A process for preparation of 'high-purity' factor VIII by controlled pore glass treatment

A simple process for large-scale manufacture of 'high-purity' factor VIII is described in detail. A crude concentrate prepared from washed cryo is treated with controlled pore glass (CPG, 500 A pore diameter) in proportion of 20-30 ml of CPG to 1 g input of protein. The slurry is poured into a separation column and the effluent purified concentrate collected. The remaining factor VIII in the void volume is displaced by a wash solution. After passage through a 0.2 micron membrane filter the product is dispensed and lyophilized. Maintaining the operating pH at 6.5-6.7 and adding synthetic amino acids improved the yield and solubility. The current concentrate contains 1 unit of factor VIII per mg protein (10 units mg fibrinogen) with a recovery of 250 units/kg plasma. The CPG stage is non-destructive, yielding more than 90% of the input factor VIII. In 1980-1983, more than 3 X 10(6) units have been used in New South Wales, mostly for massive cover in surgical patients. In collaboration with the Commonwealth Serum Laboratories, it is intended to expand production for use in other Australian States.