Welcome to CMC Strategy Forum Japan 2016 On behalf of the CASSS Board of Directors and the CMC Strategy Forum Global Steering Committee, we would like to extend to you a warm welcome to the second meeting of the CMC Strategy Forum Japan 2016. We are very pleased that with the strong support from the Pharmaceuticals and Medical Devices Agency (PMDA Japan), as well as the Japan Pharmaceutical Manufacturers Association (JPMA), and with the continued organization by CASSS and the support from the United States Food and Drug Administration, that we are continuing with the CMC Strategy Forum Japan 2016. The Forum will follow the established model of the CMC Forum series with focus on topics and regulatory updates relevant for Japan and Asia and will feature an opening regulatory session that will include presentations from PMDA, FDA, EMA, Health Canada, as well as Asian health authorities. The technical sessions will include discussions on regenerative medicine/cell therapy, established conditions in the manufacturing process of biopharmaceuticals and established conditions in the specification and analytical procedure. The success of the CMC Strategy Forum Japan will depend on your active participation in discussing and raising issues pertaining to the development of biologics. We encourage you to participate whole-heartedly in the panel discussions that have been designed to stimulate exchange of ideas and information. We would like to thank the speakers and the panel members who are giving generously of their time and resources and to you for your attendance. We would also like to acknowledge the generosity of our strategic program partners for the continued support of the Forum series: AbbVie, Inc., Astellas Pharma Inc., AYUMI Pharmaceutical Corporation, Biogen, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., Eisai Co., Ltd., F. Hoffmann-La Roche Ltd., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., MedImmune, A member of the AstraZeneca Group, Nippon Kayaku Co., Ltd., Novo Nordisk A/S and Takeda Pharmaceutical Company Limited. 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 has been invaluable.

ACKNOWLEDGEMENTS JAPAN SCIENTIFIC ORGANIZING COMMITTEE: Kazuhiko Chikazawa, Pharmaceuticals and Medical Devices Agency (PMDA) Ayako Enokida, Pharmaceuticals and Medical Devices Agency (PMDA) Futaba Honda, Pharmaceuticals and Medical Devices Agency (PMDA) Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency (PMDA) Junichi Koga, Daiichi Sankyo Co., Ltd. In Eui Lee, Kobe University, Graduate School of Science and Technology Innovation Noriyuki Matsumoto, Japan Pharmaceutical Manufacturers Association (JPMA) (Secretariat) Yuuki Miyatake, Teijin Pharma Ltd. Kei Nishimura, UCB Japan Co., Ltd. Hisako Ohnishi, Japan Pharmaceutical Manufacturers Association (JPMA) (Secretariat) Yutaka Osawa, Asahi Kasei Pharma Kazuhisa Uchida, Kyowa Hakko Kirin Co., Ltd. Masatoshi Yamada, Nippon Kayaku Co., Ltd. Reiko Yanagihara, Pharmaceuticals and Medical Devices Agency (PMDA) CMC STRATEGY FORUM GLOBAL STEERING COMMITTEE Siddharth Advant, Kemwell Biopharma, USA Daniela Cerqueira, ANVISA-Brasilian National Health Surveillance Agency, Brasil Yasuhiro Kishioka, PMDA-Pharmaceuticals and Medical Devices Agency, Japan Junichi Koga, Daiichi Sankyo Co., Ltd., Japan Steven Kozlowski, CDER, FDA, USA Ingrid Markovic, CBER, FDA, USA Rohin Mhatre, Biogen, USA Anthony Mire-Sluis, AstraZeneca., USA Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland (Chair) Ilona Reischl, AGES-Austrian Medicines and Medical Devices Agency, Austria Anthony Ridgway, Health Canada, Canada Nadine Ritter, Global Biotech Experts, LLC, USA Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland Mark Schenerman, MedImmune, A member of the AstraZeneca Group, USA Karin Sewerin, BioTech Development AB, Sweden

The Scientific Organizing Committee gratefully acknowledges the pharmaceutical and biotechnology industry for their generous support of the CMC Strategy Forum

Japan 2016.

STRATEGIC DIAMOND PROGRAM PARTNER

F. Hoffmann – La Roche Ltd. STRATEGIC PLATINUM PROGRAM PARTNER

AbbVie, Inc.

Biogen

MedImmune, A member of the AstraZeneca Group

STRATEGIC GOLD PROGRAM PARTNER

Novo Nordisk A/S

FORUM PROGRAM PARTNERS

Astellas Pharma Inc.

AYUMI Pharmaceutical Corporation

Chugai Pharmaceutical Co., Ltd.

Daiichi-Sankyo Co., Ltd.

Eisai Co., Ltd.

Kissei Pharmaceutical Co., Ltd.

Kyowa Hakko Kirin Co., Ltd.

Nippon Kayaku Co., Ltd.

Takeda Pharmaceutical Company Limited

The Scientific Organizing Committee gratefully acknowledges the following media for their promotional consideration of the CMC Strategy Forum Japan 2016.

