Viable manufacture of cell therapies throughthe integration of multiple unit processes onto a counter-flow centrifugation device

Abstract

Background & Aim With growing proof of efficacy in varied indications, regenerative medicine has reached a positive inflection point in the investment of time and money by established industry leaders and disruptive startups. With rapid growth comes the need to devote resources to the engineering challenges that currently prevent the quick and cost-effective manufacture of therapies that maintain a consistent, high-level of quality and, in turn, can support commercial manufacturing. This is especially true when looking at patient specific cell therapies that require rapid change over of equipment and benefit little from traditional sterile barriers (i.e. filters and heat inactivation). Counter-flow centrifugation (CFC) presents an intriguing technology that, when implemented using closed and automated system, provides a platform for upstream and downstream processing of cellular therapies by incorporating multiple unit processes and mitigating the risk imposed with manual equipment transfers. Methods, Results & Conclusion The CFC technology under development by a partnership Hitachi Chemical Advanced Therapeutic Solutions (HCATS) and Invetech compounds the benefits of a fully integrated, closed processing kit with easily customizable procedures to integrate multiple unit processes onto a singular device. Increased integration of unit processes will be integral to addressing the dynamic challenges of commercial cell therapy manufacturing in a scaled-out model. The CFC device has shown the capability to perform platelet wash on apheresis collections with 99% efficiency and retain 100% of the mononuclear cells. Elutriation was able to recover 95% of all monocytes from the MNC population at 78% purity. For lymphocyte isolation, CD3/CD28 beads were incubated with the MNC fraction on the device post platelet wash where 48.6% fewer beads were required to conjugate with the T-Cell population. By incorporating multiple unit processes onto a device that also meets the need for rapid change-over between lots this device offers a unique solution to the emergent challenges of cell therapy manufacturing.