2015-The-Bioprocessing-Summit-Brochure(2).Pdf

Final Agenda Final Weeks to Register!

Seventh Annual THE BIOPROCESSING SUMMIT Practical Solutions for Today’s Bioprocess Challenges

August 3-7, 2015 Westin Copley Place, Boston, MA

Premier Sponsors

REGISTER ONLINE NOW! BioprocessingSummit.com BioprocessingSummit.com Organized by Cambridge Healthtech Institute 1 About the Summit PREMIER SPONSORS:

The Bioprocessing Summit The Bioprocessing Summit brings together international leaders from over 30 countries to discuss today’s bioprocess issues, from cell line selection to manufacturing. The Summit provides practical details in a relaxed, congenial atmosphere that promotes information exchange and networking, and features Small-Group Breakout Discussions, a vibrant poster display, a busy Exhibit Hall, and networking Receptions. Spanning five days, the 2015 meeting includes 12 Conference Programs, 8 Training Seminars and 10 Short Courses.

Plenary Keynote Presentation: 4:45 pm, Wednesday, August 5 CORPORATE SPONSORS: Meeting the Needs of Patients with Rare Diseases: Innovation in Product Development Joanne T. Beck, Ph.D., Senior Vice President, Pharmaceutical Development, Shire Pharmaceuticals

2 Event-at-a-Glance

Monday - Tuesday Wednesday - Thursday AM Thursday PM - Friday August 3 - 4 August 5 - 6 August 6 - 7

STREAM #1 Optimizing Cell Culture Bioproduction: Scale, Bioreactors Optimizing Cell Line Development Cell Culture & Cell Line Technology & Disposables Development

STREAM #2 Overcoming Formulation High-Concentration Advances in Purification Challenges for Biopharmaceutical Protein Formulations Technologies Formulation & Downstream Development & Manufacturing Processing

STREAM #3 Rapid Methods to Assess Quality & Early Analytical Development for Virus Detection, Clearance & Safety of Biologics Analytical & Quality Stability of Biologics Biotherapeutics

STREAM #4 Cell Therapy Bioproduction Continuous Processing in Biopharm Advances in Purification Process Innovations & Manufacturing Technologies Cell Therapeutics

STREAM #5 Bioprocess Quality and Training Seminar: Current & Emerging Virus Detection, Clearance Regulatory Compliance Global Regulatory Expectations & Safety of Biologics Regulatory & Risk for Analytical Elements of Management Biotechnology/Biosimilar Products

August 3-4 August 5-6 August 6-7 Day 1: 1:00-5:15pm Day 1: 9:00am-5:15pm Day 1: 2:00-5:30pm Day 2: 8:30am-5:00pm Day 2: 8:30am-12:00pm Day 2: 8:30am-4:30pm

Introduction to Bioprocessing Introduction to Cell Culture Bulk API: Freeze-Thaw Operations

Introduction to Extractables & Design of Experiments (DoE) for Introduction to Lyophilization Leachables & Packaging Bioprocess Analysis Introduction to Analytical Method Current & Emerging Global Regulatory Development & Validation for Expectations for Analytical Elements of Cambridge Healthtech Therapeutic Proteins Biotechnology/Biosimilar Products

SHORT COURSES* DINNER SHORT COURSES* DINNER SHORT COURSES* Monday, August 3 Tuesday, August 4 Thursday, August 6 9:00-11:30 am 6:00-8:30 pm 6:30-9:00 pm REGISTER ONLINE NOW! BioprocessingSummit.com *Separate registration required

3 Short Courses*

MONDAY, AUGUST 3 Tuesday, August 4 Dinner Short Courses (Cont.)

Morning Short Courses | 9:00-11:30 am SC5: Operational Excellence Strategies for Bioprocessing – QbD, DoE and PAT SC1: Optimizing Media – Achieving Super Soup Ensuring quality in bioprocesses that complies with regulatory requirements and To grow mammalian cells, researchers need to provide an optimal in vitro environment. mitigates risk often results in very high bottom-line costs. Adopting best practices The key feature of successful cell growth is the culture medium. ‘Achieving Super early in the development process and customizing these approaches to operational Soup’ requires finesse and know-how in order to combine the right ingredients at excellence from other highly competitive industries are currently taking place in the right times under the right conditions to achieve high titers. This workshop will biopharmaceutical production. This course will provide both an overview of these provide a foundation for optimizing cell culture media presented by real-world experts approaches and how they work, as well as case studies of how these innovations have who will also tailor a portion of the course to fit concerns and challenges faced by the been applied successfully in bioprocessing and the development of biopharmaceuticals. workshop participants. Appropriate regulatory guidance will also be discussed. Instructors: Instructor: David Brühlmann, MSc., Biotech Technology and Innovation, Biotech Process Elizabeth Rebeil, Associate Director, Operational Excellence, Shire Sciences, Merck Serono SA Pharmaceuticals Michael Butler, Ph.D., Distinguished Professor, Microbiology, University of SC6: Protein Aggregation: Mechanism, Characterization and Manitoba Consequences Kamal A. Rashid, Ph.D., Director, Biomanufacturing Education & Training Center, Protein aggregation is recognized by regulatory agencies and the biopharmaceutical and Research Professor, Biology and Biotechnology, Worcester Polytechnic industry as a key quality attribute of biotherapeutic products. Various aggregates Institute hold the potential for adversely impacting production and patients in a variety of ways. This in-depth workshop reviews the origins and consequences of aggregation SC3: Accelerated Stability Testing of Biologics in biotherapeutics, and then examines strategies for predicting and quantifying aggregation in biopharmaceuticals. It benefits scientists engaged in development, This short course will aim to guide the researcher in designing studies for accelerated production, analytical characterization and approval of biotherapeutics and who require a stability testing of biologics. The course will begin with basic underlying concepts good working knowledge of protein aggregation. governing protein drug product stability, and focus on design principles for measuring Instructor: stress and accelerated stability testing of not only the protein of interest, but also of Thomas Laue, Ph.D., Professor, Biochemistry and Molecular Biology; Director, excipients and primary packaging components. Strategies to handle complexities arising Biomolecular Interaction Technologies Center (BITC), University of New from their interactions will also be discussed. Hampshire Instructor: Jan Jezek, Ph.D., CSO, Development, Arecor Ltd. David F. Nicoli, Ph.D., Vice President, R&D, Particle Sizing Systems, LLC

TUESDAY, AUGUST 4 THURSDAY, AUGUST 6

Dinner Short Courses | 6:00-8:30 pm Dinner Short Courses | 6:30-9:00 pm SC9: Transient Protein Production in Mammalian Cells SC4: Analytical Strategies for Comparability in Bioprocess This short course introduces both the fundamental concepts and technologies needed Development to establish transient protein production in mammalian cells. This allows for the rapid Bioprocess changes can impact quality attributes of biologics and may affect efficacy generation, purification and characterization of milligram-to-gram quantities of secreted and/or safety of the product. During development and throughout the product lifecyle, or intracellular recombinant proteins for therapeutic, functional and structural studies. when process improvements are implemented, it is essential to gather sufficient The course combines instruction and case studies in an interactive environment. data to support the conclusion that product safety or efficacy has not been adversely Instructors: affected. This demonstration exercise requires careful planning of the comparability Richard Altman, MS, Research Scientist, Molecular Sciences, Alexion studies and is based on the background knowledge of protein structure, biological Pharmaceuticals function, and clinical attribute profiles of the product accumulated during development. In this short course, we will discuss the key concepts of defining critical product quality Henry C. Chiou, Ph.D., Associate Director, Cell Biology, Life Science Solutions, attributes, the common analytical characterization technologies used, considerations Thermo Fisher Scientific in process monitoring and controls, and the iterative process of demonstrating Dominic Esposito, Ph.D., Director, Protein Expression Laboratory, Frederick REGISTER ONLINE NOW! comparability of the product in support of process changes. National Laboratory for Cancer Research, Leidos Biomedical Research, Inc. Instructor: BioprocessingSummit.com Christine P. Chan, Ph.D., Principal Scientist/Technical Lead, Manufacturing Science & Technology, Genzyme – a SANOFI company

*Separate Registration Required. Please visit the event website for more details. 4 Cambridge Healthtech

AUGUST 3-4, 2015 (TS2) Introduction to Extractables and Leachables and Packaging DAY 1 1:00-5:15 PM • DAY 2 8:30 AM-5:00 PM Diane Paskiet, MS, Director of Scientific Affairs, West Pharmaceuticals Chemical substances can be leached into biologics from various components used in the manufacture, storage or delivery of a therapeutic product leading (TS1) Introduction to Bioprocessing to a negative impact on the product and potential for an undesirable effect Frank J. Riske, Ph.D., Senior Consultant, BioProcess Technology Consultants on the patient. This training seminar will provide a background on regulatory Sheila G. Magil, Ph.D., Senior Consultant, BioProcess Technology Consultants, Inc. expectations for materials and components in contact with biologics and the unique applications to biologic delivery systems. Sources of leachables will be realized by CHI’s Introduction to Bioprocessing training seminar offers a comprehensive understanding components of delivery systems as related to the physical and chemical survey of the steps needed to produce today’s complex biopharmaceuticals, requirements for various delivery systems. Attendees will be shown how to design studies from early development through commercial manufacturing. The seminar to understand material chemistry through extractable studies and correlation to potential begins with a brief introduction to biologic drugs and the aspects of protein leachables. These learnings will put into perspective the current regulations and provide a science that drive the intricate progression of analytical and process steps means to develop best practices to manage extractables and leachable issues by applying that follows. We then step through the stages of bioprocessing, beginning science and risk based approaches for assessing extractables and acquiring appropriate with the development of cell lines and ending at scaling up for commercial information to support regulatory submissions. Over the 1.5 days the following topics will production. The seminar also explores emerging process technologies, facility design be addressed. considerations and the regulatory and quality standards that govern our industry throughout development. The important roles of analytical methods at all stages of Instructor Biography: development as well as formulation and stability assessments in developing and gaining Ms. Paskiet has over twenty years of experience in polymer analysis relating to product approval for a biopharmaceutical are also examined. This 1.5-day class is directed to failures, deformulation and migration studies. She has served as a project advisor in attendees working in any aspect of industry, including scientific, technical, business, support of qualification studies associated with container closure systems for IND and marketing or support functions, who would benefit from a detailed overview of this field. NDA filings. Her current responsibilities include coordination of studies for technical Instructor Biographies: support and R&D. Previous to this role she was in charge of site operations for West- Monarch Analytical Laboratories. Frank J Riske, Ph.D., Senior Consultant at BioProcess Technology Consultants has over 25 years of experience in the biopharmaceutical industry. Prior to joining BioProcess Technology Consultants, Dr. Riske was Senior Director in the Late Phase Process Development Group at Genzyme, a Sanofi company. Before Genzyme, Dr. Riske held positions at Epic AUGUST 5-6, 2015 Therapeutics, Repligen and Hoffmann-LaRoche. Dr. Riske has extensive experience in the DAY 1 9:00-5:15 PM • DAY 2 8:30 AM-12:00 PM development of downstream processes for cytokines, proteins and virus from plasma, E coli, Pichia and mammalian systems and in the development and manufacture of novel drug delivery systems. Dr. Riske received his B.S. in Biology from Fairfield University, Ph.D. in (TS3) Introduction to Cell Culture Biochemistry and Microbiology from Rutgers University and completed a post-doctoral position Timothy W. Fawcett, Ph.D., Director, The BioTechnical Institute of Maryland, Inc.; at Hoffmann-LaRoche. Founder, BioSciConcepts Sheila Magil has over 20 years of experience in quality and analytical method development This 1.5-day Intro to Cell Culture Training Seminar is a lecture-based course for biologics, peptides and small molecules. Her expertise includes quality assurance, protein intended for the beginner who is thinking about culturing animal cells for the and peptide biochemistry and analytical development. She was formerly Senior Manager of first time or for intermediate cell culturists wanting to know more about how Analytical Development and Quality Control at Biomeasure, Inc., and previously held positions animal cell culture works and how to improve their process. Attendees will at Waratah Pharma, Alkermes, Bion and HHMI at Massachusetts General Hospital. Dr. Magil learn about most of the critical aspects of cell culture from equipment has implemented quality systems and has managed external analytical and QC activities maintenance and media selection to cell growth and cryopreservation. Participants will for multiple biopharmaceutical products. Dr. Magil holds a Ph.D. in Biochemistry from the have ample time to ask specific questions and get worthwhile answers. University of Minnesota. Instructor Biography: Timothy Fawcett, Ph.D., has been in the biotechnology business for over 30 years. Trained as a biochemist, he has held senior positions in both academics and industry and has been a mentor to many young scientists throughout his career. For the last 13 years, Dr. Fawcett has been the Director of the BioTechnical Institute of Maryland (BTI), a non-profit institute located in Baltimore, Maryland. He is also the Founder and REGISTER ONLINE NOW! Director of BioSciConcepts, a social venture of BTI that provides hands-on training for professional scientists in cell culture, baculovirus-based expression, as well as topics BioprocessingSummit.com such as molecular biology, PCR and real-time PCR. BioSciConcepts is an internationally recognized provider of expertise in cell culture and the biological sciences and has provided consultation services to several small and large biotechnology companies. Dr. Fawcett has a deep knowledge of biotechnology and has experience in most of the technical aspects of the workflow.

5 Cambridge Healthtech

(TS5) Current and Emerging Global Regulatory Expectations for The hypothesis is tested using freeze–thaw data from a miniature (30 ml) and a 2.4 litre container. Computational fluid dynamics techniques are used to simulate the freeze

Analytical Elements of Biotechnology/Biosimilar Products process and the simulations are compared with experimental results. Protein quality Nadine M. Ritter, Ph.D., President & Senior Analytical Advisor, Global Biotech Experts LLC is assessed as a function of freeze conditions using dynamic light scattering, circular This 1.5 day class will present the driving concepts that distinguish the CD, size-exclusion and reverse-phase HPLC measurements. The results demonstrate regulatory approach to the production and testing of biologically-derived the applicability of the new approach. Freezing of protein solution at concentrations of molecules from chemical, small molecule pharmaceutical products. It provides approx. 200 mg/ml is shown to be possible with no damage to the molecule for multiple a comprehensive overview of how analytical elements come together in cycles of freeze–thaw. The results are scaled-up and confirmed using data from full-scale global regulatory dossiers, which can (should!) be used to drive the nature and timing of operation in a biomanufacturing setting. key CMC studies. It also provides an overview of how regulatory dossier CMC sections in marketing authorizations (BLA/MAA) are linked to analytical expectations in regulatory Target Audience: pre-approval inspections. All attendees will be given a searchable USB drive containing Scientists and engineers working in different functional areas in API and Drug Product over 200 current and draft global regulatory and quality guidance documents associated (DP) including Bioprocess Design and Development (BR&D), Analytical and Biophysical with the development and commercialization of biotech and biosimilar products. Characterization and Drug Product Formulation. Instructor Biography: What students will gain from attending the seminar: Nadine Ritter obtained her master and doctoral degrees in cell and molecular biology at Students attending the seminar will learn how to combine and use basic knowledge Rice University (Houston, TX) on evolutionary mechanisms for subcellular translocation of heat transfer, scale-down, first principle modeling, DOE and QBD to design unit of mitochondrial proteins. She was engaged in basic academic research in the field of operations for freezing and thawing of bulk API in a biomanufacturing setting. extracellular matrix proteins and the process of bone mineralization at the University Instructor Biography: of Texas Health Science Center in Houston for over 10 yrs. She entered the biopharm industry as a protein chemist in analytical R&D at Abbott Laboratories (Abbott Park, Dr. Shamlou is chemical engineer with over 30 years of academic and industry IL). She then became the Director of the Analytical Services Division of BioReliance experience bioprocess design and development with emphasis on biopharmaceutical (Rockville, MD), a major contract testing organization. There, she led a team of CMC therapeutics scientists in the design and conduct of method qualification, validation, and transfer, Dr. Shamlou received his first academic appointment in 1983 in the Department of product characterization and comparability studies, and QC release and stability testing. Chemical and Biochemical Engineering at University College London (UCL). At UCL, She managed quality and compliance activities for the R&D, GLP and GMP activities Dr. Shamlou pioneered new areas of bioprocessing research at the interface with life conducted in her lab, and implemented Part 11 computer system requirements. In science discoveries, with an emphasis on the creation of new scale-down methods 1999, she created the first public training course specifically focused on biotechnology and miniaturization to speed up the translation of discovery to outcome, and to allow stability programs, which later grew into an award-winning CMC analytical training prediction of full-scale bioprocessing of advanced biologics, including therapeutic genes, course. Since 2002 she has been an international consultant, trainer, speaker and writer antibodies and cellular systems. This work included biophysical characterization of for biotech and biosimilar products. In 2003, she was one of six industry and two FDA non-viral drug delivery systems, the design of miniaturized techniques for fermentation founders of the CaSSS CMC Strategy Forum, which has led to the publication of major and cell-culturing operations and the bioprocess engineering issues related to industry/regulatory white papers on CMC topics, and is now being held annually in North manufacturing of advanced vaccines and tissue-engineered products. His research at America, Europe, Asia and Latin America.Since 2002, she has been an international UCL was supported by 20 different industry and government grants and 35 PhD and consultant, trainer, speaker and writer for biotech and biosimilar products. She first postdoctoral researchers. worked independently as NMR Biotech Services (Germantown, MD), then in 2004 In 2003 Dr. Shamlou joined Eli Lilly and Company’s headquarters in Indianapolis, Indiana joined Biologics Consulting Group, Inc. (Alexandria, VA). In 2014, she decided to return to where he was responsible for innovation and technology evaluation for development independent consulting, forming Global Biotech Experts, LLC. and commercialization of biotherapeutics. At Eli Lilly and Company Dr. Shamlou extended his first principle approaches combined with scale-down techniques to improve manufacturing operations of registered products and speed up development of AUGUST 6-7, 2015 pipeline molecules from discovery to commercialization. Projects worked on included DAY 1 2:00-5:30 PM • DAY 2 8:30 AM - 4:30 PM insulin, human growth hormone and several monoclonal antibody molecules currently in development for treatment of Alzheimer’s, rheumatoid arthritis, cancers, diabetes (TS6) Bulk API: Freeze-Thaw Operations and lupus. Parviz A. Shamlou, Ph.D., George B. and Joy Rathmann Professor, and During his 30 years of industry and academic work Dr. Shamlou also served on several Director, Amgen Bioprocessing Center, Keck Graduate Institute scientific committees and boards including European Federation of Biotechnology and Freeze-thaw is a key unit operation in biomanufacturing, but despite its wide UK’s Institution of Chemical Engineers (IChemE). Dr. Shamlou was the Editor-in-Chief of REGISTER ONLINE NOW! spread use, it is treated more as activity than a unit operation. In this seminar the peer-reviewed Journal of Biotechnology and Applied Biochemistry (2003-2012). He is a new method of freeze–thaw is described using experimental data obtained a Fellow of the British Institution of Chemical Engineers. He is the co-author of over 200 BioprocessingSummit.com from freezing of purified API solution including proteins and monoclonal antibodies. publications in peer-reviewed journals, chapters in books and presentations at national The method is based on freezing protein solutions in rectangular rather than cylindrical and international conferences and reports. containers. It is hypothesized that the change in container geometry allows for linear scale-up of the freeze–thaw operation based on equivalency of temperature–time profile.

6 Cambridge Healthtech

(TS8) Introduction to Analytical Method Development and Validation for Therapeutic Proteins Jichao (Jay) Kang, Ph.D., RAC, Director, Analytical and Formulation Development, Patheon Biologics This course is a panoramic review of analytical method development and validation for therapeutic proteins, including antibodies and enzymes. It is intended for scientists working on therapeutic proteins in Analytical Development, Quality Control, Product Development or related functional areas. It starts with basic knowledge of work on therapeutic proteins: manufacturing of proteins drugs, regulatory affair knowledge and protein chemistry. It then discusses fundamentals and practical aspects of commonly used analytical methods for proteins, including methods for structure elucidation, glycan characterization, biophysical characterization, potency measurement, purity and impurity analysis. The course concludes with the strategy and common practice in method validation and method transfer, including regulatory compliance at different stages of product development, application of DOE and QbD. The course emphasizes practical applications, real-world examples and useful tips. Instructor Biography: Dr. Jichao Kang holds a Ph.D. in Pharmaceutics and has been working on characterization, method development and validation and formulation for protein therapeutics since 1995. He is an accomplished researcher with over 15 peer-reviewed journal articles and book chapters, several patents and numerous conference presentations. The proteins he has worked on extensively include cytokines, antibodies, enzymes and protein conjugates. He is a key contributor in dozens of IND/IMPD and BLA/MAA filings. He is currently the Director of Analytical and Formulation Development at Gallus BioPharmaceuticals NJ, LLC, one of the leading CMOs for biologics, and held the same position at Laureate BioPharma before it was acquired by Gallus. Prior to Laureate, he was the department head of Analytical Development at Auxilium Pharmaceuticals, Inc., and was a key contributor in Auxilium’s successful marketing application of Xiaflex in both U.S. and EU. He also worked in MedImmune, PDL, and Neose Technologies.

