ESACT Proceedings

Volume 5

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

Nigel Jenkins · Niall Barron · Paula M. AlvesEditors

Proceedings of the 21stAnnual Meeting of theEuropean Society for AnimalCell Technology (ESACT),Dublin, Ireland, June 7–10,2009

123

EditorsProf. Nigel JenkinsNational Institute of Bioprocessing

Research & TrainingUniversity College DublinEngineering Building, BelfieldDublinIrelandnigel.jenkins@nibrt.ie

Niall BarronDublin City UniversityNational Institute for Cellular

BiotechnologyDublinIrelandniall.barron@dcu.ie

Dr. Paula M. AlvesInstituto de Biologia Experimental

e Tecnológica (IBET)ITQBOeirasPortugalmarques@itqb.unl.pt

ISBN 978-94-007-0883-9 e-ISBN 978-94-007-0884-6DOI 10.1007/978-94-007-0884-6Springer Dordrecht Heidelberg London New York

Library of Congress Control Number: 2011933343

© Springer Science+Business Media B.V. 2012No 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)

Introduction

The 21st ESACT conference was held in the beautiful surroundings of the CityWestHotel resort in Dublin, Ireland. For the first time in ESACT history the number ofparticipants exceeded 900: a sign of the ever increasing importance of this area. Theconference commenced on Sunday June 5th with two sets of parallel workshops onthe subjects listed below. An additional workshop was held on Monday lunchtimeof the conference.

1. Process Analytical Technology (PAT), Quality by Design (QbD) and other recentregulatory developments.

2. Innovative media products for the twenty-first century biopharmaceuticalindustry.

3. The impact of high titre media feed-streams on monoclonal antibodypurification.

4. Advances in genomics and proteomics.5. Stem Cell Technology: new developments and clinical applications.

The first scientific session on Sunday evening included talks on the on-goingefforts to gain better understanding of and ways of improving the cell ‘factories’that are used to synthesize the ‘magic bullets’ that are modern day recombinant pro-tein therapeutics. Not that long ago, 1 g/L was considered the holy grail in termsof suspension culture of animal cell systems, yet yields of 10 times that level areachievable nowadays. Despite these gains, researchers in the field strive to fur-ther improve on these production platforms by shifting the focus from media andhardware optimization to the molecular mechanisms influencing cell behaviour andproductivity in the bioreactor. To this end, methods of applying synthetic biologyto explore more novel ways of modifying and utilizing nucleic acid sequence inorder to influence protein production or function were presented. In addition, greaterinsights into the exquisite complexity of the control mechanisms within mammaliancells were given in talks focused on temporal expression of mRNA, protein andmicroRNAs. The consensus view was that it is likely that the next significant gains

v

vi Introduction

in manipulating cell behaviour and phenotypes may come via engineering of entirenetworks rather than individual genes.

Sessions 2 and 3 focused on the burgeoning field of stem cells and tissue engi-neering. From its humble beginnings in egg-based vaccine production, Animal CellTechnology (ACT) has now progressed to such a point that the practical consid-erations of producing large volumes of cGMP cell therapies are now a reality.A diverse and accomplished panel of speakers described their work on all stages ofbringing stem cell therapies from discovery though manufacturing to the potentiallylife-altering or even life-saving applications in the clinic. Large scale productionof stem cells brings its own particular sets of challenges including: maintaining thepluri- or multi-potent state, controlled large scale differentiation, and ensuring prod-uct quality. Examples were presented of how some of these cell-based interventionsare already proving effective in both animal models and some of the first humantrials – a wonderful prospect indeed.

On Tuesday June 9th the day started with a session on Animal CellBioprocessing. Eli Lilly & Co. described how a new biotherapeutics facility is underconstruction near Cork, Ireland alongside an existing chemical pharmaceuticalplant. Similar developments are occurring at Pfizer near Cork and together bio-therapeutics, chemical therapeutics and medical devices account for almost half ofIreland’s exports. Other speakers in this session, which was sponsored by Ireland’sNational Institute for Bioprocessing Research & Training (NIBRT), covered topicssuch as using disposable bioreactors at the medium to large scale, and scaled downsystems for high throughput screens of media components and environmental con-ditions. The keynote speaker at the end of this session discussed the developmentof biogeneric drugs (i.e. follow-on biotherapeutics) that are set to increase marketshare as the older molecules such as erythropoietin (EPO) come off patent.

Tuesday afternoon also saw the first of two poster sessions, the other being onWednesday morning. Approximately 300 posters were displayed throughout theconference and prizes for best posters were awarded at the Gala Dinner on theevening of Wednesday June 10th. The final session on Tuesday focused on bio-therapeutics, i.e. what types of molecule are under development and how can thesebe modified for greater potency, safety or half-life?

Linking this session with a Wednesday session on recent developments in vac-cines and virology was a keynote talk on the immunogenicity of proteins. Vaccinesneed to be immunogenic to provoke protective humoral and cell-based responsesin humans or animals. However, for non-vaccine biotherapeutics the host immuneresponse must be minimized to avoid raising neutralizing antibodies that may com-promise the drug’s efficacy. Other topics in the vaccine & virology session includedimproving influenza virus production, and using the heat shock response to improvethe efficiency of host cell line virus production.

This volume contains much of the excellent data presented and discussed at the21st ESACT meeting.

Contents

Part I Synthetic and Molecular Biology

MicroRNAs as Potential Engineering Targets for Improvementof CHO Cell Production Phenotypes . . . . . . . . . . . . . . . . . . . . 3Niall Barron, Niraj Kumar, Noelia Sanchez, Patrick Gammell,and Martin Clynes

Are Clones Really Unstable? . . . . . . . . . . . . . . . . . . . . . . . . 13Kriti Shukla, Saravanan Desan, Ankur Bhatnagar, and Anuj Goel

An Optimised Transfection Platform for the Epi-CHO TransientExpression System in Serum-free Media . . . . . . . . . . . . . . . . . . 19Joe Codamo, Trent P. Munro, Benjamin S. Hughes, Michael Song,and Peter P. Gray

Using the “OMICS” Technologies as Complementary Tools toStudy the Molecular Mechanisms Involved with the Adaptationof Myeloma Cell Line to Protein-Free Medium . . . . . . . . . . . . . . 25K.R. de la Luz-Hernández, Y. Rabasa-Legón, A. Lage-Castellanos,A. Castillo-Vitlloch, L. Castellanos-Serra, J. Díaz-Brito, and S. Gaskell

Galectin-3 Over-Expression Enhances Survival andRecombinant Protein Expression in Mammalian Cells . . . . . . . . . . 31Fanny Delegrange, Mattia Matasci, Lucia Baldi, and Florian M. Wurm

Metabolomic Analysis of CHO Cultures with Different GrowthCharacteristics – Development of a Metabolite ExtractionProtocol for Suspension Adapted Mammalian Cells . . . . . . . . . . . 37Stefanie Dietmair, Nicholas E. Timmins,Panagiotis Chrysanthopoulos, Peter P. Gray, Jens O. Krömer,and Lars K. Nielsen

Cell Lines in Four Weeks with the CEMAX R© System . . . . . . . . . . 43Benedikt Greulich, Karlheinz Landauer, and Andreas Herrmann

vii

viii Contents

Analysis of Protein Expression via Alternate 3’ UntranslatedRegion (UTR) Signals Through the Use of Site Specific Recombination . 47Jeff Jia Cheng Hou, Michael Song, Trent P. Munro, and Peter P. Gray

A Case Study in Clone Screening: A Comprehensive Approachfor a Product With High Projected Market Demand . . . . . . . . . . . 53Kirin M. Jamison, Dacia R. Brooks, Szu-Han Wang, and Martin Gawlitzek

An Improved Clone Selection Method . . . . . . . . . . . . . . . . . . . 57Uros Jamnikar, Marjanca Blas, Dominik Gaser,Jerica Rozman-Pungercar, and Andrej Francky

Dissecting the Mechanism of Action of BHRF1 for theProtection Against Apoptosis in MAb-Producing Cell Lines . . . . . . . 61Ernest Milián, Sandra Juanola, Eva Prats, Jordi J. Cairó,Francesc Gòdia, and Joaquim Vives

Qualification of Bench and Pilot-Scale Bioreactors as Modelsof Commercial Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . 67Anne Marie Molloy, Patrick Dowling, Mairead Looby, CaitrionaCrawford, Bruce Tangarone, Mary Heenan, and Enda Moran

Quantification of Polyethylenimine in Transient GeneExpression: On the Way to GMP Compliance . . . . . . . . . . . . . . . 71Sophie Nallet, Zuzana Kadlecova, Lucia Baldi, Harm-Anton Klok,and Florian M. Wurm

Implications of Vector Fragmentation and Initial ProductionLevels in Production Cell Line Development Using MTX . . . . . . . . 77Say Kong Ng, Wenyu Lin, Rohit Sachdeva, Daniel I.C. Wang,and Miranda G.S. Yap

Characterizing the Expression Stability in Different Phenotypesof Recombinant NS0 Myeloma Cell Lines . . . . . . . . . . . . . . . . . 85Y. Prieto, L. Rojas, L. Hinojosa, K.R. de la Luz-Hernández,D. Aguiar, S. Victores, E. Faife, R. Pérez, and A.J. Castillo

A Transient Gene Expression Process with RecombinantAntibody Titer of 0.5 g/L in CHO Cells . . . . . . . . . . . . . . . . . . 91Yashas Rajendra, Gaurav Backliwal, Markus Hildinger,Sarah Wulhfard, Maria deJesus, and Florian M. Wurm

Proteomic Profiling of Temperature-Shifted CHO Cellsto Identify Genes that Impact on Both Cell Growth andRecombinant Protein Productivity in Suspension Culture . . . . . . . . 95Niraj Kumar, Noelia Sanchez, Patrick Gammell, Patrick Dowling,M. Henry, P. Meleady, Niall Barron, and Martin Clynes

Contents ix

Stabilization of Protein Expression in Mammalian CellsEmploying a Toxin/Antitoxin Based Strategy . . . . . . . . . . . . . . . 109Kristina Nehlsen, Jeannette Zauers, Sabrina Herrmann,Hansjörg Hauser, and Dagmar Wirth

Novel Cell Lines For Bioprocessing: Friend or Foe? . . . . . . . . . . . 115Paula Ravnikar, Xiaoguang (Margaret) Liu, Jian Liu,Tasha Williams-Wright, and Florence Wu

Transgene mRNA Levels and Stability are Key Factorsto Enhance Transient Gene Expression in CHO DG44 Cells . . . . . . . 121Sarah Wulhfard, Divor Kiseljak, Lucia Baldi, David L. Hacker,and Florian M. Wurm

High Cell Density Transient Gene Expression in HEK 293 EBNA Cells 125Divor Kiseljak, Gaurav Backliwal, David L. Hacker, Lucia Baldi,and Florian M. Wurm

Generation of High-Producing CHO Cell Lines by PiggybacTransposition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129Mattia Matasci, Virginie Bachmann, Fanny Delegrange,Sebastien Chenuet, David L. Hacker, and Florian M. Wurm

Cellular Proteins in Conditioned Medium InhibitPolyethylenimine-Mediated Transfection of CHO Cells . . . . . . . . . 135Ralph Duhr, Divor Kiseljak, Yashas Rajendra, Lucia Baldi,David L. Hacker, and Florian M. Wurm

A New Variant of the Affinity Matrix Method for Identificationof High Producing Cells in Mammalian Cell Culture . . . . . . . . . . . 139Daniel Landgrebe, Larissa Behr, Pierre Moretti, Johanna Walter,Frank Stahl, Cornelia Kasper, and Thomas Scheper

