Development of sustainable bioprocesses : modeling and assessment

Bioprocess technology involves the combination of living matter (whole organism or enzymes ) with nutrients under laboratory conditions to make a desired product within the pharmaceutical, food, cosmetics, biotechnology, fine chemicals and bulk chemicals sectors. Industry is under increasing pressure to develop new processes that are both environmentally friendly and cost-effective, and this can be achieved by taking a fresh look at process development; - namely by combining modern process modeling techniques with sustainability assessment methods.

Development of Sustainable Bioprocesses: Modeling and Assessment describes methodologies and supporting case studies for the evolution and implementation of sustainable bioprocesses. Practical and industry-focused, the book begins with an introduction to the bioprocess industries and development procedures. Bioprocesses and bioproducts are then introduced, together with a description of the unit operations involved. Modeling procedures, a key feature of the book, are covered in chapter 3 prior to an overview of the key sustainability assessment methods in use (environmental, economic and societal). The second part of the book is devoted to case studies, which cover the development of bioprocesses in the pharmaceutical, food, fine chemicals, cosmetics and bulk chemicals industries. Some selected case studies include: citric acid, biopolymers, antibiotics, biopharmaceuticals.

Supplementary material provides hands-on materials so that the techniques can be put into practice. These materials include a demo version of SuperPro Designer software (used in process engineering) and models of all featured case studies, excel sheets of assessment methods, Monte Carlo simulations and exercises.

Previously available on CD-ROM, the supplementary material can now be accessed via http://booksupport.wiley.com by entering the author name, book title or isbn and clicking on the desired entry. This will then give a listing of all the content available for download. Please read any text files before downloading material.

Author Notes

Professor Elmar Heinzle , Universität des Saarlandes, Germany

Dr. Charles Cooney , MIT, USA

Both internationally-recognised experts in biochemical engineering and modeling

Dr Arno Biwer , MIT/ Universität des Saarlandes, Germany

Arnd Knoll and Jochen BuechsWilfried Storhas and Rolf MetzM. Abdul Kholiq and Elmar HeinzleDemetri PetridesElizabeth Zapalac and Karen McDonaldSindelia S. Freitas and Jose A. L. Santos and D. Miguel F. Prazeres

