DR. MICHAEL C. FLICKINGER is Associate Director for Academic Programs of the Golden LEAF Biomanufacturing Training and Education Center (BTEC) and a Professor of Chemical and Biomolecular Engineering at North Carolina State University, Raleigh.

“The reference should be valuable to industry professionals as well as to advanced students of biomanufacturing, biochemical engineering, biopharmaceutical facility design, biochemistry, industrial microbiology, gene expression technology, and cell culture technology.”  (Chemical Engineering Progress, 1 August 2013)

• Preface ixContributors xiPART I INTRODUCTION 11 Bioprocess Design, Computer-Aided 5Victor Papavasileiou, Charles Siletti, Alexandros Koulouris, and Demetri PetridesPART II DOWNSTREAM RECOVERY OF CELLS AND PROTEIN CAPTURE 252 Cell Separation, Centrifugation 27Hans Axelsson3 Cell Disruption, Micromechanical Properties 49Ingo Kampen and Arno Kwade4 Cell Separation, Yeast Flocculation 65Eduardo V. Soares5 Cell Wall Disruption and Lysis 81F. A. P. Garcia6 Expanded Bed Chromatography, Surface Energetics of Biomass Deposition 95Marcelo Fernandez Lahore, Oscar Aguilar, Rami Reddy Vennapusa and Muhammad Aasin7 Filter Aids 107Tony Hunt8 Protein Adsorption, Expanded Bed 115Siddartha GhosePART III PROCESS DEVELOPMENT IN DOWNSTREAM PURIFICATION 1279 Scaledown of Biopharmaceutical Purification Operations 129Anurag S. Rathore and Varsha S. Joshi10 Adsorption in Simulated Moving Beds (SMB) 147Cesar C. Santana, Ivanildo J. Silva Jr., Diana C. S. Azevedo, and Amaro G. Barreto Jr.11 Adsorption of Proteins with Synthetic Materials 179Joseph McGuire and Omkar Joshi12 Affinity Fusions for Protein Purification 191Susanne Gräslund and Martin Hammarström13 Bioseparation, Magnetic Particle Adsorbents 201Urs Alexander Peuker, Owen Thomas, Timothy John Hobley, Mathias Franzreb, Sonja Berensmeier, Maria Shäfer, and Birgit Hickstein14 High Throughput Technologies in Bioprocess Development 221Trent Carrier, Eva Heldin, Mattias Ahnfelt, Eggert Brekkan, Richard Hassett, Steve Peppers, Gustav Rodrigo, Greg Van Slyke, and David (Xiqaojian) Zhao15 Large-Scale Protein Purification, Self-Cleaving Aggregation Tags 257Iraj Ghazi and David W. Wood16 Lipopolysaccharide, LPS removal, Depyrogenation 269Pérola O. Magalhães and Adalberto Pessoa Jr.17 Porous Media in Biotechnology 277Manuel Mota, Alexander Yelshin, and Inna Yelshina18 Protein Aggregation and Precipitation, Measurement and Control 293Catherine H. ScheinPART IV EQUIPMENT DESIGN FOR DOWNSTREAM RECOVERY AND PROTEIN PURIFICATION 32519 Cleaning and Sanitation in Downstream Processes 327Gail Sofer, Craig Robinson, Joanthan Yourkin, Tina Pitarresi, and Darcy Birse20 Clean-in-place 343Phil J. Bremer and Richard Brent Seale21 Large Scale Chromatography Columns, Modeling Flow Distribution 353Zhiwu Fang22 Pumps, Industrial 373Bob Stover and Ed DomanicoPART V DOWNSTREAM cGMP OPERATIONS 38923 Affinity Chromatography of Plasma Proteins 391Mirjana Radosevich and Thierry Burnouf24 Antibody Purification, Monoclonal and Polyclonal 405James J. Reilly and Michiel E. Ultee25 Chromatographic Purification of Virus Particles 415Pete Gagnon26 Chromatography, Hydrophobic Interactions 437Per Karsnäs27 Chromatography, Radar Flow 449Tingyue Gu28 Drying, Biological Materials 465Chung Lim Law and Arun S. Mujumdar29 Freeze-Drying, Pharmaceuticals 485Jinsong Liu30 Freezing, Biopharmaceutical 505Philippe Lam and Jamie Moore31 Membrane Chromatography 521John Pieracci and Jörg Thömmes32 Membrane Separations 545Manohar Kalyanpur33 Plasmid Purification 557H .S. C. Barbosa and J. C. Marcos34 Protein Chromatography, Manufacturing Scale 571Joseph Bertolini35 Protein Crystallization, Kinetics 579Gianluca Di Profio, Efrem Curcio, and Enrico Drioli36 Protein Purification, Aqueous Liquid Extraction 603Maria-Regina Kula and Klaus Selber37 Protein Ultrafiltration 617Robert van Reis and Andrew L. Zydney38 Virus Retentive Filters 641George Miesegaes, Scott Lute, Hazel Aranha, and Kurt BrorsonPART VI BIOPHARMACEUTICAL FACILITY VALIDATION 65539 Biopharmaceutical Facility Design and Validation 657Jeffrey N. Odum40 Closed Systems in Bioprocessing 677Jeffrey Odum41 Facility Design for Single Use (SU) Downstream Materials 685Robert Z. Maigetter, Tom Piombino, Christian Wood, Tom Gervais, Claudio Thomasin, Bryan Shingle, Dave A. Wareheim, and David Clark42 eGMPs for Production Rooms 715Claude Arlois, Jean Didelez, Patrick Florent, and Guy Godeau43 Heating, Ventilation, and Air Conditioning 731Dennis Dobie44 Sterilization-in-Place (SIP) 747P. T. NoblePART VII FDA cGMP REGULATORY COMPLIANCE 75745 Pharmaceutical Bioburden Testing 759Nathaniel G. Hentz, PhD46 Chromatography, Industrial Scale Validation 775Sandy Weinberg and Carl A. Rockburne47 GMPs and GLSPs 795Beth H. Junker48 Quality by Design (QBD) 815Rakhi B. Shah, Jun T. Park, Erik K. Read, Mansoor A. Khan, and Kurt Brorson49 Regulatory Requirements, European Community 829Gary WalshIndex 843

