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Ready to change the paradigm of cardiac safety assessment?

Current regulatory FDA guidelines for cardiac safety assessment (ICH S7B) require in vitro hERG and in vivo QT analysis. However, it has become well-accepted that hERG block is not sufficiently predictive to detect arrhythmias. A comprehensive cardiomyocyte model is required for a better prediction for cardiac liability. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) consortium aims to validate the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for implementation in regulatory testing of cardiac safety.


Published results of the CiPA Validation study support the utility of hiPSC-cardiomyocyte assays for cardiac safety evaluation.

 

CiPA Validation Study results

CiPA Steering Team

CiPA is coordinated by the CiPA Steering Team and is composed of members of the following organizations:

What is CiPA?

The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a novel safety screening initiative driven by HESI, the FDA and the Safety Pharmacology Society (SPS). The CiPA initiative aims to validate iPSC-derived assays solutions for the identification of cardiac arrhythmias as a side effect of pharmaceuticals with the ultimate aim to include the technology in the regulatory ICH S7B guideline.

 

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Our vision

The drug discovery & development market needs 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 and creates a real need for emerging technologies based on human biology in order to increase success rates. Human stem cell-based cardiomyocyte assay solutions are revolutionizing drug safety studies. Ncardia is at the forefront of this workflow transformation.

What our experts are saying

At Ncardia we believe that stem cell technology will help to get better medicines to patients faster. Our top priority is to develop products and solutions that can be used in the pharma industry on a routine basis. Alternatively, we can provide safety assays as services. We are ready to help you implementing CiPA cardiomyocyte assays in your lab.

Ncardia has adopted stringent quality management metrics to continuously improve operations and ensure quality. We are ready for regulatory acceptance…

Read interview with Greg & Ralf

The CiPA project is unique and very important for multiple reasons. First of all, it is probably the first fully functional cardiac safety model that has been extensively validated…

Read interview with Stefan

Peer-reviewed publications

Our selection of peer reviewed publications about CiPA can be found here. This selection provides the most recent insights and developments of CiPA. For a complete overview of CiPA-related publications we refer you to: The CiPA Project Home Page

CiPA Validation Study

Assessing the use of human iPSC-derived cardiomyocytes under the CiPA Paradigm, as an in vitro proarrhythmia model, 28 compounds of low, medium and high risk for torsade-de-pointes (TdP) were selected and tested in a blinded fashion at 10 international sites to validate the predictivity of the cell model.

Two validated, commercially available cardiomyocytes including Ncardia's Cor.4U® were included in the study and applied to two standardized assay systems; microelectrode array and voltage-sensing optical recording. A prediction model was developed and 3 of initially 7 predictors accurately categorized the compound effects. The responses were not significantly affected by various sites, methods or cell types, demonstrating the robustness and predictive value of human iPSC-derived cardiomyocytes for in vitro proarrhythmia risk assessment. Despite the differences in reprogramming and differentiation protocols between Cor.4U® and the other vendor cardiomyocytes, they were still able to fill the unmet need of being able to predict high/intermediate pro-arrhythmia risk versus low risk drugs.

Prediction models were developed for risk analysis and provided predictive values up to 87% using only 3 predictors, providing high value with minimal complexity in analysis allowing for higher throughput earlier in drug development work flow.

By combining the strengths of both CiPA validated human iPSC-derived cardiomyocytes with other CiPA preclinical proarrhythmia assessment strategies including in silico modeling, cardiac safety teams now have a highly predictive, translatable solution for assessing TdP risk earlier on in drug development which would reduce effort, costs and drug attrition rates.

Read the CiPA Validation Study here.

CiPA Myocyte Pilot Study

We are proud that the results reported in the published CiPA Myocyte Pilot Study support the use of our Cor.4U® Cardiomyocytes for cardiac safety evaluation as defined by FDA/HESI/CSRC’s CiPA initiative. These data from the Pilot Study demonstrate the predictive functionality of iPS-derived cardiomyocytes as a HTS-scalable tool for comprehensive cardiac risk assessment and have paved the way for future validation studies required for further adoption of CiPA strategies.

Read more about the CiPA Myocyte Study here.

Ncardia Posters

Download our White Paper

Our experts Ralf and Greg outline in a White Paper what CiPA and Ncardia can do for you.

Download it below:

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