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Project Overview: Evaluating Preclinical Cardio-Toxicity Assessment Tools
CHA is launching a multi-company technology evaluation project to explore emerging cardio-toxicity assessment practices and their potential to improve prediction of adverse effects on cardiac function caused by exposure to new chemical entities. 

The objective for the project is to guide the optimization and validation of a quantitative measure of cardiotoxic potential utilizing a profile of ion channel inhibition parameters. 

Project components will include:

  • a comprehensive, industry-wide survey made up of in-depth interviews with leaders of both preclinical screening and safety evaluation
  • blinded testing of compounds in a set of multiple ion channel screens
  • numerous peer-to-peer roundtable meetings

Blinded testing of compounds in a set of multiple ion channel screens will work as follows:

All participating companies will be given the opportunity at no extra cost to have ~ ten (10) compounds (that have in vitro and in vivo CV safety data) run through an array of ion channels assessment screens developed by the Ion Channel Group within Millipore Corporation.*  The goal is to test the system on “real” compounds with known cardiotoxic effects and appraise the “predictivity” of the system on the member companies’ own compounds, as well as across the project membership.  This will allow each participating company to assess the relative strengths and weaknesses of the tool and ultimately a process for ranking all new chemical entities well before the start of in vivo safety studies.  This component of the project is also designed to be collaborative and thus enable participating companies to discuss in a peer-to-peer forum the results of all compounds tested and leverage the shared knowledge of the test results across a large compound set, as well as be able to determine the most appropriate modifications to the assay (please note all compounds specific information, like compound structures, will be kept blinded).. 

Deliverables include:

  • a report and analysis of survey and interview results
  • a report and analysis of the blind testing results
  • participating company summit/retreat to collectively review and interpret the results

* Millipore is a co-sponsor of this Technology Evaluation Project.

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