Fully-automated roller bottle handling system for large scale culture of mammalian cells

A fully automatic and continuous cell culture system based on roller bottles is described in this paper. The system includes a culture rack storage station for storing a large number of roller bottles filled with culture medium and inoculated with mammalian cells, mass-handling facility for extracting completed cultures from the roller bottles, and replacing the culture medium. The various component units of the system were controlled either by a general-purpose programmable logic controller or a dedicated controller. The system provided four subsequent operation modes: cell inoculation, medium change, harvesting, and medium change. The operator could easily select and change the appropriate mode from outside of the aseptic area. The development of the system made large-scale production of mammalian cells, and manufacturing and stabilization of high quality products such as erythropoietin possible under total aseptic control, and opened up the door for industrial production of physiologically active substances as pharmaceutical drugs by mammalian cell culture.