Optimization of mammalian cell perfusion cultures for the end-to-end continuous integrated production of therapeutic proteins

Monoclonal antibodies (mAbs) have become a new generation of highly target specific pharmaceuticals suitable to treat an increasing number of diseases. The continuous production of these therapeutic proteins in mammalian cells combines several advantages compared to traditional batch-wise processing applied in industry. So far, this processing mode has been mainly used in the production of labile proteins. However, enhanced economics and technology, higher productivity, and product quality are pathing the way to a more general application.

This project purposes the further optimization of the state-of-the art continuous operation mode. The development of new control and automation strategies aims at the stable operation of perfusion cell cultures and facilitates the integration to the subsequent downstream purification train. Consequently, enhanced process robustness and advanced technologies will enable the online optimization of the end-to-end continuous integrated process for the production of biopharmaceuticals.

Besides, the effect of key process parameters, e.g. cell specific perfusion rate (CSPR), media formulations and supplements and temperature, on cellular growth, metabolism, productivity and product quality will be evaluated.   

The acquired knowledge will be consequently combined in order to operate the process under optimized and stable conditions to achieve higher productivities and enhanced product quality.

We want to formulate a general strategy for fast and quasi-optimal integrated continuous cultivation process design. For this task, a number of mechanistic and statistical models (metabolic flux analysis, hybrid approaches) based on the process understanding will be used. The final goal of this project is to develop a strategy which allows to perform process design and optimization for any perfusion culture.

Contact Person: Moritz Wolf