LEADING MEDIA PARTNERS

BioProcess International

International Pharmaceutical Quality

MEDIA PARTNERS

The Analytical Scientist

BioProcessing Journal

Genetic Engineering & Biotechnology News

LC/GC Asia Pacific

The Medicine Maker

The Pathologist

separationsNOW.com

Technology Networks

CMC Strategy Forum Japan 2016

Scientific Program Summary

Monday, 5 December 2016 06:30 – 08:45 Buffet Breakfast for all CMC registered guests of the Tokyo Marriott Hotel in

the Dining Grill (Lobby Level) 07:30 – 09:30 Coffee Service in the South Ballroom Foyer 07:30 – 17:00 Registration in the South Ballroom Foyer 09:00 – 09:30 CASSS Welcome and Introductory Comments in the South Ballroom Wassim Nashabeh, F. Hoffmann – La Roche Ltd., Switzerland CMC Strategy Forum Japan 2016 Welcome and Introductory Comments in

the South Ballroom Takao Yamori, Pharmaceuticals and Medical Devices Agency (PMDA), Japan

Recent Trends in the Regulation of Biopharmaceutical Products Plenary Session in the South Ballroom

Session Chairs: Ayako Enokida, Pharmaceuticals and Medical Devices Agency (PMDA) and Anthony Ridgway, Health Canada

09:30 – 10:00 PMDA Perspective: Recent Trends in the Regulation of Biopharmaceuticals

Kazuhiko Chikazawa, Pharmaceuticals and Medical Devices Agency (PMDA), Japan

10:00 – 10:30 Korean Perspectives: Recent Trends in the Regulation of Biopharmaceuticals Il Ung Oh, Ministry of Food and Drug Safety (MFDS), Republic of Korea 10:30 – 11:00 The China Regulatory Framework: Recent Trends in the Regulation of

Biopharmaceuticals He Bai, China Food and Drug Administration (CFDA), P.R. China

11:00 – 11:30 AM Break in the South Ballroom Foyer 11:30 – 12:00 EU Regulatory Update on Initiatives for Early Patient Access Niklas Ekman, Finnish Medicines Agency, Finland

Monday, 5 December continued… 12:00 – 12:30 US FDA Perspective: Recent Trends in the Regulation of Biopharmaceuticals Sarah Kennett, CDER, FDA, USA 12:30 – 13:45 Buffet Lunch in the 13:45 – 15:00 Panel Discussion – Questions and Answers

He Bai, China Food and Drug Administration (CFDA), P.R. China Kazuhiko Chikazawa, Pharmaceuticals and Medical Devices Agency (PMDA), Japan

Niklas Ekman, Finnish Medicines Agency, Finland Sarah Kennett, CDER, FDA, USA Il Ung Oh, Ministry of Food and Drug Safety (MFDS), Republic of Korea 15:00 – 15:30 PM Break in the South Ballroom Foyer

Specifications / Potency: Test Procedures and Acceptance Criteria for Cell-based Products Workshop Session in the South Ballroom

Session Chairs: Takao Hayakawa, Kindai University and Kazuhisa Uchida, Kyowa Hakko Kirin Co., Ltd.

15:30 – 15:35 Introduction 15:35 – 16:00 Determination of Potency for Cellular and Tissue-based Products:

Considerations and Challenges Kazunobu Oyama, Pharmaceuticals and Medical Devices Agency (PMDA), Japan

16:00 – 16:25 Development of Allogenic Regenerative Medicine, TEMCELL® HS inj:

Establish Test Procedure and Acceptance Criteria, Especially Specifications and Potency Assay

Kiwamu Imagawa, JCR Pharmaceuticals Co., Ltd., Japan 16:25 – 16:50 Potency Considerations for a hUTC-derived Therapy Carl Burke, Janssen Pharmaceutical R&D LLC, USA 16:50 – 17:15 EU Regulatory Activities and Experience Ilona Reischl, AGES-Austrian Medicines and Medical Devices Agency, Austria 17:15 – 18:15 Panel Discussion - Questions and Answers

Carl Burke, Janssen Pharmaceuticall R&D, LLC, USA Kiwamu Imagawa, JCR Pharmaceutical R&D LLC, USA Kazunobu Oyama, Pharmaceuticals and Medical Devices Agency (PMDA), Japan

Ilona Reischl, AGES-Austrian Medicines and Medical Devices Agency, Austria Anthony Ridgway, Health Canada, Canada

Monday, 5 December continued… 18:15 – 19:45 Networking Reception in the Iris/Camellia Room 19:45 Adjourn Day One

Tuesday, 6 December 2016 06:30 – 08:45 Buffet Breakfast for all CMC registered guests of the Tokyo Marriott Hotel in

the Dining Grill (Lobby Level) 07:30 – 09:30 Coffee Service in the South Ballroom Foyer 08:00 – 17:00 Registration in the South Ballroom Foyer

ICH Q12 Update: Established Conditions in the Manufacturing Process Workshop Session in the South Ballroom

Session Chairs: Wassim Nashabeh, F. Hoffmann-La Roche Ltd. and Haruhiro Okuda, National Institute of Health Sciences (NIHS)

09:00 – 09:25 Introduction and Update on ICH Q12 Guideline Frank Montgomery, AstraZeneca, United Kingdom 09:25 – 09:50 Established Conditions for Manufacturing Process – PMDA Perspective Kyoko Sakurai, Pharmaceuticals and Medical Devices Agency (PMDA), Japan 09:50 – 10:15 Case Studies of Established Conditions in the Manufacturing Process Toshiyuki Suzawa, Kyowa Hakko Kirin Co., Ltd., Japan 10:15 – 10:40 Established Conditions and Enhanced Process Controls

Patrick Swann, Biogen, USA 10:45 – 11:15 AM Break in the South Ballroom Foyer 11:15 – 12:30 Panel Discussion - Questions and Answers Niklas Ekman, Finnish Medicines Agency, Finland Junichi Koga, Daiichi Sankyo Co., Ltd., Japan

Frank Montgomery, AstraZeneca, United Kingdom Kyoko Sakurai, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Toshiyuki Suzawa, Kyowa Hakko Kirin Co., Ltd., Japan Patrick Swann, Biogen, USA

Jinzhong Xiang, China Food and Drug Administration (CFDA), P.R. China 12:30 – 13:45 Buffet Lunch in the Camellia and Garden View Rooms