REGISTER ONLINE NOW! BioprocessingSummit.com To view Training Seminar Agendas in full, visit: BioprocessingSummit.com/BPD/Training-Seminars

7 11th Annual STREAM #1: Cell Culture & Cell Line Optimizing Cell Culture Technology Development Enhancing Knowledge for Growing Cells

MONDAY, AUGUST 3 and component optimization, a CD basal medium 4:15 Breakout Discussions (CDM) was developed for CHO cell culture. Culture This session provides the opportunity to discuss 8:00 am Pre-Conference Registration and performance of CDM manufactured by vendors a focused topic with peers from around the world Morning Coffee was poor compared to in-house preparation. An in an open, collegial setting. Select from the list of investigation revealed key medium components topics available and join the moderated discussion to 9:00-11:30 Recommended Short Course* were sensitive to commercial manufacture. CDM share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue Optimizing Media - Achieving Super Soup was subsequently reformulated into a manufacture- compatible core medium with sensitive components the discussion as you head into the lively exhibit hall for * Separate registration required; click here supplemented separately. information about the latest technologies. for details. 2:15 Host Cell Protein Expression during Biosimilar Development: Cell Line 11:30 Main Conference Registration Extended CHO Cell Culture Screening and Process Optimization – The Right Balance? CULTURING CHO CELLS Kristin Valente, Ph.D., Associate Principal Scientist, Merck Moderator: Arnaud Périlleux, Assistant Project 1:00 pm Chairperson’s Opening Remarks As the biopharmaceutical industry moves towards Manager, Biotech Process Science, Merck Serono SA Tiffany Rau, Ph.D., Global Technical and Technology continuous bioprocessing, it is important to consider the Approaches to Establishing Product Manager, Eli Lilly and Company impact of extended CHO culture on extracellular HCP expression, particularly for impurities that are difficult to Specifications from Early Clinical »»1:10 OPENING KEYNOTE remove during purification. Proteomic techniques were Development to Commercial PRESENTATION: applied to evaluate HCP expression over 500 days of Moderator: To be Announced Getting to the Root of the Problem: culture. The effect of cell age on the HCP impurity profile Integrating Continuous Up- and What are the Fundamental Factors is presented and implications of variable HCP expression Downstream Processing to Increase R&D Limiting Growth and Productivity in on downstream purification are discussed. Protein Production CHO Cell Cultures? 2:45 Refreshment Break Gregory Hiller, Ph.D., Associate Research Fellow, Moderator: Martin Heitmann, Ph.D., Senior Scientist, Cell Culture Technology, Novo Nordisk A/S Culture Process Development, BioProcess R&D, ANALYSIS APPROACHES & AMBR Pfizer, Inc. Novel Production Systems and Why do they stop growing?!? We will describe 3:15 Optimizing Cell Culture Processes and Regulatory Considerations experimental strategies undertaken over the last Associated Analytical Methods eight years in my group to answer this most basic Moderator: Tiffany Rau, Ph.D., Global Technical and Lada Laenen, Ph.D., Senior Director, Manufacturing Technology Manager, Eli Lilly and Company question and understand the underlying cellular Science and Technologies, Genzyme metabolism. We will also explain our methods of Feeding Strategies for High Density CHO to overcoming the problem of growth cessation of 3:45 Enhanced Process Consistency, Keep Cells Growing Longer in Log Phase. CHO cells which have enabled dramatic increases Robustness and Success in Cell Line in overall culture productivity in the industry Selection Using High-Throughput Surfactants, how much and what is standard fed-batch culture and in less common Bioreactors the best? modes of bioreactor operation. Wenqi Xie, Associate Scientist II, Cell Culture Moderator: Sam Ellis, Vice President, Biochemist, Thomson Instrument Co. 1:45 Development and Manufacturability Development, Biogen Idec, Inc. · Pluronic vs. Simithecone; does your media have Assessment of Chemically-Defined Medium AMBR is now a common high-throughput bioreactor option for process development and cell line selections. enough surfactant for high density CHO for the Production of Protein Therapeutics in At Biogen, we evaluated the robustness of our platform · Amount of Surfactant needed? CHO Cells process in AMBR and determined important levers that · Transient effects? REGISTER ONLINE NOW! Wai Lam W. Ling, Ph.D., Senior Principal Scientist, affect cell culture performance and product quality attributes. BioprocessingSummit.com Process Development & Engineering, Biologics Moreover, through systematic retrospective and prospective · Stable CHO needs for surfactants? BioProcess Development, Merck Research Labs evaluations of cell line screening results from multiple · Glucose, Glutamate, cell boost, what should projects, we proposed the optimal number of cell lines to Internally developed chemically-defined (CD) we do? screen and therefore recommend using high-throughput media offers flexibility for protein production bioreactors to achieve target titer in cell line selections. process development. Through DOE screenings

8 11th Annual STREAM #1: Cell Culture & Cell Line Optimizing Cell Culture Technology Development Enhancing Knowledge for Growing Cells

Solving Development Issues with Large- is not necessarily identical. Hence, a careful evaluation METABOLIC FLUX ANALYSIS & scale Transient Transfection of systems which are already established or newly implemented is essential. Here, we describe the QUALITY Moderator: James Brady, Ph.D., Vice President, performance of 12 different recombinant CHO cell Technical Applications and Customer lines expressing the same antibody in fed-batch culture 10:30 Applying MFA to the Process Service, MaxCyte systems ranging from a few hundred microliters to lab Development Environment

· De-risk development with transient transfection scale. The 12 cell lines were selected based on distinct unpublished Neil Templeton, Ph.D., Senior Scientist, of the manufacturing cell line phenotypes covering a range which can be expected in data Bioprocess Development, Merck Research · Shorten development timelines with large-scale typical industrial process development projects. The cell Laboratories lines were cultivated using the same expansion and fed- transient transfection Metabolic flux analysis (MFA) was applied to multiple batch protocol. The following cultivation systems were fed-batch processes. A stoichiometric analysis was then · Scale-up/Scale-down of transient transfection evaluated: shaking 96-deepwell plates, 50 mL vented applied to identify potential nutrient limitations to biomass · Using Stable cell lines versus shake tubes, micro- and lab-scale bioreactors. The results and antibody synthesis. Finally, multivariate data analysis transients downstream of this study show both the limitations and the potential of each cultivation system, their suitability for process (MVDA) was applied to an experimental time-course 5:15 Discussion Report-Outs development, process characterization and scale-up. of metabolic fluxes, in an effort to identify fluxes of a fed-batch culture that correlated best with final titer. All 5:30 Grand Opening Reception in the Exhibit 9:00 Novel Virus-Like Particle and of this work was conducted in a fashion to suit the rapid Hall with Poster Viewing Nanoparticle Vaccine Production – timelines of industrial process development. An Overview of Cell Culture Process 7:00 End of Day 11:00 Towards Cell Engineering Using Development 13C-Metabolic Flux Analysis and Insight from Payal Biswas, Ph.D., Scientist, Upstream Process Cancer Metabolism TUESDAY, AUGUST 4 Development, Vaccine Production Program, Vaccine Woo Suk Ahn, Ph.D., Postdoctoral Associate, Research Center/NIAID/NIH 7:30 am Registration and Morning Coffee Chemical Engineering, Massachusetts Institute of In order to rapidly produce novel VLP vaccines Technology and nanoparticle influenza vaccines for Phase I Cancer metabolism is a promising topic to be OPTIMIZING PROCESS clinical trials, a mammalian cell culture-based, utilized for cell engineering field. Cancer cells quickly robust transient transfection platform process was DEVELOPMENT produce bioenergy and anabolic precursors by developed. Transfection conditions and process aerobic glycolysis that is increased significantly under parameters were optimized to achieve a viable yield 7:55 Chairperson’s Remarks hypoxia. Here, we quantified cancer metabolism using for clinical production and scaled up to 50L fully Martin Heitmann, Ph.D., Senior Scientist, Cell Culture 13C-metabolic flux analysis and validated by gene disposable bioreactor system for GMP manufacturing. Technology, Novo Nordisk A/S knock-down/overexpression techniques. We revealed Background and supporting data for Phase I how rapidly growing cells coordinate metabolism to manufacturing of these vaccines will be presented. »»8:00 FEATURED PRESENTATION: survive and proliferate under hypoxic condition. Delivering the Pipeline: A Global 9:30 Manufacturing Core Sponsored by Perspective of Process Development and 11:30 5-Hydroxymethylcytosine (5hmC) Competency for Biosimilar Design for Manufacturing Barcoding and Cell Identity Contenders Tiffany Rau, Ph.D., Global Technical and Technology Richard R. Meehan, Ph.D., Project Leader, Manager, Eli Lilly and Company Shun Luo, Ph.D., CEO & President, Jianshun Chromosomes and Gene Expresion, MRC Human Biosciences Co., Ltd. Genetics Unit, IGMM, University of Edinburgh 8:30 Prediction of Cell Culture Performance 10:00 Coffee Break in the Exhibit Hall with An assumption underlying the use of cultured and Molecule Quality Attributes from Micro- Poster Viewing cells is that they retain and mimic the molecular Scale Fed-Batch Cultures characteristics of the tissue from which they were REGISTER ONLINE NOW! derived or conform to an industry standard that case David Brühlmann, MSc., Biotech Technology and BioprocessingSummit.com study Innovation, Biotech Process Sciences, Merck enables their reproducible use in bio-manufacturing. Serono SA By studying the establishment of fibroblasts and The selection of a fed-batch cultivation system is often T-cells in culture, we found that adaptation resulted based on throughput and cost. However, the process in a rapid and comprehensive re-programming of the knowledge derived from different systems and scales transcriptome and epigenome, indicative of an altered

9 11th Annual STREAM #1: Cell Culture & Cell Line Optimizing Cell Culture Technology Development Enhancing Knowledge for Growing Cells

cell state. Re-programming involved almost complete 2:00 Scale-Down Tools for Evaluation of 3:00 Optimizing Osmolality and Cell Expansion loss of 5hmC in cultured cells. Restoration of 5hmC Perfusion Cultivations Strategy to Improve Cell Culture Performance profiles is indicative of restoration of cell identity. case unpublished Martin Heitmann, Ph.D., Senior Scientist, in a Perfusion-Based Bioreactor Process study data Cell Culture Technology, Novo Nordisk A/S case unpublished Christopher Rives, Ph.D., Senior 12:00 pm From Upstream to Sponsored by study data Strategies are presented to enable screening of Upstream Development Engineer, Downstream: Large-Scale, multiple process parameters at different scales, while BioProcess Development, Shire plc High Titer Transient Transfection being focused on simple, yet predictive, scale down During development of a perfusion-based bioreactor Platform for Biomanufacturing models for perfusion processes. Due to the difficulty of process for production of a therapeutic protein, a James Brady, Ph.D., Vice President, Technical implementing cell retention in small scale, a chemostat significant amount of variability in bioreactor terminal Applications and Customer Service, MaxCyte based scale-down system was developed. The viable cell density and viability profiles was observed. Harmonizing upstream and downstream processes conception of a repeated exponential fed-batch scheme This presentation describes the approaches taken to can reduce the time it takes to move a biotherapeutic to mimic chemostat cultivations is described and its investigate the potential root causes of performance to market. In this presentation, data developed with implementation in 10 mL scale ambrTM system cultures variability and summarizes the key experimental findings. MaxCyte’s flow electroporation, closed, single- is presented. This system is then compared to classical In addition, the proposed control strategy will be shared. use, cGMP-compliant system will demonstrate bench top chemostat and ATF perfusion cultures. large-scale transient transfection in CHO cells and 3:30 Refreshment Break in the Exhibit Hall biologically relevant cells and the resulting high titers. 2:30 Progress towards Efficient with Poster Viewing The results demonstrate the platform’s scalability, Implementation of Continuous Upstream high transfection efficiency, and cell viability. The Processes in Early Development TOOLS AND TECHNOLOGIES outcome is a cost-efficient, timely high yield and a case unpublished Daryl Powers, Ph.D., Senior Scientist, data TO ENHANCE CELL CULTURE harmonization between upstream and downstream. study Early Cell Culture Development, Sanofi Global Biotherapeutics PROCESSES 12:30 Luncheon Presentation (Sponsorship We have implemented several strategies to 4:15 Biologics Data Platform for Tailored Opportunity Available) or Enjoy Lunch on Your Own streamline early process development for perfusion Support of Cell Line Development 1:15 Session Break production of a therapeutic IgG that is being readied for transfer to the pilot plant for clinical material Christian Bender, Ph.D., Computational Biologist, Global generation. These strategies include some perfusion- Drug Discovery, Global Biologics, Bayer HealthCare PERFUSION PRODUCTION specific techniques in addition to many of the same We have successfully implemented the Biologics Data Platform (BDP) for tailored support of our screening and 1:55 Chairperson’s Remarks tools and methods that are used for fed-batch process development. protein production processes. In the context of our cell Wai Lam W. Ling, Ph.D., Senior Principal Scientist, line development process, we present the integration of Process Development & Engineering, Biologics BDP with our automation workstation. We demonstrate BioProcess Development, Merck Research Labs the power of using a comprehensive data management platform to track data for cell line clones and fed-batch

experiments together with molecule information such as primary sequences and experimental results.

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10 11th Annual STREAM #1: Cell Culture & Cell Line Optimizing Cell Culture Technology Development Enhancing Knowledge for Growing Cells

4:45 Portable X-Ray Fluorescence Spectrometer: A Tool for Biopharmaceutical Forensic Investigations Jessica Mondia, Ph.D., Research Scientist, Biogen Idec, Inc. A portable X-ray fluorescence (XRF) spectrometer is a small, cheap, easy and fast instrument for multi-elemental analysis. In biopharma, forensic investigations usually refer to determining the root-cause and evaluating the risks associated with deviations from GMP guidelines including batch records, procedures and SOPs. Here we introduce the use of a XRF spectrometer for biopharmaceutical forensic applications as an in-house-portable diagnostic tool to help resolve or guide investigations in a timely fashion.

5:15 Close of Conference

6:00-8:30 Recommended Dinner Short Course* Operational Excellence Strategies for Bioprocessing – QbD, DoE and PAT * Separate registration required; click here for details.

11 5th Annual STREAM #1: Cell Culture & Cell Line Bioproduction: Scale, Bioreactors Development & Disposables Making It Work

WEDNESDAY, AUGUST 5 9:30 Challenges in N-1 Perfusion Process 11:45 A High-Yield Single-Use Sponsored by Optimization System for Biosimilar Process

7:00 am Registration and Morning Coffee unpublished Weimin Lin, M.D., Process Development Development Using Eppendorf data Scientist, Biogen Idec, Inc. Bio-BLU® Single-Use Vessels and OPTIMIZING PROCESSES FOR Implementing an N-1 perfusion process at large- the BioFlo® 320 Bioprocess Control Station GREATER PRODUCTIVITY scale manufacturing can increase capacity and Stacey Willard, Ph.D., Senior Research Scientist, lower manufacturing costs at Biogen Idec. Perfusion Applications R&D Lab, Eppendorf 8:05 Chairperson’s Remarks N-1 enables high-seed fed-batch production, which Sponsored by Eric J. Wallenstein, Ph.D., Associate Principal can increase manufacturing capacity by increasing 12:00 pm Increasing Protein Scientist, Biologics Manufacturing Science & volumetric productivity. However, there are significant Production with Novel Cell Ess Commercialization, Merck & Co., Inc. challenges in N-1 perfusion process development, such Supplement without Affecting as identifying the proper equipment, improving media Metabolic Profile »»8:15 OPENING KEYNOTE formulations, developing a platform process, and scaling- PRESENTATION: up to the manufacturing facility. This talk will focus on Adam Elhofy, Ph.D., CSO, Essential Pharmaceuticals Planning for the Future: Manufacturing media aspects relating to the above challenges. Enhancing protein production is a common goal in the Capacity Versus Demand Uncertainty biomanufacturing industry. At a concentration of 1% Peter F. Moesta, Ph.D., Senior Vice President, 10:00 Coffee Break in the Exhibit Hall with Cell Ess supplement resulted in a 37% increase in Biologics Development & Operations, Bristol Poster Viewing productivity. When using the supplement as a feed it Myers Squibb Co. resulted in in a 25% increase in yield and an extension 10:45 A Risk-Based Strategy for of peak protein production. Our results suggest that The rapid advancements in Immuno-Oncology Implementing Disposables in a Commercial at BMS have created a unique challenge for an increase in protein production may not necessarily Development and Manufacturing. In-licensed Manufacturing Process require a change in the metabolic state of the cells. Chad Atwell, M.S., Associate Director, Manufacturing molecules that were in early development are 12:30 Luncheon Presentation: Sponsored by being accelerated and putting pressure on Science and Technology, Genzyme Corporation Ensuring Scalable Performance commercial process development and readiness. A risk assessment strategy is used to plan the Commercial capacity needs to be made available implementation of disposables in a commercial protein of Single-Use Bioreactors from although neither dose nor volumes are defined. The purification process. The results influence extractable Bench to Clinical Scale talk will describe the strategy that is being used and leachable study design as well as a dual vendor Janice Lloyd Simler, Ph.D., Global Senior Product combining capabilities in process development, sourcing strategy to ensure business continuity. An Manager, EMD Millipore Corporation capacity expansions, and leveraging a network overview of the implementation program is reviewed. Bioreactor process set points and parameters of CMOs to address both the potential and the developed in bench-top bioreactors are used in the risks of a rapidly developing portfolio of new 11:15 Effects of Antifoam on High Density large production scale bioreactors. It is therefore life-saving drugs. Perfusion Cultures: A Case Study Using crucial that the set points developed at the small Small Scale Models scale can be easily transferred to large scale. 9:00 Fc-Fusions Versus mABs: Opportunities This presentation will highlight how a detailed case Jonathan Wang, Process Engineer Associate, Late and Limits of Platform Processes study Stage Cell Culture Development, Sanofi understanding of the performance design space of Stefan Schmidt, Ph.D., MBA, Vice President, Process High density bioreactor perfusion processes require each sized bioreactor can enable the selection of Science & Production, Rentschler Biotechnologie GmbH antifoaming agents to manage the foam resulting from process parameters at each scale that will enable In theory, Fc-fusion proteins should behave quite comparably to high gas sparge rates. We have developed a small scale scalable performance across the platform. REGISTER ONLINE NOW! mABs, both in upstream and downstream processes. However, shake flask model to evaluate the impact of antifoam in practice some differences can be observed. Well-established addition and accumulation on cell culture growth and 1:30 Session Break BioprocessingSummit.com platform processes only rarely and partially match the requirements viability. The small scale model is a good predictor of for Fc-fusion proteins. I will discuss the range of manufacturing qualitative trends observed in the bioreactor. Small SCALING DOWN possibilities for fusion proteins with regard to platform processes, scale and bioreactor data showing the impact of varying 1:55 Chairperson’s Remarks modular concepts, and fully customized solutions in comparison to antifoam concentrations with and without the presence conventional antibody production. of additional shear inducing factors will be discussed. David Kolwyck, MBA, Director, Manufacturing Sciences, Raw Materials, Biogen Idec, Inc. 12 5th Annual STREAM #1: Cell Culture & Cell Line Bioproduction: Scale, Bioreactors Development & Disposables Making It Work

2:00 Scale-Down Models for Technology 3:30 Rapid Development of an Inclusion 5:20 Interactive Panel Discussion: Transfer and Process Characterization of an Body Production Process in E. coli Using How to Innovate Product Development Upstream Cell Culture Process Automated Mini-Bioreactor System · Technologies case case Eric J. Wallenstein, Ph.D., Associate Principal study Matthew Manahan, Scientist, Bioprocess · Strategies study Scientist, Global Vaccines & Biologics Development, Merck & Co., Inc. · Cutting Costs Commercialization, Merck & Co., Inc. This work highlights development of an inclusion · Meeting needs body fermentation process using the automated · Utilizing creativity 2:30 Overcoming Scale-Down Model mini-bioreactor system (ambr250TM). With this · Lessons Learned Development Challenges for MAb Production HTPD approach we were able to screen multiple Moderator: Sam Ellis, Vice President, Biochemist, case Stephen Hsu, MSc., Senior Research Associate II, expression plasmids, seven sequence variants, and study Gilead Sciences process parameters to achieve 50% improvement in Thomson Instrument Co. A case study is presented that highlights the fermentation productivity with comparable protein purity Panelists: challenges encountered with a sensitive CHO cell over the platform approach. The process development Joanne T. Beck, Ph.D., Senior Vice President, line expressing a therapeutic monoclonal antibody is achieved within 4 months with total of 120 batches, Pharmaceutical Development, Shire Pharmaceuticals (mAb) that exhibited reduced productivity upon scale before being successfully scaled up to 30-L. Wayne Froland, Ph.D., Associate Vice President, translation. Various scale-down model strategies were Center for Biopharmaceutical Manufacturing Sciences, leveraged to assess the scalability issues and identify 4:00 Refreshment Break in the Exhibit Hall Merck Manufacturing Division several raw materials and process parameters that with Poster Viewing Stefan Schmidt, Ph.D., M.B.A., Vice President, led to the reduced titer. Process enhancements were Process Science & Production, Rentschler made, based on the scale-down models, to enable PLENARY SESSION Biotechnologie GmbH subsequent successful large-scale production runs. Haripada Maity, Ph.D., Research Advisor, Eli Lilly and Company 4:45 Chairperson’s Remarks 3:00 Small-Scale Model Development & 6:00 Networking Reception in the Exhibit Application for a Commercial Legacy Process Sam Ellis, Vice President, Biochemist, Thomson Instrument Co. Hall with Poster Viewing case unpublished Hunter Malanson, Scientist I, Upstream study data Development, Alexion Pharmaceuticals »»4:50 PLENARY KEYNOTE 7:00 End of Day Significant disparities in scale between commercial PRESENTATION: production and laboratory bench bioreactors were Meeting the Needs of Patients with THURSDAY, AUGUST 6 observed for a legacy process. A qualified 5L small Rare Diseases: Innovation in Product scale model was iteratively developed to mimic 8:00 am Registration and Morning Coffee the commercial production bioreactor’s behavior Development Joanne T. Beck, Ph.D., Senior Vice President, and metabolic profile. Cell growth, viability, and SCALING UP AND DOWN productivity trends were closely matched while Pharmaceutical Development, Shire Pharmaceuticals At Shire, where the delivery of innovative product quality attributes were maintained. This 8:25 Chairperson’s Remarks model is now being actively applied for potential medicines to patients with rare diseases and other Stefan Schmidt, Ph.D., MBA, Vice President, GMP changes and process knowledge for this late-stage specialty conditions is a fundamental component of Operations, Rentschler Biotechnologie GmbH commercial process. the business model, creative solutions are critical to our success. Starting with the transition of drug 8:30 Reducing the Biotech Process candidates from discovery research to the clinic, Information Gap in the 21st Century: followed by late phase development and eventually REGISTER ONLINE NOW! ‘Implementing Process Analytical commercial product lifecycle management, Technologies at the Seed Expansion BioprocessingSummit.com scientists and engineers focus on both technology innovation and creative business approaches to Stage for Bioprocess Development and

deliver high quality therapies to the patients while Manufacturing of Biologics’ decreasing development timelines and costs. case Jose R. Vallejos, Ph.D., Scientist I, Manufacturing study Sciences and Technology (MS&T), AstraZeneca/

Medimmune 13 5th Annual STREAM #1: Cell Culture & Cell Line Bioproduction: Scale, Bioreactors Development & Disposables Making It Work

Manufacturing of Biologics at the seed expansion 10:00 Coffee Break in the Exhibit Hall with 12:15 pm Sponsored Presentation stage can be further optimized. Utilizing optical patch- Poster Viewing (Opportunity Available) based sensors as Process Analytical Technologies (PAT), we were able to enhance the inoculum BIOPRODUCTION STRATEGIES 12:30 Luncheon Presentation (Sponsorship expansion stage by enabling T-flasks with Dissolved Opportunity Available) or Enjoy Lunch on Your Own Oxygen and pH sensors. Our results show the 10:45 Development of a Novel Feeding potential of implementing PAT at the inoculum Strategy for an Industrial Yeast Strain 1:15 Close of Conference expansion stage to improve process understanding Simona Capone, Process Assistant, Chemical and to speed up process development, tech transfer, Engineering, Vienna University of Technology and process improvement timelines. I will present a bioprocess development strategy 9:00 Points to Consider When Scaling Up based on dynamics for an industrial yeast strain, Raw Materials in Your Manufacturing Process which is induced under de-repressing conditions. A developed novel mixed-feed strategy gave 3 David Kolwyck, MBA, Director, Manufacturing times higher space time yields than conventional Sciences, Raw Materials, Biogen Idec, Inc. feeding regimes. This presentation will review technical issues that can arise during the quantitative scale-up of raw 11:15 HCCF Air Sparging for Prevention of materials due to changes in manufacturing scale or Antibody Disulfide Bond Reduction supplier sourcing of those raw materials. It is intended Melissa Mun, Senior Engineer, Genentech, Inc. to provide guidance on technical issues to consider and discuss with suppliers during the scale-up of raw In CHO cell culture processing, mechanical shear material demand to ensure consistent performance during the harvest operations and subsequent from pilot to large manufacturing. release of intracellular factors may result in antibody disulfide bond reduction. Maintaining the harvested 9:30 Case Studies for Utilization of cell culture fluid (HCCF) dissolved oxygen level via air Conventional and CFD Approaches for sparging is an effective strategy to prevent disulfide reduction. Small-scale studies were performed to Successful Scale Up and Scale Down evaluate multiple HCCF air sparging strategies with of Bioreactor Processes for Monoclonal respect to effectiveness and product quality impact, Antibodies and to improve understanding of reaction kinetics and case Michelle LaFond, Director, Bioreactor Scale-Up oxygen consumption rates. study and Development, Regeneron Pharmaceuticals Use of both conventional and computational fluid 11:45 Effect of Microspargers on Product dynamic approaches to develop scale-down, Quality Variability in Large-Scale Perfusion pilot-scale models of production bioreactors have Bioreactors resulted in improved process understanding and Nirel Rillera, Research Associate II, BioMarin more successful transfer for late stage processes. Pharmaceuticals, Inc. The new scale-down models are more predictive of Multivariate analysis on commercial processes manufacturing and are used to map out impact of suggested a relationship between superficial gas scale-up parameters and bioreactor type to process velocities and cell death, which coincided with REGISTER ONLINE NOW! performance. Case studies of our approach to scale- variability in product quality attributes. In order to up will be discussed. better control product quality, microsparger design BioprocessingSummit.com was optimized for lower superficial gas velocities and reduced fouling susceptibility. After implementation at commercial scale, the new microspargers were successful in addressing fouling events and improved product quality control.