Novel Strategies for Improving Cell Viability and Production Yield . . . 143Hisahiro Tabuchi, Tomoya Sugiyama, and Satoshi Tainaka

Part II Stem Cells

Regulating in Vitro Motility of Human Mesenchymal StemCells with Macrophage Migration Inhibitory Factor (MIF)and a Small-Molecule MIF Antagonist . . . . . . . . . . . . . . . . . . . 149Kim C. O’Connor, Bonnie L. Barrilleaux, Donald G. Phinney,Benjamin W. Fischer-Valuck, Katie C. Russell, and Darwin J. Prockop

Impact of Growth Factors on the Proliferation of EarMesenchymal Stem Cells on Porous Microcarriers . . . . . . . . . . . . 161Sébastien Sart, Yves-Jacques Schneider, and Spiros N. Agathos

Strategies for Pancreatic Differentiation of Pluripotent Stem Cells . . . 177Insa S. Schroeder, Anna Daniel-Wojcik, and Anna M. Wobus

x Contents

Stem Cell Biology: New Applications for Studying Metabolic Diseases . 189Malte Sgodda, Reto Eggenschwiler, and Tobias Cantz

Monitoring of Long-Term Cultivation and OsteogenicDifferentiation of Human Umbilical Cord-DerivedMesenchymal Stem Cell-Like Cultures . . . . . . . . . . . . . . . . . . . 205P. Moretti, T. Hatlapatka, Magda Tomala, I. Majore, R. Hass,Thomas Scheper, and C. Kasper

cGMP-Compliant Isolation, Expansion and Quality Testingof Human Bone Marrow-Derived Mesenchymal Stem Cells . . . . . . . 209Luca Romagnoli, Ilaria Giuntini, Marta Galgano, Chiara Crosta,Enrico Lucarelli, Davide Donati, Luigi Cavenaghi, and Maria Luisa Nolli

Cancer Research, Molecular and Cell Biology: Look atthe Nanotechnology, Based Nanoparticles for Diagnostics,and Therapy. Stem Cell for Treatment of Cancer Diseases . . . . . . . . 213Katya Marinova Simeonova

A Comparative Study of Suspension Cultivation Systems for theExpansion of Undifferentiated Mouse Embryonic Stem Cells . . . . . . 219Magda Tomala, Sabrina Schmeckebier, Ruth Olmer, Pierre Moretti,Frank Stahl, Ulrich Martin, Thomas Scheper, and Cornelia Kasper

Part III Tissue Engineering

Human Endothelial Cell Lines with In Vivo Physiology . . . . . . . . . 225Tobias May, Milada Butueva, Sara Bantner, Herbert Weich,Hansjörg Hauser, and Dagmar Wirth

Quality Control and Cell Line Cross-Contamination: An OldProblem that Continues To Fester . . . . . . . . . . . . . . . . . . . . . 235John R. Masters

Functional Characterisation of Human Hepatoma Cell LineHepG2 in 3D Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241Christiane Goepfert, Wibke Scheurer, Susanne Rohn,Britta Rathjen, Hans Hoffmeister, and Ralf Pörtner

GFP-Expressing Bladder Fibroblasts for Applications in TissueEngineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247Eva-Maria Engelhardt, Agata Oberbek, Mattia Matasci,David L. Hacker, Myriam Adam, and Florian M. Wurm

3-Dimensional, Dynamic Cultivations of Human UmbilicalCord-Derived Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251Dana Maria Marten, Stefanie Röker, Stefanie Böhm,Hans Hoffmeister, and Cornelia Kasper

Contents xi

NIH/3T3 Feeder System to Engineer Corneal Epithelial Sheetswith Enhanced Positive Progenitor Populations . . . . . . . . . . . . . . 257Kishore Katiki Reddy, Martin Clynes, William Power,Andra Bobart, and Finbarr O’Sullivan

NF-κB Signalling Pathway: Generation and Characterizationof a Reporter Cell Line of Human Origin . . . . . . . . . . . . . . . . . 261Inés Tiscornia, Pablo Espósito, Valentina Porro, Paola Hernández,Hugo Cerecetto, Mercedes González, Eliezer Barreiro,and Mariela Bollati-Fogolín

Establishing Mammalian Production Cell Lines for StructuralBiology by Site-Specific Recombination . . . . . . . . . . . . . . . . . . 265Sonja Wilke, Sarah Tokarski, Volker Jäger, Joop van den Heuvel,Manfred Gossen, Ermanno Gherardi, and Konrad Büssow

Part IV Advances in Bioprocessing A

Regulation of Transferrin Receptor and IGF-I ReceptorNumbers at the Cell Surface Drives Growth and Productivityof Hybridoma Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271Andrew J. Sakko, Kenneth C. Bertram, Sally Grosvenor, ColletteSheahan, Danny Voorhamme, Anthony Simula, and Geoffrey L. Francis

Towards Enhancing Manufacturing Process PerformanceThrough Multivariate Data Mining . . . . . . . . . . . . . . . . . . . . 285Salim Charaniya, Huong Le, Keri Mills, Kevin Johnson,George Karypis, and Wei-Shou Hu

Partial Replacement of Chemically Defined CHO Mediawith Plant-Derived Protein Hydrolysates . . . . . . . . . . . . . . . . . 295James F. Babcock and Amy Antosh

An Insight into the Physiology of Insect Cells: The Roleof Energetic Metabolism on the Cell Density Effect . . . . . . . . . . . . 299Vicente Bernal, Nuno Carinhas, Francisca Monteiro,Raquel Ambrósio, Manuel J.T. Carrondo, and Paula M. Alves

Design and Development of a High-Throughput Platform forRapid Microbe Identification and Automatic Data Management . . . . 307Björn Breth

On-line Monitoring of the Live Cell Concentration in DisposableBioreactors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315J.P. Carvell, J. Williams, M. Lee, and D. Logan

The Challenge of Validating a Viable Biomass Probefor cGMP Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319J.P. Carvell, J. Williams, S. Taylor, M. Lee, and R.W. Todd

xii Contents

Study of the Effect of High pH and Alkali Addition in aCultivation of Chinese Hamster Ovary Cell . . . . . . . . . . . . . . . . 323Véronique Chotteau and Anna Lindqvist

Tuning of Dissolved Oxygen and pH PID Control Parametersin Large Scale Bioreactor by Lag Control . . . . . . . . . . . . . . . . . 327Véronique Chotteau and Håkan Hjalmarsson

Kinetic Analysis of Recombinant BHK Roller Bottle Cultures . . . . . . 331Frank Deer, Jennifer Mahoney, Abner Correia, and Kevin Stafford

Manipulation of a Perfusion Process by Medium Optimization . . . . . 335Saravanan Desan, Omkar Nandi, Ankur Bhatnagar, and Anuj Goel

Feed Flow Pulsation in the Separation of CHO Cells inHydrocyclones: Effects of Pressure Drop and Pumphead Typeon Separation Efficiency and Cell Viability . . . . . . . . . . . . . . . . 341Elsayed A. Elsayed, Leonardo A.G. Ramalho, Leda R. Castilho,and Ricardo A. Medronho

Development of a Biphasic Culture Process for RecombinantProtein Production in Human CAP Cells . . . . . . . . . . . . . . . . . 345Ruth Essers, Helmut Kewes, and Gudrun Schiedner

Crossed Mixture Design and Artificial Neural Networks:An Efficient Approach to Cell Culture Medium Optimization . . . . . . 351Guillermina Forno, Caroline Didier, Marina Etcheverrigaray,Héctor Goicoechea, and Ricardo Kratje

Improving Cell Culture Bioreactor Performance for SensitiveCell Lines by Dynamic Membrane Aeration (DMA) . . . . . . . . . . . 355B. Frahm and H. Brod

Evaluation of Disposable Bioreactor Design Comparedto Reusable Stainless Steel Reactors . . . . . . . . . . . . . . . . . . . . 359Gerhard Greller and Ute Noack

Utilising Scale Model Systems to Optimise Upstream ProcessDevelopment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363Sally Grosvenor, Larissa Chirkova, Tatyana Mitina,Danny Voorhamme, Quang Doan, and Kenneth C. Bertram

Human Platelet Lysates as a Serum Substitute in Cell Culture Media . 369Caroline Rauch, Elisabeth Feifel, Hans Peter Spötl,Eva-Maria Amann, Harald Schennach, Harald Schöffl,Walter Pfaller, and Gerhard Gstraunthaler

4 g/L.day: Monoclonal Antibody Volumetric Productivityin the iCELLisTM Disposable Fixed-Bed Bioreactor . . . . . . . . . . . 375Jean-Christophe Drugmand, Nicolas Havelange,Florence Collignon, José Castillo, and P.-A. Girod

Contents xiii

Optimisation of Cell Growth and Recombinant ProteinProduction in Small-Scale Culture Vessels by Using OpticalSensors for On-line Measurement of Dissolved Oxygen . . . . . . . . . 379Volker Jäger, Giannini Apati, and Nadine Konisch

A Protocol for Cell Detachment of Vero Cells Grown UnderFully Animal Component Free Conditions and on Cytodex 1Microcarriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383Samia Rourou, Nesrine Riahi, and Héla Kallel

Simulation and Optimization of Essential Amino Acidsin Dynamic Mammalian Cell Culture . . . . . . . . . . . . . . . . . . . 387Carolyn M.C. Lam, Alexandros Kiparissides, Danny C.F. Wong,Miranda G.S. Yap, Efstratios N. Pistikopoulos, and Athanasios Mantalaris

Biomass Sensors in iCELLisTM Fixed-Bed Reactors: Dataon CHO and Vero Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . 391Jean-Christophe Drugmand, Florence Collignon,Stéphanie Dubois, Nicolas Havelange, and José Castillo

On-line Monitoring: Animal Cell Cultivation in iCELLisTM

Fixed-Bed Reactor Using Dielectric Measurements . . . . . . . . . . . . 395Jean-Christophe Drugmand, Geoffrey Esteban, Naima Alaoui,Nadia Jafâr, Nicolas Havelange, Olivier Berteau, and José Castillo

Change of the Role for JAK/STAT3 in IL-6 Response DuringAdaptation of Hybridoma Cells to Serum-Free Media . . . . . . . . . . 401Ken Fukumoto, Masato Tanaka, Tatsuya Yamashita, and Satoshi Terada

Part V Advances in Bioprocessing B

Engineering Principles and Cell Culture Performanceof Orbitally Shaken Cylindrical Bioreactors . . . . . . . . . . . . . . . . 407S. Tissot, X. Zhang, M. Stettler, D. De Sanctis, M. Perone, C. Bürki,M. De Jesus, M. Farhat, M. Discacciati, O.W. Reif, M. Kühner,Lucia Baldi, David L. Hacker, A. Quarteroni, and Florian M. Wurm

Dynamic Ranking of Clones with Process Conditions Usinga High-Throughput Micro-bioreactor Platform . . . . . . . . . . . . . . 413Rachel Legmann, Brian Benoit, Cynthia Deppeler, Erwin Yu,Sriram Srinivasan, Ronald Fedechko, Russell Robins,David Ferrick, Ellen McCormick, Seth Rodgers, and A. Peter Russo

Improved Cell Culture Surface for Biotechnological Research . . . . . . 417Lara Breth

Platform Validation of Dissolved Oxygen Ranges for CellCulture Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421Nathan McKnight, Steven Meier, Srikanth Chary, and Robert Kiss

xiv Contents

Study of Growth Factors in Spent Medium for BetterMammalian Cell Culture . . . . . . . . . . . . . . . . . . . . . . . . . . 425Akiko Ogawa, Sadaharu Fukui, and Satoshi Terada

