Publications & Reports

Chromatographic removal and heat inactivation of hepatitis A virus during 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.

Abstract

CSL Limited, an Australian biopharmaceutical company, has recently converted its method of manufacture for human albumin from a traditional Cohn-ethanol fractionation method to a method employing chromatographic techniques. Studies were undertaken to determine the efficiency of the chromatographic and pasteurization steps used in the manufacture of Albumex® (CSL’s trade name for albumin) in removing and inactivating the potential viral contaminant, hepatitis A virus (HAV). The manufacturing process for Albumex® includes three chromatographic steps, two of which are ion-exchange steps (DEAE-Sepharose® Fast Flow and CM-Sepharose® Fast Flow) and the third is a gel-filtration step (Sephacryl® S200 HR). The final stage of the Albumex® process involves a bulk pasteurization step where product is held at 60 degrees C for 10 h. HAV partitioning experiments on the DEAE-Sepharose® FF and CM-Sepharose® FF ion-exchange and Sephacryl® S200 HR gel-filtration columns were performed with scaled-down models of the production-scale chromatographic Albumex® process. Production samples collected before each of the chromatographic steps were spiked with HAV and processed through each of the scaled-down chromatographic columns. Samples collected during processing were assayed and the log10 reduction factors calculated. Inactivation kinetics of HAV were examined during the pasteurization of Albumex® 5 and 20 [5% and 20% (w/v) albumin solutions] held at 60 degrees C for 10 h. Log10 reductions for HAV through the DEAE-Sepharose® FF, CM-Sepharose® FF and Sephacryl® S200 HR chromatographic columns were 5.3, 1.5 and 4.2 respectively, whereas a 4.4 and a greater than 3.9 log10 reduction in HAV in Albumex® 5 and 20 respectively were achieved during pasteurization.

Publication

  • Journal: Biotechnology and Applied Biochemistry
  • Published: 01/08/1998
  • Volume: 28 ( Pt 1)
  • Pagination: 85-94

Author

Health Issues