1st Edition

Fundamentals of Modern Bioprocessing

By Sarfaraz K. Niazi, Justin L. Brown Copyright 2015
    768 Pages 14 Color & 95 B/W Illustrations
    by CRC Press

    768 Pages 14 Color & 95 B/W Illustrations
    by CRC Press

    Biological drug and vaccine manufacturing has quickly become one of the highest-value fields of bioprocess engineering, and many bioprocess engineers are now finding job opportunities that have traditionally gone to chemical engineers. Fundamentals of Modern Bioprocessing addresses this growing demand.

    Written by experts well-established in the field, this book connects the principles and applications of bioprocessing engineering to healthcare product manufacturing and expands on areas of opportunity for qualified bioprocess engineers and students. The book is divided into two sections: the first half centers on the engineering fundamentals of bioprocessing; while the second half serves as a handbook offering advice and practical applications.

    Focused on the fundamental principles at the core of this discipline, this work outlines every facet of design, component selection, and regulatory concerns. It discusses the purpose of bioprocessing (to produce products suitable for human use), describes the manufacturing technologies related to bioprocessing, and explores the rapid expansion of bioprocess engineering applications relevant to health care product manufacturing. It also considers the future of bioprocessing—the use of disposable components (which is the fastest growing area in the field of bioprocessing) to replace traditional stainless steel.

    In addition, this text:

    • Discusses the many types of genetically modified organisms
    • Outlines laboratory techniques
    • Includes the most recent developments
    • Serves as a reference and contains an extensive bibliography
    • Emphasizes biological manufacturing using recombinant processing, which begins with creating a genetically modified organism using recombinant techniques

    Fundamentals of Modern Bioprocessing outlines both the principles and applications of bioprocessing engineering related to healthcare product manufacturing. It lays out the basic concepts, definitions, methods and applications of bioprocessing. A single volume comprehensive reference developed to meet the needs of students with a bioprocessing background; it can also be used as a source for professionals in the field.