Tuesday, 6 December continued…

ICH Q12 Update: Established Conditions for Specifications: Relationship with Analytical QbD

Workshop Session in the South Ballroom Session Chairs: Akiko Ishii, National Institute of Health Sciences (NIHS) and Yasuhiro Kishioka,

Pharmaceuticals and Medical Devices Agency (PMDA) 13:45 – 14:10 Established Conditions for the Specification and Analytical Procedure –

PMDA Perspective Rie Fujita, Pharmaceuticals and Medical Devices Agency (PMDA), Japan 14:10 – 14:35 An Industry Perspective on Established Conditions in the Analytical Control

System Christof Finkler, F. Hoffmann-La Roche Ltd., Switzerland 14:35 – 15:00 Case Studies of Established Conditions in Analytical Procedures

Akira Nonoyama, Santen Pharmaceutical Co., Ltd., Japan 15:00 – 15:30 PM Break in the South Ballroom Foyer 15:30 – 16:45 Panel Discussion – Questions and Answers Christof Finkler, F. Hoffmann-La Roche Ltd., Switzerland Rie Fujita, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Sarah Kennett, CDER, FDA, USA

Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland Akira Nonoyama, Santen Pharmaceutical Co., Ltd., Japan

Patrick Swann, Biogen, USA 16:45 – 17:30 Recap of Program Summary Slide Presentation Nadine Ritter, Global Biotech Experts, LLC, USA 17:30 – 17:45 Closing Remarks Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland 17:45 Adjournment

Short Biographies He Bai China Food and Drug Administration (CFDA)

Ms. He Bai is vice consultant in the division of biological products, department of drug and cosmetics registration at China Food and Drug Administration (CFDA). She is taking charge of administrative review and approval of biological products including vaccines, blood products, monoclonal antibodies, recombinant protein drug, cell therapy /gene therapy products, etc.

Ms. Bai joined the CFDA in 2007 where she has worked on the administrative review and approval for clinical trial applications, new drug applications, accelerated new drug applications, and post-marketed variations of biological products in China. Besides that, she also works on drafting/developing the regulatory requirements/guidelines for biological products and the batch release requirements for vaccines, blood products, etc. In addition, Ms. Bai also contributes to lectures and trainings on regulatory requirements.

Prior to joining the CFDA, Ms. Bai had 4 year’s experience working at Beijing Kanglian Medical Equipment Co., Ltd.

Ms. Bai holds a master’s degree from the University of Nottingham in applied biomolecular technology and a degree in biosciences from the Beijing Forestry University. Carl Burke Janssen Pharmaceutical R&D LLC Carl joined Janssen in 2008 and is currently integrating novel platforms and technologies as part of pharmaceutical development and manufacturing sciences, with recent focus on cell therapy development. He previously led the development area in the Janssen vaccines division and earlier drug product development for biologics and parenterals while at Janssen. Carl also spent 18 years at Merck in vaccine and biologics drug product development with experience in live viral, bacteria, DNA and polysaccharide-based vaccines as well as protein and RNA therapeutics. He has contributed to the licensure of many products and is involved in all phases of development efforts. Carl holds a PhD in physical biochemistry from Temple University. Kazuhiko Chikazawa Pharmaceuticals and Medical Devices Agency (PMDA) Niklas Ekman Finnish Medicines Agency Dr. Niklas Ekman has a background in molecular cell and cancer biology. Before joining the Finnish Medicines Agency in late 2006, he worked as a post-doc researcher in the cell cycle and cancer cell circuitry laboratory at the University of Helsinki, Finland. Currently, Dr. Ekman holds a position as a senior researcher and quality assessor for biological medicinal products at the Finnish Medicines Agency. His main activities and responsibilities include assessment of European Medicines Agency (EMA) centralized marketing authorization applications, scientific advices, as well as national clinical trial applications. At EMA, Dr. Ekman is a nominated member of the Biosimilar Medicinal Products Working Party (BMWP) and the Finnish alternate member of the Biologics Working Party (BWP).

Short Biographies continued Christof Finkler F. Hoffmann-La Roche Ltd.

Christof Finkler received his diploma in chemistry and a doctorate in analytical chemistry from the University of Saarland under the supervision of Prof. Dr. H. Engelhardt. In November 1997 Christof joined Roche, working as a team leader in biotechnology analytics in Switzerland. In his current position as site head analytical development biochemistry he is responsible for the establishment of new analytical technologies, protein characterization, development and validation of analytical methods, quality control of investigational medicinal products and transfer of analytics to the commercial QC units. Christof leads the QbD initiative for the development of biotech products at Roche and is member of the EFPIA “Analytical Lifecycle Team”. Rie Fujita Pharmaceuticals and Medical Devices Agency (PMDA) Kiwamu Imagawa JCR Pharmaceuticals Co., Ltd. Sarah Kennett CDER, FDA Sarah obtained her PhD in molecular cance biology at Duke University and followed that with postdoctoral training in the Laboratory of Molecular Carcinogenesis at the National Institutes of Health (NIH). Sarah joined FDA in 2005 as an interagency oncology task fellow in the Office of Cellular, Tissue and Gene Therapies in the Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA). She joined the FDA Center for Druve Evaluation and Research (CDER, Office of Biotechnology Products (OB)), division of monoclonal antibodies in 2007 and was the division’s review chief when OBP was reorganized. She is currently the review chief for OBP’s division of biotechnology review and research I. Junichi Koga Daiichi Sankyo Co., Ltd. Frank Montgomery AstraZeneca Wassim Nashabeh F. Hoffmann-La Roche Ltd. Dr. Wassim Nashabeh received his PhD in analytical chemistry from Oklahoma State University in 1993, and his post-doctoral fellowship in bioanaytical chemistry from The Barnett Institute at Northeastern University. Following a two-year research appointment at PerSeptive Biosystems, Wassim joined Genentech (A member of the Roche Group) in 1996 as a scientist and has since held several positions of increasing responsibilities including associate director of the methods validation group, director quality

