PDA_TR28 中英 无菌原料药工艺模拟验证(2006年)

无菌原料药（BPCs）的工艺模拟

PDA第28份技术报告（2006年）

This document provides guidance relative to the validation of aseptic processing activities associated with the production of sterile bulk pharmaceutical chemicals. It draws upon the concepts and principles developed in PDA's and PhRMA's prior publications on aseptic processing technology (1, 2, 3). This effort expands upon those documents to provide assistance for individuals and firms producing sterile bulk pharmaceutical chemicals. Our goal in this revision was to update the document to reflect 6 years of industry experience with it, as well as an acknowledgement of acceptance criteria limitations that were present in the first edition (4). We have also endeavored to address some of the issues raised by FDA in their review of the earlier edition.

本文档提供了无菌原料药生产加工有关的验证指导。它借鉴了FDA和PhRMA以前出版的无菌加工技术（1，2，3）的概念和原则。这使得该文件可以为个人和企业的无菌原料药生产提供帮助。我们在这次修订的目的是更新文件，以归纳6年来的行业经验，以及验收标准的规定，这将在第1版（4）中称述。我们还大量列举一些美国FDA在其早期版本的回顾中提到的一些问题。

The preparation of sterile materials in the quantity and scale used in the manufacture of bulk pharmaceutical chemicals generally requires equipment and procedures quite different from those used in the manufacture of finished pharmaceuticals. The uniqueness of the production methods for sterile bulks precludes the direct extrapolation of the process simulation approaches employed for aseptically produced sterile formulations.

原料药生产中，无菌原料在数量和规模上的准备，一般都需要相当的设备和过程，这与成品药的制造有所不同。无菌原料生产方法的独特，排除了用于无菌制剂的无菌生产上的工艺模拟直接推断方法。

This technical report was disseminated in draft for public review and comment prior to publication. Many of the submitted comments have been included in the final document. We believe this approach accomplished the widest possible review of the document and ensures its suitability as a valuable guide to industry in the area of process simulation testing for sterile bulk pharmaceutical chemicals.

This document should be considered as a guide; it is not intended to establish any mandatory or implied standard.

这份技术报告以草案形式提前发布供公众审查和评论。大多数提交的意见将被列入最后版本中。我们相信，这种方法实现了对文件最广泛的审查，并确保作为一个针对无菌原料药的工艺模拟试验领域的宝贵的指导性文件的合格性。这份文件应被视为指南，而不是任何强制规定或标准。

Table of Conents 目录

1. INTRODUCTION 简介

1.1 Purpose 目的

1.2 Sterile Bulk Pharmaceutical Chemicals. 无菌原料药

1.3 Scope 范围

1.4 Sterile BPC Production Technology 无菌BPC生产技术

1.4.1 Closed Systems 封闭系统

1.4.2 Open Systems 开放系统

1.5 Considerations 需考虑事项

2. PROCESS SIMULATION CONCEPTS AND PRINCIPLES工艺模拟的概念和原则

2.1 Number and Frequency of Tests 测试的数量的频率

2.2 Worst Case 最差条件

3 PROCESS SIMULATION TEST METHODS 工艺模拟测试的方法

3.1 Total Process Simulation 总工艺模拟

3.2 Unit Operation(s) Simulations 单元操作模拟

4. TEST MA TERIALS USED IN PROCESS SIMULATION过程模拟中用到的测试原料

4.1 Growth Medium Simulations 生长介质模拟

4.2 Placebo Material Simulation 安慰剂原料模拟

4.3 Simulation Without Material 无原料模拟

4.4 Production Material Simulation 生产原料模拟

5. EV ALUATION OF SIMULATION TEST MA TERIALS 模拟测试原料的评估

5.1 Evaluation of Entire Test Material 全体测试原料的评估

5.2 Evaluation of Test Material Samples 测试原料单体的评估

6. DOCUMENTATION文件

7. ENVIRONMENTAL MONITORING 环境监测

8. ELEMENTS OF PROCESS SIMULATION TESTS 工艺模拟测试的评估

8.1 Interventions 干扰

8.2 Duration of Simulation 时间模拟

8.3 Production Batch Size/Process Simulation Test Size 产品的批产量/工艺模拟的批量

8.4 Incubation Conditions 培养条件

8.5 Operating Procedures 作业流程

8.6 Staffing Considerations 人员的思考

8.7 Campaigns 活动

8.8 Equipment Qualification 设备限制

9. INTERPRETATION OF RESULTS AND ACCEPTANCE CRITERIA 结果的解释和可接受水平9.1 Background 背景

9.2 Approaches for Acceptance Criteria 可接受水平的判定方法

9.2.1 Quantitative 定量

9.2.2 Qualitative 品质

10. FAILURE INVESTIGATION AND CORRECTIVE ACTION 失败评估和纠正措施

11. PERIODIC REASSESSMENT 定期再评估

APPENDIX1,SELECTION AND STERILIZATION OF TEST MA TERIALS

附件1，测试原料的选择和灭菌

APPENDIX 2, DEFINITIONS

附件2，定义

APPENDIX 3, REFERENCES

附件3，参考文献