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ESACT Proceedings

Volume 4

For further volumes:http://www.springer.com/series/5936

Thomas NollEditor

Cells and Culture

Proceedings of the 20th ESACT Meeting,Dresden, Germany, June 17–20, 2007

123

EditorProf. Dr. Thomas NollUniversität BielefeldTechnische Fak.AG Zellkulturtechnik33501 BielefeldGermany

ISBN 978-90-481-3418-2 e-ISBN 978-90-481-3419-9DOI 10.1007/978-90-481-3419-9Springer Dordrecht Heidelberg London New York

Library of Congress Control Number: 2010927813

© Springer Science+Business Media B.V. 2010No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or byany means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without writtenpermission from the Publisher, with the exception of any material supplied specifically for the purposeof being entered and executed on a computer system, for exclusive use by the purchaser of the work.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

Contents

Part I Single-Cell Analysis and Engineering

Targeted Gene Knockdown Effects on Recombinant ProteinSecretion in CHO Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Trissa Borgschulte, Fanny Delegrange, Christoph L. Bausch,David L. Hacker, Daniel W. Allison, Matthew V. Caple,Florian M. Wurm, and Kevin J. Kayser

RNA Silencing Suppressors Boost the Production ofRecombinant Proteins and Viruses . . . . . . . . . . . . . . . . . . . . . 9Peter de Haan, Alfred Engel, Walter de Vries, Jeroen vander Velden, Gerrit-Jan van Holst, and Eddy Arnoldussen

Towards the Use of CHO Produced Recombinant ExtracellularMatrix Proteins as Bioactive Elements in a 3-D Scaffold forTissue Engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Eva-Maria Engelhardt, A. Oberbek, D. Aibibu, G. Backliwal,M. Adam, J. Hilborn, and F.M. Wurm

Transient Gene Expression in Chinese Hamster Ovary Cells atLow Temperature – The Effects of Cold-Induced Proteins andan mRNA Regulatory Element . . . . . . . . . . . . . . . . . . . . . . . 19Sarah Wulhfard, Stéphanie Tissot, David L. Hacker, andFlorian M. Wurm

Single-Cell Approach in Influenza Vaccine Production:Apoptosis and Virus Protein Production . . . . . . . . . . . . . . . . . . 25Josef Schulze-Horsel, Mareike Schulze, Yvonne Genzel, andUdo Reichl

Chondrogenic Differentiation of Human Mesenchymal StemCells During Multiple Subcultivation . . . . . . . . . . . . . . . . . . . 29Christian Weber, Stephanie Gokorsch, and Peter Czermak

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vi Contents

Cell XpressTM-Assisted Analysis of Clone Stability inRecombinant Chinese Hamster Ovary Cells . . . . . . . . . . . . . . . . 35Mark A. Gerber, Kimberly A. Lacy, Jennifer Cresswell, Nan Lin,Kevin J. Kayser, and Matthew V. Caple

An Evaluation of the Intrinsic IgG Production Capabilities ofDifferent Chinese Hamster Ovary Parental Cell Lines . . . . . . . . . . 41Genova A. Richardson, Daniel W. Allison, Nan Lin,Matthew V. Caple, and Kevin J. Kayser

Cell XpressTM Technology Facilitates High-Producing ChineseHamster Ovary Cell Line Generation Using GlutamineSynthetase Gene Expression System . . . . . . . . . . . . . . . . . . . . 45Genova A. Richardson, Nan Lin, Kimberly A. Lacy, Lynn A. Davis,Misa I. Gray, Jennifer Cresswell, Mark A. Gerber,Matthew V. Caple, and Kevin J. Kayser

CHO-DG44 Cell Line Development by FLP-Targeting – HighLevel Glycoprotein Expression with Significantly DecreasedTime Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49Thomas Rose, Anne Furthmann, Marie Etzien, Karsten Winkler,and Volker Sandig

Transgene Copy Number – Impact on Clone Performance . . . . . . . . 57Karsten Winkler, Thomas Rose, Anne Furthmann, Christine Paul,Andrea Franke, Rita Berthold, and Volker Sandig

Single Use Bioreactors: Expressing Protein in Mammalian CellSuspension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63Kevin A. Auton

Part II Applied Integrative Physiology

Gene Modified Hematopoietic Stem Cells for the Treatment ofPrimary Immunodeficiency Diseases . . . . . . . . . . . . . . . . . . . . 73M. Grez, S. Stein, U. Siler, and R. Seger

An Avian Cell Line for Production of Highly Attenuated Viral Vectors . 79Ingo Jordan, Deborah Horn, Kristin Höwing, and Volker Sandig

Microelectronic Cellular Vitality Monitoring . . . . . . . . . . . . . . . 89M. Schmidhuber, J. Wiest, A.M. Otto, M. Brischwein, H. Grothe,and B. Wolf

IFN-γ Glycosylation Macroheterogeneity, Energetic Cell Statusand Medium Composition During CHO Cell Cultures . . . . . . . . . . 95N. Kochanowski, F. Blanchard, R. Cacan, F. Chirat, E. Guedon,A. Marc, and J.-L. Goergen

Contents vii

Modelling of Neural Metabolism Using 13C-NMR Spectroscopyand Metabolic Flux Analysis . . . . . . . . . . . . . . . . . . . . . . . . 101Ana P. Teixeira, Sónia Sá Santos, Ana I. Amaral, Nuno Carinhas,Rui Oliveira, Manuel J.T. Carrondo, and Paula M. Alves

Influence of Glucose and Glutamine Concentration onMetabolism of rCHO Cells . . . . . . . . . . . . . . . . . . . . . . . . . 107Hiroshi Matsuoka, Jun-ya Watanabe, and Toshiya Takeda

Part III Speed and Intensification in Bioprocess Development

Delivery of Biomolecules with Non-Viral Vectors . . . . . . . . . . . . . 115Stéphanie Biri, Fabrice Stock, Abdennaji Adib, and Patrick Erbacher

Circumventing the “Pay Now or Pay Later” Dilemma:Strategies for Achieving Process Development with Speed andLong-Term Potential . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121Carole Heath, Pranhitha Reddy, Martin Allen, Ginny Price, andVictor Fung

Recombinant Human Antibody Therapeutics: Supply Strategiesfor Early and Clinical Development from CHO Cells . . . . . . . . . . . 129Ray Field, Lekan Daramola, Jonathan Dempsey, and Diane Hatton

Automated Screening of High Producer HEK293F Clones andAnalysis of Post-Translational Modifications of Secreted Proteins . . . . 137Peter Söhlemann, Claudia Kollert, Jessica Thiems,Elisabeth Casademunt, and Carola Schröder

Transcriptomic and Proteomic Analysis of Antibody ProducingNS0 Cells Cultivated at Different Cell Densities in Perfusion Culture . . 145Britta Krampe, Halina Swiderek, and Mohamed Al-Rubeai

New Disposable Fixed-Bed Bioreactor for Cell Culture andVirus Production Based on a Proprietary Agitation and Aeration System 151J. -C. Drugmand, N. Havelange, S. Osumba, F. Bosco, F. Debras,F. Collignon, E. Mathieu, and J. Castillo

Transcriptomic Analysis of Antibody Producing NS0 Cell LineUnder Hypothermic and Hypoxic Conditions . . . . . . . . . . . . . . . 157Halina Swiderek, Anna Logan, and Mohamed Al-Rubeai

Semi-Continuous Cultures as a Tool for Cell LineCharacterization During Process Development . . . . . . . . . . . . . . 161S. Victores, A. Castillo, E. Faife, Y. Rabasa, Y. Alvarez, L. Rojas,J. Palacio, and A. Figueredo

Behaviour of GS-CHO Cell Lines in a Selection Strategy . . . . . . . . 165A. J. Porter, A.J. Dickson, L.M. Barnes, and A.J. Racher

viii Contents

3D Cultures: Effect on the Hepatocytes Functionality . . . . . . . . . . 171Joana Miranda, Manuel J.T. Carrondo, and Paula M. Alves

Differential Protein Expression Inducedby c-Myc Over-Expression: Proteomic Analysis of a CHO CellLine with Increased Proliferation Capacity . . . . . . . . . . . . . . . . 177Darrin Kuystermans and Mohamed Al-Rubeai

Development of Pilot-Scale Orbital Shake Bioreactors: Ideal forCost-Effective and Efficient Transient Gene Expression . . . . . . . . . 183Matthieu Stettler, Xiaowei Zhang, Tibor Anderlei, Maria De Jesus,Pascal Lefebvre, David L. Hacker, and Florian M. Wurm

Helical Tracks in Shaken Cylindrical Bioreactors ImproveOxygen Transfer and Increase Maximum Cell DensityObtainable for Suspension Cultures of Mammalian Cells . . . . . . . . 187Xiaowei Zhang, Matthieu Stettler, Oscar Reif, Andreas Kocourek,Maria De Jesus, David L. Hacker, and Florian M. Wurm

Dynamic Optimisation of CHO-IFNγ Cell Culture Fed-BatchTime-Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193Carolyn M. Lam, Danny C.F. Wong, Miranda G.S. Yap, EfstratiosN. Pistikopoulos, and Athanasios Mantalaris

Long-Term 3D-Culture of HEP G2 Cell Line on MacroporousCeramic Carriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201Oscar Platas, Vivien Lutz, Richard Getto, and Ralf Pörtner

An Integrated Production Process for Human Growth Hormone . . . . 205T. Nottorf, H. Büntemeyer, S. Siwiora-Brenke, D. Lütkemeyer,A. Loa, T. Noll, and J. Lehmann

Efficient Production of Human Monoclonal Antibodies by anImproved Fructose-Based Human Cell Culture . . . . . . . . . . . . . . 209Yuichi Inoue, Aiko Inoue, and Hiroharu Kawahara

Coupling Between Cell Kinetics and CFD to EstablishPhysio-Hydrodynamic Correlations in Various Stirred Culture Systems 213N. Barbouche, E. Olmos, E. Guedon, and A. Marc

Confocal Microscopy Observation of CHO Cells Cultivated inPresence of Fluorescent – Labelled Rapeseed Peptides . . . . . . . . . . 219A. Kastner, C. Frochot, D. Dumas, R. Vanderesse, and A. Marc

Growth and Production Characteristics of Four MammalianCell Lines on a Cost-Effective Serum-Free Medium . . . . . . . . . . . 223M. Drews and R. Hunt

Contents ix

A Serum-Free, Transient Transfection System for EnhancingProduction of Recombinant Antibodies in Mammalian Cells . . . . . . 229Gaurav Backliwal, Sarah Wulhfard, Fanny Delegrange, Lucia Baldi,Maria deJesus, Florian M. Wurm, and Markus Hildinger

CFD Study of the Fluid and Particle Dynamics in a Spin-FilterPerfusion Bioreactor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233Alvio Figueredo, Ernesto Chico, Leda R. Castilho, andRicardo A. Medronho

High-Yielding CHO Cell Pools for Rapid Production ofRecombinant Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . 239Diane Hatton, Wyn Forrest-Owen, Greg Dean, Suzanne Gibson,Tori Crook, Amanda Lunney, Steve Ruddock, Alison Davis,Lekan Daramola, and Ray Field

Increasing Upstream Process Development Efficiency byImplementing Platform Glutamine Synthetase Cell Culture Processes . 245Robert Heckathorn, Derek Adams, Jeffrey Hunter, and Eric Frieden

Implementation of High Throughput Systems for Media andProcess Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253Soverin Karmiol, Mykle Gaynor, Robert Kenerson, John Daley,Rich Hassett, Gregory Van Slyke, and Steven Peppers

Comparison of Cell Culture Methods for Obtainingof rHU-EPO to Large Scale . . . . . . . . . . . . . . . . . . . . . . . . . 257E. Ojito, A. Castro, M. Chea, R. Lugo, E. Suárez, A. Medina,M. Arias, and E. Chico

Optimization and Comparison of Different DNA MethylTransferase and Histone Deacetylase Inhibitors for EnhancingTransient Protein Expression . . . . . . . . . . . . . . . . . . . . . . . . 261Gaurav Backliwal, Markus Hildinger, Ivan Küttel, David L. Hacker,and Florian M. Wurm

Proteomic Characterisation of a Glucose-Limited CHOPerfusion Process–Analysis of Metabolic Changes and Increasein Productivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265Marc Wingens, Jochem Gätgens, Raimund Hoffrogge, andThomas Noll

Evaluation of Alternative Signal Sequences . . . . . . . . . . . . . . . . 271J. Rance and R. Young

Process Development for the GMP Productionof N-Acetylgalactosamine-6-Sulfate Sulfatase (GALNS)Expressed by CHO Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 275Cornelia Fux, Christèle Bellon, and Christoph Heinzen

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Improvement of a CHO Fed-Batch Process by Fortifying withPlant Peptones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281Yun Jiang, Erik Svensson, and Véronique Chotteau

O-Glycans on Recombinant MUC1 Produced in CHO K1 CellsBecome Less Sialylated with Increased Protein Productivity, asDetermined by LC-ESI MS . . . . . . . . . . . . . . . . . . . . . . . . . 285Malin Bäckström, Hasse Karlsson, Jochem Gätgens, Thomas Noll,and Gunnar C. Hansson

A Multiple Minibioreactor Platform for Parallel and AutomatedMammalian Cell Culture . . . . . . . . . . . . . . . . . . . . . . . . . . 289A. Fontova, A. Soley, E. Sarró, J. Gálvez, R. Bragos, J.J. Cairó, andF. Gòdia

Cultivation of Adherent-Dependent Animal Cells onMicrocarriers in a New Disposable Reactor . . . . . . . . . . . . . . . . 295N. Havelange, C. Braet, F. Collignon, F. Debras, J.-C. Drugmand,E. Mathieu, S. Vanhamel, and J. Castillo

CHO Cells Cultivation and Antibodies Production in a NewDisposable Bioreactor Based on Magnetic Driven Centrifugal Pump . . 301F. Collignon, V. Gelbgras, N. Havelange, J.-C. Drugmand,F. Debras, E. Mathieu, V. Halloin, and J. Castillo

Stability and Productivity of CHO Pools with Respect to CultureAge, Cryopreservation and 20 L Bioreactor Cultivation . . . . . . . . . 307Anders Nelving, Ingrid Svensson, and Mats Lundgren