Process Improvements for Production of a ComplexGlycosylated Fusion Protein which Delivers a Two-Fold Increasein Product Titre and Comparable Product Quality . . . . . . . . . . . . 429Eimear O’Donovan, Patrick Gammell, Mairead Looby,Neysi Ibarra, and Enda Moran

Hydro-Kinetic Modelling of Animal Cell Response to TurbulentMixing in Bioreactors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433E. Olmos, N. Barbouche, F. Fournier, Fabrice Blanchard,E. Guedon, and Annie Marc

Near Infrared Spectroscopy as an In-Situ PAT Tool to MonitorAdherent VERO Cell Culture Processes . . . . . . . . . . . . . . . . . . 437Emma Petiot, Patrick Bernard-Moulin, Cécile Gény,Thierry Magadoux, Hervé Pinton, and Annie Marc

VERO Cell Metabolism in Animal Component-Free Media:Influence of Glucose and Glutamine Substitution . . . . . . . . . . . . . 441Emma Petiot, Cécile Gény, Fabrice Blanchard, Hervé Pinton,and Annie Marc

Metabolic Modeling of Drosophila melanogaster Cells Underthe Balanced Growth Condition . . . . . . . . . . . . . . . . . . . . . . 445R.A.M. Piccoli, F.R.X. Batista, A.M. Moraes,M.F. Barral, M.A. Aguiar, P. Léo, and E.F.P. Augusto

Mass Transfer Considerations for Scale-Up and Scale-Downof Animal Cell Bioprocesses . . . . . . . . . . . . . . . . . . . . . . . . . 451R. Puskeiler, M. Edler, K. Didzus, R. Müller, and J. Gabelsberger

Flow Characterization in Wave Bioreactors UsingComputational Fluid Dynamics . . . . . . . . . . . . . . . . . . . . . . . 455Alper A. Öncül, Yvonne Genzel, Udo Reichl, and Dominique Thévenin

Effects of Soy Peptone-Supplemented Medium on CHO-320 Cells . . . 471Jean-François Michiels, Jérémie Barbau, Sébastien Sart,Spiros N. Agathos, and Yves-Jacques Schneider

Very High Protein Production Levels with a New Transient andSerum-Free Expression System Based on Human CAP Cells . . . . . . 477Corinna Bialek, Sabine Hertel, Nadine Scholz-Neumann,Ruth Essers, and Gudrun Schiedner

Contents xv

Recombinant Albumin as an Animal-Free Supplementto Enhance Cell Culture Performance . . . . . . . . . . . . . . . . . . . 481Collette Sheahan, Marina Ross, Tatyana Mitina, Tom Linke,Tim Robinson, Sally Grosvenor, and Larissa Chirkova

The SimcellTM High-Throughput Cell Culture System: AnAutomated Approach to Integrated Cell Line Selection andProcess Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487Steve R.C. Warr, Yuen-Ting Chim, A. Peter Russo, Brian Benoit,and Mark Uden

Advanced In Situ Microscopy for On-Line Monitoringof Animal Cell Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . 491P. Wiedemann, F. Egner, H. Wiegemann, J.C. Quintana, W. Storhas,J.S. Guez, C. Schwiebert, and H. Suhr

Recombinant Antibody Yield Over 2 g/L by TransientTransfection of HEK 293 EBNA Cells in a Fed-Batch Process . . . . . . 497Divor Kiseljak, Yashas Rajendra, Gaurav Backliwal,David L. Hacker, Lucia Baldi, and Florian M. Wurm

Rapid Fed-Batch Process Development in SimCellTM . . . . . . . . . . 501Zhihua Xiao, Steve Warr, Yuen-Ting Chim, Donald Lee,Erica Wehling, Ekta Goel, David Zhao, and Steve Gorfien

Automation of Cell Line Development Using the OptiCHOExpression System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507Andrea Salmén, Kristina Lindgren, Lovisa Bylund, Gittan Gelius,Christel Fenge, and Ulrica Skoging-Nyberg

Modeling of the Evolution of Cellular Density and NutrientConcentrations in a Fixed-Bed Bioreactor for Its Optimizationand Its Scaling-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511Valérie Gelbgras, Jean-Christophe Drugmand, and Benoît Haut

Multi-parameter Process Optimization Using the SimCellTM System . . 515A. Peter Russo, Brian Benoit, Christian Wood, David Jan,and Sadettin S. Ozturk

Online Measurement of pH and O2 Values During MechanicalStimulation of Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519Stefanie Böhm, Solvig Diederichs, Thomas Scheper, Martijn vanGriensven, and Cornelia Kasper

Part VI Biotherapeutics

Reducing Protein Immunogenicity by Design: Deimmunizationand Tolerance Induction . . . . . . . . . . . . . . . . . . . . . . . . . . . 525Anne S. De Groot, Tobias Cohen, Lenny Moise, and William D. Martin

xvi Contents

Second-Generation Interferons: An Effective, Long-LastingHyperglycosylated IFN-alpha2 . . . . . . . . . . . . . . . . . . . . . . . 535Natalia Ceaglio, Marina Etcheverrigaray, Ricardo Kratje,Harald S. Conradt, and Marcos Oggero

Large Scale Ex Vivo Manufacture of Blood Cells . . . . . . . . . . . . . 557Nicholas E. Timmins and Lars K. Nielsen

Production of Recombinant Human Leukemia InhibitoryFactor (lif) in a Mammalian Cell Bioreactor: A First Approach . . . . . 573R.P. Baptista, D.M. Barata, L.P. Fonseca, M.M. Diogo,C. Lobato da Silva, and J.M.S. Cabral

Effect of Non-Ionic Surfactant Pluronic F-68 on CHO CellKinetics, IFN-γ Production and Glycosylation . . . . . . . . . . . . . . 577M.-F. Clincke, E. Guedon, F.T. Yen, V. Ogier, O. Roitel,B.E. Bihain, and J.-L. Goergen

Production and Purification of a Human Dll1(ECD)IgGFcFusion Protein in CHOSFS Cells . . . . . . . . . . . . . . . . . . . . . . 581Claas Haake, Pierre Moretti, Jeanette Woiterski,Florian P. Limbourg, Cornelia Kasper, and Thomas Scheper

Controlling Fucosylation Levels of Antibodies with OsmolalityDuring Cell Culture in Several Host Cell Lines . . . . . . . . . . . . . . 585Yoshinobu Konno, Yuki Kobayashi, Ken Takahashi, Shinji Sakae,Masako Wakitani, Toshiyuki Suzawa, Keiichi Yano,Masamichi Koike, Kaori Wakamatu, and Shinji Hosoi

A High Cell Density Approach to Fed-Batch Cell Culturefor Production of Biopharmaceuticals . . . . . . . . . . . . . . . . . . . 589Sampath Kumar, Kevin McCarthy, Linda Francullo, Kerstin Crowe,Robin Heller-Harrison, Wenge Wang, Gregory Hiller, and Mark Leonard

Approaches for Humanization of an Anti-idiotypic MurineMonoclonal Antibody . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593Alexander Mader and Renate Kunert

Optimized CGE-LIF-Based Glycan Analysisfor High-Throughput Applications . . . . . . . . . . . . . . . . . . . . . 599Jana Rödig, René Hennig, Jana Schwarzer, Udo Reichl,and Erdmann Rapp

Protein Quality Issues for Biopharmaceuticals DuringSolvent/Detergent Viral Inactivation Steps . . . . . . . . . . . . . . . . 605Raymond Tyther, Lisa Murphy, and Nigel Jenkins

Characterisation of Cultivation and Initial Proteome Analysisof the Novel Human Cell Line AGE1.hn . . . . . . . . . . . . . . . . . . 609Eva Schräder, Raimund Hoffrogge, Volker Sandig, and Thomas Noll

Contents xvii

Part VII Novel Vaccines and Virology

Avian Designer Cells AGE1.CR R© as Candidates for MVA andInfluenza Vaccine Production . . . . . . . . . . . . . . . . . . . . . . . . 615Verena Lohr, Alexander Rath, Ingo Jordan, Volker Sandig,Yvonne Genzel, and Udo Reichl

Constitutive Augmentation of Heat Shock Responsein a Producer Cell for Viral Vaccines . . . . . . . . . . . . . . . . . . . . 633Ingo Jordan, Kristin Höwing, Stefanie Oehmke, and Volker Sandig

In Vitro Approaches for Improved Rotavirus VLP’s Quality . . . . . . 651Maria Candida M. Mellado, Manuel J.T. Carrondo, and Paula M. Alves

Development of Inactivated Polio Vaccine (IPV) Derived fromAttenuated Sabin Strains . . . . . . . . . . . . . . . . . . . . . . . . . . 667Wilfried A.M. Bakker, Yvonne E. Thomassen, Aart G. van ’t Oever,Janny Westdijk, Monique G.C.T. van Oijen, Gideon F.A. Kersten,Leo A. van der Pol, Rudy Hertroys, Nico van den Heuvel, and Jan Hendriks

Development of a Manufacturing Process for the Production ofa Canine Adenovirus Type 2 (CAV-2) Vector Using MDCK Cells . . . . 671Paulo Fernandes, Virgínia Santiago, Núria Viana, Eric J. Kremer,Ana S. Coroadinha, and Paula M. Alves

Monitoring of Host-Cell Infection and Virus-Induced Apoptosisin Influenza Vaccine Production . . . . . . . . . . . . . . . . . . . . . . 675Britta Isken, Josef Schulze-Horsel, Andreas Bock, Yvonne Genzel,and Udo Reichl

Accounting for the Entire Influenza Hemagglutinin during a FluVaccine Production Process . . . . . . . . . . . . . . . . . . . . . . . . . 685T. Kröber, M.W. Wolff, S. Lehmann, A. Zimmermann, and Udo Reichl

Lentiviral Vectors for Rapid and Efficient Recombinant CHOCell Line Generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 691Agata Oberbek, Mattia Matasci, Myriam Adam, Lucia Baldi,David L. Hacker, and Florian M. Wurm

Thermal and Detergent Tolerance for a Chimeric Bionanoparticle . . . 695Luísa Pedro, Sandra S. Soares, and Guilherme N.M. Ferreira

A New Approach for Rapid Development of Spodopterafrugiperda/BEVS-Based Processes . . . . . . . . . . . . . . . . . . . . . 699Christoph Ries, Virginia Wasem, Dorothea Karrer, Corinne John,and Regine Eibl

The Role of Culture Medium Lipids and Lipid Metabolismin Retroviral Vector Production Under Serum Deprivation . . . . . . . 705A.F. Rodrigues, A.I. Amaral, M. Carmo, Paula M. Alves,and Ana S. Coroadinha

xviii Contents

Scale-Down of the Salk Inactivated Polio Vaccine Production Process . 713Yvonne E. Thomassen, Marian Vinke, Leo A. van der Pol,and Wilfried A.M. Bakker

Poxvirus Production on Chicken Embryo Fibroblastsin iCELLisTM Disposable Fixed-Bed Bioreactor . . . . . . . . . . . . . 719Nicolas Havelange, Martine Marigliano, Martine Sainte-Marie,Fabien Debras, Nadia Tazir, and José Castillo

Platform Technology for Viral Vaccine Production: ComparisonBetween Attached and Suspension Vero Cells . . . . . . . . . . . . . . . 723Yvonne E. Thomassen, Gerco van Eikenhorst, Leo A. van der Pol,and Wilfried A.M. Bakker

Part VIII Workshops

Workshop 1: New Directions in Pharmaceutical ProcessDevelopment and Manufacturing: Process AnalyticalTechnology (PAT), Quality by Design (QbD), Design Space (DS),and other FDA Initiatives . . . . . . . . . . . . . . . . . . . . . . . . . . 731Sadettin S. Ozturk and Nigel Jenkins

