Removal and inactivation of hepatitis B virus from contaminated pooled plasma in a large-scale manufacturing process for factor VIII and human serum albumin.
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.
Murozuka
T
T
The Japanese Red Cross Plasma Fractionation Center, Chitose, Japan. Bunkakul@po.iijnet.or.jp
Aoki
M
M
Kimura
N
N
Sotoyama
K
K
Abe
I
I
Izumi
H
H
Emura
H
H
Takeda
Y
Y
Nanakawa
H
H
Katsubayashi
Y
Y
Takeuchi
T
T
Ito
H
H
Hirakawa
S
S
Mitsunaga
S
S
Tadokoro
K
K
Kanemitsu
K
K
Miyamoto
M
M
Yamanaka
R
R
Nishioka
K
K
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*
D012709:Serum Albumin; D005169:Factor VIII