Fermentation and Biochemical Engineering Handbook

This is a well-rounded handbook of fermentation and biochemical engineering presenting techniques for the commercial production of chemicals and pharmaceuticals via fermentation. Emphasis is given to unit operations fermentation, separation, purification, and recovery. Principles, process design, and equipment are detailed. Environment aspects are covered.

The practical aspects of development, design, and operation are stressed. Theory is included to provide the necessary insight for a particular operation. Problems addressed are the collection of pilot data, choice of scale-up parameters, selection of the right piece of equipment, pinpointing of likely trouble spots, and methods of troubleshooting.

The text, written from a practical and operating viewpoint, will assist development, design, engineering and production personnel in the fermentation industry. Contributors were selected based on their industrial background and orientation. The book is illustrated with numerous figures, photographs and schematic diagrams.

Engineers and scientists in the chemical and pharmaceutical industries who use fermentation techniques in production. Development, design, engineering and production personnel in the fermentation industry

1. Fermentation Pilot Plant 1.1 Microbial Fermentation 1.2 Mammalian Cell Culture System 1.3 Bioreactors for Plant Cell Tissue and Organ Cultures
2. Fermentation Design 2.1 Introduction 2.2 Fermentation Department, Equipment and Space Requirements 2.3 General Design Data 2.4 Continuous Sterilizers 2.5 Fermenter Cooling 2.6 The Design of Large Fermenters (Based on Aeration) 2.7 Trouble Shooting in a Fermentation Plant
3. Nutritional Requirements in Fermentation Processes 3.1 Introduction 3.2 Nutritional Requirements of the Cell 3.3 The Carbon Source 3.4 The Nitrogen and Sulfur Source 3.5 The Source of Trace and Essential Elements 3.6 The Vitamin Source and Other Growth Factors 3.7 Physical and Ionic Requirements 3.8 Media Development 3.9 Effect of Nutrient Concentration on Growth Rate
4. Statistical Methods for Fermentation Optimization 4.1 Introduction 4.2 Traditional One-Variable-at-a-Time Method 4.3 Evolutionary Optimization 4.4 Response Surface Methodology 4.5 Advantages of RSM 4.6 Disadvantages of RSM 4.7 Potential Difficulties with RSM 4.8 Methods to Improve the RSM Model 4.9 Summary
5. Agitation 5.1 Theory and Concepts 5.2 Pumping Capacity and Fluid Shear Rates 5.3 Mixers and Impellers 5.4 Baffles 5.5 Fluid Shear Rates 5.6 Full-Scale Plant Design 5.7 Full-Scale Process Example 5.8 The Role of Cell Concentration Mass Transfer Rate 5.9 Some Other Mass Transfer Considerations 5.10 Design Problems in Biochemical Engineering 5.11 Solution-Fermentation Problems
6. Filtration 6.1 Introduction 6.2 Cake Filtration 6.3 Theory 6.4 Particle Size Distribution 6.5 Optimal Cake Thickness 6.6 Filter Aid 6.7 Filter Media 6.8 Equipment Selection 6.9 Continuous vs. Batch Filtration 6.10 Rotary Vacuum Drum Filter 6.11 Nutsches 6.12 H_-Hybrid Filter Press 6.13 Manufacturers
7. Cross-Flow Filtration 7.1 Introduction 7.2 Cross-Flow vs. Dead End Filtration 7.3 Comparison of Cross-Flow with Other Competing Technologies 7.4 General Characteristics of Cross-Flow Filters 7.5 Operating Configurations 7.6 Process Design Aspects 7.7 Applications Overview