14 7th Annual STREAM #1: Cell Culture & Cell Line Optimizing Cell Line Development Development Enhancing Expression

THURSDAY, AUGUST 6 3:45 Using Combinatorial Sponsored by lines optimized for human-type protein glycosylation. Genome Editing to Improve Furthermore, data will show those cell lines can OPTIMIZING PROCESS Production in CHO Cells produce structurally homogenous glycoproteins. DEVELOPMENT Brian Burke, Ph.D., Business Development Director, 5:45 End of Day Products, Horizon Discovery 1:55 pm Chairperson’s Remarks Horizon have started a combinatorial gene editing 6:30-9:00 Recommended Dinner Short Christina Alves, Ph.D., Scientist, Cell Culture program to improve CHO cell line performance. Course* Development, Biogen Idec, Inc. Together with the development of a high throughput Transient Protein Production in reporter system we will generate a range of cell lines Mammalian Cells »»2:00 OPENING KEYNOTE with different production traits to meet the future PRESENTATION: * Separate registration required; click here needs of biologics manufacture and develop next- for details The Future Looks Great… generation production systems. but What Is It? Alan Dickson, Ph.D., Professor and Director, Centre 4:00 Refreshment Break in the Exhibit Hall FRIDAY, AUGUST 7 of Excellence in Biopharmaceuticals (COEBP), with Poster Viewing University of Manchester 8:00 am Registration and Morning Coffee Use of understanding developed through systems CELL LINE DEVELOPMENT FOR biology, coupled to the application of synthetic BACULOVIRUS CHO CLONE SELECTION & CELL biology, will generate an exciting and brave LINE DEVELOPMENT manufacturing world in which novel CHO cell variants 4:45 Engineering the Baculovirus Genome for will be matched to expression of engineered unique Better Protein Production from Insect Cells 8:25 Chairperson’s Remarks biopharmaceutical entities … perhaps? I will give a Dominic Esposito, Ph.D., Director, Protein Expression Alan Dickson, Ph.D., Professor and Director, Centre of personalized review of the reality of progress to date Laboratory, Frederick National Lab for Cancer Excellence in Biopharmaceuticals (COEBP), University and how adoption of developing technologies has the Research of Manchester potential to make a real difference. Protein production from insect cells using the 8:30 FEATURED PRESENTATION: 2:45 Upstream Process Optimization, baculovirus expression system has proven very »» useful for the generation of high-quality heterologous An Inducible System for the Rapid Automation and Collaboration: An proteins when other systems have failed. However, Generation of CHO Pools and Stable Accelerated Path to the Clinic insect cell protein production differs from mammalian Clones Pamela Pegman, Ph.D., Senior Principal Scientist, Cell expression due to differences in post-translational Yves Durocher, Ph.D., Research Officer, Line Development, Pfizer, Inc. unpublished modification pathways. In order to overcome some data Human Health Therapeutics Portfolio, Optimizing cell line development activities has the of these differences, genome engineering of the Biologics & Biomanufacturing Program, National potential to reduce the time and resources required baculovirus can be used to “humanize” insect cell Research Council Canada for clinical entry. This presentation will summarize protein production. We describe methods for facile Using the cumate-inducible promoter, we a combination of approaches to reduce cell line modification of the baculovirus genome to both developed a CHO platform for the rapid generation development timelines including creative timing add new pathways for post-translation modification of stable pools in less than 3 weeks post- of upstream activities through collaboration and of proteins and also to enhance the stability of transfection. The pools are stable over time and harmonization with discovery partners, introduction baculovirus constructs for protein production. can be used to isolate stable CHO clones showing of automation, and the use of business practice high productivities. We will provide examples of modeling to predict the best outcomes for key 5:15 Optimizing Insect Cell Lines for pools generated for the production of monoclonal technology introduction. Production of Structurally Uniform antibodies, secreted and membrane proteins. This Glycoproteins REGISTER ONLINE NOW! 3:15 SELECTED POSTER PRESENTATION: platform is a useful and cost-effective addition to Donald Jarvis, Ph.D., Professor, Molecular Biology, the large-scale CHO transfection platform for the Bioprocess for Testing Engineered CHO Cell BioprocessingSummit.com University of Wyoming rapid production of recombinant proteins. Lines Using Single-Use Bioreactors My presentation will cover previous, as well as more Marianne Decker, Ph.D., Special Consultant, Novo recent and ongoing efforts to produce insect cells Nordisk Foundation Center for Biosustainability, with humanized glycoprotein processing pathways. Technical University of Denmark Data will show recent efforts have yielded insect cell

15 7th Annual STREAM #1: Cell Culture & Cell Line Optimizing Cell Line Development Development Enhancing Expression

9:00 Screening of CHO Cell Clones by Mass These efforts aim to enhance cell growth, tailor 12:15 pm Using Process and Sponsored by Balance of Amino Acids protein modifications, and improve protein secretion, Activity to Drive Clone Selection Wen Wang, Ph.D., Postdoctoral Associate, Chemical in order to better control biotherapeutic critical Oren Beske, Ph.D., COO, Aragen Engineering, Massachusetts Institute of Technology quality attributes. Bioscience, Inc. (MIT) During a manufacturing cell line development project 11:15 Utilizing High-Throughput Bioanalytics Post-transfection clone screening is a crucial step in in stable CHO-K1 cells, a significantly reduced for Early Detection of Product Impurities mammalian cell line development for production of specific activity of target protein was observed when case therapeutic proteins. Ideally, the screening should be study Christina Alves, Ph.D., Scientist, Cell Culture compared to a reference standard. This case study non-invasive, economical, and effective. We report a Development, Biogen Idec, Inc. highlights how the lack of activity was identified and fundamentally new method for predicting mAb titer Improvements in the throughput and efficiency of how the development of an optimized cell culture in a Chinese hamster ovary (CHO) cell culture system analytical techniques have enabled their use earlier process enabled identification of high productivity based on mass balance of two essential amino acids. on in the cell line development process. This in clones. This study provides an alternative way to screen high turn provides useful information on a large number Sponsored by therapeutic protein producers in a low-cost manner. of clones at a very early stage. In this case study 12:30 Luncheon Presentation: we demonstrate how the use of these techniques Preventing Virus Contamination 9:30 Stable Glycoengineering of CHO Cells allowed early detection of product impurities which of Bioreactors with a Virus Claus Kristensen, Ph.D., Associate Professor, in turn prevented delays in clinical timelines and the Barrier Filter Copenhagen Center for Glycomics (CCG), University need for additional resources. Christina Carbrello, Ph.D., Senior Scientist, Process of Copenhagen Solutions, EMD Millipore 11:45 High-Throughput Product Quality Recent advances in precise gene editing Cell culture media is typically sterile filtered to remove technologies such as ZFNs, TALENs and CRISPR/ Assays for Cell Line and Process Development bacteria and mycoplasma, however many bioreactors Cas9 systems have enabled stable engineering of Shashi Prajapati, Ph.D., Senior Scientist, unpublished remain unprotected from viral contamination. Ideally, mammalian cells to produce well-defined N and data High-Throughput Analytical Group, Cell a filter could be used to remove viruses, but filtration O-glycans. In this lecture we will present state-of- Culture Development, Biogen Idec, Inc. is traditionally perceived as being unsuitable for the the-art glycoengineering in CHO to produce more Cell line and process development play a major role in upstream processes. A new virus filter has been homogeneous glycans and options for novel designed producing therapeutic proteins with high productivity evaluated and demonstrated high levels of virus, glycan structures. and appropriate product quality attributes. To support bacteria and mycoplasma removal while providing this development, analyses of large number of high flow and capacity in chemically defined media 10:00 Coffee Break samples generated from thousands of clones and with little to no impact on cell culture performance. process optimization are critical. Analyzing large SYSTEMS BIOLOGY & HIGH- number of samples has been a bottleneck in biotech 1:15 Session Break THROUGHPUT TECHNIQUES FOR industries because conventional analytical assays DEVELOPING CELL LINES are low-throughput. Here we present various high- INNOVATIVE TECHNOLOGIES & throughput (HTP) analytical platforms to facilitate rapid STRATEGIES 10:45 Developing Systems Biology Models and parallel analyses of product quantity and quality Based on Whole-Genome Sequencing of using 96-well plate formats. These platforms include 1:25 Chairperson’s Remarks HTP protein quantitation followed by HTP protein CHO to Guide Cell Line Engineering Pamela Pegman, Ph.D., Senior Principal Scientist, Cell purification and product quality analyses. With these Line Development, Pfizer, Inc. Nathan Lewis, Ph.D., Assistant Professor, Systems analytical capabilities, we can assess product quality Biology Research Group, University of California, San in the early stage of clone screening, as well as 1:30 Development of Synthetic Biology Diego expedite the cell line and process development. Tools to More Predictably Clone, Express Our recent whole-genome sequencing efforts for CHO have enabled the construction of systems and Select Active Biologics in Cell Line REGISTER ONLINE NOW! biology models of metabolism, protein secretion, Development BioprocessingSummit.com and glycosylation. We now use these for detailed Ian Fotheringham, Ph.D., Managing Director, Ingenza analysis of -omics data from CHO to deepen our Ltd. understanding of differences between host cell In this talk, I will describe how Ingenza has developed lines and to guide our cell line engineering efforts. and deployed various synthetic biology tools to enable

16 7th Annual STREAM #1: Cell Culture & Cell Line Optimizing Cell Line Development Development Enhancing Expression

us to more predictably clone, express and select 3:00 Networking Refreshment Break active proteins during cell line development. I will use real-world examples of solving customer problems 3:15 GlycoExpress: A Toolbox for the High to illustrate the utility of our approach. These tools Yield Production of Glycooptimized Fully include protein engineering to address poor response Human Biopharmaceuticals in Perfusion kinetics during the control of gene expression, the Bioreactors at Different Scales development of synthetic “landing pads” to optimize Rainer Stahn, Ph.D., Head, Bioprocess Development, the genomic operating environment, and the use of Glycotope GmbH genome editing and RNA trafficking systems. GlycoExpress cells producing mAb are cultivated 2:00 Enabling Evaluation of Polysaccharide with perfusion bioreactor systems applying different Size and Content for DOE Studies in Early cell retention mechanisms such as centrifugation (centritech) or alternating tangential flow (ATF) Process Phases filtration at different scales. Growth, product yield and Erwin Swennen, Ph.D., Manager, Cell Line and product quality, especially glycosylation, are evaluated Process Analytics, Bacterial Drug Substance during the cultivation. Perfusions culture helps to keep Development, Novartis Vaccines cells in the optimal growing and production phase This talk presents the development of an innovative over the production process which leads to highly RP-SE(GPC) analytical method to monitor both stable product quality allowing a flexible duration of critical quality attributes of GBS capsular PS during the run in one batch size. all phases of the production process. This method enabled DOE studies also in early process phases 3:45 Setting Pre-Work Priorities and KPIs with complex matrix, and contains a practical to Avoid the Most Significant Challenges approach on how industrial R&D is trying to keep up during Tech Transfer with the constant increase in quality requirements by Jayant Aphale, Ph.D., MBA, Senior Vice President, regulatory agencies (QbD, DoE in early phases). The Technical Operations, Sarepta Therapeutics method represents a new out-of-the-box application Communication is essential before, during, and after of technology. the tech transfer process. Pre-tech transfer activities 2:30 Development of Human Cell Systems are critical in ensuring success of the tech transfer for Evaluating the Responses of Drugs process. You must have the appropriate skill sets and competencies in place with all of your upstream / Directed at Correcting the Function of downstream partners so that you have understood Cellular Proteins any constraints and agreed on the scope of the work Dieter Gruenert, Ph.D., Professor, Otolaryngology- and acceptable parameters months before tech Head and Neck Surgery, University of California, San transfer begins. Francisco Our lab has been a leader in the development of 4:15 Close of Conference these cell systems that have been used in academic and industry settings nationally and internationally. We have developed human airway epithelial and iPS cell systems to evaluate and screen the responses to drugs aimed at correcting the function of proteins involved in airway diseases such as cystic fibrosis. REGISTER ONLINE NOW! BioprocessingSummit.com

17 3rd Annual STREAM #2: Formulation & Overcoming Formulation Challenges for Downstream Processing Biopharmaceuticals Development: Formulation and Process Optimization, Analytics, Device Integration and New Biologics

were not greater than 20 ppm. Significant losses of MONDAY, AUGUST 3 KEYNOTE PRESENTATION: »» polysorbates were observed when PS20 and PS80 1:45 Is PS-80 a Critical Excipient? A Short 8:00 am Pre-Conference Registration and concentrations were above 50 ppm. Also, it was History and Case Studies Morning Coffee demonstrated that factors such as the presence of case Michael T. Jones, Ph.D, Research Fellow, salt, the order of addition, and the hydrophobicity 9:00-11:30 Recommended Short Course* study Biotherapeutics Pharmaceutical Sciences, of surfactants could also impact compatibility. Accelerated Stability Testing of Biologics Analytical R&D, Pfizer, Inc. Furthermore, the agitation study demonstrated that even trace levels of PS20 and PS80 (e.g., 20 ppm) * Separate registration required; click here Polysorbates are ubiquitous as excipients in protein could stabilize the protein against fibrillation and for details formulations. These surfactants are added to the formulation to help maintain the stability of the drug aggregation. 11:30 Main Conference Registration product (DP). There has been an increased interest in the biopharmaceutical industry to understand 3:45 Development of a Stability Indicating UNDERSTANDING EXCIPIENTS the fate of these surfactants over the shelf-life of Assay for Polysorbate-80 the DP. This talk will highlight some of the issues Mark Bolgar, Ph.D., Senior Research Fellow, STABILITY & PARTICLES IN unpublished with polysorbates and provide case studies on the data Analytical and Bioanalytical Development, BIOPHARMACEUTICALS criticality of PS80 addition to a protein DP. Bristol-Myers Squibb Co. 1:00 pm Chairperson’s Opening Remarks The extreme heterogeneity of polysorbate 80 creates 2:15 Critical Considerations for Surfactant challenges for its quantitation in biotheraputic Sandeep Yadav, Ph.D., Scientist, Late Stage Stability in Biopharmaceutical Formulations formulations. Ideally, any method should distinguish Pharmaceutical Development, Genentech, Inc. Sandeep Yadav, Ph.D., Scientist, Late Stage between intact PS-80 and key degraded forms. Of »»KEYNOTE PRESENTATION: Pharmaceutical Development, Genentech, Inc. particular concern is the degradation of PS-80 via 1:10 Polysorbate 80 Hydrolysis and Polysorbate is commonly used excipient in ester bond hydrolysis. This presentation will describe the development of LC/MS-based method for the Rationale for Determining the Effective biotherapeutic formulations for protection against interfacial stress and surface adsorption. In this work determination of PS-80 which due to its very high Level of Polysorbate 80 in a High we present evidence of Polysorbate degradation specificity is able to effectively differentiate between Concentration Monoclonal Antibody over long-term 5OC storage that may subsequently intact PS-80 and its hydrolyzed forms. Formulation result into visible and subvisible particles in protein 4:15 Breakout Discussions unpublished Vincent Corvari, Ph.D., Senior Research formulation. A number of challenges associated data Advisor, Bioproduct Research & with characterizing particulates, identifying potential This session provides the opportunity to discuss Development, Eli Lilly & Company reasons for Polysorbate degradation, novel methods a focused topic with peers from around the world During the development of a solution formulation to quantify the degradants as well as the solubility in an open, collegial setting. Select from the list of for a high concentration monoclonal antibody, a characteristics of the PS20 degradants are discussed. topics available and join the moderated discussion reduction in the content of polysorbate 80 occurred to share ideas, gain insights, establish collaborations on stability. Further evaluation demonstrated the 2:45 Refreshment Break or commiserate about persistent challenges. reduction resulted from hydrolysis of the fatty acid Then continue the discussion as you head into side chains. The focus of this presentation is to 3:15 Challenges in Co-Formulating the lively exhibit hall for information about the describe the knowledge gained while identifying Polysorbates and Preservatives in Multi-Use latest technologies. this degradation pathway and the development Biologics Formulations work conducted to define the effective level of Topic 1: What Does It Take To Move A Shuai Shi, Ph.D., Associate Principal Scientist, Sterile Formulation From Vials To Prefilled Syringes? polysorbate 80 required to maintain product quality. Product and Analytical Development, Merck REGISTER ONLINE NOW! Moderator: Mark Yang, Ph.D., Director, Fill Finish The compatibility between polysorbates and m-cresol Development, Genzyme - a Sanofi Company BioprocessingSummit.com was thoroughly investigated in this study. It was · What are the most efficient ways to evaluate the found that both PS20 and PS80 are compatible device-ability of current formulations? with m-cresol (at 2.8 mg/mL) when their levels

18 3rd Annual STREAM #2: Formulation & Overcoming Formulation Challenges for Downstream Processing Biopharmaceuticals Development: Formulation and Process Optimization, Analytics, Device Integration and New Biologics

· What are the “norms” for development timelines TUESDAY, AUGUST 4 9:00 QbD in Late Stage Formulation and budget? Optimization

· Key development steps/challenges to move from 7:30 am Registration and Morning Coffee case unpublished Mark Yang, Ph.D., Director, Fill Finish vials to prefilled syringes study data Development, Genzyme - a Sanofi OVERCOMING FORMULATION Company Topic 2: What Constitutes A Critical CHALLENGES: QbD, PROCESS QbD is a powerful tool for late stage formulation Excipient? optimization and process definition. However, there is Moderator: Michael T. Jones, Ph.D, Research Fellow, CHALLENGES & PRODUCT QUALITY a delicate balance between testing many variables Biotherapeutics Pharmaceutical Sciences, Analytical 7:55 Chairperson’s Remarks over a wide range for a robust process and minimizing R&D, Pfizer, Inc. the “process changes” to be implemented. A QbD Kevin Constable, Director, Technology Development, · Are specific excipients required for a stable case study will be presented. After identified key Terumo- Global Pharmaceutical Solutions. formulation or would similar excipients work excipients, the formulation was optimized by using a as well? 8:00 Transformational Science: Moving from response surface design to include multilevelsof key · What concentration of the excipient is required the Challenges of High Concentration mAbs to excipients over a manufacturing-relevant range. to guarantee it’s function? Meeting the Needs of Highly Potent Bispecifics 9:30 Physical and Colloidal Sponsored by · At the end of shelf-life, does the DP still meet Sachin Dubey, Ph.D., Head of Formulation Stability Studies of mAbs all of the specifications required regardless of Development, Process Development, Glenmark and bi-Specifics excipients present? Pharmaceuticals SA Ralf Joseph Carrillo, Ph.D., R&D-GPMA Global Project Glenmark’s proprietary BEAT® technology has Topic 3: Formulation Development of the Management, GPAS Global Pharmaceutical Analytical provided a new impetus toward developing a Sciences, Formulation, Abbvie Future – Can We Develop Better Formulations more efficient way of treating cancer. This highly Faster? Biophysical properties of two monoclonal antibodies effective therapeutic (anticipated doses ~ 1000 fold and two Dual Variable Domain Immunoglobulin Moderator: Russell Burge, Ph.D., Applications less than conventional mAbs) has conserved key (DVD-IgTM) proteins have been studied to ascertain Scientist, Freeslate, Inc. IgG properties (thermostability, effector function/ how protein – protein interactions (B22), unfolding and · Can automation help accelerate formulation antibody-like pharmacokinetics etc), but at the same aggregation onset melting temperatures and turbidity development? What are the best approaches time has thrown up new challenges, particularly in demonstrate the propensity to predict both good and to continue with rapid and innovative terms of formulation/analytical development. These poor (aggregation and phase separation) mAb and formulation development? low-concentration related challenges were rationally DVD-Ig formulations. · Are current analytics sufficient? What understood, characterized and mitigated. improvements are needed to provide better 9:45 Coffee Break in the Exhibit Hall with characterization faster? 8:30 Controlling Excipients during Poster Viewing Commercial-Scale Formulation: Modelling- · What are the best practices for implementing QbD in formulation development? Based Control Strategy Design case unpublished Rachael Lewus, Ph.D., Scientist II, 5:15 Discussion Report-Outs study data Formulation Sciences, MedImmune, Inc. Control of excipients during commercial scale 5:30 Grand Opening Reception in the Exhibit formulation is important in order to deliver a high Hall with Poster Viewing quality drug substance and ensure release criteria are met. However, an accurate scale down model REGISTER ONLINE NOW! 7:00 End of Day for the excipient spiking step is not readily available BioprocessingSummit.com for experimental characterization. Monte Carlo modelling provides an alternative method for process characterization. A case study focusing on polysorbate control in a monoclonal antibody drug substance formulation will be presented.

