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

Abstract

To indentify a plausible large-scale production system for retroviral vector, three culture systems, i.e., batch culture with medium exchange, microcarrier culture, and packed-bed reactor culture were compared. In batch cultures with medium exchange, high cell concentrations were maintained for about a month, and the harvested retroviral titer remained constant. In microcarrier cultures, although cell growth was rapid, the retroviral titer was unexpectedly low, suggesting that the low titer was due either to serious damage to the retroviral vector or to a reduction in the production rate of retroviral 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 (maximum titer, 1.91 x 10(6)), continuous production made it possible to increase 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 labor and shows excellent volumetric productivity in comparison to batch cultures with medium exchanges, it will be an appropriate production system for retroviral vector in large quantities.