曲妥珠单抗原液生产车间工艺设计.docxVIP

曲妥珠单抗原液生产车间工艺设计 摘 要 曲妥珠单抗是针对HER2蛋白细胞外区域的重组人源化单克隆抗体，用于治疗过表达HER2的转移性乳腺癌（MBC）[1]。单药治疗可用于已接受过一个或多个化疗方案的转移性乳腺癌；可与紫杉醇联合治疗未接受过化疗的转移性乳腺癌。 本设计为曲妥珠单抗原液生产车间工艺设计，设计内容主要包括种子细胞复苏及培养扩增、抗体纯化、设备选型、车间布置图设计等。本设计以生物反应器、深层过滤系统、Protein A亲和层析等方法对曲妥珠单抗原液进行生产。在满足工艺条件下，遵循高效率，低能耗，低成本的原则，设计符合GMP要求的曲妥珠单抗原液生产车间布置方案。 关键词：曲妥珠单抗；乳腺癌；生物反应器；抗体纯化；车间布置 Process design of trastuzumab monoclonal antibody Manufacturing Production Workshops Abstract Trastuzumab is a recombinant humanized monoclonal antibody directed against the extracellular region of the HER2 protein for the treatment of metastatic breast cancer (MBC) overexpressing HER2[1]. Monotherapy can be used for metastatic breast cancer that has received one or more chemotherapy regimens; it can be combined with paclitaxel to treat metastatic breast cancer that has not received chemotherapy. This design is the Process design of trastuzumab monoclonal antibody Manufacturing Production Workshops. The design contents mainly include seed cell recovery and culture expansion, antibody purification, equipment selection, and workshop layout design. The design uses a bioreactor, a deep filtration system, and Protein A affinity chromatography to produce trastuzumab antigen solution. In accordance with the process conditions, following the principles of high efficiency, low energy consumption and low cost, the layout of the trastuzumab trastuzumab monoclonal antibody Manufacturing Production Workshops in compliance with GMP requirements was designed. Key words: trastuzumab; breast cancer; bioreactor; antibody purification; workshop layout PAGE 31 目 录 TOC \o "1-4" \h \z \u 1引言 1 1.1单克隆抗体 1 1.2乳腺癌 2 1.3曲妥珠单抗 3 1.3.1简介 3 1.3.2作用机理 3 1.2.3发展趋势 4 1.2.4本设计的目的意义 4 2工艺流程 5 2.1生产工艺的选择 5 2.2生产工艺流程 5 2.2.1细胞复苏及扩大培养 5 细胞复苏及细胞传代 5 种子罐扩增培养 6 2000L生物反应器培养 6 2.2.2抗体纯化 7 深层过滤系统 7 Protein A亲和层析 8 低pH孵育 8 阳离子交换层析 9 阴离子交换层析 9 病毒过滤 10 原液分装 10 2.3工艺关键参数 11 2.3.1细胞培养 11 培养基 11 pH值 11 温度