3rd Annual Modern Challenges in Therapeutic Protein Production Event The Penridge Suite, London, N11 1NL, UK : Thursday, 14 June 2012

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1 3rd Annual Modern Challenges in Therapeutic Protein Production Event The Penridge Suite, London, N11 1NL, UK : Thursday, 14 June 2012 The purpose of this annual event is to look at the challenges facing therapeutic protein production and demystify some of the novel approaches and new technologies currently being developed This event has CPD accreditation and will have a troubleshooting panel session. Meeting Chair: Alison Mason, MedImmune, Cambridge 9:00 9:45 Registration 9:45 10:00 Introduction by the Chair: Alison Mason, MedImmune, Cambridge 10:00 10:30 A decision-support tool for the optimal design of multi-product biopharmaceutical facilities Dr Sofia Simaria, Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London Increasing pressures exist for the design of flexible and cost-effective multi-product facilities that can cope with diverse biopharmaceutical drug candidate characteristics and process variations. A computer-based decision-support tool using optimisation algorithms has been developed and applied to an industrially relevant case study on the production of therapeutic monoclonal antibodies. The most cost-effective purification sequences and chromatography column sizing strategies that meet demand and purity targets for each product in the facility are identified and graphical methods incorporated in the tool allow the visualisation of trade-offs in the set of optimal solutions so as to enhance the decision-making process. 10:30 11:00 Use of homologous recombination based gene engineering for CHO cell line optimization. Joshua Kapp, Product and Business Development Manager, Horizon Discovery Ltd, Cambridge, UK Since the sequencing and draft genome assembly of the CHO-K1 cell line was published in Nature Biotechnology in July 2011, it has set the stage for routinely modifying the CHO genome to improve the production of recombinant antibodies. Certain key genes such as FUT8, which encodes α 1,6 fucosyltransferase, an enzyme that catalyzes the post-translational fucosylation of expressed proteins, have already been targeted using gene engineering techniques to prevent fucosylation of recombinant antibodies. Many other proteins encoded by the CHO genome, however, have yet to be explored for their potential impact on the efficacy, safety and half-life of recombinant proteins. Horizon Discovery s proprietary gene targeting platform enables routine modification of the CHO genome to develop the next generation of stable modified host cell lines. 11:00 11:30 The Cell Line Development Challenge Dr Alison Porter, Head of Cell Line Development, FUJIFILM Diosynth Biotechnologies UK Limited A key challenge when creating a recombinant cell line, producing a biotherapeutic, is the identification of a small number of desirable cell lines from an initial panel of thousands. Typical strategies to achieve this comprise a series of screens to select those recombinant cell lines with desirable characteristics. More recently, industry has seen development in automatable systems, increasing speed and throughput during this process. In this presentation, processes used by those accepting the cell line development challenge will be reviewed. The impact of adding a second challenge, a recombinant protein which is hard to express, will also be discussed. 11:30 11:50 Mid-morning break, Poster Viewing and Trade Show Please try to visit all the exhibition stands during your day at this event. Not only do our sponsors enable Euroscicon to keep the registration fees competitive, but they are also here specifically to talk to you 11:50 12:20 Lessons learned for installation and operation of a 2000L SUB Ronni Glenn Refstrup Hansen, CMC Biologics A/S, Denmark CMC Biologics, an independent contract manufacturer of biological APIs, has installed the first-in-europe Hyclone 2000L single-use-bioreactor for cgmp manufacturing of biotherapeutics in their Copenhagen facility. This presentation details the practical lessons learned from installation and qualification of large-scale SUB technology 12:20 12:50 Enabling technologies for next generation products Dr Dave Simpson, Chief Operating Officer, Glythera Limited

