12:30pm Registration
1:30 Chairperson’s Remarks
Ron Taticek, Associate Director, CMC Regulatory Affairs, Genentech, Inc.
1:35 Quality by Design: From Concepts to Practical Application
Ron Taticek, Ph.D., Director, Pharma Technical Regulatory, Genentech, Inc.
The first part examines the potential benefits and draw backs of QbD in terms of the initial investment to establish a QbD and risk-based life-cycle approach, and the long term efficiencies in process development and product life-cycle management. The challenges involved with achieving the “Desired State” of sponsor selfmanagement and Regulatory flexibility will be highlighted. Various opportunities for how companies can learn about implementing QbD will be presented. In the second part, approaches for identifying Critical Quality Attributes, Design Space, Critical Process Parameters and Control Strategy will be presented with emphasis on strategic considerations and lessons learned. Considerations for implementation of Expanded Change Protocols in the US and a Post-Approval Lifecycle Management Plan globally will also be discussed. The potential implications of not implementing QbD globally on a sponsor’s Regulatory strategy and on postapproval product lifecycle management will be presented.
2:35 Critical Quality Attributes for Biologics – What Are They and How Do We Measure Them?
Tina S. Morris, Ph.D., Vice President, Biologics and Biotechnology, United States Pharmacopeial Convention
This talk focuses on defining critical quality attributes for different types of biologics (challenges for recombinant vs. naturally derived therapeutics); questions of identity, strength, and purity and how are they addressed in an orthogonal way; sameness and equivalence and how they are addressed (both for method and material); and the role of compendial tests and standards: horizontal and vertical standards and their application throughout the product life cycle.
3:05 Refreshment Break
3:30 Determining Critical Quality Attributes for Biopharmaceutical Glycosylation
Daryl Fernandes, Ph.D., Chief Executive Officer, Ludger Ltd.
Biopharmaceutical glycosylation exhibits high structural complexity with variations in glycoform patterns occurring (a) during product development and (b) from batch to batch during production. These structural variations in glycosylation can lead to changes in the safety and efficacy profiles of the product. This talk introduces the use of a QbD (Quality by Design) approach to relating specific glycosylation features of the therapeutic to its clinical profile. The main focus will be on the principles of a novel, robust method for determining Glycosylation Critical Quality Attributes (GCQAs) for a drug and ranking them in order of importance for the product in the clinic. The advantages of this system over traditional score-based methods for determining CQAs will be explained.
4:00 Regulatory Perspectives on QbD for Biotechnology Products
Michele K. Dougherty, Ph.D., Product Quality Reviewer, Division of Monoclonal Antibodies, OBP/OPS/CDER/FDA
FDA’s Office of Biotechnology Products Quality by Design Pilot program continues to accept proposals for QbD submissions, and has already accepted a number of programs into the pilot. The success of the pilot program and successful implementation of QbD for therapeutic protein and monoclonal antibody manufacturing will require that both industry and the FDA develop an updated approach to product and process development, regulatory submission content and format, and the CMC regulatory expectations and review. Representatives of OBP have participated in a number of public forums where discussions of QbD concepts have taken place. This talk will summarize highlights of FDA - industry interactions focusing on QbD and will offer a current perspective on regulatory issues relating to QbD for biotechnology manufacturing.
4:30 Discussion
5:00 End of Quality by Design Short Course
8:00am Registration
9:00 Chairperson’s Remarks
William F. Bennett, Ph.D., Principal, Bioscope Associates, formerly Senior Director, Science & Policy Assessment and Head, Bioprocess Development, Genentech, Inc.
9:05 Analytical CMC Challenges for Biosimilars in EU & US Regulatory Environments
Tony Weighous, MBA, Director, Solvias, A.G.
Often the analytical aspects of CMC are hidden in the bigger picture of product registration. Manufacturing and clinical trials, however, owing to the complexity of protein biologics success require a high degree of expertise in CMC analysis that meets both the scientific and the quality standards acceptable to regulators. These requirements go far beyond the traditional guidelines for the registration of small molecule drugs. At the time of writing we are on the verge of having a regulatory pathway for approval to market biosimilars in the USA. Pathways have been in place for several years in Europe. We will examine via case studies some key precedents in Europe and the United States and anticipate the opportunities and challenges that may lay ahead.
9:35 Biosimilars from an Innovator Perspective
William F. Bennett, Ph.D., Principal, Bioscope Associates, formerly Senior Director, Science & Policy Assessment and Head, Bioprocess Development, Genentech, Inc.