In Vitro Disassembly and Reassembly of Triple-LayeredRotavirus-Like Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . 313Maria Candida M. Mellado, Jimmy A. Mena, Manuel J.T. Carrondo,Octavio T. Ramírez, Laura A. Palomares, and Paula M. Alves

Influence of Culture Conditions on Insect Cell Growthand Protein Production – Comparison of Wave Bioreactorand Shake Flasks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319Mareike Rausch, Jörg Knäblein, Ralf Pörtner, and Petra Helfrich

Process Intensification Based on Nano-Structured CarbonCarrier Materials and Disposable Devices . . . . . . . . . . . . . . . . . 325Markus Kürschner and Sohéil Asgari

Accelerating Fed-Batch Process Development Using RationallyDesigned Feed Media . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331Scott D. Storms, Jenny Y. Bang, and Tom Fletcher

Contents xi

Development of a Robust Small-Scale Production Format thatIs Predictive of Bioreactor Performance . . . . . . . . . . . . . . . . . . 337Gene W. Lee, D. Troy Richards, Katie Kopycinski, Steve Brennan,Alyssa Handler, and Martin Sinacore

Biomass Monitoring and CHO Cell Culture Optimization UsingCapacitance Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 343Rodrigo C.V. Pinto, Paulo A.N. Marinho, Aline B. Oliveira,Geoffrey Esteban, Príamo A. Melo, Ricardo A. Medronho, andLeda R. Castilho

Characterizing Physiology and Metabolism of High-DensityCHO Cell Perfusion Cultures Using 2D-NMR Spectroscopy . . . . . . . 349Chetan Goudar, Richard Biener, C. Boisart, Rüdiger Heidemann,Chun Zhang, Albert de Graaf, James Piret, andKonstantin Konstantinov

BI HEXTM – Platform for Fast Track Generation of HighProducer Cell Lines Leading to High-Titer Processes forProduction of Therapeutic Proteins from Mammalian Cells . . . . . . . 359Torsten W. Schulz, Stefan Schlatter, Hitto Kaufmann,Barbara Enenkel, Helmut Hoffmann, and Stefanos Grammatikos

Management of Handling, Long-Term Stability and Shipping ofHuman T-Lymphocytes Bags for Clinical Studies . . . . . . . . . . . . . 365I. Giuntini, C. Crosta, L. Romagnoli, M. Galgano, A. Orlandi,S. Castiglioni, S. Trasciatti, L. Cavenaghi, and M.L. Nolli

Mass Transfer in the CELL-tainer R© Disposable Bioreactor . . . . . . . 371Nico M.G. Oosterhuis and Pieter van der Heiden

Efficient Production of Human Monoclonal Antibodies byCombining In Vitro Immunization and Phage Display Methods . . . . . 375Shinei Matsumoto, Makiko Yamashita, Yeon-suk Jung,Kosuke Tomimatsu, Kiichiro Teruya, Yoshinori Katakura, andSanetaka Shirahata

Measurement and Control of Viable Cell Density in aMammalian Cell Bioprocessing Facility: Validation of the Software . . 379D. Sergeant, M. Moser, and J.P. Carvell

Development, Validation, and Application of a Fully IntegratedAutomation System for Screening and Selection of High YieldingProduction Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385Tim Gryseels, Lin Zhang, YingPing Zhang, Brian Hossfeld,Heather Jones, Adekunle Onadipe, and John Mott

Monitoring of Cell Activity: Online Oxygen Uptake Rates inPulsed Aerated Cell Culture . . . . . . . . . . . . . . . . . . . . . . . . 391A. Bock, Y. Genzel, and U. Reichl

xii Contents

Part IV Systems Biotechnology

Metabolite Analysis in Mammalian Cells: How to GenerateReliable Data Sets? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397Joachim B. Ritter, Yvonne Genzel, and Udo Reichl

Cell-to-Cell Communication for Cell Density-Controlled Bioprocesses . 407Wilfried Weber and Martin Fussenegger

Metabolome Analysis in Mammalian Cells: Development andApplication of a Sampling Technique . . . . . . . . . . . . . . . . . . . 413C. Wiendahl, J.J. Brandner, B. Klein, C. Küppers, B. Luo,S. Ritchie, S. Mazurek, H. Scheefers, T. Noll, U. Schygulla, andM. Oldiges

Differential Expression Profiling of Industrially Relevant CHOCell Phenotypes Using a Proprietary CHO-Specific Microarrayand Proteomics Technology Platforms . . . . . . . . . . . . . . . . . . . 421Mark Melville, Martin S. Sinacore, Dana Di Nino, Kevin McCarthy,Karin Anderson, Kathleen Kopycinski, Gene W. Lee, Steven Max,Patrick Gammell, Padraig Doolan, Paula Meleady, Niall Barron,Mark Leonard, Martin Clynes, and Tim Charlebois

Towards a Systems-Level Understanding of Increased SpecificProductivity in Proliferation Arrested Myeloma NS0 Cells . . . . . . . 425Soo Hean Gary Khoo and Mohamed Al-Rubeai

Proteomic Analysis of Influenza a Virus Infected MammalianCells by 2D-DIGE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429D. Vester, E. Rapp, Y. Genzel, D. Gade, and U. Reichl

Involvement of SRC- and MAP Kinase-Signalings in the Effectof Sericin on Cellular Proliferation and Survival . . . . . . . . . . . . . 433Kana Yanagihara, Takuya Saito, Satoshi Takeshita, Masao Miki,Akiko Ogawa, Masahiro Sasaki, Hideyuki Yamada, andSatoshi Terada

The Unfolded Protein Response and Recombinant ProteinProduction from In Vitro Cultured Mammalian Cells . . . . . . . . . . 437Rosalyn Marchant, Jenny Barker, Peter Klappa, Alan Dickson,and Mark Smales

A Scalable Process for Helper-Dependent AdenoviralVector Production Using PEI-Derived Transfection Strategyin Suspension Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441E. Dormond, A. Meneses-Acosta, D. Jacob, Y. Durocher, M. Perrier,and A. Kamen

Functional Analysis of ER Stress Pathway Genes for Apoptosisof NS/0 Cell Line Using RNAi Methods . . . . . . . . . . . . . . . . . . 447Jianguo Yang, Jing Shi, Raghavan Venkat, and Kripa Ram

Contents xiii

Identification of New Protein Substrate Candidates ofTransglutaminase in Rat Liver Extracts: Use of 5-(Biotinamido)Pentylamine as a Probe . . . . . . . . . . . . . . . . . . . . . . . . . . . 453Akira Ichikawa, Jin Ishizaki, Manabu Morita, Kentaro Tanaka,and Koji Ikura

Metabolic Flux Distributions of Adherently Growing MDCKCells in Different Media . . . . . . . . . . . . . . . . . . . . . . . . . . . 459A. Wahl, Y. Sidorenko, Y. Genzel, and U. Reichl

Expression of Dermal Extracellular Matrix Proteins in a NewlyDeveloped Full-Thickness Skin Model . . . . . . . . . . . . . . . . . . . 463Karsten R. Mewes, Nadja N. Zöller, August Bernd, AlexandraPrießner, Bart DeWever, Rüdiger Graf, and Klaus R. Schröder

Development of Preparations with Antiviral andImmunostimutory Effects from Extracts of Green Partsof Coniferous Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469E. Nechaeva, N. Varaksin, T. Ryabicheva, T. Ilicheva, T. Sen’kina,R. Martynyuk, and A. Vilesov

Serum-Free Transfection of CHO Cells with Chemically DefinedTransfection Systems to Generate Transient and Stable Cell Lines . . . 475Reisinger Hannes, Vorauer-Uhl Karola, Steinfellner Willibald,Wagner Andreas, Katinger Hermann, and Kunert Renate

“Glycomics”: Development and Characterization ofGlycan-Based Biotechnological Products . . . . . . . . . . . . . . . . . 479Matthias Kaup, Véronique Blanchard, Detlef Grunow, Stefan Risch,Silke Langhammer, Werner Reutter, Rudolf Tauber, andMarkus Berger

Development of a Cell-Culture-Based Platform for Viral VaccineProduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481G. Forno, C. Paillet, R. Kratje, and M. Etcheverrigaray

Screening of Natural Compounds Affecting Type I Interferon Signalling 485M. Bollati-Fogolín, M. Oggero, S. Mirazo, R. Frank, R. Kratje, andW. Müller

Part V Competing and Complementary Approaches toAnimal Cell Technologies

Therapeutic Proteins from Transgenic Cows’ Milk . . . . . . . . . . . . 491J.A. Bercovich, C.A. Melo, and M.E. Criscuolo

Development of Edible Plant Vaccines . . . . . . . . . . . . . . . . . . . 497Heike Mikschofsky, Patricia König, Günther Keil, HorstSchirrmeier, and Inge Broer

xiv Contents

Human Cell Lines for Production of Biopharmaceuticals . . . . . . . . 503Gudrun Schiedner, Nikos Gaitatzis, Sabine Hertel, Corinna Bialek,Helmut Kewes, Christoph Volpers, and Gero Waschütza

Concentration and Purification of Densonucleosis Virus byTangential Membrane Filtration and by Ion Exchange Membranes . . . 513Peter Czermak, David L. Grzenia, Anne Wolf, Jonathan O. Carlson,Rachel Specht, Binbing Han, and S. Ranil Wickramasinghe

Effect of ManNAc and its Derivatives on Glycosylation toProteins Produced by Mammalian Cell Culture . . . . . . . . . . . . . . 517Kaori Doi, Megumi Hayashi, Ichiro Ebata, Shinya Yamaguchi,Yasuhiro Ohta, and Satoshi Terada

Purification of a Chimeric Simian – Human ImmunodeficiencyVirus-Like Nanoparticle from HEK293 Cell Culture . . . . . . . . . . . 521Luísa Pedro and Guilherme N. M. Ferreira

Effects of Plant Peptones Supplemented Medium on CHO Cells . . . . 529Barbau Jérémie, Michiels Jean-François, De Boel Sébastien,Spiros N. Agathos, and Schneider Yves-Jacques

Synthetic Low Density Lipoprotein a Novel Biomimetic LipidSupplement for Serum Free Tissue Culture . . . . . . . . . . . . . . . . 533G.W. Halbert, G. Duncan, and S. Hayavi

Part VI Solutions and Applications

Scale-Down Approach for Animal-Free Polio Vaccine Production . . . . 541Wilfried A.M. Bakker, Yvonne E. Thomassen, and Leo A. van der Pol

“Novel Scaffolds for Tissue Engineering – Nano-StructuredSurfaces Promote Selective Cell Attachment and Cell Differentiation” . 551Sohéil Asgari and Markus Kürschner

Unconventional Experimental Concepts Enabling High SpeedHigh Performance Media/Process Development . . . . . . . . . . . . . . 559Martin Jordan, Damien Voisard, Nadia Bencherif,Antoine Berthoud, Laetitia Tercier, Beate Kleuser, and Gianni Baer

A Study on Bioscaffolds of Polysialic Acid and β-Glucan for CellCulture and Tissue Engineering Applications . . . . . . . . . . . . . . . 567Yvonne Stark, Stephanie Bruns, Bastian Rode, Silke Berski,Gerald Dräger, Frank Stahl, Cornelia Kasper, Andreas Kirschning,and Thomas Scheper

A Preliminary Study on Spider Silk as Biomaterial forPeripheral Nerve Regeneration . . . . . . . . . . . . . . . . . . . . . . . 573Stephanie Bruns, Yvonne Stark, Dana Marten, Christina Allmeling,Cornelia Kasper, Frank Stahl, and Thomas Scheper

Contents xv

Investigation of the Effect of Mechanical Strain on theOsteogenic Differentiation of Mesenchymal Stem Cells . . . . . . . . . . 579Solvig Diederichs, Daniel Riechers, Friederike Sempf,Susanne Kall, Cornelia Kasper, Martijn van Griensven, andThomas Scheper

Biofunctional Polymer-Mineral Composites as Scaffolds forBone Tissue Engineering . . . . . . . . . . . . . . . . . . . . . . . . . . 591Stefanie Röker, Solvig Diederichs, Victor Korzhikov,Thomas Scheper, Tatiana Tennikova, and Cornelia Kasper

New Water-Soluble Polymers for Construction ofBiofunctionalized Scaffolds for Bone Tissue Engineering:Synthesis and Adsorption Study . . . . . . . . . . . . . . . . . . . . . . 599V. Korzhikov, E. Vlakh, S. Diederichs, S. Roeker, T. Tennikova, andC. Kasper

Selection of High-Producing Cells Via Cell Sorting Using anAffinity Matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607Larissa Behr, Pierre Moretti, Fabienne Anton, Cornelia Kasper,and Thomas Scheper

The Effects of Medium Supplement on High-Level Productionof Recombinant Human Factor IX in CHO Cell . . . . . . . . . . . . . 613InHwan Lim, Jung-Seob Kim, Guehwa Lee, Murim Choi, andYeup Yoon

Case Study Large Scale Cell Culture Facility . . . . . . . . . . . . . . . 619Dirk Steinhäuser

Glycosylation of Influenza A Virus Hemagglutinin . . . . . . . . . . . . 621J. Schwarzer, E. Rapp, and U. Reichl

Production of Retroviral Pseudotype Vectors in Fixed BedReactors for Use in Gene Therapy . . . . . . . . . . . . . . . . . . . . . 625Dirk Nehring, Ralf Pörtner, and Peter Czermak

Swellscreen – Rapid Baculovirus Titration Methodin Microplate Format . . . . . . . . . . . . . . . . . . . . . . . . . . . . 629Eva Lindskog, Thomas Falkman, and Elke Lüllau

Comparing Vero and MDCK Cells for Influenza A VirusProduction in Microcarrier Systems . . . . . . . . . . . . . . . . . . . . 635Y. Genzel, C. Dietzsch, and U. Reichl

Expansion of Human Articular Chondrocytes on MicrocarriersEnhances the Production of Cartilage Specific Matrix Components . . . 639Christiane Goepfert, Vivien Lutz, Svenja Lünse, Sabrina Kittel,Katharina Wiegandt, Michael Kammal, Klaus Püschel, andRalf Pörtner

xvi Contents

Automated Cell Culture Handling – Characteristics and Procedures . . 645Stephanie Mathes, Roland Durner, Uwe Müller, andUrsula Graf-Hausner

