Perfusion development and its potential for cell therapy manufacturing with adherent cells.

Perfusion processing has established itself as a powerful intensification strategy for biopharmaceutical production processes of recombinant proteins. However, in the relatively young field of cell therapeutics manufacturing, this tool has been overlooked so far and with rising approvals, this field is in dire need of scalable and efficient production processes. In this regard, perfusion operation mode and related cell retention devices can be used to support upstream and downstream processing by automating operations, reducing contamination risk and ensuring stable cell quality. In this review, the history of cell retention technologies developed for suspension cell processing is laid out alongside the perfusion-based process intensification strategies they made possible. It is summarized how these technologies could be used to intensify the upstream processing of therapeutic adherent cells and to what degree perfusion processing of these demanding cells is already described in literature. Additionally, the applicability of cell retention devices for harvesting and downstream processing of therapeutic cells, which mainly consists of cell washing and formulation steps, is elaborated. In conclusion, through the implementation of scalable, single-use, good manufacturing practices compliant cultivation systems and cell retention devices, it should be possible substantially to accelerate the development of therapeutic adherent cell manufacturing strategies. KEY POINTS: • Perfusion can automate medium exchanges in therapeutic adherent cell manufacturing •  Perfusion technologies from suspension cell processing can be translated to adherent cell manufacturing • Scalable single-use perfusion systems are needed for the production of cell therapies.