Cell Culture Systems for Cell Manufacturing

All-in-one closed-system processing platforms offer cell therapy companies an immediate closed and automated solution for cell therapy manufacturing. While realistic during early and small-scale clinical trials, these systems quickly become cost-prohibitive during scale out – burdened with escalating capital equipment costs and an overwhelming requirement for additional space to accommodate high volume parallel patient processing. In addition, the translation from research to large scale protocols require intensive process development work which puts the consistency and quality of the final product at risk.

Improving unit operation efficiency and reconsidering basic principles of cell culture are critical to finding the right balance between scalability and a commercially sustainable manufacturing process.

A few concepts that can make a big impact on this challenge are below:

• Eliminate, then automate – All-in-one automated platforms can place unnecessary limitations on manufacturing capacity, at the level of cell yield per system as well as in practicality of scaling out. An alternate path to sustainable manufacturing is to first eliminate scale-limiting complexities at each unit operation, then tie the optimized operational units together through automation.
• Uncouple cell culture from cell processing – Unit operations utilizing fit-for-purpose technologies (instruments, bioreactor) allows cell culture to be uncoupled from cell processing. This can greatly increase (up to 10x) the potential patient processing power of a manufacturing process. In this scenario, cell production for dozens of patients occurs in parallel within a single incubator, while optimized cell processing systems are designed to output cells for multiple patients per day, both upstream and downstream of cell expansion. For example, G-Rex bioreactors are designed to provide oxygen and nutrients to cells on-demand, increasing the reliability of cell production and removing the necessity of complex instruments for media exchange.
• Use a process that scales-up AND scales-down – A cell production platform that enables the same culture protocol to be used at both small scale and large scale can increase the pace of model development, primary/secondary reagent qualification, and the reproducibility of target cell phenotype during scale-up.

Cell phenotypes can drift during scale up, especially when moving from a flask-based cell expansion system into a gas permeable bag or stirred tank bioreactors. In this case, cell populations and individual phenotypes may vary outside of critical quality attributes (CQAs) defined at small scale. It’s key to keep this challenge in mind even before scaling up and to choose a production system that either uses the same protocols for small and large culture batches or requires very slight process changes. Doing so will help reduce process development time, costs, and regulatory headaches that accompany redefining CQAs.

Bio-Techne’s partners at ScaleReady adhere to the aforementioned concepts and are focused on helping the industry address these manufacturing challenges. They have assembled a platform that enables a truly scalable and commercially viable manufacturing process for autologous and allogeneic cell therapies.

ScaleReady is a powerful partnership between Bio-Techne, Fresenius Kabi, and Wilson Wolf. Their goal is to provide a platform that helps you seamlessly transition your preclinical research into clinical manufacturing with a focus on scalability and financial sustainability. ScaleReady provides an innovative platform for rapid cell expansion, flexible and fully validated instrumentation, and GMP reagents.