As more and more cell and gene therapies are being developed and with the increasing number of regulatory approvals being obtained, there is an emerging and pressing need for industrial translation. Process efficiency, associated cost drivers and regulatory requirements are issues that need to be addressed before industrialisation of cell and gene therapies can be established. Automation has the potential to address these issues and pave the way towards commercialisation and mass production as it has been the case for ‘classical’ production industries. This review provides an insight into how automation can help address the manufacturing issues arising from the development of large-scale manufacturing processes for modern cell and gene therapy. The existing automated technologies with applicability in cell and gene therapy manufacturing are summarized and evaluated here.

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Laboratory automation is a key driver in biotechnology and an enabler for powerful new technologies and applications. In particular, in the field of personalized therapies, automation in research and production is a prerequisite for achieving cost efficiency and broad availability of tailored treatments. For this reason, we present the StemCellDiscovery, a fully automated robotic laboratory for the cultivation of human mesenchymal stem cells (hMSCs) in small scale and in parallel. While the system can handle different kinds of adherent cells, here, we focus on the cultivation of adipose-derived hMSCs. The StemCellDiscovery provides an in-line visual quality control for automated confluence estimation, which is realized by combining high-speed microscopy with deep learning-based image processing. We demonstrate the feasibility of the algorithm to detect hMSCs in culture at different densities and calculate confluences based on the resulting image. Furthermore, we show that the StemCellDiscovery is capable of expanding adipose-derived hMSCs in a fully automated manner using the confluence estimation algorithm. In order to estimate the system capacity under high-throughput conditions, we modeled the production environment in a simulation software. The simulations of the production process indicate that the robotic laboratory is capable of handling more than 95 cell culture plates per day.

Stem cell-based therapies are a central element of regenerative medicine and provide new treatment modalities for chronic and life-threatening conditions. Mesenchymal stem/stromal cells (MSCs) represent an important technology in regenerative medicine, although less developed with respect to clinical translation than hematopoietic stem cells (HSCs). MSC therapies may be based on the potential of the cells to differentiate to mesenchymal lineages or on their paracrine effects on host tissue. Both autologous and allogeneic applications are possible, the latter enabled by the low immunogenicity of the cells. Although stem cell therapy holds much promise for the treatment of chronic and debilitating diseases, there are still many obstacles to be overcome. In addition to the compelling need to generate strong and unambiguous clinical evidence, there are major technical gaps that must be filled. Chief among these is the development of manufacturing platforms for cell products that are efficient, cost effective and reproducible. Automated, robotic and closed production systems will provide the most efficient manufacturing strategy. Here we describe advances in automation for the clinical-scale production of MSCs and challenges associated with translating from lab-scale to automated large-scale manufacturing processes.

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