Preface	p. xiii
Acknowledgments	p. xvii
List of Contributors	p. xix
Part I Theoretical Introduction
1 Introduction	p. 3
1.1 Bioprocesses	p. 3
1.1.1 History of Biotechnology and Today's Situation	p. 3
1.1.2 Future Perspectives	p. 6
1.2 Modeling and Assessment in Process Development	p. 7
2 Development of Bioprocesses	p. 11
2.1 Types of Bioprocess and Bioproduct	p. 11
2.1.1 Biocatalysts and Process Types	p. 11
2.1.2 Raw Materials	p. 17
2.1.3 Bioproducts	p. 20
2.2 Bioreaction Stoichiometry, Thermodynamics, and Kinetics	p. 23
2.2.1 Stoichiometry	p. 23
2.2.2 Thermodynamics	p. 28
2.2.3 Kinetics	p. 29
2.3 Elements of Bioprocesses (Unit Operations and Unit Procedures)	p. 32
2.3.1 Upstream Processing	p. 33
2.3.2 Bioreactor	p. 36
2.3.3 Downstream Processing	p. 40
2.3.4 Waste Treatment, Reduction and Recycling	p. 50
2.4 The Development Process	p. 52
2.4.1 Introduction	p. 52
2.4.2 Development Steps and Participants	p. 53
3 Modeling and Simulation of Bioprocesses	p. 61
3.1 Problem Structuring, Process Analysis, and Process Scheme	p. 62
3.1.1 Model Boundaries and General Structure	p. 62
3.1.2 Modeling Steps	p. 63
3.2 Implementation and Simulation	p. 66
3.2.1 Spreadsheet Model	p. 66
3.2.2 Modeling using a Process Simulator	p. 66
3.3 Uncertainty Analysis	p. 71
3.3.1 Scenario Analysis	p. 72
3.3.2 Sensitivity Analysis	p. 73
3.3.3 Monte Carlo Simulation	p. 75
4 Sustainability Assessment	p. 81
4.1 Sustainability	p. 81
4.2 Economic Assessment	p. 82
4.2.1 Capital-Cost Estimation	p. 83
4.2.2 Operating-Cost Estimation	p. 88
4.2.3 Profitability Assessment	p. 94
4.3 Environmental Assessment	p. 95
4.3.1 Introduction	p. 95
4.3.2 Structure of the Method	p. 96
4.3.3 Impact Categories and Groups	p. 99
4.3.4 Calculation of Environmental Factors	p. 103
4.3.5 Calculation of Indices	p. 105
4.3.6 Example Cleavage of Penicillin G	p. 105
4.4 Assessing Social Aspects	p. 107
4.4.1 Introduction	p. 107
4.4.2 Indicators for Social Assessment	p. 108
4.5 Interactions between the Different Sustainability Dimensions	p. 112
Part II Bioprocess Case Studies
Introduction to Case Studies	p. 121
5 Citric Acid - Alternative Process using Starch	p. 125
5.1 Introduction	p. 125
5.2 Fermentation Model	p. 125
5.3 Process Model	p. 128
5.4 Inventory Analysis	p. 130
5.5 Environmental Assessment	p. 132
5.6 Economic Assessment	p. 134
5.7 Conclusions	p. 135
6 Pyruvic Acid - Fermentation with Alternative Downstream Processes	p. 137
6.1 Introduction	p. 137
6.2 Fermentation Model	p. 137
6.3 Process Model	p. 138
6.3.1 Bioreaction and Upstream	p. 138
6.3.2 Downstream Processing	p. 141
6.4 Inventory Analysis	p. 142
6.5 Environmental Assessment	p. 144
6.6 Economic Assessment	p. 145
6.7 Conclusions	p. 145
7 L-Lysine - Coupling of Bioreaction and Process Model	p. 155
7.1 Introduction	p. 155
7.2 Basic Strategy	p. 156
7.3 Bioreaction Model	p. 156
7.4 Process Model	p. 159
7.5 Coupling of Bioreaction and Process Model	p. 162
7.5.1 Assumptions	p. 163
7.6 Results and Discussion	p. 164
8 Riboflavin - Vitamin B[subscript 2]	p. 169
8.1 Introduction	p. 169
8.2 Biosynthesis and Fermentation	p. 170
8.3 Production Process and Process Model	p. 171
8.3.1 Upstream Processing	p. 172
8.3.2 Fermentation	p. 174
8.3.3 Downstream Processing	p. 174
8.4 Inventory Analysis	p. 174
8.5 Ecological Assessment	p. 175
8.6 Economic Assessment	p. 176
8.7 Discussion and Concluding Remarks	p. 177
9 [Alpha]Cyclodextrin	p. 181
9.1 Introduction	p. 181
9.2 Reaction Model	p. 182
9.3 Process Model	p. 182
9.3.1 Solvent Process	p. 182
9.3.2 Non-solvent Process	p. 184
9.4 Inventory Analysis	p. 185
9.5 Environmental Assessment	p. 186
9.6 Economic Assessment	p. 186
9.7 Conclusions	p. 189
10 Penicillin V	p. 193
10.1 Introduction	p. 193
10.2 Modeling Base Case	p. 193
10.2.1 Fermentation Model	p. 193
10.2.2 Process Model	p. 194
10.3 Inventory Analysis	p. 196
10.4 Environmental Assessment	p. 197
10.5 Economic Assessment	p. 197
10.6 Monte Carlo Simulations	p. 198
10.6.1 Objective Functions, Variables, and Probability Distributions	p. 198
10.6.2 Results	p. 201
10.7 Conclusions	p. 206
11 Recombinant Human Serum Albumin	p. 211
11.1 Introduction	p. 211
11.2 Bioreaction Model	p. 212
11.2.1 Stoichiometry	p. 212
11.2.2 Multi-stage Fermentation and Feeding Plan	p. 213
11.2.3 Total Broth Volume in Production Scale and Raw Material Consumption	p. 214
11.3 Process Model	p. 215
11.3.1 Bioreaction	p. 215
11.3.2 Downstream Processing	p. 215
11.4 Economic Assessment	p. 218
11.5 Ecological Assessment	p. 219
11.6 Conclusions	p. 221
12 Recombinant Human Insulin	p. 225
12.1 Introduction	p. 225
12.1.1 Two-chain Method	p. 226
12.1.2 Proinsulin Method	p. 226
12.2 Market Analysis and Design Basis	p. 226
12.2.1 Process Description	p. 227
12.2.2 Inventory Analysis and Environmental Assessment	p. 233
12.2.3 Production Scheduling	p. 234
12.3 Economic Assessment	p. 235
12.4 Throughput-Increase Options	p. 237
12.5 Conclusions	p. 238
13 Monoclonal Antibodies	p. 241
13.1 Introduction	p. 241
13.2 Process Model	p. 241
13.3 Inventory Analysis	p. 243
13.4 Economic Assessment	p. 245
13.5 Environmental Assessment	p. 246
13.6 Uncertainty Analysis	p. 247
13.6.1 Scenarios	p. 247
13.6.2 Sensitivity Analysis	p. 248
13.6.3 Monte Carlo Simulations	p. 249
13.7 Conclusions	p. 255
14 [Alpha]-1-Antitrypsin from Transgenic Plant Cell Suspension Cultures	p. 261
14.1 Introduction	p. 261
14.2 Process Description	p. 263
14.3 Model Description	p. 263
14.4 Discussion	p. 265
14.5 Conclusions	p. 268
15 Plasmid DNA	p. 271
15.1 Introduction	p. 271
15.1.1 General	p. 271
15.1.2 Case Introduction	p. 272
15.1.3 Process Description	p. 272
15.2 Model Description	p. 275
15.2.1 Bioreaction Section	p. 275
15.2.2 Downstream Sections	p. 276
15.3 Inventory Analysis	p. 277
15.4 Economic Assessment	p. 278
15.5 Environmental Assessment	p. 281
15.6 Discussion	p. 282
15.7 Conclusions	p. 283
Index	p. 287

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