DR. MICHAEL C. FLICKINGER is Associate Director for Academic Programs of the Golden LEAF Biomanufacturing Training and Education Center (BTEC) and a Professor of Chemical and Biomolecular Engineering at North Carolina State University, Raleigh.

“The reference should be valuable to industry professionals as well as to advanced students of biomanufacturing, biochemical engineering, biopharmaceutical facility design, biochemistry, industrial microbiology, gene expression technology, and cell culture technology.”  (Chemical Engineering Progress, 1 August 2013)

• Preface ixContributors xiPART I INTRODUCTION 11 Bioprocess Design, Computer-Aided 5Victor Papavasileiou, Charles Siletti, Alexandros Koulouris, and Demetri PetridesPART II DOWNSTREAM RECOVERY OF CELLS AND PROTEIN CAPTURE 252 Cell Separation, Centrifugation 27Hans Axelsson3 Cell Disruption, Micromechanical Properties 49Ingo Kampen and Arno Kwade4 Cell Separation, Yeast Flocculation 65Eduardo V. Soares5 Cell Wall Disruption and Lysis 81F. A. P. Garcia6 Expanded Bed Chromatography, Surface Energetics of Biomass Deposition 95Marcelo Fernandez Lahore, Oscar Aguilar, Rami Reddy Vennapusa and Muhammad Aasin7 Filter Aids 107Tony Hunt8 Protein Adsorption, Expanded Bed 115Siddartha GhosePART III PROCESS DEVELOPMENT IN DOWNSTREAM PURIFICATION 1279 Scaledown of Biopharmaceutical Purification Operations 129Anurag S. Rathore and Varsha S. Joshi10 Adsorption in Simulated Moving Beds (SMB) 147Cesar C. Santana, Ivanildo J. Silva Jr., Diana C. S. Azevedo, and Amaro G. Barreto Jr.11 Adsorption of Proteins with Synthetic Materials 179Joseph McGuire and Omkar Joshi12 Affinity Fusions for Protein Purification 191Susanne Gräslund and Martin Hammarström13 Bioseparation, Magnetic Particle Adsorbents 201Urs Alexander Peuker, Owen Thomas, Timothy John Hobley, Mathias Franzreb, Sonja Berensmeier, Maria Shäfer, and Birgit Hickstein14 High Throughput Technologies in Bioprocess Development 221Trent Carrier, Eva Heldin, Mattias Ahnfelt, Eggert Brekkan, Richard Hassett, Steve Peppers, Gustav Rodrigo, Greg Van Slyke, and David (Xiqaojian) Zhao15 Large-Scale Protein Purification, Self-Cleaving Aggregation Tags 257Iraj Ghazi and David W. Wood16 Lipopolysaccharide, LPS removal, Depyrogenation 269Pérola O. Magalhães and Adalberto Pessoa Jr.17 Porous Media in Biotechnology 277Manuel Mota, Alexander Yelshin, and Inna Yelshina18 Protein Aggregation and Precipitation, Measurement and Control 293Catherine H. ScheinPART IV EQUIPMENT DESIGN FOR DOWNSTREAM RECOVERY AND PROTEIN PURIFICATION 32519 Cleaning and Sanitation in Downstream Processes 327Gail Sofer, Craig Robinson, Joanthan Yourkin, Tina Pitarresi, and Darcy Birse20 Clean-in-place 343Phil J. Bremer and Richard Brent Seale21 Large Scale