    Frontiers of Bioprocessing

    Defining Bioprocessing

    Current and Emerging Trends in Bioprocess Engineering

    Materials Advances

    Nanoscale Advances

    Bioprocessing for Chemical and Biologic Product Manufacturing

    Bioprocessing Leaders Worldwide

    Economic Predictions and Careers in Bioprocess Engineering

    Skills Needed for Future Bioprocess Engineers

    Appendix A: A Time Line of Biotechnology Development

    Introduction to Molecular Biology


    Building Blocks of Life: DNA, RNA, and Proteins

    DNA Replication






    DNA Cloning

    Introduction to Biochemistry


    DNA Structure

    RNA Structure

    Protein Structure and Function


    Lipids, Fats, and Steroids

    Basic Metabolic Pathways

    Introduction to Cellular Microbiology


    General Cell Structure

    Eukaryotes, Prokaryotes, Archaea, and Viruses

    Intracellular Organelles

    Cellular Transport

    Intracellular Signal Transduction

    Reaction Stoichiometry, Thermodynamics, and Kinetics


    Mass and Energy Balances

    Fundamentals of Chemical Reactions

    Basic Mass Transfer: Diffusion and Convection

    Basic Fluid Dynamics

    Basic Thermodynamics

    Basic Reaction Kinetics

    Kinetics of Enzymes and Cell Growth


    Basic Michaelis–Menten Kinetics

    Michaelis–Menten Kinetics with Inhibition

    pH and Transport Limitations

    Other Enzyme Kinetics

    Prokaryotic and Eukaryotic Growth Models

    Advanced Prokaryotic and Eukaryotic Growth Models

    Data Management


    Good Laboratory Practices

    Electronic Data Handling

    Data Errors

    Statistical Analysis

    Data Conclusions

    Flow Diagrams

    Exercises and Solutions


    Elements of Bioprocessing


    Upstream Processing


    Downstream Processing

    Genetically Modified Organisms


    Cell Line Characterization

    Characterization of Cell and Virus Banks

    Cell Line Construction

    Designing GMCS


    Host Systems

    Expression System in E Coli

    Configuration of Efficient Expression Vectors

    Protein Production

    Genetic Manipulations to Improve Yield

    Manufacturing Overview


    Cell Culture Expression Systems

    Transgenic Animals

    Cell Lines and Characterization


    Culture Growth

    Extraction, Isolation, and Purification



    Impurity Removal


    Intermediate Purification



    Process Overview

    Tech Transfer and Documentation


    Scale Up

    Specific Economy Issues

    Process Materials

    Environment Control

    Good Manufacturing Controls of Active Pharmaceutical Ingredients

    Manufacturing Systems and Layout

    Cleaning Procedures

    Processing and Filling

    Laboratory Testing

    Laboratory Controls


    Technical Package

    Outsourcing in Biotech Manufacturing

    Issues to Discuss

    Disposable Bioprocessing Systems


    Safety of Disposable Systems

    Regulatory Matters

    Risk Assessment

    Disposable Containers

    Tank Liners

    Mixing Systems

    Disposable Bioreactors

    Disposable Connectors and Transfers

    Disposable Control and Monitoring Systems

    Downstream Processing


    Upstream Processing



    Batch Culture

    Continuous Culture

    Fed-Batch Culture

    Perfusion Culture

    Suspension Culture

    Microcarrier Support

    Roller Bottle Culture System

    Spinner Flask Culture

    Other Scale up Options

    Wave Bioreactor

    Cell Cube Technology

    Rotary Culture System


    Scaling and Production Costs

    Problem Resolution in Fusion Protein Expression

    Downstream Processing



    System Suitability

    Downstream Processing Systems

    Process Flow



    Protein Properties

    Affinity Chromatography

    Immobilized Metal Affinity Chromatography

    Anion Exchange Chromatography

    Cation Exchange Chromatography

    Size Exclusion Chromatography

    Reversed Phase Chromatography

    Hydroxyapatite Chromatography

    Hydrophobic Interaction Chromatography

    Scale-up and Optimization

    Manufacturing Systems

    Bacterial Expression Systems

    Genetically Modified Bacteria

    Mammalian Cells Manufacturing Systems

    Yeast Cell Expression System

    Insect Cells Systems

    Quality Consideration


    Management Responsibilities


    Manufacturing Operations

    Evaluation Activities


    QA Systems

    Validation Master Plan

    Raw Materials

    Column Life


    Virus Validation

    Testing of Product

    In-Process Control

    Regulatory Affairs

    Regulatory Issues

    Protein Degradation

    Stability Considerations

    Intellectual Property


    Patenting Systems and Strategies

    The Patent Laws

    Types of Patent Laws

    Anatomy of a Patent


    Patentability and Technical Information Search

    Components of a Patent Application

    Inventions of Interest to Pharmaceutical Scientists

    Biotechnology Inventions

    Patenting Strategies



    Sarfaraz K. Niazi, Ph.D., is the founding executive chairman of Therapeutic Proteins International, LLC. He began his career teaching pharmacy at the University of Illinois, where he was a tenured professor, before entering the pharmaceutical industry with Abbott International, where he became a Volwiler fellow. Dr. Niazi is a licensed practitioner of patent law, has published numerous books and papers, and has been recognized with several awards for his contributions to science and literature. His inventions, philanthropy, and passion for science, literature, music, and photography have also been documented in publications such as Forbes, Chicago Tribune, and Crain’s Chicago Business.

    Justin L. Brown, Ph.D., joined the biomedical engineering faculty of The Pennsylvania State University in 2010. Prior to joining Penn State, Dr. Brown spent seven years at the University of Virginia where he obtained his Ph.D. in biomedical engineering and completed a postdoctoral fellowship in cell and microbiology. His current research interests focus on exploring the signaling cascades and lineage commitment of mesenchymal stem cells in response to biomaterial surfaces that have potential for translation to clinical strategies. Dr. Brown’s lab applies both a reductionist and high-throughput systems approach towards understanding the mechanistic cellular response to extracellular biomaterial geometries.

    "… destined to become a standard handbook for bioprocess engineers. It provides a detailed discussion of emerging areas, such as disposable bioreactors, that are scarcely covered in the books that are currently available."
    —Jules Magda, University of Utah, Salt Lake City, USA