Table of Contents. Symposium Program Partners...2. Exhibitor and Media Partners...3. Acknowledgements...4. General Information...6

Transcription

1 Table of Contents Symposium Program Partners...2 Exhibitor and Media Partners...3 Acknowledgements...4 General Information...6 Student Travel Grants...9 Floor Plans of Meeting Space...10 Bird s Eye View...11 Scientific Program Summary...12 Plenary Session Abstracts...22 Workshop Session 1 (Tuesday, January 29) Descriptions...59 Workshop Session 2 (Wednesday, January 30) Descriptions...63 Workshop Session 3 (Thursday, January 31) Descriptions...67 Workshop Session 4 (Thursday, January 31) Descriptions...71 Technical Seminars (Tuesday, January 29) Abstracts...75 Technical Seminars (Wednesday, January 30) Abstracts...78 Poster Session One (Tuesday, January 29) Abstracts...88 Poster Session Two (Wednesday, January 30) Abstracts

2 The Organizing Committee gratefully acknowledges the Symposium Program Partners for their generous support of WCBP 2013 Sustaining Gold Program Partner AbbVie Inc. Sustaining Silver Program Partner Pfizer, Inc. Sustaining Bronze Program Partner Agilent Technologies Diamond Program Partner Genentech, a Member of the Roche Group Gold Program Partners Biogen Idec MedImmune Waters Corporation Silver Program Partners Amgen Inc. Bristol-Myers Squibb Company Eli Lilly and Company Novo Nordisk A/S Bronze Program Partners Baxter Healthcare Corporation BioMarin Pharmaceutical Inc. GlaxoSmithKline Pharmaceuticals Friend of CASSS Program Partners Genzyme, A Sanofi Company Janssen Research & Development, LLC 2

3 Exhibitor Partners ABC Laboratories, Inc. AAPS AB SCIEX Agilent Technologies ARTEL Associates of Cape Cod, Inc. Beckman Coulter, Inc. Bruker Daltonics, Inc. Catalent Pharma Solutions Ezose Sciences, Inc. Fluid Imaging Technologies, Inc. FortéBio, A Division of Pall Life Sciences HunterLab Lancaster Laboratories, Inc. Laureate Biopharmaceutical Services, Inc. Life Technologies Corporation NanoImaging Services NanoSight Postnova Analytics PPD, Inc. ProteinSimple ProZyme, Inc. Sepax Technologies, Inc. SGS Life Science Services Solvias AG Thermo Scientific Waters Corporation Wyatt Technology Corporation WuXi AppTec, Inc. Leading Media Partner Bio Process International Media Partners Analytical Methods BioProcessing Journal Genetic Engineering and Biotechnology News IPQ Publications LCGC North America Technology Networks Limited 3

4 Symposium Co-Chairs Roman Drews, CBER, FDA Kathy Francissen, Genentech, a Member of the Roche Group Marjorie Shapiro, CDER, FDA Permanent Committee Robert Cunico, Bay Bioanalytical Laboratory, Inc. John Dougherty, Eli Lilly and Company John Frenz, GlobeImmune, Inc. (Chair) Acknowledgements Special Thanks to all the Workshop Session Co-Leaders Workshop Committee Co-Chairs Laura Bass, Pfizer, Inc. Arifa Khan, CBER, FDA Susan Kirshner, CDER, FDA Edwin Moore, Baxter Healthcare Corporation Christopher Joneckis, CBER, FDA Robert Sitrin, SitrinSolutions LLC Program Committee Sid Advant, ImClone Systems Corporation Mehrshid Alai-Safar, Baxter Healthcare Corporation Robert Baffi, BioMarin Pharmaceutical, Inc. Marcus Blȕmel, Novartis Pharma AG Ilse Blumentals, GlaxoSmithKline Phil Carter, Baxter Healthcare Corporation John Champagne, Wyatt Technology Corporation John (JR) Dobbins, Eli Lilly and Company Julia Edwards, Genentech, a Member of the RocheGroup Elizabeth Fowler, CMC Consulting Services Michelle Frazier Amgen Inc. John Hennessey, NovaDigm Therapeutics, Inc. Peter Johnson, 3M Drug Delivery Systems Chulani Karunatilake, Nektar Therapeutics Jon Kauffman, Lancaster Laboratories, Inc. Bob Kuhn, Amgen Inc. Joe Kutza, MedImmune Karen Lee, Genzyme, A Sanofi Company Anthony Lubiniecki, Janssen Research & Development, LLC Stacey Ma, Genentech, a Member of the Roche Group Lotte K. McNamara, PAREXEL International Consulting Shawn Novick, Seattle Genetics, Inc. Brian K. Nunnally, Biogen Idec, Inc. Stefanie Pluschkell, Pfizer, Inc. Lesley Redfern, Abbvie Inc. Nadine Ritter, Biologics Consulting Group, Inc. Reb Russell, Bristol-Myers Squibb Company Mark Schenerman, MedImmune Timothy Schofield, MedImmune Michael Schwartz, GlaxoSmithKline Sally Seaver, Seaver Associates, LLC Zahra Shahrokh, ZDev Consulting Joe Siemiatkoski, Development Insights, LLC Arne Staby, Novo Nordisk A/S Garry Takle, Merck, Sharp and Dohme Michael Washabaugh, MedImmune Ziping Wei, Novavax, Inc. Andy Weiskopf, Biogen Idec, Inc. Yuan Xu, Novartis 4

5 Acknowledgements - Continued Collaborating Organizations American Association of Pharmaceutical Scientists (AAPS) Biotech Section American Chemical Society, Division of Analytical Chemistry (ACS, DAC) Association of Biomolecular Resource Facilities (ABRF) Central New England Chromatography Council (CNECC) Fédération of Internationale Pharmaceutique (FIP), Special Interest Group Pharmaceutical Biotechnology International Association for Biologicals (IAB s) National Institute of Biological Standards and Control (NIBSC) National Institute of Standards and Technology (NIST) PDA West Coast Chapter Audio Visual: Michael Johnstone, MJ Audio-Visual Productions CASSS Staff: Karen A. Bertani, CMP, Director of Meetings Stephanie L. Flores, CAE, Executive Director Linda Mansouria, CMP, CMM, Symposium Manager Renee Olson, Manager of Meetings and Events Mikaela Sanford, Project Coordinator Catherine Stewart, Finance Manager 5

