[4] Large-scale production of human interferon from lymphoblastoid cells

This chapter discusses large-scale production of human interferon from lymphoblastoid cells. Samples are tested to demonstrate freedom from moulds, bacteria, mycoplasmas, and other infective agents. The frozen stock has subsequently been maintained as a Master Cell Bank from which fresh cells are withdrawn as needed for revival and establishment in culture. For production purposes, the cells are grown in tanks and stirred with an impeller, which is coupled magnetically to the drive motor, thus avoiding the need for a complicated gland and allowing the tank to be operated while completely sealed. Cultures are subjected to aeration to control the redox potential; temperature and pH are also controlled. At the end of the period of induction, purification begins with the removal of the cellular components of the culture to yield a crude solution of interferon. This step can be carried out either by the use of a sterilizable continuous centrifuge or by filtration. The former approach is convenient, but the equipment is complex, difficult to clean effectively without dismantling, and expensive to repair and replace. Filtration systems can be time consuming to develop and involve a significant operating cost in terms of preformed filters.