L Focke5; H Benjes5; A Loa5; T Strassmaier2; I Rinke-Weis3; S Hebeisen4; J Schuster4; A Baer4; M Frey6; T Danker1;
1 NMI TT Pharmaservices, Germany; 2 Nanion Technologies Inc., United States; 3 Nanion Technologies GmbH, Germany; 4 B'SYS, Switzerland; 5 acCELLerate GmbH, Germany; 6 Seinbeis Innovation Center, Germany
AbstractThe reliable determination of potential side effects of new drug candidates at an early stage of development is of great importance. A panel of ion channels, that are known to be targeted by drugs causing heart failure, is recommended by the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. With this set of ion channels, a more precise classification of effective substances is possible in comparison to the insufficient testing on hERG blockage and QT prolongation alone (ICH S7A & S7B). The Swiss CRO B’SYS as well as the Steinbeis Innovation Center Cell Culture Technology together with the NMI TT Pharmaservice generated and validated recombinant cell lines that stably express the recommended ion channels of the CiPA panel. It can be difficult to maintain a constant quality of these cell lines in a continually passaged culture making this process incompatible, with a routine screening in high-throughput mode. Optimized for these cell lines, acCELLerate developed a protocol to freeze the cells in a highly functional state. Instantly after thawing and without further cultivation, these Patch Ready Cells (PRCs) exhibit a strong functional expression of the ion channels and display a smooth but durable cell membrane. The PRCs have been qualified by automated patch-clamping on a SyncroPatch 384 (Nanion Technologies, Germany) to demonstrate their applicability in high-throughput cardiotoxicity testing.