8. Solvent Extraction 8.1 Extraction Concepts 8.2 Distribution Data 8.3 Solvent Selection 8.4 Calculation Procedures 8.5 Drop Mechanics 8.6 Types of Extraction Equipment 8.7 Selection of Equipment 8.8 Procedure Summary 8.9 Additional Information
9. Ion Exchange 9.1 Introduction 9.2 Theory 9.3 Ion Exchange Materials and Their Properties 9.4 Laboratory Evaluation of Resin 9.5 Process Considerations 9.6 Ion Exchange Operations 9.7 Industrial Chromatographic Operations
10. Evaporation 10.1 Introduction 10.2 Evaporators and Evaporation Systems 10.3 Liquid Characteristics 10.4 Heat Transfer in Evaporators 10.5 Evaporator Types 10.6 Energy Considerations for Evaporation System Design 10.7 Process Control Systems for Evaporators 10.8 Evaporator Performance 10.9 Heat Sensitive Products 10.10 Installation of Evaporators 10.11 Troubleshooting Evaporation Systems
11. Crystallization 11.1 Introduction 11.2 Theory 11.3 Crystallization Equipment 11.4 Data Needed for Design 11.5 Special Considerations for Fermentation Processes 11.6 Method of Calculation 11.7 Troubleshooting 11.8 Summary 11.9 American Manufacturers
12. Centrifugation 12.1 Introduction 12.2 Theory 12.3 Equipment Selection 12.4 Components of the Centrifuge 12.5 Sedimentation Centrifuges 12.6 Tubular-Bowl Centrifuges 12.7 Continuous Decanter Centrifuges (with Conveyor) 12.8 Disk Centrifuges 12.9 Filtering Centrifuges vs. Sedimentation Centrifuge 12.10 Filtering Centrifuges 12.11 Vertical Basket Centrifuges 12.12 Horizontal Peeler Centrifuges 12.13 Inverting Filter Centrifuge 12.14 Maintenance: Centrifuge 12.15 Safety
13. Water Systems for Pharmaceutical Facilities 13.1 Introduction 13.2 Scope 13.3 Source of Water 13.4 Potable Water 13.5 Water Pretreatment 13.6 Multimedia Filtration 13.7 Water Softening 13.8 Activated Carbon 13.9 Ultraviolet Purification 13.10 Deionization 13.11 Purified Water 13.12 Reverse Osmosis 13.13 Water for Injection 13.14 Water System Documentation
14. Sterile Formulations 14.1 Introduction 14.2 Sterile Bulk Preparation 14.3 Isolation of Sterile Bulk Product 14.4 Crystallization 14.5 Filtering/Drying 14.6 Milling/Blending 14.7 Bulk Freeze Drying 14.8 Spray Drying 14.9 Equipment Preparation 14.10 Validation 14.11 Filling Vials with Sterile Bulk Materials 14.12 Environment 14.13 Equipment List
15. Environmental Concerns 15.1 Environmental Regulations and Technology 15.2 Laws, Regulations and Permits 15.3 Technology (Waste Water) 15.4 Waste Water Treatment Strategy 15.5 Air (Emission of Concern) 15.6 Selecting a Control Technology 15.7 Volatile Organic Compound (VOC) Emissions Control 15.8 Particulate Control 15.9 Inorganics
16. Instrumentation and Control Systems 16.1 Introduction 16.2 Measurement Technology 16.3 Biosensors 16.4 Cell Mass Measurement 16.5 Chemical Composition 16.6 Dissolved Oxygen 16.7 Exhaust Gas Analysis 16.8 Measurement of pH 16.9 Water Purity 16.10 Temperature 16.11 Pressure 16.12 Mass 16.13 Mass Flow Rate 16.14 Volumetric Flow Rate 16.15 Broth Level 16.16 Regulatory Control 16.17 Dynamic Modeling 16.18 Multivariable Control 16.19 Artificial Intelligence 16.20 Distributed Control
17. Drying 17.1 Indirect Drying 17.2 Direct Drying
18. Plant Design and Cost 18.1 Introduction to the Capital Project Life Cycle 18.2 Conceptual Phase 18.3 Preliminary Design Phase 18.4 Detail Design Phase 18.5 Construction Phase 18.6 Start-up Phase 18.7 The Fast Track Concept 18.8 The Impact of Validation 18.9 Introduction to the Costing of a Capital Project 18.10 Order of Magnitude Estimate 18.11 Approval Grade Estimate 18.12 Control Estimate 18.13 Dynamics of an Estimate