Contents 1 Fermentation Pilot Plant Yujiro Harada, Kuniaki Sakata, Seiji Sato and Shinsaku Takayama PROLOGUE(by Yujiro Harada) 1.0 MICROBIAL FERMENTATION (by Kuniaki Sakato 1.1 Fermentation Pilot Plant 1.2 Bioreactors and Culture Techniques 233 for microbial Processes 1. 3 Application of Computer Control and Sensing Technologies for Fermentation Process 1.5 Bioreactors for Recombinant DNA Technology.... 22 2.1 Introduction 2.2 Culture media 2.3 Microcarrier Culture and General Control Parameters. 26 2.4 Perfusion Culture Systems as a New High Density Culture Technolog 2.5 Sedimentation Column Perfusion Systems 2.6 High Density Culture Using a Perfusion Culture System with Sedimentation Column 2.7 Acknowledgment References and Bibliography (Section 2)
Contents 1 Fermentation Pilot Plant ........................................ 1 Yujiro Harada, Kuniaki Sakata, Seiji Sat0 and Shinsaku Takayama PROLOGUE (by Yujiro Harada) ................................................. 1 1 .O MICROBLAL FERMENTATION (by Kuniaki Sakato) ........ 2 ........... 3 ........... 3 1.1 Fermentation Pilot Plant ...... 1.2 Bioreactors and Culture Techniques 1.3 Application of Computer Control and 1.4 Scale-up ................................................... 1.5 Bioreactors for Recombinant DNA Technolo References (Section 1) ....................................... 2.0 MAMMALIAN CELL CULTURE SYSTEM (by 2.1 Introduction ............................... ......................... 25 2.2 Culture Media ........................................ 2.3 Microcarrier Culture and General Contro 2.4 Perfision Culture Systems as a New High Density for Microbial Processes ........................ Sensing Technologies for Fermentation Process ............... 8 Culture Technology ....................................................... 3 1 2.5 Sedimentation Column Perfision Systems ...................... 33 2.6 High Density Culture Using a Perfision Culture System with Sedimentation Column. 2.7 Acknowledgment ................. References and Bibliography (Se xiii
Contents 3.0 BIOREACTORS FOR PLANT CELL TISSUE AND ORGAN CULTURES (by Shinsaku Takayama)....41 3. 1 Background of the Technique--Historical Overview...41 3.2 Media Formulations 3.3 General applications 3.4 Bioreactors-Hardware Configuration 3.5 Bioreactor Size 3.6 Culture Period 3.7 Aeration and Agitation 3.8 Microbial Contamination 3.9 Characteristics 3.10 Manipulation 3. 11 Scale-up Problems 3. 12 Bioprocess Measurement and Control References( Section 3) 2 Fermentation Design.... 67 Allan C Soderberg L 0 INTRODUCTION 2.0 FERMENTATION DEPARTMENT, EQUIPMENT AND SPACE REQUIREMENTS......68 2. 1 The Microbiological Laboratories... 68 2.2 Analytical Support Laboratories 2.3 Production: Raw Material Storage…… 71 2.4 Media Preparation or Batching Area 2. 5 The Seed Fermenter Layout 2. 6 The Main Fermenter Layout 234 2.7 Nutrient Feed Tanks 2. 8 Sterile Filters ……75 2.9 Air Compressors 2.10 Valves(To Maintain Sterility) 2.11 Pumps 78 2. 12 Cooling Equipment 2. 13 Environmental Control 3.0 GENERAL DESIGN DATA 4.0 CONTINUOUS STERILIZERS 4. 1 A Justification for Continuous Sterilization 4.2 Support Equipment for a sterilizer 4.3 The Sterilizing Section 89 4.4 The Cooling Section 5.0 FERMENTER COOLING
xiv Contents 3.0 BIOREACTORS FOR PLANT CELL TISSUE AND ORGAN CULTURES (by Shinsaku Takayama) ...... 3.1 Background of the Technique-Historical Overview ..... .4 1 3.2 Media Formulations ............................. 3.3 General Applications ........................... 3.4 Bioreactors-Hardware Configuration.. 3.5 Bioreactor Size ..................................... 3.6 Culture Period ...................................... 3.7 Aeration and Agitation ....................... 3.8 Microbial Contamination .................... 3.9 Characteristics ...................................................... 3.10 Manipulation ................................... 3.11 Scale-up Problems .. 3.12 Bioprocess Measure References (Section 3) ............................................... .................... 55 2 Fermentation Design ............................................. 67 Allan C. Soderberg 1 .O INTRODUCTION ..................................... 