Comprehensive Biotechnology, Second Edition

4531 Pages·2011·99.76 MB·English

by  Michael Butler

EDITOR-IN-CHIEF
Murray Moo-Young
University of Waterloo, Waterloo, Ontario, Canada
EDITOR-IN-CHIEF

Murray Moo-Young is a distinguished professor emeritus at the University of
Waterloo, Canada. Before academia, he worked in England for the British Ministry
of Industry. A Jamaican-Chinese Canadian, Dr. Moo-Young received his degrees from
the University of London (BSc in chemistry; PhD in biochemical engineering) and
University of Toronto (MSc in chemical engineering) followed by a postdoctoral
fellowship at the University of Edinburgh. He has been a visiting professor at world-
famous universities including MIT, UC Berkeley, Oxford University, EPFL Lausanne,
University of Karlsruhe, Dalian University of Technology, and Osaka University. To
date, his research has produced 13 books, nine patents, and over 355 papers. He is a
consultant worldwide, and the executive editor of the journal Biotechnology Advances
(Impact Factor 8.250). Dr. Moo-Young’s honors include the premiere awards of the
Canadian Society for Chemical Engineering and the American Chemical Society, Biochemical Technology
Division. As an elected fellow of the American Institute for Medical and Biological Engineering (FAIMBE)
and the Royal Society of Canada (FRSC), “the highest accolade for a Canadian academic,” Dr. Moo-Young is
intentionally acclaimed as a leader in the field of biotechnology.
ii
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Copyright ª 2011 Elsevier B.V. All rights reserved.
The following articles are US Government works in the public domain and not subject to copyright:
1.49 ANALYSIS AND CONTROL | Immunoassays in Biotechnology
3.03 BULK COMMODITIES | Multifunctional Enzyme Systems for Plant Cell Wall Degradation
3.32 BIOLOGICS | Recent and Emerging Trends and Concerns Related to the Manufacturing and Testing of Monoclonal Antibodies
Intended for Clinical Use
3.35 BIOLOGICS | Combination Products Are Not Solely Biological Products, Drugs, or Devices: A Regulatory Perspective
3.38 BIOLOGICS | Regulatory Aspects of Chemistry Manufacturing and Controls for Investigational New Drug applications and Biologic
License Applications to the United States Food and Drug Administration
3.39 BIOLOGICS | Raw Materials in the Manufacture of Biotechnology Products
6.11 INDUSTRIAL AND TOXIC WASTES | Proteomic Applications to Elucidate Bacterial Aromatic Hydrocarbon Metabolic Pathways
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VOLUME EDITORS

