of the data with respect to cardiac effects of the tested drugs (Refinement). We expect that this will lead to a much broader in vitro testing as with existing assays, already during early phases of drug development. Just through exclusion of many substances with undesired side effects at an early stage, wastage of animals for safety pharmacology and consequential follow-up costs can be reduced considerably.

A further application of the system may be toxicologic testing of existing compounds (REACH). As at present the majority of toxicological analyses are based on animal experiments, a considerable reduction of animal experiments can be expected in this field, also.

The envisaged development is based 1) on heart muscle cells generated from rhesus monkey embryonic stem cells and 2) on an already technically fully developed electrophysiological high throughput test system (http://www.qt-screen.com, Multi Channel Systems, Reutlingen) for detection of QT-prolongation. Although technically mature, this system is so far not accepted due to the fact that it is based on chicken cardiomyocytes.