19 3rd Annual STREAM #2: Formulation & Overcoming Formulation Challenges for Downstream Processing Biopharmaceuticals Development: Formulation and Process Optimization, Analytics, Device Integration and New Biologics

11:30 Application of Automated Sponsored by 10:30 FEATURED PRESENTATION: Mixing 2:00 A Novel Analytical Approach to and High-Throughput Systems Monoclonal Antibody Formulations Using Investigate the Effect of Methionine to Formulation Development of Bottom-Mounted Mixers – Impact of Oxidation on Antibody PK Biopharmaceuticals case Mechanism and Design on Drug Product study Jan Stracke, Ph.D., Principal Scientist, Pharmaceutical Development & Supplies, PTD Quality Russell Burge, Ph.D., Applications Scientist, Freeslate, Inc. Biologics can be prone to degradation and instability, Biologics Europe, F. Hoffmann-La Roche Ltd. Yuh-Fun Maa, Ph.D., Principal Engineer, case both of which pose challenges to drug developers. Preserving the chemical and structural integrity of study Pharmaceutical Processing and Technology In this presentation, we describe the application of antibodies during manufacturing and storage is a Development, Genentech, Inc. automation and high throughput data management major challenge during development. Oxidation of Fc Although BMM is becoming a choice of mixing systems to drug development workflows. Results of methionines is frequently observed, which leads to but impact of BBM on protein drug product is yet case studies demonstrating the ability of automated reduced affinity to FcRn and faster plasma clearance to be understood. This study evaluated multiple workflows to increase throughput, improve efficiency, if present at high levels. A novel pH-gradient FcRn disposable BBMs to assess their impact on a and streamline data management. affinity chromatography method was developed to shear-sensitive mAb formulation. Aggregation of isolate antibody oxidation variants from an oxidized mAb, and particle formation were determined after 12:00 pm Panel Discussion: Challenges IgG1 preparation based on their FcRn binding mixing. The results suggested that mixer designs and Opportunities in QbD Approach in properties. The subsequent physico-chemical and with contact between the impeller and the drive Formulation Development and Product biological characterization of these oxidation variants unit resulted in higher particle counts. The shear- Quality demonstrated the value of the new method to study induced particles are proteinaceous but soluble structure-function relationships. aggregated protein molecules were not detected. Moderator: Mark Yang, Ph.D., Director, Fill Finish Development, Genzyme – a Sanofi Company This study fills an important gap in understanding a 2:30 Developability Assessment Sponsored by critical bioprocessunit operation. Panelists: and Formulations Optimization Sachin Dubey, Ph.D., Head of Formulation 11:00 Molar Mass, Size, Charge Sponsored by of Biologics Using Isothermal Chemical Development, Process Development, Glenmark Denaturation (ICD) and Conformation: Light Pharmaceuticals SA Scattering Tools for Biophysical Richard K. Brown, Ph.D., Unchained Labs Rachael Lewus, Ph.D., Scientist II, Formulation Characterization of Macromolecules Stability optimization and aggregation minimization are Sciences, MedImmune, Inc. two of the most important hurdles in the development John Champagne, Ph.D., Northeast Regional Manager of biologics. ICD provides the most accurate & Senior Applications Scientist, Wyatt Technology Yuh-Fun Maa, Ph.D., Principal Engineer, way of measuring protein stability under different Corporation Pharmaceutical Processing and Technology formulation conditions. ICD experiments performed This seminar describes a comprehensive suite of Development, Genentech, Inc. at different protein conc. provide a quantitative characterization tools based on static and dynamic Russell Burge, Ph.D., Applications Scientist, Freeslate, Inc. assessment of protein aggregation in the native and light scattering, which work together with size-based denatured states. ICD is ideally suited to optimize separation, to provide first principles biophysical 12:30 Luncheon Presentation (Sponsorship the formulation of highly concentrated formulations, characterization of macromolecules. Some of the key Opportunity Available) or Enjoy Lunch on Your Own bispecific antibodies and antibody drug conjugates. In applications of the light scattering toolbox include this talk, the fundamentals of ICD and its application analyses of molar mass and size distributions, 1:15 Session Break to the evaluation of protein stability and optimization aggregation, branching and other measures of of formulation conditions will be discussed. conformation, and the composition of complex protein RAPID SCREENING OF REGISTER ONLINE NOW! systems and other conjugated macromolecules. FORMULATION STABILITY IN EARLY 3:00 Sponsored Presentation (Opportunity BioprocessingSummit.com DEVELOPMENT Available) 1:55 Chairperson’s Remarks Hardeep Samra, Ph.D., Senior Scientist, Formulation Sciences, MedImmune, Inc.

20 3rd Annual STREAM #2: Formulation & Overcoming Formulation Challenges for Downstream Processing Biopharmaceuticals Development: Formulation and Process Optimization, Analytics, Device Integration and New Biologics

3:15 Poster Highlight Presentation: 4:45 HDX-MS Sheds Mechanistic Insights Leveraging Automation in Development of on Mutation Induced Changes in Physical High Concentration Protein Formulations Stability of an IgG1 mAb Engineered For Aastha Puri, M.Sc., Associate Scientist II, Drug Extended Serum Half-Life

Product Science & Technology, Bristol-Myers Squibb case Ranajoy Majumdar, Ph.D., Research Scientist, Formulation development of high concentration study Biophysical Characterization, Biopharmaceutical products, brings a unique set of challenges, including Research and Development, Eli Lilly and Company the potential for increased physical and chemical A triple mutation in the CH2 domain of an IgG1 stability risks, as well as challenges related to handling mAb intended to increase in vivo half-life resulted in of viscous material. This work demonstrates the decreased physical stability. Although the mutation utility of new automation technologies in proficiently induced minimal differences in H/D exchange kinetics executing experimental workflows on a viscous high at the mutation sites and the FcRn binding epitopes, it concentration protein formulation and assisting a data- increased the flexibility of an established aggregation driven decision making process as part of a material hotspot in the CH2 domain. This case study reinforces sparing, multi-well screening methodology. our understanding of the correlations between mAb physical stability and its local flexibility. 3:30 Refreshment Break in the Exhibit Hall with Poster Viewing 5:15 Close of Conference 4:15 A Comparison of Biophysical 6:00-8:30 Recommended Dinner Short Characterization Techniques in Predicting Course* Drug Product Stability Protein Aggregation: Mechanism, Andrew Semple, Scientist, Sterile Product and Characterization and Consequences Analytical Development, Merck & Co. * Separate registration required; click here To predict stability behavior, solution-mediated for details. interactions (Colloidal, self-association propensity) and key molecular characteristics of ten formulated protein-therapeutics were compared to their stability at accelerated (25C and 40C) and long- term storage conditions (2-8C) as measured by size exclusion chromatography. Our results show that colloidal stability, self-association propensity, and conformational characteristics (exposed Trp) provide reasonable prediction of accelerated stability, with limited predictive value at 2-8C stability. Other measurements (e.g., thermal unfolding temperature) did not show any correlation.

21 4th Annual STREAM #2: Formulation & High-Concentration Protein Formulations: Downstream Processing Formulation, Manufacturing, Analytics, High Viscosity, Aggregation, Devices and Delivery

TUESDAY, AUGUST 4 specification range can have a significant impact FORMULATION & CMC on product viscosity. Likewise, product viscosity is CHALLENGES OF HIGH- 6:00-8:30 Recommended Dinner Short significantly higher at storage temperature of 2-8 °C Course* than it is at ambient temperature. Viscosity ranges CONCENTRATION PROTEIN of a model antibody and implications for formulation FORMULATIONS Protein Aggregation: Mechanism, development, manufacturing, and device development Characterization and Consequences will be discussed. 10:45 Preformulation Screening for Risk * Separate registration required; click here Mitigation during the Development of 9:30 Cluster Formation in Dense Protein for details. Biopharmaceuticals Solutions and Its Implications to Solution case unpublished Randall Mauldin, Ph.D., Scientist II, Viscosity study data WEDNESDAY, AUGUST 5 Protein Formulation and Process case Yun Liu, Ph.D., Research Associate Professor/ study Development, Biogen Idec 7:00 am Registration and Morning Coffee Instrument Scientist, Chemical & Bimolecular In order to address unmet patient needs, drug Engineering/Center for Neutron Research, University candidates are becoming more complex and delivered PROTEIN-PROTEIN INTERACTIONS of Delaware/National Institute of Standards and at higher concentration than ever before. Furthermore, Technology & DEALING WITH VISCOSITY aggressive CMC timelines necessitate the need for a Protein cluster formation in solutions is of rigorous assessment of early-stage drug candidates 8:05 Chairperson’s Remarks fundamental interest for both academics and to de-risk future development. This talk will provide industries, and is very important for solution viscosity Jan Jezek, Ph.D., CSO, Development, Arecor Ltd. an overview of the challenges and strategies for control in concentrated protein solutions. We will characterizing the multidimensional formulation »»KEYNOTE PRESENTATION: present our recent research efforts to directly identify space of novel biopharmaceuticals with limited 8:15 Protein-Protein Solvation in High- the structures of small reversible protein clusters sample availability. in monoclonal antibody solutions. The fundamental Concentration Solutions physical mechanisms of high viscosity in monoclonal 11:15 HESylation® - A Versatile Polymer Thomas Laue, Ph.D., Professor, Biochemistry and protein solutions will be discussed within the context Modification Technology Enabling High- Molecular Biology; Director, Biomolecular Interaction of our research examples. Technologies Center (BITC), University of New Concentration Protein Formulations Hampshire 9:45 High-Concentration Protein Analysis via Thomas Hey, Ph.D., Director, Biochemistry, Innovation At high concentrations, proteins will distribute Slope Spectroscopy and Variable Pathlength Center Complex Formulations, Fresenius Kabi Deutschland GmbH themselves in a manner that minimizes the Technology system free energy. Mechanistically, this means The attachment of the biodegradable and poorly Joe Ferraiolo, Senior Product Specialist, C Technologies that proteins will form an increasingly important immunogenic polymer hydroxyethyl starch (HES) to The traditional method for measuring highly component of the solvation shell around any given biologicals leads to increased efficacy by stabilization concentrated protein solutions typically requires protein. The importance of considering protein- of the protein and prevention of renal excretion. the sample to be diluted prior to analysis in a fixed protein solvation for both single-protein solutions, as The resulting conjugates show high solubility, but pathlength spectrophotometer. The time, error and well as for mixtures of proteins, will be described, comparably low viscosity, allowing s.c. administration costs associated with dilutions impacts analysis and experimental data showing these effects will be of highly concentrated solutions. In addition, from formulation through in-process and release ® presented. HESylation was used to develop next-generation testing. This talk focuses on the Slope Spectroscopy ADCs allowing site-specific conjugation and higher technique which enables measurements on neat 9:00 Viscosity in High-Concentration Protein payload density while maintaining excellent binding samples with concentrations ranging up to 300 mg/ activity with the target protein and cancer cells. Formulations ml by increasing the linear range of the instrument REGISTER ONLINE NOW! unpublished Thomas Palm, Ph.D., Senior Research through dynamic optimization of the measurement data Investigator II, Drug Product Science and pathlengths. BioprocessingSummit.com Technology, Bristol-Myers Squibb Co. At high protein concentration, small changes in 10:00 Coffee Break in the Exhibit Hall with concentration or pH that are within the typical Poster Viewing

22 4th Annual STREAM #2: Formulation & High-Concentration Protein Formulations: Downstream Processing Formulation, Manufacturing, Analytics, High Viscosity, Aggregation, Devices and Delivery

11:45 Designing a Unique Sponsored by 2:30 CMC Strategies on Scaling Up and PLENARY SESSION Drug Delivery Device for Down for High-Concentration Protein Viscous Drug Products with Novel Needle Formulations 4:45 Chairperson’s Remarks Technology and Polymer Syringes Jamie Tsung, Ph.D., Principal Scientist, Momenta Sam Ellis, Vice President, Biochemist, Thomson Kevin Constable, Director, Technology Development, Pharmaceuticals, Inc. Instrument Co. Terumo- Global Pharmaceutical Solutions Highly concentrated therapeutic proteins are prone to New drug products being developed today are often be viscous and aggregate posing developmental and »»4:50 PLENARY KEYNOTE created as concentrated proteins which can result CMC challenges in purification, formulation, analytical PRESENTATION: in a viscous solution that may require novel devices development, manufacturing, product stability, Meeting the Needs of Patients with syringeability and injectability. This talk provides a for drug delivery. Using a systems approach to review of current strategies and technologies used Rare Diseases: Innovation in Product device design, we will explore how the combination in product development to overcome these CMC Development of a silicone oil free polymer syringe system with a challenges and minimize the impact on product quality. Joanne T. Beck, Ph.D., Senior Vice President, tapered needle can be combined to reduce the force Pharmaceutical Development, Shire of injection, improve functionality, and reduce the 3:00 Aromatic Amino Acid Salts Rescue the Pharmaceuticals potential degradation of these complex protein based Solubility of a Poorly Soluble Multivalent At Shire, where the delivery of innovative formulation. Protein medicines to patients with rare diseases and other specialty conditions is a fundamental component of 12:15 pm Luncheon Presentation case unpublished Yu (Eunice) Tang, Ph.D., Principal study data (Sponsorship Opportunity Available) or Enjoy Scientist, Drug & Combination Product the business model, creative solutions are critical to our success. Starting with the transition of drug Lunch on Your Own Development Group, Shire HGT A multivalent protein demonstrates poorly solubility candidates from discovery research to the clinic, 1:30 Session Break across wide pH range with temperature dependency. followed by late phase development and eventually Conventional “salt in” ions further facilitate the commercial product lifecycle management, FORMULATION & CMC precipitation of the protein. Interestingly, aromatic scientists and engineers focus on both technology amino acid salts successfully rescue the protein innovation and creative business approaches to CHALLENGES OF HIGH- solubility. A systemic investigation was performed deliver high quality therapies to the patients while CONCENTRATION PROTEIN to reveal the cause of the poor solubility and the decreasing development timelines and costs. mechanism of solubility enhancement by aromatic FORMULATIONS (cont.) amino acid salts. 5:20 Interactive Panel Discussion: 1:55 Chairperson’s Remarks 3:30 Simplest Concepts and Measurements How to Innovate Product Development Thomas Palm, Ph.D., Senior Research Investigator II, Drug May Become Challenges at High Protein · Technologies · Strategies Product Science and Technology, Bristol-Myers Squibb Co. Concentration · Cutting Costs 2:00 Drug Product Design and High Erinc Sahin, Ph.D., Sr. Research Investigator, Drug · Meeting needs Concentration Formulation Development Product Science & Technology, Bristol-Myers Squibb Co. · Utilizing creativity case · Lessons Learned study Bruce Kerwin, Ph.D., Head, Drug Product Design, 4:00 Refreshment Break in the Exhibit Hall Moderator: Sam Ellis, Vice President, Biochemist, Just Biotherapeutics, Inc. with Poster Viewing Protein formulation development is an evolving Thomson Instrument Co. field that now encompasses the concept of drug Panelists: product design rather than focusing solely on Joanne T. Beck, Ph.D., Senior Vice President, stabilization and concentration of the protein. Pharmaceutical Development, Shire Pharmaceuticals REGISTER ONLINE NOW! Increasingly, an integrated approach to drug product Wayne Froland, Ph.D., Associate Vice President, Center design encompasses in silico tools, high throughput for Biopharmaceutical Manufacturing Sciences, Merck BioprocessingSummit.com screening and development of predictive tools that Manufacturing Division integrate with the commercialization process. At this meeting examples and ideas will be combined to Stefan Schmidt, Ph.D., M.B.A., Vice President, Process provide a vision of the future as it evolves into the Science & Production, Rentschler Biotechnologie GmbH field of drug product design. Haripada Maity, Ph.D., Research Advisor, Eli Lilly and Company 23 4th Annual STREAM #2: Formulation & High-Concentration Protein Formulations: Downstream Processing Formulation, Manufacturing, Analytics, High Viscosity, Aggregation, Devices and Delivery

6:00 Networking Reception in the Exhibit and quality control. Current methods available for the Hall with Poster Viewing determination of low levels of polysorbates in high concentration drug substances and drug products 7:00 End of Day will be presented. Sensitivity and robustness of three different methods will be discussed. THURSDAY, AUGUST 6 9:30 Characterization of and Relationship between Soluble and Insoluble Aggregate 8:00 am Registration and Morning Coffee Populations Ronald Maurer, Ph.D., Scientist, Process Development ANALYTICAL STRATEGY FOR – Downstream, Bristol-Myers Squibb Co. HIGH-CONCENTRATION PROTEIN Protein aggregation presents serious challenges in all stages of biotherapeutic development, compromising FORMULATIONS both product yield and patient safety. However, 8:25 Chairperson’s Remarks many fundamental aspects of aggregation are poorly described and prevent robust characterization and Bruce Kerwin, Ph.D., Head, Drug Product Design, Just prediction of aggregation behavior. In this work, we Biotherapeutics, Inc Present a Poster & Save! investigate the relationship, if any, between soluble 8:30 Building a Better Bridge: Biophysical and insoluble protein particle formation and correlate Cambridge Healthtech Institute encourages Tools to Better Understand the Complexities their growth and stability to experimentally-tenable attendees to gain further exposure by biophysical properties. of High Concentration Biotherapeutics presenting their work in the poster sessions. To secure a poster board and inclusion in the Michael S. Marlow, Ph.D., Senior Staff Scientist, Protein 10:00 Coffee Break in the Exhibit Hall with conference materials, your abstract must be Biochemistry, Regeneron Pharmaceuticals, Inc. Poster Viewing submitted, approved and your registration paid The thermodynamic interactions that govern a in full by June 26, 2015. variety of protein therapeutic and solution properties DELIVERY & DEVICE APPROACHES • Your research will be seen by leaders from are distinctly protein concentration dependent. IN HIGH-CONCENTRATION / HIGH- Manufacturing and dosing of therapeutic monoclonal top pharmaceutical, biotech, academic and antibodies frequently calls for high protein VOLUME PROTEIN FORMULATIONS government institutes concentration solutions and the resulting non-ideality 10:45 Device & Formulation – Two • Your poster abstract will be published in the complicates reliable estimation of critical properties conference materials from measurements under dilute conditions. We Inseparable Aspects of a Successful Product • Receive $50 off your registration fee illustrate the utility of different biophysical tools Jan Jezek, Ph.D., CSO, Development, Arecor Ltd. in bridging the dilute - high concentration gap by The biologics market is becoming increasingly characterizing two antibodies that exhibit contrasting competitive with multiple products competing for concentration-dependent behavior. the same indication and a number of biosimilars 11:15 Reconstitution of Highly Concentrated, in development. Therefore, there is a strong Dried Proteins: What Have We Learned in the 9:00 Challenges with Measuring Detergents pressure for product differentiation offering Past 5 Years? and Excipients Used in Biopharmaceuticals distinct advantages over other products. Stability Bakul Bhatnagar, Ph.D., Principal Scientist, together with a convenient injection device are Shiranthi Jayawickreme, Ph.D., Associate Director, Formulation & Process Development, Pfizer, Inc. Analytical Development, Biogen Idec two key aspects of successful products. This talk The reconstitution time of lyophilized will focus on unique formulation strategies and A variety of detergents are used for solubilization, biopharmaceuticals is a quality attribute where REGISTER ONLINE NOW! related device choices that enable development of viral-inactivation, and as excipients in it is desirable and often critical to achieve fast competitive biopharmaceuticals. BioprocessingSummit.com Biopharmaceutical drug substances and products. reconstitution (for example, in an emergency Lack of chromaphores in many of these detergents environment) without compromising the product poses a challenge for the detection and quantitation quality. The reconstitution times of highly of these components during process development concentrated freeze-dried proteins can be often

24 4th Annual STREAM #2: Formulation & High-Concentration Protein Formulations: Downstream Processing Formulation, Manufacturing, Analytics, High Viscosity, Aggregation, Devices and Delivery

quite long. The presentation will address recent 12:15 pm Crystalomics – A Sponsored by advances in our understanding of the dissolution Strategy for High-Concentration behavior and will cover aspects of mechanisms Protein Formulation contributing to reconstitution, strategies to obtain Tan Leminh, MBA, Director, Technology Transfer, rapid reconstitution, and methods to determine the Althea end of reconstitution. Crystalomics® is a technology platform that offers a 11:45 Adocia Viscosity Reducers (AVRs®) – A formulation solution for protein therapies that must New Alternative to Reduce the Viscosity of be delivered at high concentrations or as sustained release formulations. The technology can be used to Highly Concentrated mAb Formulations formulate antibodies to up to 350 mg/ml, allowing Emmanuel Dauty, Ph.D., Head of the Physico- IV infusions to be converted to SC injections. Chemistry Department, Adocia Crystalomics® is an ideal technology to formulate Highly concentrated monoclonal antibody (mAb) “BioSuperior” biologics that deliver superior dosing formulations are often highly viscous, which poses regiments and expanded patent protection for manufacturing and administration challenges. established protein therapeutics. Adocia has developed two distinct families of small molecules that have impressive viscosity-reduction 12:30 Luncheon Presentation (Sponsorship properties in highly concentrated mAb formulations – Opportunity Available) or Enjoy Lunch on Your Adocia Viscosity Reducers (AVR®). Through low-affinity Own electrostatic and hydrophobic interactions, AVR® excipients are capable of disrupting the mAb-mAb 1:15 Close of Conference interaction network responsible for the high viscosity of highly-concentrated mabs, resulting in significant viscosity reduction.

