Mpandi M, Schmutz P, Legrand E, Duc R, Geinoz J, Henzelin-Nkubana C, Giorgia S, Clerc O, Genoud D, Weber T
R & D, Serolab s.a., Chemin de la Vulliette 4, CP 36, 1000 Lausanne 25, Switzerland.
Biologicals. 2007 Oct;35(4):335-41. doi: 10.1016/j.biologicals.2007.02.004. Epub 2007 Apr 30.
Caprylic acid (octanoic acid), has been used for over 50 years as a stabilizer of human albumin during pasteurization. In addition caprylic acid is of great interest, by providing the advantage of purifying mammalian immunoglobulins and clearing viruses infectivity in a single step. Exploiting these two properties, we sequentially used the caprylic acid precipitation and the pasteurization to purify horse hyperimmune globulins used in the manufacturing of Sérocytol. To evaluate the effectiveness of the process for the removal/inactivation of viruses, spiking studies were carried out for each dedicated step. Bovine viral diarrhoea virus (BVDV), pseudorabies virus (PRV), encephalomyocarditis virus (EMCV) and minute virus of mice (MVM) were used for the virological validation. Our data show that the treatment with caprylic acid 5% (v/v) can effectively be used as well to purify or to ensure viral safety of immunoglobulins. Caprylic acid precipitation was very efficient in removing and/or inactivating enveloped viruses (PRV, BVDV) and moderately efficient against non-enveloped viruses (MVM, ECMV). However the combination with the pasteurization ensured an efficient protection against both enveloped and non-enveloped viruses. So that viruses surviving to the caprylic acid precipitation will be neutralized by pasteurization. Significant log reduction were achieved > or =9 log(10) for enveloped viruses and 4 log(10) for non-enveloped viruses, providing the evidence of a margin of viral safety achieved by our manufacturing process. Its a simple and non-expensive manufacturing process of immunoglobulins easily validated that we have adapted to a large production scale with a programmable operating system.
辛酸（正辛酸）在巴氏灭菌过程中作为人白蛋白的稳定剂已使用了50多年。此外，辛酸备受关注，因为它具有一步纯化哺乳动物免疫球蛋白并清除病毒感染性的优势。利用这两个特性，我们依次使用辛酸沉淀和巴氏灭菌法来纯化用于生产赛罗西托尔的马超免疫球蛋白。为了评估该工艺去除/灭活病毒的有效性，对每个专门步骤进行了加标研究。牛病毒性腹泻病毒（BVDV）、伪狂犬病病毒（PRV）、脑心肌炎病毒（EMCV）和小鼠微小病毒（MVM）用于病毒学验证。我们的数据表明，5%（v/v）的辛酸处理也可有效地用于纯化或确保免疫球蛋白的病毒安全性。辛酸沉淀在去除和/或灭活包膜病毒（PRV、BVDV）方面非常有效，对非包膜病毒（MVM、EMCV）的效果中等。然而，与巴氏灭菌相结合可确保对包膜病毒和非包膜病毒都有高效的保护作用。这样，在辛酸沉淀后存活的病毒将被巴氏灭菌中和。包膜病毒的对数减少量显著达到≥9 log₁₀，非包膜病毒为4 log₁₀，这证明了我们的生产工艺实现了病毒安全裕度。这是一种简单且成本不高的免疫球蛋白生产工艺，易于验证，我们已通过可编程操作系统将其应用于大规模生产。
