Robustness of nanofiltration for increasing the viral safety margin of biological products
Robustness of nanofiltration for increasing the viral safety margin of biological products
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DOI：
10.1016/j.biologicals.2013.10.003
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发表时间：
2014-03-01
期刊：
影响因子：
1.7
通讯作者：
Jorquera, Juan I.
中科院分区：
文献类型：
--
作者：
Caballero, Santiago;Diez, Jose M.;Jorquera, Juan I.
在这项研究中，使用经过验证的实验室规模模型对各种病毒进行了纳滤的病毒去除能力评估（伪狂犬病病毒;人类免疫缺陷病毒;牛病毒性腹泻病毒;西尼罗河病毒;甲型肝炎病毒;鼠脑心肌炎病毒;和猪细小病毒），并应用存在于多种Grifols血浆中的不同工艺条件，衍生生产工艺（凝血酶、α 1-蛋白酶抑制剂、因子IX、抗凝血酶、纤溶酶、静脉注射免疫球蛋白和纤维蛋白原）。在工艺中间产物中进行加标实验（n = 133），随后通过感染性滴定测定清除率。通过比较各产品纯化条件下纳滤前后的病毒载量，计算降低因子（RF）。在所有实验中，RF接近或大于4 log（10）（>99.99%的病毒消除）。在测定限度内（pH值、离子强度、温度、过滤比和蛋白浓度），工艺条件对RF值无显著影响。纳滤的病毒去除能力仅与去除剂的大小相关。总之，用于生产多种Grifols产品的纳滤具有一致性、耐用性，且不受工艺条件的显著影响。(C)2013年国际生物标准化联盟。由爱思唯尔有限公司出版。保留所有权利。
In this study, the virus-removal capacity of nanofiltration was assessed using validated laboratory scale models on a wide range of viruses (pseudorabies virus; human immunodeficiency virus; bovine viral diarrhea virus; West Nile virus; hepatitis A virus; murine encephalomyocarditis virus; and porcine parvovirus) with sizes from 18 nm to 200 nm and applying the different process conditions existing in a number of Grifols' plasma-derived manufacturing processes (thrombin, alpha 1-proteinase inhibitor, Factor IX, antithrombin, plasmin, intravenous immunoglobulin, and fibrinogen). Spiking experiments (n = 133) were performed in process intermediate products, and removal was subsequently determined by infectivity titration. Reduction Factor (RF) was calculated by comparing the virus load before and after nanofiltration under each product purification condition. In all experiments, the RFs were close to or greater than 4 log(10) (>99.99% of virus elimination). RF values were not significantly affected by the process conditions within the limits assayed (pH, ionic strength, temperature, filtration ratio, and protein concentration). The virus-removal capacity of nanofiltration correlated only with the size of the removed agent. In conclusion, nanofiltration, as used in the manufacturing of several Grifols' products, is consistent, robust, and not significantly affected by process conditions. (C) 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.