2 12:50 13:50 Lunch, Poster Viewing and Trade Show This is also a good time to fill out your feedback forms 13:50-14:20 Question and Answer Session and Speakers photo Delegates will be asked to submit questions to a panel of experts. Questions can be submitted before the event or on the day 14:20 14:35 Capillary Electrophoresis as a Powerful Tool in Therapeutic Protein Production Analytics Dr Mei-an Sung, Deltadot, UK Capillary Electrophoresis is a powerful and versatile analytical tool that can be used to address many aspects of bioprocessing analytics. deltadot s High Performance Capillary Electrophoresis system benefits from its unique design and core Label Free Intrinsic Imaging technology (LFII system), which allows improved dynamic range (conc. & MW), resolution, quantification and reproducibility. The lack of labels also frees LFII system to perform Universal analysis on a wide variety of analytes. This allows the system to monitor the bioprocess from inception to QA/QC, looking not just at proteins, peptides and DNA but also at small molecules such as amino acids or even ionic salts present in the growth media as well as contaminants such as endotoxin and cellular DNA. 14:35-15:05 Can microbial systems play a role in therapeutic protein production? Professor P C Wright, Sheffield University, UK Approximately 30% of genuinely new biopharmaceuticals approved between employ Escherichia coli as a production host. There are limitations on products or modifications, meaning that that higher eukaryotic systems are employed despite increased costs and complexity. Using bacteria to make complex post-translationally modified protein therapeutics is challenging. The motivation to use microbial systems is that they are are less costly than mammalian systems and have a higher level of product control, i.e. little or no heterogeneity. This presentation shows that progress has been made in glycosyation of human proteins and antibody fragments in bacteria and the the potential for future progress. 15:05 15:30 Afternoon Tea/Coffee, Last Poster Viewing and Trade show 15:30 16:00 Characterisation of protein aggregation: why it is important and how nanosight can help Dr Matthew Wright, NanoSight Ltd, Amesbury, UK Characterisation of protein aggregation is of vital importance when trying to understand biopharmaceutical product stability and quality. It is widely recognised that there is potential risk associated with protein aggregation and that biological activity and immunogenicity can be influenced by the state of aggregation. Therefore, careful monitoring is needed during development, manufacture and subsequent storage of the formulated product, but current technologies are limited in their ability to detect early stage aggregates. This talk will describe the unique ability of the NanoSight technique to detect and measure protein aggregates in the 30nm -1000nm size range by tracking their Brownian motion on a particle-by-particle basis. Nanoparticle Tracking Analysis (NTA) enables protein aggregates to be directly and individually visualised and counted in real-time, generating high-resolution data in a region that is often poorly served by other techniques like dynamic light scattering (DLS), where a low number of large, bright aggregates often dominates the signal even over a high concentration of protein monomer. The added speciation that can be gained by a fluorescence add-on to the system will also be discussed. 16:00-16:30 Improving the scalability for single use bioreactors for large-scale manufacturing processes Alison Rees-Manley, Sartorius Stedim Biotech, Fermentation Applications Specialist for North Europe Although single-use bioreactors are widely accepted for R&D and seed train applications their use in real production environments is still limited. However, with the introduction of classically designed stirred single-use bioreactors this is now changing. These bioreactors reduce the need for additional optimisation when moving away from stainless steel and simplify the upscaling process. This presentation will look at characterization of stirred single use bioreactors, cover its comparability to conventional bioreactors and demonstrate how these single-use systems are increasingly being used in large-scale manufacturing processes. 16: 30 17:00 Biosimilars Next Generation Therapeutics Laura Bailey, Eden Biodesign, Liverpool, UK 17:00 Chairman s summing up