2.0 FERMENTATION DEPARTMENT, EQUI AND SPACE REQUIREMENTS ............... 2.1 The Microbiological 2.2 Analytical S 2.3 Production: 2.4 Media Preparation or Batchin 2.5 The Seed Fermenter Layout .. 2.7 Nutrient Feed Tanks ............. 2.8 Sterile Filters ........... 2.9 Air Compressors ................ 2.10 Valves (To Maintain Steril 2.11 Pumps 78 2.12 Cooling Equipment .......... 2.13 Environmental Control ................................... 2.6 The Main Fermenter Layout .... ................... 74 3 .O GENERAL DESIGN DATA .......... 4.0 CONTINUOUS STERILIZERS ................. 4.1 A Justification for Continuo 4.2 Support Equipment for a St 4.3 The Sterilizing Section ..................... 4.4 The Cooling Section ....................................... ......................... 79 5.0 FERMENTER COOLING
Contents 6.0 THE DESIGN OF LARGE FERMENTERS (BASED ON AERATION 6. 1 Agitator Effectiveness 6.2 Fermenter Height 6. 3 Mixing Horsepower by Aeration 6.4 Air Sparger Design 107 6.5 Comparison of Shear of Air Bubbles by Agitators and Jets… 6.6 The Effect of Shear on Microorganisms 6. 7 Other Examples of Jet Air/Liquid Mixing 6.8 Mechanical Versus Non-mechanical Agitation l10 7.0 TROUBLE SHOOTING IN A FERMENTATION PLANTlll 8.0 GENERAL COMMENTS REFERENCES 120 3 Nutritional Requirements in Fermentation Processes 122 willem A Kampen L0 INTRODUCTION 20 NUTRITIONAL REQUIREMENTS OF THE CELL……125 3.0 THE CARBON SOURCE 128 0 THE NITROGEN AND SULFUR SOURCE 135 5.0 THE SOURCE OF TRACE AND ESSENTIAL ELEMENTS 6.0 THE VITAMIN SOURCE AND OTHER GROWTH FACTORS 7.0 PHYSICAL AND IONIC REQUIREMENTS 147 8.0 MEDIA DEVELOPMENT 9.0 EFFECT OF NUTRIENT CONCENTRATION ON GROWTH RATE REFERENCES 4 Statistical Methods For Fermentation Optimization 161 Edwin 0. Geiger 1.0 INTRODUCTION 161 2.0 TRADITIONAL ONE-VARIABLE-AT-A-TIME METHOD 3.0 EVOLUTIONARY OPTIMIZATION 162 4.0 RESPONSE SURFACE METHODOLOGY 166
Contents xv 6.0 THE DESIGN OF LARGE FERMENTERS (BASED ON AERATION) ................................................. 99 6.2 Fermenter Height ......................................................... 100 6.3 Mixing Horsepower by Aeration .................................. 10 1 by Agitators and Jets ................................................... 107 6.7 Other Examples of Jet Airkiquid Mixing .................... 109 6.8 Mechanical Versus Non-mechanical Agitation ............. 1 10 7.0 TROUBLE SHOOTING IN A FERMENTATION PLANT 11 1 8.0 GENERAL COMMENTS ................................................. 1 19 REFERENCES ................................................................... 120 6.1 Agitator Effectiveness ................................................... 99 6.4 Air Sparger Design ...................................................... 107 6.5 Comparison of Shear of Air Bubbles 6.6 The Effect of Shear on Microorganisms ....................... 109 3 Nutritional Requirements in Fermentation Processes .............................................................. 122 Willem H. Kampen 1 .O INTRODUCTION ............................................ 2.0 NUTRITIONAL REQUIREMENTS OF THE C 3 .O THE CARBON SOURCE ....................... 4.0 THE NITROGEN AND SULFUR SOUR 5.0 THE SOURCE OF TRACE AND ESSENTIAL ELEMENTS ....................... 6.0 THE VITAMIN SOURCE AND OTHER GROWTH FACTORS ............................................. 7.0 PHYSICAL AND IONIC REQUIREMENTS .......... 8.0 MEDIA DEVELOPMEN ......................................... 149 9.0 EFFECT OF NUTRIEN CENTRATION GROWTH RATE ............................................. REFERENCES ...... ........................................... 159 4 Statistical Methods For Fermentation Optimization ................................ 161 Edwin 0. Geiger 1 .O INTRODUCTION ............................................................ 16 1 2.0 TRADITIONAL ONE-VARIABLE-AT-A-TIME METHOD ................................................................... 16 1 3 .O EVOLUTIONARY OPTIMIZATION ............................... 162 4.0 RESPONSE SURFACE METHODOLOGY ..................... 166
