Course Detail

Mammalian cell biotechnology has been an explosively growing field for the last 25 years.  Recombinant Chinese Hamster Ovary (CHO) cells now far surpass E. coli and all other expression systems for recombinant protein production.  Levels of recombinant protein production have gone up a 100-fold or more, are now often measured in grams per liter, and are expected to continue to increase.   Mammalian cell culture is the most commonly used system for production of both marketed recombinant proteins and those undergoing clinical testing.  This situation is also true for vaccines.  Ground breaking ceremonies for new, large-scale cell culture plants that were once rare, now occur with regularity . Stem cell and engineered tissue therapies will ultimately require many new cell culture and/or cell processing operations.   Individuals skilled in mammalian cell biotechnology are in high demand.

The primary goal of this course is to provide students with an advanced background in mammalian cell biotechnology.   The scientific, engineering, and practical industrial aspects will be presented in a series of lectures and will constitute approximately half of the course.  The other half will consist of a series of a laboratory exercises.  By the end of the course, students should not only have a broad understanding of the key issues, but should also have a certain degree of first hand experience and skill in culturing cells in bioreactors at the laboratory scale.

Textbook
Culture of Animal Cells: A Manual of Basic Technique, by R. Ian Freshney, John Wiley and Sons, Hoboken, New Jersey, 5^th edition, 2005

• History and biology of cultured cells
• Products from mammalian cell biotechnology
• Industry overview, including vaccines 
• Laboratory design, equipment, and aseptic technique
• Safety, bioethics, and validation
• Kinetics of cell growth and death
• Measurement of cell number, size and viability
• Stoichiometry and kinetics of cell growth and metabolism
• Recombinant protein production and post-translational processing
• Formulation of culture medium
• Mortality and transformation
• Differentiation and de-differentiation
• Viral kinetics and vaccine production
• Cell line engineering and common host cells
• Kinetics and nature of adaptation
• Stem cells
• Engineered tissues as replacement body parts for humans
• Engineered tissues as replacements for animal testing
• Cell culture under current Good Manufacturing Practices (cGMPs)
• Standard Operating Procedures (SOPs)
• Master batch records (MBRs)
• Deviations and incident reports
• Testing, calibration, and validation
• Cleaning and sterilization
• Kinetics of sterilization
• Autoclaves
• Large-scale Steam-In-Place (SIP) systems
• Control of culture environment
• Cell culture bioreactors
• Large-scale cell culture operations

In completing this course, students will acquire

• an understanding of the history and status of mammalian cell biotechnology, including past, current and future products, as well as challenges faced
• the ability to culture cells and prepare medium using proper aseptic technique
• an understanding of the biology of cultured cells, including cell growth, death, metabolism, mortality, transformation, differentiation, and adaptation
• the ability to measure cell growth, death, and metabolism
• knowledge of cell line engineering techniques and common host cell lines for recombinant protein production and vaccine production
• an understanding of stem cell biology and the current status of stem cell therapy
• knowledge regarding the use of engineered tissues as replacement body parts and as replacements for animal testing
• familiarity with large-scale cell culture operations,
• an understanding of how mammalian cell culture operations are performed under current Good Manufacturing Practices (cGMPs)
• the ability to follow a Standard Operating Procedures (SOP) and a Master Batch Record (MBR)
• an understanding of the cleaning and sterilization of cell culture bioreactors, at both the laboratory scale and large scale.
• an understanding of the design and operation of bioreactors, including key issues such as mode of operation, mixing, scale-up, oxygen supply, carbon dioxide removal, cell line sensitivity to damage from agitation and sparging, and perfusion devices
• the ability to clean, sterilize, set-up, and operate a small-scale bioreactor, for growth of a suspension culture
• the ability to assess, track, and control culture pH, oxygen, temperature and other environmental parameters
• an understanding of the key issues and tools used in large-scale cell culture operations, including economies of scale, operations management, control charts, and process flow diagrams

Laboratory exercises:    50%
Homework assignments, reports and exams:    50%