Downstream Industrial Biotechnology: Recovery and Purification

An affordable, easily accessible desk reference on biomanufacturing, focused on downstream recovery and purification Advances in the fundamental knowledge surrounding biotechnology, novel materials, and advanced engineering approaches continue to be translated into bioprocesses that bring new products to market at a significantly faster pace than most other industries. Industrial scale biotechnology and new manufacturing methods are revolutionizing medicine, environmental monitoring and remediation, consumer products, food production, agriculture, and forestry, and continue to be a major area of research. The downstream stage in industrial biotechnology refers to recovery, isolation, and purification of the microbial products from cell debris, processing medium and contaminating biomolecules from the upstream process into a finished product such as biopharmaceuticals and vaccines. Downstream process design has the greatest impact on overall biomanufacturing cost because not only does the biochemistry of different products ( e.g., peptides, proteins, hormones, antibiotics, and complex antigens) dictate different methods for the isolation and purification of these products, but contaminating byproducts can also reduce overall process yield, and may have serious consequences on clinical safety and efficacy. Therefore downstream separation scientists and engineers are continually seeking to eliminate, or combine, unit operations to minimize the number of process steps in order to maximize product recovery at a specified concentration and purity. Based on Wiley′s Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, this volume features fifty articles that provide information on down– stream recovery of cells and protein capture; process development and facility design; equipment; PAT in downstream processes; downstream cGMP operations; and regulatory compliance. It covers: Cell wall disruption and lysis Cell recovery by centrifugation and filtration Large–scale protein chromatography Scale down of biopharmaceutical purification operations Lipopolysaccharide removal Porous media in biotechnology Equipment used in industrial protein purification Affinity chromatography Antibody purification, monoclonal and polyclonal Protein aggregation, precipitation and crystallization Freeze–drying of biopharmaceuticals Biopharmaceutical facility design and validation Pharmaceutical bioburden testing Regulatory requirements Ideal for graduate and advanced undergraduate courses on biomanufacturing, biochemical engineering, biophar– maceutical facility design, biochemistry, industrial microbiology, gene expression technology, and cell culture technology, Downstream Industrial Biotechnology is also a highly recommended resource for industry professionals and libraries.

Preface ix Contributors xi PART I INTRODUCTION 1 1 Bioprocess Design, Computer–Aided 5 Victor Papavasileiou, Charles Siletti, Alexandros Koulouris, and Demetri Petrides PART II DOWNSTREAM RECOVERY OF CELLS AND PROTEIN CAPTURE 25 2 Cell Separation, Centrifugation 27 Hans Axelsson 3 Cell Disruption, Micromechanical Properties 49 Ingo Kampen and Arno Kwade 4 Cell Separation, Yeast Flocculation 65 Eduardo V. Soares 5 Cell Wall Disruption and Lysis 81 F. A. P. Garcia 6 Expanded Bed Chromatography, Surface Energetics of Biomass Deposition 95 Marcelo Fernandez Lahore, Oscar Aguilar, Rami Reddy Vennapusa and Muhammad Aasin 7 Filter Aids 107 Tony Hunt 8 Protein Adsorption, Expanded Bed 115 Siddartha Ghose PART III PROCESS DEVELOPMENT IN DOWNSTREAM PURIFICATION 127 9 Scaledown of Biopharmaceutical Purification Operations 129 Anurag S. Rathore