cGMP Production Core

cGMP 生产核心

• 批准号: 10207731
• 负责人: Michael M Meagher
• 金额: $ 34.51万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207731
• 关键词: Achievement; Beds; Biological; Biological Assay; Bioreactors; Blood Component Removal; Bone Marrow; CD34 gene; Cell Line; Cells; Certification; Clinical; Clinical Trials; Collection; Cryopreservation; Cyclic GMP; Development; Devices; Disease Vectors; Doxycycline; Emerging Technologies; Enrollment; Ensure; Enzymes; Food and Drug Administration Drug Approval; Funding; Future; Gene therapy trial; Generations; Genes; Immunologic Deficiency Syndromes; Infant; Investigational Drugs; Laboratories; Lentivirus; Lentivirus Vector; Methods; Monitor; Pharmaceutical Preparations; Play; Procedures; Process; Production; Protocols documentation; Quality Control; Recombinants; Records; Research Personnel; Role; Saint Jude Children' s Research Hospital; Services; Sickle Cell Anemia; Suspension Culture; Suspensions; System; Techniques; Technology; Testing; TimeLine; Transfection; Validation; Work; adeno-associated viral vector; analytical method; base; bone cell; cGMP production; cellular transduction; clinical development; clinical implementation; experience; gene therapy; genome editing; improved; lentivirally transduced; method development; novel; particle; peripheral blood; scale up; stable cell line; vector

PROJECT SUMMARY – CORE C Core C: cGMP Manufacturing Core (cGMP Core) serves as a full service "turn key" vector and cell manufacturing for the PPG by providing cGMP lentiviral vectors and transduced CD34+ cells (Drug Product) for clinical trials in all three projects. The function of the cGMP Core is the development, scale-up, and cGMP manufacturing of vector and the assays required for release and characterization of the lentiviral vectors and the development, scale-up, cGMP manufacturing and the assays required for release and characterization of transduced CD34+ cells from bone marrow or apheresis collections. The cGMP Core must work directly with the each of the Project PIs and the Vector Core as the complexity of these products requires a highly orchestrated and well-thought out project timeline that takes into account all of the aspects defined in a Target Product Profile The cGMP Core is tightly integrated with the Vector Development Core and the PI's laboratories and meets with both groups every two weeks to discuss development and production activities. This allows the other investigators to test vectors and cell products to insure biological potency and functionality. Once a cGMP process is ready for transition into clinical trial, the investigators and/or Vector Core transfer the vector and product-specific bioanalytical methods to the cGMP Core for process and analytical methods development, process scale-up, and cGMP manufacturing. Examples of this integration during that past funding period include the first clinical use of the GPRG lentiviral packaging cell line for use in the LVXSCID trials and the recent transfer of the second generation stable producing cell line for WAS. A similar process is anticipated for development and production of a lentiviral vector for sickle cell disease and will likely require the use of transient transfection for cGMP production. Other achievements in the past funding period have been the development and clinical implementation of bone marrow processing and transduction batch records for the infant XSCID trial, which has now been successfully used in four infant cases. The cGMP Core has over 10 years of experience and Dr. Meagher (leader of the cGMP Core) has 30 years of experience in the field and will oversee the development and optimization of improved and scalable technology for production of lentivirus (LV), genetically modified peripheral blood and bone marrow CD34+ cells, and eventually genome editing technologies including AAV vectors and recombinant genome editing enzymes as requested by the PIs. The cGMP Core will also work with the new Experimental Cellular Gene Therapy (ECGT) Core at St. Jude on the development and scale-up of the transduction of CD34+ cells. All cGMP products will be manufactured by the cGMP Core.

项目摘要 - 核心C 核心C：CGMP制造核心（CGMP Core）用作全方位服务的“转向键”矢量和单元 通过提供CGMP慢病毒载体和翻译CD34+细胞（药物产品）来为PPG制造 在所有三个项目中进行临床试验。 CGMP核心的功能是开发，扩展和 矢量的CGMP制造以及释放和表征慢病毒所需的测定法 向量与开发，扩展，CGMP制造以及释放所需的分析和 从骨髓或刻度收集中的翻译CD34+细胞的表征。 CGMP核心 必须直接与PIS和向量核心一起工作，作为这些产品的复杂性 需要一个精心策划且经过深思熟虑的项目时间表，该时间表考虑了所有方面 在目标产品配置文件中定义的CGMP核心与向量开发核心紧密整合 PI的实验室并每两周与两个小组会面，讨论发展和 生产活动。这使其他研究人员可以测试载体和细胞产品确保生物学 效力和功能。一旦CGMP工艺准备好过渡到临床试验，研究人员就会 和/或矢量核心将矢量和产品特异性生物分析方法转移到CGMP核心 过程和分析方法开发，过程扩大和CGMP制造。这个例子 在过去的资金期间的整合包括GPRG慢病毒包装细胞的首次临床使用 在LVXSCID试验中使用的线和第二代稳定生产细胞系的最新转移 是。预计镰状细胞的慢病毒载体的开发和生产也会有类似的过程 疾病，可能需要将瞬时翻译用于CGMP生产。其他成就 过去的融资期是骨髓加工的开发和临床实施 和婴儿XSCID试验的翻译批次记录，现在已成功使用了四个 婴儿病例。 CGMP Core拥有超过10年的经验，Meagher博士（CGMP Core的负责人） 在该领域拥有30年的经验，并将监督改进的发展和优化 可扩展的慢病毒（LV），转基因外周血和骨髓的可伸缩技术 CD34+细胞，有时是基因组编辑技术，包括AAV载体和重组基因组 根据PIS的要求编辑酶。 CGMP核心也将与新的实验性细胞一起使用 CD34+翻译的开发和规模上，圣裘德的基因治疗（ECGT）核心 细胞。所有CGMP产品将由CGMP Core生产。