6 General Information Name Badges Please wear your name badge in order to gain admittance to the meetings, power sessions, exhibit hall and social functions. A name badge with a yellow circle represents a one-day registration, which does not include the cost of the Welcome Reception for the CASSS County Fair. Tickets to the Welcome Reception may be purchased at the registration desk at a cost of $ Business Center The Business Center, it is located along the main Promenade Hallway about halfway in between the main lobby and the Grand Ballroom. It is open 24 hours/7 days a week, and is 100% accessible. It is self-automated by swiping a credit card. Photographic Equipment The use of cameras is not permitted during the lecture program, workshops or poster sessions. Cameras are permitted on the exhibit floor. However, permission from the vendors involved must be obtained before photographs can be taken. Poster Sessions All posters will be set up the entire three days of the Symposium in the Promenade Ballroom. This ballroom is located across from the East / State Rooms which is the Exhibit Area on the first floor. Posters in the P-101-T to P-137-T series will be presented on Tuesday at 15:45 16:45. Posters in the P- 201-W to P-237-W series will be presented on Wednesday at 15:00 16:00. The posters have been assigned a Poster Board Number due to the layout in the Promenade Ballroom. Please refer to the map diagram in your registration bag to locate the poster. The map appears on a light green handout. Poster abstracts can be found beginning on page 88 in this book. Registration Registration will be set up in the Cabinet Room located off the Promenade Lobby on the left-hand side from Monday, January 28 through Thursday, January 31. Social Program Tuesday, January 29, :30 22:30 Welcome Reception - CASSS County Fair NOTE: Transportation will be provided. Attendees should be on the bus no later than 6:30 pm. This is a casual event and jeans may be worn. Wednesday, January 30, :45 20:00 Exhibitor Reception East/State Rooms If you have special dietary needs, please notify the Symposium Manager Tuesday morning so that an alternate menu may be prepared. Also, please note that tickets to the Welcome Reception for nonregistered guests or one-day registrants may be purchased at the Symposium registration desk for $

7 Technical Seminars Three technical seminars will be held on Tuesday, January 29 from 13:00 14:00 (lunch is provided). Three technical seminars will be held on Wednesday, January 30 from 12:15 13:15 (lunch is provided). Four technical seminars will be held on Wednesday, January 30 from 17:45 18:45. Please refer to the program summary for more details. Technical Seminar abstracts may be found beginning on page 75. Vendor Passport Program This year CASSS is sponsoring a Kindle Fire giveaway. A Vendor Passport is included in your registration bag. You must visit 12 out of the 28 Exhibitors to be eligible to participate in the drawing. The vendors you visit will stamp your passport. Once you receive 12 stamps or more, you may drop your passport in the raffle drum which is located in the Exhibit Hall. The winner will be announced right after Thursday s luncheon at 13:30 in the Exhibit Hall. The winner MUST be present to win. FDA may not participate. 7

8 In Memory of John O Connor John O'Connor, Ph.D. March 3, December 11, 2012 John O Connor was the WCBP Symposium Co-Chair in Washington, D.C. in 2007 and was a contributor to WCBP for many years. John had a successful thirty-year career at Genentech and most recently served as Head of Global Quality Inspection Management. He earned his undergraduate degree at the University of Notre Dame and his doctorate at the University of Iowa. John brought his sense of humor to his work, and his WCBP presentations, and all that he did. John will be missed by his many friends and colleagues. 8

9 CASSS WCBP 2013 Student Travel Grants CASSS is pleased to provide a limited number of student travel grants for PhD students and post-docs who present applicable posters at the 17 th Symposium on the Interface of Regulatory and Analytical Sciences for Biotechnology Health Products (WCBP 2013). PhD students or post-doctoral fellows conducting research at academia throughout the world are eligible. Requirements are: Present a poster on a WCBP 2013 topic Proof of studentship/post-doc status Recommendation from the supervisor/advisor An abstract submission A CV for the candidate This year s winners include: Comparison of Structure Stability Between Biosimilar and Innovator Drugs Under Stressed Conditions by LC-MS Analysis Suli Liu Northeastern University. Boston, MA USA Comprehensive Characterization of Recombinant Phenylalanine Ammonia Lyase by LC-MS/MS Fangfei Yan Northeastern University, Boston, MA USA 9

10 Hotel Meeting Space Floor Plan 10

11 Bird s Eye View 11

12 WCBP 2013 Final Scientific Program Summary TUESDAY, JANUARY 29, :00 17:00 Registration in the Cabinet Room 07:00 08:15 Continental Breakfast in the East/State Rooms 08:15 08:25 CASSS Welcome and Introductory Comments John Dougherty, Eli Lilly and Company 08:25 08:35 2nd Annual William S. Hancock Award Announcement in the Grand Ballroom Sponsored by CASSS Presented by: Gene Murano, Bioscope Associates 08:35 08:45 WCBP Welcome and Introductory Comments Kathy Francissen, Genentech, a Member of the Roche Group 08:45 10:45 Regulation of Biopharmaceutical Products: Government Perspectives Roundtable Discussion in the Grand Ballroom Session Chair: Kathy Francissen, Genentech, a Member of the Roche Group Moderator: Wassim Nashabeh, Genentech, a Member of the Roche Group Panel Members: Laura Gomes Castanheira, National Health Surveillance Agency (ANVISA), Brasilia, Brazil Churn-Shiouh Gau, Center for Drug Evaluation, Taipei, Taiwan Christopher Joneckis, CBER, FDA, Rockville, MD USA Steven Kozlowski, CDER, FDA, Bethesda, MD USA Anthony Ridgway, Health Canada, Ottawa, Canada Kenneth Seamon, University of Cambridge, Cambridge, United Kingdom 10:45 11:15 AM Break Visit the Exhibits in the East/State Rooms and the Posters in the Promenade Ballroom 12