xvi Contents 5.0 ADVANTAGES OF RSM 5. 1 Maximum Information from Experiments 169 5.2 Forces One To plan 170 5. 3 Know How Long Project Will Take 5.4 Interaction Between Variables 5.5 Multiple Responses 171 5.6 Design Data 171 6.0 DISADVANTAGES OF RSM 174 7.0 POTENTIAL DIFFICULTIES WITH RSM 174 7. 1 Correlation Coefficient 7. 2 Regression Coefficients 7.3 Standard Error of the Regression Coefficient…………176 7. 4 Computed T value 177 7.5 Standard Error of the Estimate 7. 6 analysis of variance 8.0 METHODS TO IMPROVE THE RSM MODEL 9.0 SUMMARY… REFERENCES 5 Agitation.....……181 James Y Oldshue 1.0 THEORY AND CONCEPTS 2.0 PUMPING CAPACITY AND FLUID SHEAR RATES 132 3.0 MIXERS AND IMPELLERS 183 1 Fluidfoil Impellers 191 4.0 BAFFLES 5.0 FLUID SHEAR RATES 203 5.1 Particles 206 5.2 Impeller Power Consumption 5.3 Mass Transfer Characteristics of Fluidfoil Impellers..217 6.0 FULL-SCALE PLANT DESIGN 6. 1 Some General Relationships in Large Scale Mixers Compared to Small Scale mixers 219 6. 2 Scale-Up Based on Data from Existing 22 6.3 Data Based on Pilot Plant Work 6. 4 Sulfite Oxidation Data 6.5 Oxygen Uptake Rate in the Broth 6.6 Some General Concepts 6.7 Reverse Rotation dual Power Impellers 228 7.0 FULL SCALE PROCESS EXAMPLE 229 8.0 THE ROLE OF CELL CONCENTRATION ON MASS TRANSFER RATE 231
mi Contents 5.0 ADVANTAGES OF RSM ................................................ 168 5.1 Maximum Information from Experiments .................... 169 5.2 Forces One To Plan ..................................................... 170 5.3 Know How Long Project Will Take ............................. 170 5.4 Interaction Between Variables ..................................... 170 5.5 Multiple Responses ............................... 5.6 Design Data .......................................... 6.0 DISADVANTAGES OF RSM .................... 7.0 POTENTIAL DIFFICULTIES WITH RSM ...................... 174 7.1 Correlation Coefficient ................................................ 176 7.2 Regression Coefficients ........................................ 7.3 Standard Error of the Regression Coefficient ............... 176 7.4 Computed T Value ....................................... 7.5 Standard Error of the Estimate ..................... 7.6 Analysis of Variance ................................................... 177 8.0 METHODS TO IMPROVE THE RSM MODEL .............. 178 9.0 SUMMARY ..................... ................................... 179 REFERENCES ..................... .................... 179 5 Agitation ....................... .............. ....................... 181 James I: Oldshue 1 . 0 THEORY AND CONCEPTS ......................... 2.0 PUMPING CAPACITY AND FLUID SHEAR RATES .... 182 3.0 MIXERS AND IMPELLERS ................... 183 3.1 Fluidfoil Impellers ...................................................... 191 4.0 BAFFLES ................................................................... 201 5.0 FLUID SHEAR RATES ........................... 5.1 Particles .................................................................. 206 5.2 Impeller Power Consumption ...... ............................ 207 5.3 Mass Transfer Characteristics of idfoil Impellers .... 217 6.1 Some General Relationships in Large Scale Mixers Compared to Small Scale Mixers ............................. 6.2 Scale-up Based on Data from Existing Production Plant ........................... ................... 220 6.3 Data Based on Pilot Plant Work ............... .. 223 6.4 Sulfite Oxidation Data ................................................. 226 6.5 Oxygen Uptake Rate in the Broth ......... ................... 227 227 6.7 Reverse Rotation Dual Power Impellers ....................... 228 .............. 229 ................... 231 6.0 FULL-SCALE PLANT DESIGN ................................ 6.6 Some General Concepts ................................. 7.0 FULL SCALE PROCESS EXAMPLE ......... 8.0 THE ROLE OF CELL CONCENTRATION MASS TRANSFER RATE
