Lothert Keven, Wolff Michael W
Institute of Bioprocess Engineering and Pharmaceutical Technology, Department Life Science Engineering, University of Applied Sciences Mittelhessen (THM), 35390 Giessen, Germany.
Membranes (Basel). 2023 Aug 30;13(9):770. doi: 10.3390/membranes13090770.
Several chromatographic approaches have been established over the last decades for the production of pharmaceutically relevant viruses. Due to the large size of these products compared to other biopharmaceuticals, e.g., proteins, convective flow media have proven to be superior to bead-based resins in terms of process productivity and column capacity. One representative of such convective flow materials is membranes, which can be modified to suit the particular operating principle and are also suitable for economical single-use applications. Among the different membrane variants, affinity surfaces allow for the most selective separation of the target molecule from other components in the feed solution, especially from host cell-derived DNA and proteins. A successful membrane affinity chromatography, however, requires the identification and implementation of ligands, which can be applied economically while at the same time being stable during the process and non-toxic in the case of any leaching. This review summarizes the current evaluation of membrane-based affinity purifications for viruses and virus-like particles, including traditional resin and monolith approaches and the advantages of membrane applications. An overview of potential affinity ligands is given, as well as considerations of suitable affinity platform technologies, e.g., for different virus serotypes, including a description of processes using pseudo-affinity matrices, such as sulfated cellulose membrane adsorbers.
在过去几十年里，已经建立了几种色谱方法用于生产与药物相关的病毒。与其他生物制药产品（如蛋白质）相比，由于这些产品的尺寸较大，在工艺生产率和柱容量方面，对流流动介质已被证明优于基于珠子的树脂。这种对流流动材料的一个代表是膜，它可以被改性以适应特定的操作原理，并且也适用于经济的一次性应用。在不同的膜变体中，亲和表面允许从进料溶液中的其他成分，特别是从宿主细胞衍生的DNA和蛋白质中最选择性地分离目标分子。然而，成功的膜亲和色谱需要鉴定和应用配体，这些配体在经济上可行，同时在过程中稳定，并且在任何浸出情况下均无毒。本综述总结了目前对基于膜的病毒和病毒样颗粒亲和纯化的评估，包括传统树脂和整体柱方法以及膜应用的优点。给出了潜在亲和配体的概述，以及对合适的亲和平台技术的考虑，例如针对不同病毒血清型的技术，包括使用假亲和基质（如硫酸化纤维素膜吸附剂）的工艺描述。
