A perfusion system for antibody production by shear-sensitive hybridoma cells in a stirred reactor

Summary A shear-sensitive hybridoma cell line, incapable of growth or antibody production in spinner or shake flasks agitated at 40 rpm, was grown successfully in a perfusion propagation system consisting of a bioreactor (1.5 liter), stirred with a cell-lift impeller at 60 rpm, and a tangential flow filtration unit for removal of spent culture medium from the reactor. The culture was maintained over a 48 day period and cell numbers reached 1.8 × 10⁷ cells/ml. Maximal monoclonal antibody concentration was 800 ug/ml, indicating a productivity of 504 mg/day.