(41c) Membrane Processes in the Biotechnology Industry

van Reis, R. - Presenter, Genentech, Inc.

Membranes are used extensively throughout the production, purification, and filling of biotechnology products. Upstream applications include sterile filtration of fermentation media and gases. Filters with 0.1 µm pore size provide retention of both mycoplasma as well as larger organisms. Depth filtration may also be used for turbid feed streams such as peptone solutions. Tangential flow micro filtration is used for medium exchange, perfusion, and harvest. Virus filtration may be used to protect cell cultures from introduction of viral contaminants in media raw materials. Downstream applications include sterile filtration of products, buffers, and gases. Depth filtration is used for product feed streams that are particularly difficult to filter with other types of membranes. Virus filters are often used in the downstream processing of cell culture derived products to insure removal of both endogenous virus particles as well as any adventitious viruses that may enter into the cell culture through contaminated raw materials. Virus filtration was initially implemented as a tangential flow filtration operation that was subsequently replaced with normal flow filtration. Membrane chromatography can be used for purification of both products and raw materials. For example, it may be advantageous to remove endotoxins from raw materials before using them in the downstream process. Ultrafiltration is used to concentrate and buffer exchange product pools throughout the downstream process. It is also used as the method of choice for final formulation of bulk product. High Performance Tangential Flow Filtration is an emerging technology that enables concentration, purification, and buffer exchange in a single unit operation. An overview of membrane applications in the biotechnology industry will be provided covering fundamentals, technology, process applications, and scale-up.