x 9.0 SOME OTHER MASS TRANSFER CONSIDERATIONS 235 10.0 DESIGN PROBLEMS IN BIOCHEMICAL ENGINEERING 236 11.0 SOLUTION-FERMENTATION PROBLEMS 238 LIST OF ABBREⅤ IATIONS 240 REFERENCES 6 Filtration.................... 242 Celeste todaro L0 INTRODUCTION 242 1. 1 Depth Filtration 243 2.0 CAKE FILTRATION 3.0 THEORY 243 3. 1 Flow Theory 243 3.2 Cake Compressibility 40 PARTICLE SIZE DISTRIBUTION 245 5.0 OPTIMAL CAKE THICKNESS 6.0 FILTER AID 247 70 FILTER MEDIA 248 8.0 EQUIPMENT SELECTION 250 8.1 Pilot testing………… 250 9.0 CONTINUOUS vS BATCH FILTRATION 251 100 ROTARY VACUUM DRUM FILTER 251 10.1 Operation and Applications 10.2 Optimization 258 110 NUTSCHES 258 ll.1 Applications… 258 11.2 Operation 260 11. 3 Maintenance 264 12.0 HP-HYBRID FILTER PRESS 12. 1 Applications 266 12.2 Operation 12. 3 Maintenance 269 13.0 MANUFACTURERS Rotary Drum Vacuum Filters 269 Nutsche 269 Hybrid Filter Press REFERENCES 270 7 Cross-Flow Filtration. Ramesh. bhave 1.0 INTRODUCTION 271
Contents xvii 9.0 SOME OTHER MASS TRANSFER CONSIDERATIONS235 10.0 DESIGN PROBLEMS IN BIOCHEMICAL ENGINEERING ............................................................... 23 6 1 1 .O SOLUTION-FERMENTATION PROBLEMS ............... 238 LIST OF ABBREVIATIONS .................................................... 240 REFERENCES ................................................................... 241 6 Filtration ............................................................. 242 1 .O INTRODUCTION ............................................................ 242 ................................................... 243 2.0 CAKE FILTRATION ....................................................... 243 3.0 THEORY ....................................... 3.1 Flow Theory ................................... 4.0 PARTICLE SIZE DISTRIBUTION ...... 5.0 OPTIMAL CAKE THICKNESS ........... 6.0 FILTER AID ................................................................... 247 7.0 FILTER MEDIA .............................. 8 .O EQUIPMENT SELECTION ............ 8.1 Pilot Testing ............................... Celeste L Todaro 1.1 Depth Filtration .... 3.2 Cake Compressibility ...................... .................... 244 10.1 Operation and Applications .............. ............................................ 258 11.1 Applications ......................... 11.2 Operation .................................................................. 260 11.3 Maintenance ............................................................. 264 12.0 HP-HYBRID FILTER PRESS .......................................... 266 12.1 Applications .......... ........................................ 266 12.2 Operation ........................................................ 267 12.3 Maintenance ......... ......................................... 269 13.0 MANUFACTURERS ............................ Rotary Drum Vacuum Filters ................. Nutsches .......................................... Hybrid Filter Press ............. REFERENCES ......... 7 Cross-Flow Filtration .......................................... 271 1 .O INTRODUCTION ............................................................ 27 1 Ramesh R. Bhave
xviii Contents 2.0 CROSS-FLOW vS. DEAD END FILTRATION 273 3.0 COMPARISON OF CROSS-FLOW WITH OTHER COMPETING TECHNOLOGIES 277 4 Polymeric Microfilters and Ultrafilters…… 4.2 Inorganic Microfilters and Ultrafilters 5.0 OPERATING CONFIGURATIONS 5. 1 Batch System 5.2 Feed and Bleed 292 5.3 Single vs. Multistage Continuous System 6.0 PROCESS DESIGN ASPECTS 6. 1 Minimization of Flux Decline With Backpulse or Backwash 6.2 Uniform Transmembrane Pressure Filtration 6. 3 Effect of Operating Parameters on Filter Performance. 305 6.4 Membrane Cleaning 6.5 Pilot Scale Data and scale 316 6.6 Troubleshooting 318 6.7 Capital and Operating Cost 318 6. 8 Safety and Environmental Considerations 322 7.0 APPLICATIONS OVERVIEW 322 7. 1 Clarification of Fermentation Broths 7.2 Purification and Concentration of Enzymes 7.3 Microfiltration for Removal of Microorganisms or Cell Debris 324 7. 4 Production of Bacteria-free Water 329 7.5 Production of Pyrogen-free Water 331 8.0 GLOSSARY OF TERMS 333 ACKNOWLEDGMENT 337 APPENDIX: LIST OF MEMBRANE MANUFACTURERS (MICROFILTRATION AND ULTRAFILTRATION).338 REFERENCES 343 8 Solvent Extraction................. 348 david b. todd L0 EXTRACTION CONCEPTS 1. 1 Theoretical St 2.0 DISTRIBUTION DATA 352 3.0SOLⅤ ENT SELECTION 4.0 CALCULATION PROCEDURES 355 4. 1 Simplified Solution 358 4.2 Sample Stage Calculation 360 5.0 DROP MECHANICS