Short Biographies continued control, director in the CMC regulatory affairs group, senior director of CMC policy & strategy, global head of technical regulatory policy for the Roche Pharma Medicines Group and most recently as the global head of policy and international operations in PTR. His current responsibilities include development and advocacy of Roche key external positions and policies with global health authorities, industry associations and scientific organizations, as well as management of Roche technical regulatory international operations. Akira Nonoyama Santen Pharmaceutical Co., Ltd. Akira Nonoyama is currently a senior researcher leading pharmaceutical development at Santen since 2016. Before that, he was a senior researcher in the analytical development group at Santen. His areas of expertise include manufacturing process development obtained from his experiences in collaboration with academia and analytical development. He is a member of the Technology Working Committee of Biopharmaceutical Committee in JPMA since 2012. He has a master’s degree in pharmacy from Tokushima University. Il Ung Oh Ministry of Food and Drug Safety (MFDS) Dr. Il Ung Oh received his Ph.D. degree in molecular biology from Kyungpook National University, Korea in 1997. He joined the Korea Food and Drug Administration (KFDA) in 1997 as a scientific officer and has twenty years of experience in review and research of the recombinant protein products. Dr. Oh currently serves as the deputy director of the recombinant protein products division in the Ministry of Food and Drug Safety, Korea. His duties at MFDS include reviewing dossiers of recombinant protein products as well as biosimilar products in authorization, in clinical approval and in post marketing surveillance. He also has responsibilities for establishing evaluation guidelines and monographs for relevant products. For international regulatory convergence, he plays active roles in organizing ‘Biosimilar Working Group” in International Pharmaceutical Regulator’s Forum (IPRF) under ICH. He also participated as a drafting/working group member for the establishment of WHO guidelines regarding the evaluation of monoclonal antibodies as similar biotherapeutic products and procedures and data requirements for changes to approved biotherapeutic products. Kazonobu Oyama Pharmaceuticals and Medical Devices Agency (PMDA) Dr. Oyama is a principal reviewer in the Office of Cellular and Tissue-based Products of the Japanese regulatory agency Pharmaceuticals and Medical Devices Agency (PMDA). Since joining PMDA in 2008, his main work is the pharmaceutical quality review of regenerative medical products and biotechnological/biological products. His areas of expertise also include cell therapy products, gene therapy products, biosimilars and GMP inspection. He holds a PhD from Kobe University in medicine with an emphasis in regenerative medical science.

Short Biographies continued Ilona Reischl AGES-Austrian Medicines and Medical Devices Agency

Ilona Reischl joined the Austrian Medicines and Medical Devices Agency AGES/MEA in March 2006 and is currently the head of the clinical trials unit in the Institute Surveillance. This unit is responsible for clinical trials with medicinal products and medical devices as well as GCP inspections.

The transition to regulatory work from basic science was gradual. After an initial degree in pharmacy, a PhD in immunology/allergology and postdoctoral experience at an industrial research institute, post-doctoral positions followed at the University of Southampton (UK) and the National Institutes of Health (USA) in immunology. The experience of a dual research/regulatory position at the US Food and Drug Administration (FDA) led to the current regulatory focus.

Amongst other activities, she is the Austrian member of the European Medicines Agency Committee for Advanced Therapies and the Biologics Working Party. Anthony Ridgway Health Canada Dr. Ridgway completed his PhD at McGill University in Montreal, and then proceeded to post-doctoral studies followed by an assistant professorship in the Cancer Research Laboratory and Department of Microbiology and Immunology at the University of Western Ontario. Academic research activities included work on the structure and expression of oncogenes, retroviral and HIV regulatory elements and inducible expression vectors. He has been with Health Canada since 1991 and in 1999, became manager of the biotherapeutics division, with responsibility for regulation of a wide range of products. In 2004, he guided the separation of his former division into three new divisions and became the senior regulatory scientist in the office of the director in the newly formed Centre for Evaluation of Radiopharmaceuticals and Biotherapeutics, BGTD. He holds a range of advisory and supervisory responsibilities that includes retaining managerial responsibility for the evaluation of product quality for radiopharmaceuticals and gene therapy products. He has been active with the ICH* since 1993, serving on Expert Working Groups addressing the quality of biotechnology products and is currently with Q12. He has been active on consecutive US Pharmacopoeia Committees of Experts, since June 2000. Dr. Ridgway has been extensively involved in the Canadian approach to subsequent-entry biologics (biosimilars), and the drafting and dissemination of Canadian guidance. *International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Kyoko Sakurai Pharmaceuticals and Medical Devices Agency (PMDA) Dr. Sakurai is a reviewer in the Office of Cellular and Tissue-based Products of the Japanese regulatory agency Pharmaceuticals and Medical Devices Agency (PMDA) since 2011. She is responsible for the pharmaceutical quality review of biotechnological/biological products and performing review of biosimilars.