Chromatography Columns, Modeling Flow Distribution 353Zhiwu Fang22 Pumps, Industrial 373Bob Stover and Ed DomanicoPART V DOWNSTREAM cGMP OPERATIONS 38923 Affinity Chromatography of Plasma Proteins 391Mirjana Radosevich and Thierry Burnouf24 Antibody Purification, Monoclonal and Polyclonal 405James J. Reilly and Michiel E. Ultee25 Chromatographic Purification of Virus Particles 415Pete Gagnon26 Chromatography, Hydrophobic Interactions 437Per Karsnäs27 Chromatography, Radar Flow 449Tingyue Gu28 Drying, Biological Materials 465Chung Lim Law and Arun S. Mujumdar29 Freeze-Drying, Pharmaceuticals 485Jinsong Liu30 Freezing, Biopharmaceutical 505Philippe Lam and Jamie Moore31 Membrane Chromatography 521John Pieracci and Jörg Thömmes32 Membrane Separations 545Manohar Kalyanpur33 Plasmid Purification 557H .S. C. Barbosa and J. C. Marcos34 Protein Chromatography, Manufacturing Scale 571Joseph Bertolini35 Protein Crystallization, Kinetics 579Gianluca Di Profio, Efrem Curcio, and Enrico Drioli36 Protein Purification, Aqueous Liquid Extraction 603Maria-Regina Kula and Klaus Selber37 Protein Ultrafiltration 617Robert van Reis and Andrew L. Zydney38 Virus Retentive Filters 641George Miesegaes, Scott Lute, Hazel Aranha, and Kurt BrorsonPART VI BIOPHARMACEUTICAL FACILITY VALIDATION 65539 Biopharmaceutical Facility Design and Validation 657Jeffrey N. Odum40 Closed Systems in Bioprocessing 677Jeffrey Odum41 Facility Design for Single Use (SU) Downstream Materials 685Robert Z. Maigetter, Tom Piombino, Christian Wood, Tom Gervais, Claudio Thomasin, Bryan Shingle, Dave A. Wareheim, and David Clark42 eGMPs for Production Rooms 715Claude Arlois, Jean Didelez, Patrick Florent, and Guy Godeau43 Heating, Ventilation, and Air Conditioning 731Dennis Dobie44 Sterilization-in-Place (SIP) 747P. T. NoblePART VII FDA cGMP REGULATORY COMPLIANCE 75745 Pharmaceutical Bioburden Testing 759Nathaniel G. Hentz, PhD46 Chromatography, Industrial Scale Validation 775Sandy Weinberg and Carl A. Rockburne47 GMPs and GLSPs 795Beth H. Junker48 Quality by Design (QBD) 815Rakhi B. Shah, Jun T. Park, Erik K. Read, Mansoor A. Khan, and Kurt Brorson49 Regulatory Requirements, European Community 829Gary WalshIndex 843

DR. MICHAEL C. FLICKINGER is Associate Director for Academic Programs of the Golden LEAF Biomanufacturing Training and Education Center (BTEC) and a Professor of Chemical and Biomolecular Engineering at North Carolina State University, Raleigh.

“The reference should be valuable to industry professionals as well as to advanced students of biomanufacturing, biochemical engineering, biopharmaceutical facility design, biochemistry, industrial microbiology, gene expression technology, and cell culture technology.”  (Chemical Engineering Progress, 1 August 2013)