xviii Contents 2.0 CROSS-FLOW VS. DEAD END FILTRATION ................ 273 3.0 COMPARISON OF CROSS-FLOW WITH OTHER COMPETING TECHNOLOGIES ................................ 4.2 Inorganic Microfilters and Ultrafilters .......................... 285 5 .O OPERATING CONFIGURATIONS ................................. 289 5.2 Feed and Bleed ............................................................ 292 5.3 Single vs. Multistage Continuous System ..................... 297 6.0 PROCESS DESIGN ASPECTS ........................................ 297 6.1 Minimization of Flux Decline With Backpulse or Backwash ..... ............................ ..................... 297 6.2 Uniform Transmembrane Pressure Filtration ................ 300 6.3 Effect of Operating Parameters on Filter Performance .. 305 6.4 Membrane Cleaning ................................ 6.6 Troubleshooting ........................................ 3 18 ......................... 318 6.8 Safety and Environmental Consi 7.1 Clarification of Fermentation Broths ......... 7.2 Purification and Concentration of Enzymes .................. 323 7.3 Microfiltration for Removal of Microorganisms 7.4 Production of Bacteria-free Water ............................... 329 7.5 Production of Pyrogen-free Water .. 8.0 GLOSSARY OF TERMS ................... ACKNOWLEDGMENT ............................. 4.1 Polymeric Microfilters and Ultrafilters ........................ 28 1 5.1 Batch System .............................................................. 289 6.5 Pilot Scale Data and Scaleup ....................................... 3 16 6.7 Capital and Operating Cost ...... 7.0 APPLICATIONS OVERVIEW ......................... or Cell Debris ........................................................ AP-PENDIX: LIST OF MEMBRANE MAN (MICROFILTRATION AND ULTRAFILTRATION) ...... 33 8 REFERENCES ................................................. ......... 343 8 Solvent Extraction ............................................... 348 1 .O EXTRACTION CONCEPTS ............................................ 348 2.0 DISTRIBUTION DATA ............... 3.0 SOLVENT SELECTION .............................. 4.0 CALCULATION PROCEDURES ........................... 355 4.2 Sample Stage Calculation ............................................ 360 363 DavidB. Todd 1.1 Theoretical Stage ........................... 4.1 Simplified Solution .................................. 5 .O DROP MECHANICS
Contents ri 6.0 TYPES OF EXTRACTION EQUIPMENT 6. 1 Non-Agitated gravity Flow Extractors 6. 2 Stirred gravity Flow Extractors 6.3 Pulsed Gravity Flow Extractors 6. 4 Centrifugal Extractors 373 6.5 Equipment Size Calculation ,374 7.0 SELECTION OF EQUIPMENT 8.0 PROCEDURE SUMMARY 9.0 ADDITIONAL INFORMATION 380 REFERENCES 9 lon Exchange 382 frederick J Dechow 1.0 INTRODUCTION 382 I lon Exchange Processes 1.2 Chromatographic Separation 384 2.0 THEORY 2. 1 Selectivity 2.2 Kinetics 395 2.3 Chromatographic Theory .400 3.0 ION EXCHANGE MATERIALS AND THEIR PROPERTIES 3. 1 lon Exchange Matrix 407 3.2 3.3 Porosity and Surface Area 3. 4 Particle Density 4l8 3.5 Particle Size 419 4.0 LABORATORY EVALUATION OF RESIN 5.0 PROCESS CONSIDERATIONS 426 5. 1 Design Factors 426 5.2 Scaling-up Fixed Bed Operations 5.3 Sample Calculation 429 5. 4 Comparison of Packed and Fluidized Beds 5.5 Chromatographic Scale-Up Procedures 433 5.6 Pressure Drop 5.7 lon Exchange Resin Limitations 439 5.8 Safety Considerations 44l 6.0 ION EXCHANGE OPERATIONS 6.1 Pretreatment 445 6.2 Batch Operations 445 6.3 Column Operations 6. 4 Elution/Regeneration 458 7.0 INDUSTRIAL CHROMATOGRAPHIC OPERATIONS. 462 REFERENCES 470
