Objective
The Comprehensive In Vitro
Proarrhythmia Assay (CiPA) is a new mechanistical approach to assess the cardiac
risk of drug candidates replacing the insufficient testing on hERG blockage and
QT prolongation alone (ICH S7A & S7B). CiPA which has been proposed by
expert teams of the Cardiac Safety Research Consortium (CSRC), the Health and
Environmental Sciences Institute (HESI) and the Food and Drug Administration
(FDA) employ analysis of a panel of cardiac ion channels known to be targeted by
drugs resulting in Torsades-de-Pointes in combination with in silico
consideration and additional tests using cardiomyocytes.
Here we demonstrate the application
of patch ready cells which express recombinant ion channels of the CiPA panel. The
cells are cryopreserved at a highly functional state and can be used instantly
after thawing in patch clamp assays without any prior cultivation or passaging.
The cells provide a good and stable membrane seal and display strong and consistent
currents of the voltage gated ion channels. A test with selected reference
compounds show that patch ready frozen cells are neither hypersensitive nor
more resistant to channel blocking effects.