Development of a closed wash/formulation process for CAR-T drug product

Background & Aim Chimeric-Antigen-Receptor T(CAR-T) cells have shown impressive clinical outcomes for hematologic malignancies and are also being actively investigated as a potential treatment for solid tumors. With the benefit of reduced cost of goods, improved product quality and reduce sterility concerns, a closed and automated manufacturing process is one of the major focuses in process development for CAR-T cell manufacturing. Closed processing platforms for early stages of the manufacturing process, such as cell selection and cell expansion, are available, for example the CliniMACS Prodigyâ. However, there is a lack of a ready-to-implement systems for the final formulation steps due to the need to utilize cryopreservation medias that typically contain DMSO. Methods, Results & Conclusion Based on the performance parameters provided by vendors, we have analyzed three different cell wash/formulation systems (Sepax C-ProÒ from GE, LOVOÒ from Fresenius Kabi, and Roteaâ from Thermo Fisher) that are commercially available, for their versatility, flexibility, and costs. We demonstrated the potential to successfully close the process utilizing those systems, and to generate cell product with similar quality compared to the existing open process involving centrifugation. Chimeric-Antigen-Receptor T(CAR-T) cells have shown impressive clinical outcomes for hematologic malignancies and are also being actively investigated as a potential treatment for solid tumors. With the benefit of reduced cost of goods, improved product quality and reduce sterility concerns, a closed and automated manufacturing process is one of the major focuses in process development for CAR-T cell manufacturing. Closed processing platforms for early stages of the manufacturing process, such as cell selection and cell expansion, are available, for example the CliniMACS Prodigyâ. However, there is a lack of a ready-to-implement systems for the final formulation steps due to the need to utilize cryopreservation medias that typically contain DMSO. Based on the performance parameters provided by vendors, we have analyzed three different cell wash/formulation systems (Sepax C-ProÒ from GE, LOVOÒ from Fresenius Kabi, and Roteaâ from Thermo Fisher) that are commercially available, for their versatility, flexibility, and costs. We demonstrated the potential to successfully close the process utilizing those systems, and to generate cell product with similar quality compared to the existing open process involving centrifugation.