PDA TR28 无菌原料药(BPCs)的工艺模拟

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 reflect6years 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.

本文提供了无菌原料药生产加工有关的验证指导。它借鉴了PDA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。我们还尽量列举一些FDA对其早期版本的审查中提出的一些问题。

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，一般都需要与成品药的制造完全不同的设备和程序。无菌原料生产方法的独特性，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

1.1Purpose目的

1.2Sterile Bulk Pharmaceutical Chemicals.无菌原料药

1.3Scope范围

1.4Sterile BPC Production Technology无菌BPC生产技术

1.4.1Closed Systems封闭系统

1.4.2Open Systems开放系统

1.5Considerations需考虑事项

2.PROCESS SIMULATION CONCEPTS AND PRINCIPLES

工艺模拟的概念和原理

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

2.2Worst Case最差条件

3PROCESS SIMULATION TEST METHODS工艺模拟的测试方法

3.1Total Process Simulation总工艺模拟

3.2Unit Operation(s)Simulations单元操作模拟

3.TEST MATERIALS USED IN PROCESS SIMULATION

工艺模拟中用到的测试原料

4.1Growth Medium Simulations培养基模拟

4.2Placebo Material Simulation安慰剂原料模拟

4.3Simulation Without Material无原料模拟

4.4Production Material Simulation生产原料模拟

5.EVALUATION OF SIMULATION TEST MATERIALS模拟测试原料的评估

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

5.2Evaluation of Test Material Samples测试原料样品的评估

6.DOCUMENTATION文件

7.ENVIRONMENTAL MONITORING环境监测

8.ELEMENTS OF PROCESS SIMULATION TESTS工艺模拟测试的要素

8.1Interventions干扰

8.2Duration of Simulation模拟的持续时间

8.3Production Batch Size/Process Simulation Test Size生产批量/工艺模拟测

试的批量

8.4Incubation Conditions培养条件

8.5Operating Procedures操作程序

8.6Staffing Considerations全体人员的考虑

8.7Campaigns活动

8.8Equipment Qualification设备资质