Short Biographies continued Toshiyuki Suzawa Kyowa Hakko Kirin Co., Ltd. Dr. Toshiyuki Suzawa, through nearly 10 years’ discovery research in protein chemistry at Kyowa Hakko, received his PhD degree from Tokyo Institute of Technology in 2003. Since then he has been involved in process development activities (cell culture and purification) at the company as a senior scientist and his current responsibility is to manage and lead a cell culture process development group. He has a lot of experience in process development activities in the biopharmaceutical field such as monoclonal antibodies and recombinant proteins from early-stage to late-phase products as well as scientific support of commercial LCM products. During this period, he has been a general manager of the production & development center at Fujifilm Kyowa Kirin Co., Ltd. and worked with biosimilar development works for a couple of years. Based on his expertise, he joined Technology Working Committee of Biopharmaceutical Committee in JPMA in 2015 and was also recently assigned as an expert of Q12 EWG. Patrick Swann Biogen Dr. Swann received his PhD in pharmacology from the University of Illinois at Chicago. After completing a post-doctoral fellowship at the National Institutes of Health, Dr. Swann joined FDA’s division of monoclonal antibodies in 1998. He served as a primary reviewer, team leader and finally deputy director of the division. He also served as the biotechnology product representative for FDA on the ICH Q11 Expert Working Group. Dr. Swann joined Biogen in 2013 and is currently a senior director in the CMC regulatory affairs group where he is responsible for providing cross-program strategic CMC regulatory direction to Biogen programs and pharmaceutical operations & technology initiatives. Prior to his current role, he led Biogen’s analytical development group which was responsible for developing and implementing bioassay and biochemical methods that directly support multiple preclinical and clinical programs. He is a frequent speaker at international biotechnology conferences and has authored numerous publications on analytical methods and process development for biotechnology products. Jinzhong Xiang China Food and Drug Administration Mr. Jinzhong Xiang has been a CMC reviewer in the Center for Drug Evaluation, Chinese Food and Drug Administration since 2002. As a CMC reviewer, Mr. Xiang reviews chemistry, manufacturing and controls information for recombinant protein, therapeutic monoclonal antibody products, other antibody related molecules and biosimilars under CTA (Clinical Trial Application), NDA (New Drug Application) and post approval. In addition, Mr. Xiang conducts pre-approval inspections. Prior to joining the CFDA he worked in the National Vaccine & Serum Institute, responsible for research and manufacturing of biological products. He received his bachelor’s degree in microbiology in 1984 from Wuhan University.

Welcome and Introductory Comments Wassim Nashabeh F. Hoffmann – La Roche Ltd., Switzerland AND Takao Yamori Pharmaceuticals and Medical Devices Agency (PMDA), Japan NOTES:

Recent Trends in the Regulation of Biopharmaceutical Products Session Chairs: Ayako Enokida, Pharmaceuticals and Medical Devices Agency (PMDA) and Anthony Ridgway, Health Canada In this opening scientific session, an international group of regulators will present their views on recent trends in the regulation of biopharmaceutical products. In addition to reports from the US FDA, EMA and PMDA will be updates and perspectives from ASEAN. Presenters will include information that will contribute to, and be further explored in, panel discussions covering several themes, including:

1. Options for accelerating manufacturing process development and the associated technical issues and regulatory challenges;

2. Innovative regulatory strategies for enabling the rapid development and the potential for early marketing approval of highly promising new biotherapeutic products, the associated challenges, and progress being made;

3. Updates on relevant guidelines, new or planned, and any ongoing developments regarding Asian trans-national approaches to biopharmaceutical product regulation.

NOTES:

Presenter’s Abstracts and Presentations PMDA Perspective: Recent Trends in the Regulation of Biopharmaceuticals Kazuhiko Chikazawa Pharmaceuticals and Medical Devices Agency (PMDA), Japan NOTES:

Korean Perspective: Recent Trends in the Regulation of Biopharmaceuticals Il Ung Oh Ministry of Food and Drug Safety (MFDS), Republic of Korea The Ministry of Food & Drug Safety has established and pushed ahead with strategies to secure safety & quality of biopharmaceuticals and strengthen Korea’s status in the global community, thereby achieving the goal of becoming one of the world’s 10 biopharmaceutical powerhouses. An increasing number of biopharmaceuticals has been authorized in Korea and their import and expert have also been on a constant rise. What is noteworthy is that large companies such as Samsung, Celltrion and Dong-A are investing in the development of biosimilars building on which in 3-4 years time the world’s first cell therapy product Hearticellgram, was authorized in 2011 followed by the approval of Remsima, which is the world’s first monoclonal antibody biosimilar product. Recently, a number of systems are under refinement or in development to secure drug safety. To promote patient-centric use, relief system of adverse drug reactions and risk management plan were introduced and long-term follow-up studies are in place to assure vigilance about safety of cell therapy products. Renewal of drug approval system is scheduled for 2018. Furthermore, to build a quality assurance system based on scientific assessments, we are planning to launch a scientific National Lot Release System and also make GMP inspection mandatory for orphan drugs in order to improve manufacturing and quality control. At the same time, for accelerated drug review and approval our fast-track review programs underwent some improvements. We created Bio IT platform to provide information on overseas biopharmaceutical industries and regulations. MFDS has been spearheading the APEC biotherapeutics roadmap project since 2013. In 2016, we participated in providing the training courses that were proposed in the 2015 workshop, titled Center of Excellence (CoE) for biotherapeutics which were led by Northeast University and Seoul National University. Such training courses will be continued in 2017. NEU held sessions on theories of analytical comparability for manufacturing changes together with hands-on training in collaboration with Waters. SNU provided training on clinical design to prove biosimilarity both in the U.S. (Sep. 13-16) and Korea (Nov. 8-11). Up until now, MFDS has approved a total of 4 biosimilar products. As of 2015, 21 biosimilar candidates were being tested. In conclusion, MFDS is dedicated to enter the league of global biopharmaceutical powerhouses, we are in the middle of realigning various relevant regulations and formulating support systems. MFDS is also pursuing high level regulatory convergence in biopharmaceuticals through participation in APEC and RHS activities. NOTES:

