Bioprocess intensification with model-assisted DoE-strategies for the production of biopharmaceuticals

Abstract The demand for highly effective biopharmaceuticals and the need to reduce manufacturing costs are increasing the pressure to develop productive and efficient bioprocesses. For this purpose, model-based process design concepts have been developed. Although first approaches were proposed, model-based process designs are still not state-of-the-art for cell culture processes during development or manufacturing. This highlights a need for improved methods and tools for optimal experimental design, optimal and robust process design and process optimization for the purposes of monitoring and control during manufacturing. In this review, an overview of the state of the art of model-based methods, their applications, further challenges, possible solutions and specific case studies for intensification of process development for production of biopharmaceuticals is presented. As a special focus, problems related to data generation (culture systems, process mode, specifically designed experiments) will be addressed.