25 2nd Annual STREAM #2: Formulation & Advances in Purification Technologies: Downstream Processing Novel Advances and Continuing Improvements for Higher Downstream Productivity and Purity

THURSDAY, AUGUST 6 3:15 Development of Robust Impurity 5:15 Investigation of Fouling Mechanism of Clearance Methods Using Chromatographic Hydrophobic Interaction Chromatography NOVEL AND ALTERNATIVE and Non-Chromatographic Techniques Resin during Monoclonal Antibody

case unpublished Srinivas Chollangi, Ph.D., Scientist II, Purification APPROACHES TO PURIFICATION study data Biologics Process Development, Bristol- unpublished Theodore T. Diakov, MSc, Associate Scientist, AND AGGREGATE REMOVAL Myers Squibb data Downstream Process Development, Bristol-Myers Squibb 1:55 pm Chairperson’s Remarks 3:45 Production Scale Sponsored by Fouling of chromatography resins during repeated Yi Li, Ph.D., Sr Scientist, Biologics Process Pre-Packed Chromatography cycles of use can be a significant problem as it can Development, Bristol-Myers Squibb for Use with 1000L & 2000L Bioreactors compromise the capacity to clear impurities as well »»2:00 KEYNOTE PRESENTATION Christine Gebski, Vice President, Product as cause inconsistent performance. Identifying the How to Scale-Up Precipitation of Management, Repligen fouling species and mechanism can provide valuable Recombinant Antibodies How do we scale pre-packed chromatography to understanding and assist in designing more efficient production-scale? The OPUS® 45 and 60 cm columns cleaning strategies. In this work we examined fouling Alois Jungbauer, Professor, Department of can purify a feed stream from 1000L - 2000L of hydrophobic interaction chromatography resin Biotechnology, BOKU and Head of Bioprocess bioreactors. We will show how the unique design during a monoclonal antibody purification process. Engineering, Austrian Centre of Industrial of these GMP-scale columns deliver equivalent or Historically, HIC resins have been shown to allow Biotechnology better performance as self-packed glass columns, and protein unfolding on the surface under favorable Precipitation and flocculation has been considered demonstrate how usage can result in substantial time conditions and we propose that protein deposits as potential methods for capture of antibodies and cost savings. adsorbed by this mechanism are exhibiting resistance especially when perfusion culture is used for to traditional cleaning approaches. We report our production. Ethanol precipitation and precipitation 4:00 Refreshment Break in the Exhibit Hall comparisons of the resin performance in fouled by non-charged polymers reached equilibrium with Poster Viewing and non-fouled state, the results of our pursue in in less than 1 minute. As rectors for such fast identifying the nature of the foulant and its localization operations tubular reactors have been studied. As 4:45 High Pressure Refolding as an within the resin and our approaches in cleaning. scale-up criteria fractal dimension of the flocks Alternative Technology for the Manufacture have been used. Mechanical compression during of Biopharmaceuticals 5:45 End of Day harvesting is influenced by dissolution kinetics. case study Linda Gombos, Ph.D., Postdoc, Institute of 6:30 - 9:00 Recommended Dinner Short 2:45 Fatty Acid Extraction Of Chromatin Biotechnology (BOKU), Process Science Downstream Course* Processing, BOKU-Boehringer Ingelheim RCV Heteroaggregates From Mammalian Cell SC10: Anything but Chromatography We evaluated the application of high hydrostatic Culture Harvests – Precipitation, Crystallization and pressure for refolding a variety of biopharmaceuticals. unpublished Wei Zhang, Ph.D., Research Scientist, Flocculation data Our aim was to systematically compare this emerging Downstream Processing, Bioprocessing technology to conventional refolding and to identify * Separate registration required; click here Technology Institute, Singapore its potential economic benefits. We also compared for details. Saturated and unsaturated fatty acids ranging in chain the structure and activity of the two protein variants length from 6 to 12 carbon atoms were evaluated to address concerns on therapeutic effect and safety. over a range of pH and conductivity values to identify Our results indicate that high-pressure is a potent the combinations supporting the most effective technology for refolding proteins with significantly reduction of aggregates, product-related impurities, higher productivity and in unaltered quality compared and host contaminants while conserving high with conventional refolding techniques. REGISTER ONLINE NOW! recovery of native IgG. Sensitive analytical methods BioprocessingSummit.com were also developed. Results will be presented tracking contaminants and fatty acids through several

2-step IgG purification processes.

26 2nd Annual STREAM #2: Formulation & Advances in Purification Technologies: Downstream Processing Novel Advances and Continuing Improvements for Higher Downstream Productivity and Purity

FRIDAY, AUGUST 7 9:30 Assembly of Knob and Hole Bispecific 11:45 Purification of a Highly Disulfide Linked Antibodies Protein by Cation Exchange Chromatography 8:00 am Registration and Morning Coffee Josefine Persson, Ph.D., Senior Group Leader, Thomas Linke, Ph.D., Senior Scientist, Purification Purification, Genentech, Inc. Process Sciences, MedImmune PURIFICATION OF NEW & COMPLEX We have produced glycosylated and aglycosylated We present an informative case study on the FORMATS CHO and E. coli Knob & Hole Bispecific Antibodies. development of a direct capture step of a refolded, In all cases the assembly conditions and assembly novel biotherapeutic by ion exchange chromatography 8:25 Chairperson’s Remarks effectiveness are very similar. Our data shows that without prior buffer exchange. High yield and product Gregory Zarbis-Papastoitsis, Ph.D., Vice President the assembly step is very robust and efficient in purity in a single step made it possible to replace two of Process and Manufacturing Sciences, Eleven producing the Knob & Hole Bispecific Antibodies affinity columns used in the pre-clinical manufacturing Biotherapeutics while minimizing the amounts of homodimers (mAb). process. Low solubility in solution and a propensity toward aggregation presented special challenges for 8:30 Modular Approaches to Express and 10:00 Coffee Break process development. Purify Complex Therapeutic Proteins 10:45 The Challenges of Developing Sponsored by Stefan Schmidt, Ph.D., Vice President DSP Production, 12:30 Luncheon Presentation: Rentschler Biotechnologie GmbH Processes for New Protein Formats Preventing Virus Contamination Difficult to express proteins represent an increasing Andreas Schaubmar, Ph.D., Head of Downstream of Bioreactors with a Virus amount of therapeutic molecules. This causes Processing, Large Molecule Research, Roche Barrier Filter Pharmaceutical Research and Early Development, bioprocessing challenges such as controlling Christina Carbrello, Ph.D., Senior Scientist, Process pRED, Roche Innovation Center Penzberg glycosylation, increasing titers and yields and Solutions, EMD Millipore Innovative biologics often combine several protein suppressing aggregation. Here I demonstrate how to Cell culture media is typically sterile filtered to remove domains in increasingly complex formats to develop modular processes based on DoE principles bacteria and mycoplasma, however many bioreactors achieve superior therapeutic effects. We developed solving these issues. Various case studies highlight remain unprotected from viral contamination. Ideally, manufacturing processes for several new formats successful process design, optimization strategies a filter could be used to remove viruses, but filtration that provide the required yield and purity for clinical and critical manufacturing parameters. Additionally is traditionally perceived as being unsuitable for the studies. For that we considered the design of the practical advice will be given on what to consider upstream processes. A new virus filter has been therapeutic format and integrated the selection of when designing a novel molecule. evaluated and demonstrated high levels of virus, a suitable cell line, the development of a productive bacteria and mycoplasma removal while providing fermentation process and a complementary 9:00 Single Step Purification of high flow and capacity in chemically defined media purification scheme in a process effectively minimizing Biotherapeutic Proteins in a Highly with little to no impact on cell culture performance. Simplified Process Using an Optimized, product related impurities. Proprietary Fragment Complementation 11:15 Scaling-Up of a Downstream 1:15 Session Break System Purification Process for a New Recombinant PURIFICATION OF MEMBRANE David O’Connell, Ph.D., Lecturer, Director, MSc Product (rhFVIII) Programmes, Biotechnology, School of Biomolecular Martin Linhult, Ph.D., Head of Bio100 line 1, PROTEINS AND ANTIGENS & Biomedical Research, University College Dublin Octapharma Engineering of a very high affinity complementation 1:25 Chairperson’s Remarks Octapharma has developed a new process for the between two calcium-binding protein domains has led Julie Bomholt, Ph.D., Protein Specialist, Research & production of a recombinant human FVIII product to the development of a robust purification system Development, Aquaporin A/S derived from a human cell line (HEK293F cells). that in a single step produces high yields of very pure Clinical trials are ongoing with positive results. During protein for downstream analysis, dispensing with time 1:30 Membrane Proteins: From Lab-Scale REGISTER ONLINE NOW! process development several different approaches consuming dialysis step. Through collaborations with towards Large-Scale Production have been tested, old established techniques as well BioprocessingSummit.com leading biopharmaceutical companies and research case unpublished Julie Bomholt, Ph.D., Protein Specialist, as new ones has been evaluated. In this presentation study data institutes the purification of proteases, kinases and Research & Development, Aquaporin A/S I will discuss scale-up of a new downstream binder proteins will be presented. purification process and also different affinity ligands Downstream processing of membrane proteins that could be applied. is further complicated by the amphipathic nature

27 2nd Annual STREAM #2: Formulation & Advances in Purification Technologies: Downstream Processing Novel Advances and Continuing Improvements for Higher Downstream Productivity and Purity

of membrane proteins that even in the purified 3:00 Networking Refreshment Break form are ternary complexes consisting of protein, lipid and detergent in unknown ratios. By use of SCALED-DOWN PROCESSES AS the physiologically important trans-membrane protein family of aquaporins as model proteins, we PREDICTIVE MODELS FOR LARGE developed a S. cerevisiae-based expression system and SCALE PRODUCTION identified conditions that allowed us to substantially increase the membrane density of recombinant 3:15 Scaled-Down Model Qualification and functional aquaporin. Use for Process Improvement Adam J. Meizinger, Ph.D., BS, Process Engineer II, 2:00 Antigen Purification for Biologics Manufacturing Science and Technology Laboratory, Projects Genzyme, A Sanofi Company case Medha J. Tomlinson, Ph.D., Principal Research study Scientist, Global Biologics – Protein Sciences, 3:45 Challenges in Developing Predictive Abbvie Bioresearch Center Downstream Scaled-Down Models The early discovery stage of antibody programs Omkar Joshi, Ph.D., Head, Downstream requires generation of proteins and cell lines. Development, Global Biologics, Bayer Healthcare Appropriate construct design and expression systems are needed to retain antigen biophysical 4:15 Close of Conference characteristics and activity. Proprietary antibody generation requires expression and purification of This Conference is various orthologues for screening and optimizing affinity. Rapid turnaround and antigen supply are also part of: paramount for success. This talk will focus on working STREAM #4: towards building a robust platform to overcome many of these challenges. Process Innovations & Cell Therapeutics MINIATURIZATION AND AUTOMATION 2:30 Miniaturized and Automated Inclusion Click here for details. Body Processing – From Homogenization to Purification

case unpublished Cornelia Walther, Ph.D., Post-Doc, study data Institute of Applied Microbiology/ Biopharma Austria Process Science, University of Natural Resources and Life Sciences Vienna Biopharmaceuticals overexpressed in E. coli are often deposited as high density aggregates in inclusion bodies requiring additional process steps such as inclusion body recovery, solubilization and refolding. For each product, individual needs of the process REGISTER ONLINE NOW! might present a bottleneck during downstream processing. We present a miniaturized platform for BioprocessingSummit.com parallel screening of cell disruption, IB washing, solubilization and refolding conditions and purification compatible with the concept of DOE.

28 rd 3 Annual STREAM #3: Rapid Methods to Assess Quality & Analytical & Quality Stability of Biologics: Improving Prediction and Screening

MONDAY, AUGUST 3 QC labs has positively impacted the industry, leading 3:45 Analytical Testing Strategy for to improved throughput, accuracy, precision, and Admixture Testing of Therapeutics 8:00 am Pre-Conference Registration and sensitivity, as well as reduced labor and cost. Talk will Shenjiang Yu, Ph.D., Associate Principal Scientist, Morning Coffee discuss some recent changes in the QC world. Sterile Product and Method Development, MRL, Merck Co. & Inc. 9:00-11:30 Recommended Short Course* 2:15 A Unique High Throughput Assay for A pharmaceutical admixture consists of a drug Biophysical Characterization in Assessing Determination of the Potency and Stability product mixed with a suitable diluent in a intended the Higher Order Structure (HOS) of Biologics dosing/delivery device for the purpose of parenteral Fingerprint of Biopharmaceuticals case unpublished Michael Tovey, Ph.D., INSERM Director infusion to the patient. Regulatory agencies have study data * Separate registration required; click here of Research, Laboratory of Biotechnology specific requirements for the demonstration of the for details and Applied Pharmacology, Ecole Normale Supérieure compatibility of the drug product with reconstitution de Cachan, France diluents, because many of the therapeutic proteins 11:30 Main Conference Registration Biologic activity is essential for the assessment are dosed intravenously in the form of admixtures. of potency and stability of biologics and Therefore, analytical strategies are presented to show CHALLENGES AND OPPORTUNITIES successful development of biologics depends the compatibility with dosing/delivery device. A few upon establishment of validated and standardized case studies is discussed with the implementation of FOR NEW METHODS FOR TESTING assays that allow direct comparisons of the relative our analytical strategies. QUALITY &STABILITY potency and stability between batches. A validated standardized high throughput assay platform using 4:15 Breakout Discussions 1:00 pm Chairperson’s Opening Remarks engineered reporter-genes allows direct comparison This session provides the opportunity to discuss Jianmei Kochling, Ph.D., Director, Quality Science and of drug potency and stability within two hours for a focused topic with peers from around the world Analytical Technology, Genzyme - a Sanofi Company structurally diverse TNF-α antagonists or closely in an open, collegial setting. Select from the list of related novel forms of human insulin and FGF-21. topics available and join the moderated discussion »»1:10 KEYNOTE PRESENTATION: Introducing to share ideas, gain insights, establish collaborations Emerging Technologies into the QC Laboratory 2:45 Refreshment Break or commiserate about persistent challenges. Then continue the discussion as you head into case Paul Bigwarfe, Ph.D., Director, Analytical 3:15 Challenges to Implementing High study the lively exhibit hall for information about the Sciences, Regeneron Pharmaceuticals, Inc. Throughput Methods in a QC Environment Introducing new and emerging technologies latest technologies. unpublished Michelle Joubert, Staff Scientist, Genzyme a to the QC laboratory presents its own set of data Sanofi Company Topic 1: What are Current Control Strategies challenges. Regulatory hurdles and training are only a few of them. This presentation will address Capillary electrophoresis using Beckman Coulter’s PA for Submicron and Subvisible Particles in how to overcome these challenges and present 800 and the Caliper Labchip® GXII instruments are Biologics? case studies on where it has worked and not two platforms used to evaluate the purity of biologics. Moderator: Nataliya Afonina, Ph.D, President and worked well. These platforms have a higher throughput than SDS- Principle Consultant, AN Biologics Consulting LLC PAGE, as well as the ability to return quantitative · How protein aggregation in 0.1 -10 µm particle results. Analytical methods using these technologies 1:45 Emerging Technology for Biologics range may impact CQA related to product quality have been established for the analysis of products Stability Testing and purity? in early stages of development. Challenges and Jianmei Kochling, Ph.D., Director, Quality Science and opportunities of implementing these methods in a QC · What are regulatory expectations? Analytical Technology, Genzyme - a Sanofi Company environment will be discussed. · How industry is handling and controlling REGISTER ONLINE NOW! Biologics are monitored for purity, potency, and subvisible and submicron particles? biological activity in stability. The use of appropriate BioprocessingSummit.com stability-indicating physicochemical, biochemical, and immunochemical analytical methodologies permits a comprehensive characterization and monitoring the quality of the drug substance and/or drug product. The effort of introducing advanced technologies to the

29 rd 3 Annual STREAM #3: Rapid Methods to Assess Quality & Analytical & Quality Stability of Biologics: Improving Prediction and Screening

Topic 2: Commercial Release Specification TUESDAY, AUGUST 4 9:00 Stability Challenges for Protein Setting Therapeutics: Anticipating Aggregation Moderator: Paul Bigwarfe, Ph.D., Director, Analytical 7:30 am Registration and Morning Coffee Phenomena at Early Development Stage case Sciences, Regeneron Pharmaceuticals, Inc. study Joël Richard, Ph.D., Senior Vice President Peptides, · Control strategies for various product PROTEIN AGGREGATION, Technical Operations, Ipsen forms/production stages PARTICLES & STABILITY The paradigm of protein formulation development · What tests are necessary? has moved from a posteriori detection and control 7:55 Chairperson’s Remarks · Justification of acceptance criteria of aggregation to the anticipation/prediction of Joël Richard, Ph.D., Senior Vice President Peptides, formulation, storage and processing conditions that Topic 3: High-Throughput and High Technical Operations, Ipsen will lead to aggregation in a QbD approach. In order to Resolution Screening to Assess Physical and anticipate potential aggregation issues, it is proposed 8:00 Strategy for Characterization and Chemical Instabilities in Protein to focus on the early steps of aggregation, which Control of Submicron and Subvisible most of the time may involve higher order structure Moderator: Ranajoy Majumdar, Ph.D., Research Particles in Biologics (HOS) alterations and loss of colloidal stability. Scientist, Biophysical Characterization, Nataliya Afonina, Ph.D., President and Principle Biopharmaceutical Research and Development, Eli 9:30 For the First Time, Sponsored by Lilly and Company Consultant, AN Biologics Consulting LLC Aggregation of proteins, including formation of Simultaneous Detection of · What is the predictability correlation from in early submicron (0.2 -2 µm) and subvisible (2 -10 µm) Protein Aggregation and Affinity development to late stage? particles, is one of the major concerns in biologics drug Measurements in the Same Single · Are there stability indicating techniques that products related to their stability, purity, and quality SPR Experiment correlate with shelf-life and in-use stability? and is defined as Critical Quality Attribute. Finding Aaron Martin, Senior Principal Scientist, SensíQ · Does the success of early phase stability the right risk-based approach and establishing the Technologies Inc prediction depend on product modality? tractability between particle evaluation at formulation No technologies have been capable of delivering step and in final drug product is critical. New strategic · How should an early stage stability screen information on both drug affinity and protein approach for 0.2 -10 µm particle characterization and look like to provide maximum knowledge aggregation simultaneously in the same experiment. control including regulatory requirements, evaluation of for development? SensiQ presents data from a collaboration with orthogonal methods, and establishing of morphological Genentech where this limitation is overcome by Topic 4: Admixture Testing Strategy libraries for subvisible particles will be discussed. simultaneously detecting protein aggregation and Moderator: Shenjiang Yu, Ph.D., Associate Principal 8:30 Addressing the Gaps in Particle determining affinity in the same experiment using Scientist, Sterile Product and Method Development, Pioneer FE SPR instrumentation. MRL, Merck Co. & Inc. Measurements for Biotherapeutic Solutions · Clinical support and regulatory expectation unpublished Reema Raghavendra, MS, MBA, Scientist II, 9:45 Coffee Break in the Exhibit Hall with data Global Protein Sciences, AbbVie, Inc. · Analytical tool box and strategy Poster Viewing Non-native protein structures, which are increasing · Special analytical development and investigation in use, have potentially altered propensities to self- 10:30 Investigate Protein Aggregation in associate. Concerns regarding the immunogenicity of 5:30 Grand Opening Reception in the Exhibit Process Change through Forced Degradation protein aggregates motivate particle characterization Studies Hall with Poster Viewing in the sub-visible range (0.1-100 µm). Flow cytometry unpublished Yimin Hua, Scientist II, Quality Science and holds the promise of distinguishing between particle data 7:00 End of Day Analytical Technology, Genzyme, a Sanofi types for sizes down to less than 1 µm. Here, we REGISTER ONLINE NOW! Company present two methods of standardizing flow-cytometry Aggregation is one of the main concerns of BioprocessingSummit.com diameter readings: the use of novel protein-like biotherapeutics when there is a process change. standards of discrete sizes and commercial beads. Detection and characterization of aggregation to identify the root cause will allow appropriate actions

30 rd 3 Annual STREAM #3: Rapid Methods to Assess Quality & Analytical & Quality Stability of Biologics: Improving Prediction and Screening

which will help to improve protein quality, minimize 12:00 pm Poster Highlight Presentation: RAPID SCREENING OF protein aggregation during process and on storage. Determination of Multiple Product Attributes FORMULATION STABILITY IN EARLY Proteins are subjected to different stress conditions With a High-Throughput Automated to induce aggregation in the lab. Various analytical Purification Assay DEVELOPMENT techniques will be used to characterize the forced degraded protein samples. The results will further the Jasmine Wang, M.S. Associate Scientist II, Analytical 1:55 Chairperson’s Remarks understanding of leading factors that contribute to the Biotechnology, MedImmune, Inc. Hardeep Samra, Ph.D., Senior Scientist, Formulation aggregation of recombinant proteins. A high-throughput assay was developed and Sciences, MedImmune, Inc. automated for the determination of multiple product POST-TRANSLATIONAL attributes of monoclonal antibodies in conditioned 2:00 A Novel Analytical Approach to medium. The samples containing monoclonal Investigate the Effect of Methionine MODIFICATIONS antibodies in conditioned media were purified using Oxidation on Antibody PK Protein A affinity magnetic beads and analyzed for 11:00 Fast LC/MS Methods for Monitoring case Jan Stracke, Ph.D., Principal Scientist, multiple quality attributes, including fragmentation, study Sites of Modification in Development, PC/PV Pharmaceutical Development & Supplies, PTD aggregation, oligosaccharides, charge isoform Biologics Europe, F. Hoffmann-La Roche Ltd. and Beyond levels, oxidation, deamidation, and other chemical Preserving the chemical and structural integrity of Amy Hilderbrand, Ph.D., Technical Development degradation. Results on protein recovery and product antibodies during manufacturing and storage is a major Scientist, Protein Analytical Chemistry, Genentech, Inc. quality attributes under various optimizing conditions challenge during development. Oxidation of Fc methionines will be presented. This high-through-put integrated Being able to monitor site specific modifications in is frequently observed, which leads to reduced affinity platform allows rapid and efficient sample processing biological molecules is important from a process, to FcRn and faster plasma clearance if present at high of up to 96 samples in three hours, and allows stability and quality perspective in development. This levels. A novel pH-gradient FcRn affinity chromatography monitoring multiple quality attributes of IgG1, IgG2, talk will focus on rapid relative quantitation using method was developed to isolate antibody oxidation and IgG4 during upstream process development. liquid chromatography/mass spectrometry methods variants from an oxidized IgG1 preparation based on their that are being evaluated and used to monitor sites Sponsored by FcRn binding properties. The subsequent physico-chemical that are vulnerable to modification. 12:30 Luncheon Presentation: iCE3: A Powerful Analytical and biological characterization of these oxidation variants demonstrated the value of the new method to study 11:30 High-Throughput Peptide Mapping to Tool for Protein Charge Heterogeneity structure-function relationships. Support Early Prediction of Biologics Quality Characterization unpublished Sponsored by data Yan Wang, Ph.D., Scientist, Analytical Jiaqi Wu, Principal Scientist, Biologics, ProteinSimple 2:30 Developability Assessment Development, Biogen Idec Traditional tools for quantitative protein charge and Formulations Optimization Peptide mapping is a sensitive and precise technique characterization include IEC and conventional cIEF. of Biologics Using Isothermal Chemical that is capable of detecting single amino acid However, these tools have limited application for Denaturation (ICD) analyzing complex therapeutic proteins. Whole changes and post-translational modifications (PTMs) Richard K. Brown, Ph.D., Unchained Labs in a single run. We have recently developed a novel column detection cIEF instrument, iCE3, does not Stability optimization and aggregation minimization are high-throughput (HT) peptide mapping workflow, require mobilization of the focused bands. Its open two of the most important hurdles in the development which targets four bottle-neck problems and enables capillary minimizes unspecific protein interactions of biologics. ICD provides the most accurate analyst to complete multiple sample comparison with column. iCE3’s fast speed increases throughput way of measuring protein stability under different in a single day starting from cell harvest to final and minimizes sample precipitation and aggregation formulation conditions. ICD experiments performed quantitative report. Our new HT peptide mapping during IEF. iCE3 is the best tool for quantitative at different protein conc. provide a quantitative workflow is transferrable to assess quality of analysis of charge heterogeneity of complex proteins. assessment of protein aggregation in the native and biologics in manufacturing, cell lines development and REGISTER ONLINE NOW! denatured states. ICD is ideally suited to optimize formulation development. 1:15 Session Break BioprocessingSummit.com the formulation of highly concentrated formulations, bispecific antibodies and antibody drug conjugates. In this talk, the fundamentals of ICD and its application to the evaluation of protein stability and optimization of formulation conditions will be discussed.