Bioreactor Satellite Culture Experiments in the Start-Up of aCell Culture Technical Support Lab . . . . . . . . . . . . . . . . . . . . 647Jean-Philippe Goisnard, Leopold Bertea, Thibaud Stoll, andPatrick Salou

Advantages of Hydrodynamic Cell Separation in Industrial CellCulture Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 657Bernd Schröder, Elsayed Ahmed Elsayed, Johanna Olownia,and Roland Wagner

Optimization and Characterization of the Process for LargeVolume Cell Banking in Bags . . . . . . . . . . . . . . . . . . . . . . . . 665S. Lünse, Rüdiger Heidemann, and Chun Zhang

Development of Screening Method for IgA-Promoting FactorsDerived from Food Extracts Using a Human Myeloma Cell Line . . . . 669Kouhei Mizuno, Yusuke Tanii, Yuichi Inoue, Aiko Inoue,and Hiroharu Kawahara

Cryopreservative Solution Using Sericin . . . . . . . . . . . . . . . . . . 675Kenji Ikeda, Yoko Oumi, Akiko Ogawa, Masahiro Sasaki,Hideyuki Yamada, and Satoshi Terada

Fructan as a Novel Effective Factor for Mammalian Cell Culture . . . . 679Hideharu Higashiya, Kyoichi Kobayashi, and Satoshi Terada

Online Determination of Oxygen Uptake and Carbon DioxideProduction Rates in Mammalian Cell Culture Using Mass Spectrometry 683J. Haas, T. Tröbs, C. Clemens, M. Wunder, M. Rüger, andT.W. Schulz

Optimisation of mAb Concentration in Microcarrier BasedPerfusion Compared to Batch/Fed-Batch Cultivation . . . . . . . . . . . 689Christian Kaisermayer and Gerald Blüml

Characterization of the Novel Human AGE1hn Cell Line forProduction of Recombinant Proteins . . . . . . . . . . . . . . . . . . . . 693S. Northoff, H. Büntemeyer, V. Sandig, S. Zietze, and T. Noll

Rapid Selection of Optimal Formulations for Divergent ClonesThrough Screening Chinese Hamster Ovary Media Library . . . . . . . 699Avril A. Lawshé, Min Zhang, Ashley Smith, Wade Nudson,James S. Ross, and Matthew V. Caple

Development of a Vaccine Candidate Against Heartwater . . . . . . . . 703I. Marcelino, M.F.Q. Sousa, C. Peixoto, A.I. Amaral, N. Vachiery,T. Lefrançois, D. Martinez, M.J.T. Carrondo, and P.M. Alves

Contents xvii

Animal Component Free T-Cell Culture . . . . . . . . . . . . . . . . . . 711W.G. Whitford, B.B. Barnett, and J.H. Manwaring

Characterization of Cholesterol-Independent GS-NS/0Recombinant Antibody Cell Lines . . . . . . . . . . . . . . . . . . . . . 717Jianguo Yang, Jing Shi, Raghavan Venkat, and Kripa Ram

Development of a Fed-Batch Process for the Production of aRecombinant Protein X in CHO-GS System – Case Study fromthe Cell to Reactor Process Ready for Pilot Scale Cultivation . . . . . . 723Véronique Chotteau, Yun Jiang, Jeannette Westin,Kerstin Dahlenborg, Anna Sjöblom-Hallén, Erik Svensson, andMichael Öberg

Scaffolds for Articular Joint Tissue Engineering . . . . . . . . . . . . . 727A. Pla, E. Sarró, M. Caminal, D. Peris, L. Vidal, J.J. Cairó, andF. Gòdia

Effect of Tunisian Aromatic Plant Extracts on Melanogenesis . . . . . . 735Kyoko Matsuyama, Mitsuko Kawano, Mohamed Elyes Kchouk,Hiroshi Shinmoto, and Hiroko Isoda

Effects of Capsaicin on Energy Metabolism by Human IntestinalEpithelial Cell Line Caco-2 . . . . . . . . . . . . . . . . . . . . . . . . . 739Junkyu Han and Hiroko Isoda

Human A1AT Production – Propagating a Newly DevelopedHuman Cell Line in a Novel Disposable Perfusion Bioreactor . . . . . . 743Silke Langhammer, Ralf Pörtner, Volker Sandig, Genadii Suchich,Sascha Tonevitzky, Markus Berger, Veronique Blanchard,Matthias Kaup, Vanessa Frenz, Rudolf Tauber, René Brecht,Susann Koch, and Uwe Marx

Characterization of Diffusion and Flow Relations in the NovelMembrane Based Perfusion Bioreactor . . . . . . . . . . . . . . . . . . 749Silke Langhammer, Anke Wellmann, Richard Ammer,Thomas Linz, Rudolf Tauber, Ralf Pörtner, and Uwe Marx

Protective Effect of Di-O-Caffeoylquinic Acid onHuman-Derived Neurotypic SH-SY5Y Cells AgainstAlzheimer’s Disease Amyloid-Beta-Induced Toxicity . . . . . . . . . . . 755Hiroko Isoda, Junkyu Han, and Hideyuki Shigemori

Flow Through Ceramic Foams – A Future Cell Culture Challenge . . . 759V. Goralczyk, A. Bischof, A. Berthold, L. Blessing, H. Schubert,and R. King

Measles Virus Production in MRC-5 Cells Grown onMicrocarriers in a Stirred Bioreactor . . . . . . . . . . . . . . . . . . . 765Khaled Trabelsi, Semy Majoul, Fatma Charfi, and Héla Kallel

xviii Contents

A New System for the Enrichment of Cell Subclones SecretingHigh Levels of IgG Using Magnetic Cell Sorting (MACS R© Technology) 771Alexandra S.H. Hoch, Kerstin Zörner, Stefanie Kattenbach,Mayke Busch, Erik Schneider, Iris Bürger, and Ulf Bethke

Soy Hydrolysate Optimization for Cell Culture Applications . . . . . . 777Jeanette N. Hartshorn, Sandra McNorton, Chas Hernandez, Ed vander Ent, and Matthew V. Caple

The Effect of Bioreactor pH and Temperature on ProteinGlycosylation in Perfusion Cultures of Mammalian Cells . . . . . . . . 785Eva Sajan, Ricaredo Matanguihan, Rüdiger Heidemann,Susan Abu-Absi, Wilfred Asuncion, Glenn Yamasaki, Xue Wu,Jianmin Chen, John E. Murphy, and Chun Zhang

Evaluation of Cell Growth Characteristics on Chitosan-AlginateMembranes to Assess Their Potential Application on HighlyExuding Skin Lesions and In Vivo Evaluation in Wounded Cat . . . . . 789Ana Paula Rodrigues, Selma C. Genari, Neusa M. Paulo, Maria daConceição, Marcelo S. de Brito e Silva, and Ângela Maria Moraes

Vaccine Production Utilizing the Potential of Microcarriers inDisposable Bioreactor . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795J.E. Schouwenberg, T. Van der Velden-de Groot, and G. Blueml

Characterization of an Anti-Idiotypic Antibody Blocking theCapacity of the HIV-1 Specific nMAb 2F5 . . . . . . . . . . . . . . . . . 803Johannes Gach, Willibald Steinfellner, Martina Löschel,Rainer Hahn, Heribert Quendler, Hermann Katinger, andRenate Kunert

Cultivation of PER.C6 R© Cells in the Novel CELL-TainerTM

High-Performance Disposable Bioreactor . . . . . . . . . . . . . . . . . 807G. M. Zijlstra and N. Oosterhuis

Scale-Up of a PER.C6 R© Fed-Batch Process in 50 and 250 LHyclone Single Use Bioreactors Compared to 50 and 250 LStainless Steel Bioreactors . . . . . . . . . . . . . . . . . . . . . . . . . . 809G. M. Zijlstra

Capacitance Sensor as a Robust Tool for Cell CultureMonitoring in Process Development and Manufacturing . . . . . . . . . 811Damien Voisard, Geoffrey Esteban, and Gianni Baer

Effect of Different Cell Culture Medium Surfactants on CellGrowth and Viability . . . . . . . . . . . . . . . . . . . . . . . . . . . . 819Kristina Martinelle, Annika Mattsson, Brita Rippner-Blomqvist,and Elisabeth Lindner

Contents xix

Conventional Stirred Bioreactor Control System for Monitoringand Controlling pH and DO in a Wave Bioreactor . . . . . . . . . . . . 823Peter Aizawa, Charlotte Benemar, Cecilia Wingenblixt,Kristina Martinelle, and Elisabeth Lindner

On-Line Monitoring of Vero Cells Cultures During the Growthand Rabies Virus Process Using Biomass Spectrometer . . . . . . . . . 829Samia Rourou, Stéphanie Gaumon, and Héla Kallel

Inducing of Human IgE Antibodies by In Vitro Immunization . . . . . 833Shuichi Hashizume and Hiroharu Kawahara

Oxygen Uptake Rate (OUR) Estimation in High DensityMammalian Cell Perfusion Cultures . . . . . . . . . . . . . . . . . . . . 837C. Cruz, K. Joeris, C. Goudar, C. Zhang, and K. Konstantinov

Use of Yeast Derived Nutrients for Cell Culture in Serum-Free Media . 843I. Chevalot, C. Dziukala, E. Olmos, I. Marc, D. Druaux-Borreill,E. Oriol, and A. Marc

A Novel Approach to the Production of Plant-DerivedHydrolysates Yields Medium Supplements with EnhancedPerformance in Cell Culture Systems . . . . . . . . . . . . . . . . . . . 847James F. Babcock, Debra A. Merrill, and Shawn R. Smith

Monitoring the Cell Size Distribution of Mammalian CellCultures Using On-Line Capacitance Measurements . . . . . . . . . . . 853Sven Ansorge, Olivier Henry, Marc Aucoin, Robert Voyer,John P. Carvell, and Amine Kamen

Biosimilarity of Recombinant Human EPO Products from CHOCell Lines: A Carbohydrate Structural View . . . . . . . . . . . . . . . 861Nicolas Grammel, Frank Dittrich, Sebastian Kandzia,Eckart Grabenhorst, and Harald S. Conradt

Quantitative N-Glycan Mapping of Glycoprotein Therapeuticsby HPAEC-PAD: Glycosylation Characteristics of DifferentRecombinant Human EPO Products . . . . . . . . . . . . . . . . . . . . 867Sebastian Kandzia, Nicolas Grammel, Eckart Grabenhorst,and Harald S. Conradt

Contributors

Susan Abu-Absi Bayer HealthCare, Pharmaceuticals, Global BiologicalDevelopment, Cell Culture Development, 800 Dwight Way, Berkeley, CA94710, USA

M. Adam Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Derek Adams Fermentation and Cell Culture Development Group, AlexionPharmaceuticals, Inc., Cheshire, CT, USA

Abdennaji Adib Polyplus-Transfection S.A., Bioparc, Boulevard Sébastien Brant,BP 90018, 67401 Illkirch, France

D. Aibibu Rheinisch-Westfälische Technische Hochschule Aachen, Germany

Peter Aizawa Octapharma AB, SE-11275 Stockholm, Sweden,[email protected]

Martin Allen Process and Analytical Sciences, Amgen Inc., Seattle, WA, USA

Daniel W. Allison Cell Sciences and Development, SAFC Biosciences, 2909Laclede Ave, Saint Louis, MO 63103, USA, [email protected]

Christina Allmeling Medizinische Hochschule Hannover, Klinik für Plastische-,Hand- und Wiederherstellungschirurgie, Podbielskistr. 380, D-30659 Hannover,Germany, [email protected]

Mohamed Al-Rubeai School of Chemical and Bioprocess Engineering andCentre for Synthesis and Chemical Biology (CSCB), University College Dublin,Belfield, Dublin 4, Ireland

Paula M. Alves IBET/ITQB (Instituto de Biologia Experimental eTecnológica/Instituto de Tecnologia Química e Biológica), Oeiras, Portugal,[email protected]

Y. Alvarez Center of Molecular Immunology (CIM), P.O. Box 16040, HavanaCity 11600, Cuba

Ana I. Amaral IBET/ITQB (Instituto de Biologia Experimental eTecnológica/Instituto de Tecnologia Química e Biológica), Oeiras, Portugal

xxi

xxii Contributors

Richard Ammer ProBioGen AG, Berlin, Germany

Tibor Anderlei Adolf Kühner AG, 4127 Birsfelden, Switzerland

Karin Anderson Cell and Molecular Sciences, Wyeth BioPharma, Andover,MA, USA

Wagner Andreas Polymun Scientific, Immunbiologische Forschung GmbH,Nussdorfer Lände 11, A-1190 Vienna, Austria

Sven Ansorge Institut de Recherche en Biotechnologie, CNRC, 6100 AvenueRoyalmount, Montréal, Québec H4P 2R2, Canada; École Polytechnique deMontréal, C.P. 6079, succ. Centre-ville, Montréal, Québec H3C 3A7, Canada

Fabienne Anton Institut für Technische Chemie, Universität Hannover,Callinstraße 3, 30167 Hannover, Germany

M. Arias Center of Molecular Inmunology, Havana, Cuba

Eddy Arnoldussen Phytovation B.V., Wassenaarseweg 72, 2333 AL Leiden, TheNetherlands

Sohéil Asgari Cinvention AG, Rheingaustr. 190-196, D-65203 Wiesbaden,Germany, [email protected]

Wilfred Asuncion Bayer HealthCare, Pharmaceuticals, Global BiologicalDevelopment, Cell Culture Development, 800 Dwight Way, Berkeley, CA94710, USA

Marc Aucoin Institut de Recherche en Biotechnologie, CNRC, 6100 AvenueRoyalmount, Montréal, Québec H4P 2R2, Canada

Kevin A. Auton Cellexus Limited, 12 Ramsay Court, Hinchingbrooke BusinessPark, Huntingdon, Cambridgeshire, PE29 6FY United Kingdom,[email protected]

G. Backliwal Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Malin Bäckström Department of Medical Biochemistry/Mammalian ProteinExpression core facility, Göteborg University, Box 440, 405 30 Göteborg, Sweden,[email protected]

