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

IF 3.7 3区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
G. Delwiche , A. Fossion , S. Borensztein , G. Fonkou Tchinda , D. Delvaux , J. Bravo-Alegria , A. Michaux
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引用次数: 0

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.

开发白血球冷冻自动保存程序,以支持 CGT 供应链。
背景&& AimCryoport Systems 是生命科学行业关键材料温控供应链解决方案的全球市场领导者,目前正在为细胞疗法行业提供 IntegriCell™--一个集成的白细胞疗法供应链平台。IntegriCell™ 的目标是提供一致、合规、高质量的白细胞分离起始材料,用于细胞疗法的生产,通过优化生产时间安排降低成本。Cryoport Systems公司通过IntegriCell™平台,正在美国和欧盟建立一个低温保存中心网络,以确保接近患者,并在一个综合储存和配送网络内优化和标准化白细胞冷冻保存。该流程分为缓冲液制备、Cue系统处理、后处理和冷冻。Cue系统处理是一个关键步骤,包括纺丝膜过滤清洗白细胞、缓冲液交换和冷冻配制。我们开发了一个 "质量源于设计 "流程,并据此定义了冷冻保存白细胞的 "质量目标产品简介"(QTPP)。此外,还根据风险评估确定了关键质量属性 (CQA)、关键材料属性 (CMA) 和关键工艺参数 (CPP)。在这些先决条件的基础上,通过优化 CPPs(如洗涤缓冲溶液含量、处理过程中的细胞浓度和旋转器洗涤流速),开发出了自动封闭式冷冻流程。开发过程中获得的数据证明了冷冻保存白细胞的 CQAs 是正确的,流程回收率≥80%,解冻后存活率≥90%。结果还表明,缓冲液交换不会明显改变原始新鲜白细胞包的特性。总之,与更传统的手工流程相比,自动化封闭流程减少了解冻后回收率和存活率的变化。这证实了 IntegriCell™ 自动化流程能够降低 CGT 生产商的产品变异性。这项研究强调了使用 IntegriCell 自动化低温保存工艺提高 CGT 生产过程中起始白细胞的工艺和产品一致性的好处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cytotherapy
Cytotherapy 医学-生物工程与应用微生物
CiteScore
6.30
自引率
4.40%
发文量
683
审稿时长
49 days
期刊介绍: The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.
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