A solvent/detergent-treated and 15-nm filtered factor VIII:: a new safety standard for plasma-derived coagulation factor concentrates
A solvent/detergent-treated and 15-nm filtered factor VIII:: a new safety standard for plasma-derived coagulation factor concentrates
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DOI：
10.1111/j.1423-0410.2007.00892.x
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发表时间：
2007-01-01
期刊：
影响因子：
2.7
通讯作者：
Mazurier, C.
中科院分区：
文献类型：
--
作者：
Chtourou, S.;Porte, P.;Mazurier, C.
背景自20世纪90年代初以来，专利药品委员会（Committee for Proprietary Medicinal Products）已经制定了强制性要求，即所有血液制品的生产工艺包括两个病毒去除/灭活步骤，这两个步骤在其作用中是互补的。将15 nm纳米过滤步骤添加到包括溶剂/去污剂（S/D）处理的先前FVIII生产工艺中，以生成称为Factane（R）的新FVIII浓缩物。纳米过滤对FVIII的结构和功能特性的影响，以及病毒/传染性海绵状脑病减少factors进行了assessed.Results使用创新的方法，FVIII成功地在35-15 nm的纳米过滤，而活性物质的生物学特性是未经修改的。Factane（R）和之前S/D处理的FVIII（FVIII-LFB，商品名为Facteur VIII-LFB（R））的FVIII凝血剂和抗原含量相当。FVIII一阶段显色和凝血剂/抗原比证实，纳米过滤的FVIII未被活化。纳滤后，共纯化的血管性血友病因子（vWF）减少，但vWF/FVIII结合特性不受影响。磷脂结合和凝血酶蛋白水解研究显示Factane（R）和FVIII-LFB之间无差异。与FVIII-LFB相比，Factane（R）的因子Xa生成率略低。不同病毒的病毒验证研究表明，在filtration.Conclusions在15 nm的纳米过滤的FVIII是可行的，尽管大分子量的FVIII和vWF。已被证明，纳米过滤可以非常有效地去除传染性病原体，同时保留凝血因子VIII的结构和功能完整性。
Background Since the early 1990s the Committee for Proprietary Medicinal Products has set the mandatory requirement that all manufacturing processes for blood products include two virus removal/inactivation steps that are complementary in their action.Objectives The objective was to develop a manufacturing process for factor VIII (FVIII) including two complementary steps of viral inactivation/elimination.Methods A 35-15 nm nanofiltration step was added to a former FVIII manufacturing process that included solvent/detergent (S/D) treatment to generate a new FVIII concentrate called Factane (R). The impact of nanofiltration on the structural and functional characteristics of FVIII, as well as virus/transmissible spongiform encephalopathy reduction factors were assessed.Results Using an innovative approach, FVIII was successfully nanofiltered at 35-15 nm, while the biological properties of the active substance were unmodified. FVIII coagulant and antigen content for Factane (R) and previous S/D-treated FVIII (FVIII-LFB, commercialized as Facteur VIII-LFB (R)) were comparable. The FVIII one-stage chromogenic and coagulant/antigen ratios confirmed that nanofiltered FVIII was not activated. After nanofiltration, the copurified von Willebrand factor (vWF) was reduced but vWF/FVIII binding properties were unaffected. Phospholipid binding and thrombin proteolysis studies displayed no differences between Factane (R) and FVIII-LFB. The rate of factor Xa generation was slightly lower for Factane (R) when compared to FVIII-LFB. Viral validation studies with different viruses showed no detectable virus in the filtrate.Conclusions Nanofiltration of FVIII at 15 nm is feasible despite the large molecular weight of FVIII and vWF. Nanofiltration has been proven to be highly effective at removing infectious agents while preserving the structural and functional integrity of FVIII.