CiPA Initiative Safety Pharmacology Society Ion Channel Working Group (SPS ICWG) Bernard Fermini and Najah Abi Gerges 31 January 2014 CiPA Initiative SPS ICWG - Brief background • HESI, CSRC, FDA and the SPS have been actively discussing the CiPA paradigm over the past months. • Workstreams have been formed to validate this new paradigm. • Due to the significant impact ion channel data will have on validating the CiPA paradigm, the SPS Board of Directors has endorsed the formation of an “Ion Channel Best Practices” workstream. 2 NAG-BF | 31 January 2014 Set area descriptor | Sub level 1 CiPA Initiative SPS ICWG - Brief background • Where SPS ICWG fits in CiPA? CiPA Steering Committee HESI/FDA/EMA/CSRC PHARMA/Academia HESI Logistic support Communications Safety Pharmacology Society (SPS) Ion Channel Best Practice 3 NAG-BF | 31 January 2014 FDA HESI Regulatory In Silico Model Design Stem Cell Working HESI/FDA Testing, Implementation Group EMA/Health Canada Set area descriptor | Sub level 1 CiPA Initiative SPS ICWG - Task • Bring together expertise and resources needed to deliver best practice recommendations for generating the ion channel data required to evaluate the proarrhythmic liability of a new drug using in silico cardiac cellular simulations. • ICWG members bring the expertise needed to deliver best practice recommendations. Bernard Fermini Najah Abi-Gerges Gary Gintant John Imredy Paul Levesque Khuram Chaudray Bruce Damiano Aurore Colomar Gul Erdmeli John Koerner Jim Kramer William Crumb James Constantin Andrea Brüggemann Stanley Nattel Gail Robertson Jules C Hancox 4 NAG-BF | 31 January 2014 Pfizer AstraZeneca AbbVie Merck BMS GSK Janssen R&D UCB (No response yet) Novartis FDA ChanTest Zenas technologies Molecular Devices Nanion Technologies Montreal University Wisconsin University Bristol University Set area descriptor | Sub level 1 CiPA Initiative Steering Committee Membership Name Norman Stockbridge Tom Colatsky Gary Gintant Hugo Vargas Derek Leishman Jean-Pierre Valentin Philip Sager Jiwen Zhang Krishna Prasad Colette Strnadova Natalia Trayanova Syril Pettit Jennifer Pierson 5 NAG-BF | 31 January 2014 Organization FDA FDA AbbVie Amgen Lilly AZ CSRC GE Healthcare EMA Health Canada Johns Hopkins HESI HESI Representing US Regulators US Regulators Pharm/Non-clinical community Pharma/SPS Pharma/SPS Pharma/Non-clinical community Clinical Community Pharma/Stem Cell Community Non-US Regulators Non-US Regulators Modeling Community HESI Cardiac Safety Committee HESI Cardiac Safety Committee Work Stream Represented All In Silico Work Stream All Ion Channel Work Stream Ion Channel Work Stream Ion Channel Work Stream Regulatory Work Stream Myocyte Work Stream Regulatory Work Stream Regulatory Work Stream In Silico Work Stream All All Set area descriptor | Sub level 1 CiPA Initiative SPS ICWG – Tasks and Timelines • Task 1: How are ion channel data being generated and used to support development of new drugs (i.e., internal decision making, in silico modeling, regulatory submissions)? 1. 2. 3. 4. 6 ICWG agrees the content of the survey (to be completed by Feb 14). Survey current ion channel screening practices (responses to be returned by Mar 5). Process the survey’s data (to be completed by Mar 7). Best practice f-2-f meeting at FDA HQ (March 10-11). NAG-BF | 31 January 2014 Set area descriptor | Sub level 1 CiPA Initiative SPS ICWG – Tasks and Timelines • Task 2: What ion channel data are needed to support in silico APD/proarrhythmia modeling? (to be completed by Jun 2014) 1. Agree the list of ion channels. 2. Agree requirement for “change in conductance” data (effect-concentration curve, IC50, etc…). 3. Agree requirement for “drug-channel interaction” data (voltage dependency, use dependency, frequency dependency, state dependency, mode of action (trapped or not), binding kinetics). 4. Agree voltage protocols to be used. 5. Share recommendations with the CiPA Steering Committee. 7 NAG-BF | 31 January 2014 Set area descriptor | Sub level 1 CiPA Initiative SPS ICWG – Tasks and Timelines • Task 3: Plan experiments (to be completed by July 2014). 1. 2. 3. 4. Biological validation Pharmacological validation (with translational component) Assay validation (Z-factor) Share recommendations with the CiPA Steering Committee. • Task 4: Generate data (to be completed by end of 2014) 1. 2. 3. 8 Agree next steps with the CiPA Steering Committee and working groups. Data to be generated. Data to be used for validating the in silico CiPA model. NAG-BF | 31 January 2014 Set area descriptor | Sub level 1 Confidentiality Notice This file is private and may contain confidential and proprietary information. If you have received this file in error, please notify us and remove it from your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized use or disclosure of the contents of this file is not permitted and may be unlawful. AstraZeneca PLC, 2 Kingdom Street, London, W2 6BD, UK, T: +44(0)20 7604 8000, F: +44 (0)20 7604 8151, www.astrazeneca.com 9 Author | 00 Month Year Set area descriptor | Sub level 1
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