Radomski Kai Uwe, Lattner Georg, Schmidt Torben, Römisch Jürgen
Virus and Prion Validation, Octapharma Biopharmaceuticals GmbH, Altenhöferallee 3, 60438, Frankfurt am Main, Germany.
R&D Plasma, Octapharma Pharmazeutika Produktionsges.m.b.H., Oberlaaer Str. 235, Vienna, Austria.
BioDrugs. 2017 Apr;31(2):125-134. doi: 10.1007/s40259-017-0212-y.
The manufacturing process of a new intravenous immune globulin (IVIG) 10% liquid product incorporates two dedicated pathogen safety steps: solvent/detergent (S/D) treatment and nanofiltration (20 nm). Ion-exchange chromatography (IEC) during protein purification also contributes to pathogen safety. The ability of these three process steps to inactivate/remove viruses and prions was evaluated.
The objective of this study was to evaluate the virus and prion safety of the new IVIG 10% liquid.
Bovine viral diarrhea virus (BVDV), human immunodeficiency virus type 1 (HIV-1), mouse encephalomyelitis virus (MEV), porcine parvovirus (PPV), and pseudorabies virus (PRV) were used as models for common human viruses. The hamster-adapted scrapie strain 263K (HAS 263K) was used for transmissible spongiform encephalopathies. Virus clearance capacity and robustness of virus reduction were determined for the three steps. Abnormal prion protein (PrP) removal and infectivity of the samples was determined.
S/D treatment and nanofiltration inactivated/removed enveloped viruses to below detection limits. IEC supplements viral safety and nanofiltration was highly effective in removing non-enveloped viruses and HAS 263K. Overall virus reduction factors were: ≥9.4 log (HIV-1), ≥13.2 log (PRV), ≥8.2 log (BVDV), ≥11.7 log (MEV), ≥11.6 log (PPV), and ≥10.4 log (HAS 263K).
Two dedicated and one supplementing steps in the manufacturing process of the new IVIG 10% liquid provide a high margin of pathogen safety.
一种新型10%静脉注射免疫球蛋白（IVIG）液体产品的生产工艺包含两个专门的病原体安全步骤：溶剂/去污剂（S/D）处理和纳滤（20纳米）。蛋白质纯化过程中的离子交换色谱法（IEC）也有助于病原体安全。评估了这三个工艺步骤灭活/去除病毒和朊病毒的能力。
本研究的目的是评估新型10%IVIG液体的病毒和朊病毒安全性。
牛病毒性腹泻病毒（BVDV）、人类免疫缺陷病毒1型（HIV-1）、小鼠脑脊髓炎病毒（MEV）、猪细小病毒（PPV）和伪狂犬病病毒（PRV）被用作常见人类病毒的模型。仓鼠适应型羊瘙痒病毒株263K（HAS 263K）被用于传染性海绵状脑病研究。测定了这三个步骤的病毒清除能力和病毒减少的稳健性。测定了样品中异常朊病毒蛋白（PrP）的去除情况和感染性。
S/D处理和纳滤将包膜病毒灭活/去除至检测限以下。IEC补充了病毒安全性，纳滤在去除非包膜病毒和HAS 263K方面非常有效。总体病毒减少因子为：≥9.4对数（HIV-1）、≥13.2对数（PRV）、≥8.2对数（BVDV）、≥11.7对数（MEV）、≥11.6对数（PPV）和≥10.4对数（HAS 263K）。
新型10%IVIG液体生产工艺中的两个专门步骤和一个补充步骤提供了高病原体安全性保障。
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