Gianni Baer Merck Serono S.A., Z.I.B, 1809 Fenil-sur-Corsier, Switzerland

James F. Babcock Sheffield Pharma Ingredients, Division of Kerry Bio-Science,158 State Highway 320, Norwich, NY 13815, USA

Wilfried A.M. Bakker Netherlands Vaccine Institute (NVI), ProcessDevelopment department, P.O. Box 457, 3720 AL Bilthoven, The Netherlands,[email protected]

Lucia Baldi Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratory ofCellular Biotechnology, Lausanne, Switzerland

Contributors xxiii

Jenny Y. Bang Irvine Scientific, Santa Ana, CA, USA

N. Barbouche CNRS-INPL, Laboratoire des Sciences du Génie Chimique UPR6811, 2, av. de la Forêt de Haye – BP 172 – 54505, Vandœuvre-les-Nancy Cedex,France

Jenny Barker Protein Science Group, Department of Biosciences, University ofKent, Canterbury, Kent, CT2 7NJ, UK

L.M. Barnes The Michael Smith Building, The University of Manchester, OxfordRoad, Manchester, M13 9PT, UK

B.B. Barnett Thermo Fisher Scientific, Logan, UT, USA

Niall Barron National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland

Christoph L. Bausch Cell Sciences and Development, SAFC Biosciences, 2909Laclede Ave, Saint Louis, MO 63103, USA, [email protected]

Larissa Behr Institut für Technische Chemie, Universität Hannover, Callinstraße3, 30167 Hannover, Germany

Christèle Bellon Inotech Labor AG, Eulerstrasse 55, CH-4051 Basel, Switzerland

Nadia Bencherif Merck Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland

Charlotte Benemar Octapharma AB, SE-11275 Stockholm, Sweden

J.A. Bercovich Bio Sidus S.A., Constitución 4234 (C1254ABX), Buenos Aires,Argentina, [email protected]

Markus Berger Institute of Clinical Chemistry and Pathobiochemistry, CharitéPlatz 1, 10117 Berlin, Germany, [email protected]

August Bernd Department of Dermatology and Venerology, University Hospital,Frankfurt/Main, Germany

Silke Berski Leibniz Universität Hannover, Institut für Organische Chemie,D-30167 Hannover, Germany

A. Berthold Department of Ceramic Materials, Technische Universitaet Berlin,Germany

Antoine Berthoud Merck Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland

Rita Berthold ProBioGen AG, Berlin, Germany

Leopold Bertea BioPharmaceutical Operations (BPO) Manufacturing Huningue,Centre de Biotechnologie, Novartis Pharma S.A.S., 8, rue de l’Industrie, B.P. 355,F-68333 Huningue Cedex, France

Ulf Bethke Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429 BergischGladbach, Germany

xxiv Contributors

Corinna Bialek CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany

Richard Biener University of Applied Sciences Esslingen, Department of NaturalSciences, Kanalstrasse 33, 73728 Esslingen, Germany

Stéphanie Biri Polyplus-Transfection S.A., Bioparc, Boulevard Sébastien Brant,BP 90018, 67401 Illkirch, France

A. Bischof Engineering Design and Methodology, Technische Universitaet Berlin,Germany

F. Blanchard Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France

Véronique Blanchard Institute of Clinical Chemistry and Pathobiochemistry,Charité Platz 1, 10117 Berlin, Germany

L. Blessing Engineering Design and Methodology, Technische UniversitaetBerlin, Germany

Gerald Blüml GE Healthcare, Vienna, Austria

G. Blueml GE Healthcare, Uppsala, Sweden

A. Bock Max Planck Institute for Dynamics of Complex Technical Systems,Sandtorstrasse 1, 39106 Magdeburg, Germany, [email protected]

C. Boisart METabolic EXplorer SA, Biopole Clermont-Limagne, F-63360 St.Beauzire, France

M. Bollati-Fogolín Cell Biology Unit, Institut Pasteur de Montevideo,Montevideo, Uruguay; Laboratorios de Cultivos Celulares, Universidad Nacionaldel Litoral, Santa Fe, Argentina, [email protected]

Trissa Borgschulte Cell Sciences and Development, SAFC Biosciences, SaintLouis, MO 63103, USA, [email protected]

F. Bosco Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium

C. Braet ATMI LifeSciences, Hoegaarden, Belgium

R. Bragos Departament d’Enginyeria Electrònica, Universitat Politècnica deCatalunya, Barcelona, Spain

J.J. Brandner Institute for Micro Process Engineering IMVT, Research CenterKarlsruhe, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen,Germany

René Brecht ProBioGen AG, Berlin, Germany

Steve Brennan Wyeth BioPharma, Andover, MA, USA

Contributors xxv

M. Brischwein Technical University of Munich, Arcisstr. 21, D-80333 Munich,Germany

Inge Broer Agrobiotechnologie, Universität Rostock, Justus-von-Liebig-Weg 8,18059 Rostock, Germany, [email protected]

Stephanie Bruns Leibniz Universität Hannover; Institut für Technische Chemie,D-30167 Hannover, Germany

H. Büntemeyer Institute of Cell Culture Technology, University of Bielefeld,Bielefeld, Germany

Iris Bürger Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429 BergischGladbach, Germany

Mayke Busch Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429 BergischGladbach, Germany

R. Cacan Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS 8576,59655 Villeneuve d’Ascq, France

J.J. Cairó Departament d’ Enginyeria Química, Universitat Autònoma deBarcelona, 08193 Bellaterra, Barcelona, Spain

M. Caminal Grup d’Enginyeria Cellular i Tissular, Departament d’EnginyeriaQuímica, Universitat Autònoma de Bacelona, 08193 Bellaterra, Barcelona, Spain

Matthew V. Caple Cell Sciences and Development, SAFC Biosciences, 2909Laclede Ave, Saint Louis, MO 63103, USA, [email protected]

Nuno Carinhas IBET/ITQB (Instituto de Biologia Experimental eTecnológica/Instituto de Tecnologia Química e Biológica), Oeiras, Portugal

Jonathan O. Carlson Department of Microbiology, Immunology and Pathology,Colorado State University, Fort Collins, CO, USA

Manuel J.T. Carrondo IBET/ITQB (Instituto de Biologia Experimental eTecnológica/Instituto de Tecnologia Química e Biológica), Oeiras, Portugal;FCT/UNL (Faculdade de Ciências e Tecnologia/Universidade Nova Lisboa),Monte da Caparica, Portugal

John P. Carvell Aber Instruments Ltd, Aberystwyth, UK,[email protected]

Elisabeth Casademunt Octapharma Biopharmaceuticals GmbH, AmKlopferspitz 19/19a, 82152 Martinsried, Germany, [email protected]

S. Castiglioni Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy

Leda R. Castilho Federal University of Rio de Janeiro, COPPE, PEQ, CellCulture Engineering Laboratory (LECC), Caixa Postal 68502, 21941-972 Rio deJaneiro/RJ, Brazil, [email protected]

xxvi Contributors

A. Castillo Center of Molecular Immunology (CIM), P.O. Box 16040, HavanaCity 11600, Cuba

J. Castillo Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium

A. Castro Center of Molecular Inmunology, Havana, Cuba

L. Cavenaghi Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy

Fatma Charfi Viral Vaccines Research and Development Unit, Institut Pasteur deTunis, 13, place Pasteur, BP.74, 1002 Tunis, Tunisia

Tim Charlebois Cell and Molecular Sciences, Wyeth BioPharma, Andover,MA, USA

M. Chea Center of Molecular Inmunology, Havana, Cuba

Jianmin Chen Bayer HealthCare, Pharmaceuticals, Global BiologicalDevelopment, Expression Technology, Berkeley, CA 94710, USA

I. Chevalot Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France, [email protected]

F. Chirat Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS 8576,59655 Villeneuve d’Ascq, France

Murim Choi Mogam Biotechnology Research Institute, Yongin, Gyonggi-Do446-799, Republic of Korea

Véronique Chotteau Biovitrum, Biopharmaceutical Process Development,Process Sciences Stockholm and Göteborg, Sweden,[email protected]

C. Clemens Department of Biopharmaceutical Process Science, UpstreamDevelopment, Cell Culture Technology, Boehringer Ingelheim Pharma GmbH& Co. KG, Biberach an der Riss, Germany,[email protected]

Martin Clynes National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland

F. Collignon Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium,[email protected]

Maria da Conceição School of Veterinary, Federal University of Goiás, Goiânia,SP, Brazil

Harald S. Conradt GlycoThera GmbH, 38124 Braunschweig, Germany

Jennifer Cresswell Cell Sciences and Development, SAFC Biosciences, SaintLouis, MO, USA

Contributors xxvii

M.E. Criscuolo Bio Sidus S.A., Constitución 4234 (C1254ABX), Buenos Aires,Argentina

Tori Crook Cambridge Antibody Technology, Milstein Building, Granta Park,Cambridge CB21 6GH, UK

C. Crosta Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA, Italy

C. Cruz Global Biologics Development, Bayer HealthCare, Berkeley, CA94710, USA

Peter Czermak Institute of Biopharmaceutical Technology, University of AppliedSciences Wiesentrasse 14, 35390, Giessen, Germany; Department of ChemicalEngineering, Kansas State University, Manhattan KS, USA,[email protected]

Kerstin Dahlenborg Biovitrum, Biopharmaceutical Process Development,Process Sciences, Stockholm and Göteborg, Sweden

John Daley Invitrogen Corporation, 3175 Staley Road, Grand Island, New York14072, USA

Lekan Daramola Cambridge Antibody Technology, Granta Park, Cambridge,CB21 6GH, UK

Alison Davis Cambridge Antibody Technology, Milstein Building, Granta Park,Cambridge CB21 6GH, UK

Lynn A. Davis Cell Sciences and Development, SAFC Biosciences, 13804 W.107th Street, Lenexa, KS 66215, USA

Greg Dean Cambridge Antibody Technology, Milstein Building, Granta Park,Cambridge CB21 6GH, UK

F. Debras Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium

Maria De Jesus ExcellGene SA, 1870 Monthey, Switzerland

Fanny Delegrange Laboratory of Cellular Biotechnology, EPFL SV IBI LBTC,CH B41 424 (bâtiment CH), Station 6, CH-1015 Lausanne, Switzerland,[email protected]

Jonathan Dempsey Cambridge Antibody Technology, Granta Park, Cambridge,CB21 6GH, UK; Invitrogen, 3 Fountain Drive, Inchinnan, PA4 9RF, UK

Bart DeWever Phenion GmbH & Co. KG, Düsseldorf, Germany

A.J. Dickson The Michael Smith Building, The University of Manchester, OxfordRoad, Manchester, M13 9PT, UK

Solvig Diederichs Institut für Technische Chemie, Universität Hannover,Callinstraße 3, 30167 Hannover, Germany, [email protected]

xxviii Contributors

C. Dietzsch Max Planck Institute for Dynamics of Complex Technical Systems,Bioprocess Engineering group, Sandtorstr. 1, 39106 Magdeburg, Germany;Lehrstuhl für Bioverfahrenstechnik, Technical University Dresden, Dresden,Germany

Frank Dittrich GlycoThera GmbH, Inhoffenstr.7, 38124 Braunschweig,Germany, [email protected]

Kaori Doi Department of Applied Chemistry and Biotechnology, Universityof Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan, [email protected]

Padraig Doolan National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland

E. Dormond Animal Cell Technology Group, Biotechnology Research Institute,National Research Council Canada, 100 Royalmount Avenue, Montréal, Québec,H4P 2R2 Canada; Chemical Engineering Department, Ecole Polytechnique deMontréal, Campus de l′Université de Montréal, 2500, chemin de Polytechnique,Montréal, Québec, H3T 1J4 Canada

Gerald Dräger Leibniz Universität Hannover, Institut für Organische Chemie,D-30167 Hannover, Germany

M. Drews Tallinn University of Technology and Competence Centre for CancerResearch, Akadeemia tee 15, 12618, Tallinn, Estonia, [email protected]

D. Druaux-Borreill BIOSPRINGER, 103 rue Jean Jaurès-94701, Maisons-Alfortcedex, France

J.-C. Drugmand Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium,[email protected]

D. Dumas Laboratoire d′Energétique et de Mécanique Théorique et Appliquée,UMR 7563, CNRS-INPL, Nancy-Université, Nancy, France

G. Duncan Strathclyde Institute of Pharmacy and Biomedical Sciences,University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK

Roland Durner Tecan AG, Männedorf, Switzerland

Y. Durocher Animal Cell Technology Group, Biotechnology Research Institute,National Research Council Canada, 100 Royalmount Avenue, Montréal, Québec,H4P 2R2 Canada

C. Dziukala Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France

Ichiro Ebata Marukin Bio Inc., 27 Monnomae, Todo, Uji, Kyoto 611-0013, Japan

Elsayed Ahmed Elsayed National Research Centre, Cairo, Egypt

Contributors xxix

Barbara Enenkel Department of Biopharmaceutical Process Science, UpstreamDevelopment, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an derRiss, Germany

Alfred Engel Roche Diagnostics GmbH, Nonnenwald 2, D-82372 Penzberg,Germany

Eva-Maria Engelhardt Ecole Polytechnique Fédérale de Lausanne, Switzerland,[email protected]

Ed van der Ent DMV International, Delhi, NY 13753, USA

Patrick Erbacher Polyplus-Transfection S.A., Bioparc, Boulevard SébastienBrant, BP 90018, 67401 Illkirch, France, [email protected]

Geoffrey Esteban FOGALE Nanotech, Nîmes, France

M. Etcheverrigaray Laboratorio de Cultivos Celulares. Facultad de Bioquímica yCiencias, Biológicas. UNL. C.C. 242, Ciudad Universitaria (S3000ZAA) Santa Fe,Pcia, Santa Fe, Argentina

Marie Etzien ProBioGen AG, Berlin, Germany

E. Faife Center of Molecular Immunology (CIM), P.O. Box 16040, Havana City11600, Cuba

Thomas Falkman Protein Science and Supply, DECS, AstraZeneca R&DSödertälje, Building 841, S-151 85 Södertälje, Sweden

Guilherme N.M. Ferreira IBB – Institute for Biotechnology and Bioengineering,Centre for Molecular and Structural Biomedicine, Universidade do Algarve, Faro,Portugal, [email protected]

