Goldsmith J C
Centeon L.L.C., King of Prussia, Pennsylvania 19406, USA.
Blood Coagul Fibrinolysis. 2000 Mar;11(2):203-15.
A factor VIII concentrate (Monoclate-P) manufactured using a combination of pasteurization and immunoaffinity chromatography has been chosen to compare and contrast manufacturing aspects of plasma-derived factor VIII concentrates. Pasteurization is a virucidal method with a long safety record in clinical practice, while immuno-affinity chromatography selectively isolates and purifies the procoagulant protein of factor VIII, and partitions potential viral contaminants and nonessential proteins to the unbound fraction. The complete Monoclate-P production process reduces human immunodeficiency virus by > or = 10.5 log10, Sindbis (a model for hepatitis C virus) by > or = 6.5 log10, and murine encephalomyocarditis virus (a non-enveloped model virus) by 7.1 log10. The viral safety of Monoclate-P has been further demonstrated in clinical studies in patients not previously treated with blood or plasma-derived products. Additionally, the manufacture of Monoclate-P includes careful donor screening and plasma testing for antibodies to syphilis and human immunodeficiency, hepatitis B, and hepatitis C viruses to enhance source plasma safety. Combined with donor selection and plasma testing, multiple viral reduction steps effectively eliminate both lipid-enveloped viruses (e.g. human immunodeficiency, hepatitis B and C) and non-lipid-enveloped viruses (e.g. hepatitis A). In addition, polymerase chain reaction-based nucleic acid detection tests for hepatitis B and C viruses and for human immunodeficiency virus-1 have been introduced as part of an investigational new drug mechanism.
已选用一种采用巴氏消毒法和免疫亲和层析法相结合生产的凝血因子 VIII 浓缩剂（Monoclate-P），以比较和对照血浆源性凝血因子 VIII 浓缩剂的生产方面。巴氏消毒法是一种在临床实践中有长期安全记录的灭病毒方法，而免疫亲和层析法可选择性地分离和纯化凝血因子 VIII 的促凝蛋白，并将潜在的病毒污染物和非必需蛋白分配到未结合部分。完整的 Monoclate-P 生产工艺可使人类免疫缺陷病毒减少≥10.5 log10，辛德毕斯病毒（丙型肝炎病毒模型）减少≥6.5 log10，鼠脑心肌炎病毒（一种无包膜模型病毒）减少 7.1 log10。Monoclate-P 的病毒安全性已在未接受过血液或血浆源性产品治疗的患者的临床研究中得到进一步证实。此外，Monoclate-P 的生产包括仔细的供体筛查以及对梅毒、人类免疫缺陷病毒、乙型肝炎病毒和丙型肝炎病毒抗体的血浆检测，以提高原料血浆的安全性。结合供体选择和血浆检测，多个病毒去除步骤可有效消除包膜病毒（如人类免疫缺陷病毒、乙型肝炎病毒和丙型肝炎病毒）和非包膜病毒（如甲型肝炎病毒）。此外，作为研究性新药机制的一部分，已引入基于聚合酶链反应的乙型肝炎病毒、丙型肝炎病毒和人类免疫缺陷病毒-1 的核酸检测试验。
