CHROMATOGRAPHIC REMOVAL AND HEAT INACTIVATION OF HEPATITIS-B VIRUS DURING THE MANUFACTURE OF HUMAN ALBUMIN

The purpose of the present study was to examine the efficacy of the ch romatographic and pasteurization steps, employed in the manufacture of human albumin, in the removal and/or inactivation of hepatitis B viru s (HBV). Most human albumins manufactured today are prepared from dono r plasma by fractionation methods that use precipitation with cold eth anol, CSL Limited, an Australian biopharmaceutical company, has recent ly converted its method of manufacture for albumin from a traditional Cohn fractionation method to a method employing chromatographic techni ques. A step-by-step validation of virus removal and inactivation was performed on this manufacturing process, which includes a DEAE-Sepharo se(R) and CM-Sepharose(R) Fast Flow ion-exchange step, a Sephacryl(R) S200 High-Resolution gel-filtration step and a bulk pasteurization ste p where product is held at 60 degrees C for 10 h, HBV partitioning exp eriments were conducted on scaled-down chromatographic columns with he patitis B surface antigen (HBsAg) as a marker, whereas the HBV model v irus, duck HBV, was used to study the inactivation kinetics during pas teurization, Reductions for HBsAg through the three chromatographic st eps resulted in a total log,, decrease of 1.5 log(10), whereas more th an 6.5 log(10) decrease in duck HBV in Albumex(R) was achieved during pasteurization.