ESACT Workshop: Stem Cell Technology and TissueEngineering New Developments and Clinical Applications . . . . . . . . 735John R. Masters and Finbarr O’Sullivan

The Impact of High-Titer Feedstreams on Monoclonal AntibodyPurification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 741Brian Kelley

Workshop on Genomics Technology . . . . . . . . . . . . . . . . . . . . 745Tim Charlebois and Wei-Shou Hu

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 749

Contributors

Myriam Adam Laboratory of Cellular Biotechnology, School of Life Sciences,École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Spiros N. Agathos Unit of Bioengineering, Institut des Sciences de la Vie,Université Catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; GenieBiologique, Institut Des Sciences De La Vie, Université Catholique de Louvain,B-1348 Louvain-La-Neuve, Belgium

D. Aguiar Research and Development Direction, Center of MolecularImmunology, Havana, 11600, Cuba

M.A. Aguiar Laboratory of Industrial Biotechnology, IPT, S. Paulo, SP, Brazil

Naima Alaoui ATMI LifeSciences/Artelis, Brussels, Belgium

Paula M. Alves Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa (UNL), 2780-157 Oeiras, Portugal; Animal CellTechnology Unit, Instituto de Biologia Experimental e Tecnológica (IBET),2780-157 Oeiras, Portugal, marques@itqb.unl.pt

Eva-Maria Amann Central Institute of Blood Transfusion and Immunology,University Hospital, Innsbruck, Austria

A.I. Amaral Instituto de Biologia Experimental e Tecnológica (IBET), 2780-901Oeiras, Portugal; Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa, 2781-901 Oeiras, Portugal

Raquel Ambrósio Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa (UNL), Oeiras, Portugal; Animal Cell TechnologyUnit, Instituto de Biologia Experimental e Tecnológica (IBET), Oeiras, Portugal

Amy Antosh Sheffield Life Sciences, Center for Cell Culture Technology, Ithaca,NY 14850, USA

Giannini Apati Recombinant Protein Expression Group, Helmholtz Centre forInfection Research, Braunschweig, Germany; Universidade da Região de Joinville,Joinville, Brazil

xix

xx Contributors

E.F.P. Augusto Laboratory of Industrial Biotechnology, IPT, S. Paulo, SP, Brazil

James F. Babcock Sheffield Life Sciences, Center for Cell Culture Technology,Ithaca, NY 14850, USA, james.babcock@kerry.com

Virginie Bachmann Laboratory of Cellular Biotechnology, School of LifeSciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

Gaurav Backliwal Laboratory of Cellular Biotechnology, School of LifeSciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland; Excellgene S.A., Monthey, Switzerland

Wilfried A.M. Bakker National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands,wilfried.bakker@rivm.nl

Lucia Baldi Laboratory of Cellular Biotechnology, School of Life Sciences,Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Sara Bantner Department of Gene Regulation and Differentiation,HZI – Helmholtz Centre for Infection Research, Braunschweig, Germany

R.P. Baptista Institute for Biotechnology and Bioengineering, Centre forBiological and Chemical Engineering, Instituto Superior Técnico, Av RoviscoPais, Torre Sul-piso8, 1049-001 Lisbon, Portugal, ricardopb@ist.utl.pt

D.M. Barata Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa,Lisbon, Portugal

Jérémie Barbau Biochimie Cellulaire, Nutritionnelle & Toxicologique, InstitutDes Sciences De La Vie, Université Catholique de Louvain, B-1348Louvain-la-Neuve, Belgium

N. Barbouche LRGP, CNRS UPR 3349 Nancy-Université, INPL, F-54505Vandœuvre-lès-Nancy, France

M.F. Barral Santo André Foudation, S. André, SP, Brazil

Eliezer Barreiro LASSBio, Universidad Federal de Rio de Janeiro, Rio deJaneiro, Brazil

Bonnie L. Barrilleaux Department of Chemical and Biomolecular Engineeringand Tulane Center for Gene Therapy, Tulane University, New Orleans, LA 70118,USA

Niall Barron National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland, niall.barron@dcu.ie

F.R.X. Batista School of Chemical Engineering, State University of Campinas,Campinas, SP, Brazil

Contributors xxi

Larissa Behr Institute for Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

Brian Benoit Seahorse Bioscience, North Billerica, MA, USA; BioProcessorsCorp., Woburn, MA, USA

Vicente Bernal Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa (UNL), Oeiras, Portugal; Animal Cell TechnologyUnit, Instituto de Biologia Experimental e Tecnológica (IBET), Oeiras,Portugal; Facultad de Química, Departamento de Bioquímica y Biología MolecularB e Inmunología, Universidad de Murcia, E-30100 Murcia, Spain

Patrick Bernard-Moulin Thermo Fisher Scientific, F-91963 Courtaboeuf Cedex,France

Olivier Berteau Fogale nanotech, Nîmes, France

Kenneth C. Bertram Novozymes Biopharma AU Ltd, Thebarton, SA 5031,Australia

Ankur Bhatnagar Biocon Limited, Bangalore, India,ankur.bhatnagar@biocon.com

Corinna Bialek CEVEC Pharmaceuticals GmbH, 51105 Cologne, Germany

B.E. Bihain Genclis SAS, 54500 Vandoeuvre-lès-Nancy, France

Fabrice Blanchard LRGP, CNRS UPR 3349 Nancy-Université, INPL, F-54505Vandœuvre-lès-Nancy, France; Laboratoire des Sciences du Génie Chimique, UPRCNRS 6811, Nancy-Université, F-54505 Vandoeuvre-lès-Nancy Cedex, France

Marjanca Blas Biopharmaceuticals-Cell and Molecular Biology, LekPharmaceuticals d.d., Menges Site, SI-1234 Menges, Slovenia

Andra Bobart Royal Victoria Eye & Ear Hospital, Dublin-2, Ireland

Andreas Bock Bioprocess Engineering Group, Max Planck Institute forDynamics of Complex Technical Systems, 39106 Magdeburg, Germany

Stefanie Böhm Institute of Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

Mariela Bollati-Fogolín Cell Biology Unit, Institut Pasteur de Montevideo,Montevideo, Uruguay, mbollati@pasteur.edu.uy

Björn Breth Greiner Bio-One GmbH, 72636 Frickenhausen, Germany,info@de.gbo.com

Lara Breth Greiner Bio-One GmbH, Maybachstr. 2, 72636 Frickenhausen,Germany, lara.breth@gbo.com

H. Brod Bayer Technology Services, 51368 Leverkusen, Germany

xxii Contributors

Dacia R. Brooks Late Stage Cell Culture, Pharma Technical Development,Genentech, A Member of the Roche Group, South San Francisco, CA 94080, USA

C. Bürki ExcellGene SA, CH-1870 Monthey, Switzerland

Konrad Büssow Recombinant Protein Expression (RPEX), Departmentof Structural Biology, Helmholtz Centre for Infection Research, Braunschweig,Germany

Milada Butueva Department of Gene Regulation and Differentiation,HZI – Helmholtz Centre for Infection Research, Braunschweig, Germany

Lovisa Bylund RecipharmCobra Biologics, 152 57 Södertälje, Sweden

J.M.S. Cabral Institute for Biotechnology and Bioengineering, Centre forBiological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal

Jordi J. Cairó Department d’Enginyeria Química (ETSE), Universitat Autònomade Barcelona, Edifici Q, 08193 Bellaterra, Barcelona, Spain

Tobias Cantz Stem Cell Biology, Cluster-of-Excellence “REBIRTH”, HannoverMedical School, Hanover, Germany, Cantz.tobias@mh-hannover.de

Nuno Carinhas Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa (UNL), Oeiras, Portugal; Animal Cell TechnologyUnit, Instituto de Biologia Experimental e Tecnológica (IBET), Oeiras, Portugal

M. Carmo Instituto de Biologia Experimental e Tecnológica (IBET), 2780-901Oeiras, Portugal; Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa, 2781-901 Oeiras, Portugal

Manuel J.T. Carrondo Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa (UNL), Oeiras, Portugal; Animal Cell TechnologyUnit, Instituto de Biologia Experimental e Tecnológica (IBET), Oeiras,Portugal; Laboratório de Engenheria Bioquímica, Faculdade de Ciênciase Tecnología, Universidade Nova de Lisboa, Lisbon, Portugal

J.P. Carvell Aber Instruments Ltd., 5 Science Park, Aberystwyth, Ceredigion,SY23 3AH, UK, johnc@aberinstruments.com

L. Castellanos-Serra Center for Genetic Engineering and Biotechnology,Havana, Cuba

A.J. Castillo Research and Development Direction, Center of MolecularImmunology, Havana, 11600, Cuba

A. Castillo-Vitlloch Research and Development Direction, Center of MolecularImmunology, Havana, Cuba

Leda R. Castilho Cell Culture Engineering Laboratory (LECC), FederalUniversity of Rio de Janeiro (UFRJ), COPPE, Rio de Janeiro/RJ, 21941-972,Brazil

Contributors xxiii

José Castillo ATMI LifeSciences/Artelis, Brussels, Belgium

Luigi Cavenaghi Areta International, 21040 Gerenzano (VA), Italy

Natalia Ceaglio Laboratorio de Cultivos Celulares, Facultad de Bioquímicay Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina,nceaglio@fbcb.unl.edu.ar

Hugo Cerecetto Laboratorio de Química, Orgánica Facultad de Ciencias-Facultadde Química, Montevideo, Uruguay

Salim Charaniya Genentech, Inc., Oceanside, CA 92056, USA

Tim Charlebois Wyeth, New York, NY, USA, TCharlebois@pfizer.com

Srikanth Chary Late Stage Cell Culture, Pharma Technical Development,Genentech, Inc., South San Francisco, CA, USA

Sebastien Chenuet Laboratory of Cellular Biotechnology, School of LifeSciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

Yuen-Ting Chim Mammalian Process Research, GlaxoSmithKline, Stevenage,UK; BioPharm Process Research, GlaxoSmithKline Medicines Research Centre,SG1 2NY Stevenage, Herts, UK

Larissa Chirkova Novozymes Biopharma Au Ltd, Thebarton, SA, Australia

Véronique Chotteau Biovitrum, presently at Animal Cell Technology Group,School of Biotechnology, Royal Institute of Technology (KTH), Stockholm,Sweden, veronique.chotteau@biotech.kth.se

Panagiotis Chrysanthopoulos Australian Institute for Bioengineering andNanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia

M.-F. Clincke Laboratoire Réactions et Génie des Procédés, UPR-CNRS 3349,Vandoeuvre-lès-Nancy, France; Lipidomix (EA4422), ENSAIA-INPL, NancyUniversité, 54500 Vandoeuvre-lès-Nancy, France; Genclis SAS, 54500Vandoeuvre-lès-Nancy, France

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

Joe Codamo Australian Institute for Bioengineering and Nanotechnology,The University of Queensland, Brisbane, QLD 4072, Australia; Acyte Biotech PtyLtd, Brisbane, QLD 4072, Australia

Tobias Cohen EpiVax and Institute for Immunology and Informatics (I-cubed),University of Rhode Island, Kingston, RI, USA

Florence Collignon ATMI LifeSciences/Artelis, Brussels, Belgium

Harald S. Conradt GlycoThera GmbH, Hanover, Germany

xxiv Contributors

Ana S. Coroadinha Instituto de Biologia Experimental e Tecnológica (IBET),2780-157 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa (UNL), Av. da República, Estação AgronómicaNacional, 2780-157 Oeiras, Portugal, avalente@itqb.unl.pt

