New Recommendations for Assessing the Cardiac Safety of New Medicines
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Metrion Biosciences, a specialist ion channel CRO and drug discovery company, has announced it has contributed to two new peer-reviewed papers under the U.S. Food and Drug Administration’s (FDA) CiPA (Comprehensive in vitro Proarrhythmia Assay) initiative. The papers focus on application of improved cardiac safety testing protocols and recommendations for best practice for the drug discovery industry.
The CiPA Initiative, which began in July 2013 following a workshop at the US FDA, has the objective to revise and enhance the regulatory framework assessing cardiac safety of new chemical entities. Under current guidelines, new therapeutics undergo initial assessment of proarrhythmic risk by measuring activity against the hERG cardiac ion channel, before progressing to studies in preclinical animal models and ultimately, a Thorough QT interval study in the clinic.
The CiPA initiative aims to extend the use of advances in early electrophysiology-based cardiac ion channel screening, in silico predictive modeling, and human induced pluripotent stem cell derived cardiomyocytes to improve the accuracy and reduce the cost of predicting the cardiac liability of new drug candidates. Metrion’s research forms part of the first stage of the proposed harmonization work, to provide clarity on how to standardize cardiac ion channel assays to ensure they deliver consistent data for in silico models of clinical cardiac arrythmia risk.
The first paper, published in Nature Scientific Reports, was coordinated by the Health and Environmental Sciences Institute (HESI). It reviews data from a multi-year, multi-site collaboration across industry, academia and the FDA regulatory agency to optimize experimental protocols and reduce experimental variability and bias. The goal of the study was to guide the development of best practices for the use of automated patch clamp technologies in early cardiac safety screening. High quality in vitro cardiac ion channel data is required for accurate and reliable characterization of the risk of delayed repolarization and proarrhythmia in the human heart and to guide subsequent clinical studies and regulatory submissions.
The second paper, published online in Toxicology and Applied Pharmacology, uses automated patch clamp data from the CiPA consortium to address the lack of statistical quantification of variability, which hinders the use of primary hERG potency data to predict cardiac arrhythmia. The consortium establishes a more systematic approach to estimate hERG block potency and safety margins.
Dr Marc Rogers, CSO, Metrion Biosciences, said: “The Metrion team has been a participant in the international CiPA Initiative since inception and we are now pleased to be able to announce the publication of our data from this global collaborative scientific effort. We believe these projects will make a significant contribution to the eventual revision of cardiac safety testing guidelines by the FDA and other international regulatory agencies. They also contribute to deepening our knowledge of the underlying causes of proarrhythmia, which will help prevent early attrition of potentially promising drugs.”