Robotic decontamination of a cell production platform

Advanced therapy medicinal products (ATMPs) are of increasing relevance for disease and injury treatment, thereby also their automated manufacturing is of growing interest in academics as well as industry. While already several examples exist for the automation of the production processes, the decontamination as well as monitoring of the contamination status of an ATMP production site consists of mostly manual steps. The main goal of this thesis is to provide solutions for the automation of these, to close the loop of completely automated ATMP production platforms. Contamination monitoring is required by regulations to confirm a sufficient production environment for ATMP production. It consists of measuring dead particles as well as viable contaminants, of which the first is already executable with automated devices available on the market. The regulations define the limits of viable contaminants in colony-forming units (CFUs), which are achieved by collecting contaminants on sample plates and incubating them to make the contaminants grow into CFUs. Sampling air as well as surfaces for viable contaminants by using sample plates is currently a manual task. Therefore, a focus topic of this thesis is the automation of sampling, incubation as well as analysis to count grown CFUs by developing corresponding processes, concepts, implementations, and validating these in a test setup. The results show, that the achieved measurements are in the same range as for manual execution, however, further improvements are required for an application in industrial production. Decontamination consists of two steps, which are the removal of unwanted particles, called cleaning, and the deactivation of all remaining viable contaminants by disinfection or sterilization. While the latter step is trivial to automate, cleaning is currently a manual task. Of all cleaning methods wiping and flushing are identified as applicable in an ATMP production environment. As both have their advantages and disadvantages, processes, technical concepts, and implementations are developed for cleaning by wiping as well as flushing. While the developed automation modules for wiping are validated in a test setup, flushing was regarded by simulation. Similar to automated sampling, the results show, that automated wiping provides similar cleaning results to manual wiping, however, further optimizations are required to reach sufficient process efficiency and stability. The investigation and simulation of flushing shows promising results, indicating, that this method is probably the most efficient automated cleaning technology and should be regarded in future research. The developed concepts for automated decontamination and contamination monitoring in ATMP production indicate that their automation is generally possible and provide a foundation for further developments toward fully automated production.