CLINICAL PRODUCTION

临床生产核心C的职责是生产足够数量和纯度的重组抗体、抗体片段和免疫细胞因子，用于作为本计划项目重点的I期治疗研究。为了实现这些目标，核心C有三个支持功能：1）临床试验的生产，2）临床试验的纯化和3）临床试验的结合和装瓶。 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），该中心设有一个按照现行药品生产质量管理规范（cGMP）运行的试点生物生产设施。CBG提供质量保证、质量控制以及设施维护。核心C在CBG内操作，并且先前已经生产了嵌合T84.66抗体、T84.66微抗体、T84.66双抗体和人源化hT84.66-M5 A抗体的临床批次。对于1 - 2克规模的中试规模生产，已制定了标准操作规程。该生产包括主细胞库的生成、大规模生物反应器生产、纯化、结合（如需要）和装瓶。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。此外，市售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。细胞、纯化原液和最终产品的质量保证生物安全性放行测试符合FDA规定的安全指南

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