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