title: Removal and inactivation of hepatitis B virus from contaminated pooled plasma in a large-scale manufacturing process for factor VIII and human serum albumin.
abstract: OBJECTIVE
  The Japanese Red Cross Society recalled one lot of monoclonal-antibody-purified factor VIII (F VIII) and two lots of human serum albumin (HSA) 5 months after preparation of the final products, because of a procedural error that led to contamination by a unit of plasma positive for hepatitis B surface antigen (HBsAg). We evaluated the effectiveness of virus inactivation/removal in a large-scale process for manufacturing F VIII and HSA.
  
  
  METHODS
  HBV DNA in the retained samples in process was measured by the polymerase chain reaction (PCR). The kinetics of virus inactivation by solvent-detergent (S/D) treatment was examined using model viruses. We also did a look-back survey of the patients who received corresponding products.
  
  
  RESULTS
  Contaminated hepatitis B virus (HBV) DNA became undetectable beyond fraction S IV-I in the albumin process and immunoaffinity chromatography in the F VIII process, respectively. The model viruses were inactivated within 5 s by S/D treatment. There is no evidence that patients were infected by HBV after transfusion of these products.
  
  
  CONCLUSIONS
  We conclude that virus inactivation/removal was effectively achieved in a large-scale manufacturing process for F VIII and HSA.
authors.affiliation: The Japanese Red Cross Plasma Fractionation Center, Chitose, Japan. Bunkakul@po.iijnet.or.jp
authors.forename: T
authors.initials: T
authors.lastname: Murozuka
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: N
authors.initials: N
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Sotoyama
authors.forename: I
authors.initials: I
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Izumi
authors.forename: H
authors.initials: H
authors.lastname: Emura
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: H
authors.initials: H
authors.lastname: Nanakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Katsubayashi
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Hirakawa
authors.forename: S
authors.initials: S
authors.lastname: Mitsunaga
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: K
authors.initials: K
authors.lastname: Kanemitsu
authors.forename: M
authors.initials: M
authors.lastname: Miyamoto
authors.forename: R
authors.initials: R
authors.lastname: Yamanaka
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
mesh_terms: D005169:Factor VIII / Q000302:isolation & purification*; D019981:Health Care Sector; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D010949:Plasma / Q000821:virology*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012709:Serum Albumin / Q000302:isolation & purification*
chemical_list: D012709:Serum Albumin; D005169:Factor VIII