10:05 Scientific Considerations for the Development of Follow-On Protein Products
Marjorie A. Shapiro, Ph.D., Chief, Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, CDER/FDA
Legislation providing a pathway for Follow-On Biologics, or Biosimilars, in the US is anticipated in the near future. Scientific considerations for the development of these products will be discussed including current regulatory statutes, biochemical and functional analysis and a historical perspective of factors that have influenced the type of data required to support approval of follow-on protein products.
10:35 Refreshment Break
11:00 Biosuperiors Pipeline through Fc Engineering: Low-Risk Approach to Improved Performance Antibodies
John Desjarlais, Ph.D., Vice President, Research, Xencor, Inc.
Building enhancements into clinically validated antibodies to create biosuperiors offers a compelling alternative to the biosimilars approach. We have created and validated a suite of antibody Fc variants that enhance in vivo pharmacokinetics and/or cytotoxicity of targeted antibodies. These modifications have been shown to improve half-life and efficacy in mouse and cynomolgus monkey studies, and thus have the potential to confer commercially superior properties onto offpatent antibodies, including more convenient dosing, lower cost of goods, and improved efficacy.
11:30 Deciphering the Intellectual Property of Biologic Therapeutics
Kathleen M. Williams, Ph.D., J.D., Partner, Intellectual Property Law, Edwards, Angell, Palmer & Dodge LLP
This presentation focuses on the issues that face companies developing therapeutics which are biologics. Whether new, generic or follow-on biologic therapeutics, the commercial markets are significant, and the regulatory pathways still uncertain. How do intellectual property issues such as patent protection as well as third party patent infringement arise and get resolved for biologics? How do concerns as to equivalency--bioactivity, glycosylation, half-life, immunogenicity play a role in IP? What have we learned from history? EPO (Amgen/TKT; Amgen/Roche), Avonex, Pergonal? How does one create a clear pathway as to one’s patent strategy and make statements to the FDA in seeking product approval that is clear and consistent?
12:00pm Discussion
12:30 End of Biosimilars Short Course
*Separate Registration is required for short courses
Speaker Biographies
Ron Taticek
Ron received his Ph.D. in Chemical Engineering and Molecular Cell Biology from Cornell University in 1995. He has over 15 years of experience working in biotechnology. From 1988-1989, he worked on scaling up animal cell cultures in the Pilot Plant at the Biotechnology Research Institute in Montreal. He led a process development group working on optimizing the production of recombinant proteins in perfusion culture at Bayer Biotechnology in Berkeley from 1995-1997. In 1997, he joined Genentech, working in the Cell Culture and Fermentation R&D department. From 1998 through early 2004, he led a group focused on large scale CHO process development. His group developed the commercial cell culture processes for two licensed products (RaptivaTM and AvastinTM). In addition to process development activities, Ron was also involved in start-up activities at the Vacaville plant, process transfer of three antibody products to various cell culture manufacturing sites, implementation of new cell banking and seed train processes, and establishing a standard for cell culture process characterization and validation at Genentech. From 2004-2007, Ron led the Fermentation Manufacturing Sciences and Technology Group that provided scientific and technical support to South San Francisco Production. Ron is currently a Director in Pharma Technical Regulatory and is the Lead on implementation of Quality by Design for Biologics at Genentech.
Tina S. Morris
Dr. Morris is Vice President, Biologics and Biotechnology in the Division of Documentary Standards at USP, which she joined in 2003. She coordinates standard-setting activities in the division related to biologics and biotechnology and manages the scientific liaisons responsible for the relevant Expert Committees. Before joining USP, Dr. Morris’ industrial experience includes major biotech companies in the areas of analytical development, especially mass spectrometry, and recombinant protein characterization. Dr. Morris is the holder of several United States patents in the areas of virology and mass spectrometry assay development. She is the author of more than 20 publications in peer-reviewed journals and a frequent invited speaker at national and international scientific conferences. Before working in industry, Dr. Morris was a Young Investigator Award Fellow for the German Cancer Research Center at the National Institute of Allergy and Infectious Diseases in Bethesda, working on the Virology of Hepatitis A with Dr. Robert H. Purcell. Dr. Morris earned her Ph.D. degree in molecular virology at the Medical University of Lübeck, Germany and her MS and BA degrees in biology at the University of Oldenburg, Germany.