31 rd 3 Annual STREAM #3: Rapid Methods to Assess Quality & Analytical & Quality Stability of Biologics: Improving Prediction and Screening

3:00 Sponsored Presentation (Opportunity 4:45 HDX-MS Sheds Mechanistic Insights Available) on Mutation Induced Changes in Physical Stability of an IgG1 mAb Engineered For 3:15 Poster Highlight Presentation: Extended Serum Half-Life Leveraging Automation in Development of case Ranajoy Majumdar, Ph.D., Research Scientist, High Concentration Protein Formulations study Biophysical Characterization, Biopharmaceutical Aastha Puri, M.Sc., Associate Scientist II, Drug Research and Development, Eli Lilly and Company Product Science & Technology, Bristol-Myers Squibb A triple mutation in the CH2 domain of an IgG1 Formulation development of high concentration mAb intended to increase in vivo half-life resulted in products, brings a unique set of challenges, including decreased physical stability. Although the mutation the potential for increased physical and chemical induced minimal differences in H/D exchange kinetics stability risks, as well as challenges related to handling at the mutation sites and the FcRn binding epitopes, it of viscous material. This work demonstrates the increased the flexibility of an established aggregation utility of new automation technologies in proficiently hotspot in the CH2 domain. This case study reinforces executing experimental workflows on a viscous high our understanding of the correlations between mAb concentration protein formulation and assisting a data- physical stability and its local flexibility. driven decision making process as part of a material sparing, multi-well screening methodology. 5:15 Close of Conference 3:30 Refreshment Break in the Exhibit Hall with Poster Viewing 6:00-8:30 Recommended Dinner Short 4:15 A Comparison of Biophysical Course* Characterization Techniques in Predicting Protein Aggregation: Mechanism, Drug Product Stability Characterization and Consequences Andrew Semple, Scientist, Sterile Product and * Separate registration required; click here for details Analytical Development, Merck & Co. To predict stability behavior, solution-mediated interactions (Colloidal, self-association propensity) and key molecular characteristics of ten formulated protein-therapeutics were compared to their stability at accelerated (25C and 40C) and long- term storage conditions (2-8C) as measured by size exclusion chromatography. Our results show that colloidal stability, self-association propensity, and conformational characteristics (exposed Trp) provide reasonable prediction of accelerated stability, with limited predictive value at 2-8C stability. Other measurements (e.g., thermal unfolding temperature) REGISTER ONLINE NOW! did not show any correlation. BioprocessingSummit.com

32 nd 2 Annual STREAM #3: Early Analytical Development Analytical & Quality for Biotherapeutics Optimizing the Selection and Performance of Preclinical Analytical Studies

WEDNESDAY, AUGUST 5 antibodies based on Taylor dispersion analysis and UV 11:15 Biophysical Assays for Study of area imaging using nanoliters of samples. Aggregation and Subvisible Particles 7:00 am Registration and Morning Coffee case 9:30 Biophysical Analysis of the study Mario Hubert, Ph.D., Principal Scientist, Bristol- 8:05 Chairperson’s Remarks Compatibility of Monoclonal Antibodies in Myers Squibb The presence of subvisible particles can have a Mario Hubert, Ph.D., Principal Scientist, Bristol-Myers Intravenous Infusion Solutions to Overcome critical impact on drug product efficacy and potentially Squibb Possible Adverse Effects During Clinical induce immunogenicity. Strategies and health »»8:15 KEYNOTE PRESENTATION: Practice authority expectations for characterization of particles case Haripada Maity, Ph.D., Research Advisor, Eli Lilly Early Analytical Development of study below 10 um are evolving. This talk describes high Biotherapeutics; Case Studies and Lessons and Company throughput assay development for subvisible particle Learned Administration of therapeutic monoclonal antibodies concentration and characterization. Flow imaging case through the intravenous route can involve dilution of technique, supported by fluorescence and Raman study Ivan Correia, Ph.D., Senior Principal Research drug product using intravenous infusion solutions such microscopy was used to develop the assay. A Scientist; Head, Global Protein Sciences, AbbVie as saline or 5% dextrose. As a result, the original drug statistical model is used to evaluate assay precision Bioresearch Center product is diluted with potential changes in physical and recommended minimum sample sizes. The pre-clinical effort to identify and advance and chemical stability of the API. This presentation therapeutic molecules is challenging as resources will discuss structural characterization, protein- 11:45 Featured Poster Presentation: are scarce for enabling rapid first-in-human studies. protein interaction, concentration dependent inverse Determination of Multiple Product Attributes High throughput automation, platform methods and correlation of aggregation, and methods to monitor with a High-Throughput Automated adopting best practices are all important. However, time-dependent self-association in intravenous Purification a commitment to innovate is needed to rapidly infusion solutions. advance therapeutic programs. This presentation Jasmine Wang, Scientist, MedImmune will use case studies and lessons learned to 10:00 Coffee Break in the Exhibit Hall with 12:15 pm Luncheon Presentation illustrate how AbbVie is rapidly advancing best in Poster Viewing class therapeutics for patients. (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own ASSAY DEVELOPMENT AND MOLECULAR ASSESSMENT TROUBLESHOOTING 1:30 Session Break AND EARLY STAGE ANALYTICAL STRATEGIES 10:45 Strategies and Challenges for Early EARLY ANALYTICAL DEVELOPMENT Bioassay Method Development and FOR NOVEL BIOTHERAPEUTICS 9:00 Early Developability Screen of Specification Setting Therapeutic Antibody Candidates Using case AND BIOSIMILARS study Debra Meyer, Senior Principal Scientist, Analytical Taylor Dispersion Analysis and UV Area R&D, Pfizer 1:55 Chairperson’s Remarks Imaging Detection Pfizer has a robust pipeline of biotherapeutics Haripada Maity, Ph.D., Research Advisor, Formulation case study Alexandra Lavoisier, Scientist, Biologics Center, including multiple modalities. Supplying biologically Development, CMC Development, Eli Lilly and Novartis, Switzerland relevant bioassays across a large portfolio requires an Company Therapeutic antibodies represent one of the fastest evolution of a strategic, resource-flexible approach. growing segments in the pharmaceutical market. Case studies will be used to illustrate a strategy for 2:00 Analytical Development for Knob-into- Early quality control and risk assessment of their staged method development that delivers fit-for- Hole Bispecific Antibodies REGISTER ONLINE NOW! biophysical parameters help prevent failure in later purpose bioassays for early product development. Hongbin Liu, Ph.D., Scientist, Protein Analytical BioprocessingSummit.com stages of development, reducing costs and time The challenges and issues setting percent relative Chemistry, Genentech consumption. We report on a novel micro-capillary- potency specification ranges for qualified bioassays Bispecific antibodies have shown great promise to based instrument (Viscosizer) for measuring both the early in development (prior to ICH validation) will be be versatile and effective biotherapeutics. However, hydrodynamic radius and the absolute viscosity of emphasized. manufacturing of large quantity bispecifics with

33 nd 2 Annual STREAM #3: Early Analytical Development Analytical & Quality for Biotherapeutics Optimizing the Selection and Performance of Preclinical Analytical Studies

consistent quality remains to be a challenge. This approval is the demonstration of comparability; there Moderator: Sam Ellis, Vice President, Biochemist, presentation will focus on the analytical methods must be no meaningful difference in efficacy, safety Thomson Instrument Co. for a major format, knob-into-hole bispecifics, in and overall quality between the biosimilar and the Panelists: development at Genentech. Details on method originator. To achieve this, it is essential to know the Joanne T. Beck, Ph.D., Senior Vice President, development for analyzing unique impurities, as well critical quality attributes of the molecule and to control Pharmaceutical Development, Shire Pharmaceuticals as overall analytical strategy for characterization and them properly during the development and production. Wayne Froland, Ph.D., Associate Vice President, control systems will be discussed. 4:00 Refreshment Break in the Exhibit Hall with Center for Biopharmaceutical Manufacturing Sciences, Merck Manufacturing Division 2:30 Analytical Development for Cell-Based Poster Viewing Therapeutics Stefan Schmidt, Ph.D., M.B.A., Vice President, case Process Science & Production, Rentschler study PLENARY SESSION Gautam Banik, Ph.D., Vice President, Cellerant Biotechnologie GmbH Therapeutics Haripada Maity, Ph.D., Research Advisor, Eli Lilly and CLT-008 is an off-the-shelf cellular product containing 4:45 Chairperson’s Remarks Company myeloid progenitor cells derived from adult Sam Ellis, Vice President, Biochemist, Thomson hematopoietic stem cells that have the ability to Instrument Co. 6:00 Networking Reception in the Exhibit Hall mature into neutrophils in vivo. Cellerant is developing with Poster Viewing CLT-008 as a treatment for neutropenia caused »»4:50 PLENARY KEYNOTE by chemotherapy or radiation. CLT-008 is under PRESENTATION: 7:00 End of Day evaluation in a Phase II clinical trial in AML patients Meeting the Needs of Patients with receiving chemotherapy. This talk will discuss the Rare Diseases: Innovation in Product development of CLT-008 with a focus on analytical THURSDAY, AUGUST 6 Development techniques for lot release. Joanne T. Beck, Ph.D., Senior Vice President, 8:00 am Registration and Morning Coffee 3:00 PEGylation of Antibody-Based Pharmaceutical Development, Shire Pharmaceuticals Therapeutics with Reduced Serum Half-Lives At Shire, where the delivery of innovative DEVELOPMENT AND medicines to patients with rare diseases and other Nathan Brown, Ph.D., Senior Scientist, AbbVie TROUBLESHOOTING OF CELL- specialty conditions is a fundamental component of Bioresearch Center the business model, creative solutions are critical BASED POTENCY ASSAYS The influence of PEG conjugation on therapeutics to our success. Starting with the transition of drug 8:25 Chairperson’s Remarks above the renal clearance threshold is not well candidates from discovery research to the clinic, understood. We have pursued strategies for followed by late phase development and eventually Kathleen Shields, Senior Research Scientist, Pfizer incorporating PEG onto engineered antibodies with commercial product lifecycle management, 8:30 Development and Troubleshooting of diminished half-lives, including chemical conjugation scientists and engineers focus on both technology to native, interchain disulfides as well as to innovation and creative business approaches to Cell-Based Potency Assays to Demonstrate engineered, unpaired thiol mutations. The engineered deliver high quality therapies to the patients while Drug Mechanism of Action mutations and PEG attachments were evaluated for case decreasing development timelines and costs. study Peggy Criswell, Ph.D., Senior Scientist, Merck & alterations to the protein’s biophysical properties, Company conjugation efficiency and specificity, antigen affinity, For an immunomodulatory biological therapeutic, three and in vivo half-life. 5:20 Interactive Panel Discussion: How to Innovate Product Development potency assays were developed, a competitive binding ELISA, a cell-based competitive binding ELISA, and a 3:30 Identification of Quality Attributes in · Technologies REGISTER ONLINE NOW! functional cell-based assay, utilizing a co-culture system Early Biosimilar Development · Strategies case of human Jurkat T-cells expressing the target and ligand BioprocessingSummit.com study Tilen Praper, Department Head, Analytical · Cutting Costs presenting APCs. Each assay was implemented in the Development, Sandoz, Slovenia · Meeting needs contract lab in parallel and validated or qualified. A case Biosimilars are biologics approved via stringent study is presented for assay implementation for product · Utilizing creativity regulatory pathways, following a loss of exclusivity release and/or process characterization for licensure. of their originator reference products. The basis for · Lessons Learned

34 nd 2 Annual STREAM #3: Early Analytical Development Analytical & Quality for Biotherapeutics Optimizing the Selection and Performance of Preclinical Analytical Studies

9:00 Method Development Guidance to 10:45 A High-Throughput Capillary Isoelectric 12:15 pm Sponsored Presentation Reduce Variability in Complex Cell-Based Focusing Immunoassay for Protein (Opportunity Available) Potency Assays Sialylation Fingerprinting case case 12:30 Luncheon Presentation (Sponsorship study Kathleen Shields, Senior Research Scientist, study Lam Raga Anggara Markely, Ph.D., Scientist, Biogen Idec Opportunity Available) or Enjoy Lunch on Your Pfizer We developed a high-throughput method for semi- Own Development of mechanistically relevant biological quantitative fingerprinting of protein sialylation using assays necessitates the execution of well-planned cIEF-immunoassay. The method is specific, sensitive, 1:15 Close of Conference experiments. Accelerated drug development precise, and robust. It can analyze 2 µL unpurified cell timelines and regulatory expectations for early culture samples within 4 hours (8 samples) to 14 hours introduction of functional bioassays in specific (96 samples) without analyst supervision. It can be used product categories (e.g. ADCs) challenge the for initial screening in cell line and process development, method development scientist to efficiently based on which a subset of samples can be further optimize key assay parameters. A case study will characterized by elaborate assays, such as LC and MS. be presented to illustrate the evaluation of assay parameters considered to be essential for delivery 11:15 Fully Automated Host Cell Protein of a robust potency assay capable of supporting (HCP) Analysis using the AlphaLISA Assay for phase-appropriate specifications. High Throughput Process Development

case Zheng Ouyang, Automation Specialist, Biologics AUTOMATION AND EMERGING study Process Development, Bristol-Myers Squibb TECHNOLOGIES An HCP AlphaLISA was fully automated and developed to enable “best in class” HTPD program 9:30 Application of Differential Scanning development. The improvements introduced by this Calorimetry in Biotherapeutic Comparability accomplishment include a cost reduction of 600% Analysis as compared to the traditional approach at improved William M. Matousek, Ph.D., Staff Scientist, Protein sample throughput, and provided reliable insight into Biochemistry, Regeneron Pharmaceuticals, Inc. the HCP impurity reduction capability and robustness. This high-throughput assay capability is instrumental Differential Scanning Calorimetry (DSC) is a sensitive to support HT process development and to meet the technique commonly used to define protein thermal Fast-to-FIH timelines. unfolding transitions, assess relative thermal stability, and compare higher order structural content. 11:45 Application of High Throughput Multiple characteristic unfolding transitions are often observed, making the method amenable for both Analytical Methods and Instrumentation case establishing identity and the estimation of impurities. study Ling Santora, Ph.D., Senior Scientist, AbbVie Thermodynamic properties such as Tm, enthalpy, Bioresearch Center and heat capacity were evaluated as indicators of Success of a drug discovery and development structural similarity and purity. campaign depends on the adequate supply and quality of targets and other protein reagents. Scarce 10:00 Coffee Break in the Exhibit Hall with resources and aggressive development timelines Poster Viewing demand the need for reliable methods to rapidly REGISTER ONLINE NOW! screen and select for these reagents. At AbbVie

BioprocessingSummit.com we have developed various high throughput (HT) automated multi-dimensional HPLC platforms to purify and assess the quality of protein reagents to support early target discovery and cell line development. This talk will highlight these methods.

35 Inaugural STREAM #3: Virus Detection, Clearance and Analytical & Quality Safety of Biologics: Adventitious Agent Contamination, Risk Mitigation, New Technologies and Case Studies

THURSDAY, AUGUST 6 3:15 Anion Exchange Membrane Adsorber evaluated the effect of extensive resin cycling on and Viral Clearance Capacity – an Alternative the capacity to bind virus in flow-through mode. A VIRAL SAFETY, RISK ASSESSMENT to Anion Exchange Chromatography? single column of new resin was tested alongside a single column of used resin, with both columns Horst Ruppach, Ph.D., Global Manager Viral Clearance AND MANAGEMENT showing consistent capacity to clear two virus types and Global Coordinator Virology, Biologics Testing in duplicate as well as demonstrating no viral particles Solutions, Charles River Biopharmaceutical GmbH 1:55 pm Chairperson’s Remarks in carryover (“mock”) pools produced after each viral Horst Ruppach, Ph.D., Global Manager Viral Clearance Anion Exchange Chromotography shows frequently clearance run. and Global Coordinator Virology, Biologics Testing high viral removal capacity when run under certain Solutions, Charles River Biopharmaceutical GmbH conditions. This presentation will summarize 5:15 Panel Discussion: Advances in Viral experiences made with different types of Anion Clearance and QbD Approach to Viral Safety Exchange Membrane Adsorbers. The general »»KEYNOTE PRESENTATIONS: Moderator: Horst Ruppach, Ph.D., Global Manager Viral capacity and robustness to remove viruses will be 2:00 Application of Regulatory Guidance Clearance and Global Coordinator Virology, Biologics demonstrated and compared with the capacity of to New Molecular Detection Methods for Testing Solutions, Charles River Biopharmaceutical GmbH Anion Exchange Chromatography. The pros and cons Virology and Mycoplasmology of using Membrane adsorbers for viral clearance Panelists: case Barbara J. Potts, Ph.D., Senior Consultant, Paul W. Barone, Ph.D., Associate Director, study removal will be outlined and discussed based on Potts and Nelson Consulting LLC experimental data. Consortium on Adventitious Agent Contamination Molecular detection methods both old (PCR) and in Biomanufacturing, MIT Center for Biomedical new including massively parallel sequencing, chip 3:45 Poster Highlight Presentation: Use Innovation technology, and PCR combined with MASS Spec of Virus Like Particle’s as Viral Clearance Otmane Boussif, Ph.D., Director, Purification & Time of Flight are ready to replace some of the Spiking Surrogates during Downstream Formulation Processes, Sanofi Pasteur classical virology detection methods. This talk Process Development Studies Siemon Ng, Ph.D., Scientist, Microbiology & Virology will outline a path forward that the biotechnology David A. Cetlin, Founder & C.E.O., MockV Solutions LLC Platform, Department of Analytical Research & industry can follow to successfully accomplish this Development North America, Sanofi Pasteur change. An example of this path that has yielded Viral clearance studies are accomplished by Barbara J. Potts, Ph.D., Senior Consultant, Potts and success for mycoplasma PCR replacement of a challenging scaled-down versions of purification Nelson Consulting LLC culture method will be provided. steps with live viral “spikes”. These studies are typically conducted in BSL-2 facilities and are costly. 5:45 End of Day 2:45 Mitigating Viral Contamination in A non-infectious viral surrogate would be useful for scientists developing or characterizing downstream Vaccines and Biologics Manufacturing 6:30-9:00 Recommended Dinner Short purification process steps. Discussed here is an case Otmane Boussif, Ph.D., Director, Purification & Course* study Formulation Processes, Sanofi Pasteur attempt to use a Virus Like Particle to determine the Mouse Minute Virus removal efficacy of a ABC: Anything But Chromatography Contaminations of mammalian cell culture chromatography column step. bioreactors are still being reported. In order to – Precipitation, Crystallization and Flocculation prevent this threat, manufacturers developed 4:00 Refreshment Break in the Exhibit Hall * Separate registration required; click here several risk mitigation strategies. Raw materials, with Poster Viewing media and solutions are the most likely source of for details. contamination of mammalian cell-based operations, 4:45 An Alternative Approach to Evaluation of with risk related to material source and supply Viral Clearance on New vs. End-of-Life Anion chain. Therefore implementations of additional Exchange Chromatography Resin REGISTER ONLINE NOW! point-of-use barriers risk, as well as sensitive analytical tools are considered. This presentation case unpublished William Daniels, MSc, Senior Scientist, BioprocessingSummit.com study data will discuss alternative technologies for media Purification Process Development, Pfizer, Inc. treatment through case studies. A viral clearance study for new and used (end-of- life) anion exchange chromatography (AEX) resin

36 Inaugural STREAM #3: Virus Detection, Clearance and Analytical & Quality Safety of Biologics: Adventitious Agent Contamination, Risk Mitigation, New Technologies and Case Studies

