DEVELOPMENT OF AN AUTOMATED CRYOPRESERVATION PROCESS FOR LEUKAPHERESIS TO SUPPORT CGT SUPPLY CHAIN.

Abstract

Background & Aim

Cryoport Systems is the global market leader in temperature-controlled supply chain solutions for critical materials in the life sciences industry and is currently supporting the Cell Therapy Industry with IntegriCell™ – an integrated Leukapheresis Supply Chain Platform. IntegriCell™ aims to deliver consistent, compliant, high-quality leukapheresis starting material for use in the manufacture of cell-based therapies leading to cost reduction through optimized manufacturing slot scheduling.

Cell therapies require an optimized cryopreservation process to achieve consistent results. Cryoport Systems, through the IntegriCell™ platform, is building a network of cryopreservation centers across the US and EU to ensure close proximity to patients, and to optimize and standardize cryopreservation of leukapheresis together within an integrated storage and distribution network.

Methods, Results & Conclusion

Here, we illustrate the development of an automated closed process using the Cue® Cell Processing System from Fresenius Kabi. This process is subdivided into buffer preparation; Cue system processing, post processing and freezing. Cue system processing is a critical step which involves wash of leukapheresis by spinning membrane filtration, buffer exchange and cryo-formulation. We developed a Quality by Design process upon which Quality Target Product Profile (QTPP) for cryopreserved leukapheresis was defined. In addition, Critical Quality Attributes (CQAs), Critical Material Attribute (CMAs) and Critical Process parameters (CPPs) were identified based on Risk Assessment. Built on those prerequisites, an Automated closed cryo-process was developed by optimizing CPPs such as wash buffer solution content, cell concentration upon processing and spinner wash flow rate.

Data obtained upon development justified the CQAs for cryopreserved leukapheresis with ≥80% process recovery and ≥90% viability after thawing. The results also demonstrated that buffer exchange did not significantly modifies the profile of the original fresh leukopack. Together, the automated closed process leads to reduced variability in post thaw recovery and viability compared to the more traditional manual processes. This confirming the capacity of the IntegriCell™ automated process to reduce product variability for the CGT manufacturers. This study highlights the benefits of using the IntegriCell Automated Cryopreservation Process for improving process and product consistency of the starting leukapheresis for CGT manufacturing.