Burnouf T, Radosevich M
Human Plasma Product Service, Lille, France.
Haemophilia. 2003 Jan;9(1):24-37. doi: 10.1046/j.1365-2516.2003.00701.x.
This review presents the current status on the use and benefits of viral removal filtration systems--known as nanofiltration--in the manufacture of plasma-derived coagulation factor concentrates and other biopharmaceutical products from human blood origin. Nanofiltration of plasma products has been implemented at a production scale in the early 1990s to improve margin of viral safety, as a complement to the viral reduction treatments, such as solvent-detergent and heat treatments, already applied for the inactivation of human immunodeficiency virus, hepatitis B and hepatitis C virus. The main reason for the introduction of nanofiltration was the need to improve product safety against non-enveloped viruses and to provide a possible safeguard against new infectious agents potentially entering the human plasma pool. Nanofiltration has gained quick acceptance as it is a relatively simple manufacturing step that consists in filtering protein solution through membranes of a very small pore size (typically 15-40 nm) under conditions that retain viruses by a mechanism largely based on size exclusion. Recent large-scale experience throughout the world has now established that nanofiltration is a robust and reliable viral reduction technique that can be applied to essentially all plasma products. Many of the licensed plasma products are currently nanofiltered. The technology has major advantages as it is flexible and it may combine efficient and largely predictable removal of more than 4 to 6 logs of a wide range of viruses, with an absence of denaturing effect on plasma proteins. Compared with other viral reduction means, nanofiltration may be the only method to date permitting efficient removal of enveloped and non-enveloped viruses under conditions where 90-95% of protein activity is recovered. New data indicate that nanofiltration may also remove prions, opening new perspectives in the development and interest of this technique. Nanofiltration is increasingly becoming a routine step in the manufacture of biopharmaceutical products.
本综述介绍了病毒去除过滤系统（即纳滤）在生产源自人血的血浆源性凝血因子浓缩物及其他生物制药产品中的应用现状及益处。血浆产品的纳滤技术于20世纪90年代初开始在生产规模上应用，以提高病毒安全性，作为对已用于灭活人类免疫缺陷病毒、乙型肝炎病毒和丙型肝炎病毒的病毒灭活处理（如溶剂-去污剂处理和热处理）的补充。引入纳滤的主要原因是需要提高产品对非包膜病毒的安全性，并为可能进入人类血浆库的新传染源提供一种潜在的防护措施。纳滤已迅速得到认可，因为它是一个相对简单的生产步骤，即在能通过主要基于尺寸排阻机制截留病毒的条件下，将蛋白质溶液通过孔径非常小（通常为15 - 40纳米）的膜进行过滤。目前全球范围内的大规模经验已证实，纳滤是一种强大且可靠的病毒灭活技术，可应用于基本上所有的血浆产品。许多已获许可的血浆产品目前都经过了纳滤处理。该技术具有主要优势，因为它具有灵活性，并且可以高效且在很大程度上可预测地去除超过4至6个对数级的多种病毒，同时对血浆蛋白没有变性作用。与其他病毒灭活方法相比，纳滤可能是迄今为止唯一一种在能回收90 - 95%蛋白质活性的条件下有效去除包膜病毒和非包膜病毒的方法。新数据表明，纳滤还可能去除朊病毒，为该技术的发展和应用开辟了新的前景。纳滤正日益成为生物制药产品生产中的常规步骤。