Ray Field Cambridge Antibody Technology, Granta Park, Cambridge, CB216GH, UK, [email protected]

A. Figueredo Center of Molecular Immunology, Calle 15 esq. 216, Havana, Cuba,[email protected]

Tom Fletcher Irvine Scientific, Santa Ana, CA, USA

A. Fontova Departament d’Enginyeria Electrònica, Universitat Politècnica deCatalunya, Barcelona, Spain

Wyn Forrest-Owen Cambridge Antibody Technology, Milstein Building, GrantaPark, Cambridge CB21 6GH, UK

G. Forno Zelltek S.A., Biológicas. UNL. C.C. 242, Ciudad Universitaria(S3000ZAA) Santa Fe, Pcia, Santa Fe, Argentina, [email protected]

R. Frank Department of Chemical Biology, Helmholtz Centre for InfectionResearch (HZI), Braunschweig, Germany

Andrea Franke ProBioGen AG, Berlin, Germany

xxx Contributors

Vanessa Frenz Charité Universitätsmedizin, Berlin, Germany

Eric Frieden Fermentation and Cell Culture Development Group, AlexionPharmaceuticals, Inc., Cheshire, CT, USA

C. Frochot DCPR, UMR 7630, CNRS-INPL, Nancy-Université, Nancy, France

Victor Fung Process and Analytical Sciences, Amgen Inc., Seattle, WA, USA

Martin Fussenegger Institute for Chemical and Bioengineering, ETH Zurich,8093 Zurich, Switzerland, [email protected]

Anne Furthmann ProBioGen AG, Berlin, Germany

Cornelia Fux Inotech Labor AG, Eulerstrasse 55, CH-4051 Basel, Switzerland,[email protected]

Johannes Gach Department of Biotechnology, University of Natural Resourcesand Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria,[email protected]

D. Gade Max Planck Institute for Dynamics of Complex Technical Systems,Sandtorstraße 1, 39106 Magdeburg, Germany

Nikos Gaitatzis CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany

M. Galgano Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy

J. Gálvez Departament d’ Enginyeria Química, Universitat Autònoma deBarcelona, 08193 Bellaterra, Barcelona, Spain

Patrick Gammell National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland

Jochem Gätgens Cell Culture/Fermentation Group, Institute for Biotechnology 2,Research Center Jülich, 52425 Jülich

Stéphanie Gaumon FOGALE Nanotech, 25 rue de l’Hostellerie, Ville Active,30 900 Nîmes, France

Mykle Gaynor Invitrogen Corporation, 3175 Staley Road, Grand Island, NewYork 14072, USA

V. Gelbgras Chemical Engineering, Applied Sciences Faculty, ULB, Brussels,Belgium

Selma C. Genari UNIPINHAL – Centro Regional Universitário Espírito Santo doPinhal, SP, Brazil

Yvonne Genzel Max Planck Institute for Dynamics of Complex TechnicalSystems, Bioprocess Engineering group, Sandtorstr. 1, 39106 Magdeburg,Germany, [email protected]

Contributors xxxi

Mark A. Gerber Cell Sciences and Development, SAFC Biosciences, SaintLouis, MO, USA, [email protected]

Richard Getto Hamburg University of Technology, Institute of Bioprocess andBiosystems Engineering, Denickestr. 15, D-21071 Hamburg, Germany

Suzanne Gibson Cambridge Antibody Technology, Milstein Building, GrantaPark, Cambridge CB21 6GH, UK

I. Giuntini Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy, [email protected]

F. Gòdia Departament d’ Enginyeria Química, Universitat Autònoma deBarcelona, 08193 Bellaterra, Barcelona, Spain

Christiane Goepfert Hamburg University of Technology, Institute of Bioprocessand Biosystems Engineering, Denickestr. 15, D-21071 Hamburg, Germany

J.-L. Goergen Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France, [email protected]

Jean-Philippe Goisnard BioPharmaceutical Operations (BPO) ManufacturingHuningue, Centre de Biotechnologie, Novartis Pharma S.A.S., 8, rue de l’Industrie,B.P. 355, F-68333 Huningue Cedex, France

Stephanie Gokorsch Institute of Biopharmaceutical Technology, University ofApplied Sciences Giessen-Friedberg, Giessen, Germany

V. Goralczyk Department of Measurement and Control, Technische UniversitaetBerlin, Germany

Chetan Goudar Bayer Healthcare, Biological Products Division, 800 DwightWay, Berkeley, CA 94710, USA

Albert de Graaf METabolic EXplorer SA, Biopole Clermont-Limagne, F-63360St. Beauzire, France

Rüdiger Graf Phenion GmbH & Co. KG, Düsseldorf, Germany

Ursula Graf-Hausner Zurich University of Applied Sciences, Winterthur,Switzerland

Eckart Grabenhorst GlycoThera GmbH, 38124 Braunschweig, Germany

Stefanos Grammatikos Department of Biopharmaceutical Process Science,Upstream Development, Boehringer Ingelheim Pharma GmbH & Co. KG,Biberach an der Riss, Germany

Nicolas Grammel GlycoThera GmbH, 38124 Braunschweig, Germany,[email protected]

xxxii Contributors

Misa I. Gray Cell Sciences and Development, SAFC Biosciences, 13804 W.107th Street, Lenexa, KS 66215, USA

M. Grez Georg-Speyer-Haus, Frankfurt, Germany, [email protected]

Martijn van Griensven Ludwig Boltzmann Institute for Experimental andClinical Traumatology, Donaueschingenstraße 13, A-1200 Vienna, Austria

H. Grothe Technical University of Munich, Arcisstr. 21, D-80333 Munich,Germany

Detlef Grunow Institute of Clinical Chemistry and Pathobiochemistry, CharitéPlatz 1, 10117 Berlin, Germany

Tim Gryseels Pfizer Global Research & Development, St. Louis Laboratories,Pfizer Inc, St. Louis, MO 63017, USA, [email protected]

David L. Grzenia Institute of Biopharmaceutical Technology, University ofApplied Sciences, Wiesenstrasse 14, 35390 Giessen, Germany; Department ofChemical Engineering, Colorado State University, Fort Collins, CO, USA

E. Guedon Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France

Peter de Haan Phytovation B.V., Wassenaarseweg 72, 2333 AL Leiden, TheNetherlands, [email protected]

J. Haas Department of Biopharmaceutical Process Science, UpstreamDevelopment, Cell Culture Technology, Boehringer Ingelheim Pharma GmbH &Co. KG, Biberach an der Riss, Germany

David L. Hacker Laboratory of Cellular Biotechnology, EPFL SV IBI LBTC, CHB41 424 (bâtiment CH), Station 6, CH-1015 Lausanne, Switzerland,[email protected]

Rainer Hahn Department of Biotechnology, University of Natural Resources andApplied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria

G.W. Halbert Strathclyde Institute of Pharmacy and Biomedical Sciences,University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK,[email protected]

V. Halloin Chemical Engineering, Applied Sciences Faculty, ULB, Brussels,Belgium

Binbing Han Department of Chemical Engineering, Colorado State University,Fort Collins, CO, USA

Junkyu Han Graduate School of Life and Environmental Sciences, University ofTsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan

Alyssa Handler Wyeth BioPharma, Andover, MA, USA

Contributors xxxiii

Reisinger Hannes Department of Biotechnology, University of Natural Resourcesand Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria

Gunnar C. Hansson Department of Medical Biochemistry/Mammalian ProteinExpression core facility, Göteborg University, Box 440, 405 30 Göteborg, Sweden

Jeanette N. Hartshorn Cell Sciences and Development, SAFC Biosciences,Lenexa, KS 66215, USA

Shuichi Hashizume Research Institute, Morinaga & Co. Ltd., Yokohama230-8504, Japan

Rich Hassett Invitrogen Corporation, 3175 Staley Road, Grand Island, New York14072, USA

Diane Hatton Cambridge Antibody Technology, Milstein Building, Granta Park,Cambridge, CB21 6GH, UK

N. Havelange Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium,[email protected]

Megumi Hayashi Department of Applied Chemistry and Biotechnology,University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan

S. Hayavi Strathclyde Institute of Pharmacy and Biomedical Sciences, Universityof Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK

Carole Heath Process and Analytical Sciences, Amgen Inc., Seattle, WA, USA,[email protected]

Robert Heckathorn Fermentation and Cell Culture Development Group, AlexionPharmaceuticals, Inc., Cheshire, CT, USA, [email protected]

Rüdiger Heidemann Bayer Healthcare, Biological Products Division, 800Dwight Way, Berkeley, CA 94710, USA

Pieter van der Heiden CELLution Biotech BV, Cereslaan 2, 9641 MJ Veendam,The Netherlands

Christoph Heinzen Inotech Labor AG, Eulerstrasse 55, CH-4051 Basel,Switzerland

Petra Helfrich Bayer Schering Pharma, Berlin, Germany

Olivier Henry Institut de Recherche en Biotechnologie, CNRC, 6100 AvenueRoyalmount, Montréal, Québec H4P 2R2, Canada

Katinger Hermann Department of Biotechnology, University of NaturalResources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria;Polymun Scientific, Immunbiologische Forschung GmbH, Nussdorfer Lände 11,A-1190 Vienna, Austria

xxxiv Contributors

Chas Hernandez Cell Sciences and Development, SAFC Biosciences, Lenexa,KS 66215, USA

Sabine Hertel CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany

Hideharu Higashiya Department of Applied Chemistry and Biotechnology,University of Fukui, 3-9-1, Bunkyo, Fukui, 910-8507, Japan

J. Hilborn Polymer Chemistry, Uppsala University, Sweden

Markus Hildinger ExcellGene S.A., Monthey, Switzerland

Alexandra S.H. Hoch Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429Bergisch Gladbach, Germany, [email protected]

Helmut Hoffmann Department of Biopharmaceutical Process Science, UpstreamDevelopment, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an derRiss, Germany

Raimund Hoffrogge Institute of Cell Culture Technology, University ofBielefeld, Universitätsstr. 25, 33615 Bielefeld, Germany

Gerrit-Jan van Holst Phytovation B.V., Wassenaarseweg 72, 2333 AL Leiden,The Netherlands

Deborah Horn ProBioGen AG, Goethestrasse 54, 13086 Berlin, Germany

Brian Hossfeld Pfizer Global Research & Development, St. Louis Laboratories,Pfizer Inc, St. Louis, MO 63017, USA

Kristin Höwing ProBioGen AG, Goethestrasse 54, 13086 Berlin, Germany

R. Hunt Tallinn University of Technology and Competence Centre for CancerResearch, Akadeemia tee 15, 12618, Tallinn, Estonia, [email protected]

Jeffrey Hunter Protein Sciences Group, Alexion Pharmaceuticals, Inc., Cheshire,CT, USA

D. Jacob Animal Cell Technology Group, Biotechnology Research Institute,National Research Council Canada, 100 Royalmount Avenue, Montréal, Québec,H4P 2R2 Canada

Michiels Jean-François Laboratoire de Biochimie Cellulaire, Croix du sud 5/3,Institut des Sciences de la vie, Université catholique de Louvain, B-1348,Louvain-la-Neuve, Belgium

Barbau Jérémie Laboratoire de Biochimie Cellulaire, Croix du sud 5/3, Institutdes Sciences de la vie, Université catholique de Louvain, B-1348,Louvain-la-Neuve, Belgium

Yun Jiang Biovitrum, Biopharmaceutical Process Development, SE-112 76,Stockholm, Sweden, [email protected]

Contributors xxxv

K. Joeris Global Biologics Development, Bayer HealthCare, Berkeley, CA94710, USA

Heather Jones Pfizer Global Research & Development, St. Louis Laboratories,Pfizer Inc, St. Louis, MO 63017, USA

Ingo Jordan ProBioGen AG, Goethestr. 54, 13086 Berlin, Germany,[email protected]

Martin Jordan Merck Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland

Yeon-suk Jung Department of Genetic Resources Technology, Faculty ofAgriculture, Kyushu University, Fukuoka, Japan

Kenji Ikeda Department of Applied Chemistry and Biotechnology, Universityof Fukui, Fukui, Japan, [email protected]

T. Ilicheva State Research Center of Virology and Biotechnology VECTOR,Koltsovo, Novosibirsk region, Russia

Aiko Inoue Kitakyushu National College of Technology; The Cell EngineeringCenter, 5-20-1 Shii Kokuraminamiku, 803-0985 Kitakyushu, Japan

Yuichi Inoue Kitakyushu National College of Technology, The Cell EngineeringCenter, 5-20-1 Shii Kokuraminamiku, 803-0985 Kitakyushu, Japan

Hiroko Isoda Graduate School of Life and Environmental Sciences, University ofTsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan,[email protected]

Christian Kaisermayer Department of Biotechnology, University of NaturalResources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria,[email protected]

Susanne Kall Klinik für Plastische, Hand- und Wiederherstellende Chirurgie,Medical School Hannover, Podbielskistraße 380, 30659 Hannover, Germany

Héla Kallel Institut Pasteur de Tunis, Viral vaccines Research and DevelopmentUnit, 13, place Pasteur. BP.74, 1002 Tunis, Tunisia, hela.kallel @pasteur.rns.tn

A. Kamen Animal Cell Technology Group, Biotechnology Research Institute,National Research Council Canada, 6100 Royalmount Avenue, Montréal, Québec,H4P 2R2 Canada, [email protected]

Michael Kammal University Medical Center Hamburg-Eppendorf, Departmentof Legal Medicine, Martinistr. 52, D-20246 Hamburg, Germany

Sebastian Kandzia GlycoThera GmbH, 38124 Braunschweig, Germany,[email protected]

Hasse Karlsson Department of Medical Biochemistry/Mammalian ProteinExpression core facility, Göteborg University, Box 440, 405 30 Göteborg, Sweden

xxxvi Contributors

Soverin Karmiol Invitrogen Corporation, 3175 Staley Road, Grand Island, NewYork 14072, USA, [email protected]

Vorauer-Uhl Karola Department of Biotechnology, University of NaturalResources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria

Cornelia Kasper Institut für Technische Chemie, Universität Hannover,Callinstraße 3, 30167 Hannover, Germany, [email protected]