13 TUESDAY, JANUARY 29 continued Operating Globally Plenary Session in the Grand Ballroom Session Chairs: Stefanie Pluschkell, Pfizer, Inc. and Yuan Xu, Novartis 11:15 11:40 Challenges and Opportunities in the Global Regulatory Environment Diane Zezza, Novartis Pharmaceuticals Corporation, East Hanover, NJ USA 11:40 12:05 Global Development: "We're Not In Kansas Any More!" Bruce Meiklejohn, Eli Lilly and Company, Indianapolis, IN USA 12:05 12:30 Appropriate Control Strategies Eliminate the Need for Redundant Testing of Pharmaceutical Products Thomas Schreitmueller, F. Hoffmann-La Roche, Ltd., Basel, Switzerland on behalf of IFPMA (International Federation of Pharmaceutical Manufacturers & Association), Biotherapeutics Group 12:30 12:45 Panel Discussion - Questions and Answers 12:45 14:15 Lunch Break - Participants on their own 13:00 14:00 Technical Seminars Advancing High Resolution Biopharmaceutical Analytics: Why Intact Mass, Peptide Mapping, and Glycan Analysis Should be Routine and Automated Across Your Organization Sponsored by Waters Corporation Chinese Room NOTE: Lunch is provided for first 100 attendees Not Just Numbers, from Spectra to Decisions Sponsored by Bruker Daltonics, Inc. NOTE: Lunch is provided for first 100 attendees Colonial Room High-Speed, High-Resolution MS/MS Measurements Coupled with Amino Acid Substitution- Specific Searching for Rapid Sequence Variant Analysis Sponsored by AB SCIEX Senate Room NOTE: Lunch is provided for first 100 attendees 13

14 TUESDAY, JANUARY 29 continued Characterization Strategies Plenary Session in the Grand Ballroom Session Co-Chairs: Andrew Weiskopf, Biogen Idec, Inc. and Ziping Wei, Novavax, Inc. 14:15 14:40 From Peaks to Attributes: Leveraging Recent Advances in Analytical Technology to Enable a QbD-focused Analytical Strategy Drew Kelner, Amgen, Inc., Longmont, CO USA 14:40 15:05 Embracing ICH Q11 Our Approach to Recombinant Enzymes Used to Treat Lysosomal Storage Disorders Karen Lee, Genzyme, A Sanofi Company, Framingham, MA USA 15:05 15:30 Characterization of Biotechnology Products: An FDA Perspective Laurie Graham, CDER, FDA, Silver Spring, MD USA 15:30 15:45 Panel Discussion - Questions and Answers 15:45 16:45 Poster Session I in the Promenade Ballroom 16:45 18:00 Workshop Session 1 Operating Globally Chinese Room Sid Advant, ImClone Systems Corporation; Christopher Joneckis, CBER, FDA; Susan Kirshner, CDER, FDA; Joseph Kutza, MedImmune Setting Impurity Limits for Biopharmaceuticals Colonial Room Lokesh Bhattacharyya, CBER, FDA; Nathan Ihle, Seattle Genetics, Inc.; Richard Ledwidge, CDER, FDA; Tom Van Wijk, Abbott Laboratories Characterization Strategies Grand Ballroom Anthony Lubiniecki, Janssen Pharmaceutical Research & Development, LLC; Maria Teresa Gutierrez, CDER, FDA; Oscar Salas-Solano, Seattle Genetics, Inc; Willie Vann, CBER, FDA TUTORIAL: Reference Standards Senate Room Markus Blümel, Novartis Pharma AG; Barry Cherney, Amgen, Inc.; Nancy Kirschbaum, CBER, FDA; Dieter Schmalzing, Genentech, a Member of the Roche Group 18:30 22:30 Welcome Reception at the National Building Museum CASSS County Fair Transportation will be provided 14

15 WEDNESDAY, JANUARY 30, :00 17:00 Registration in the Cabinet Room 07:30 08:30 Continental Breakfast in the East/State Rooms 08:30 08:45 Announcements by Kathy Francissen, Genentech, a Member of the Roche Group Vaccines: Heterogeneity May Be Our Best Bet Parallel Session in the Grand Ballroom Session Chairs: John Frenz, GlobeImmune, Inc. and Arifa Khan, CBER, FDA 08:45 09:10 Analytical Control Strategy for a VLP-peptide Conjugate Vaccine John Amery, Pfizer, Inc., Chesterfield, MO, USA 09:10 09:35 A Multi-dimensional Fingerprint of Recombinant Als3 Glycoprotein Heterogeneity John Hennessey, NovaDigm Therapeutics, Inc., Lower Gwynedd, PA USA 09:35 10:00 Characterization of Glycoconjugate Vaccines from a Regulatory Perspective Willie Vann, CBER, FDA, Bethesda, MD USA 10:00 10:15 Panel Discussion - Questions and Answers Regions with Rapidly Changing Regulatory Expectations Parallel Session in the Colonial Room Session Chairs: Wassim Nashabeh, Genentech, a Member of the Roche Group and Patrick Swann, CDER, FDA 08:45 09:15 Regulations of Biologics in Taiwan Churn-Shiouh Gau, Center for Drug Evaluation, Taipei, Taiwan 09:15 09:45 Biological Regulatory Framework in Brazil Laura Gomes Castanheira, National Health Surveillance Agency (ANVISA) Brasilia, Brazil 09:45 10:15 Panel Discussion - Questions and Answers 10:15 10:45 AM Break - Visit the Exhibits in the East/State Rooms and the Posters in the Promenade Ballroom 15