Michael Butler is a professor of animal cell technology in the Department of
Microbiology, University of Manitoba, Canada. Born in Wales, he gained his BSc
degree in biochemistry at Birmingham University, MSc at University of Waterloo and
PhD at King’s College, London. Following this, he became a lecturer and subse­
quently principal lecturer in biotechnology at Manchester Metropolitan University
(1974–90). He was appointed, in 1990, to an Industrial Chair in Fermentation
Technology at the University of Manitoba, where he was awarded the title of
Distinguished Professor in 2008. He has published >100 articles in peer-reviewed
journals and has written and edited seven books in the area of animal cell technol­
ogy. He is an editor for Biotechnology Advances and Comprehensive Biotechnology and
serves on the editorial board of Biotechnology and Bioengineering. In 2004 he was
given a National Synergy Award by NSERC, Canada for innovation involving University–Industry collabora­
tion. Presently he is leader of MabNet, which is a Canadian sponsored network for monoclonal antibody
production. His previous experience has included an appointment as associate dean of science at Manitoba and
several periods as visiting scientist or professor at MIT, Animal Virus Institute, (Pirbright), Universities of
Oxford and Rio de Janeiro. In the past, he has served on several grant awarding committees, including NSERC
(Ottawa), NSF (Washington), MHRC (Winnipeg), and Alberta Ingenuity (Edmonton). He was a founding
member of Protein Expression in Animal Cells (PEACe) and elected to the executive committee of ESACT. He
was a leader of a biotechnology subgroup for a Canadian government Department of Foreign Affairs mission to
Brazil; on the advisory panel to a Swedish program on Biotechnology; and Chair of the SFI advisory panel
(Dublin). He is President and Chief Scientific Officer of Biogro Technologies Inc, a research spin-off company.
His research interests include the production of glycoproteins from animal cells in culture, particularly with
respect to the control of glycosylation.
Professor Colin Webb, BSc, PhD, CEng, CSci, FIChemE, FIAFoST, graduated with a
first class honours degree in Chemical Engineering from the University of Aston in
Birmingham in 1976, followed by a PhD in Biochemical Engineering in 1980. He
moved to UMIST (Manchester) in 1979 and became professor and director of the
Satake Centre for Grain Process Engineering in 1994. In 1999, he was honored as the
UK’s first distinguished fellow of the International Academy of Food Science and
Technology. From 2000 to 2007, he was Head of Chemical Engineering at the
University of Manchester. He has been an external advisor to a large number of
Universities worldwide and is currently international scientific advisor to Kobe
University, Japan as well as a visiting professor at both the University of Oviedo
and the University of Cádiz in Spain. His publications include 7 books, more than 225 research papers, and 5
patents. He has been editor of Elsevier’s Biochemical Engineering Journal since its launch as a stand-alone journal
in 1998. He is a fellow of the Institution of Chemical Engineers (IChemE) and chair of Accreditation for the
IChemE. His research is largely directed toward the sustainable bioconversion of agricultural raw materials and
the development of the biorefinery concept.
v
vi Volume Editors
Dr. Antonio Moreira is vice provost for Academic Affairs and professor of
Chemical and Biochemical Engineering at UMBC (University of Maryland,
Baltimore County). He was chairman of the Chemical and Biochemical
Engineering Department, associate dean for the College of Engineering, and associ­
ate provost for Academic Affairs. Prior to UMBC, He spent nearly ten years in
industry, with senior management positions with International Flavors and
Fragrances, Inc. and Schering-Plough Corp. He has significant experience with
R&D and commercialization of biopharmaceuticals. He holds a BS degree in
Chemical Engineering from the University of Porto, Portugal, and MS and PhD
degrees in Chemical and Biochemical Engineering from the University of
Pennsylvania. He has an active research program in bioprocess engineering, is author
or co-author to over 150 publications and presentations, has overseen over $4 million in contracts and grants,
and consults with various biotechnology and pharmaceutical companies. He received a NATO Senior
Fellowship and the Parenteral Drug Association James Agalloco Award. He was founding president for the
Chesapeake Bay Area Chapter of the International Society for Pharmaceutical Engineers, chair of the Council
for Biotechnology Centers for BIO, and serves on various scientific advisory boards. He is a graduate of
Leadership Maryland.
Bernard Grodzinski earned his BSc degree from the University of Toronto, MSc
and PhD from York University before becoming a Postdoctorate Fellow of Botany,
Oxford, UK, in 1974. During 1975–79, he served as The Demonstrator of Botany at
the University of Cambridge, UK, where he received an honorary MA. In 1979, he
returned home to Canada, and today is a professor in the Department of Plant
Agriculture at the University of Guelph and the Director of the Biotron’s Low
Temperature Research Facility at Guelph (www.thebiotron.ca). His primary interests
are photosynthesis, respiration, assimilate partitioning, and plant productivity. In
addition, to investigating CO2 and hydrocarbon exchanges in natural environments,
he also studies plant homeostasis and development in controlled environments such
as commercial greenhouses and specialized chambers being tested for the manned
space program. His team is currently developing protocols, based on remote 3D imaging and gas exchange
kinetics, for monitoring health and growth using the plant as the sensor. However, his group’s main focus is a
better understanding of natural ecotype variation and phenotype responses to environmental stresses. The
genetic approaches currently being pursued include modifying plants for better light interception and
improved source-sink development. Candidate species are being selected for more efficient carbon use effi­
ciency, nitrogen use efficiency, and growth under varying environmental conditions. He is the lead Editor of
Vol. 4. “Agriculture and Related Biotechnologies” of Comprehensive Biotechnology 2 (Elsevier Publishers).
Zhanfeng Cui has been the Donald Pollock Professor of Chemical Engineering,
University of Oxford since the Chair was established in 2000. He is the founding
Director of the Oxford Centre for Tissue Engineering and Bioprocessing (OCTEB). He
was educated in China and got his BSc degree from Inner Mongolia University of
Technology (1982) and MSc (1984) and PhD (1987) from Dalian University of
Technology. After a postdoctoral experience in Strathclyde University in Scotland, he
joined Edinburgh University as a lecturer in Chemical Engineering (1991). He then
held academic appointments at Oxford Engineering Science Department as University
Lecturer (1994–98) and Reader (1999–2000). He was a Visiting Professor of Georgia
Institute of Technology, USA (1999), the Braun Intertec Visiting Professor to
University of Minnesota, USA (2004), and a Chang-Jiang Visiting Professor to
Dalian University of Technology, China (2005). He is a Chartered Engineer, a Chartered Scientist, and a Fellow
of the Institution of Chemical Engineers. In 2009, he was awarded a Doctor of Science (DSc) by Oxford
University to recognize his research achievement. His research interests include tissue engineering and stem cell
technologies, bioseparation and bioprocessing, and membrane science and technology. He and his co-workers
have published over 120 articles in refereed journal papers and filed seven patent applications in the last 5 years.
He is the academic founder of Zyoxel Limited, an Oxford University spin-off in 2009.
Volume Editors vii
Spiros N Agathos is full professor of bioengineering at the Catholic University of
Louvain in Belgium and group leader within its Earth & Life Institute (ELI) where he
is involved in research on bioprocess optimization, pollutant biodegradation, and
biotechnology for sustainability. He studied chemical engineering (Diploma,
National Technical University of Athens, Greece; MEng, McGill University,
Canada) and obtained a PhD in biochemical engineering from the Massachusetts
Institute of Technology. He has previously served as a faculty member at the
University of Western Ontario and Rutgers University. His publications include
more than 160 papers and book chapters, three books, and four patents, and his
research funding has exceeded $6 million in the past decade. He is associate editor of
Biochemical Engineering Journal and editorial board member of four other journals. He
is a consultant to government agencies and industry worldwide and has lectured at many universities, including
Greece, Brazil, Ecuador, Mexico, Spain, and France. He is an elected fellow of the Society for Industrial
Microbiology (SIM). As a member of the Environmental Working Group within the EU-US Task Force on
Biotechnology Research (1996–present), he is a strong advocate for young researchers and especially
for women in science and engineering.
SECTION EDITORS

