モノクロト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)及び筋注用人免疫グロブリン製剤(抗HBs人免疫グロブリン「日赤」~R,人免疫グロブリン「日赤」~Rの製造工程におけるウイルス除去膜の効果について

摘要

We examined the effectiveness of PLANO VA 35 N filter with a mean pore size of 35 nm in the elimination of viruses in monoclonal antibody-purified freeze-dried human coagulation factor VIII concentrate (CROSS EIGHT M~R) and intramuscular human immunoglobulin (Anti-HBs Human Immune Globulin "Nisseki"and Human Immune Globulin "Nisseki"?). The filtration process was validated for removal of a variety of enveloped and non-enveloped viruses ranging in size from 200 nm to 20 nm including sindbis virus (SIN), vesicular stomatits virus (VSV), herpes simplex virus type 1 (HSV-1), hepatitis B virus (HBV), bovine viral diarrhea virus (BVDV) , hepatitis A virus (HAV) and human parvovirus B 19 (B 19).Results showed that logarithmic reduction values (LRVs) of viruses were >4.7 in SIN, >3.7 in VSV, >2.8 in HSV-1 and 5.0 in HBV.Similarly, PLANOVA 35 N filtration removed SIN, VSV, BVDV and HBV in intramuscular immunoglobulin with LRVs of >4.5, >4.0, >3.7, 5.0, respectively.While filtration did not effectively remove HAV and B 19 in CROSS EIGHT M~R, these viruses were partly reduced after filtration in intramuscular immunoglobulin solution.From the above data, we conclude that the introduction of a PLANOVA 35 N filtration step to our manufacturing process will improve the viral safety of these plasma derivatives.