Contents xix 6.0 TYPES OF EXTRACTION EQUIPMENT ....................... 366 6.1 Non-Agitated Gravity Flow Extractors ........................ 3 66 6.2 Stirred Gravity Flow Extractors ............ 6.3 Pulsed Gravity Flow Extractors ................................... 37 1 6.4 Centnfbgal Extractors ................................................. 373 6.5 Equipment Size Calculation ....................... 7.0 SELECTION OF EQUIPMENT ..................... 8.0 PROCEDURE SUMMARY ............................ 9.0 ADDITIONAL INFORMATION ......................... REFERENCES ........ ............................................. 380 9 Ion Exchange ............ ..... .................. ............ ...... 382 Frederick J. Dechow 1 .O INTRODUCTION ............................................................ 3 82 1.1 Ion Exchange Processes ............................................... 383 .... 384 2.0 THEORY ................................................................... 389 1.2 Chromatographic Separation .......................... 2.1 Selectivity .......................................... 2.2 Kinetics ........................................ 2.3 Chromatographic Theory ............................................. 400 3.0 ION EXCHANGE MATERIALS AND THEIR PROPERTIES ...................................................... 407 3.1 Ion Exchange Matrix ................................................... 407 3.2 Functional Groups .......................................... 3.3 Porosity and Surface Area .............................. 3.4 Particle Density ............................................. 418 3.5 Particle Size ............................................. 4.0 LABORATORY EVALUATION OF RESIN. 5.0 PROCESS CONSIDERATIONS ...................................... 426 5.1 Design Factors ................................................. 5.2 Scaling-up Fixed Bed Operations . 5.3 Sample Calculation .................................... 5.4 Comparison of Packed and Fluidized Beds .. 5.6 Pressure Drop ............................................................. 436 5.7 Ion Exchange Resin Limitations ......... 5.8 Safety Considerations ........................ 6.0 ION EXCHANGE OPERATIONS .................................... 443 6.1 Pretreatment ................................................................ 445 6.2 Batch Operations ......................................................... 445 6.3 Column Operations ................................ 6.4 ElutiodRegeneration ................................................... 45 8 7.0 INDUSTRIAL CHROMATOGRAPHIC OPERATIONS , ,462 REFERENCES ................................................................... 470 5.5 Chromatographic Scale-up Procedures
Contents 10 Evaporation 476 Howard Freese 10 INTRODUCTION 476 2.0 EVAPORATORS AND EVAPORATION SYSTEMS. 477 3.0 LIQUID CHARACTERISTICS 4.0 HEAT TRANSFER IN EVAPORATORS 5.0 EVAPORATOR TYPES 5.1 Jacketed vessels 52 Horizontal Tube Evaporators…… 5.3 Short-Tube Vertical Evaporators 493 5. 4 Propeller Calanda 5.5 Long-Tube Vertical Evaporators 5.6 Falling Film Evaporators 495 5.7 Forced Circulation Evaporator 5.8 Plate Evaporators 59 Mechanically Agitated Thin-Film Evaporators…………502 5.10 Flash Pots and Flash Evaporators 505 5.11 Multiple Effect Evaporators 506 6.0 ENERGY CONSIDERATIONS FOR EVAPORATION SYSTEM DESIGN 510 7.0 PROCESS CONTROL SYSTEMS FOR EVAPORATORS518 8.0 EVAPORATOR PERFORMANCE 522 9.0 HEAT SENSITTVE PRODUCTS 10.0 INSTALLATION OF EVAPORATORS 11.0 TROUBLESHOOTING EVAPORATION SYSTEMS.. 528 REFERENCES AND SELECTED READING MATERIAL.. 532 11 Crystallization………………… 535 Stephen M. Glasgow 1.0 INTRODUCTION 535 2.0 THEOR 536 2. 1 Field of Supersaturation ... 2.2 Formation of a Supersaturated Solution 2.3 Appearance of Crystall ne Nuc 2. 4 Growth of Nuclei to size 539 3.0 CRYSTALLIZATION EQUIPMENT 3. 1 Evaporative Crystallizer 3. 2 Vacuum Cooling Crystallizer 3 Cooling Crystallizer 3. 4 Batch Crystallization 4.0 DATA NEEDED FOR DESIGN 546
xx Contents 10 Evaporation .......................................................... 476 Howard L. Freese 1.0 INTRODUCTION ..................................................... 2.0 EVAPORATORS AND EVAPORATION SYSTEMS 3.0 LIQUID CHARACTERISTICS ................................. 4.0 HEAT TRANSFER IN EVAPORATORS ... 5 .O EVAPORATOR TYPES ............................. 5.1 Jacketed Vessels .......................................................... 49 1 5.2 Horizontal Tube Evaporators ....................................... 493 5.3 Short-Tube Vertical Evaporators ............................. 5.4 Propeller Calandrias .................................................... 