ISSUES IN THE DEVELOPMENT OF MEDICAL PRODUCTS BASED ON HUMAN PLASMA

Product development and process validation are shown in the case of se veral 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 pr oduct control and in-process control. For the production of virus-inac tivated human plasma a down-scale protocol is presented, allowing a si mulation of the production on a laboratory scale. Virus validation has shown that the reduction of transfusion-relevant viruses in the proce ss was higher than six log steps. Determination of leachables from the RP-column, which was used in this production, proved that they appear in the final produce in quantities below the detection limits only. I t was also shown that the chemicals used for virus inactivation could be quantitatively removed from the product. For the isolation of other products, here intravenous gamma globulins and the clotting factors V III and IX, similar validation steps had to be taken. In the case of c lotting factor VIII the following data were determined, the reduction of viruses, the amount of leachables from the column, 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 t he columns used for chromatographic purification was found to be far b elow the permissible levels. (C) 1997 Elsevier Science B.V.