Bioreactors and process monitoring for scale-up of stem cell production

For almost two decades it is claimed that cell-based therapies will revolutionize the field of medicine. Albeit major scientific breakthroughs that present cells as the active ingredient of a clinical therapy are succeeding each other at increasing speed, today only few of these research successes are able to materialise their full clinical potential and develop into a widely available commercial cell-based treatment. Besides the remaining scientific challenges (e.g. exact mechanisms of action), costly product development, and a complex regulatory and reimbursement landscape, it is hypothesised that the lack of automated, controlled and cost-effective production strategies forms a major hurdle towards a wide-spread clinical translation of cell based therapies. This work therefore aims at creating enabling tools and knowledge for monitored and controlled large-scale stem cell production, with the ultimate goal of facilitating the manufacturing of qualitative and cost-effective cell-based therapies. Flask-based cell expansion processes are currently still the gold standard despite the disadvantage of their limited scale-up and automation potential. In a first phase the translation from flask-based cell production processes to a bioreactor-based process was investigated, without adversely influencing the properties of the cells. In parallel to the bioreactor-based scale-up, this work describes how the data from these bioreactor processes can be utilised to non-invasively monitor critical process parameters in real-time, then utilise this information for process control strategies that enable more informed process decisions, ultimately leading to an improved product quality.nrpages: 193status: publishe