FRIDAY, AUGUST 7 predictable capacity for virus removal and inactivation. 12:15 Extended Q&A with Session Speakers In order to minimize viral clearance testing for early This session provides the opportunity to discuss 8:00 am Registration and Morning Coffee phase clinical programs, we have established modular a focused topic with peers from around the world claims for dedicated clearance steps within our in an open, collegial setting. Select from the list of VIRAL CLEARANCE IN platform manufacturing process. The claims have been topics available and join the moderated discussion to successfully submitted in IND filings and have enabled DOWNSTREAM PROCESSING & share ideas, gain insights, establish collaborations or greater efficiency in early and phase trials. commiserate about persistent challenges. Then continue PURIFICATION the discussion as you head into the lively exhibit hall for 10:00 Coffee Break information about the latest technologies. 8:55 Chairperson’s Remarks Sponsored by Kathryn Martin Remington, Ph.D., Principal Scientist, 10:45 Viral Risk Mitigation Strategies for Cell 12:30 Luncheon Presentation: Development Services, BioReliance Culture Media and Other Raw Materials Preventing Virus Contamination unpublished data Kathryn Martin Remington, Ph.D., Principal of Bioreactors with a Virus 9:00 FEATURED PRESENTATION: A Survey Scientist, Development Services, Barrier Filter of Industry Data on HTST, UV-C and BioReliance Christina Carbrello, Ph.D., Senior Scientist, Process Contamination prevention strategies should involve a Nanofiltration for Media Treatment and Solutions, EMD Millipore multi-faceted approach, including cell line screening, Their Efficacy of Removal and Inactivation Cell culture media is typically sterile filtered to remove of Virus raw material testing and implementation of viral inactivation and removal steps in the downstream bacteria and mycoplasma, however many bioreactors unpublished Paul W. Barone, Ph.D., Associate Director, remain unprotected from viral contamination. Ideally, data process. Other measures, such as viral reduction Paul W. Barone, Consortium on procedures for culture media and raw materials a filter could be used to remove viruses, but filtration Adventitious Agent Contamination in complement the strategy and may reduce the is traditionally perceived as being unsuitable for the Biomanufacturing (CAACB), MIT Center for potential for viral contaminants to enter the upstream processes. A new virus filter has been Biomedical Innovation downstream process. Data will be presented to evaluated and demonstrated high levels of virus, To reduce the risk of virus contamination in cell demonstrate the efficacy of procedures such as UVC bacteria and mycoplasma removal while providing culture based biomanufacturing operations many treatment and virus reduction filtration to reduce high flow and capacity in chemically defined media manufacturers have implemented or begun to viruses in cell culture media. with little to no impact on cell culture performance. consider implementing large scale media treatment to remove or inactivate virus. Typical technologies 11:15 Process Strategies to Improve Virus 1:15 Session Break that have been considered for this task are HTST Clearance in Early Downstream Processing treatment, UV-C irradiation and nanofiltration. TECHNOLOGIES FOR DETECTION case unpublished Deqiang Yu, Ph.D., Senior Scientist, Process CAACB consortium has collected member data study data Development, Bristol-Myers Squibb Co. OF NEW & EMERGING VIRUSES and surveyed the literature to begin to assess the efficacy of each of these three media treatment This talk will focus on virus clearance in early steps AND PATHOGENS technologies. A preliminary assessment of the of downstream processing. Protein A step is used for 1:25 Chairperson’s Remarks results will be presented. virus clearance but not very effective. The strategies to improve virus clearance in Protein A will be discussed. Yoshifumi Hashimoto, Ph.D., Senior Scientist, Process 9:30 Successful Implementation of Modular Harvest treatment will be also discussed as a potential Development, Protein Sciences Corporation Viral Clearance Claims for Early Phase virus clearance step to increase process capability. Clinical Filings 1:30 Implementation of an Adventitious 11:45 Poster Highlight Presentation: Detection Assay Using High Throughput case Shilpa Ananthakrishnan, MSc, Scientist I, Process REGISTER ONLINE NOW! study Prefiltration and Process Improvements: Sciences, Purification, AbbVie Bioresearch Center Sequencing within a Vaccine Manufacturer Enhancing Virus Filter Performance with Use BioprocessingSummit.com Demonstration of viral clearance capability is integral Siemon Ng, Ph.D., Scientist, Microbiology & Virology of Surface Modified Membrane Prefilter to developing downstream process. Dedicated viral Platform, Department of Analytical Research & clearance steps are incorporated into the process Benjamin Cacace, R&D Engineer, EMD Millipore Development North America, Sanofi Pasteur to ensure patient safety by providing robust and NGS has great potential for testing cell substrates, raw materials, viral seed lots and crude harvests for

37 Inaugural STREAM #3: Virus Detection, Clearance and Analytical & Quality Safety of Biologics: Adventitious Agent Contamination, Risk Mitigation, New Technologies and Case Studies

adventitious agents. This technology has exquisite SCALED-DOWN PROCESSES AS sensitivity and broad specificity. Implementing NGS can potentially streamline the adventitious testing package PREDICTIVE MODELS FOR LARGE and replace animal testing. Data will be presented SCALE PRODUCTION comparing the performance of NGS against qPCR and in vitro assay as well as the detecting adventitious 3:15 Scaled-Down Model Qualification and agent in viral seed lots and other biological samples. Use for Process Improvement Adam J. Meizinger, Ph.D., BS, Process Engineer II, 2:00 Next-Generation Sequencing Detection Manufacturing Science and Technology Laboratory, of Adventitious Agents Genzyme - a Sanofi Company Brenda Richards, Staff Scientist, Functional Genomics, Genzyme, a Sanofi Company 3:45 Challenges in Developing Predictive Next-generation sequencing (NGS) is an Downstream Scaled-Down Models emerging technology for pathogen detection Omkar Joshi, Ph.D., Head, Downstream in biopharmaceutical manufacturing allowing Development, Global Biologics, Bayer Healthcare for the identification of both known and novel Scale-down models as appropriate representation of microorganisms. We have used this approach the manufacturing process are indispensable tools in to confirm the identity of a causative agent in a characterization of biopharmaceutical manufacturing bioreactor contamination and to establish the limits processes. During process development, such models of detection for DNA and RNA viruses and bacteria enable evaluation of variability in input materials and in a background of Chinese hamster ovary cells. parameters on a process and its impact on product The presentation will include strategies, data, and quality to an extent that simply is not feasible at conclusions from these experiments. manufacturing scale. The key is to keep it simple and appropriate to needs. The presentation shows a 2:30 Incomplete Novel Sf9 Rhabdovirus is pragmatic and systematic approach how to increase Detected in a Sf9 Cell Line understanding of an antibody purification process by Yoshifumi Hashimoto, Ph.D., Senior Scientist, Process elements like scale-down modelling and qualification, Development, Protein Sciences Corporation cross-functional risk assessments, and process A novel Sf9 rhabdovirus has been identified by next characterization studies. generation sequencing (NGS). We performed an 4:15 Close of Conference analysis to verify Sf9 rhabdovirus RNA and searched for virus structures in cell culture supernatant. Our results showed an incomplete Sf rhabodovirus RNA containing a deletion of 320 nt of and absence of This Conference is also rhabodovirus-like particles in 1.14 g/ml fraction of the culture supernatant. We discuss discrepancy of data part of: between NGS and conventional methods. STREAM #5: Regulatory & 3:00 Networking Refreshment Break Risk Management REGISTER ONLINE NOW! Click here for details. BioprocessingSummit.com

38 2nd Annual STREAM #4: Process Innovations & Cell Therapy Bioproduction: Cell Therapeutics Industrializing Cell Therapies

MONDAY, AUGUST 3 tissue-based products. These materials can have a topics available and join the moderated discussion profound effect on the expansion, differentiation, or to share ideas, gain insights, establish collaborations 8:00 am Pre-Conference Registration and activity of the processed cellular components, and or commiserate about persistent challenges. Morning Coffee can therefore have a significant impact on the finished Then continue the discussion as you head into product quality attributes. Thus, ensuring the quality the lively exhibit hall for information about the 9:00-11:30 Recommended Short Course* of a cell- or tissue-based therapeutic requires rigorous latest technologies. Analytical Strategies for Comparability in evaluation and qualification of the components used Table: Chimeric Antigen Receptor (CAR)-T Bioprocess Development in its manufacture. Cells: History, Success, Challenges and * Separate registration required; click here 2:45 Refreshment Break Advancement for details. 3:15 Sourcing and Qualification of Starting Moderator: Pranay D. Khare, Ph.D., Independent Consultant 11:30 Main Conference Registration Materials for Cell Therapy Products · CAR molecule development and advancement 1:00 pm Chairperson’s Opening Remarks Elizabeth Read, M.D., Principal, EJ Read Consulting LLC. · CAR-T cell manufacturing Anthony Davies, Ph.D., President, Dark Horse The cellular starting material becomes an integral · CAR-T cell safety and efficacy Consulting, Inc. part of the living, functional cells that constitute Table: Hidden Challenges in Cell Therapy 1:10 KEYNOTE PRESENTATION the active drug substance of cell therapy products. »» Processing I’m from the Government and I’m Here to This presentation will review the common types of cellular starting materials and cover approaches for Moderator: Knut Niss, Ph.D., CMC Team Director, Help - Navigating the Global Regulatory their sourcing and qualification. Specific challenges PO&T, Biogen Maze for Cellular Therapeutics in starting material qualification for patient-specific Anthony Davies, Ph.D., President, Dark Horse products (autologous or allogeneic) vs. off-the-shelf Table: Regulatory Pathways and Differences Consulting, Inc. allogeneic products (multipotent or pluripotent stem in US, Europe and Japan – Opportunities for The global regulatory framework for cell and gene cell-derived) will be addressed. Accelerating Development therapies and regenerative medicine is in an era Moderator: Anthony Davies, Ph.D., President, Dark of rapid change and potential harmonization. This 3:45 Raw Materials in the Manufacture of Horse Consulting, Inc. presentation will provide an up-to-the-minute road Advanced Therapies Medicinal Products: map of the path to approval for these drugs and Quality Attributes and Quality Assurance 5:15 Discussion Report-Outs their associated delivery devices. Bernd Leistler, Ph.D., Director, Development & 5:30 Grand Opening Reception in the Exhibit Production, CellGenix GmbH COLD CHAIN, PROCUREMENT AND Hall with Poster Viewing Regulatory agencies recognize an increasing need for QUALIFICATION OF RAW MATERIALS & guidance for raw materials used for ATMP production 7:00 End of Day FINISHED PRODUCTS and started developing guidelines that outline risk- mitigation strategies and qualification programs for 1:45 Cold Chain Design for Allogeneic Cell AM selection. AM manufacturers must ensure critical TUESDAY, AUGUST 4 Therapies quality attributes to meet increasing quality and safety 7:30 am Registration and Morning Coffee Brian Murphy, Ph.D., Director, Bioprocess concerns. GMP grade and animal-derived component- Development, Celgene Cellular Therapies free materials derived from well-characterized cell banks will reduce qualification and validation efforts of STRATEGIES FROM CLINIC TO 2:15 Qualification of Raw and Ancillary ATMP manufacturers and help to ensure consistency, COMMERCIALIZATION Materials Used in Cell Therapy safety and purity of the ATMP. Manufacturing 7:55 Chairperson’s Remarks REGISTER ONLINE NOW! 4:15 Breakout Discussions Fouad Atouf, Ph.D., Director, Biologics & Pranay Khare, Ph.D., Independent Consultant This session provides the opportunity to discuss BioprocessingSummit.com Biotechnology, U.S. Pharmacopeial Convention a focused topic with peers from around the world Raw and ancillary materials are important in an open, collegial setting. Select from the list of components used in the manufacturing of cell- and

39 2nd Annual STREAM #4: Process Innovations & Cell Therapy Bioproduction: Cell Therapeutics Industrializing Cell Therapies

8:00 Translation of Cell-Based Gene Therapy SCALING UP AND talk will give a basic overview of kSep technology and Product into Clinical Phase II Trial MANUFACTURING CHALLENGES discuss strategies used to develop processes for cell Ulrike Verzetnitsch, MSc, CTO, apceth GmbH therapy and vaccine products 10:30 Manufacturing Challenges and Treatment options based on genetically modified cells 2:30 Perfused Bioreactor for the Optimization may add alternative therapeutic modalities to medical Solutions for Autologous Cell Therapies of Human Stem Cell Culture oncology. The in-house developed investigational Knut Niss, Ph.D., CMC Team Director, PO&T, Biogen Veronique Chotteau, Ph.D., Principal Investigator, Cell medicinal product represented in this case study Compared to traditional drugs where a bulk of drug is a genetically modified mesenchymal-stem-cell- Technology Group, School of Biotechnology, KTH, substance is produced and dispersed to several Royal Institute of Technology suspension (gmMSC) for IV infusion. The product for individual patients, autologous cell therapy products We have created small perfusion bioreactors supporting clinical Phase I was manufactured inhouse within are derived from the patient’s own cells. With this, the culture of human stem cells adhering on electrospun the established GMP manufacturing capabilities. The a unique manufacturing scenario exists where each nanofiber scaffold of biocompatible and biodegradable Phase I study demonstrated the excellent tolerability patient equals one manufacturing batch. Thus, the polymer in EU project HESUB. The bioreactors are of this first-in-man and first-in-class drug and data commercialization strategy for such products needs to scale-down of a novel 50 mL perfusion bioreactor and allowed for continuation in Phase II in Q1/2015. consider several unique issues. This presentation will are used to develop and optimize perfusion processes discuss these issues in detail in light of establishing a 8:30 Optimization and Clinical Manufacturing of human stem cells. We will review our achievements large market for an autologous therapy. of Chimeric Antigen Receptor (CAR) T Cells for the culture of human myogenic progenitors and of for Solid Tumors 11:00 Translating Cell Therapies: Academic vs. human pluripotent stem cells, embryonic and induced.

unpublished Pranay D. Khare, Ph.D., Independent Industry Model data 3:00 Oral Poster Presentation Consultant Alexey Bersenev, Ph.D., Director, Advanced Cell An optimal production process for the chimeric antigen Therapy Lab, Yale University Scalable Manufacturing Solutions for T-Cell receptor (CAR) expressing T cells (CAR-T) is required and MSC Cell Therapy Products 11:30 Panel Discussion: Manufacturing and for their success in Adaptive T cell therapy clinical trials. Martha S. Rook, Ph.D., Director, Stem Cell Recently, outstanding results in several clinical trials Commercialization of Cell Therapy Products Bioprocessing Group, Process Solutions, EMD with CAR-T in acute lymphoid leukemia (ALL) and Millipore Corporation chronic lymphoid leukemia (CLL]) has been achieved. 12:15 Luncheon Presentation (Sponsorship As more cell therapies progress through clinical But limited data and success is observed from solid Opportunity Available) or Enjoy Lunch on Your Own testing, current in vitro culture methods are highly tumors CAR-T clinical trials. This talk will focus on the manual, cumbersome to scale and have limited optimization process and clinical manufacturing of 1:15 Session Break options for in-process monitoring and control. We CAR-T production process for solid tumors. SCALING UP AND have developed an expansion paradigm that uses 9:00 Stem Cell Therapy – The Road to a scalable, single-use, stirred tank bioreactor for MANUFACTURING CHALLENGES both T-cell and human mesenchymal stromal/stem Commercialization (cont.) cell (hMSC) cultures. Director monitoring for the Jasmin Kee, Ph.D., Head, Engineering, ReNeuron specific cell characteristics can be implemented at Our lead product, CTX, is a therapy for the treatment of patients 1:55 Chairperson’s Remarks any point during the culture assuring product quality left disabled by a stroke and for critical limb ischaemia. Both and consistency. In addition, we have evaluated 2:00 Development Strategies for kSep treatments are currently in Phase I and II clinical trials. This human platelet lysate as a serum alternative for presentation will discuss the challenges faced through clinical Single-Use Continuous Centrifuge Processes hMSC cultures and demonstrated similar growth

trials and the strategy to commercialization. Topics will include case Jonathan Rubin, Ph.D., Scientist, API Large Molecules, performance when compared to FBS containing study the use of contract manufacturers versus in-house manufacturing, Janssen Pharmaceuticals media. the bioreactor expansion process provides process scale-up and the use of automation to meet clinical trial Centrifugation is often employed during downstream ease of use in handling, in-process monitoring and needs and future commercial supply. processing to clarify or concentrate biologics (e.g. lower medium volume requirements leading to robust REGISTER ONLINE NOW! antibodies, vaccines, and cell therapies). Disposable processes and reduced cost of goods. 9:30 Sponsored Presentation (Opportunity centrifuge technology has greatly reduced preparation/ BioprocessingSummit.com Available) cleaning time and contamination risk. Generally, cell 3:15 Refreshment Break in the Exhibit Hall therapy products are concentrated in the centrifuge with Poster Viewing 9:45 Coffee Break in the Exhibit Hall with (retentate), whereas clarified vaccine and antibody Poster Viewing products flowthrough the centrifuge (centrate). This

40 2nd Annual STREAM #4: Process Innovations & Cell Therapy Bioproduction: Cell Therapeutics Industrializing Cell Therapies

TOOLS AND TECHNOLOGIES 5:15 Close of Conference TO ENHANCE CELL CULTURE 6:00-8:30 Recommended Dinner Short PROCESSES Course* 4:15 Biologics Data Platform for Tailored Incorporating the Concepts of Support of Cell Line Development Pharmaceutical Quality Systems into Christian Bender, Ph.D., Computational Biologist, Cell Therapy Products Global Drug Discovery, Global Biologics, Bayer * Separate registration required; click here HealthCare for details. We have successfully implemented the Biologics Data Platform (BDP) for tailored support of our screening and protein production processes. In the context of our cell line development process, we present the integration of BDP with our automation workstation. We demonstrate the power of using a comprehensive data management platform to track data for cell line clones and fed-batch experiments together with molecule information such as primary sequences and experimental results.

41 Inaugural STREAM #4: Process Innovations & Continuous Processing in Biopharm Cell Therapeutics Manufacturing Economics, Regulatory, Integration and Practical Implementation

WEDNESDAY, AUGUST 5 skepticism. This talk will present an assessment of Continuous capture multicolumn chromatography continuous bioprocessing against well-established (MCC) is a key unit operation in the development 7:00 am Registration and Morning Coffee fed-batch platform and provide a historical and of continuous, integrated processes. But how are futuristic perspective. continuous capture MCC processes developed and CONTINUOUS PROCESSING AS optimized using only small quantities of feedstock? 10:00 Coffee Break in the Exhibit Hall with We have developed and tested a new method to A DISRUPTIVE INNOVATION IN Poster Viewing accurately translate data from a minimal number BIOPROCESSING of single column runs into a low cost multicolumn CONTINUOUS PROCESSING VS. process. This new simple process transfer from batch 8:05 Chairperson’s Remarks FED-BATCH: ECONOMIC AND to continuous enables process optimization to fit Massimo Morbidelli, Ph.D., Professor, Institute REGULATORY PERSPECTIVES business needs. for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich 10:45 Economics of Continuous Processing 12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy 8:15 KEYNOTE PRESENTATION: Vs. Traditional Batch »» Lunch on Your Own Continuous Processing – Rewrite of Jeff Johnson, New Technology Lead, Merck & Co. Inc. the Rules? Opportunities for applying new technologies 1:30 Session Break Wayne Froland, Ph.D., Associate Vice President, integrated with continuous processing and enabled by Center for Biopharmaceutical Manufacturing single use will be discussed for monoclonal antibody INTEGRATION OF UP- AND DOWN- Sciences, Merck Manufacturing Division production. The combined efficiencies gained by continuous processing will be compared by economic STREAM PROCESSING 9:00 The Future State of Bioprocessing criteria to current manufacturing methods. In addition the impact of the new approaches to multi product 1:55 Chairperson’s Remarks Lawrence Weiner, Senior Director, Strategic manufacturing facilities will be described. Andrew Sinclair, FREng, MSc, President & Founder, Innovation, Biogen Biopharm Services Ltd. Disruptive innovation is required to deliver game 11:15 The Regulatory and Quality Perspective changing improvements demanded by the market on Continuous Processing 2:00 Integration of Up- and Downstream and industry. We will discuss Biogen’s approach Robert Kozak, Ph.D., Senior Regulatory Science Continuous Processing to implementing near term sustaining and long Advisor, Global Regulatory Affairs, Bayer Healthcare Massimo Morbidelli, Ph.D., Professor, Institute term disruptive technologies. The discussion Continuous perfusion production has enabled for Chemical and Bioengineering, Department of will include how technologies are selected and Chemistry and Applied Biosciences, ETH Zürich driven forward to implementation. We will also flexible manufacturing of rFVIII, a large complex biotech product, for over two decades. Continuous We discuss here a series of experiments where a discuss a few opportunities for innovation within perfusion reactor with CHO cells for the production existing technologies and share thoughts on improvement has driven frequent process, equipment and facility changes supported by comparability of a monoclonal antibody has been operated in the continuous manufacturing as an alternate route to continuous mode and connected to a two column maximize productivity. exercises assessing the impact to quality product attributes throughout the entire fermentation continuous protein A chromatographic unit for product 9:30 The Old Is New Again: A Fair and campaign which can be months in duration. capture. A few steady states are examined and the Examples of process changes implemented and non- use of simulation models for process design and Balanced Assessment of Continuous control is illustrated. Bioprocessing implemented will be reviewed along with the impact of a changing regulatory environment. Sadettin S. Ozturk, Ph.D., Assoc Deputy Director, 2:30 Continuous Manufacturing: Upstream REGISTER ONLINE NOW! Process & Analytical Development, MassBiologics 11:45 Simplifying Continuous Sponsored by vs. Downstream Issues and the Drivers BioprocessingSummit.com Although it is somehow branded as new, continuous Chromatography Process Andrew Sinclair, FREng, MSc, President & Founder, bioprocessing has been utilized over 25 years that has Biopharm Services Ltd. resulted in more than 15 licensed biopharmaceuticals. Development - Optimisation Our experience of modelling continuous bioprocess Recent attempts of re-popularizing the continuous Parameters to Fit Business Need operations allow us to provide insights into the bioprocessing receive mixed reactions form René Gantier, Ph.D., R&D Director, Biopharm status of continuous bioprocessing. This allows us the industry: great enthusiasm, confusion, and Applications, Pall Life Sciences to identify those factors that require optimization/ 42 Inaugural STREAM #4: Process Innovations & Continuous Processing in Biopharm Cell Therapeutics Manufacturing Economics, Regulatory, Integration and Practical Implementation

development and to understand the potential now and Table: An Examination of Barriers to the PLENARY SESSION for the future. In particular we focus on the influence Commercial Adoption of Continuous of upstream versus downstream and the implication Processes for Production of Biologicals of technology trends on the value proposition for 4:45 Chairperson’s Remarks Todd Przybycien, Ph.D., Professor, Chemical continuous operation. Sam Ellis, Vice President, Biochemist, Thomson Engineering and Biomedical Engineering, Carnegie Instrument Co. 3:00 Continuous Operations in Biopharm Mellon University Manufacturing: Back to the Future »»4:50 PLENARY KEYNOTE Table: The Challenges of Keeping PRESENTATION: unpublished Jean-Marc Bielser, Scientist, BioProcess Pharmaceutical Aging Facilities Fit for Purpose data Science, Merck Serono Meeting the Needs of Patients with Moderator: Morten Munk, Senior Technology Partner, Rare Diseases: Innovation in Product At early stage of bioprocess science, continuous Global Business Development, NNE PharmaPlan operations were the workhorse in the industry. Then, Development Aging facilities are a major concern for industry and for the past 10 years, we moved towards fed-batch Joanne T. Beck, Ph.D., Senior Vice President, regulators, due to the risk of supply of suboptimal quality operations. Recently, continuous operations is Pharmaceutical Development, Shire Pharmaceuticals products and possibly drug shortage situations. Join this considered again as a lever to boost process productivity At Shire, where the delivery of innovative medicines to roundtable discussion to share insight on the challenges and control product quality. Looking at bioprocess patients with rare diseases and other specialty conditions and what might hold the industry back from implementing history, this presentation will discuss the reasons of is a fundamental component of the business model, up-to-date solutions. The focus will not only be around the those “back and forth” trends. It will also present results creative solutions are critical to our success. Starting with facilities, but also the processes, analytical methods and obtained at EMD-Serono using continuous operations in the transition of drug candidates from discovery research manufacturing control strategies, and with special focus cell-culture and also in purification of biopharmaceuticals. to the clinic, followed by late phase development and on the regulatory impact and strategy for implementing Finally, it will discuss the challenges and opportunities eventually commercial product lifecycle management, the needed changes in all the mentioned areas. of continuous operations versus current established scientists and engineers focus on both technology fed-batch platform. Table: Implementing Continuous innovation and creative business approaches to deliver high quality therapies to the patients while decreasing Bioprocesses in GMP Manufacture 3:30 Breakout Discussions development timelines and costs. This session provides the opportunity to discuss a Moderator: Peter R. Levison, Ph.D., Senior Marketing Director, Downstream Processing, Pall Life Sciences focused topic with peers from around the world in an 5:20 Interactive Panel Discussion: · Assuming the purification technologies and open, collegial setting. Select from the list of topics How to Innovate Product Development materials used in both batch and continuous available and join the moderated discussion to share · Technologies ideas, gain insights, establish collaborations or explore processes are identical are these processes potential solutions to persistent challenges. interchangeable during design, development, · Strategies scale-up and production? · Cutting Costs Table: Perfusion processes have several · Large fed batch culture is today’s start point for · Meeting needs advantages, which make them perceived as DSP. Does the future include a series of staged · Utilizing creativity smaller fed batch bioreactors and/or perfusion possible solutions for the future. What are the · Lessons Learned impediments for perfusion process expansion cell culture processes Moderator: Sam Ellis, Vice President, Biochemist, · What other platforms and/or continuous today and how should we tackle these? Thomson Instrument Co. processes are required for non-Mab applications? Moderator: Veronique Chotteau, Ph.D., Principal Investigator, Cell 4:00 Refreshment Break in the Exhibit Hall Technology Group, School of Biotechnology, KTH, with Poster Viewing REGISTER ONLINE NOW! Royal Institute of Technology BioprocessingSummit.com

