A Semi-Continuous Method for Purification of Factor IX Complex from Human Plasma

Abstract

We report the development of a semi-continuous method for preparation of factor IX complex from human plasma using ion exchange resins. Traditionally, stirred batch adsorption has been used due to the high pressure drops and low flow rates associated with soft gels in packed columns. Batch methods, however, typically involve higher labor costs and are more cumbersome in process environments. In the semi-continuous process, cryo-supernatant plasma is pumped through a ‘stirred column’ containing the resin. At both lab and pilot scale, higher recoveries of factor IX (FIX) were obtained at decreased total process times, compared to batch adsorption. A residence time of 15 min was found to be sufficient for capture of 95% of the FIX in the starting plasma. In the pilot plant, 550 liters of plasma was passed through a 50-liter column containing 8.5 liters of resin, yielding a 68% recovery of FIX. The results suggest that the recovery of FIX depends on the mode of contact (batch, continuous or packed column) between plasma and resin.