Chromatography is an indispensable tool for the industrial production of proteins and other biotechnology products. Process development usually begins with laboratory scale scouting tests to determine suitable stationary phases and operating conditions. If successful, the next step is the optimization of operating conditions and scale-up. The aim of this course is to provide insight in the theory of chromatography, an understanding of fundamental engineering scale-up relationships, and an overview of methodologies for the experimental measurement of scale-up parameters and of optimization tools.
The scope of the course is to provide insight in the application of chromatographic theory with special emphasis on the determination and use of key scale-up parameters. The course will include both lectures and hands-on laboratories. The lectures will cover downstream processing of biotechnological products, the different modes of operation of chromatography, the characteristics of chromatographic media, the description of adsorption equilibria and mass transfer and their effects on chromatographic performance, frontal analysis and linear gradient elution theories, and protein-protein and protein-surface interactions. The laboratory sessions will comprise pulse response experiments, the determination of retention factor and HETP, frontal analysis and dynamic binding capacity experiments, and linear gradient elution experiments. An optional column packing session on Sunday will address practical aspects of packing and validating lab columns. The experiments will be carried out with typical chromatography media using ÄKTA Prime chromatographic workstations from GE Healthcare using the latest version of Unicorn software and will explore the effects of pore size, particle size, the size of the protein, and the choice of operating conditions. The participants, divided in teams, will set up the experimental runs, analyze the experimental results, calculate performance metrics, determine scale-up parameters, and present the results for discussion in a group setting. A final exercise will provide the opportunity to develop a column design that maximizes productivity based on the experimental data acquired during the week. Detailed course notes and spreadsheet-based tools for data analysis will be available. Ample opportunities will also be provided for interactions among participants, lecturers, and staff.
The course is aimed at bioprocess development engineers, separation scientists, biologists, biochemists, technical managers, validation specialists, and regulatory agents having some familiarity with downstream process development who want to develop a deeper understanding of chromatographic processes and their scale-up. Graduate students and separation scientists in academia will also benefit from this course.