Development of Medical Products Based on Human Plasma
Djuro Josić* and Katharina Pock
Octapharma Pharmazeutika Produktionsges. m.b.H., Oberlaaer Strasse 235, A–1100 Vienna, Austria
Article history:
Received January 25, 1999
Accepted February 15, 1999
Key words:
virus inactivated human plasma, intravenous γ-globulins, clothing factors VIII and IX, chromatographic separation
Summary:
Product development and process validation are shown in the case of several products obtained from human plasma. These are virus inactivated plasma, intravenous immunoglobulins and the clotting factors VIII and IX. Different analytical methods are presented, which are used for product development, quality 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 with high resolution such as 2D-electrophoresis will lead to corresponding results even in the case of components with high molecular masses such as clotting factor VIII and von Willebrand factor. These methods have recently been 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. Virus validation has shown that the reduction of transfusion-relevant viruses in the process was higher than 6 log units. Determination of leachables from the RP-column, which was used in this production, proved that they appear in the final product in quantities below the detection limits only. It was also shown that the chemicals used for virus inactivation could be quantitatively removed from the product. For the isolation of other products, like intravenous gamma globulins and the 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 residues of chemicals from the solvent/ detergent treatment for virus inactivation. Virus reduction was successfully performed as well as the removal of chemicals used for virus inactivation. The amount of leachables from the columns used for chromatographic purification was found to be far below the permissible levels.
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