494 5.5 Long-Tube Vertical Evaporators ......... ................. 494 5.6 Falling Film Evaporators ...................................... 5.7 Forced Circulation Evaporators ................................... 497 5.8 Plate Evaporators ................................................. 5.9 Mechanically Agitated %-Film Evaporators ...... 5.10 Flash Pots and Flash Evaporators ........... 5.11 Multiple Effect Evaporators ................... 6.0 ENERGY CONSIDERATIONS FOR EVAPORATION SYSTEM DESIGN ........................................................... 5 10 7.0 PROCESS CONTROL SYSTEMS FOR EVAPORATORS518 10.0 INSTALLATION OF EVAPORATORS ............ 11 Crystallization ..................................................... 535 Stephen M. Glasgow 1.0 INTRODUCTION .. ........................... 2.0 THEORY .................................................... 2.1 Field of Supersaturation ................ 2.2 Formation of a Supersaturated Solution 2.3 Appearance of Crystalline Nuclei .. 2.4 Growth of Nuclei to Size ............... 3 .O CRYSTALLIZATION EQUIPMENT ............................... 54 1 3.1 Evaporative Crystallizer ................ 3.2 Vacuum Cooling Crystallizer ....................................... 545 3.3 Cooling Crystallizer ...... 3.4 Batch Crystallization .................................... 4.0 DATA NEEDED FOR DESIGN ....... 544 .................. 546
Content 5.0 SPECIAL CONSIDERATIONS FOR FERMENTATION PROCESSES 547 5. 1 Temperature Limitation 547 5.2 High Viscosity 547 5.3 Long Supersaturation Time 548 5.4 Slow Crystal Growth Rate 548 6.0 METHOD OF CALCULATION 548 7.0 TROUBLESHOOTING 7. I Deposits 7. 2 Crystal Size Too Small 552 7.3 Insufficient Vacuum 553 7.4 Instrument Malfunction 7.5 Foaming 4 7.6 Pump Performance 555 8.0 SUMMARY 555 9.0 AMERICAN MANUFACTURERS 556 REFERENCES 557 12 Centrifugation…,,… Celeste l todaro 1.0 INTRODUCTION 558 2.0 THEORY 558 3.0 EQUIPMENT SELECTION 561 3. I Pilot Testing... 3.2 Data Collection 563 3. 3 Materials of Construction 4.0 COMPONENTS OF THE CENTRIFUGE 5.0 SEDIMENTATION CENTRIFUGES 6.0 TUBULAR-BOWL CENTRIFUGES 6. 1 Operation 7.0 CONTINUOUS DECANTER CENTRIFUGES (WITH CONVEYOR) 7. 1 Maintenance 570 7. 2 Typical Problem For Continuous Decanter Centrifuge with Conveyor 8.0 DISK CENTRIFUGES 571 8. 1 Operatic 8.2 Maintenance 572 9.0 FILTERING CENTRIFUGES VS SEDIMENTATION CENTRIFUGES 573 10.0 FILTERING CENTRIFUGES 573 11.0 VERTICAL BASKET CENTRIFUGES 575 I1 I Applications
Contents xui 5.0 SPECIAL CONSIDERATIONS FOR FERMENTATION PROCESSES .............. ............... 547 5.1 Temperature Limitation 547 5.3 Long Desupersaturation Time .............................. 5.4 Slow Crystal Growth Rate ..................... 6.0 METHOD OF CALCULATION ............................... 7.0 TROUBLESHOOTING ............................................ 7.1 Deposits ................................................................... 551 7.2 Crystal Size Too Small ................................................ 552 7.3 Insufficient Vacuum .................................................... 553 7.4 Instrument Malfimction ........................... ,554 7.5 Foaming ................................................................... 554 7.6 Pump Performance ...................................................... 555 .................................... 5.2 High Viscosity ............................................................ 547 8.0 SUMMARY ................................................................... 555 9.0 AMERICAN MANUFACTURERS ....... REFERENCES ...................... 12 Centrifugation ..................................................... 558 Celeste L Todaro 1 .O INTRODUCTION ............................... 3.0 EQUIPMENT SEL ................... 558 3.1 Pilot Testing ..... ......................... 4.0 COMPONENTS 5.0 SEDIMENTATI 6.0 TUBULAR-BO 6.1 Operation ............................................. 7.0 CONTINUOU 7.1 Maintenance ................ ............................ 8.1 Operation ........................................................ 8.2 Maintenance ............................ ....................... 572 9.0 FILTERING CENTRIFUGES VS.