16 WEDNESDAY, JANUARY 30, continued 10:45 12:00 Workshop Session 2 Vaccines: Heterogeneity May Be Our Best Bet Chinese Room Robin Levis, CBER, FDA; Roberto Rodriguez, Pfizer, Inc; Tina Roecklein, CDER, FDA; Robert Sitrin, Sitrin Solutions, LLC QbD: Experience with QbD Implementation Colonial Room Roman Drews, CBER, FDA; Sean Fitzsimmons, CDER, FDA; Lynne Krummen, Genentech, a Member of the Roche Group; Gregg Nyberg, Amgen, Inc. Analytical Control Strategies Grand Ballroom Ilse Blumentals, GlaxoSmithKline, Rajesh Gupta, CBER, FDA; Ashutosh Rao, CDER, FDA; Reb Russell, Bristol-Myers Squibb Company Pharmacopeial Monographs for Biologics Senate Room Jeff Baker, CDER, FDA; John Bishop, CBER, FDA; Fouad Atouf, United States Pharmacopeia; John Dougherty, Eli Lilly & Company 12:00 13:30 Lunch Break Participants on their own 12:15 13:15 Technical Seminars High-Resolution Characterization of Biologics and Particles Sponsored by Beckman Coulter, Inc. NOTE: Lunch is provided for first 100 attendees Chinese Room New Developments in Chromatography and Mass Spectrometry for Improved Performance, Speed and Data Confidence in Biopharmaceutical Analytics from Research to Routine Workflows Sponsored by Thermo Scientific Colonial Room NOTE: Lunch is provided for first 100 attendees Practical Application of Subvisible Particle Characterization in Biotherapeutic Research and Development Sponsored by ProteinSimple Senate Room NOTE: Lunch is provided for first 100 attendees 16

17 WEDNESDAY, JANUARY 30 continued Specifications: Challenges and Successes in Managing the Diversity of Global Regulatory Expectations Plenary Session in the Grand Ballroom Session Chairs: Laura Bass, Pfizer, Inc. and Shawn Novick, Seattle Genetics, Inc. 13:30 13:55 The Challenge of Establishing Risk-based, Phase Appropriate Specifications in the Real World Chuck Smith, Seattle Genetics, Inc., Bothell, WA USA 13:55 14:20 Specification Development and Evolution: Unique Challenges of Enzyme Therapeutics Victoria Sluzky, BioMarin Pharmaceutical Inc. Novato, CA USA 14:20 14:45 Analytical Control Strategy for Biologics Stephan Krause, MedImmune, Gaithersburg, MD USA 14:45 15:00 Panel Discussion - Questions and Answers 15:00 16:00 Poster Session II in the Promenade Ballroom Host Cell Impurities: You Don't Know What You Don't Know Plenary Session in the Grand Ballroom Session Chairs: Torben Frandsen, Symphogen and Nadine Ritter, Biologics Consulting Group, Inc. 16:00 16:25 Host Cell Protein ELISAs and the Use of Orthogonal Methods Judy Shimoni, Genentech, a Member of the Roche Group, South San Francisco, CA USA 16:25 16:50 Product and Process Related Impurities and Their Impact on Product Quality-A Regulatory Perspective Barbara Rellahan, CDER, FDA, Rockville, MD USA 16:50 17:15 Host Cell Proteins A Case Study Martin Schiestl, Sandoz Biopharmaceuticals, Kundl, Austria 17:15 17:30 Panel Discussion - Questions and Answers 17:30 17:45 Mini Break 17

18 17:45 18:45 Technical Seminars WEDNESDAY, JANUARY 30, continued Establishment and Optimization of a Potency Assay for an Effector mab using "ADCC Reporter Bioassay" Sponsored by Catalent Pharma Solutions Chinese Room New Tools and Methods for Label-free Characterization of Biotherapeutic Molecules Sponsored by FortéBio, A Division of Pall Life Sciences Colonial Room Absolute Macromolecular Characterization of Proteins Using Light Scattering and Related Techniques Sponsored by Wyatt Technology Corporation Grand Ballroom ProteinSEQ Protein Quantitation System: Bringing the Sensitivity and Range of qpcr to Antibody-based Quantitative Protein Assays Sponsored by Life Technologies Corporation Senate Room 18:45 20:00 Exhibitor Reception in the East/State Rooms 18

19 THURSDAY, JANUARY 31, :30 17:15 Registration in the Cabinet Room 07:30 08:30 Continental Breakfast in the East/State Rooms 08:30 08:45 Announcements by Kathy Francissen, Genentech, a Member of the Roche Group Assessment of Color as a Quality Attribute Parallel Session in the Grand Ballroom Session Chairs: Mark Schenerman, MedImmune and John Stults, Genentech, a Member of the Roche Group 08:45 09:10 The Investigational Approach to Identifying the Cause of Color in Biopharmaceutical Products Paul Czajak, Pfizer, Inc., Andover, MA USA 09:10 09:35 What Color Is Your Drug Product Solution? A Quantitative Color Assessment Method Trevor Swartz, Genentech, a Member of the Roche Group, South San Francisco, CA USA 09:35 10:00 Origins of Color Change in Biopharmaceuticals: Identification of Proteinand Excipient-related Factors Alla Polozova, MedImmune, Gaithersburg, MD USA 10:00 10:15 Panel Discussion - Questions and Answers Impurities in Plasma-Derived Therapeutic Protein Products Parallel Session in the Colonial Ballroom Session Chairs: Mehrshid Alai-Safar, Baxter Healthcare Corporation and Tim Lee, CBER, FDA 08:45 09:10 Advanced Analytical Techniques: Examples How These Match Routine Laboratory Analytics of Protein Bio-therapeutics Peter Turecek, Baxter Innovations GmbH, Vienna, Austria 09:10 09:35 Impurities in Human Immunoglobulin Products Peter Vandeberg, Grifols, Inc., Apex, NC USA 09:35 10:00 Thrombotic Adverse Events and Procoagulant Impurities in Immune Globulin Products Mikhail V. Ovanesov, CBER, FDA, Bethesda, MD USA 19