A. Kastner Laboratoire des Sciences du Génie Chimique, UPR 6811,CNRS-INPL, Nancy-Université, Nancy, France

Yoshinori Katakura Department of Genetic Resources Technology, Faculty ofAgriculture, Kyushu University, Fukuoka, Japan

Hermann Katinger Department of Biotechnology, University of NaturalResources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria;Polymun Scientific, Immunbiologische Forschung GmbH, Nussdorferlände 11,A-1190 Vienna, Austria

Stefanie Kattenbach Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429Bergisch Gladbach, Germany

Hitto Kaufmann Department of Biopharmaceutical Process Science, UpstreamDevelopment, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an derRiss, Germany

Matthias Kaup Institute of Clinical Chemistry and Pathobiochemistry, CharitéPlatz 1, 10117 Berlin, Germany, [email protected]

Hiroharu Kawahara Kitakyushu National College of Technology, The CellEngineering Center, 5-20-1 Shii Kokuraminamiku, 803-0985 Kitakyushu, Japan

Mitsuko Kawano University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8572, Japan

Kevin J. Kayser Cell Sciences and Development, SAFC Biosciences, 2909Laclede Ave, Saint Louis, MO 63103, USA, [email protected]

Mohamed Elyes Kchouk Technopole de Borj-Cedria-Centre de Biotechnologie,BP 901, Hammam-Lif 2050, Tunisia

Jung-Seob Kim Mogam Biotechnology Research Institute, Yongin, Gyonggi-Do446-799, Republic of Korea

R. King Department of Measurement and Control, Technische UniversitaetBerlin, Germany, [email protected]

Andreas Kirschning Leibniz Universität Hannover, Institut für OrganischeChemie, D-30167 Hannover, Germany

Sabrina Kittel Hamburg University of Technology, Institute of Bioprocess andBiosystems Engineering, Denickestr. 15, D-21071 Hamburg, Germany

Contributors xxxvii

Günther Keil Institute of Diagnostic Virology, Friedrich-Loeffler-Institutes,Federal Research Centre for Virus Diseases of Animals, Boddenblick 5a, 17493Greifswald-Insel Riems, Germany

Robert Kenerson Invitrogen Corporation, 3175 Staley Road, Grand Island, NewYork 14072, USA

Helmut Kewes CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany

Soo Hean Gary Khoo Department of Chemical Engineering, Universityof Brimingham, Edgbaston B15 2TT, UK and School of Chemical and BioprocessEngineering, University College Dublin, Belfield, Dublin 4, Ireland

Peter Klappa Protein Science Group, Department of Biosciences, Universityof Kent, Canterbury, Kent, CT2 7NJ, UK

B. Klein Institute of Biotechnology 2, Research Center Juelich GmbH,Leo-Brandt-Str. 20, 52425 Juelich, Germany

Beate Kleuser Merck Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland

Jörg Knäblein Bayer Schering Pharma, Berlin, Germany

Kyoichi Kobayashi Fukui Prefectural Food Processing Research Institute, 1-1-1,Tsubonouchi, Maruoka-Cho, Sakai, Fukui, 910-0343, Japan

Susann Koch ProBioGen AG, Berlin, Germany

N. Kochanowski Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France, [email protected]

Andreas Kocourek Sartorius AG, D-37075 Goettingen, Germany

Claudia Kollert Octapharma Biopharmaceuticals GmbH, Am Klopferspitz19/19a, 82152 Martinsried, Germany

Patricia König Institute of Diagnostic Virology, Friedrich-Loeffler-Institutes,Federal Research Centre for Virus Diseases of Animals, Boddenblick 5a, 17493Greifswald-Insel Riems, Germany

Konstantin Konstantinov Bayer Healthcare, Biological Products Division, 800Dwight Way, Berkeley, CA 94710, USA

Kathleen Kopycinski Cell and Molecular Sciences, Wyeth BioPharma, Andover,MA, USA

Katie Kopycinski Wyeth BioPharma, Andover, MA, USA

Victor Korzhikov Institute of Macromolecular Compounds, Russian Academyof Sciences, Bolshoi pr. 31, 199004 St. Petersburg, Russia, [email protected]

xxxviii Contributors

Britta Krampe School of Chemical and Bioprocess Engineering and Centrefor Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield,Dublin 4, Ireland, [email protected]

R. Kratje Laboratorio de Cultivos Celulares. Facultad de Bioquímica y Ciencias,Biológicas. UNL. C.C. 242, Ciudad Universitaria (S3000ZAA) Santa Fe, Pcia,Santa Fe, Argentina

C. Küppers Institute of Biotechnology 2, Research Center Juelich GmbH,Leo-Brandt-Str. 20, 52425 Juelich, Germany

Markus Kürschner Cinvention AG, Rheingaustr. 190–196, D-65203 Wiesbaden,Germany, [email protected]

Ivan Küttel Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratory ofCellular Biotechnology, CH-1015 Lausanne, Switzerland

Renate Kunert Department of Biotechnology, University of Natural Resourcesand Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria

Darrin Kuystermans School of Chemical and Bioprocess Engineeringand Centre for Synthesis and Chemical Biology (CSCB), University CollegeDublin, Belfield, Dublin 4, Ireland, [email protected]

Kimberly A. Lacy Cell Sciences and Development, SAFC Biosciences, SaintLouis, MO, USA

Carolyn M. Lam Biological Systems Engineering Lab., Centre for ProcessSystems Engineering, Department of Chemical Engineering, Imperial CollegeLondon, London SW7 2AZ, UK

Silke Langhammer Institute of Clinical Chemistry and Pathobiochemistry,Charité Platz 1, 10117 Berlin, Germany

Avril A. Lawshé Cell Sciences and Development, SAFC Biosciences, 2909Laclede Avenue, Saint Louis, Missouri 63103, USA, [email protected]

Gene W. Lee Wyeth BioPharma, Andover, MA, USA

Guehwa Lee Mogam Biotechnology Research Institute, Yongin, Gyonggi-Do446-799, Republic of Korea

Pascal Lefebvre Lonza SPRL, 4800 Verviers, Belgium

T. Lefrançois CIRAD-EMVT, Domaine de Duclos, Petit-Bourg, Guadeloupe

J. Lehmann Institute of Cell Culture Technology, University of Bielefeld,Bielefeld, Germany

Mark Leonard Cell and Molecular Sciences, Wyeth BioPharma, Andover,MA, USA

Contributors xxxix

InHwan Lim Mogam Biotechnology Research Institute, Yongin, Gyonggi-Do446-799, Republic of Korea

Nan Lin Cell Sciences and Development, SAFC Biosciences, Saint Louis,MO, USA

Elisabeth Lindner Octapharma AB, SE 112 75 Stockholm, Sweden

Eva Lindskog Protein Science and Supply, DECS, AstraZeneca R&D Södertälje,Building 841, S-151 85 Södertälje, Sweden, [email protected]

Thomas Linz TU Hamburg-Harburg, Germany

A. Loa Cell Culture Service GmbH, Hamburg, Germany

Anna Logan School of Chemical and Bioprocess Engineering and Centre forSynthesis and Chemical Biology (CSCB), University College Dublin, Belfield,Dublin 4, Ireland

Martina Löschel Polymun Scientific, Immunbiologische Forschung GmbH,Nussdorferlände 11, A-1190 Vienna, Austria

R. Lugo Center of Molecular Inmunology, Havana, Cuba

Elke Lüllau Protein Science and Supply, DECS, AstraZeneca R&D Södertälje,Building 841, S-151 85 Södertälje, Sweden

Svenja Lünse Bayer HealthCare, Pharmaceuticals, Global BiologicalDevelopment, Cell Culture Development, 800 Dwight Way, Berkeley, CA94710, USA

B. Luo Institute of Biotechnology 2, Research Center Juelich GmbH,Leo-Brandt-Str. 20, 52425 Juelich, Germany

Mats Lundgren AstraZeneca BioProcess R&D, S-151 85 Södertälje, Sweden

Amanda Lunney Cambridge Antibody Technology, Milstein Building, GrantaPark, Cambridge CB21 6GH, UK

Svenja Lünse Hamburg University of Technology, Institute of Bioprocess andBiosystems Engineering, Denickestr. 15, D-21071 Hamburg, Germany

D. Lütkemeyer BiBiTec GmbH, Bielefeld, Germany

Vivien Lutz Hamburg University of Technology, Institute of Bioprocess andBiosystems Engineering, Denickestr. 15, D-21071 Hamburg, Germany

Semy Majoul Viral Vaccines Research and Development Unit, Institut Pasteur deTunis, 13, place Pasteur, BP.74, 1002 Tunis, Tunisia

Athanasios Mantalaris Biological Systems Engineering Lab., Centre for ProcessSystems Engineering, Department of Chemical Engineering, Imperial CollegeLondon, London SW7 2AZ, UK

xl Contributors

J.H. Manwaring Thermo Fisher Scientific, Logan, UT, USA

A. Marc Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France

I. Marc Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France

I. Marcelino ITQB/IBET, Apt. 12, 2781 Oeiras, Portugal, [email protected]

Rosalyn Marchant Protein Science Group, Department of Biosciences,University of Kent, Canterbury, Kent, CT2 7NJ, UK, [email protected]

Paulo A.N. Marinho Federal University of Rio de Janeiro, COPPE, PEQ, CellCulture Engineering Laboratory (LECC), Caixa Postal 68502, 21941-972 Rio deJaneiro/RJ, Brazil

Dana Marten Leibniz Universität Hannover, Institut für Technische Chemie,Callinstraße 3, D-30167 Hannover, Germany

Kristina Martinelle Octapharma AB, SE 112 75 Stockholm, Sweden,[email protected]

D. Martinez CIRAD-EMVT, Montpellier, France

R. Martynyuk State Research Center of Virology and Biotechnology VECTOR,Koltsovo, Novosibirsk region, Russia

Uwe Marx ProBioGen AG, Berlin, Germany

Ricaredo Matanguihan Bayer HealthCare, Pharmaceuticals, Global BiologicalDevelopment, Cell Culture Development, 800 Dwight Way, Berkeley, CA94710, USA

Stephanie Mathes Zurich University of Applied Sciences, Winterthur,Switzerland

E. Mathieu Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium

Shinei Matsumoto Department of Genetic Resources Technology, Facultyof Agriculture, Kyushu University, Fukuoka, Japan

Hiroshi Matsuoka Department of Biosciences, Teikyo University of Science &Technology, 2525 Uenohara, Yamanashi 409-0193, Japan, [email protected]

Kyoko Matsuyama University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki305-8572, Japan

Annika Mattsson Octapharma AB, SE 112 75 Stockholm, Sweden

Steven Max Cell and Molecular Sciences, Wyeth BioPharma, Andover, MA, USA

Contributors xli

S. Mazurek ScheBo Biotech AG, Netanyastr. 3, 35394 Gießen, Germany

Kevin McCarthy Cell and Molecular Sciences, Wyeth BioPharma, Andover,MA, USA

Sandra McNorton Cell Sciences and Development, SAFC Biosciences, Lenexa,KS 66215, USA

A. Medina Center of Molecular Inmunology, Havana, Cuba

Ricardo A. Medronho Federal University of Rio de Janeiro, UFRJ, CT. Bl. E,Ilha do Fundão, CEP 21941-914, Rio de Janeiro, RJ, Brazil, [email protected]

C.A. Melo Bio Sidus S.A., Constitución 4234 (C1254ABX), Buenos Aires,Argentina

Príamo A. Melo Federal University of Rio de Janeiro, COPPE, PEQ, Cell CultureEngineering Laboratory (LECC), Caixa Postal 68502, 21941-972 Rio deJaneiro/RJ, Brazil

Paula Meleady National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland

Maria Candida M. Mellado IBET/ITQB, Apartado 12, 2781-901, Oeiras,Portugal

Mark Melville Cell and Molecular Sciences, Wyeth BioPharma, Andover,MA, USA, [email protected]

Jimmy A. Mena IBT/UNAM, Ave. Universidad 2001, 62210, Cuernavaca,Mexico

A. Meneses-Acosta Animal Cell Technology Group, Biotechnology ResearchInstitute, National Research Council Canada, 100 Royalmount Avenue, Montréal,Québec, H4P 2R2 Canada

Debra A. Merrill Sheffield Pharma Ingredients, Division of Kerry Bio-Science,158 State Highway 320, Norwich, NY 13815, USA

Karsten R. Mewes Phenion GmbH & Co. KG, Düsseldorf, Germany

Masao Miki Department of Applied Chemistry and Biotechnology, University ofFukui, 3-9-1 Bunkyo, Fukui, 910-8507, Japan

Heike Mikschofsky Agrobiotechnologie, Universität Rostock,Justus-von-Liebig-Weg 8, 18059 Rostock, Germany,[email protected]

Joana Miranda Instituto de Biologia Experimental e Tecnológica (IBET) andInstituto de Tecnologia Química e Biológica (ITQB), Oeiras, Portugal,[email protected]

S. Mirazo Cell Biology Unit, Institut Pasteur de Montevideo, Uruguay

xlii Contributors

Kouhei Mizuno The Cell Engineering Center, Kitakyushu National Collegeof Technology, 5-20-1 Shii, Kokuraminami-ku, Kitakyushu 802-0985, Japan

Ângela Maria Moraes School of Chemical Engineering, State University ofCampinas - UNICAMP, Campinas, SP, Brazil, [email protected]

Pierre Moretti Institut für Technische Chemie, Universität Hannover, Callinstraße3, 30167 Hannover, Germany

M. Moser Cilbiotech sa, Mons, Belgium

John Mott Pfizer Global Research & Development, St. Louis Laboratories, PfizerInc, St. Louis, MO 63017, USA

Uwe Müller Zurich University of Applied Sciences, Winterthur, Switzerland

W. Müller Department of Experimental Immunology Helmholtz Centre forInfection Research (HZI), Braunschweig, Germany, [email protected]

John E. Murphy Bayer HealthCare, Pharmaceuticals, Global BiologicalDevelopment, Expression Technology, Berkeley, CA 94710, USA

E. Nechaeva State Research Center of Virology and Biotechnology VECTOR,Koltsovo, Novosibirsk region, Russia

Dirk Nehring University of Applied Sciences Giessen-Friedberg, Institute ofBiopharmaceutical Technology, Wiesenstr. 14, D-35390 Giessen, Germany

