Welcome to the CMC Strategy Forum We are pleased to welcome you to the CMC Strategy Forum. The purpose of the CMC Strategy Forum is to provide a venue for biotechnology/biological product discussion. The meetings focus on relevant CMC issues throughout the lifecycle of a product and thereby foster collaborative technical and regulatory interactions. The Forum strives to share information with the regulatory agencies to assist them in merging good scientific and regulatory practices. Outcomes of the Forum meetings are published in an appropriate peer-reviewed journal. Each meeting will focus on a CMC related issue such as product characterization, comparability, specifications, etc. The format of each meeting will consist of case studies and presentations by Industry and/or FDA experts to introduce the topic and the key issues of concern. Breakout sessions will then be conducted to allow for additional discussion on the technical and regulatory details of the topics. It is envisioned that the final outcome of the workshop discussions will be the development of a document to be submitted to the appropriate Regulatory Agency designees for their consideration in developing and/or clarifying good regulatory practice guidelines for biotechnology derived products. The success of the CMC Strategy Forum will depend on your active participation in discussing and raising issues pertaining to development of biologics. We encourage you to participate wholeheartedly in the workshops that have been designed to stimulate exchange of ideas and information. We would like to thank the speakers who are giving generously of their time and resources, and to you, for your attendance. We acknowledge the generosity of our program partners: AbbVie, Inc., Amgen Inc., Biogen Idec, Eli Lilly and Company, Genentech, a Member of the Roche Group, Genzyme, A Sanofi Company, Janssen Pharmaceutical R&D, LLC, MedImmune, National Institute of Standards and Technology (NIST) and Pfizer Inc. We are grateful for the expert management from CASSS and the audio-visual expertise of Michael Johnstone from MJ Audio-Visual Productions. Their experience and guidance in the preparation of this Forum have been invaluable. ACKNOWLEDGEMENTS CMC STRATEGY FORUM GLOBAL STEERING COMMITTEE Siddharth Advant, Kemwell Biopharma, USA John Dougherty, Eli Lilly and Company, USA Steven Kozlowski, CDER, FDA, USA Junichi Koga, Daiichi Sankyo Co., Ltd., Japan Rohin Mhatre, Biogen Idec, USA Anthony Mire-Sluis, Amgen Inc., USA Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland Ilona Reischl, BASG/AGES, Austria Anthony Ridgway, Health Canada, Canada Nadine Ritter, Global Biotech Experts, LLC, USA Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland Mark Schenerman, MedImmune, USA Karin Sewerin, BioTech Development AB, Sweden CMC STRATEGY FORUM NORTH AMERICA PROGRAM COMMITTEE Siddharth Advant, Kemwell Biopharma Yves Aubin, Health Canada John Bishop, CBER, FDA Barry Cherney, Amgen Inc. JR Dobbins, Eli Lilly and Company Julia Edwards, Alnylam Pharmaceuticals, Inc. John Hennessey, Novadigm Therapeutics, Inc. Joseph Kutza, MedImmune Kimberly May, Merck & Co., Inc. Anthony Mire-Sluis, Amgen Inc. Stefanie Pluschkell, Pfizer, Inc. Nadine Ritter, Global Biotech Experts, LLC Reb Russell, Bristol-Myers Squibb Company Dieter Schmalzing, Genentech, a Member of the Roche Group Timothy Schofield, MedImmune Zahra Shahrokh, ZDev Consulting Jeffrey Staecker, Genzyme Corporation, a Sanofi company Patrick Swann, CDER, FDA Andrew Weiskopf, Biogen Idec The Organizing Committee gratefully acknowledges the pharmaceutical and biotechnology industry for their generous support of the CMC Strategy Forum series: SUSTAINING DIAMOND PROGRAM PARTNER Genentech, a Member of the Roche Group SUSTAINING PLATINUM PROGRAM PARTNER Biogen Idec SUSTAINING GOLD PROGRAM PARTNER Abb Vie, Inc. SUSTAINING SILVER PROGRAM PARTNER Pfizer, Inc. PROGRAM PARTNERS Amgen Inc. Eli Lilly and Company Genzyme, A Sanofi Company Janssen Pharmaceutical R & D, LLC MedImmune National Institute of Standards and Technology (NIST) LEADING MEDIA PARTNERS BioProcess International International Pharmaceutical Quality MEDIA PARTNERS American Laboratory American Pharmaceutical Review The Analytical Scientist BioProcessing Journal BioTech International Genetic Engineering & Biotechnology News LCGC North America The Medicine Maker The Pathologist Pharmaceutical Outsourcing RSC Advances separationsNOW.com Technology Networks Limited Forum Abstract Current Perspectives on Host Cell Protein Analysis and Control: Science, Risks and Regulations FORUM CO-CHAIRS: Dieter Schmalzing, Genentech, a Member of the Roche Group, USA Zahra Shahrokh, STC Biologics, USA SCIENTIFIC ORGANIZING COMMITTEE: John Bishop, CBER, FDA, USA Bruce Meiklejohn, Eli Lilly and Company, USA Rashmi Rawat, CDER, FDA, USA Nadine Ritter, Global Biotech Experts, LLC, USA Victoria Sluzky, BioMarin Pharmaceutical Inc., USA For thorough understanding, effective removal and