title: Comprehensive in vitro Proarrhythmia Assay (CiPA): Pending issues for successful validation and implementation.
abstract: BACKGROUND
  The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a nonclinical Safety Pharmacology paradigm for discovering electrophysiological mechanisms that are likely to confer proarrhythmic liability to drug candidates intended for human use.
  Key talks delivered at the 'CiPA on my mind' session, held during the 2015 Annual Meeting of the Safety Pharmacology Society (SPS), are summarized. Issues and potential solutions relating to crucial constituents [e.g., biological materials (ion channels and pluripotent stem cell-derived cardiomyocytes), study platforms, drug solutions, and data analysis] of CiPA core assays are critically examined.
  
  
  CONCLUSIONS
  In order to advance the CiPA paradigm from the current testing and validation stages to a research and regulatory drug development strategy, systematic guidance by CiPA stakeholders is necessary to expedite solutions to pending and newly arising issues. Once a study protocol is proved to yield robust and reproducible results within and across laboratories, it can be implemented as qualified regulatory procedure.
authors.affiliation: 54 Rue de la Glacière, 75013 Paris, France. Electronic address: iciliocavero@outlook.com.
authors.forename: Icilio
authors.initials: I
authors.lastname: Cavero
authors.affiliation: Sanofi, Preclinical Safety, Pharmacology, 13 quai Jules Guesde, 94403 Vitry sur Seine, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Guillon
authors.affiliation: Sanofi, Preclinical Safety, Pharmacology, 13 quai Jules Guesde, 94403 Vitry sur Seine, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Ballet
authors.affiliation: GE Healthcare Life Sciences, Maynard Centre, Forest Farm, Whitchurch, Cardiff CF14 7YT, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Clements
authors.affiliation: Inria Paris, and Sorbonne Universités UPMC Paris 6, France.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Gerbeau
authors.affiliation: 13765 Seabiscuit Drive, Reno, NV, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Holzgrefe
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D032383:Myocytes, Cardiac; D010600:Pharmacology; D015203:Reproducibility of Results; D012449:Safety; D013234:Stem Cells
keywords: Comprehensive in vitro Proarrhythmia Assay (CiPA); Field potential data sampling and analysis; Induced pluripotent cell cardiomyocytes (hiPSC-CMs); Multi electrode array (MEA); Patch clamp technologies; Pending issues and solutions; Validation; Voltage sensitive dye (VSD)