モノクロレナル抗体精製乾燥濃縮人血液凝固第VIII因子製剤(クロスエイトM~R)の製造工程におけるウイルスの不括化/除去効果について

摘要

GROSS EIGHT M~R is a monoclonal antibody-purified factor VIII concentrate produced by the Japanese Red Cross from donated blood plasma. During its manufacture, viruses are expected to be inactivated and eliminated by either solvent/detergent (S/D) treatment or both immunoaffinity and anion exchange chromatography.To validate virus inactivation/elimination during the manufacture of CROSS EIGHT M~R, the amount of virus spiked in the manufacturing materials was measured before and after treatment, and the efficiency of virus clearance was calculated for each step. The viruses used were as follows '. sindbis virus (SIN), vesicular stomatitis virus (VSV), human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and herpes simplex virus type 1 (HSV-1) as enveloped viruses ', and hepatitis A virus (HAV) and polio virus (Polio V) as non-enveloped viruses.The result shows that enveloped viruses were effectively inactivated to below detection level after S/D treatment with logarithmic reduction values (LRVs) of 5.6 in SIN, >4.4 in VSV, >5.2 in HSV-1 and >4.9 in HIV-1. In contrast, non-enveloped viruses were not inactivated by S/D treatment. Using the immunoaffinity chromatography process, both enveloped and non-enveloped viruses were eliminated with the LRVs of >3.1 in polio V, >5.4 in VSV, >4.4 in SIN, 4.5 in HAV and 5.4 in HBV. LRVs with anion exchange chromatography varied among viruses, from 0 in HAV to 1.9 in Polio V, depending on the condition of the viral particles.