Biotechnol Appl Biochem 1998 Oct;28 ( Pt 2):169-78
Chromatographic removal and
heat inactivation of hepatitis B virus during the manufacture of human
albumin.
Adcock WL, MacGregor A, Davies JR, Hattarki M, Anderson DA, Goss NH.
Research and Development, CSL Limited, Bioplasma Division, 189-209 Camp
Road, Broadmeadows, Victoria 3047, Australia.
The purpose of the present study was to examine the efficacy of the
chromatographic and pasteurization steps, employed in the manufacture of
human albumin, in the removal and/or inactivation of hepatitis B virus
(HBV). Most human albumins manufactured today are prepared from donor
plasma by fractionation methods that use precipitation with cold
ethanol. CSL Limited, an Australian biopharmaceutical company, has
recently converted its method of manufacture for albumin from a
traditional Cohn fractionation method to a method employing
chromatographic techniques. A step-by-step validation of virus removal
and inactivation was performed on this manufacturing process, which
includes a DEAE-Sepharose(R) and CM-Sepharose(R) Fast Flow ion-exchange
step, a Sephacryl(R) S200 High-Resolution gel-filtration step and a bulk
pasteurization step where product is held at 60 degreesC for 10 h. HBV
partitioning experiments were conducted on scaled-down chromatographic
columns with hepatitis B surface antigen (HBsAg) as a marker, whereas
the HBV model virus, duck HBV, was used to study the inactivation
kinetics during pasteurization. Reductions for HBsAg through the three
chromatographic steps resulted in a total log10 decrease of 1.5 log10,
whereas more than 6.5 log10 decrease in duck HBV in Albumex(R)5 was achieved during pasteurization.
PMID: 9756468 [PubMed - indexed for MEDLINE]
