In order to scale up production without significantly increasing cost, ideally there is no requirement to significantly add equipment or space to the production area (i.e., incubators, cleanroom space). The data in Figure 2 demonstrates that the product output from HYPERStack Vessels is approximately three times higher when compared to vessels that utilize traditional multilayered flask technology while occupying the same space in the incubator or warm room.
MDBK cell growth in the traditional two-layer multilayered vessel was compared to growth in the HYPERStack-12 Vessel (Figure 2A). CHO-K1 and Mesenchymal Stem Cells (MSC) were cultured in either the HYPERStack-36 Vessel or traditional 10-layer vessels and total cell yield compared (Figure 2B and 2C, respectively). This is significant for large-scale manufacturing, as the end result is an increase in the product throughput per manufacturing area, thereby controlling costs.
Another key feature incorporated into this vessel design making the scaling to production level easier, is the use of BSE/TSE-compliant C-Flex tubing for liquid manipulations. All liquid transfer is conducted through the liquid-handling tubing connected to one manifold while air escape and entry occurs through the other manifold. (Figure 1). For closed systems, addition and removal of fluids occurs between the HYPERStack Vessel tubing set and various auxiliary vessels, such as media bags, tube welding, or the use of aseptic connectors.
Working with an optimized set of flexible bioprocess containers, such as TheraPEAK™ bioprocess containers by Lonza, a product expansion project can be conducted from vessel seeding through culture expansion and harvest in a completely closed system. Utilizing a closed system not only greatly reduces the risk of culture loss due to contamination, but makes the process more suitable for cGMP manufacturing.
The Lonza Walkersville cell therapy development team has developed closed systems allowing up to 70 vessels to be handled in a single harvest, yielding 10 billion cells or greater harvests for many cell types.
The HYPERStack cell culture vessel family has been developed as a modular system, with the HYPERStack-12 as the single module. These modules can be stacked, allowing the process to be scaled as required for the manufacturing facility and the annual dosage requirements of the product. Currently, the HYPERStack-12 and HYPERStack-36 Vessels are available, and the HYPERStack-120 Vessels are expected to be available by the end of 2011.