Daryl Fernandes
Daryl is Founder and CEO of Ludger Ltd, Oxford, UK. He has over 25 years experience in developing and using glycoanalysis techology. He gained his doctorate at the Glycobiology Institute, University of Oxford in the 1980s, was a consultant on biopharmaceutical glycoprofiling to Monsanto and G.D. Searle and helped spin out Oxford GlycoSciences (OGS) from the University. He joined OGS as Process Development Manager and then as the Head of Analytical Services. Daryl left OGS to set up Ludger in 1999. Ludger has laboratories at the Culham Science Centre near Oxford, UK and develops technology to measure and control biopharmaceutical glycosylation throughout the drug life cycle. The company provides a range of glycoprofiling systems and analytical services to biologics developers and manufacturers worldwide.
Michele K. Dougherty
Dr. Dougherty has been a Product Quality Reviewer in the Division of Monoclonal Antibodies, US Food and Drug Administration since 2008. As a Product Quality Reviewer, Dr. Dougherty reviews Chemistry, Manufacturing and Controls information for therapeutic monoclonal antibody products and other antibody related molecules under IND, BLA and post approval. In addition, Dr. Dougherty contributes to mechanism of action and signaling discussions regarding antibody activity as they relate to drug labeling, such as the class-labeling issues for the anti-EGFR monoclonal antibodies. More recently, she has focused on Quality by Design for Biotechnology products; participating in workshops and training sessions exploring QbD concepts and implementation. Prior to joining the FDA, Dr. Dougherty completed her post-doctoral studies in Dr. Deborah Morrison’s laboratory at the National Cancer Institute in Frederick, MD. Her work focused on characterization of the ERK-scaffold Kinase Suppressor of Ras 2 and defining mechanisms of Raf-1 and B-Raf regulation. She received her Ph.D. in Cancer Biology in 2001 from Georgetown University, where she studied the signaling pathways critical for estrogen receptor negative breast cancer proliferation and survival.
Bill Bennett
Bill is a Principal of Bioscope Associates LLC. Until 2009, he was Senior Director of Regulatory Policy at Genentech, and led the Genentech Biosimilars working group. In 2007-2009, he lectured on the emerging topic of Biosimilars and Follow-on-Biologics on five continents. He was at Genentech for 18 years altogether, having held high-level positions in Research, Bioprocess Development, and Regulatory Affairs. He helped guide Genentech over many years through his participation on the Research Review, Product Development, Process Development Review, and Appointments and Promotions Committees. Scientifically, his work on human growth hormone and tissue-type plasminogen activator has resulted in over 50 peer-reviewed publications and 19 US patents. He led the Research and Development of Activase & TNKase, (first and second generation thrombolytic treatments for Acute Myocardial Infarction, Pulmonary Embolism, and Stroke). During a period away from Genentech, as CSO at Sensus Corporation, he led the research & development of Somavert (a treatment for acromegaly) and was the VP of Research at Cor Therapeutics, and the Senior VP of R&D at Hyseq/Nuvelo. He returned to Genentech in 2003. Bill has a B.A. in Chemistry from TCU and a Ph.D. in Biochemistry from the University of Texas Southwestern Medical School.
Marjorie Shapiro
Dr. Shapiro joined the Division of Monoclonal Antibodies, FDA in 1993. She is currently Chief of the Laboratory for Molecular and Developmental Immunology in the Division of Monoclonal Antibodies where she supervises regulation of monoclonal antibodies, antibody- drug conjugates and Fc fusion proteins against B cell, stem cell, and myeloid cell surface antigens, cytokines and cytokine receptors, and microbial agents. Dr. Shapiro received her Ph.D. in immunology from the University of Pennsylvania where she studied the molecular mechanisms underlying antibody diversity. Her current research continues towards understanding both molecular and epigenetic mechanisms in the development of the antibody repertoire, the diversity generated under artificial selection conditions (phage display) relative to natural selection conditions (hybridomas) and the usage of specific antibody sequences in different B cell subsets.
Kathleen Madden Williams
Dr. Williams is an intellectual property attorney who specializes in complex legal issues surrounding the protection of discoveries in the life sciences. She has extensive experience advising biotech and pharmaceutical clients on strategic legal issues relating to intellectual property, which includes helping companies avoid roadblocks and laying the groundwork for new commercial efforts. She provides advice to clients on patent portfolio creation and management, patentability and freedom to operate legal opinions, patent prosecution, and intellectual property due diligence for investments. Kathy works closely with companies to ensure that intellectual property is effectively protected and/or avoided in their business deals. Her clients include start-up biotech companies, as well as mature biotech and pharmaceutical companies, and research institutions.