Continuous and Intensified Processing
in Upstream Cell Culture

This course combines lectures, hands on laboratory practices and simulation exercises covering the most critical concepts in upstream animal cell culture technology, specifically focusing on continuous and intensified processes.

Topics include cell line engineering and development, animal cell culture media and its optimization, and understanding critical bioreactor parameters and scalability.

• Gain an understanding of current trends in the industry, advantages and disadvantages of intensified upstream processes and critical parameters for the various upstream manufacturing processes used in the biopharmaceutical industry.
• Perfusion techniques and types of cell separation technologies will be described.

• Common methods used for cell line engineering and development will be described, along with considerations for critical Go/No-Go decision points and discussion of troubleshooting for common issues and technical difficulties.
• Protein structure and other critical quality attributes impacting their function will be reviewed.
• Classroom instruction and hands-on laboratory experience with specific cell manipulation techniques. Critical practical aspects of these techniques will be reviewed through simulated results.

• Review the critical groups of components and forms of animal cell culture media as well as techniques used for media optimization and development, including small scale models and statistical analysis.
• Practice performing small scale models to mimic perfusion systems.
• Hydration and filtration studies with different formulations will be performed.

• Review different types of bioreactors, control loops, critical process parameters and their optimization, scalability from benchtop to manufacturing bioreactors
• Overview of the differences between traditional fed-batch and intensified process applications.
• Learn how to operate bioreactors at benchtop and pilot scale, focusing on perfusion processes.

• Perfusion systems and their potential applications, as well as general knowledge on available cell retention devices
• Overview of the process and techniques used in the development of recombinant cell lines, including troubleshooting and Go/No-Go decisions throughout
• Critical steps utilized during a transfection process and recognition of technical challenges and potential solutions
• Principles of methods and criteria used for screening and for selection of recombinant cell lines
• Cell culture media forms, properties, and components, including their characterization
• Differences between fed batch and perfusion small scale models and media optimization methods and selection criteria
• Hydration methods with different types of media and feeds
• Assessment techniques for filter sizing and selection for different formulations and scales
• Understanding of bioreactor components and controls
• Basic operation of a perfusion system using a filtration base cell retention device
• Principles of bioreactor scalability
• Tests to assess learning objectives and presenting results