suitable control of host cell proteins (HCPs) in recombinant biotechnology products, state-of-the art analytics are key to properly guide process development and to minimize potential risks to patients such as immunogenic response. Arrays of classic and state-of-the art analytical techniques and approaches are being used to establish control strategies for host cell proteins. They include 2D gel electrophoresis (direct stains or labeled comixtures), 2D-HPLC, immunoassays (commercial kits, in-house platform and product-specific methods) and increasingly, mass spectrometry. Nonetheless, the inherent complexity of hundreds of HCPs challenges the capability of each method to detect, identify and quantify HCPs, some of which can be highly similar and others significantly different in molecular characteristics, abundance and affinity to antibodies raised against them for immunoassays. The latter, for example, limits the capability of immunoassay methods to accurately represent the HCP population and content, resulting in some HCPs potentially evading detection. Moreover, some HCPs may co-purify with the product even with affinity binding steps, if their molecular properties are sufficiently similar. This one-day Forum integrates perspectives on the science, product quality/safety and regulatory aspects of HCPs and their control. Specifically, it aims to provide a critical evaluation of the existing and emerging technologies for characterization, clearance, comparability and control of host cell proteins in biotechnology derived products. Case studies will be presented that exemplify best practices to maximize HCP coverage, the utility of product-specific versus platform methods and the applications of mass spectrometry to aid in detection and estimation of HCPs that evade immunoassays. In addition, industry and regulatory agency experiences on risks to product quality and manufacturing consistency with potential impact on clinical outcomes will be shared. Current regulatory expectations and pharmacopeia efforts will be presented and discussed. CMC Strategy Forum Program Summary Current Perspectives on Host Cell Protein Analysis and Control: Science, Risks and Regulations Monday, January 26, 2015 07:30 – 17:00 Registration on the Mezzanine Level 07:30 – 08:30 Breakfast in the 08:30 – 08:45 CASSS Welcome and Introductory Comments in the Nadine Ritter, Global Biotech Experts, LLC CMC Strategy Forum Welcome and Introductory Comments in the Zahra Shahrokh, STC Biologics Best Practices and Emerging Analytical Technologies to Achieve Optimal Detection of HCPs in Process and Product Workshop Session One in the Session Chairs: ???? 08:45 – 09:15 Advances in HCP Analytics (review of current and newer methodologies to assess and improve coverage) Florian Wolschin, Sandoz GmbH, Kundl, Austria (invited) 09:15 – 09:45 Case Examples of Immunogenic HCPs (application of mass spectrometry to characterization of HCPs and facilitating process improvement) Kevin Van Cott, University of Nebraska, Lincoln, NE USA (invited) 09:45 – 10:15 Product-specific versus Platform Assays: Pros, Cons and Challenges Martin Vanderlaan, Genentech, a Member of the Roche Group, South San Francisco, CA USA 10:15 – 10:45 AM Break in the 10:45 – 12:15 PANEL DISCUSSION – Questions and Answers Kevin Van Cott, University of Nebraska, Lincoln, NE USA (invited) Martin Vanderlaan, Genentech, a Member of the Roche Group, South San Francisco, CA USA Florian Wolschin, Sandoz GmbH, Kundl, Austria (invited) TBD industry or regulator TBD regulator TBD regulator 12:15 – 13:45 Hosted Lunch in the Monday, January 26 continued… Clinical Experience and Regulatory Expectations for HCP Testing and Control Workshop Session Two in the Session Chairs: ????? 13:45 – 14:15 USA Regulatory Experiences and Expectations – Blood Products and Monoclonal Antibodies Laurie Graham, CBER, FDA, Silver Spring, MD USA Alexey Khrenov, CBER, FDA, Silver Spring, MD USA 14:15 – 14:45 European Regulatory Experiences and Expectations – Blood Products and Monoclonal Antibodies Jörg Engelbergs Paul-Ehrlich-Institut, Langen, Germany Erika Friedl, Paul-Ehrlich-Institut, Langen, Germany (invited) 14:45 – 15:15 USP and EDQM Host Cell Protein Guidance Documents – Convergence and Differences Kowid Ho, F. Hoffmann-La Roche Ltd., Basel, Switzerland Anthony Mire-Sluis, Amgen Inc., Thousand Oaks, CA USA 15:15 – 15:45 PM Break in the 15:45 – 17:15 PANEL DISCUSSION – Questions and Answers Oliver Anderka, Novartis Pharma AG, Switzerland (invited) Jörg Engelbergs Paul-Ehrlich-Institut, Germany Erika Friedl, Paul-Ehrlich-Institut, Germany Laurie Graham, CBER, FDA, USA Nancy Green, Health Canada, Canada (invited) Kowid Ho, F. Hoffmann-La Roche Ltd., Switzerland Alexey Khrenov, CBER, FDA, USA Anthony Mire-Sluis, Amgen Inc., USA 17:15 – 17:45 Recap of Program Summary Slide Presentation TBD 17:45 – 18:00 Invitation to CMC Strategy Forum July 2015 18:00 – 19:00 Networking Reception in the Chinese Room Presenters Abstracts