20 THURSDAY, JANUARY 31 continued 10:00 10:15 Panel Discussion - Questions and Answers 10:15 10:45 AM Break - Visit the Exhibits in the East/State Rooms and Posters in the Promenade Ballroom 10:45 12:00 Workshop Session 3 Assessment of Color as a Quality Attribute Chinese Room Patricia Cash, MedImmune; Audrey Jia, CDER, FDA; Ewa Marszal, CBER, FDA; Joseph Siemiatkoski, Development Insights, LLC Process Related Impurities Colonial Room John Bishop, CBER, FDA; Ben Del Tito, Auxilium; Helena Madden, Biogen Idec, Inc; Subramanian Muthukkumar, CDER, FDA Specification Setting Strategies Grand Ballroom Chana Fuchs, CDER, FDA; Al Del-Grosso, CBER, FDA; Lotte McNamara, PAREXEL International Consulting; Zahra Shahrokh, ZDev Consulting Understanding and Controlling Source Impurities for Plasma-derived Therapeutic Protein Products Senate Room Tim Hayes, Prometic; Michael Kennedy, CBER, FDA; Yiping Jia, CBER, FDA; Hugh Price, Cangene 12:00 13:45 Hosted Lunch Break in the East/State Rooms 13:45 15:00 Workshop Session 4 Drug Delivery Devices and Biological Medicines as Combination Products Understanding the Additional Challenges Chinese Room JR Dobbins, Eli Lilly and Company; Peter Johnson, 3M Drug Delivery Systems; Kathy Lee, CDER, FDA; Lana Shiu, CDRH, FDA Characterization of Complex Products Colonial Room Harold Dickensheets, CDER, FDA; Eric Dollins, CBER, FDA; Beth Fowler, CMC Consulting Services, Sally Seaver, Seaver Associates, LLC Biosimilars Grand Ballroom Michele Dougherty, CDER, FDA; Christopher Joneckis, CBER, FDA; Gustavo Grampp, Amgen, Inc.; Andreas Seidl, Sandoz Biopharmacenticals Reprocessing of Biotechnology-derived Products Senate Room Michele Frazier, Amgen, Inc.; Patricia Hughes, CDER, FDA; Sarah Kennett, CDER, FDA; Arne Staby, Novo Nordisk A/S 20

21 THURSDAY, JANUARY 31 continued 15:00 15:30 PM Break in the Promenade Foyer Biosimilars in the United States: A Horse is a Horse of Course of Course Plenary Session in the Grand Ballroom Session Chairs: Brian K. Nunnally, Biogen Idec, Inc. and Marjorie Shapiro, CDER, FDA 15:30 15:55 The Momenta Approach to Developing Biosimilar and Potentially Interchangeable Biologics James Roach, Momenta Pharmaceuticals, Inc., Cambridge, MA USA 15:55 16:30 Biologics Price Competition and Innovation Act of 2009: FDA s Overview of the Regulatory Guidance for the Development and Approval of Biosimilar Products in the US Steven Kozlowski, CDER, FDA, Silver Spring MD USA 16:30 17:00 Panel Discussion - Questions and Answers 17:00 17:15 Closing Comments and Invitation to WCBP 2014 Laura Bass, Pfizer, Inc. 21

22 Plenary Session Abstracts Innovation and Risk in a Globally/Locally Regulated Environment: A Dialogue Session Chair: Kathleen Francissen, Genentech, a Member of the Roche Group Moderator: Wassim Nashabeh, Genentech, a Member of the Roche Group Panel Members: Laura Gomes Castanheira, National Health Surveillance Agency (ANVISA), Brasilia, Brazil Churn-Shiouh Gau, Center for Drug Evaluation, Taipei, Taiwan Christopher Joneckis, CBER, FDA, Rockville, MD USA Steven Kozlowski, CDER, FDA, Bethesda, MD USA Anthony Ridgway, Health Canada, Ottawa, Canada Kenneth Seamon, University of Cambridge, Cambridge, United Kingdom Building on the success of the WCBP 2012 opening regulatory panel, the dialogue in this year s panel will focus on two related themes: 1) balancing innovation and risk in CMC biopharmaceutical development and 2) building true alliances and collaborations to achieve global regulatory convergence. These themes will be addressed following brief introductory remarks from the panelists. The first theme is driven by the recent by the passage of the "Breakthrough Therapies" law in the US and the on-going efforts in the EU on" Adaptive Drug Licensing Procedure". While these efforts are seen as supportive and highly applauded for enabling access of life-saving medicines to patients in potentially record times, the envisioned acceleration and shrinkage of the clinical development program will certainly challenge the existing CMC/GMP development paradigm and raise key questions for the panel to engage in. For instance: what will a 4 vs. 7 years total CMC program development and associated regulatory expectations look like? Given that the cgmp and CMC regulations and expectations have been developed to ensure product quality and consistency relative to the material used to establish safety and efficacy, would deferral of some of these activities or loosening the requirements lead to passing on undesired risk to the patient? Another important area to engage in is impact of such truncated programs on the emerging markets regulatory approval process as likely less information will be available at time of submission. The second (recurring) theme will focus on convergence of global regulations and means of building true alliances and collaborations among regulatory agencies. This theme is driven by the increasing complexity and globalization of biologics, especially in the manufacturing and supply chain related areas. The previous system of highly specialized and focused manufacturing practices will continue to evolve into a "commodity" like practices where key raw materials, intermediates and even drug substances or products will be sourced from a variety of locations, often outside of a regulatory agency direct jurisdiction. This clearly drives the need for closer collaboration and increased reliance on local agencies in ensuring integrity of global supply, and is ultimately predicated on convergence of regulatory practices globally. Selected areas that the panelists will discuss include their respective 22

23 agencies engagement globally, whether they see a meaningful shift in focus compared to historical practices, as well as key priorities and venues are seen to be effective in achieving regulatory convergence. An open Q&A session where conference participants are encouraged to engage the panelists on other topics of interest will also be included in the program. 23