Abner Correia New England Controls, Inc., Foxborough, MA, USA

Caitriona Crawford Pfizer, Grange Castle Business Park, Clondalkin, Dublin 22,Ireland

Chiara Crosta Areta International, 21040 Gerenzano VA, Italy

Kerstin Crowe Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810, USA

C. Lobato da Silva Institute for Biotechnology and Bioengineering, Centre forBiological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal

Anna Daniel-Wojcik Leibniz Institute of Plant Genetics and Crop Plant Research(IPK), D-06466 Gatersleben, Germany

Anne S. De Groot EpiVax, Providence, RI, USA; Institute for Immunologyand Informatics (I-cubed), University of Rhode Island, Kingston, RI, USA,AnnieD@epivax.com

M. De Jesus ExcellGene SA, CH-1870 Monthey, Switzerland

K.R. de la Luz-Hernández Research and Development Direction, Centerof Molecular Immunology, Havana, Cuba; Michael Barber Center for MassSpectrometry, School of Chemistry and Manchester Interdisciplinary Biocenter,University of Manchester, Manchester, UK, katiar@cim.sld.cu

D. De Sanctis Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

Fabien Debras Artelis, Brussels, Belgium

Frank Deer Ipsen Biomeasure, Milford, MA, USA, frank.deer@ipsen.com

Maria de Jesus Excellgene S.A, Monthey, Switzerland

Fanny Delegrange Laboratory of Cellular Biotechnology, School of LifeSciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

Cynthia Deppeler Pfizer, Inc., St. Louis, MO, USA

Saravanan Desan Biocon Limited, Bangalore, India,Saravanan.Desan@biocon.com

J. Díaz-Brito Faculty of Biology, University of Havana, Havana, Cuba

Caroline Didier Laboratorio de Cultivos Celulares, Facultad de Bioquímicay Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

Contributors xxv

K. Didzus Pharma Biotech Production and Development, Roche DiagnosticsGmbH, Penzberg, Germany

Solvig Diederichs Institute of Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany; Ludwig Boltzmann Institute for Experimental andClinical Traumatology, 1200 Vienna, Austria

Stefanie Dietmair Australian Institute for Bioengineering and Nanotechnology,The University of Queensland, Brisbane, QLD 4072, Australia,s.dietmair@uq.edu.au

M.M. Diogo Institute for Biotechnology and Bioengineering, Centre forBiological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal

M. Discacciati Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

Quang Doan Novozymes Biopharma Au Ltd, Thebarton, SA, Australia

Davide Donati Istituto Ortopedico Rizzoli, 40136, Bologna (BO), Italy

Patrick Dowling Pfizer, Grange Castle Business Park, Clondalkin, Dublin 22,Ireland

Jean-Christophe Drugmand ATMI LifeSciences/Artelis, Brussels, Belgium,jcdrugmand@atmi.com

Stéphanie Dubois Artelis, Brussels, Belgium

Ralph Duhr Laboratory of Cellular Biotechnology, School of Life Sciences,Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

M. Edler Institute of Chemistry, University of Loeben, Loeben, Austria

Reto Eggenschwiler Stem Cell Biology, Cluster-of-Excellence “REBIRTH”,Hannover Medical School, Hanover, Germany

F. Egner InVivo BioTech Services, D-16761 Hennigsdorf, Germany,f.egner@invivo.de

Regine Eibl Zurich University of Applied Sciences, School of Life Sciences andFacility Management, Institute of Biotechnology, Grüental, 8820 Wädenswil,Switzerland

Elsayed A. Elsayed Faculty of Science, Advanced Chair for Proteomics &Cytomics Research, King Saud University, Riyadh 1145, Kingdom of SaudiArabia, eaelsayed@ksu.edu.sa

Eva-Maria Engelhardt Laboratory of Cellular Biotechnology, School of LifeSciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

xxvi Contributors

Pablo Espósito Cell Biology Unit, Institut Pasteur de Montevideo, Montevideo,Uruguay

Ruth Essers CEVEC Pharmaceuticals GmbH, 51105 Köln, Germany,essers@cevec.com

Geoffrey Esteban Fogale nanotech, Nîmes, France

Marina Etcheverrigaray Laboratorio de Cultivos Celulares, Facultad deBioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe,Argentina

E. Faife Research and Development Direction, Center of Molecular Immunology,Havana 11600, Cuba

M. Farhat Laboratory for Hydraulic Machines, Ecole Polytechnique Fédérale deLausanne, CH-1015 Lausanne, Switzerland

Ronald Fedechko Pfizer, Inc., St. Louis, MO, USA

Elisabeth Feifel Division of Physiology, Innsbruck Medical University,Innsbruck, Austria

Christel Fenge RecipharmCobra Biologics, 152 57 Södertälje, Sweden

Paulo Fernandes Instituto de Biologia Experimental e Tecnológica (IBET),2780-157 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal

Guilherme N.M. Ferreira IBB – Institute for Biotechnology and Bioengineering,Centre for Molecular and Structural Biomedicine, University of Algarve, Faro,Portugal

David Ferrick Seahorse Bioscience, North Billerica, MA, USA

Benjamin W. Fischer-Valuck Department of Chemical and BiomolecularEngineering and Tulane Center for Gene Therapy, Tulane University, NewOrleans, LA 70118, USA

L.P. Fonseca Institute for Biotechnology and Bioengineering, Centre forBiological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal

Guillermina Forno Laboratorio de Cultivos Celulares, Facultad de Bioquímicay Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe,Argentina; Zelltek S.A, Santa Fe, Argentina, gforno@fbcb.unl.edu.ar

F. Fournier LRGP, CNRS UPR 3349 Nancy-Université, INPL, F-54505Vandœuvre-lès-Nancy, France

B. Frahm Bayer Technology Services, 51368 Leverkusen, Germany,bjoern.frahm@bayertechology.com

Geoffrey L. Francis Novozymes Biopharma AU Ltd, Thebarton, SA 5031,Australia

Contributors xxvii

Andrej Francky Biopharmaceuticals-Cell and Molecular Biology, LekPharmaceuticals d.d., Menges Site, SI-1234 Menges, Slovenia

Linda Francullo Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810, USA

Sadaharu Fukui Department of Chemistry and Biochemistry, Suzuka NationalCollege of Technology, Shiroko-cho, Suzuka, Mie, 510-0294, Japan

Ken Fukumoto Department of Applied Chemistry and Biotechnology, GraduateSchool of Engineering, University of Fukui, Fukui 910-8507, Japan

J. Gabelsberger Pharma Biotech Production and Development, RocheDiagnostics GmbH, Penzberg, Germany

Marta Galgano Areta International, 21040 Gerenzano VA, Italy

Patrick Gammell National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland; Bio-Manufacturing Sciences Group, Pfizer, Inc.,Grange Castle International Business Park, Clondalkin, Dublin, Ireland

Dominik Gaser Biopharmaceuticals-Cell and Molecular Biology, LekPharmaceuticals d.d., Menges Site, SI-1234 Menges, Slovenia

S. Gaskell Michael Barber Center for Mass Spectrometry, School of Chemistryand Manchester Interdisciplinary Biocenter, University of Manchester,Manchester, UK

Martin Gawlitzek Late Stage Cell Culture, Pharma Technical Development,Genentech, A Member of the Roche Group, South San Francisco, CA 94080, USA

Valérie Gelbgras Transfers, Interfaces and Processes, Université Libre deBruxelles, Brussels, Belgium, Valerie.Gelbgras@ulb.ac.be

Gittan Gelius RecipharmCobra Biologics, 152 57 Södertälje, Sweden

Cécile Gény Sanofi Pasteur, F-69280 Marcy L’Etoile, France

Yvonne Genzel Bioprocess Engineering Group, Max Planck Institute forDynamics of Complex Technical Systems, 39106 Magdeburg, Germany,genzel@mpi-magdeburg.mpg.de

Ermanno Gherardi Laboratory of Molecular Biology, MRC Centre, CB2 2QHCambridge, UK

P.-A. Girod Selexis, Geneva, Switzerland

Ilaria Giuntini Areta International, 21040 Gerenzano VA, Italy

Francesc Gòdia Department d’Enginyeria Química (ETSE), UniversitatAutònoma de Barcelona, Edifici Q, 08193 Bellaterra, Barcelona, Spain

Anuj Goel Biocon Limited, Bangalore, India, anuj.goel@biocon.com

Ekta Goel Life Technologies, Grand Island, NY 14072, USA

xxviii Contributors

Christiane Goepfert Hamburg University of Technology, Hamburg, Germany

J.-L. Goergen Laboratoire Réactions et Génie des Procédés, UPR-CNRS 3349,Vandoeuvre-lès-Nancy, France, jean-louis.goergen@ensaia.inpl-nancy.fr

Héctor Goicoechea Laboratorio de Desarrollo Analítico y Quimiometría(LADAQ), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacionaldel Litoral, Santa Fe, Argentina

Mercedes González Laboratorio de Química, Orgánica Facultad deCiencias-Facultad de Química, Montevideo, Uruguay

Steve Gorfien Life Technologies, Grand Island, NY 14072, USA

Manfred Gossen Max-Delbrück-Center for Molecular Medicine, 13125 Berlin,Germany

Peter P. Gray NCRIS Biologics Facility, Australian Institute for Bioengineeringand Nanotechnology, The University of Queensland, Brisbane, QLD 4072,Australia; Acyte Biotech Pty Ltd, Brisbane, QLD 4072, Australia

Gerhard Greller Sartorius Stedim Biotech GmbH, Göttingen, Deutschland,Germany, Gerhard.Greller@Sartorius-Stedim.com

Benedikt Greulich Celonic AG, Basel, Switzerland,Benedikt.Greulich@celonic.ch

Sally Grosvenor Novozymes Biopharma AU Ltd., Thebarton, SA 5031,Australia, slyg@novozymes.com

Gerhard Gstraunthaler Division of Physiology, Innsbruck Medical University,A-6020 Innsbruck, Austria, gerhard.gstraunthaler@i-med.ac.at

E. Guedon Laboratoire Réactions et Génie des Procédés, UPR-CNRS 3349,Nancy-Université, INPL, F-54505 Vandoeuvre-lès-Nancy, France

J.S. Guez Laboratoire ProBioGEM, UPRES-EA 1024, Polytech-Lille/IUT A,Université des Sciences et Technologies de Lille, Avenue Paul Langevin, F-59655Villeneuve d’Ascq, France, jean-sebastien.guez@polytech-lille.fr

Claas Haake Institute for Technical Chemistry, Leibniz University Hanover,D-30167 Hanover, Germany

David L. Hacker Laboratory of Cellular Biotechnology, School of Life Sciences,Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

R. Hass Laboratory of Biochemistry and Tumor Biology, Department ofObstetrics and Gynecology, Medical University, Hannover, 30625 Hannover,Germany

T. Hatlapatka Institute of Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

Contributors xxix

Hansjörg Hauser Department of Gene Regulation and Differentiation,HZI – Helmholtz Centre for Infection Research, Braunschweig, Germany

Benoît Haut Transfers, Interfaces and Processes, Université Libre de Bruxelles,Brussels, Belgium

Nicolas Havelange ATMI LifeSciences/Artelis, Brussels, Belgium,nha@atmi.com

Mary Heenan Pfizer, Grange Castle Business Park, Clondalkin, Dublin 22,Ireland

Robin Heller-Harrison Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810,USA

Jan Hendriks National Institute for Public Health and the Environment (RIVM),P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

René Hennig Max-Planck-Institute Magdeburg, Magdeburg, Germany

M. Henry National Institute for Cellular Biotechnology, Dublin City University,Dublin 9, Ireland

Paola Hernández Laboratorio de Química, Orgánica Facultad deCiencias-Facultad de Química, Montevideo, Uruguay