The China Regulatory Framework: Recent Trends in the Regulation of Biopharmaceuticals He Bai China Food and Drug Administration (CFDA), P.R. China CFDA has initiated regulatory reform of medical device and medicinal product review and approval system since 2015. In this presentation, the goals and major tasks of the regulatory reform and their progress will be introduced, such as accelerated review, optimization of clinical trial approval process. Furthermore, this presentation will cover key considerations on the reform of regulatory system for biologics. NOTES:

EU Regulatory Update on Initiatives for Early Patient Access Niklas Ekman Finnish Medicines Agency, Finland In recent years, the European Medicines Agency (EMA) has put emphasis on timely access to new medicinal products, particularly in areas of unmet need. This presentation will focus on two such initiatives; adaptive pathways for marketing authorisation and the priority medicines (PRIME) scheme. In addition, recent trends in the approval of biosimilars will be reviewed. NOTES:

US FDA Perspective: Recent Trends in the Regulation of Biopharmaceuticals Sarah Kennett CDER, FDA, USA Biopharmaceutical products have experienced a significant amount of success, which has led to enhanced interest and investment in the development of these products. Increased knowledge of biopharmaceutical products and their manufacturing processes, the development of new technologies, and communication among manufacturers and regulatory authorities have led to the advancement and increased use of new or improved mechanisms for managing the products throughout their lifecycles. The FDA has published the “Draft Guidance for Industry: Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products” ahead of the proposed ICH document for pharmaceutical lifecycle management (ICH Q12). This draft guidance is intended to provide FDA’s current thinking regarding the topic of established conditions, including the reporting of and changes to established conditions in BLA, NDA, or ANDA submissions. One mechanism for making post-approval changes to established conditions involves the use of comparability protocols; in recent years, the Agency has seen numerous such protocols submitted to BLAs. The increased understanding of biopharmaceutical products and processes, combined with advanced analytical techniques and approaches, has also supported the development of biosimilar products and biopharmaceutical “breakthrough therapy” products. A brief introduction to the current FDA perspective of these lifecycle management topics will be presented. NOTES:

Recent Trends in the Regulation of Biopharmaceutical Products Plenary Session

Panel Discussion – Questions and Answers He Bai, China Food and Drug Administration (CFDA), P.R. China Kazuhiko Chikazawa, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Niklas Ekman, Finnish Medicines Agency, Finland Sarah Kennett, CDER, FDA, USA Il Ung Oh, Ministry of Food and Drug Safety (MFDS), Republic of Korea The following questions will guide the panel discussion: Theme 1) - Options for accelerating manufacturing process development and the associated technical issues and regulatory challenges:

What is the current regulatory position on the use of pooled clones in the manufacturing of product for use in early clinical trials?

What other strategies are being proposed by industry, or are under consideration? In what areas do regulators think there may be room for some regulatory flexibility?

Theme 2) - Innovative regulatory strategies for enabling the rapid development and the potential for early marketing approval of highly promising new biotherapeutic products, the associated challenges, and progress being made:

What regulatory frameworks and pathways are available for the potential accelerated development and approval of promising new products and how extensively are they being used?

What are the perceived advantages and disadvantages of different approaches and the associated challenges? (Breakthrough vs Sakigake vs PRIME).

The initial approval of such products often relies on less extensive or well-developed data. What are the implications for regulatory convergence and how will regulators in emerging markets address these concepts (e.g., with regard to benchmarking approaches for approving globally marketed products)?

Theme 3) - Updates on relevant guidelines, new or planned, and any ongoing developments regarding Asian trans-national approaches to biopharmaceutical product regulation:

What’s new regarding guideline development in the different regulatory jurisdictions? What’s new that has implications for harmonization?

Regarding regulatory convergence and regional harmonization, what progress is being made at several discussion forums (e.g., APEC, ASEAN, and APAC)?

What is ongoing and what might the future hold in regard to work sharing between health authorities, regionally and globally?

NOTES:

NOTES:

Specifications / Potency: Test Procedures and Acceptance Criteria for Cell-based Products

Session Chairs: Takao Hayakawa, Kindai University and Kazuhisa Uchida, Kyowa Hakko Kirin Co., Ltd. Products consisting of viable cells have attributes that are different in many respects from medical drugs. Manufacturing and quality controls for cell-based products need to be established in consideration of their unique attributes. Moreover, acceptance criteria for quality control should be set to include contributions from non-uniformity of product. Factors attributable to non-uniformities will include those variations present in raw materials as well as in starting cell/tissue banks and the cell manufacturing processes. Furthermore, viable cells can exert their clinical effects through multiple attributes and mechanisms. Thus, identification of the critical quality attributes and correlation to their efficacy and safety is a complex task. In this session, procedures for establishing specifications of cell-based products will be discussed, with a focus on potency specifications. NOTES:

Presenter’s Abstracts and Presentations Determination of Potency for Cellular and Tissue-based Products: Considerations and Challenges Kazunobu Oyama Pharmaceuticals and Medical Devices Agency (PMDA), Japan NOTES:

Development of Allogenic Regenerative Medicine, TEMCELL® HS inj: Establish Test Procedure and Acceptance Criteria, Especially Specifications and Potency Assay Kiwamu Imagawa JCR Pharmaceuticals Co., Ltd., Japan Cell Therapy Products (CTPs) consist of viable cells and present a variation derived from raw materials, as well as the starting cells and the manufacturing processes. Manufacturing and quality controls for CTPs need to be established in consideration of their unique attributes and clinical effects. In order to assure their clinical effects by quality control tests, it is important to set their specifications, especially potency. But in general, CTPs have multiple targets and mechanisms to exert them. Therefore, multiple assays will be required in order to characterize CTPs. Ideally, potency assays are based on the mechanism of action which is assumed from POC studies and it should link with clinical efficacy. This presentation will show the establishment of test procedure and acceptance criteria in a case of TEMCELL ® HS inj, the first allogenic cell-based products in Japan, and it will become the example for discussing how to establish and determine specifications and potency assay of CTPs. NOTES:

