Luttmann Reiner, Borchert Sven-Oliver, Mueller Christian, Loegering Kai, Aupert Florian, Weyand Stephan, Kober Christian, Faber Bart, Cornelissen Gesine
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
Research Center of Bioprocess Engineering and Analytical Techniques, Hamburg University of Applied Sciences, Hamburg, Germany.
J Biotechnol. 2015 Nov 10;213:83-96. doi: 10.1016/j.jbiotec.2015.02.022. Epub 2015 Feb 28.
An intensification of pharmaceutical protein production processes can be achieved by the integration of unit operations and application of recurring sequences of all biochemical process steps. Within optimization procedures each individual step as well as the overall process has to be in the focus of scientific interest. This paper includes a description of the development of a fully automated production plant, starting with a two step upstream followed by a four step downstream line, including cell clarification, broth cleaning with microfiltration, product concentration with ultrafiltration and purification with column chromatography. Recursive production strategies are developed where a cell breeding, the protein production and the whole downstream is operated in series but also in parallel, each main operation shifted by one day. The quality and reproducibility of the recursive protein expression is monitored on-line by Golden Batch and this is controlled by Model Predictive Multivariate Control (MPMC). As a demonstration process the production of potential Malaria vaccines with Pichia pastoris is under investigation.
通过整合单元操作以及应用所有生化过程步骤的循环序列，可以实现药物蛋白生产过程的强化。在优化程序中，每个单独步骤以及整个过程都必须成为科学关注的焦点。本文描述了一个全自动生产工厂的开发过程，该过程从两步上游工艺开始，接着是四步下游工艺线，包括细胞澄清、微滤肉汤清洗、超滤产物浓缩和柱色谱纯化。开发了递归生产策略，其中细胞培养、蛋白质生产和整个下游工艺既可以串联运行，也可以并行运行，每个主要操作错开一天。通过金批次在线监测递归蛋白表达的质量和可重复性，并由模型预测多变量控制（MPMC）进行控制。作为一个示范过程，正在研究利用毕赤酵母生产潜在的疟疾疫苗。
