Justification of continuous packed-bed reactor for retroviral vector production from amphotropic Psi CRIP murine producer cell

To indentify a plausible large-scale production system for retroviral vecto r, three culture systems, i.e., batch culture with medium exchange, microca rrier culture, and packed-bed reactor culture were compared. In batch cultu res with medium exchange, high cell concentrations were maintained for abou t a month, and the harvested retroviral titer remained constant. In microca rrier cultures, although cell growth was rapid, the retroviral titer was un expectedly low, suggesting that the low titer was due either to serious dam age to the retroviral vector or to a reduction in the production rate of re troviral vector, caused by mechanical shear forces. Although the retroviral titer (maximum titer, 1.56 x 10(6)) in the packed-bed reactor was a little bit lower than that obtained in the batch culture with medium exchange (ma ximum titer, 1.91 x 10(6)), continuous production made it possible to incre ase the cumulative titer up to 16-fold of that from the batch culture with medium exchange. Moreover, as the packed-bed reactor system requires less l abor and shows excellent volumetric productivity in comparison to batch cul tures with medium exchanges, it will be an appropriate production system fo r retroviral vector in large quantities.