Andreas Herrmann Celonic AG, Basel, Switzerland

Sabrina Herrmann Department of Gene Regulation and Differentiation,Helmholtz Centre for Infection Research, Braunschweig, Germany

Sabine Hertel CEVEC Pharmaceuticals GmbH, 51105 Cologne, Germany

Rudy Hertroys Netherlands Vaccine Institute, 3720 AL, Bilthoven,The Netherlands

Markus Hildinger Excellgene S.A., Monthey, Switzerland

Gregory Hiller Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810, USA

L. Hinojosa Research and Development Direction, Center of MolecularImmunology, Havana, 11600, Cuba

Håkan Hjalmarsson School of Electrical Engineering, Automatic Control, RoyalInstitute of Technology (KTH), Stockholm, Sweden, hakan.hjalmarsson@ee.kth.se

Hans Hoffmeister Zellwerk GmbH, 16727 Oberkraemer, Germany

Raimund Hoffrogge Institute for Cell Culture Technology, University ofBielefeld, Bielefeld, Germany

Shinji Hosoi Bio Process Research and Development Laboratories, Kyowa HakkoKirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

xxx Contributors

Jeff Jia Cheng Hou Australian Institute for Bioengineering and Nanotechnology,The University of Queensland, Brisbane, QLD 4072, Australia, j.hou1@uq.edu.au

Kristin Höwing ProBioGen AG, Berlin, Germany

Wei-Shou Hu Department of Chemical Engineering and Materials Science,University of Minnesota, Minneapolis, MN 55455, USA, acre@cems.umn.edu

Benjamin S. Hughes Australian Institute for Bioengineering andNanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia

Neysi Ibarra Pfizer, Grange Castle Business Park, Dublin 22, Ireland

Britta Isken Bioprocess Engineering Group, Max Planck Institute for Dynamicsof Complex Technical Systems, 39106 Magdeburg, Germany,isken@mpi-magdeburg.mpg.de

Nadia Jafâr ATMI LifeSciences/Artelis, Brussels, Belgium

Volker Jäger Recombinant Protein Expression Group, Helmholtz Centrefor Infection Research, Braunschweig, Germany, Volker.Jaeger@helmholtz-hzi.de

Kirin M. Jamison Late Stage Cell Culture, Pharma Technical Development,Genentech, A Member of the Roche Group, South San Francisco, CA 94080, USA,kirin@gene.com

Uros Jamnikar Biopharmaceuticals-Cell and Molecular Biology, LekPharmaceuticals d.d., Menges Site, Kolodvorska 27, SI-1234 Menges, Slovenia,uros.jamnikar@sandoz.com

David Jan Centocor, Malvern, PA, USA

Jean-François Michiels Biochimie Cellulaire, Nutritionnelle & Toxicologique,Institut Des Sciences De La Vie, Université Catholique de Louvain, B-1348Louvain-la-Neuve, Belgium

Nigel Jenkins Upstream Bioprocessing Group, National Institute forBioprocessing Research and Training (NIBRT), NICB Building, DCU, Dublin,Ireland

Corinne John Redbiotec AG, Wagistrasse 23, 8952 Schlieren, Switzerland

Kevin Johnson Genentech, Inc., Vacaville, CA 95688, USA

Ingo Jordan ProBioGen AG, Berlin, Germany, ingo.jordan@probiogen.de

Sandra Juanola Department d’Enginyeria Química (ETSE), UniversitatAutònoma de Barcelona, Edifici Q, 08193 Bellaterra, Barcelona, Spain

Zuzana Kadlecova Laboratory of Polymers, École Polytechnique Fédérale deLausanne, Institute of Materials, Lausanne, Switzerland

Héla Kallel Viral Vaccines R&D Unit, Institut Pasteur de Tunis, 1002 Tunis,Tunisia, hela.kallel@pasteur.rns.tn

Dorothea Karrer Redbiotec AG, Wagistrasse 23, 8952 Schlieren, Switzerland

Contributors xxxi

George Karypis Department of Computer Science and Engineering, Universityof Minnesota, Minneapolis, MN 55455, USA

Cornelia Kasper Institute of Technical Chemistry, Leibniz Universityof Hannover, 30167 Hannover, Germany, kasper@iftc.uni-hannover.de

Brian Kelley Bioprocess Development, Genentech, Inc., San Francisco, CA,USA, kelley.brian@gene.com

Gideon F.A. Kersten National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

Helmut Kewes CEVEC Pharmaceuticals GmbH, 51105 Köln, Germany

Alexandros Kiparissides Department of Chemical Engineering, Centre forProcess Systems Engineering, Imperial College London, SW7 2AZ London, UK

Divor Kiseljak Laboratory of Cellular Biotechnology, School of Life Sciences,Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Robert Kiss Late Stage Cell Culture, Pharma Technical Development,Genentech, Inc., South San Francisco, CA, USA

Harm-Anton Klok Laboratory of Polymers, École Polytechnique Fédérale deLausanne, Institute of Materials, Lausanne, Switzerland

Yuki Kobayashi Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

Masamichi Koike Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

Nadine Konisch Recombinant Protein Expression Group, Helmholtz Centre forInfection Research, Braunschweig, Germany

Yoshinobu Konno Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD., Takasaki-shi, Gunma 370-0013, Japan; Graduate Schoolof Engineering, Gunma University, Kiryu-shi 376-8515, Japan,yoshinobu@kyowa-kirin.co.jp

Ricardo Kratje Laboratorio de Cultivos Celulares, Facultad de Bioquímicay Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

Eric J. Kremer Institut de Génétique Moléculaire de Montpellier, CNRS,Montpellier, France

T. Kröber Max Planck Institute for Dynamics of Complex Technical Systems,39106 Magdeburg, Germany, kroeber@mpi-magdeburg.mpg.de

Jens O. Krömer Australian Institute for Bioengineering and Nanotechnology,The University of Queensland, Brisbane, QLD 4072, Australia

M. Kühner Adolf Kühner AG, CH-4127 Birsfelden, Switzerland

xxxii Contributors

Niraj Kumar National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin, Ireland

Sampath Kumar Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810, USA,Sampath.kumar@Pfizer.com

Renate Kunert Department of Biotechnology, Institute for AppliedMicrobiology, BOKU – University of Natural Resources and Life Sciences,A-1190 Vienna, Austria

A. Lage-Castellanos Cuban Neuroscience Center, Havana, Cuba

Carolyn M.C. Lam Department of Chemical Engineering, Centre for ProcessSystems Engineering, Imperial College London, SW7 2AZ London, UK

Karlheinz Landauer Celonic AG, Basel, Switzerland

Daniel Landgrebe Institute for Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

Huong Le Department of Chemical Engineering and Materials Science,University of Minnesota, Minneapolis, MN 55455, USA

Donald Lee Life Technologies, Grand Island, NY 14072, USA

M. Lee Aber Instruments Ltd., SY23 3AH Aberystwyth, UK

Rachel Legmann Seahorse Bioscience, North Billerica, MA, USA,rlegmann@seahorsebio.com

S. Lehmann Max Planck Institute for Dynamics of Complex Technical Systems,39106 Magdeburg, Germany

P. Léo Laboratory of Industrial Biotechnology, IPT, S. Paulo, SP, Brazil

Mark Leonard Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810, USA

Florian P. Limbourg Institute for Molecular Cardiology of the Hanover MedicalSchool, D-30625 Hanover, Germany

Wenyu Lin Bioprocessing Technology Institute, Agency for Science, Technologyand Research (A∗STAR), 20 Biopolis Way, #06-01, Centros, Singapore 138668

Kristina Lindgren RecipharmCobra Biologics, 152 57 Södertälje, Sweden

Anna Lindqvist AstraZeneca, Sodertalje, Sweden

Tom Linke Novozymes Biopharma Au Ltd, Thebarton, SA, Australia

Xiaoguang (Margaret) Liu Cell Line Development Cell Systems Division, LifeTechnologies Corporation, Frederick, MD 21704, USA

Jian Liu Cell Line Development Cell Systems Division, Life TechnologiesCorporation, Frederick, MD 21704, USA

Contributors xxxiii

D. Logan Aber Instruments Ltd., SY23 3AH Aberystwyth, UK

Verena Lohr Bioprocess Engineering Group, Max Planck Institute for Dynamicsof Complex Technical Systems, 39106 Magdeburg, Germany

Mairead Looby Pfizer, Grange Castle Business Park, Clondalkin, Dublin 22,Ireland

Enrico Lucarelli Istituto Ortopedico Rizzoli, 40136, Bologna (BO), Italy

Alexander Mader Department of Biotechnology, Institute for AppliedMicrobiology, BOKU – University of Natural Resources and Life Sciences,A-1190 Vienna, Austria, alexander.mader@boku.ac.at

Thierry Magadoux Sanofi Pasteur, F-69280 Marcy L’Etoile, France

Jennifer Mahoney Ipsen Biomeasure, Milford, MA, USA

I. Majore Institute of Technical Chemistry, Leibniz University Hanover, 30167Hanover, Germany

Athanasios Mantalaris Department of Chemical Engineering, Centre for ProcessSystems Engineering, Imperial College London, SW7 2AZ London, UK,a.mantalaris@imperial.ac.uk

Annie Marc Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,Nancy-Université, F-54505 Vandoeuvre-lès-Nancy Cedex, France

Martine Marigliano Transgene, Strasbourg, France

Dana Maria Marten Institute of Technical Chemistry, Leibniz UniversityHanover, 30167 Hanover, Germany

Ulrich Martin Department of Cardiac-, Thoracic-, Transplantation and VascularSurgery, REBIRTH-Center for Regenerative Medicine, Hannover Medical School,30625 Hanover, Germany

William D. Martin EpiVax and Institute for Immunology and Informatics(I-cubed), University of Rhode Island, Kingston, RI, USA

John R. Masters Division of Surgery and Interventional Sciences, UniversityCollege London, London, UK, j.masters@ucl.ac.uk

Mattia Matasci Laboratory of Cellular Biotechnology, School of Life Sciences,Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Tobias May Department of Gene Regulation and Differentiation, HZI –Helmholtz Centre for Infection Research, Braunschweig, Germany

Kevin McCarthy Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810, USA

Ellen McCormick Pfizer, Inc., St. Louis, MO, USA

xxxiv Contributors

Nathan McKnight Late Stage Cell Culture, Pharma Technical Development,Genentech, Inc., San Francisco, CA, USA, mcknight.nathan@gene.com

Ricardo A. Medronho School of Chemistry, Federal University of Rio de Janeiro(UFRJ), Rio de Janeiro/RJ 21941-900, Brazil, medronho@eq.ufrj.br

Steven Meier Late Stage Cell Culture, Pharma Technical Development,Genentech, Inc., South San Francisco, CA, USA

P. Meleady National Institute for Cellular Biotechnology, Dublin City University,Dublin 9, Ireland

Maria Candida M. Mellado Instituto de Tecnologia Química e Biológica(ITQB), Universidade Nova de Lisboa, Oeiras, Portugal; Instituto de BiologiaExperimental e Tecnológica (IBET), Oeiras 2780-901, Portugal

Ernest Milián Department d’Enginyeria Química (ETSE), Universitat Autònomade Barcelona, Edifici Q, 08193 Bellaterra, Barcelona, Spain, ernest.milian@uab.cat

Keri Mills Genentech, Inc, Vacaville, CA 95688, USA

Tatyana Mitina Novozymes Biopharma Au Ltd, Thebarton, SA, Australia

Lenny Moise EpiVax and Institute for Immunology and Informatics (I-cubed),University of Rhode Island, Kingston, RI, USA