24 Operating Globally Session Co-Chairs: Stefanie Pluschkell, Pfizer, Inc. and Yuan Xu, Novartis This session will focus on the challenges companies and local regulatory agencies are facing when biopharmaceutical products are being developed and ultimately marketed with the intent of global reach. Producing clinical (GMP) Drug Substance and Drug Product and submitting the associated clinical trial applications to meet the regulatory requirements of a diversity of international Boards of Health while minimizing delays to development progression will be discussed. This session will also emphasize lifecycle aspects of commercial products marketed in multiple countries or geographical regions, including issues such as diverse expectations with respect to manufacturing sites, release testing and stability data, GMP inspections, as well as differences in expectations for initial marketing applications and post-approval change management. The dialogue is expected to include innovative ideas on how to improve harmonization, enable parallel clinical development in multiple geographical regions, and overcome hurdles to global access to commercial products in the future. 24

25 Challenges and Opportunities in the Global Regulatory Environment Diane Zezza, Novartis Pharmaceuticals Corporation, East Hanover, NJ USA Operating in a global environment allows many opportunities to facilitate bringing important critical medicines to patients. However, in a regulatory environment where the requirements are evolving and often not globally harmonized, it can also bring challenges. Key regulatory issues will be discussed for products in development through global registration and into the commercial product lifecycle. Logistical challenges, specific regional requirements and diversity, non-harmonized standards, and CMC content differences will be explored. 25

26 Global Development: "We're Not In Kansas Any More!" Bruce Meiklejohn, Eli Lilly and Company, Indianapolis IN USA To be competitive in today s pharmaceutical industry companies need to be able to develop and distribute their products on a global basis. The development of a globally acceptable biotechnology pharmaceutical product adds complexity to the development process and requires multiple areas of scientific and regulatory expertise to be successful. Regional specific expectations must be considered throughout the development process to ensure a timely transition from development to global commercialization. As the development and commercialization of these products becomes a global activity the need to meet regional requirements is becoming more diverse. ICH has helped to normalize expectations in certain regions of the globe, however, as the industry moves to a global focus regional or specific country expectations are emerging resulting in added complexity. The differing expectations include specifications, testing requirements, expiry dating, and sample requirements to name a few. Case studies of the differing expectations and strategies across the development and commercial lifecycle will be discussed. 26

27 Appropriate Control Strategies Eliminate the Need for Redundant Testing of Pharmaceutical Products Thomas Schreitmueller, F. Hoffmann-La Roche, Ltd., Basel, Switzerland on behalf of IFPMA (International Federation of Pharmaceutical Manufacturers & Association), Biotherapeutics Group Importation quality control testing for pharmaceutical, biological/biotechnology and vaccine products at the country level is unlikely to increase public health protection, can delay batch release and therefore access to life saving medicines, and creates an unnecessary burden for the global pharmaceutical industry. 1. Pharmaceutical, biological/biotechnology and vaccine manufacturers have established appropriate control over the production of products through in-process controls, validation of the manufacturing process and release testing of the finished drug products, in line with internationally recognized current good manufacturing practice (GMP) standards. 2. Robust quality systems are in place guiding manufacturing and distribution practices including appropriate validation, control and risk management strategies for the handling, storage, transportation and distribution of the finished drug products. 3. The adequacy of a manufacturer s quality oversight is ensured through reporting requirements as well as regular inspections by competent health authority inspectorates confirming the adequacy of the established processes and the compliance with the product license. 4. National requirements to undertake such redundant importation testing unnecessarily increases inventories, delays product distribution and patient access to high quality, safe and efficacious lifesaving therapeutic and preventative medicines. 5. Regulatory Authorities may use a risk-based approach, by assessing regular and satisfactory inspection results of the Quality Control facilities, to determine whether elimination of redundant importation testing is warranted. For these reasons, this type of importation testing is considered redundant, in many cases, and should not be required in all circumstances. 27

28 Characterization Strategies Session Co-Chairs: Andrew Weiskopf, Biogen Idec, Inc. and Ziping Wei, Novavax, Inc. The introduction of an ever-expanding arsenal of advanced characterization tools in the past decade has enabled us to build in-depth understanding about biopharmaceutical products. But these new technical capabilities, along with emerging regulatory guidances such as ICH Q11, raise important strategic questions about product characterization for biopharmaceutical developers. The enhanced approach to product development requires more scientific knowledge for product understanding throughout the development process. Identification of critical quality attributes (CQAs) and their acceptable ranges have become integral to designing sound manufacturing processes and control strategies. And postapproval, lifecycle management inevitably poses the challenge of continuous improvement in understanding our products. In this session, we aim to gain a variety of perspectives on the strategic aspects and examples of product characterization. How do the objectives and scopes for conducting product characterization evolve over the course of product development and lifecycle management? What role does product characterization play in establishing an initial list of potential CQAs in early stages of clinical development? How does risk-based product and process development change expectations for the extent and timing of product characterization? What influence does Quality-by-Design have on the methodologies we choose to put in our analytical toolbox? Where do we draw the line on characterization with respect to the sensitivity of our analytical instrumentation? How low should one go? 28

29 From Peaks to Attributes: Leveraging Recent Advances in Analytical Technology to Enable a QbD-focused Analytical Strategy Drew Kelner, Amgen Inc., Longmont, CO USA It has long been recognized that the inherent micro-heterogeneity of proteins poses significant challenges in the design of rational, comprehensive release and stability testing strategies for complex biopharmaceutical products. This presentation will demonstrate how the advent of advanced biochemical characterization technologies enables the implementation of testing strategies focused on high criticality product attributes, thereby facilitating the development of a Quality by Design-based analytical strategy. 29

