Effective Small-scale Production of Antibodies.

Using a CELLine 350 cell culture system, supplied by Integra Biosciences AG, the Institute for Molecular Medicine & Experimental Immunology (IMMEI) (Bonn, Germany) has transformed the effectiveness of its small-scale antibody production.

Designed for ease-of-use the CELLine 350 utilises proprietary membrane technology to separate off the cultivation chamber with an upper semi-permeable membrane through which nutrient can diffuse and a lower one that allows gases to diffuse. Separate ports allow selective access to the upper nutrient supply chamber and the central cultivation chamber. This novel compartmentalised arrangement means that medium can be exchanged without influencing the function or growth of the cells and gases. Consequently, traditional cell growth limitations brought about by a lack of nutrients or the accumulation of metabolic waste can be overcome just as easily as oxygen deficiency. Such optimised conditions promote significant cell growth and lead to drastically increased cell densities.

Cells growing under the optimal conditions created in CELLine reach densities of 107 to 108 cells per ml and the concentration of expressed protein is typically 50 to 100 times above what is found in standard cell culture disposables. By combining high product concentration with recurring product collection, large amounts of highly concentrated proteins are routinely obtained in CELLine. In the case of monoclonal antibodies (MAb), average concentrations range from 1 to 2 mg/ml of MAb (in both CELLine 350 and the larger CELLine 1000) and monthly yields typically range from 100 to 250 mg (using a CELLine 1000).

The CELLine has been designed to bring considerable cost savings to cell cultivation. The novel bioreactor drastically reduces the need for high capital investments in cell culture instrumentation or handling large amounts of cell culture disposables in order to be able to obtain milligram amounts of a designated protein. High production yields together with a 90% reduction in media supplement requirements enable further cost and time-savings in downstream processing steps.