Anders Nelving AstraZeneca BioProcess R&D, S-151 85 Södertälje, Sweden,[email protected]

Dana Di Nino Cell and Molecular Sciences, Wyeth BioPharma, Andover,MA, USA

T. Noll Institute of Cell Culture Technology, University of Bielefeld, Bielefeld,Germany

M.L. Nolli Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy

S. Northoff Institute of Cell Culture Technology, University of Bielefeld,Germany, [email protected]

T. Nottorf Institute of Cell Culture Technology, University of Bielefeld, Germany,[email protected]

Wade Nudson Cell Sciences and Development, SAFC Biosciences, 2909 LacledeAvenue, Saint Louis, Missouri 63103, USA

A. Oberbek Ecole Polytechnique Fédérale de Lausanne, Switzerland

Michael Öberg Biovitrum, Biopharmaceutical Process Development, ProcessSciences, Stockholm and Göteborg, Sweden

Contributors xliii

Akiko Ogawa SEIREN CO., LTD 48-113-2 Yonozu, Mikuni-Cho, Sakai, Fukui,913-0038, Japan; Suzuka National College of Technology, Shiroko-Cho, Suzuka,Mie, 510-0294, Japan

M. Oggero Laboratorios de Cultivos Celulares, Universidad Nacional del Litoral,Santa Fe, Argentina

Yasuhiro Ohta Marukin Bio Inc., 27 Monnomae, Todo, Uji, Kyoto 611-0013,Japan

E. Ojito Center of Molecular Inmunology, Havana, Cuba, [email protected]

M. Oldiges Institute of Biotechnology 2, Research Center Juelich GmbH,Leo-Brandt-Str. 20, 52425 Juelich, Germany, [email protected]

Rui Oliveira FCT/UNL (Faculdade de Ciências e Tecnologia/Universidade NovaLisboa), Monte da Caparica, Portugal

Aline B. Oliveira Federal University of Rio de Janeiro, COPPE, PEQ, CellCulture Engineering Laboratory (LECC), Caixa Postal 68502, 21941-972 Rio deJaneiro/RJ, Brazil; Federal University of Rio de Janeiro, School of Chemistry,Brazil

E. Olmos Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,ENSAIA-INPL – 2, avenue de la Forêt de Haye, 54 505 Vandoeuvre-lès-Nancy,France

Johanna Olownia Miltenyi Biotec GmbH, Teterow, Germany

Nico M.G. Oosterhuis CELLution Biotech BV, Cereslaan 2, 9641 MJ Veendam,The Netherlands, [email protected]

Adekunle Onadipe Pfizer Global Research & Development, St. LouisLaboratories, Pfizer Inc, St. Louis, MO 63017, USA

E. Oriol BIOSPRINGER, 103 rue Jean Jaurès-94701, Maisons-Alfort cedex,France

A. Orlandi Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy

S. Osumba Artelis SA, Rue de Ransbeek 310, 1120 Brussels, Belgium

A.M. Otto Technical University of Munich, Arcisstr. 21, D-80333 Munich,Germany

Yoko Oumi Department of Applied Chemistry and Biotechnology, University ofFukui, Fukui, Japan

C. Paillet Zelltek S.A., Biológicas. UNL. C.C. 242, Ciudad Universitaria(S3000ZAA) Santa Fe, Pcia, Santa Fe, Argentina

xliv Contributors

J. Palacio Center of Molecular Immunology (CIM), P.O. Box 16040, Havana City11600, Cuba

Laura A. Palomares IBT/UNAM, Ave. Universidad 2001, 62210, Cuernavaca,Mexico

Christine Paul ProBioGen AG, Berlin, Germany

Neusa M. Paulo School of Veterinary, Federal University of Goiás, Goiânia, SP,Brazil

Luísa Pedro IBB – Institute for Biotechnology and Bioengineering, Centre forMolecular and Structural Biomedicine, Universidade do Algarve, Faro, Portugal

C. Peixoto ITQB/IBET, Apt. 12, 2781 Oeiras, Portugal

Steven Peppers Invitrogen Corporation, 3175 Staley Road, Grand Island, NewYork 14072, USA

D. Peris Grup d’Enginyeria Cellular i Tissular, Departament d’EnginyeriaQuímica, Universitat Autònoma de Bacelona, 08193 Bellaterra, Barcelona, Spain

M. Perrier Chemical Engineering Department, Ecole Polytechnique de Montréal,Campus de l’Université de Montréal, 2500, chemin de Polytechnique, Montréal,Québec, H3T 1J4 Canada

James Piret Michael Smith Laboratories and Department of Chemical andBiological Engineering, University of British Columbia, Vancouver, BC V6T 1Z4,Canada

Efstratios N. Pistikopoulos Biological Systems Engineering Lab., Centre forProcess Systems Engineering, Department of Chemical Engineering, ImperialCollege London, London SW7 2AZ, UK

Rodrigo C.V. Pinto Federal University of Rio de Janeiro, COPPE, PEQ, CellCulture Engineering Laboratory (LECC), Caixa Postal 68502, 21941-972 Rio deJaneiro/RJ, Brazil, [email protected]

A. Pla Grup d’Enginyeria Cellular i Tissular, Departament d’Enginyeria Química,Universitat Autònoma de Bacelona, 08193 Bellaterra, Barcelona, Spain

Oscar Platas Hamburg University of Technology, Institute of Bioprocess andBiosystems Engineering, Denickestr. 15, D-21071 Hamburg, Germany

Leo A. van der Pol Netherlands Vaccine Institute (NVI), Process Developmentdepartment, P.O. Box 457, 3720 AL Bilthoven, The Netherlands

A.J. Porter Lonza Biologics plc, Cell Culture Process Development, 228 BathRoad, Slough, Berkshire, SL1 4DX, UK, [email protected]

Ralf Pörtner Institute of Bioprocess and Biosystems Engineering, HamburgUniversity of Technology, Denickestr. 15, D-21071 Hamburg, Germany,[email protected]

Contributors xlv

Ginny Price Process and Analytical Sciences, Amgen Inc., Seattle, WA, USA

Alexandra Prießner Phenion GmbH & Co. KG, Düsseldorf, Germany

Klaus Püschel University Medical Center Hamburg-Eppendorf, Department ofLegal Medicine, Martinistr. 52, D-20246 Hamburg, Germany

Heribert Quendler Department of Biotechnology, University of NaturalResources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria;Polymun Scientific, Immunbiologische Forschung GmbH, Nussdorferlände 11,A-1190 Vienna, Austria

Y. Rabasa Center of Molecular Immunology (CIM), P.O. Box 16040, HavanaCity 11600, Cuba

A.J. Racher Lonza Biologics plc, Cell Culture Process Development, 228 BathRoad, Slough, Berkshire, SL1 4DX, UK

Kripa Ram Process Cell Culture, Development, MedImmune Inc., OneMedImmune Way, Gaithersburg, MD 20878, USA

Octavio T. Ramírez IBT/UNAM, Ave. Universidad 2001, 62210, Cuernavaca,Mexico

J. Rance Lonza Biologics plc, Cell Culture Process Development, 228 Bath Road,Slough, Berkshire SL1 4DX, UK, [email protected]

E. Rapp Max Planck Institute for Dynamics of Complex Technical Systems,Sandtorstraße 1, 39106 Magdeburg, Germany

Mareike Rausch Bayer Schering Pharma, Berlin, Germany,[email protected]

Pranhitha Reddy Process and Analytical Sciences, Amgen Inc., Seattle,WA, USA

Udo Reichl Max Planck Institute for Dynamics of Complex Technical Systems,Sandtorstr. 1, 39106 Magdeburg, Germany; Otto-von-Guericke-University,Magdeburg, Germany

Oscar Reif Sartorius AG, D-37075 Goettingen, Germany

Kunert Renate Department of Biotechnology, University of Natural Resourcesand Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria

Werner Reutter Institute of Clinical Chemistry and Pathobiochemistry, CharitéPlatz 1, 10117 Berlin, Germany

Troy Richards Wyeth BioPharma, Andover, MA, USA; Vaccinex, Rochester,NY, USA

Genova A. Richardson Cell Sciences and Development, SAFC Biosciences,Saint Louis, MO, USA

xlvi Contributors

Daniel Riechers Institut für Technische Chemie, Universität Hannover,Callinstraße 3, 30167 Hannover, Germany

Brita Rippner-Blomqvist Octapharma AB, SE 112 75 Stockholm, Sweden

Stefan Risch Institute of Clinical Chemistry and Pathobiochemistry, Charité Platz1, 10117 Berlin, Germany

S. Ritchie Phenomenome Discoveries Inc., 204-407 Downey Road, Saskatoon,Saskatchewan, S7N 4L8, Canada

Joachim B. Ritter Max Planck Institute for Dynamics of Complex TechnicalSystems, Magdeburg, Sandtorstr. 1, 39106 Magdeburg, Germany,[email protected]

Bastian Rode Leibniz Universität Hannover; Institut für Technische Chemie,D-30167 Hannover, Germany

Ana Paula Rodrigues School of Chemical Engineering, State University ofCampinas - UNICAMP, Campinas, SP, Brazil

S. Roeker Institut für Technische Chemie, Universität Hannover, Callinstraße 3,30167 Hannover, Germany, [email protected]

L. Rojas Center of Molecular Immunology (CIM), P.O. Box 16040, Havana City11600, Cuba

Stefanie Röker Institut für Technische Chemie, Universität Hannover, Callinstr. 3,30167 Hannover, Germany

L. Romagnoli Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy

Thomas Rose ProBioGen AG, Goethestrasse 54, 13086 Berlin, Germany,[email protected]

James S. Ross Cell Sciences and Development, SAFC Biosciences, 2909 LacledeAvenue, Saint Louis, Missouri 63103, USA

Samia Rourou Institut Pasteur de Tunis, Viral vaccines Research andDevelopment Unit, 13, place Pasteur. BP.74, 1002 Tunis, Tunisia

Steve Ruddock Cambridge Antibody Technology, Milstein Building, Granta Park,Cambridge CB21 6GH, UK

M. Rüger Department of Biopharmaceutical Process Science, UpstreamDevelopment, Cell Culture Technology, Boehringer Ingelheim Pharma GmbH &Co. KG, Biberach an der Riss, Germany

T. Ryabicheva State Research Center of Virology and Biotechnology VECTOR,Koltsovo, Novosibirsk region, Russia

Contributors xlvii

Takuya Saito Department of Applied Chemistry and Biotechnology, University ofFukui, 3-9-1 Bunkyo, Fukui, 910-8507, Japan

Eva Sajan Bayer HealthCare, Pharmaceuticals, Global Biological Development,Cell Culture Development, 800 Dwight Way, Berkeley, CA 94710, USA

Patrick Salou BioPharmaceutical Operations (BPO) Manufacturing Huningue,Centre de Biotechnologie, Novartis Pharma S.A.S., 8, rue de l’Industrie, B.P. 355,F-68333 Huningue Cedex, France, [email protected]

Volker Sandig ProBioGen AG, Goethestrasse 54, 13086 Berlin, Germany,[email protected]

E. Sarró Departament d’ Enginyeria Química, Universitat Autònoma deBarcelona, 08193 Bellaterra, Barcelona, Spain

Sónia Sá Santos IBET/ITQB (Instituto de Biologia Experimental eTecnológica/Instituto de Tecnologia Química e Biológica), Oeiras, Portugal

Masahiro Sasaki SEIREN CO., LTD 48-113-2 Yonozu, Mikuni-Cho, Sakai,Fukui, 913-0038, Japan

H. Scheefers ScheBo Biotech AG, Netanyastr. 3, 35394 Gießen, Germany

Thomas Scheper Leibniz Universität Hannover, Institut für Technische Chemie,Callinstraße 3, D-30167 Hannover, Germany, [email protected]

Gudrun Schiedner CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany, [email protected]

Horst Schirrmeier Institute of Diagnostic Virology, Friedrich-Loeffler-Institutes,Federal Research Centre for Virus Diseases of Animals, Boddenblick 5a, 17493Greifswald-Insel Riems, Germany

Stefan Schlatter Department of Biopharmaceutical Process Science, UpstreamDevelopment, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an derRiss, Germany

M. Schmidhuber Technical University of Munich, Arcisstr. 21, D-80333 Munich,Germany, [email protected]

Erik Schneider Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429Bergisch Gladbach, Germany

Bernd Schröder Miltenyi Biotec GmbH, Teterow, Germany,[email protected]

J.E. Schouwenberg Netherlands Vaccine Institute (NVI), Bilthoven, TheNetherlands

Carola Schröder OCTAGENE GmbH, Am Klopferspitz 19, 82152 Martinsried,Germany, [email protected]; www.octagene.com

xlviii Contributors

Klaus R. Schröder Phenion GmbH & Co. KG, Düsseldorf, Germany

H. Schubert Department of Ceramic Materials, Technische Universitaet Berlin,Germany

Torsten W. Schulz Department of Biopharmaceutical Process Science, UpstreamDevelopment, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an derRiss, Germany, [email protected]

Mareike Schulze Max Planck Institute for Dynamics of Complex TechnicalSystems, Sandtorstr. 1, 39106 Magdeburg, Germany,[email protected]

Josef Schulze-Horsel Max Planck Institute for Dynamics of Complex TechnicalSystems, Sandtorstr. 1, 39106 Magdeburg, Germany,[email protected]

J. Schwarzer Max Planck Institute for Dynamics of Complex Technical Systems,Sandtorstrasse 1, 39106 Magdeburg, Germany, [email protected]

U. Schygulla Institute for Micro Process Engineering IMVT, Research CenterKarlsruhe, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen,Germany

De Boel Sébastien Laboratoire de Biochimie Cellulaire, Croix du sud 5/3, Institutdes Sciences de la vie, Université catholique de Louvain, B-1348,Louvain-la-Neuve, Belgium

R. Seger Division of Immunology/Hematology, University-Children′s Hospital,Zurich, Switzerland

Friederike Sempf Institut für Technische Chemie, Universität Hannover,Callinstraße 3, 30167 Hannover, Germany

