Automated closed systems for cell manufacturing

• Published in: Cytotherapy (Oxford, England) England), 2019-05, Vol.21 (5), p.S41-S41
• Main Authors: Wu, Y, Rahim, A. Abdul, Lee, J, Sitoe, W, Naing, M. Win
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Other
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2019.03.380

Background & AimAs more autologous cell therapy products are coming through the FDA approval and clinical trial pipeline, there is a need for validated cell manufacturing system that scales across phases of production, from the development to the manufacturing of novel and existing cell therapies. Currently, the manufacturing process involves culturing patient's cells with open culture vessels, especially in the initial phases. This process is labour-intensive and requires skilled operators working in cleanrooms and with biosafety cabinets. Automated closed systems enable one operator to oversee the manufacture of multiple batches of cell therapy products, reducing the number of and demand in skilled operators. For validated manufacturing processes, automated closed systems also increase the reliability and repeatability of each step, and thus contributing to the principle of Quality by Design (QbD) in the current Good Manufacturing Practice (cGMP) framework. While there are a few closed all-in-one cell manufacturing systems in the market, the common complaint is that these systems are not flexible enough to accommodate different manufacturing protocols.Methods, Results & ConclusionWe developed a modular system which automates routine menial steps in a closed environment to reduce overall manufacturing costs with respect to labour and facility, with the flexibility to adjust to different manufacturing protocols. In addition to climate control to maintain temperature, humidity and pCO2, our automated closed system performs routine steps such as removal and top up of the cell culture media; addition of raw and ancillary materials; agitation of the cell culture; sampling of the cell culture; and harvesting of the cells. These steps are programmable to suit the protocol of choice. The current system is validated according to a five-week process for culturing T cells with feeder cells. Each system contains one batch of cell culture which corresponds to one or more therapeutic dose of autologous cell therapy product. With a closed and automated system, resources can be transferred from the manual handling of cell culture to developing new cell therapy products. Our system enables seamless translation of cell therapy products through the clinical trial pipeline, starting from initial research and development and to the final cell manufacturing for administration into patients.