Feng-Wu Bai received his BSc and MSc degrees from Dalian University of
Technology, China and PhD degree from the University of Waterloo, Canada. He
has been a visiting professor at world-famous universities including MIT and a
consultant for government and industry. Currently, he is a biochemical engineering
professor at Dalian University of Technology, China, and his research interest
comprises the combination of chemical engineering principles with biotechnology
advances for the production of biofuels, bioenergy, and bio-based chemicals at large
scale as an alternative to petroleum-based products. To date, his academic achieve­
ment and technical innovation have produced two books, three invited book chapters,
over 120 peer-reviewed articles, and two patents that have been commercialized in fuel
ethanol production. He is an editor of Biotechnology Advances and editorial board
member of Journal of Biotechnology and Chinese Journal of Biotechnology.
Dr. Ruth Cordoba-Rodriguez is a quality team leader in the Division of Monoclonal
Antibodies in the Office of Biotechnology Products at the Center for Drug Evaluation
and Research, US Food and Drug Administration (FDA). She received her PhD in
biophysics from the University of Maryland and pursued postdoctoral research in the
Department of Pharmacology and Experimental Therapeutics at the University of
Maryland before joining the FDA. During her graduate research, she studied calcium
homeostasis and evaluated calcium current in embryonic skeletal muscle. Her post­
doctoral research work involved the localization and characterization of neuronal
receptors and neuronal channel proteins of primary vagal afferent neurons in naïve
animals and animal models of upper-airway inflammation. At the FDA, she studied the
role of anthrax lethal factor in the induction and activation of proinflammatory cytokines interleukin-1 and
interleukin-18 in murine cells, and the lethality of mice strains exposed to anthrax lethal factor. Dr. Cordoba-
Rodriguez joined the FDA in 2002 as a researcher/reviewer and moved to a full-time regulatory reviewer position
in 2005. She is currently responsible for the primary and secondary assessment of chemistry and manufacturing
controls of therapeutic and diagnostic antibodies submitted to the FDA.
Ms. Kathy Lee has been with the FDA in the Division of Therapeutic Proteins since July
of 2003 as a full time chemistry manufacturing and controls (CMC) reviewer. Recently
she was promoted to team leader. She specializes in thrombolytic proteins and
complex combination products that involve implantable devices and therapeutic
proteins such as bone morphogenetic proteins. Prior to joining the FDA, Ms. Lee
worked at a contract research organization for ten years performing a large variety of in
vitro and protein characterization assays. She holds a M.S. degree from Johns Hopkins
University in Biotechnology and a B.A. degree from St. Mary’s College of MD in
Biology.
x Section Editors
Dr. Rickey Yada received his PhD from the Department of Food Science at the
University of British Columbia in 1984. He has served as Chair of the Department
of Food Science and as the Assistant Vice President Research, Agri-Food Programs,
both at the University of Guelph. He is presently a professor in the Department of
Food Science, a Canada Research Chair in Food Protein Structure, and the scientific
director of the Advanced Foods and Materials Network in Canada. He has participated
on numerous research awards panels and committees, both at the national
and international levels. Among other activities, he, currently, chairs the Scientific
Council, International Union of Food Science and Technology, is the North American
Editor for Trends in Food Science and Technology, and is on editorial boards for
several journals. He is the author of over 150 refereed journal publications and several
book chapters. He is a fellow of the Canadian Institute of Food Science and Technology and of the International
Academy, International Union of Food Science and Technology. He has recently been named a Fellow of the
Institute of Food Technologists (IFT).
William Allan King graduated with a BSc and an MSc degree from the University of
Guelph (Guelph, Canada) and a PhD degree from the Faculty of Veterinary Medicine
of the Swedish University of Agricultural Sciences (Uppsala, Sweden). He was a
postdoctoral fellow and subsequently an assistant professor at the Faculty of
Veterinary Medicine, University of Montreal (St. Hyacinthe, Canada). He is currently
a professor in the Department of Biomedical Sciences, Ontario Veterinary College,
University of Guelph, and holds a tier 1 Canada Research Chair in Animal
Reproductive Biotechnology. His research interests include the impact of reproductive
biotechnologies on chromosome stability, gametogenesis, embryo development, and
pregnancy outcome.
Fabio Fava (1963), with a Laurea degree cum laude in chemistry and pharmaceutical
technologies (University of Bologna, Italy) and a PhD in microbiology (ICT,
University of Prague, Czech Republic), is a full professor of industrial & environmen­
tal biotechnology at the Faculty of Engineering of the University of Bologna (Italy). He
published about 170 scientific papers (80 of which on medium/high IF peer-reviewed
international journals) in the area of industrial and environmental biotechnology
where he is actively working in the frame of the projects (a) BIOCHEM (Innova-FP7),
(b) NAMASTE (FP7)(as coordinator), (c) ECOBIOCAP (FP7), (d) MINOTAURUS
(FP7), (e) ULIXES (FP7), and (f) ROUTES (FP7). He is chairing the Environmental
Biotechnology section of the European Federation of Biotechnology (EFB), the Industrial
and Environmental Biotechnology section of the Italian SusChem Technology
Platform, and is a member of the Task Forces on Industrial Biotechnology and on Environmental
Biotechnology of the Organisation for Economic Co-operation and Development (OECD, Paris). He is also a member
of the Ad-hoc Advisory Group for the Lead Market Initiative for Bio-based Products (DG-Enterprise and Industry of
the European Commission, Brussels) and member of the Key Enabling Technology group on Industrial
Biotechnology.
GENERAL PREFACE