and Varsha S. Joshi 10 Adsorption in Simulated Moving Beds (SMB) 147 Cesar C. Santana, Ivanildo J. Silva Jr., Diana C. S. Azevedo, and Amaro G. Barreto Jr. 11 Adsorption of Proteins with Synthetic Materials 179 Joseph McGuire and Omkar Joshi 12 Affinity Fusions for Protein Purification 191 Susanne Gräslund and Martin Hammarström 13 Bioseparation, Magnetic Particle Adsorbents 201 Urs Alexander Peuker, Owen Thomas, Timothy John Hobley, Mathias Franzreb, Sonja Berensmeier, Maria Shäfer, and Birgit Hickstein 14 High Throughput Technologies in Bioprocess Development 221 Trent Carrier, Eva Heldin, Mattias Ahnfelt, Eggert Brekkan, Richard Hassett, Steve Peppers, Gustav Rodrigo, Greg Van Slyke, and David (Xiqaojian) Zhao 15 Large–Scale Protein Purification, Self–Cleaving Aggregation Tags 257 Iraj Ghazi and David W. Wood 16 Lipopolysaccharide, LPS removal, Depyrogenation 269 Pérola O. Magalhães and Adalberto Pessoa Jr. 17 Porous Media in Biotechnology 277 Manuel Mota, Alexander Yelshin, and Inna Yelshina 18 Protein Aggregation and Precipitation, Measurement and Control 293 Catherine H. Schein PART IV EQUIPMENT DESIGN FOR DOWNSTREAM RECOVERY AND PROTEIN PURIFICATION 325 19 Cleaning and Sanitation in Downstream Processes 327 Gail Sofer, Craig Robinson, Joanthan Yourkin, Tina Pitarresi, and Darcy Birse 20 Clean–in–place 343 Phil J. Bremer and Richard Brent Seale 21 Large Scale Chromatography Columns, Modeling Flow Distribution 353 Zhiwu Fang 22 Pumps, Industrial 373 Bob Stover and Ed Domanico PART V DOWNSTREAM cGMP OPERATIONS 389 23 Affinity Chromatography of Plasma Proteins 391 Mirjana Radosevich and Thierry Burnouf 24 Antibody Purification, Monoclonal and Polyclonal 405 James J. Reilly and Michiel E. Ultee 25 Chromatographic Purification of Virus Particles 415 Pete Gagnon 26 Chromatography, Hydrophobic Interactions 437 Per Karsnäs 27 Chromatography, Radar Flow 449 Tingyue Gu 28 Drying, Biological Materials 465 Chung Lim Law and Arun S. Mujumdar 29 Freeze–Drying, Pharmaceuticals 485 Jinsong Liu 30 Freezing, Biopharmaceutical 505 Philippe Lam and Jamie Moore 31 Membrane Chromatography 521 John Pieracci and Jörg Thömmes 32 Membrane Separations 545 Manohar Kalyanpur 33 Plasmid Purification 557 H .S. C. Barbosa and J. C. Marcos 34 Protein Chromatography, Manufacturing Scale 571 Joseph Bertolini 35 Protein Crystallization, Kinetics 579 Gianluca Di Profio, Efrem Curcio, and Enrico Drioli 36 Protein Purification, Aqueous Liquid Extraction 603 Maria–Regina Kula and Klaus Selber 37 Protein Ultrafiltration 617 Robert van Reis and Andrew L. Zydney 38 Virus Retentive Filters 641 George Miesegaes, Scott Lute, Hazel Aranha, and Kurt Brorson PART VI BIOPHARMACEUTICAL FACILITY VALIDATION 655 39 Biopharmaceutical Facility Design and Validation 657 Jeffrey N. Odum 40 Closed Systems in Bioprocessing 677 Jeffrey Odum 41 Facility Design for Single Use (SU) Downstream Materials 685 Robert Z. Maigetter, Tom Piombino, Christian Wood, Tom Gervais, Claudio Thomasin, Bryan Shingle, Dave A. Wareheim, and David Clark 42 eGMPs for Production Rooms 715 Claude Arlois, Jean Didelez, Patrick Florent, and Guy Godeau 43 Heating, Ventilation, and Air Conditioning 731 Dennis Dobie 44 Sterilization–in–Place (SIP) 747 P. T. Noble PART VII FDA cGMP REGULATORY COMPLIANCE 757 45 Pharmaceutical Bioburden Testing 759 Nathaniel G. Hentz, PhD 46 Chromatography, Industrial Scale Validation 775 Sandy Weinberg and Carl A. Rockburne 47 GMPs and GLSPs 795 Beth H. Junker 48 Quality by Design (QBD) 815 Rakhi B. Shah, Jun T. Park, Erik K. Read, Mansoor A. Khan, and Kurt Brorson 49 Regulatory Requirements, European Community 829 Gary Walsh Index 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)