rii Contents 11.2 Solids Discharge 11.3 Operational Speeds 577 11. 4 Maintenance 12.0 HORIZONTAL PEELER CENTRIFUGE 577 12. 1 Applications 577 12.2 Oper 13.0 INVERTING FILTER CENTRIFUGE 579 13. 1 Operation 13.2 Maintenance 14.0 MAINTENANCE: CENTRIFUGE 583 14. 1 Bearings 584 15.0 SAFETY 16.0 PRESSURE-ADDED CENTRIFUGATION 585 17.0 MANUFACTURERS 17. 1 Filtering Centrifuges 588 17.2 Sedimentation Centrifuges 17.3 Oxygen Analyzer 589 REFERENCES 13 Water Systems For Pharmaceutical Facilities. 590 Mark Keyashian 1. 0 INTRODUCTION <o0 2.0 SCOPE 590 3. 0 SOURCE OF WATER 4.0 POTABLE WATER 593 5.0 WATER PRETREATMENT 6.0 MULTIMEDIA FILTRATION 595 7.0 WATER SOFTENING 8.0 ACTIVATED CARBON O ULTRAVIOLET PURIFICATION 598 10.0 DEIONIZATION 110 PURIFIED WATER 12.0 REVERSE OSMOSIS 603 13.0 WATER FOR INJECTION 14.0 WATER SYSTEM DOCUMENTATION APPENDIX I: EXISTING AND PROPOSED U. S. EPA DRINKING WATER STANDARDS APPENDIX II: DEP ARTMENT OF HEALTH EDUCATION AND WELFARE PUBLIC HEALTH SERVICE 613 Criteria for the Acceptability of an Ultraviolet Disinfecting Unit 6l4 REFERENCES
xxii Contents 11.2 Solids Discharge ................................ 1 1.4 Maintenance ...................................... 12.1 Applications ....................................... 1 1.3 Operational Speeds ............................ 12.0 HORIZONTAL PEELER CENTRIFUGE ......................... 577 12.2 Operation .................................................................. 578 13 .O INVERTING FILTER CENTRIFUGE .................... 13.1 Operation ........................................................ 13.2 Maintenance ...................................... ...... 14.1 Bearings ............................................... 14.0 MAINTENANCE: CENTRIFUGE .................................... 583 15.0 SAFETY ................................................................... 585 17.0 MANUFACTURERS ........................................................ 588 16.0 PRESSURE-ADDED CENTRIFUGATION ..................... 585 17.1 Filtering Centrifuges ................................................. 588 17.3 Oxygen Analyzers . . 17.2 Sedimentation Centrifuges ..................... ...................................... 589 REFERENCES ........ 13 Water Systems For Pharmaceutical Facilities ... 590 Mark Keyashian 1 .O INTRODUCTION ....... 2.0 SCOPE .................................................... 3.0 SOURCE OF WATER. 4.0 POTABLE WATER ......................................... 5 .O WATER PRETREATMENT ............................. 6.0 MULTIMEDIA FILTRATION 7.0 WATER SOFTENING ........................... 8.0 ACTIVATED CARBON ................................................... 596 9.0 ULTRAVIOLET PURIFICATION ................................... 598 10.0 DEIONIZATION .......................................... 598 1 1 .O PURIFIED WATER .......... ..................................... 601 12.0 REVERSE OSMOSIS ................................... 13 .O WATER FOR INJECTION ............................................... 604 14.0 WATER SYSTEM DOCUMENTATION .... APPENDIX I: EXISTING AND PROPOSED U. DRINKING WATER STANDARDS ........... APPENDIX 11: DEPARTMENT OF HEALTH, E AND WELFARE PUBLIC HEALTH SERVICE .............. 613 Criteria for the Acceptability of an Ultraviolet Disinfecting Unit ........ ....................... 614 REFERENCES ................................ .............. 615