30 Embracing ICH Q11 Our Approach to Recombinant Enzymes Used to Treat Lysosomal Storage Disorders Karen Lee, Genzyme, A Sanofi Company, Framingham, MA USA Drug substance and drug product knowledge are key elements of the enhanced development approach described in ICH Q11. Conducting effective risk assessments, identification of critical quality attributes and constructing process control strategies depend upon leveraging and applying both process and product knowledge. Information gathered during protein characterization studies, often performed at the drug substance stage, plays a critical role in the establishment and evolution of product knowledge. The focus of this presentation will be on the philosophies, components and methods used in the characterization of recombinant lysosomal enzymes. The influence of drug mechanism of action on characterization strategy as well as the value of employing orthogonal characterization tools, particularly in the analysis of glycosylation and receptor binding, will be discussed. Examples of the role that characterization studies have played in the identification of critical quality attributes, evaluation of protein variants and the importance of continued characterization post-approval, will also be provided. 30

31 Characterization of Biotechnology Products: An FDA Perspective Laurie Graham, CDER, FDA, Silver Spring, MD USA During product development and life-cycle management, characterization studies help to determine Critical Quality Attributes (CQAs) or those attributes which impact the safety and efficacy of the product. Due to the large number of attributes associated with biotechnology products, determining the criticality of an attribute can be challenging. Once identified, CQAs can help focus the development and continuous improvement of the manufacturing process and control strategy. In an enhanced approach, per ICH Q11, a increased understanding of how CQAs are influenced by the manufacturing process and material attributes can be used with quality risk management tools to establish a more flexible control strategy and, potentially, a design space. The development of characterization strategies, which utilize current technologies and assess all relevant, including emerging, quality attributes can, however, be challenging. Ms. Graham will discuss the current regulatory expectations with regard to characterization strategies, and their lifecycle management, for monoclonal antibody products. 31

32 Vaccines: Heterogeneity May Be Our Best Bet Session Co-Chairs: John Frenz, GlobeImmune, Inc. and Arifa Khan, CBER, FDA Effective vaccines include both an appropriate antigen and the delivery vehicle that presents the antigen to the immune system in the appropriate fashion. Hence they are complex biological products. Vaccines have become ever more important to the biopharmaceutical industry as they represent a global, highvalue product type that in many cases can be produced with similar infrastructure as used for other biological products. As has been shown with several recently licensed vaccines, a new vaccine with limited competition can provide long-term revenue to companies that solve the riddle of how to make these complex products at moderate cost and exploit the sophistication of modern biotechnology. This session will focus on the challenge of characterizing the inherent heterogeneity in these types of products, how to defend the range of that variability as acceptable for human use and for collecting representative release and stability data that will reflect both the process/analytical capability as well as the biological suitability of the output product. Case studies based on licensed vaccines as well as development candidates will be presented to address these topics. 32

33 Analytical Control Strategy for a VLP-peptide Conjugate Vaccine John Amery, Pfizer, Inc. Chesterfield, MO, USA The Qbeta phage capsid is expressed recombinantly to form a Virus Like Particle (VLP). Peptides are linked to the VLP for the purpose of generating a vaccine against the peptide. The RNA inside the VLP, the linker, and the attached peptide are all characterized and their impact on immunogenicity is evaluated in order to set meaningful specifications. 33

34 A Multi-dimensional Fingerprint of Recombinant Als3 Glycoprotein Heterogeneity John P. Hennessey, NovaDigm Therapeutics, Inc., Lower Gwynedd, PA USA While we tend to think of recombinant proteins as highly purified preparations of very uniform active molecules, the reality is that demonstration of consistent heterogeneity can become the standard of acceptability for some protein products. This is abundantly clear for proteins that undergo posttranslational processing to add N-linked glycosylation to the peptide chain (e.g. monoclonal antibodies). In the case of the recombinant Candida albicans agglutinin-like sequence 3 (Als3) protein being used as a vaccine antigen, post-translational modification is primarily O-linked mannosylation, and appears to result in a diverse and consistent array of molecular variants. This presentation will provide some indication of how we have approached the analytical characterization of this unusual glycoprotein. 34

35 Characterization of Glycoconjugate Vaccines from a Regulatory Perspective Willie Vann, CBER, FDA, Bethesda, MD USA Glycoconjugate vaccines are very effective at preventing diseases caused by encapsulated bacteria. The regulatory life of glycoconjugate vaccines begins in the development and IND stages and extends through post licensure for as long as the vaccines are a part of the drug supply. Characterization is essential throughout this life span. In this presentation we outline some of the goals for characterization of glycoconjugates and their intermediates. We present examples of methodology used to address these goals for characterization. Informal Communication Disclaimer: My comments are an informal communication and represent my own best judgment. These comments do not bind or obligate FDA 35

36 Regions with Rapidly Evolving Regulatory Expectations Session Co-Chairs: Wassim Nashabeh, Genentech, a Member of the Roche Group and Patrick Swann, CDER, FDA The biopharmaceutical industry operates in an increasingly global environment with supply chains and manufacturing networks that can include multiple continents, and products that are imported and exported among regions with differing regulations and review timelines. The expanding availability of biotechnology pharmaceutical products has benefited patients globally, though this has also resulted in new challenges due to country specific regulation of biologics. In certain regions, there are rapidly evolving regulatory expectations and new legislation that bring challenges as well as opportunities to the convergence of regulations. In order to continue to expand the global dialogue and ensure the safety and efficacy of the biological products that are being developed, manufactured, and regulated, this session will address aspects of the regulatory environments in emerging markets. The presentations will focus on the regulatory environments in Taiwan and Brazil and the progress toward regulatory convergence. 36

37 Regulations of Biologics in Taiwan Churn-Shiouh Gau, Center for Drug Evaluation, Taipei, Taiwan Division of Drug & New Biotechnology Products of Taiwan Food and Drug Administration (TFDA) is responsible for assessment, licensure, control and surveillance of drugs and biological products. In order to expedite the regulation process, drug review expertise of the Center of Drug Evaluation (CDE) is integrated into the drug evaluation system of TFDA. After primary report from the review team is completed, cases that pose challenges and/or further considerations will be transferred to the advisor committee (AC) and discussed with review team from which the final recommendation is reached and sent to TFDA. Regulation of biological products requires continuing communication and takes update experience into consideration. In Taiwan, biological products in development cover areas including Mab to cell-based products. Besides guidance from TFDA, regulation of biologics in the trial or NDA stage takes reference from the guidance published by ICH/WHO/FDA/EU. 37

