Clinical grade cell separation technologies in the Newcastle Cellular Therapies Facility

生产细胞作为药物是一个受管制的过程，只能按照生产程序，质量控制过程，并在许可的场所根据欧盟指令进行。纽卡斯尔大学和纽卡斯尔在泰恩NHS基金会信托投资了必要的基础设施，以建立，维护和许可生产设施符合良好的生产规范（GMP）。已经获得了将细胞作为药物生产的必要许可证，并且与皇家维多利亚医院的临床试验部门和弗里曼医院的移植研究所一起，通过为细胞治疗患者提供特定床位，为患者提供临床支持。纽卡斯尔细胞疗法设施目前正在进行两项细胞疗法的临床试验。第一个是与弗朗西斯科菲吉雷多教授一起进行的MRC自体角膜缘干细胞试验，第二个是与约翰·艾萨克斯教授一起进行的致耐受性树突状细胞（TolDC）试验。此外，Stephen白色教授的自体胰岛细胞治疗已获得HTA批准。此外，迪金森教授是造血干细胞移植实验室的主任，该实验室目前负责每年向患有恶性血液病和免疫缺陷的成人和儿童患者提供约400种细胞治疗产品。NCTF内部雇用了一些具有实践，科学和监管专业知识的合格工作人员，他们能够启动和开发用于细胞疗法临床试验的产品。NCTF接受MHRA、HTA和内部审计的检查。雇用的工作人员包括一名药房质量受权人、一名质量保证经理，及健康专业理事会-注册生物医学科学家与临床医生和临床试验团队密切合作。目标和承诺我们通过MRC再生医学资本资助计划寻求支持，用于购买安装在生产GMP洁净室内的设备，这些设备能够通过细胞表达来纯化细胞群。表面标记。与磁珠缀合的抗体允许选择或耗尽所选细胞类型是已建立的技术。Miltenyi-Biotec生产两种不同的机器或平台，可以利用磁珠技术来纯化细胞群。第一种是Clinimacs Plus，它使用磁珠，但设计用于将选定的细胞纯化到无菌袋中，然后可以准备用于输注或进一步操作。第二个是新的Clinimacs Prodigy，它提供了一个封闭的工作站，能够以可编程的方式处理、纯化和培养细胞，并且可以设计和优化特定的过程。这是最先进的技术，可用于新工艺开发以及细胞疗法的临床级制造。应用与优势Clinimacs Plus将支持TolDC试验。Clinimacs Prodigy将立即用于开发新的方案，利用我们与伊娃·魏辛格教授领导的汉诺威小组的合作，用于异基因骨髓输注后感染CMV的患者的病毒特异性T细胞治疗。Miltenyi-Biotec设计的方案使Prodigy适用于本研究且可行。因此，所要求的设备将使NCTF有能力帮助当前的临床试验和研究新的临床试验，并开发新的细胞治疗方案，以满足MRC战略。此外，细胞治疗制造的研究，教学和培训将通过在我们的设施中托管该设备来支持整个欧盟，因为迪金森教授参与了欧盟资助的建立细胞治疗标准的计划，以支持多中心试验的一致性。

CONTEXTThe production of cells as medicines is a regulated process and can only be conducted in accordance with manufacturing procedures, quality control processes, and in licensed premises according to EU Directives. Newcastle University and Newcastle upon Tyne NHS Foundation Trust have invested in the necessary infrastructure to build, maintain and license production facilities compliant with Good Manufacturing Practice (GMP). The necessary licenses for manufacturing cells as medicines have been obtained, and with the Clinical Trials Unit at the Royal Victoria Infirmary and the Institute for Transplantation at the Freeman Hospital, clinical support for patients is enabled by the provision of specific beds for cell therapy patients. The Newcastle Cellular Therapies Facility is currently running two clinical trials in cellular therapies. The first is the MRC Autologous Limbal Stem Cell trial for eye trauma with Professor Francisco Figuieredo, and the second is the tolerogenic dendritic cell (TolDC) trial for rheumatoid arthritis with Professor John Isaacs. In addition, HTA approval has been granted for autologous pancreatic islet cell therapy with Professor Stephen White. Furthermore, Professor Dickinson is Director of the Haematopoietic Stem Cell Transplant laboratory which is currently responsible for releasing approximately 400 cell therapy products per year to adult and paediatric patients suffering from malignant blood disorders and immune deficiency. A number of qualified staff with practical, scientific and regulatory expertise are employed within the NCTF who are able to initiate and develop products for clinical trials in cellular therapies. The NCTF is subjected to inspections by the MHRA, HTA and internal audits. The staff employed include a Pharmacy Qualified Person, a Quality Assurance Manager, and Health Professional Council-registered Biomedical Scientists who work closely with clinicians and clinical trial teams.AIMS AND OBJECTIVESWe seek support through the MRC Regenerative Medicine Capital Funding scheme for the purchase of equipment to be housed within the production GMP cleanrooms that have the capacity to purify populations of cells by their expression of cell surface markers. Antibodies conjugated to magnetic beads that permit the selection or depletion of chosen cell types is established technology. Miltenyi-Biotec produces two different machines, or platforms, that can exploit the magnetic bead technology to purify cell populations. The first is the Clinimacs Plus that uses magnetic beads but is designed to purify chosen cells into sterile bags that can then be issued ready for infusion or further manipulation. The second is the new Clinimacs Prodigy that offers a closed workstation capable of processing and purifying and culturing cells in a programmable way and for which specific processes can be designed and optimised. It is state-of-the-art technology that can be used for new process development as well as clinical grade manufacturing of cell therapies.APPLICATIONS & BENEFITSThe Clinimacs Plus would support the TolDC trial. The Clinimacs Prodigy will find immediate use in development of new protocols, exploiting our collaboration with the Hannover group led by Professor Eva Weissinger, for virus-specific T-cell therapy in patients who contract CMV after allogeneic bone marrow infusions. Protocols designed by Miltenyi-Biotec render the Prodigy appropriate and feasible for this research. The equipment requested will therefore give NCTF the capacity to aid current clinical trials and research into new clinical trials, and develop new protocols in cell therapy to meet the MRC strategy. In addition, research, teaching and training in cell therapy manufacture will be supported across the EU by hosting this equipment in our facility as Professor Dickinson participates in EU funded initiatives to establish standards in cell therapy to support consistency across multi-centre trials.