The second edition of Comprehensive Biotechnology provides a comprehensive coverage of the broad
multidisciplinary field of biotechnology with important updates of its principles and practices in industry,
medicine, agriculture, and the environment. It organizes and expands on material that is dispersed among different
specialized publications. It is a response to many enquiries from many quarters. From the publisher records,
the first edition was accepted worldwide with much appreciation. For example, a review of the publication in
the prestigious periodical Nature observed that it “will be an essential purchase for all departments and
institutions, academic or industrial that claim an interest in…biotechnology”. As before, this publication
would be valuable to researchers, instructors, students, policy makers, and others in biotechnology-related
activities.
In addition to traditional hard-copy print, this edition is also published as an online digitized document,
which allows the use of modern electronic tools for seamless connections to the first edition and other relevant
information with hyperlinks. For convenience, each article carries a glossary and a professional summary of the
authors indicating their appropriate credentials. In a few instances, recent reprints are provided to acquire
expertise in a timely manner. An extensive index for the entire publication gives a complete list of the many
topics treated in the increasingly expanding field.
To facilitate ‘one-stop shopping’ for rapid service, the work is designed as an integrated compendium of six
volumes covering all the essential elements of the field. The first two volumes provide the basics of the
underlying scientific and engineering principles of biotechnology; the following four volumes treat the major
application branches that have an impact on industry, agriculture, medicine, and environment. Each volume
has several sections to address various aspects of the given constituent areas. The volume editors provide a
specific introduction to the nature and scope of the contents of a given volume. The volume titles, section titles,
and respective editors of the six volumes are as follows.
Volume 1: Scientific fundamentals of biotechnology
Section 1. The biochemical basis
Section 2. The biological basis
Section 3. The genetic basis
Section 4. Systems biology
Section 5. The metabolic basis
Section 6. The biophysical basis
Section 7. The computational basis
Section 8. Analysis and control
Editor: Michael Butler, University of Manitoba, Canada
Volume 2: Engineering fundamentals of biotechnology
Section 1. Underlying principles
Section 2. Upstream processing
Section 3. Bioreactors
3A. Design
3B. Application
Section 4. Bioreactions and bioreactor operation
xi
xii General Preface
Section 5. Downstream processing and product recovery