Potency Considerations for a hUTC-derived Therapy Carl Burke Janssen Pharmaceutical R&D LLC, USA A human umbilical tissue-derived cell (hUTC) therapy is currently being evaluated for treatment of age-related macular degeneration. The novelty and complexity of cell therapies, in general, makes development of a potency approach challenging. This presentation will give the background for the disease target and pathogenesis as well as describe the characteristics of hUTCs. The mechanism of action and approach to selection of potency assays will also be discussed. NOTES:

EU Regulatory Activites and Experience Ilona Reischl AGES-Austrian Medicines and Medical Devices Agency, Austria NOTES:

Specifications / Potency: Test Procedures and Acceptance Criteria for Cell-based Products Workshop Session

Panel Discussion – Questions and Answers Carl Burke, Janssen Pharmaceuticall R&D, LLC, USA Kiwamu Imagawa, JCR Pharmaceutical R&D LLC, USA Kazunobu Oyama, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Ilona Reischl, AGES-Austrian Medicines and Medical Devices Agency, Austria Anthony Ridgway, Health Canada, Canada The following questions will guide the panel discussion:

What techniques/processes are useful to narrow down the critical quality attributes from exhaustive characteristic analysis?

How many product lots are necessary to set acceptance criteria for starting cells/tissues and products?

To what extent should the manufacturing conditions (e.g. raw materials, processes, scale and equipment) be fixed before manufacturing of products for non-clinical studies? How about products for clinical trials?

What manufacturing changes are acceptable during development? What techniques/processes are available to assess comparability of cell-based products?

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ICH Q12 Update: Established Conditions in the Manufacturing Process

Session Chairs: Wassim Nashabeh, F. Hoffmann-La Roche Ltd. and Haruhiro Okuda, National Institute of Health Sciences (NIHS) Due to the complexity of post-approval change management, which is derived from variability in data requirements, regulatory reporting categories of CMC changes as well as timeline for the approvals among countries, global implementations of post-approval CMC changes is currently quite time-consuming and unpredictable. In order to enhance innovation and continual improvement across the entire product lifecycle that are proposed in ICH Q8, Q10 and Q11, more post-approval operational flexibility should be achieved. To resolve this, the new ICH Quality topic, Q12, was proposed and has been discussed in the expert working group (EWG) as well as in regulatory and/or industry groups supporting the EWG. Through these discussions, one of the most important topics in the ICH-Q12, Established Conditions (ECs), that defines regulatory-binding information amongst information in quality modules of CTD, is gradually in shape for next steps of the guideline. Last CMC Strategy Forum Japan introduced the overall concept of ICH-Q12. This year’s session will focus on ECs. It will start with the update of ICH-Q12 from EWG member, and discuss how ECs concept will be implemented in connection with Japanese Application Form (Approved Matters) using the detailed examples of ECs for manufacturing process and specification. A strategy to determine whether control parameters (e.g., temperature, pH and volume) in manufacturing process steps are ECs or non-ECs will be proposed and discussed. Primary strategy of this determination can be derived from the quality-by-design (QbD) concepts proposed in the ICH Q Quartet. The process to identify critical quality attributes (CQAs) and critical process parameters (CPPs) could be utilized also for the determination of the ECs in the process parameters, because the identification and linkage of CQAs and CPPs are the basis to design a control strategy of the manufacturing process. It will be also explored whether outcome rather than each process parameter could be ECs. Examples of these descriptions are presented. NOTES:

Presenter’s Abstracts and Presentations Introduction and Update on ICH Q12 Guideline Frank Montgomery AstraZeneca, United Kingdom NOTES:

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Established Conditions for Manufacturing Process – PMDA Perspective Kyoko Sakurai Pharmaceuticals and Medical Devices Agency (PMDA), Japan The new ICH quality topic, Q12 will provide a framework to facilitate the management of post-approval manufacturing changes in a more predictable and efficient manner across the product lifecycle. This presentation will provide current PMDA perspective on Established Conditions (ECs) for Manufacturing process and relationship between ECs and Approved Matters in Japanese Application Form. NOTES:

Case Studies of Established Conditions in the Manufacturing Process Toshiyuki Suzawa Kyowa Hakko Kirin Co., Ltd., Japan This case study provides an example for determination of Established Conditions (ECs) in manufacturing process of biopharmaceuticals. A typical model manufacturing process of monoclonal antibody developed under QbD concept is assumed, and a procedure to classify the process parameters into ECs will be proposed for Japanese market approval application using a risk and science-based approach. NOTES:

Established Conditions and Enhanced Process Controls Patrick Swann Biogen, USA Public presentations from members on the ICH Q12 expert working group have referenced the concept of “established conditions”. Established conditions have been defined as “… the description of the product, manufacturing process, facilities and equipment, and elements of the associated control strategy, as defined in an application, that assure process performance and quality of an approved product.” Biogen’s Enhanced Process Controls approach is based on an increased understanding of the product and the process. ICH Q8 describes the differences between traditional and enhanced development approaches and states that a “…greater understanding of the product and its manufacturing process can create a basis for more flexible regulatory approaches.” This presentation will describe Biogen’s vision for Enhanced Process Controls and describe/exemplify what Established Conditions could look like for Enhanced Process Controls as compared to a traditional development program. Additional considerations for a possible enabling role of Q12 concepts on development and lifecycle management will be discussed. NOTES:

