Translating Research into Clinical Scale Manufacturing of Mesenchymal Stromal Cells

Figure 1

Flow chart illustrating essential processing and testing steps during MSC manufacture. This scheme summarises a GMP-compliant manufacturing process of MSC expansion separated into processing and related testing activities. On day zero the tissue is harvested and transported to the processing lab. Here donor eligibility criteria are checked again and donor testing/reception control initiated (viral, bacterial, blood group, condition, weight, if applicable cell counting, etc.). Verified reception control is a prerequisite for starting processing in the GMP facility. Here cell isolation is performed and expansion cultures initiated or the product is directly applied to the patient. Predefined in-process controls shall be taken at any critical processing step to verify cellular qualities and sterility. If expansion is initiated, normal protocols include a medium exchange step concomitantly depleting contaminating cells. Cell growth can be monitored visually as well as potential contamination. Passaging of the cells can be performed within the next 14 days involving controls for morphology, viability, and sterility. Assuming day 14 for the day of harvest and product release, cells have to be specified against predefined final product release criteria. The product can then be cryopreserved allowing for additional potency assays or directly transported to the recipient. Packaging, labeling, and shipment conditions again have to follow GMP rules.