Anne Marie Molloy Pfizer, Grange Castle Business Park, Clondalkin, Dublin 22,Ireland, annemarie.molloy@pfizer.com

Francisca Monteiro Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa (UNL), Oeiras, Portugal; Animal Cell TechnologyUnit, Instituto de Biologia Experimental e Tecnológica (IBET), Oeiras, Portugal

A.M. Moraes School of Chemical Engineering, State University of Campinas,Campinas, SP, Brazil

Enda Moran Pfizer, Grange Castle Business Park, Clondalkin, Dublin 22, Ireland

Pierre Moretti Institute for Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

R. Müller Pharma Biotech Production and Development, Roche DiagnosticsGmbH, Penzberg, Germany

Trent P. Munro Australian Institute for Bioengineering and Nanotechnology,The University of Queensland, Brisbane, QLD 4072, Australia; Acyte Biotech PtyLtd, Brisbane, QLD 4072, Australia, t.munro@uq.edu.au

Lisa Murphy Upstream Bioprocessing Group, National Institute forBioprocessing Research and Training (NIBRT), NICB Building, DCU, Dublin,Ireland

Contributors xxxv

Sophie Nallet Laboratory of Cellular Biotechnology, School of Life Sciences,École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Omkar Nandi Biocon Limited, Bangalore, India

Kristina Nehlsen Department of Gene Regulation and Differentiation, HelmholtzCentre for Infection Research, Braunschweig, Germany

Say Kong Ng Bioprocessing Technology Institute, Agency for Science,Technology and Research (A∗STAR), 20 Biopolis Way, #06-01, Centros,Singapore 138668, ng_say_kong@bti.a-star.edu.sg

Lars K. Nielsen Australian Institute for Bioengineering and Nanotechnology, TheUniversity of Queensland, Brisbane, QLD 4072, Australia, lars.nielsen@uq.edu.au

Ute Noack Sartorius Stedim Biotech GmbH, Göttingen, Deutschland, Germany

Thomas Noll Institute for Cell Culture Technology, University of Bielefeld,Bielefeld, Germany

Maria Luisa Nolli Areta International, 21040 Gerenzano VA, Italy

Kim C. O’Connor Department of Chemical and Biomolecular Engineering andTulane Center for Gene Therapy, Tulane University, New Orleans, LA 70118,USA, koc@tulane.edu

Eimear O’Donovan Pfizer, Grange Castle, Pilot Lab, Grange Castle BusinessPark, Clondalkin, Dublin 22, Ireland, Eimear.ODonovan@Pfizer.com

Finbarr O’Sullivan National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin-9, Ireland, finbarr.osullivan@dcu.ie

Agata Oberbek Laboratory of Cellular Biotechnology, School of Life Sciences,École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Stefanie Oehmke ProBioGen AG, Berlin, Germany

Akiko Ogawa Department of Chemistry and Biochemistry, Suzuka NationalCollege of Technology, Shiroko-cho, Suzuka, Mie 510-0294, Japan,ogawa@chem.suzuka-ct.ac.jp

Marcos Oggero Laboratorio de Cultivos Celulares, Facultad de Bioquímicay Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

V. Ogier Genclis SAS, 54500 Vandoeuvre-lès-Nancy, France

Ruth Olmer Department of Cardiac-, Thoracic-, Transplantation and VascularSurgery, REBIRTH-Center for Regenerative Medicine, Hannover Medical School,30625 Hanover, Germany

E. Olmos LRGP, CNRS UPR 3349 Nancy-Université, INPL, F-54505Vandœuvre-lès-Nancy, France, eric.olmos@ensaia.inpl-nancy.fr

xxxvi Contributors

Alper A. Öncül Laboratory of Fluid Dynamics and Technical Flows (ISUT/LSS),University of Magdeburg “Otto von Guericke”, 39106 Magdeburg, Germany,oencuel@ovgu.de

Sadettin S. Ozturk Centocor R&D, Malvern, PA, USA; Johnson & Johnson &Johnson, Skillman, NJ, USA, s_ozturk@earthlink.net

Luísa Pedro IBB – Institute for Biotechnology and Bioengineering, Centre forMolecular and Structural Biomedicine, University of Algarve, Faro, Portugal,lpedro@ualg.pt

R. Pérez Research and Development Direction, Center of MolecularImmunology, Havana, 11600, Cuba

M. Perone Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

Emma Petiot Laboratoire des Sciences du Génie Chimique, UPR CNRS 6811,Nancy-Université, F-54505 Vandoeuvre-les-Nancy Cedex, France; BiotechnologyResearch Institute – CNRC, Montréal, Québéc, Canada, emma.petiot@nrc-cnrc.ca

Walter Pfaller zet – Centre for Alternative and Complementary Methods toAnimal Testing, Linz, Austria; Division of Physiology, Innsbruck MedicalUniversity, Innsbruck, Austria

Donald G. Phinney Department of Molecular Therapeutics, The ScrippsResearch Institute, Jupiter, FL 33458, USA

R.A.M. Piccoli Laboratory of Industrial Biotechnology, IPT, Av. Prof. AlmeidaPrado, 532, CEP 05508-901, S. Paulo, SP, Brazil, rpiccoli@ipt.br

Hervé Pinton Sanofi Pasteur, F-69280 Marcy L’Etoile, France

Efstratios N. Pistikopoulos Department of Chemical Engineering, Centre forProcess Systems Engineering, Imperial College London, SW7 2AZ London, UK

Valentina Porro Cell Biology Unit, Institut Pasteur de Montevideo, Montevideo,Uruguay

Ralf Pörtner Hamburg University of Technology, Hamburg, Germany,poertner@tuhh.de

William Power Royal Victoria Eye & Ear Hospital, Dublin-2, Ireland

Eva Prats Institut de Biologia Molecular de Barcelona – CSIC, 08034 Barcelona,Spain

Y. Prieto Research and Development Direction, Center of MolecularImmunology, Havana 11600, Cuba, yadirap@cim.sld.cu

Darwin J. Prockop Department of Molecular and Cellular Medicine, Collegeof Medicine, Texas A&M Health Science Center, Temple, TX 76508, USA

Contributors xxxvii

R. Puskeiler Pharma Biotech Production and Development, Roche DiagnosticsGmbH, Penzberg, Germany, robert.puskeiler@roche.com

A. Quarteroni Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland

J.C. Quintana Mannheim University of Applied Sciences, D-68163 Mannheim,Germany, juan.quintana@uni-konstanz.de

Y. Rabasa-Legón Research and Development Direction, Center of MolecularImmunology, Havana, Cuba

Yashas Rajendra Laboratory of Cellular Biotechnology, School of Life Sciences,Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Leonardo A.G. Ramalho Cell Culture Engineering Laboratory (LECC), FederalUniversity of Rio de Janeiro (UFRJ), COPPE, Rio de Janeiro/RJ 21941-972,Brazil; School of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio deJaneiro/RJ 21941-900, Brazil

Erdmann Rapp Max-Planck-Institute Magdeburg, Magdeburg, Germany,rapp@mpi-magdeburg.mpg.de

Alexander Rath Bioprocess Engineering Group, Max Planck Institute forDynamics of Complex Technical Systems, 39106 Magdeburg, Germany

Britta Rathjen Hamburg University of Technology, Hamburg, Germany

Caroline Rauch zet – Centre for Alternative and Complementary Methods toAnimal Testing, Linz, Austria; Division of Physiology, Innsbruck MedicalUniversity, Innsbruck, Austria

Paula Ravnikar Cell Line Development Cell Systems Division, LifeTechnologies Corporation, Frederick, MD 21704, USA,Paula.Ravnikar@lifetech.com

Kishore Katiki Reddy National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin-9, Ireland, kishore.katikireddy2@mail.dcu.ie

Udo Reichl Bioprocess Engineering Group, Max Planck Institute for Dynamicsof Complex Technical Systems, 39106 Magdeburg, Germany; Lehrstuhl fürBioprozesstechnik, Otto-von-Guericke University Magdeburg, Magdeburg,Germany; Bioprocess Engineering, Otto von Guericke University Magdeburg,Magdeburg, Germany

O.W. Reif Sartorius-Stedim Biotech AG, D-37075 Göttingen, Germany

Nesrine Riahi Viral Vaccines R&D Unit, Institut Pasteur de Tunis, 1002 Tunis,Tunisia

Christoph Ries Zurich University of Applied Sciences, School of Life Sciencesand Facility Management, Institute of Biotechnology, Grüental, 8820 Wädenswil,Switzerland, christoph.ries@zhaw.ch

xxxviii Contributors

Russell Robins Pfizer, Inc., St. Louis, MO, USA

Tim Robinson Novozymes Biopharma Au Ltd, Thebarton, SA, Australia

Seth Rodgers Seahorse Bioscience, North Billerica, MA, USA

Jana Rödig Max-Planck-Institute Magdeburg, Magdeburg, Germany

A.F. Rodrigues Instituto de Biologia Experimental e Tecnológica (IBET),2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa, 2781-901 Oeiras, Portugal

Susanne Rohn Hamburg University of Technology, Hamburg, Germany

O. Roitel Genclis SAS, 54500 Vandoeuvre-lès-Nancy, France

L. Rojas Research and Development Direction, Center of MolecularImmunology, Havana, 11600, Cuba

Stefanie Röker Institute of Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

Luca Romagnoli Areta International, 21040 Gerenzano (VA), Italy,lromagnoli@aretaint.com

Marina Ross Novozymes Biopharma Au Ltd, Thebarton, SA, Australia

Samia Rourou Viral Vaccines R&D Unit, Institut Pasteur de Tunis, 1002 Tunis,Tunisia

Jerica Rozman-Pungercar Biopharmaceuticals-Cell and Molecular Biology, LekPharmaceuticals d.d., Menges Site, SI-1234 Menges, Slovenia

Katie C. Russell Department of Chemical and Biomolecular Engineering andTulane Center for Gene Therapy, Tulane University, New Orleans, LA 70118, USA

A. Peter Russo Seahorse Bioscience, North Billerica, MA, USA; BioProcessorsCorporation, Woburn, MA 01801, USA, peter.russo@merck.com

Rohit Sachdeva Bioprocessing Technology Institute, Agency for Science,Technology and Research (A∗STAR), 20 Biopolis Way, #06-01, Centros,Singapore 138668

Martine Sainte-Marie Transgene, Strasbourg, France

Shinji Sakae Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

Andrew J. Sakko Novozymes Biopharma AU Ltd, Thebarton, SA 5031,Australia, awjs@novozymes.com

Andrea Salmén RecipharmCobra Biologics, 152 57 Södertälje, Sweden

Contributors xxxix

Noelia Sanchez National Institute for Cellular Biotechnology, Dublin CityUniversity, Dublin 9, Ireland, noelia.sanchez2@mail.dcu.ie

Volker Sandig ProBioGen AG, Berlin, Germany

Virgínia Santiago Instituto de Biologia Experimental e Tecnológica (IBET),2780-157 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal

Sébastien Sart Université Catholique de Louvain, Institut des Sciences de la Vie,Unit of Bioengineering, Place Croix du Sud 2/19, 1348 Louvain-la-Neuve,Belgium, sebastien.sart@gmail.com

Harald Schennach Central Institute of Blood Transfusion and Immunology,University Hospital, Innsbruck, Austria

Thomas Scheper Institute for Technical Chemistry, Leibniz University Hanover,D-30167 Hanover, Germany, scheper@iftc.uni-hannover.de

Wibke Scheurer Hamburg University of Technology, Hamburg, Germany

Gudrun Schiedner CEVEC Pharmaceuticals GmbH, Gottfried-Hagen-Str. 62,51105 Köln, Germany, schiedner@cevec.com