ICH Q12 Update: Established Conditions in the Manufacturing Process

Workshop Session Panel Discussion – Questions and Answers Niklas Ekman, Finnish Medicines Agency, Finland Junichi Koga, Daiichi Sankyo Co., Ltd., Japan Frank Montgomery, AstraZeneca, United Kingdom Kyoko Sakurai, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Toshiyuki Suzawa, Kyowa Hakko Kirin Co., Ltd., Japan Patrick Swann, Biogen, USA Jinzhong Xiang, China Food and Drug Administration (CFDA), P.R. China The following questions will guide the panel discussion:

How will EC concept be implemented in ICH region? In Japan, are the ECs similar to, less than or expanded from those described in current Japanese Application Form?

What extent and how can we achieve global harmonization of the ECs?

How should changes to non-ECs be handled? Whether can they be handled solely under company’s PQS or should they be reported to agencies periodically (i.e., annual report, Type IA variation)?

How should ECs and non-ECs be selected from procedure steps, process parameters and in-process controls?

Are CPPs always equivalent to ECs? Is there anything to add to ECs or, vice versa, is there anything to remove from ECs?

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ICH Q12 Update: Established Conditions for Specifications: Relationship with Analytical QbD

Session Chairs: Akiko Ishii, National Institute of Health Sciences (NIHS) and Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency (PMDA) Due to the complexity of post-approval change management, which is derived from variability in data requirements, regulatory reporting categories of CMC changes as well as timeline for the approvals among countries, global implementations of post-approval CMC changes is currently quite time-consuming and unpredictable. In order to enhance innovation and continual improvement across the entire product lifecycle that are proposed in ICH Q8, Q10 and Q11, more post-approval operational flexibility should be achieved. To resolve this, the new ICH Quality topic, Q12, was proposed and has been discussed in the expert working group (EWG) as well as in regulatory and/or industry groups supporting the EWG. Through these discussions, one of the most important topics in the ICH-Q12, Established Conditions (ECs), that defines regulatory-binding information amongst information in quality modules of CTD, is gradually in shape for next steps of the guideline. This session will discuss how to determine which elements are ECs for specifications. One of the arguments in setting ECs for specifications is how “operational flexibility” can be achieved (e.g., change from HPLC methods to UHPLC methods with no regulatory notification)? Recent development of analytical QbD concept can possibly support development of the performance-based ECs for analytical procedures. Tools and concept which are suitable for developing the ECs are presented. NOTES:

Presenter’s Abstracts and Presentations Established Conditions for the Specification and Analytical Procedure – PMDA Perspective Rie Fujita Pharmaceuticals and Medical Devices Agency (PMDA), Japan The ICH Q12 topic provide a framework to facilitate management of post-approval manufacturing changes in a more predictable and efficient manner throughout the product lifecycle. In this presentation, I would like to explain how to think about the Established Conditions (EC) in the Specification and Analytical Procedure. NOTES:

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An Industry Perspective on Established Conditions in the Analytical Control System Christof Finkler F. Hoffmann-La Roche Ltd., Switzerland The application of the principles described in ICHQ8(R2), “Pharmaceutical Development”,ICHQ9 “Quality Risk Management” and ICHQ11 “Development and Manufacture of Drug Substances” are leading to an increased product and process understanding. Product lifecycle management and continual improvement as outlined ICH Q10 “Pharmaceutical Quality System” are important elements to ensure product quality and supply to patients. QbD in analytics transfers these elements into analytical development and contributes to the precise, accurate and robust control of critical quality attributes. The presentation will give an overview how product and process knowledge could lead to different level of details submitted as established conditions for the control of a recombinant antibody in dependence on the level of knowledge and the remaining residual risk. Opportunities for post approval change management considering the regulatory frame work will be discussed. NOTES:

Case Studies of Established Conditions in Analytical Procedures Akira Nonoyama Santen Pharmaceutical Co., Ltd., Japan This case study provides an example of Established Conditions (ECs) determination for biologics-specific analytical procedures. Based on a model SOP for potency assay of G-CSF, two ECs cases, optimized description and performance-based description, will be proposed. This will also present a key concept for determination of ECs. NOTES:

ICH Q12 Update: Established Conditions for Specifications: Relationship with Analytical QbD

Workshop Session Panel Discussion – Questions and Answers Christof Finkler, F. Hoffmann-La Roche Ltd., Switzerland Rie Fujita, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Sarah Kennett, CDER, FDA, USA Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland Akira Nonoyama, Santen Pharmaceutical Co., Ltd., Japan Patrick Swann, Biogen, USA The following questions will guide the panel discussion:

How will EC concept be implemented in ICH region? In Japan, are the ECs similar to, less than or expanded from those described in current Japanese Application Form?

What extent and how can we achieve global harmonization of the ECs?

How should changes to non-ECs be handled? Whether can they be handled solely under company’s PQS or should they be reported to agencies periodically (i.e., annual report, Type IA variation)?

How should ECs and non-ECs be selected / how much details should be described as ECs for specifications? Is the principle of their identification same as the ECs for manufacturing process?

Can concept and tools of analytical QbD be utilized for the ECs for specifications?

(1) In the analytical QbD, what concepts/parameters correspond to the CQAs and CPPs in the QbD for manufacturing process?

(2) What elements should be ECs? For example, considering relationship of the various performance criteria (e.g., analytical target profile (ATP), validation criteria, system and sample suitability), what should be described as ECs?

Do we need to link the discussion on ECs for specifications to Pharmacopeia (i.e., JP)?

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