Designing fully automated in-process controls for cell and gene therapy manufacturing

Ensuring cell based therapies are commercially viable requires scalable manufacturing platforms.

These platforms must support cell growth, while maintaining the cells phenotype, genomic stability and health. To measure these parameters during manufacture, accurate markers must be identified to determine the state of the cells inside the closed system.

The challenge

Induced pluripotent stem cells (iPSCs) have the ability to be differentiated into a wide range of cell types and they are therefore an attractive target for cell therapy development. However the manufacturing process to turn these cells into a living medicine is extremely complex, requiring highly trained scientists performing long and technical processes. This level of complexity adds a significant cost burden and has been a significant barrier in realising the potential of cell and gene therapies in the clinic. Automating the manufacturing process can lower production costs and mitigate risk through reducing human error, helping to overcome some of these barriers.

The Japanese company Tokyo Electron was looking to develop standardised Smart Cell Processing Technologies for cell culture and inspection. Together with Tokyo Electron Europe Ltd., the CGT Catapult team investigated the companies scale up manufacturing system to automate iPSC manufacture, and explored the use of in process analytics to monitor the quality of the iPSCs during manufacture.

The collaborative solution 

To monitor the quality of the cells during manufacture CGT Catapult investigated a wide range of techniques including flow cytometry, quantitative imaging, gene expression and Liquid chromatography mass spectrometry (LCMS). Multivariate data analysis algorithms were used to identify markers indicative of cell identity, proliferation status and phenotype.

Using these analytical techniques, the team were able to identify rapid changes in marker expression indicative of cell quality. These changes could be monitored in near real-time using LCMS, a technique which can identify metabolites produced by the cells during the process, providing information on cell health at a given time point.

Measuring the identified markers will provide a robust platform for the monitoring of cells during manufacture. Using Tokyo Electron’s Pre-Alpha automated culture system, it demonstrated that automation can be superior to manual processes in achieving tighter levels of consistency in the number and the metabolic activity of the cells during culture. This not only reduces production costs but also ensure product quality.

Generating health and wealth

This project has tested the functionality of  an automated system for the monitoring of iPSCs during manufacture. When compared to a manual process it is superior for achieving consistency of the cells, and therefore product quality. This step towards the automated manufacture of cell and gene therapies is important to ensure their commercialisation.

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