Section 6. Process considerations

Section 7. Other considerations

Editor: Colin Webb, University of Manchester, UK
Volume 3: Industrial biotechnology and commodity products
Section 1. Bulk commodities

1A. Industrial enzymes

1B. Biofuels and bioenergy

1C. Bio-based chemicals

1D. Biomaterials

Section 2. Healthcare products

2A. Small molecules

2B. Biologics

Section 3. Food ingredients

Section 4. Other considerations

Editors: Antonio Moreira, University of Maryland Baltimore County, USA; Ruth Cordoba-
Rodriguez, Kathy Lee, US Food and Drug Administration; Fengwu Bai, Dalian University of
Technology, China
Volume 4: Agricultural and related biotechnologies
Section 1. Plant systems

Section 2. Animal systems

Section 3. Food systems

Section 4. Integration of biotechnologies

Section 5. Socioeconomic considerations

Editors: Bernard Grodzinski, W. Allan King, Rickey Yada, University of Guelph, Canada
Volume 5: Medical biotechnology and healthcare
Section 1. Enabling technologies

Section 2. Tissue engineering and stem cell therapy

Section 3. Biopharmaceuticals, in vitro drug testing, and drug delivery

Section 4. Artificial organs and life support devices

Editor: Zhanfeng Cui, University of Oxford, UK
Volume 6: Environmental biotechnology and safety
Section 1. Industrial and toxic wastes

Section 2. Municipal wastes

Section 3. Wastes from agriculture, forestry, and food processing

Section 4. Other considerations

Editors: Spiros Agathos, Catholic University of Louvain, Belgium; Fabio Fava,

University of Bologna, Italy

This work is unique as a comprehensive review of a multifaceted field in a single publication venue with
all volumes published simultaneously rather than as a traditional book series. It is intended to meet the need
of neophytes as well as veterans in the field and can potentially serve as teaching material for graduates
and undergraduate students (especially seniors) in various subjects, including biological sciences, micro­
biology, biochemistry, chemical engineering, biochemical engineering, bioengineering, biomedical engineer­
ing, environmental sciences/engineering, food science/engineering, biotechnology, and bioprocessing.
Other stakeholders in industry and government who cannot ignore the importance of biotechnology in
commerce and society will also benefit from the contents of this work, making this a major reference for a
diverse readership.
Many authors worldwide have contributed in accomplishing the multidimensional work with appropriate
expertise. General guidance was provided by a prestigious international advisory board, which includes two