3 About the chair Alison has been working in the Cell Sciences group at MedImmune for the past 11 years, most recently as a senior scientist within the Cell Sciences group. Alison and her team work on development of cell culture media, feeds and bioreactor processes suitable for GMP production. The team also has a keen interest in implementing scale-down bioreactor systems which mimic a larger bioreactor at the millilitre scale. Previous to Alison s position at MedImmune she worked at Lonza Biologics for 2 years as a Fermentation Scientist. Alison holds a degree in Applied Microbiology from the University of Manchester. About the Speakers Joshua Kapp heads the Bio-production Business unit at Horizon Discovery Ltd. Joshua was previously involved in the planning of the company s diagnostics reagents division which has become a cash generating business within 12 months. Horizon Bio-production applies a patented homologous recombination-mediated gene-editing platform exploiting the unique precision of raav targeting vectors to the field of bioprocessing through the provision of custom host cell line engineering services. Joshua has a background in preclinical medicine and business, attending medical school at Guy s and St Thomas Hospital in London and business school at Imperial College s, London Business School. Sofia Simaria, an Industrial Engineer by training and is post-doc at UCL developing computer-based decision-support tools that capture the process-business interface of biopharmaceutical manufacture. She has been working on collaborative TSB funded projects between UCL and major biotech companies (eg MedImmune, Lonza) and has joined the newly formed EPSRC Centre for Innovative Manufacturing on Emergent Macromolecular Therapies at UCL. Alison Porter joined Fujifilm Diosynth Biotechnologies (FFDB) in 2011 as Head of Cell Line Development in the Mammalian Cell Culture group. Alison has considerable industrial experience in the construction of recombinant cell lines using mammalian cell lines, having previously spent 13 years in the Cell Culture Process Development group at Lonza prior to joining FFDB. Whilst at Lonza, Alison specialised in working with the GS expression system. Prior to this, Alison spent two years at Bio Products Laboratory, United Kingdom, working with recombinant antibody producing cell lines and utilising hollow fibre culture systems. Phillip Wright (PCW) (University of Sheffield, UoS) (Skills: proteomics, biochemical engineering, biosystems modelling) was an EPSRC Advanced Research Fellow (01-06), and is Professor of Systems Biology and Engineering in Chemical and Biological Engineering (CBE) (2002-) and Head of Dept (2008-). He has a BE(Hons) ( 91) and PhD in Chemical Engineering ( 97) from the University of NSW and an ME(Hons) in Mechanical Engineering (1994) from Wollongong. He worked as a cadet then graduate engineer at BHP in Wollongong ('86-94). He was a lecturer then reader in chemical engineering at Heriot-Watt (97-02). He has published >125 journal papers, on quantitative proteomics, biological engineering, microfluidics and modelling. He focuses on biological engineering, measurement and integration of multi-level biological data (e.g. proteomic and mrna data), mathematical tools and characterising -omics-scale data. Matthew Wright is currently NanoSight's Applications Engineer and has been with the company four years. Previously he completed a BSc in Forensic Science and Analytical Techniques at the Nottingham Trent University. He has focussed on developing applications for which the NanoSight technology can be applicable, working with early adopters and building on pioneering work conducted byresearch institutes around the world. Alison Rees-Manley joined Sartorius Stedim Biotech in October 2011 as Fermentation Applications Specialist for North Europe providing technical support to customers and the sales team for fermentation processes and equipment. Prior to joining Sartorius Alison worked for over 10 years in the Upstream Process Development at Cantab Biopharmaceuticals (formerly Xenova Biomanufacturing, Cambridge) as a R&D scientist and later on as group leader gaining extensive experience in the development and GMP manufacturing of bacterial and animal/ insect cell culture processes for protein and viral vaccine products. Alison completed a BSC (hons) in Biotechnology with a 1 year industrial placement in the Bioprocess Development Group at Pfizer, Sandwich working on a vetinary feed additive produced from microbial fermentation. Dave Simpson joined Glythera as Chief Operating Officer in March 2012 to lead the development of the business from its new facilities in Newcastle upon Tyne. Dave spent six years with Eden Biodesign where he supported the growth of the business through a variety of roles including head of process development until its acquisition by Watson Pharmaceuticals, when he moved to lead a biosimilar product development programme. Prior to this Dave was responsible for developing patented, commercially available expression technologies at Cobra biomanufacturing. He has a PhD in Genetics and a BSc in Applied Biochemistry

4 Media partners Dont forget to sign up to Euroscicons e-newsletter at to keep up to date with European Life Science news and events and to be notified of the follow up to this event Registration Web Site: Keywords: Gene correction/modification, AAV vectors, Cell line engineering, biopharmaceutical manufacturing processes, antibody purification, process economics, genetic algorithms, multi-product facility design, homologous recombination, cell line engineering, CHO cell lines, gene targeting, endogenous genome, Cell line development, cell line selection, screening, CHO, mammalian expression systems, glycosylation, protein therapeutics, E.coli, microbial, antibody, NTA, Protein Aggregation, Nanoscale, Analysis POSTERS FACILITATING MULTI-SITE BIOPROCESS TRANSFER: MULTI-INSTRUMENT AND MULTI-PLATFORM COMPARABILITY AND LONG TERM STABILITY OF NOVA BIOMEDICAL S BIOPROFILE CHEMISTRY AND GAS ANALYZERS M. McRae, R. Bulman, J. McHale, S. Granger, B. Goulart, E. Kilcoyne Nova Biomedical Innovation House, Aston Lane South, Runcorn, Cheshire, WA7 3FY r.bulman@novabiomedical.co.uk The Biopharmaceutical industry has grown exponentially and more companies are now operating in a global market with sites thousands of miles apart. The need is now even greater for robust bioprocess monitoring solutions that can provide consistent instrument-to-instrument results. The seamless transfer of information across multiple sites relies heavily on the comparability of process data from various technologies, ensuring effective monitoring and control of critical process parameters. This study provides data supporting comparability of the BioProfile chemistry and gas analyzers across several development and manufacturing sites in the United States. In addition, the long-term performance stability of the BioProfile systems was also tested. Five BioProfile FLEX and four BioProfile 100+ analyzers were used to determine linearity, precision, accuracy, and instrument-to-instrument comparability. The age of the instruments used for this study ranged from new to over 8 years old, with several hundred samples to over 20,000 samples run on a given analyzer. The results of this study show a high level of comparability between the BioProfile analyzers. In addition, comparability was also demonstrated between both the new and aged analyzers, providing evidence of the long-term robustness and the quality of data can be generated from the BioProfile analyzers. Nova Biomedical s BioProfile analyzers provide the tools to facilitate multisite bioprocess transfer in the Biopharmaceutical industry.

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