38 Biological Regulatory Framework in Brazil Laura Gomes Castanheira, National Health Surveillance Agency (ANVISA), Brasilia, Brazil Due to the increase in the number of expiring patents on biological products during the last three years, the interest and investment of private and public national producers in the biological market has increased. A large number of national producers have started projects to develop and produce biological products in Brazil. The aim is to produce new products as well as re-creating biological products that are not innovations. Updating the biological regulations to deal with this new scenario will have a key role in developing the biological industry in Brazil. The new Brazilian regulation, Resolution 55/2010, is based on different regulations and guidelines from around the world, including the WHO SBP Guidelines. They follow the same scientific principles as the WHO Guidelines but also have some differences which are due to specific country needs. According to the new regulation in Brazil, the new biotherapeutic products are called new biological products and the copies are called biological products that can be licensed by the comparative pathway or the individual development pathway. The information about the pathway used to license the copies are available in the approval letter, inserts and package of the product. During the presentation the two different regulatory pathways will be explained with some examples. An overview of Latin American regulations and some regional initiatives will be presented too. 38

39 Specifications: Challenges and Successes in Managing the Diversity of Global Regulatory Expectations Session Co-Chairs: Laura Bass, Pfizer, Inc. and Shawn Novick, Seattle Genetics, Inc. \In today s pharmaceutical environment, approval for a product from a single health authority is only the beginning of a long road towards receiving global acceptance. Key sections in the CMC portion of any submission are the specifications and the justifications for the acceptance criteria proposed. While it may be the desired gold standard, the biopharmaceutical industry often cannot establish acceptance criteria based solely on clinical experience due to the fact that clinical studies are not designed to assess effects of products at the limits for all quality attributes. The actual clinical experience is usually gained with product representing the average target product profile. In addition, process understanding is still being accumulated due to limited manufacturing experience, and on-going development of analytical and manufacturing procedures. As a result, the industry often depends on strategies of using confidence intervals or tolerance intervals to help predict future manufacturing capability. However, when the manufacturing experience is very limited, these statistical measures may not accurately reflect the true inherent long-term process variability. In addition, many of the Health Authorities may have specific areas of concern that are reflected in requests to tighten one specification or another, or to include tests for quality attributes that another authority may agree is not necessary. This creates an intricate web of region specific specifications throughout the world that can be challenging to manage. This session will focus on industry experiences in establishing and managing global specifications throughout development, as well as for commercialization, of biopharmaceutical products. 39

40 The Challenge of Establishing Risk-based, Phase Appropriate Specifications in the Real World Chuck Smith, Seattle Genetics, Inc., Bothell, WA USA In principle, the establishment of specifications should be straight forward. A target product profile is defined and a list of critical quality attributes (CQA) is established. Select test methods are chosen for assessing the CQAs and then acceptance criteria or limits are defined appropriately to ensure safety, efficacy, purity and product consistency. In practice, defining specifications for biological products is often a challenge due to the limitations of both product and process knowledge and manufacturing and clinical experience. This presentation will explore these challenges in the context of therapeutic antibody-drug conjugates and examine various ideas toward establishing and managing specifications across the development lifecycle. 40

41 Specification Development and Evolution: Unique Challenges of Enzyme Therapeutics. Victoria Sluzky, BioMarin Pharmaceutical Inc., Novato, CA USA Enzyme replacement therapies are becoming more prevalent, especially for the treatment of rare, genetically inherited disorders. Production and control of these biopharmaceuticals can present unique challenges: they don t readily lend themselves to a platform approach (manufacturing or analytical), often require complex analytical methods, and their control system has to satisfy requirements of multiple regulatory jurisdictions to enable world-wide distribution. Several case studies will be presented to illustrate BioMarin s approach to developing and refining release and stability specifications as we gain process and product understanding during clinical development. The impact of process optimization and scale up on the control system will be considered, together with the role of analytical tools being employed for product release and characterization. Examples of specification modifications when new analytical methodologies were introduced post-approval will also be presented. 41

42 Analytical Control Strategy for Biologics Stephan Krause, MedImmune, Gaithersburg, MD USA The purpose of the analytical control strategy is to assure that materials are manufactured within control and that product is safe and effective throughout shelf-life. The control strategy should be developed with emphasis on sound scientific principles and with attention to international and regional guidelines. Those guidelines while not always explicit are clear on the fundamental principle of the control strategy - assurance of product quality. The analytical control strategy is based upon both process and product attributes. Some attributes are critical to quality while others signal process consistency. Still others may be reported and used to gain continuous knowledge about the process. During development the sponsor gathers information on potential quality attributes and uses this to formulate the analytical control strategy. Key to a rational analytical control strategy is the acknowledgement of risk. Identification of critical quality attributes and justification of acceptance criteria are subject to risks associated with both patient and manufacturing impact. This talk will describe the process of identifying critical quality attributes and developing meaningful acceptance criteria. 42

43 Host Cell Impurities: You Don't Know What You Don't Know Session Co-Chairs: Torben Frandsen, Symphogen and Nadine Ritter, Biologics Consulting Group, Inc. Process related impurities from the host cell have long been monitored in biopharmaceutical production processes and in the final product. Demonstration of process consistency and robustness is critical throughout product and process development. Over the years, several approaches have been taken to measuring host cell proteins and DNA. This session will focus on analytical methods and their capabilities for characterizing and monitoring host cell proteins and DNA. In light of new analytical capabilities and evolving regulatory expectations, the use of orthogonal methods to complement immunoassays and the use of mass spectrometry to assess host cell proteins in originator products will also be discussed, as will insights from the application of established DNA and HCP methods to a large number of biopharmaceutical products. Case studies will be used to highlight the current challenges with this established topic. 43