• Preface ixContributors xiPART I INTRODUCTION 11 Bioprocess Design, Computer-Aided 5Victor Papavasileiou, Charles Siletti, Alexandros Koulouris, and Demetri PetridesPART II DOWNSTREAM RECOVERY OF CELLS AND PROTEIN CAPTURE 252 Cell Separation, Centrifugation 27Hans Axelsson3 Cell Disruption, Micromechanical Properties 49Ingo Kampen and Arno Kwade4 Cell Separation, Yeast Flocculation 65Eduardo V. Soares5 Cell Wall Disruption and Lysis 81F. A. P. Garcia6 Expanded Bed Chromatography, Surface Energetics of Biomass Deposition 95Marcelo Fernandez Lahore, Oscar Aguilar, Rami Reddy Vennapusa and Muhammad Aasin7 Filter Aids 107Tony Hunt8 Protein Adsorption, Expanded Bed 115Siddartha GhosePART III PROCESS DEVELOPMENT IN DOWNSTREAM PURIFICATION 1279 Scaledown of Biopharmaceutical Purification Operations 129Anurag S. Rathore and Varsha S. Joshi10 Adsorption in Simulated Moving Beds (SMB) 147Cesar C. Santana, Ivanildo J. Silva Jr., Diana C. S. Azevedo, and Amaro G. Barreto Jr.11 Adsorption of Proteins with Synthetic Materials 179Joseph McGuire and Omkar Joshi12 Affinity Fusions for Protein Purification 191Susanne Gräslund and Martin Hammarström13 Bioseparation, Magnetic Particle Adsorbents 201Urs Alexander Peuker, Owen Thomas, Timothy John Hobley, Mathias Franzreb, Sonja Berensmeier, Maria Shäfer, and Birgit Hickstein14 High Throughput Technologies in Bioprocess Development 221Trent Carrier, Eva Heldin, Mattias Ahnfelt, Eggert Brekkan, Richard Hassett, Steve Peppers, Gustav Rodrigo, Greg Van Slyke, and David (Xiqaojian) Zhao15 Large-Scale Protein Purification, Self-Cleaving Aggregation Tags 257Iraj Ghazi and David W. Wood16 Lipopolysaccharide, LPS removal, Depyrogenation 269Pérola O. Magalhães and Adalberto Pessoa Jr.17 Porous Media in Biotechnology 277Manuel Mota, Alexander Yelshin, and Inna Yelshina18 Protein Aggregation and Precipitation, Measurement and Control 293Catherine H. ScheinPART IV EQUIPMENT DESIGN FOR DOWNSTREAM RECOVERY AND PROTEIN PURIFICATION 32519 Cleaning and Sanitation in Downstream Processes 327Gail Sofer, Craig Robinson, Joanthan Yourkin, Tina Pitarresi, and Darcy Birse20 Clean-in-place 343Phil J. Bremer and Richard Brent Seale21 Large Scale Chromatography Columns, Modeling Flow Distribution 353Zhiwu Fang22 Pumps, Industrial 373Bob Stover and Ed DomanicoPART V DOWNSTREAM cGMP OPERATIONS 38923 Affinity Chromatography of Plasma Proteins 391Mirjana Radosevich and Thierry Burnouf24 Antibody Purification, Monoclonal and Polyclonal 405James J. Reilly and Michiel E. Ultee25 Chromatographic Purification of Virus Particles 415Pete Gagnon26 Chromatography, Hydrophobic Interactions 437Per Karsnäs27 Chromatography, Radar Flow 449Tingyue Gu28 Drying, Biological Materials 465Chung Lim Law and Arun S. Mujumdar29 Freeze-Drying, Pharmaceuticals 485Jinsong Liu30 Freezing, Biopharmaceutical 505Philippe Lam and Jamie Moore31 Membrane Chromatography 521John Pieracci and Jörg Thömmes32 Membrane Separations 545Manohar Kalyanpur33 Plasmid Purification 557H .S. C. Barbosa and J. C. Marcos34 Protein Chromatography, Manufacturing Scale 571Joseph Bertolini35 Protein Crystallization, Kinetics 579Gianluca Di Profio, Efrem Curcio, and Enrico Drioli36 Protein Purification, Aqueous Liquid Extraction 603Maria-Regina Kula and Klaus Selber37 Protein Ultrafiltration 617Robert van Reis and Andrew L. Zydney38 Virus Retentive Filters 641George Miesegaes, Scott Lute, Hazel Aranha, and Kurt BrorsonPART VI BIOPHARMACEUTICAL FACILITY VALIDATION 65539 Biopharmaceutical Facility Design and Validation 657Jeffrey N. Odum40 Closed Systems in Bioprocessing 677Jeffrey Odum41 Facility Design for Single Use (SU) Downstream Materials 685Robert Z. Maigetter, Tom Piombino, Christian Wood, Tom Gervais, Claudio Thomasin, Bryan Shingle, Dave A. Wareheim, and David Clark42 eGMPs for Production Rooms 715Claude Arlois, Jean Didelez, Patrick Florent, and Guy Godeau43 Heating, Ventilation, and Air Conditioning 731Dennis Dobie44 Sterilization-in-Place (SIP) 747P. T. NoblePART VII FDA cGMP REGULATORY COMPLIANCE 75745 Pharmaceutical Bioburden Testing 759Nathaniel G. Hentz, PhD46 Chromatography, Industrial Scale Validation 775Sandy Weinberg and Carl A. Rockburne47 GMPs and GLSPs 795Beth H. Junker48 Quality by Design (QBD) 815Rakhi B. Shah, Jun T. Park, Erik K. Read, Mansoor A. Khan, and Kurt Brorson49 Regulatory Requirements, European Community 829Gary WalshIndex 843