Sabrina Schmeckebier Department of Cardiac-, Thoracic-, Transplantation andVascular Surgery, REBIRTH-Center for Regenerative Medicine, HannoverMedical School, 30625 Hanover, Germany

Yves-Jacques Schneider Biochimie Cellulaire, Nutritionnelle & Toxicologique,Institut des Sciences de la Vie, Université Catholique de Louvain, B-1348,Louvain-la-Neuve, Belgium, yjs@uclouvain.be

Harald Schöffl zet – Centre for Alternative and Complementary Methods toAnimal Testing, Linz, Austria

Nadine Scholz-Neumann CEVEC Pharmaceuticals GmbH, 51105 Cologne,Germany

Eva Schräder Institute for Cell Culture Technology, University of Bielefeld,Bielefeld, Germany, esc@zellkult.techfak.uni-bielefeld.de

Insa S. Schroeder Department of Anatomy and Cell Biology, Martin LutherUniversity Halle-Wittenberg, D-06097 Halle/S., Germany

Josef Schulze-Horsel Bioprocess Engineering Group, Max Planck Institute forDynamics of Complex Technical Systems, 39106 Magdeburg, Germany

Jana Schwarzer Max-Planck-Institute Magdeburg, Magdeburg, Germany

C. Schwiebert InVivo BioTech Services, D-16761 Hennigsdorf, Germany,c.schwiebert@invivo.de

xl Contributors

Malte Sgodda Stem Cell Biology, Cluster-of-Excellence “REBIRTH”, HannoverMedical School, Hanover, Germany

Collette Sheahan Novozymes Biopharma Au Ltd., Thebarton, SA 5031,Australia, cose@novozymes.com

Kriti Shukla Biocon Limited, Bangalore, India, Kriti.Shukla@biocon.com

Katya Marinova Simeonova Institute of Mechanics, Bulgarian Academy ofSciences, Sofia, Bulgaria, katyas@bas.bg

Anthony Simula Novozymes Biopharma AU Ltd, Thebarton, SA 5031, Australia

Ulrica Skoging-Nyberg RecipharmCobra Biologics, 152 57 Södertälje, Sweden,Ulrica.Skoging-Nyberg@recipharm.com

Sandra S. Soares IBB – Institute for Biotechnology and Bioengineering, Centrefor Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal

Michael Song Australian Institute for Bioengineering and Nanotechnology, TheUniversity of Queensland, Brisbane, QLD 4072, Australia

Hans Peter Spötl Central Institute of Blood Transfusion and Immunology,University Hospital, Innsbruck, Austria

Sriram Srinivasan Pfizer, Inc., St. Louis, MO, USA

Kevin Stafford Inspiration Biopharmaceuticals, Laguna Niguel, CA, USA

Frank Stahl Institute for Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

M. Stettler Laboratory of Cellular Biotechnology, Ecole Polytechnique Fédéralede Lausanne, CH-1015 Lausanne, Switzerland

W. Storhas Mannheim University of Applied Sciences, D-68163 Mannheim,Germany, w.storhas@hs-mannheim.de

Tomoya Sugiyama Chugai Pharmaceutical Co., Ltd., Kita-Ku, Tokyo, Japan

H. Suhr Mannheim University of Applied Sciences, D-68163 Mannheim,Germany, h.suhr@hs-mannheim.de

Toshiyuki Suzawa Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

Hisahiro Tabuchi API Process Development Dept. (Bio Technology)Pharmaceutical Technology Div., 5-5-1, Ukima, Kitaku, Tokyo, 115-8543, Japan,tabuchihsh@chugai-pharm.co.jp

Satoshi Tainaka Chugai Pharmaceutical Co., Ltd., Kita-Ku, Tokyo, Japan

Ken Takahashi Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

Contributors xli

Masato Tanaka Department of Applied Chemistry and Biotechnology, GraduateSchool of Engineering, University of Fukui, Fukui 910-8507, Japan

Bruce Tangarone Pfizer, Grange Castle Business Park, Clondalkin, Dublin 22,Ireland

S. Taylor Aber Instruments Ltd., SY23 3AH Aberystwyth, UK

Nadia Tazir Artelis, Brussels, Belgium

Satoshi Terada Department of Applied Chemistry and Biotechnology, GraduateSchool of Engineering, University of Fukui, Fukui 910-8507, Japan,terada@acbio.fukui-u.ac.jp

Dominique Thévenin Laboratory of Fluid Dynamics and Technical Flows(ISUT/LSS), University of Magdeburg “Otto von Guericke”, 39106 Magdeburg,Germany

Yvonne E. Thomassen National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands,yvonne.thomassen@rivm.nl

Nicholas E. Timmins Australian Institute for Bioengineering andNanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia,n.timmins@uq.edu.au

Inés Tiscornia Cell Biology Unit, Institut Pasteur de Montevideo, Montevideo,Uruguay

S. Tissot Laboratory of Cellular Biotechnology, Ecole Polytechnique Fédérale deLausanne, CH-1015 Lausanne, Switzerland

R.W. Todd Aber Instruments Ltd., SY23 3AH Aberystwyth, UK

Sarah Tokarski Recombinant Protein Expression (RPEX), Department ofStructural Biology, Helmholtz Centre for Infection Research, Braunschweig,Germany

Magda Tomala Institute of Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

Raymond Tyther Upstream Bioprocessing Group, National Institute forBioprocessing Research and Training (NIBRT), NICB Building, DCU, Dublin,Ireland, r_tyther@hotmail.com

Mark Uden Mammalian Process Research, GlaxoSmithKline, Stevenage, UK

Joop van den Heuvel Recombinant Protein Expression (RPEX), Department ofStructural Biology, Helmholtz Centre for Infection Research, Braunschweig,Germany

xlii Contributors

Nico van den Heuvel National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

Leo A. van der Pol National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

Gerco van Eikenhorst National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

Martijn van Griensven Ludwig Boltzmann Institute for Experimental andclinical Traumatology, 1200 Vienna, Austria

Monique G.C.T. van Oijen National Institute for Public Health and theEnvironment (RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

Aart G. van’t Oever National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

Núria Viana Instituto de Biologia Experimental e Tecnológica (IBET), 2780-157Oeiras, Portugal; Instituto de Tecnologia Química e Biológica (ITQB),Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal

S. Victores Research and Development Direction, Center of MolecularImmunology, Havana, 11600, Cuba

Marian Vinke National Institute for Public Health and the Environment (RIVM),P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

Joaquim Vives Divisió de Teràpies Avançades/XCELIA, Banc de Sang i Teixits,Edifici Doctor Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona,Spain, jvives@bstcat.net

Danny Voorhamme Novozymes Biopharma AU Ltd, Thebarton, SA 5031,Australia

Kaori Wakamatu Graduate School of Engineering, Gunma University,Tenjin-cho, Kiryu-shi 376-8515, Japan

Masako Wakitani Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

Johanna Walter Institute for Technical Chemistry, Leibniz University Hanover,30167 Hanover, Germany

Szu-Han Wang Late Stage Cell Culture, Pharma Technical Development,Genentech, A Member of the Roche Group, South San Francisco, CA 94080, USA

Daniel I.C. Wang Department of Chemical Engineering, Massachusetts Instituteof Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA;Singapore-MIT Alliance, National University of Singapore, 4 Engineering Drive 3,E4-04-10, Singapore 117576

Contributors xliii

Wenge Wang Bioprocessing R&D, Pfizer, Inc., Andover, MA 01810, USA

Steve Warr BioPharm Process Research, GlaxoSmithKline Medicines ResearchCentre, SG1 2NY Stevenage, Herts, UK

Steve R.C. Warr Mammalian Process Research, GlaxoSmithKline, Stevenage,UK, steve.r.warr@gsk.com

Virginia Wasem Zurich University of Applied Sciences, School of Life Sciencesand Facility Management, Institute of Biotechnology, Grüental, 8820 Wädenswil,Switzerland

Erica Wehling Life Technologies, Grand Island, NY 14072, USA

Herbert Weich Department of Gene Regulation and Differentiation,HZI – Helmholtz Centre for Infection Research, Braunschweig, Germany

Janny Westdijk National Institute for Public Health and the Environment(RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands

P. Wiedemann Mannheim University of Applied Sciences, D-68163 Mannheim,Germany, p.wiedemann@hs-mannheim.de

H. Wiegemann Mannheim University of Applied Sciences, D-68163 Mannheim,Germany, h.wiegemann@hs-mannheim.de

Sonja Wilke Recombinant Protein Expression (RPEX), Department of StructuralBiology, Helmholtz Centre for Infection Research, Braunschweig, Germany,sonja.wilke@helmholz-hzi.de

J. Williams Aber Instruments Ltd., SY23 3AH Aberystwyth, UK

Tasha Williams-Wright Cell Line Development Cell Systems Division, LifeTechnologies Corporation, Frederick, MD 21704, USA

Dagmar Wirth Department of Gene Regulation and Differentiation, HZI –Helmholtz Centre for Infection Research, D-38124, Braunschweig, Germany,dagmar.wirth@helmholtz-hzi.de

Anna M. Wobus In Vitro Differentiation Group, Leibniz Institute of PlantGenetics and Crop Plant Research (IPK), D-06466 Gatersleben, Germany,wobusam@ipk-gatersleben.de

Jeanette Woiterski Institute for Technical Chemistry, Leibniz UniversityHanover, D-30167 Hanover, Germany

M.W. Wolff Max Planck Institute for Dynamics of Complex Technical Systems,39106 Magdeburg, Germany; Bioprocess Engineering, Otto von GuerickeUniversity Magdeburg, Magdeburg, Germany

Danny C.F. Wong Bioprocessing Technology Institute, Agency for Science andTechnology Research (A∗STAR), Centros, Singapore 138668

xliv Contributors

Christian Wood Centocor, Malvern, PA, USA

Florence Wu Cell Line Development Cell Systems Division, Life TechnologiesCorporation, Frederick, MD 21704, USA

Sarah Wulhfard Laboratory of Cellular Biotechnology, School of Life Sciences,École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland,Sarah.Wulhfard@wanadoo.fr

Florian M. Wurm Laboratory of Cellular Biotechnology, School of LifeSciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne,Switzerland; ExcellGene S.A., CH-1870 Monthey, Switzerland,florian.wurm@epfl.ch

Zhihua Xiao Life Technologies, Grand Island, NY 14072, USA,zhihua.xiao@lifetech.com

Tatsuya Yamashita Department of Applied Chemistry and Biotechnology,Graduate School of Engineering, University of Fukui, Fukui, 910-8507, Japan

Keiichi Yano Bio Process Research and Development Laboratories, KyowaHakko Kirin Co., LTD, Takasaki-shi, Gunma 370-0013, Japan

Miranda G.S. Yap Bioprocessing Technology Institute, Agency for Science,Technology and Research (A∗STAR), 20 Biopolis Way, #06-01, Centros,Singapore 138668; Singapore-MIT Alliance, National University of Singapore,4 Engineering Drive 3, E4-04-10, Singapore 117576

F.T. Yen Lipidomix (EA4422), ENSAIA-INPL, Nancy Université, 54500Vandoeuvre-lès-Nancy, France

Erwin Yu Pfizer, Inc., St. Louis, MO, USA

Jeannette Zauers Department of Gene Regulation and Differentiation, HelmholtzCentre for Infection Research, Braunschweig, Germany

X. Zhang Laboratory of Cellular Biotechnology, Ecole Polytechnique Fédéralede Lausanne, CH-1015 Lausanne, Switzerland

David Zhao Life Technologies, Grand Island, NY 14072, USA

A. Zimmermann Max Planck Institute for Dynamics of Complex TechnicalSystems, 39106 Magdeburg, Germany