医学生物制药工艺验证部分翻译.pdf

70 Godavarti et al. 4 Scale-Down Models for Purification Processes: Approaches and Applications 纯化工艺缩小模型：方法与应用 RANGA GODAVARTI, JON PETRONE, JEFF ROBINSON, RICHARD WRIGHT, AND BRIAN D. KELLEY CONTENTS 目录 4.1 Introduction 70 引言 4.2 Design of Scale-Down Systems 73 缩小体系的设计 4.2.1 Principles 73 原则 4.2.2 Evaluation of Scale-Up before Scale-Down 73 缩小前对放大的估测 4.2.3 Scale-Down Model Limitations: Equipment 74 缩小的局限性：设备 4.2.4 Scale-Down Model of an Entire Process Train 74 一个完整工艺的缩小模型 4.3 Examples of Scale-Down Models 75 有关缩小模型的例子 4.3.1 Chromatography 75 色谱 4.3.2 Protein Modification Reactions 85 蛋白质修饰作用 4.3.3 Precipitation 91 沉淀 4.3.4 Microfiltration 97 微滤 Scale-Down Models f or Purifi cation Processes 71 4.3.5 Ultrafiltration 101 超滤 4.3.6 Centrifugation 105 离心 4.3.7 Viral Inactivation 108 病毒失活 4.3.8 Virus Removal Filtration 111 过滤法去除病毒 4.4 Evaluation of Suitability of Scale-Down Systems as Models of Full-Scale Operation 117 估测缩小模型对最大规模操作模型的适用性 4.5 Application of Scale-Down Systems 121 缩小系统的应用 4.5.1 Clinical Development Phase-Process Validation 122 临床开发阶段-工艺验证 4.5.2 Commercial Processes 129 商业化生产工艺 4.6 Summary 131 摘要