Development of medical products based on human plasma

Product development and process validation are shown in the case of several products obtained from human plasma. These are virus inactivated plasma, i ntravenous immunoglobulins and the clotting factors VIII and IX. Different analytical methods are presented, which are used for product development, q uality control and in-process control. The introduction of fast chromatographic methods allows in-process analyses to be carried out within two or three minutes only. Analytical methods wit h high resolution such as 2D-electrophoresis will lead to corresponding res ults even in the case of components with high molecular masses such as clot ting factor VIII and von Willebrand factor. These methods have recently bee n introduced into the process. For the production of virus inactivated human plasma a down-scale protocol is presented, allowing a simulation of the production on a laboratory scale . Vints validation has shown that the reduction of transfusion-relevant vir uses in the process was higher than 6 log units. Determination of leachable s from the RP-column, which was used in this production, proved that they a ppear in the final product in quantities below the detection limits only. I f was also shown that the chemicals used for virus inactivation could be qu antitatively removed from the product. For the isolation of other products, like intravenous gamma globulins and t he clotting factors VIII and IX, similar validation steps had to be taken. In the case of clotting factor VIII the following data were determined: the reduction of viruses, the amount of leachables from the column and the res idues of chemicals from the solvent/detergent treatment for virus inactivat ion. Virus reduction was successfully performed as well as the removal of c hemicals used for virus inactivation. The amount of leachables from the col umns used for chromatographic purification was found to be far below the pe rmissible levels.