COMPANION CONFERENCE: Advances in Purification Technologies (August 6-7) – click here for details 43 Inaugural STREAM #4: Process Innovations & Continuous Processing in Biopharm Cell Therapeutics Manufacturing Economics, Regulatory, Integration and Practical Implementation

Panelists: 9:00 Continuous Chromatography – Why, 10:45 A Continuous Precipitation Process for Joanne T. Beck, Ph.D., Senior Vice President, When and How? High-Titer Recombinant Protein Capture and

Pharmaceutical Development, Shire Pharmaceuticals unpublished Andrew Zydney, Ph.D., Distinguished Purification data Wayne Froland, Ph.D., Associate Vice President, Professor, Chemical Engineering, The unpublished Todd Przybycien, Ph.D., Professor, Chemical Center for Biopharmaceutical Manufacturing Sciences, Pennsylvania State University data Engineering and Biomedical Engineering, Merck Manufacturing Division There is growing interest in the use of continuous Carnegie Mellon University Stefan Schmidt, Ph.D., M.B.A., Vice President, unit operations for bioprocessing with the ultimate Coupled precipitation-filtration operations can form Process Science & Production, Rentschler goal of developing an integrated continuous the basis of a continuous, scalable, economical Biotechnologie GmbH process. This talk will focus on the opportunities and generalizable platform process for the primary Haripada Maity, Ph.D., Research Advisor, Eli Lilly and for continuous chromatographic separations, recovery of high titer recombinant proteins. We Company including both the challenges and the potential have used synergistic combinations of precipitants advantages of this approach. Specific examples to selectively precipitate target proteins, spanning 6:00 Networking Reception in the Exhibit will be shown for the application of periodic (multi- a broad range of physical properties, against Hall with Poster Viewing column), simulated moving bed, and countercurrent backgrounds of complex contaminants. We have tangential flow chromatography to the purification of evaluated the performance of the proposed process 7:00 End of Day monoclonal antibodies. with simulations and reduced it to practice with an industrial partner. THURSDAY, AUGUST 6 9:30 Continuous Multi-Column and Integrated Purification Strategies for 11:15 Behavior of a Ceramic Membrane- 8:00 am Registration and Morning Coffee Enveloped Virus-Like Particles and Non- Based Perfusion CHO Culture System for Enveloped Viruses Production of IgG1 IMPLEMENTATION CHALLENGES Ricardo Silva, Ph.D., Downstream Processing Jean-Francois Hamel, Ph.D., BPEC Core Laboratory IN UPSTREAM PERFUSION Research, iBET - Instituto de Biologia Experimental e Supervisor, MIT Tecnológica AND DOWNSTREAM The growing interest on enveloped virus-like particles 11:45 Continuous Chromatography in Downstream CHROMATOGRAPHY and non-enveloped viruses for vaccines and gene Processing – How to Make It a Reality therapy applications led to the development of Kathleen Mihlbachler, Ph.D., Global Director, 8:25 Chairperson’s Remarks new purification strategies capable of coping with Separations Development, LEWA Process Technologies Andrew Zydney, Ph.D., Distinguished Professor, the challenges presented by these new products. Multi-column continuous chromatography has Chemical Engineering, The Pennsylvania State University Innovation in downstream processing should recently become an enabling technology that will therefore aim not only at productivity increase but “break the bottleneck” in downstream processing of 8:30 Perfusion Process for Very High Cell also at process economy whilst complying with biopharmaceuticals. Continuous chromatography has Density of CHO Cells regulatory requirements. Evaluation of integrated shown promises in reduction of manufacturing cost. Veronique Chotteau, Ph.D., Principal Investigator, Cell purification strategies and two-column semi- However, up to today there has not been a reported Technology Group, School of Biotechnology, KTH, continuous chromatographic systems for virus case at the production scale. What are the remaining Royal Institute of Technology and enveloped virus-like particles will be reported. technical barriers when implementing the technology Perfusion processes at high cell densities are Significant improvements in yield and product quality in the GMP environment? This presentation highlights perceived as a viable solution for the production of thus obtained will be highlighted. how to overcome the major barriers when developing biopharmaceuticals, allying small volume bioreactors, this technology platform. compatibility with disposable equipment and 10:00 Coffee Break in the Exhibit Hall with REGISTER ONLINE NOW! continuous manufacturing concept reclaimed by the Poster Viewing BioprocessingSummit.com Health Authorities. We will review our strategy for the development of high cell density processes looking in particular at the medium renewal rate minimization using cell separation by Alternating Tangential Flow filtration.

44 Inaugural STREAM #4: Process Innovations & Continuous Processing in Biopharm Cell Therapeutics Manufacturing Economics, Regulatory, Integration and Practical Implementation

12:15 pm What is Holding the Industry back from Implementing Continuous Processing More Broadly? Morten Munk, Ph.D., Senior Technology Partner, Global Business Development, NNE PharmaPlan Based on a survey among industry peers on continuous processing, this presentation will address various concerns around continuous processing, and real concerns are distinguished from perceived concerns. This presentation will not be another presentation on the financial benefits of continuous processing or a report on the newest equipment on the market. The aim of the presentation is to discuss and illustrate other elements which make the difference between success and failure when a continuous processing strategy is evaluated and implemented. 12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own 1:15 Close of Conference

45 Inaugural STREAM #5: Regulatory & Risk Bioprocess Quality and Regulatory Management Compliance A best practices forum for process characterization, control strategies and maintaining quality throughout the product lifecycle

MONDAY, AUGUST 3 therefore immunogenicity risk identification, 3:45 Regulatory Issues in the Development analysis, evaluation, mitigation and management of a Biosimilar Rituximab need to be incorporated into your programs as an 8:00 am Pre-Conference Registration and case Mauricio Seigelchifer, Ph.D., Director, Tech study Morning Coffee iterative process. Immunogenicity risk assessment Transfer, Mabxience, Argentina strategy, process and regulatory expectations will The development pathway for biosimilar medicines be discussed. 9:00-11:30 Recommended Short Course* is established in guidelines from WHO, EMA and Optimizing Media – Achieving 2:15 Implementation of QbD Principles into more recently FDA and different Latin American countries. The process, from the cloning, passing Super Soup Commercial Process Development and through upstream and downstream, has to be driven * Separate registration required; click here Process Characterization for mAbs and to obtain a highly similar molecule to the reference for details. Fc-fusion Proteins product. Here we present a case study of a biosimilar case Angela Lewandowski, Ph.D., Manager, Biologics Rituximab developed and produced to fulfill these 11:30 Main Conference Registration study Process Development, Bristol-Myers Squibb biosimilar requirements. We also present the 1:00 pm Chairperson’s Opening Remarks Risk assessments are a useful tool during commercial comparison with the market reference. process development and process characterization Bob Kozak, Ph.D., Senior Regulatory Science Advisor, 4:15 Breakout Discussions Bayer HealthCare Pharmaceuticals to drive process control strategies, thereby ensuring consistent process performance and product quality. This session provides the opportunity to discuss »»1:10 KEYNOTE PRESENTATION: This talk will focus on the implementation of QbD a focused topic with peers from around the world Analytical Methods and Specification principles (via risk assessment and management) in an open, collegial setting. Select from the list of during upstream and downstream commercial topics available and join the moderated discussion to Revisions during the Product Lifecycle case process development and characterization. Case share ideas, gain insights, establish collaborations or study Stephan O. Krause, Ph.D., Director, QA Technical studies for both mAbs and Fc-fusion proteins will commiserate about persistent challenges. Then continue Support, AstraZeneca Biologics be discussed. the discussion as you head into the lively exhibit hall for This presentation provides best practices for information about the latest technologies. specifications setting for clinical biological products 2:45 Refreshment Break within the framework of ICH guidelines on 5:15 Discussion Report-Outs pharmaceutical development (Q8(R2) and Q11), 3:15 Risk Management of Regulatory quality risk management (Q9) and quality systems Submissions 5:30 Grand Opening Reception in the Exhibit (Q10). The need to link the life cycles of test James Stonecypher, Regulatory Affairs Executive Hall with Poster Viewing method(s) and specifications is illustrated. A case Identifying and managing risks is an essential and 7:00 End of Day study illustrates how the IMP specification revision continuous activity in the development of (bio) process can be managed and how specifications pharmaceutical products. ICH Guideline Q9 outlines can be set and justified for early and late the principles, process, and tools for utilizing quality TUESDAY, AUGUST 4 development stages. risk management in the pharmaceutical industry. Risk management activities are often overlooked 7:30 am Registration and Morning Coffee RISK ASSESSMENT AND REGULATORY or underutilized in the regulatory submissions COMPLIANCE process. This presentation will discuss the benefits PROCESS CHARACTERIZATION and applications of risk management for regulatory AND IDENTIFICATION OF CRITICAL REGISTER ONLINE NOW! 1:45 Strategies for Immunogenicity Risk submissions and practical examples of how it can be implemented. PROCESS PARAMETERS BioprocessingSummit.com Assessment and Regulatory Compliance Bob Kozak, Ph.D., Senior Regulatory Science Advisor, 7:55 Chairperson’s Remarks Bayer HealthCare Pharmaceuticals Karthik P. Jayapal, Ph.D., Deputy Director, Many biotherapeutic products are immunogenic Manufacturing Technologies, Sanofi-Pasteur with minimal tools for predicting clinical outcome,

46 Inaugural STREAM #5: Regulatory & Risk Bioprocess Quality and Regulatory Management Compliance A best practices forum for process characterization, control strategies and maintaining quality throughout the product lifecycle

8:00 Challenges and Learnings Applying 9:30 Sponsored Presentation (Opportunity 11:30 Bioprocess Characterization Approach Retrospective QbD for Marketed Biologics Available) for a Marketed Biosimilar case Kenneth Green, Ph.D., Head, Manufacturing Science study Daliborka Dušanić Ph.D., Validation Lead, MS&T, and Technology, Shire 9:45 Coffee Break in the Exhibit Hall with Lek Pharmaceuticals, Slovenia For clinical candidates, QbD is generally applied Poster Viewing For the registration of legacy products marketed during development and commercialization phases 10:30 Using New Analytical Technologies for outside the US, FDA regulations demanding in as a standardized business process. However, this is depth understanding of sources of variability in the Process Characterization not typically the case for marketed products where production of a biosimilar can be challenging. The retrospective QbD requires consideration of established Nadine M. Ritter, Ph.D., President and Analytical knowledge gained during process characterization controls and regulatory commitments. This talk discusses Advisor, Global Biotech Experts, LLC can be beneficial from the manufacturing and QA Shire’s approach for retrospective QbD for marketed Initiatives such as PAT and QbD, plus the desire perspective; however, it can also pose business risks products including establishing a business process, to continuously improve production by leveraging such as the need for re-validation and changes in associated criticality and change control strategy via process comparability paradigms, have enhanced filings in other countries. This case study reviews the application of risk assessments, and the behavioral the need to utilize both classic and state-of- approach for PC of a legacy biosimilar product. changes required for successful implementation. the-art analytics for upstream and downstream characterization and comparability exercises. This 12:00 pm Sponsored Presentation 8:30 Product Characterization Methods and talk will provide an overview of current applications (Opportunity Available) Strategies for Process Development of analytics in process development, and highlight practical issues to be considered in selecting and 12:30 Luncheon Presentation (Sponsorship case Christine P. Chan, Ph.D., Principal Scientist and study Technical Lead, Manufacturing Science & applying a wide array of analytical technologies to Opportunity Available) or Enjoy Lunch on Your Own Technology, Genzyme - a SANOFI company biotechnology processes. 1:15 Session Break Development of complex glycoproteins requires 11:00 Analytical Characterization to an array of analytical techniques to adequately understand and control product quality during the Support Development of Antibody CONTROL STRATEGIES AND manufacturing process. This presentation will discuss Biopharmaceuticals: Identity, Purity, Potency ONLINE PROCESS MONITORING strategies in product testing and review case studies and Safety case 1:55 Chairperson’s Remarks on characterization of different proteins in support of study Xuan Gao, Ph.D., Scientist, Sutro Biopharma, Inc. process development. During our early development of an IgG1 molecule, Zhimei Du, Ph.D., Principal Scientist, Teva LC/MS/MS was used to identify sequence variants Pharmaceuticals 9:00 Troubleshooting Bacterial Vaccine and post translational modifications; Biacore and Production 2:00 Utilization of Advanced Process Control other assays were used to determine consequences to Drive Consistent Processes in Mammalian case Karthik P. Jayapal, Ph.D., Deputy Director, of such variants and modifications on potency and study Cell Culture Manufacturing Technologies, Sanofi-Pasteur safety. We correlated characterization results with Vijay Janakiraman, Ph.D., Senior Engineer, Biogen Idec The use of complex raw materials like casamino process procedures to identify the root cause of acids or soy hydrolysates in bacterial fermentation sequence variants and modifications. Furthermore, Advances in online process monitoring have paved can contribute to process and ultimately product rapid analytical methods were developed to support the way for the next generation of control strategies variability. This case study will focus on our approach screening and production of desired molecule for achieving advanced process control. The end to mitigating such risks for a bacterial vaccine during development. result will be more consistent process performance REGISTER ONLINE NOW! production process by exploring opportunities for and product quality control. This talk will provide better raw material characterization, improved insight into new process analytical technologies (PAT), BioprocessingSummit.com process robustness and simplifying, and/or such as spectroscopy and biocapacitance, to assist in the implementation of online process monitoring. modernizing the current manufacturing process.

47 Inaugural STREAM #5: Regulatory & Risk Bioprocess Quality and Regulatory Management Compliance A best practices forum for process characterization, control strategies and maintaining quality throughout the product lifecycle

2:30 Control Strategy Approach for a Well- 3:30 Refreshment Break in the Exhibit Hall constitute a potential risk to bioreactor operations. Characterized Vaccine with Poster Viewing Contamination events result in costly delays and case restarts but most importantly, threaten the supply of study Parag Kolhe, Ph.D., Senior Principal Scientist, lifesaving products to our patients. This presentation Pfizer 4:15 Deciphering Factors that Have Impacts on Glycosylation of mAb and its Biophysical identifies those core components of contamination Robust control strategy as proposed in ICH Q10 prevention which if implemented can provide the is the foundation for ensuring consistent process Properties greatest impact in minimizing the microbiological risks performance and product quality. This presentation Zhimei Du, Ph.D., Principal Scientist, Teva in our manufacturing sites. will describe approach towards developing control Pharmaceuticals strategy during development lifecycle. Case study Consistent and reproducible generation of mAb 5:15 Close of Conference will be presented for well-characterized vaccine glycoform profiles still remains a considerable product that illustrates the approach and its utility challenge in biopharmaceutical industry. To assess 6:00-8:30 Recommended Dinner Short during process performance qualification (PPQ) and the mechanism of immature glycan process, and Course* commercial manufacturing. to minimize the environment-mediated lot-to-lot Patent Strategies for Bioprocess Scientists variations, we identified a broad range of factors that * Separate registration required; click here 3:00 Practical Considerations of Using impact on the glycosylation maturation of mAbs. for details Real-Time Multivariate Statistical Process Our results indicate that high mannose may lead to Monitoring to Ensure Batch Consistency changes in biophysical properties including protein case conformation, thermal stability, colloidal stability, and study Eric Kwei, Process Engineer, Amgen aggregation propensity. Commercial bioprocess manufacturing facilities generate significant amounts of continuous data that 4:45 Core Components for Contamination can be challenging to analyze effectively. Presenting Prevention and Control in Biopharmaceutical meaningful, accessible, and timely conclusions about this data requires a broad understanding of Manufacturing Operations statistical methodology, process design, process Gary C. du Moulin, Ph.D., M.P.H, RAC, Adjunct automation, and human factors. The intersection Associate Professor of Drug Regulatory Affairs, of these elements will be discussed in the context Massachusetts College of Pharmacy and Health of a real-time multivariate process monitoring Sciences University program implementation. Microbial contamination in bioprocessing operations remains a key concern in plant operations. Microorganisms, such as Acinetobacter baumanii, find areas in our manufacturing facilities to reside and

COMPANION TRAINING SEMINAR AND CONFERENCE: Current and Emerging Global Regulatory Expectations for Analytical Elements of REGISTER ONLINE NOW! Biotechnology/Biosimilar Products (August 5-6) – click here for details BioprocessingSummit.com Virus Detection, Clearance and Safety of Biologics (August 6-7) – click here for details

48 Sponsorship, Exhibit, and Lead Generation Opportunities

CHI offers comprehensive sponsorship packages which include Exhibit presentation opportunities, exhibit space, branding and networking Exhibitors will enjoy facilitated networking opportunities with qualified with specific prospects. Sponsorship allows you to achieve your delegates. Speak face-to-face with prospective clients and showcase your objectives before, during, and long after the event. Any sponsorship latest product, service, or solution. can be customized to meet your company’s needs and budget. Signing on early will allow you to maximize exposure to qualified Additional branding and sponsorship opportunities available! decision-makers. Looking for additional ways to drive leads to your sales Podium Presentations – Available Within the team? One move can make all the difference! Main Agenda! Showcase your solutions to a guaranteed, targeted audience. Package CHI’s Lead Generation Programs will help you obtain more targeted, quality includes a 15- or 30-minute podium presentation within the scientific agenda, leads throughout the year. We will mine our database of 800,000+ life science exhibit space, on-site branding, access to cooperative marketing efforts by professionals to your specific needs. We guarantee a minimum of 100 leads CHI, and more. per program! Opportunities include: • Whitepapers Breakfast & Luncheon Podium Presentations Opportunity includes a 30-minute podium presentation. Boxed lunches are • Web Symposia delivered into the main session room, which guarantees audience attendance • Custom Market Research Surveys and participation. A limited number of presentations are available for sponsorship and they will sell out quickly. Sign on early to secure your talk! • Podcasts

Invitation-Only VIP Dinner/Hospitality Suite Sponsors will select their top prospects from the conference pre-registration For additional sponsorship and exhibit information, list for an evening of networking at the hotel or at a choice local venue. CHI will please contact: extend invitations and deliver prospects, helping you to make the most out of this invaluable opportunity. Evening will be customized according to sponsor’s Sherry Johnson objectives i.e.: Business Development Manager • Purely social 781-972-1359 • Focus group [email protected] • Reception style • Plated dinner with specific conversation focus

2015 Sponsors & Exhibitors (As of March 23, 2015) ANSYS, Inc. Corning Incorporated Infors USA SensiQ Technologies, Inc. REGISTER ONLINE NOW! Aragen Cytovance Biologics, Inc. Malvern Instruments Terumo Medical Corporation BioprocessingSummit.com ArrayXpress, Inc. EMD Millipore MaxCyte, Inc. Thomson Instrument Company Asahi Kasei Bioprocess America, Inc. Eppendorf Pall Life Sciences Tosoh Bioscience LLC AVIA Biosystems Freeslate ProMetic Life Sciences Inc. Worthington Biochemical Corporation Biomonitor – part of the Euro Diagnostica Horizon Discovery ProteinSimple group Hyglos GmbH ProZyme, Inc. 49 Hotel & Travel Information

Conference Venue and Hotel: Westin Copley Place 10 Huntington Ave. Boston, MA 02216 Reservations: Phone: 617-262-9600 Please visit the Travel page of Discounted Room Rate: $259 s/d www.bioprocessingsummit.com Discounted Cut-off Date: July 7, 2015 for further details and to book your hotel.

REASONS TO STAY AT THE WESTIN COPLEY PLACE: • Complimentary Wireless Internet in your guest room • Restaurant and Shops are just minutes from the hotel • Local attractions including Boston’s South End, the Prudential Tower Skywalk and Boston Public Gardens within walking distance from hotel • No Commute - conference takes place at the hotel

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50 How to Register: BioprocessingSummit.com [email protected] • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288 Please use keycode 1581 F when registering

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