CLINICAL PRODUCTION

核心C核心主任矢崎，保罗首席研究员：劳比切克。安德鲁 产品说明： 临床生产核心C的职责是生产重组抗体， 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， 这个项目的重点。为了实现这些目标，核心C有三个支持功能：1）生产 临床试验，2）用于临床试验的纯化和3）用于临床试验的缀合和装瓶。 希望之城已经建造了一个1200万美元，20,000平方米。英尺，生物医学和遗传学中心（CBG）， 容纳按照现行药品生产质量管理规范运行的中试生物生产设施 （cGMP）。CBG提供质量保证、质量控制以及设施维护。芯C 在CBG内操作，并且先前生产了嵌合T84.66抗体T84.66的临床批次， 微抗体、T84.66双抗体和人源化hT84.66-M5 A抗体。标准操作程序在 在一至两克规模进行中试规模生产。该制造包括生成 主细胞库、大规模生物反应器生产、纯化、结合（如果需要）和装瓶。期间 在本项目期间，拟定用于生产的抗体包括hT84.66-M5 A抗体、T84.66-IL 2 免疫细胞因子和用于预靶向的人源化抗体。除了商业抗体， 赫赛汀和安维汀以及用于预靶向的半抗原将与螯合物DOTA缀合。质量 确保细胞、纯化原液和最终产品的生物安全性放行试验符合安全性要求 FDA“单克隆抗体生产和检测中的考虑要点”中规定的指南 人用产品”和美国联邦法规。实现这些生产目标将提供 该计划项目与当前和未来几代的放射和免疫治疗剂， 治疗实体瘤。

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.