CiPA – Novel safety screening initiative driven by HESI, FDA and Safety Pharmacology Society
Drug toxicity is a pervasive issue in pharmaceutical drug development that is difficult to avoid but needs to be identified and well mitigated. The current regulatory FDA guidelines for cardiac safety assessment require in vitro hERG and in vivo QT analysis. However, recent studies have shown that hERG block is not a sufficient predictor of arrhythmias. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative aims to evaluate potential modifications to current requirements under the ICH S7B safety pharmacology guidelines. CiPA proposes to utilize complementary approaches which include:
CiPA Work Streams
Comprehensive In Vitro Proarrhythmia Assay:
ACEA Biosciences Supports Efficacious Safety Testing
ACEA Biosciences was selected as core technology for validation testing through the use of the xCELLigence RTCA CardioECR system was chosen as a main instruments for the tests in Phase I and Phase II validation set. Phase I included 8 compounds and Phase II included 28 compounds. Below is a summary of the results for Phase I and Phase II.
ACEA Biosciences joined the CiPA initiative to support one of our core mission of “curing diseases.” Advancements in science now allows reproducible, predictive and translatable human cellular models to facilitate decisions about drug candidates in the drug discovery & development process. Safety assessment plays a key role in this decision-making process and creates a real need for emerging technologies based on human biology to increase success rates of bring life saving therapies to people suffering from cancer, heart disease, diabetes, infections, etc.
CiPA Myocyte Pilot Study
The results of the CiPA Myocyte Pilot Study are published! The use of the xCELLigence CardioECR in the recently published results of the CiPA Myocyte Pilot Study support the use cardiomyocytes for cardiac safety evaluation as defined by FDA/HESI/CSRC’s CiPA initiative. One of the CiPA initiative aims to validate technologies supporting iPSC-derived cardiomyocyte models for the prediction of potential cardiac arrhythmia risks during pharmaceutical therapeutic compound development. These data show the summarized data from the initial Myocyte Team’s blinded “Pilot Studies”. As a validation site, ACEA executed studies confirming the electrophysiological effects, as well as sensitivity, specificity and reproducibility of hiPSC-derived cardiomyocytes in response to eight well-characterized drugs. Concentration-dependent effects on repolarization and observations of arrhythmia-related events consistent with known ionic mechanisms of single and multi-channel blocking drugs were clearly observed in the study. The Myocyte Pilot Study demonstrated the predictive functionality of iPS-derived cardiomyocytes as a HTS-scalable tool for comprehensive cardiac risk assessment to support the adoption of CiPA strategies.
ACEA Biosciences – The Cell Analysis Company
At ACEA Biosciences, our goal is to apply innovative technologies to the analysis of cellular mechanism and response, making studies possible that were not even imaginable just a few years ago. As a global company that places high value on collaborative interactions, rapid delivery of solutions, and providing the highest level of quality, we strive to meet our customers’ needs by delivering innovative, flexible, and scalable solutions to advance the next breakthrough in elucidating mechanisms of the human body. ACEA real-time cell analysis and flow cytometry technologies are fueling groundbreaking advancements in life science research and molecular diagnostics.