Integrating quality control with manufacturing. Automating autologous and allogeneic cell therapy manufacturing

Although major developments in the field of regenerative medicine have been made, osteoarthritis (OA) remains one of the major illnesses of our day. Aside from induced pluripotent stem cells (iPSC) derived mesenchymal stem cells (iMSCS), chondrocytes (iCHO) and extracellular vesicles (EV) are also potential candidates for treatment of OA. As manufacturing and quality control of iPSC derived therapies is so far highly manual, it is currently time consuming and susceptible to human error. A main problem in mak-ing iPSC-based treatments more widely available is the lack of sufficiently scaled pro-duction technologies from seed to fill-and-finish integrating the much needed quality controls. Formerly, the platform AUTOSTEM has been developed for the expansion of MSCs at scale in stirred tank bioreactors and subsequent fill and finish. Additionally, the StemCellDiscovery platform has been developed to handle plate-based cultivation of adherent cells including microscopic analysis of the cells. To shorten release times, release testing such as mycoplasma and endotoxin detection needs to be incorporated into these platforms. Additionally, the production process of iPSC derived cell types is much more extensive requiring steps such as cell differentiation and various quality controls for efficacious production of iMSCs, iCHOs and EVs. By combining the existing technology of the platforms AUTOSTEM and StemcellDiscovery and adapting them to the requirement and adding new technologies and devices, all bioprocesses can be in-tegrated in the AutoCRAT system. It is designed to handle iPSC expansion, differentia-tion to iMSCs and iCHOs, pilot scale expansion and formulation of iMSCs as well as ex-tracellular vesicles and their purification. Most importantly, the platform is equipped with several on-line and at-line assays to determine product quality, purity and safety to take a step closer to real-time release.