T. Sen’kina State Research Center of Virology and Biotechnology VECTOR,Koltsovo, Novosibirsk region, Russia

D. Sergeant Awardee of a Walloon Region “Bourse de préactivité”, Mons,Belgium

Jing Shi Process Cell Culture, Development, MedImmune Inc., One MedImmuneWay, Gaithersburg, MD 20878, USA

Hideyuki Shigemori Graduate School of Life and Environmental Sciences,University of Tsukuba, Japan

Hiroshi Shinmoto National Food Research Institute (NFRI), 2-1-12 Kannondai,Tsukuba Ibaraki 305-8642, Japan

Sanetaka Shirahata Department of Genetic Resources Technology, Faculty ofAgriculture, Kyushu University, Fukuoka, Japan

Contributors xlix

Y. Sidorenko Otto-von-Guericke-Universität Magdeburg, Lehrstuhl fürBioprozeßtechnik, Universitätsplatz 2, 39106 Magdeburg, Germany

U. Siler Division of Immunology/Hematology, University-Children’s Hospital,Zurich, Switzerland

Marcelo S. de Brito e Silva School of Veterinary, Federal University of Goiás,Goiânia, SP, Brazil

Martin S. Sinacore Wyeth BioPharma, Andover, MA, USA

S. Siwiora-Brenke Institute of Cell Culture Technology, University of Bielefeld,Bielefeld, Germany

Anna Sjöblom-Hallén Biovitrum, Biopharmaceutical Process Development,Process Sciences, Stockholm and Göteborg, Sweden

Gregory Van Slyke Invitrogen Corporation, 3175 Staley Road, Grand Island,New York 14072, USA

Mark Smales Protein Science Group, Department of Biosciences, University ofKent, Canterbury, Kent, CT2 7NJ, UK

Ashley Smith Cell Sciences and Development, SAFC Biosciences, 2909 LacledeAvenue, Saint Louis, Missouri 63103, USA

Shawn R. Smith Sheffield Pharma Ingredients, Division of Kerry Bio-Science,158 State Highway 320, Norwich, NY 13815, USA

Peter Söhlemann Octagene GmbH, Am Klopferspitz 19, 82152 Martinsried,Germany, [email protected]

A. Soley Departament d’ Enginyeria Química, Universitat Autònoma deBarcelona, 08193 Bellaterra, Barcelona, Spain

M.F.Q. Sousa ITQB/IBET, Apt. 12, 2781 Oeiras, Portugal

Rachel Specht Department of Chemical Engineering, Colorado State University,Fort Collins, CO, USA

N. Agathos Spiros Laboratoire de Génie Biologique, Croix du sud 2/19, Institutdes Sciences de la vie, Université catholique de Louvain, B-1348,Louvain-la-Neuve, Belgium

Frank Stahl Leibniz Universität Hannover; Institut für Technische Chemie,D-30167 Hannover, Germany

Yvonne Stark Leibniz Universität Hannover; Institut für Technische Chemie,D-30167 Hannover, Germany, [email protected]

S. Stein Georg-Speyer-Haus, Frankfurt, Germany

Willibald Steinfellner Department of Biotechnology, University of NaturalResources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria

l Contributors

Dirk Steinhäuser Linde-KCA-Dresden GmbH, Dresden, Germany,[email protected]

Matthieu Stettler École Polytechnique Fédérale de Lausanne, Faculty of LifeSciences, 1015 Lausanne, Switzerland

Fabrice Stock Polyplus-Transfection S.A., Bioparc, Boulevard Sébastien Brant,BP 90018, 67401 Illkirch, France

Thibaud Stoll Global BPO, Novartis Pharma AG, Basel

Scott D. Storms Irvine Scientific, Santa Ana, CA, USA

E. Suárez Center of Molecular Inmunology, Havana, Cuba

Genadii Suchich Russian Academy of Medical Sciences, Moscow

Erik Svensson Biovitrum, Biopharmaceutical Process Development, SE-112 76,Stockholm, Sweden

Ingrid Svensson AstraZeneca BioProcess R&D, S-151 85 Södertälje, Sweden

Halina Swiderek School of Chemical and Bioprocess Engineering and Centre forSynthesis and Chemical Biology (CSCB), University College Dublin, Belfield,Dublin 4, Ireland, [email protected]

Toshiya Takeda Department of Materials and Life Sciences, Kanto GakuinUniversity, 1-50-1 Mutsuurahigashi, Kanazawa, Yokohama 236-8501, Japan

Satoshi Takeshita Department of Applied Chemistry and Biotechnology,University of Fukui, 3-9-1 Bunkyo, Fukui, 910-8507, Japan

Yusuke Tanii The Cell Engineering Center, Kitakyushu National College ofTechnology, 5-20-1 Shii, Kokuraminami-ku, Kitakyushu 802-0985, Japan

Rudolf Tauber Institute of Clinical Chemistry and Pathobiochemistry, CharitéPlatz 1, 10117 Berlin, Germany

Ana P. Teixeira IBET/ITQB (Instituto de Biologia Experimental eTecnológica/Instituto de Tecnologia Química e Biológica), Oeiras, Portugal;FCT/UNL (Faculdade de Ciências e Tecnologia/Universidade Nova Lisboa),Monte da Caparica, Portugal

Tatiana Tennikova Institute of Macromolecular Compounds, Russian Academyof Sciences, Bolshoi pr. 31, 199004 St. Petersburg, Russia, [email protected]

Satoshi Terada Department of Applied Chemistry and Biotechnology, Universityof Fukui, 3-9-1 Bunkyo, Fukui, 910-8507, Japan

Laetitia Tercier Merck Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland

Kiichiro Teruya Department of Genetic Resources Technology, Faculty ofAgriculture, Kyushu University, Fukuoka, Japan

Contributors li

Jessica Thiems Octapharma Biopharmaceuticals GmbH, Am Klopferspitz 19/19a,82152 Martinsried, Germany

Yvonne E. Thomassen Netherlands Vaccine Institute (NVI), ProcessDevelopment department, P.O. Box 457, 3720 AL Bilthoven, The Netherlands

Stéphanie Tissot Laboratory of Cellular Biotechnology, École PolytechniqueFédérale de Lausanne, CH-1015 Lausanne, Switzerland

Kosuke Tomimatsu Department of Genetic Resources Technology, Faculty ofAgriculture, Kyushu University, Fukuoka, Japan

Sascha Tonevitzky Russian Academy of Science, Moscow

Khaled Trabelsi Viral Vaccines Research and Development Unit, Institut Pasteurde Tunis, 13, place Pasteur, BP.74, 1002 Tunis, Tunisia

S. Trasciatti Areta International S.r.l., Via R. Lepetit 34, 21040 Gerenzano, VA,Italy

T. Tröbs Department of Biopharmaceutical Process Science, UpstreamDevelopment, Cell Culture Technology, Boehringer Ingelheim Pharma GmbH &Co. KG, Biberach an der Riss, Germany

N.Vachiery CIRAD-EMVT, Domaine de Duclos, Petit-Bourg, Guadeloupe

R. Vanderesse Laboratoire de Chimie Physique Macromoléculaire, UMR 7568,CNRS-INPL, Nancy-Université, Nancy, France

S. Vanhamel ATMI LifeSciences, Hoegaarden, Belgium

Jeroen van der Velden Phytovation B.V., Wassenaarseweg 72, 2333 AL Leiden,The Netherlands

T. Van der Velden-de Groot Netherlands Vaccine Institute (NVI), Bilthoven, TheNetherlands

N. Varaksin State Research Center of Virology and Biotechnology VECTOR,Koltsovo, Novosibirsk region, Russia

Raghavan Venkat Process Cell Culture, Development, MedImmune Inc., OneMedImmune Way, Gaithersburg, MD 20878, USA

D. Vester Otto-von-Guericke-University Magdeburg, Bioprocess Engineering,Univeristätsplatz 2, 39106 Magdeburg, Germany, [email protected]

S. Victores Center of Molecular Immunology (CIM), P.O. Box 16040, HavanaCity 11600, Cuba, [email protected]

L. Vidal Grup d’Enginyeria Cellular i Tissular, Departament d’EnginyeriaQuímica, Universitat Autònoma de Bacelona, 08193 Bellaterra, Barcelona, Spain

A. Vilesov ZAO DELSI, St. Petersburg, Russia

lii Contributors

E. Vlakh Institute of Macromolecular Compounds, Russian Academy ofSciences, Bolshoi pr. 31, 199004 St. Petersburg, Russia, [email protected]

Damien Voisard Merck Serono S.A., Z.I.B, 1809 Fenil-sur-Corsier, Switzerland

Christoph Volpers CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany

Robert Voyer Institut de Recherche en Biotechnologie, CNRC, 6100 AvenueRoyalmount, Montréal, Québec H4P 2R2, Canada

Walter de Vries Academic Medical Center of the University of Amsterdam,Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands

Roland Wagner Miltenyi Biotec GmbH, Teterow, Germany

A. Wahl MPI for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106Magdeburg, Germany, [email protected]

Gero Waschütza CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany

Jun-ya Watanabe Department of Biosciences, Teikyo University of Science andTechnology, 2525 Uenohara, Yamanashi 409-0193, Japan

Christian Weber Institute of Biopharmaceutical Technology, Universityof Applied Sciences Giessen-Friedberg, Giessen, Germany

Wilfried Weber Institute for Chemical and Bioengineering, ETH Zurich, 8093Zurich, Switzerland, [email protected]

Anke Wellmann Charité Universitätsmedizin, Berlin, Germany; ProBioGen AG,Berlin, Germany

Jeannette Westin Biovitrum, Biopharmaceutical Process Development, ProcessSciences, Stockholm and Göteborg, Sweden

W.G. Whitford Thermo Fisher Scientific, Logan, UT, USA

S. Ranil Wickramasinghe Department of Chemical Engineering, Colorado StateUniversity, Fort Collins, CO, USA

Katharina Wiegandt Hamburg University of Technology, Institute of Bioprocessand Biosystems Engineering, Denickestr. 15, D-21071 Hamburg, Germany

C. Wiendahl Institute of Biotechnology 2, Research Center Juelich GmbH,Leo-Brandt-Str. 20, 52425 Juelich, Germany

J. Wiest Technical University of Munich, Arcisstr. 21, D-80333 Munich, Germany

Steinfellner Willibald Department of Biotechnology, University of NaturalResources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria

Cecilia Wingenblixt Octapharma AB, SE-11275 Stockholm, Sweden

Contributors liii

Marc Wingens Institute of Cell Culture Technology, University of Bielefeld,Universitätsstr. 25, 33615 Bielefeld, Germany, [email protected]

Karsten Winkler ProBioGen AG, Berlin, Germany

Anne Wolf Institute of Biopharmaceutical Technology, University of AppliedSciences, Wiesenstrasse 14, 35390 Giessen, Germany

B. Wolf Technical University of Munich, Arcisstr. 21, D-80333 Munich, Germany

Danny C.F. Wong Bioprocessing Technology Institute, Agency for Science andTechnology Research (A∗STAR), 20 Biopolis Way, #06-01, Centros, 138668,Singapore

Xue Wu Bayer HealthCare, Pharmaceuticals, Global Biological Development,Expression Technology, Berkeley, CA 94710, USA

Sarah Wulhfard Laboratory of Cellular Biotechnology, École PolytechniqueFédérale de Lausanne, CH-1015 Lausanne, Switzerland, [email protected]

M. Wunder Department of Biopharmaceutical Process Science, UpstreamDevelopment, Cell Culture Technology, Boehringer Ingelheim Pharma GmbH& Co. KG, Biberach an der Riss, Germany

Florian M. Wurm École Polytechnique Fédérale de Lausanne, Faculty of LifeSciences, 1015 Lausanne, Switzerland; ExcellGene SA, 1870 Monthey,Switzerland, [email protected]

Hideyuki Yamada SEIREN CO., LTD 48-113-2 Yonozu, Mikuni-Cho, Sakai,Fukui, 913-0038, Japan

Makiko Yamashita Department of Genetic Resources Technology, Faculty ofAgriculture, Kyushu University, Fukuoka, Japan

Shinya Yamaguchi Marukin Bio Inc., 27 Monnomae, Todo, Uji, Kyoto 611-0013,Japan

Glenn Yamasaki Bayer HealthCare, Pharmaceuticals, Global BiologicalDevelopment, Expression Technology, Berkeley, CA 94710, USA

Kana Yanagihara Department of Applied Chemistry and Biotechnology,University of Fukui, 3-9-1 Bunkyo, Fukui, 910-8507, Japan,[email protected]

Jianguo Yang Process Cell Culture, Development, MedImmune Inc., OneMedImmune Way, Gaithersburg, MD 20878, USA, [email protected]

Miranda G.S. Yap Bioprocessing Technology Institute, Agency for Science andTechnology Research (A∗STAR), 20 Biopolis Way, #06-01, Centros, 138668,Singapore

liv Contributors

Yeup Yoon Mogam Biotechnology Research Institute, 341 Bojeong-Ri,Giheung-Gu, Yongin, Gyonggi-Do 446-799, Republic of Korea,[email protected]

R. Young Lonza Biologics plc, Cell Culture Process Development, 228 BathRoad, Slough, Berkshire SL1 4DX, UK

Schneider Yves-Jacques Laboratoire de Biochimie Cellulaire, Croix du sud 5/3,Institut des Sciences de la vie, Université catholique de Louvain, B-1348,Louvain-la-Neuve, Belgium, [email protected]

Chun Zhang Bayer Healthcare, Biological Products Division, 800 Dwight Way,Berkeley, CA 94710, USA

Lin Zhang Pfizer Global Research & Development, St. Louis Laboratories, PfizerInc, St. Louis, MO 63017, USA

Min Zhang Cell Sciences and Development, SAFC Biosciences, 2909 LacledeAvenue, Saint Louis, Missouri 63103, USA

Xiaowei Zhang École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

YingPing Zhang Pfizer Global Research & Development, St. Louis Laboratories,Pfizer Inc, St. Louis, MO 63017, USA

S. Zietze ProBioGen AG, Berlin, Germany

G.M. Zijlstra DSM Biologics, P.O. Box 454, 9700 AL Groningen, TheNetherlands, [email protected]

Nadja N. Zöller Department of Dermatology and Venerology, UniversityHospital, Frankfurt/Main, Germany

Kerstin Zörner Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429Bergisch Gladbach, Germany