Integration and Digitalization in the Manufacturing of Therapeutic Proteins

Abstract The biopharmaceutical market has experienced a tremendous growth in the last years. However, this growth should be balanced considering the difficulty in bioproduct development and the associated high manufacturing costs. These limitations are pushing towards process intensification, stimulated by the Quality by Design (QbD) initiative. Integrated continuous biomanufacturing has emerged as a promising approach towards high throughputs and reliable product quality attributes. At the same time, to face the increased management complexity and compensate fluctuations at the level of the different unit operations, model-based digitalization stands as a fundamental element. In this review, we discuss the state of the art in integrated biomanufacturing and digitalization to highlight their potential towards process intensification. The continuous technologies adopted in the upstream and downstream processing are first reviewed, with a focus on perfusion bioreactors and continuous chromatography. Then, model-based digitalization and its potential in the monitoring and control of integrated bioprocesses are discussed.