Cell culture processes for monoclonal antibody production
Cell culture processes for monoclonal antibody production
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DOI：
10.4161/mabs.2.5.12720
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发表时间：
2010-09-01
期刊：
影响因子：
5.3
通讯作者：
Amanullah, Ashraf
中科院分区：
文献类型：
--
作者：
Li, Feng;Vijayasankaran, Natarajan;Amanullah, Ashraf
在过去的几十年里，动物细胞培养技术有了很大的进步，现在被普遍认为是一项可靠、健壮和相对成熟的技术。目前，一系列生物疗法是在大规模生产设施中使用细胞培养方法合成的，这些设施生产的产品既可用于商业用途，也可用于临床研究。这项技术的大力实施需要对一些变量进行优化，包括：(1)能够以高生产率合成所需分子的细胞系，以确保较低的运营成本；(2)达到所需生产率并满足产品质量要求的培养介质和生物反应器培养条件；(3)适当的在线和离线传感器，能够提供加强过程控制的信息；以及(4)对不同规模的培养性能有很好的了解，以确保顺利放大。成功实施还需要制定适当的流程开发、扩大和流程特性及验证战略，使之能够稳健运作，并确保遵守现行法规。本文综述了细胞培养关键方面的最新技术，如高效细胞系的产生和细胞培养工艺条件的优化。我们还总结了当前关于适当的工艺开发战略和可能影响工艺开发的工艺进步的想法。
Animal cell culture technology has advanced significantly over the last few decades and is now generally considered a reliable, robust and relatively mature technology. A range of biotherapeutics are currently synthesized using cell culture methods in large scale manufacturing facilities that produce products for both commercial use and clinical studies. The robust implementation of this technology requires optimization of a number of variables, including (1) cell lines capable of synthesizing the required molecules at high productivities that ensure low operating cost; (2) culture media and bioreactor culture conditions that achieve both the requisite productivity and meet product quality specifications; (3) appropriate online and off-line sensors capable of providing information that enhances process control; and (4) good understanding of culture performance at different scales to ensure smooth scale-up. Successful implementation also requires appropriate strategies for process development, scale-up and process characterization and validation that enable robust operation and ensure compliance with current regulations. This review provides an overview of the state-of-the art technology in key aspects of cell culture, e.g., generation of highly productive cell lines and optimization of cell culture process conditions. We also summarize the current thinking on appropriate process development strategies and process advances that might affect process development.