Adopting automation for the manufacture of cell products - considerations and best practices: Blog-Beitrag auf https://www.regmednet.com, July 29, 2019

In this community post, Jelena Ochs, Fraunhofer Institute for Production Technology, discusses the challenges of utilizing automated solutions in biological processes

Automation in the context of stem cell production - where are we heading with Industry 4.0?

As the field of cell and gene therapy continues to progress, the need for cell products for therapeutic application is increasing. In order to meet the demands, novel challenges particularly within the manufacturing of these products need to be overcome. By translating and applying automation solutions from the production industries into cell culture applications, standardized processing procedures can be introduced in order to reduce the variability, which is a critical issue within the manufacturing workflow. Additionally, the Industry 4.0 philosophy offers a variety of concepts for the design of adaptive processes that address the specific challenges in stem cell production. Novel tools such as data tracking, data analysis and machine learning are enabling technologies that will help support the safe manufacturing of effective products for future cell and gene therapies

Advances in automation for the production of clinical-grade mesenchymal stromal cells: The AUTOSTEM robotic platform

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

Highly modular and generic control software for adaptive cell processing on automated production platforms

The expansion of patient derived stem cells requires adaptive processing protocols that consider the growth behavior. In order to minimize human errors and enhance reproducibility, the industry moves towards automated platforms. This bears several challenges for a control software, such as coping with non-deterministic processes and the prevalent heterogeneity of device interfaces. We have developed a service-oriented approach to meet the demand for flexibility while at the same time giving maximum control over data and devices. Hardware modules are integrated via agents into the control software following a plug-and-produce approach. This generic software is also easily adaptable for other applications

Automated tissue dissociation for rapid extraction of viable cells

Viable cells from healthy tissues are a rich resource in high demand for many next-generation therapeutics and regenerative medicine applications. Cell extraction from the dense connective matrix of most tissues is a labor-intensive task and high variability makes cGMP compliance difficult. To reduce costs and ensure greater reproducibility, automated tissue dissociators compatible with robotic liquid handling systems are required. Here we demonstrate the utility of our automated tissue dissociator that is compatible with standard microtiter well plates for high-throughput processing. We show that viable cell yields match or exceed manual methods while reducing processing time by at least 85%

Das Stammzelllabor der Zukunft. Forschen in einer automatisierten Testumgebung: Beitrag auf der Internetseite des GIT-Labor - Portal für Anwender in Wissenschaft und Industrie (http://www.git-labor.de)

Stammzellen sind heiß begehrte Forschungsobjekte, doch die Herstellung und Erforschung der Zellen ist aufwendig. Hier wird eine vollautomatisierte Plattform vorgestellt, die Forschern Arbeit abnehmen soll. Im robotergestützten Labor sollen nicht nur die bisher manuell durchgeführten Zellkulturprozesse automatisiert, sondern auch an neuen Konzepten für die Laborautomatisierung geforscht werden

Parallelization in automated stem cell culture

Stem cells play a dominant role in biological research and have a significant potential, as test systems for drug screening, disease modeling and therapeutic applications. The automated production of different stem cell types such as iPS and MSC has been realized in recent years by a few research groups. Yet, it requires different approaches in parallelization compared to conventional automated production because of the nature of the living cells on the one hand, and the production system with various interconnected devices on the other hand. Within this work, we present an approach for parallel processing on an automated cell culture platform

Novel platform for fully automated generation and expansion of highly standardized iPS cells

The medical prospects of human induced pluripotent stem cells (hiPSCs) have created an urgent need for standardized and automated processes for reprogramming and expansion of hiPSC lines from large patient cohorts. This demand can be met by the StemCellFactory (www.stemcellfactory.de), an automated platform that runs and controls all required cell culture steps, ranging from adult human dermal fibroblast expansion via feeder-free, Sendai virus-based reprogramming to clonal selection and enzyme-free expansion of the obtained hiPSC clones and lines. The platform requires a highly flexible control software with extensive data management, robust device communication and a metrology based process control. For this purpose, a control software was developed, which allows to run the platform completely automatically. The measurement of confluence in regular time intervals of every well in a microtiter plate is done by high speed microscopy that was developed for the StemCellFactory platform. To achieve a complete automated run of microtiter plates with patient specific cells, threshold based decision logics are implemented that compute and translate the acquired data during the process and adapts the workflow according to the measured results. The automated process was implemented on microtiter plates and scheduled. Eventually, extensive biological validation was performed to confirm that automatically expanded hiPSCs remain pluripotent upon automated long-term (10 passages) cultivation. In summary, our data show that analysis of in-process generated data largely facilitates automation of highly dynamic cell culture processes