CLINICAL PRODUCTION

CORE C CORE董事Yazaki，Paul首席研究员：Raubitschek。安德鲁 说明： 核心C，临床生产的责任是制造重组抗体，抗体 足够数量和纯度的片段和免疫细胞因子，用于I期治疗研究，即 本计划项目的重点。为了实现这些目标，Core C有三个支持功能：1)生产 临床试验，2)临床试验的纯化，3)临床试验的接合和维拉宁。 这座希望之城耗资1200万美元，建造了一个2万平方米的建筑。生物医学和遗传学中心(CBG) 拥有一个在当前良好制造规范下运行的试点生物制造设施 (CGMP)。CBG提供质量保证、质量控制以及设施的维护。核心C 在CBG内工作，以前曾生产过临床批量的嵌合T84.66抗体，T84.66 微体、T84.66 Diabody和人源化hT84.66-M5A抗体。标准操作程序载于 一至二克规模的中试生产场所。这种制造包括产生一种 主细胞库，大规模生物反应器的生产，纯化，如果需要，接合，和瓶装。在.期间 本项目期间，拟研制的抗体包括hT84.66-M5A抗体、T84.66-IL2 免疫细胞因子和人源化抗体用于预靶向。除了市面上的抗体， 赫赛汀、阿瓦斯丁和用于预靶向的半抗原将与螯合物DOTA偶联。质量 确保细胞、纯化原料药和最终产品的生物安全释放试验符合安全性 FDA在生产和检测单抗时需要考虑的几个问题 和美国联邦法规。实现这些生产目标将提供 与当前和未来几代放射和免疫治疗药物合作的计划项目 实体肿瘤的治疗。

Core C core Director Yazaki, Paul Principal investigator: Raubitschek. Andrew DESCRIPTION: The responsibility of Core C, Clinical Production, is to manufacture recombinant antibodies, antibody fragments and immunocytokines of sufficient quantity and purity for the Phase I therapy studies that are the focus of this Program Project. To achieve these goals, Core C has three support functions: 1) Production for clinical trials, 2) Purification for clinical trials and 3) Conjugation and Vialing for clinical trials. The City of Hope has built a $12 million, 20,000 sq. ft., Center for Biomedicine and Genetics (CBG), which houses a pilot Biological Manufacturing Facility operating under current Good Manufacturing Practice (cGMP). The CBG provides Quality Assurance,Quality Control as well as maintenance of the facility. Core C operates within the CBG and has previously produced clinical lots of the chimeric T84.66 antibody, T84.66 minibody, T84.66 diabody and humanized hT84.66-M5A antibody. Standard operating procedures are in place for pilot scale manufacturing at the one to two gram scale. This manufacturing includes generation of a master cell bank, large scale bioreactor production, purification, conjugation if required, and vialing. During this project period, the antibodies proposed for manufacture include the hT84.66-M5A antibody, T84.66-IL2 immunocytokine, and a humanized antibody for pretargeting. In addition the commercial antibodies, Herceptin and Avastin and a hapten for pretargeting will be conjugated with the chelate DOTA. Quality Assurance biosafety release tests of cells, purified bulk and final products are according to the safety guidelines set forth in the FDA "Points to consider in the manufacture and testing of monoclonal antibody products for human use" and US Federal Code of Regulations. Achieving these production goals will provide the Program Project with the current and future generations of radiation and immunotherapy agents for the treatment of solid tumors.