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PDA_TR28 中英 无菌原料药工艺模拟验证(2006年)

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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1. INTRODUCTION 简介1.1. Purpose 目的The preparation of sterile bulk pharmaceutical chemicals requires the combination of classical chemical/ biological production methods with the well-defined concepts for the preparation of sterile materials. The integration of these fields entails process equipment and operating procedures which are often substantially different from ordinary practice in either discipline. This document outlines process simulation practices for sterile bulk pharmaceutical chemicals (sterile BPCs), utilizing concepts drawn from both bulk pharmaceutical chemical operations and sterile product manufacturing and adapted to fit the unique nature of these materials. It presents options for determining the adequacy of aseptic operations performed during large scale manufacturing while allowing for realistic acceptance criteria for such operations.无菌原料药的制备需要典型的生化生产方法与无菌原料制备概念的明确理解相结合。

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PDA TR 80 《制药实验室数据完整性管理体系》中英文对照版

PDA TR 80 《制药实验室数据完整性管理体系》中英文对照版


The consequences of failing to uncover data integrity problems through self­discovery or internal internal audit programs before they are found by regulatory agency inspectors can impact the outcome of the business. Similarly, the business impact on contract manufacturers, contract laboratories, and suppliers can be very serious if they fail to uncover and disclose data integrity problems before regulators or their customers’ auditors do. One of the responsibilities of regulatory agency investigators is to verify the accuracy, reliability, and integrity of data submitted in written form or other media prior to, during, or after an inspection, or as part of a drug submission for market authorization, annual report, mandatory quality defect report (e.g., Field Alert), or Adverse
原料药无菌工艺模拟验证国际认证要求

原料药无菌工艺模拟验证国际认证要求

原料药⽆菌⼯艺模拟验证国际认证要求原料药⽆菌⼯艺模拟验证国际认证要求⾼海燕1　陈军丽2　丁恩峰3（1. ⽯药集团恩必普药业有限公司，⽯家庄　050031；2. ⽯家庄市第三医院制剂科，⽯家庄　050031；3. 英国施达化学集团公司中国代表处，⽯家庄　050031）在欧美药政法规体系⾥⾯，如果⽆菌制剂采⽤⽆菌原料药（API ）来制备，那么，⽆菌原料药的⽆菌性质对于制剂来说是⾄关重要的。

⽆菌原料药⼀般采⽤两种⽅法来制造：灭菌⼯艺和⽆菌⼯艺。

当原料药采⽤⽆菌⼯艺制造时，因为这种⼯艺⽆菌保证⽔平（SAL ）较低，因此，需要采⽤模拟验证来评估⽆菌⼯艺的保证能⼒。

在⽬前制药⾏业，通常采⽤⽆菌⼯艺模拟验证（也称为培养基灌装）⽅式评估⼯艺⽆菌保证能⼒。

API ；⽆菌⼯艺；模拟验证；培养基灌装；国际认证；美国注射剂协会；⽆菌保证⽔平；微⽣物数据偏差中图分类号： R951⽂献标识码： A⽂章编号： 1008-455X(2011) 02-0024-08International Certification Requirements for Simulating Validation ofAsepsis Process for Raw Material DrugsGao Haiyan, Chen Junli, Ding Enfeng(1. Shijiazhuang Pharma Group EBP Pharmaceutical Co., Ltd Shijiazhuang, 050031;2. Shiajiazhuang No. Hospital Shijiazhuang, 050031;3. China Representative Office, Great Briton Shida Chemical Group Co. Shijiazhuang, 050031)Abstract: In European and American pharmaceutical system, the asepsis level of asepsis raw material drugs is greatly important if asepsis agent is prepared with asepsis raw material drugs. Generally, asepsis raw material drugs are produced with two processes – sterilization process or asepsis process. If raw material drugs are produced with asepsis process, the simulation validation is needed because sterile assurance level in asepsis process is comparatively low. This is the reason that currently simulation validation is often used for asepsis process.Keywords: asepsis process; simulation validation is; media filling, international certification; PDA; sterile assurance level; microbial data deviation关键词摘要收稿⽇期：2010-12-28作者简介：⾼海燕（1976－），⾼级⼯程师，主要从事质量检验、质量保证、质量标准的制定、新药开发、eCTD 编制、计算机系统验证和国际注册等⼯作。

PDATR-29清洁验证中英对照（第一章—简介）

PDATR-29清洁验证中英对照（第一章—简介）

1. Introduction介绍1.1 Background背景In recent years, cleaning has achieved a position of increasing importance in the pharmaceutical industry. The current good manufacturing practices (CGMP) regulations recognize that cleaning is a critical issue to ensure product quality. Virtually every aspect of manufacturing involves cleaning, from the initial stages of bulk production to the final dosage form.近年来清洁作业逐渐在制药界占有重要的地位。

现行的GMP法规也指出清洁作业是保证产品质量的关键性工作。

自大宗原料的生产以迄最终剂型的制造作业，几乎每一个制造工序均含有清洁作业。

The CGMPs in the United States, Europe and other parts of the world have provided the pharmaceutical industry with general guidance for cleaning requirements. For example, in the U.S., section 211.67 of part 21 of the Code of Federal Regulations (CFR) states that "Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements." Section 211.182 of part 21 of the CFR identifies that cleaning procedures must be documented appropriately, and that a cleaning and use log should be established. In addition to CGMPs, various inspectional guideline documents published by the FDA contain expectations regarding cleaning in the pharmaceutical industry. Cleaning is also addressed in the PIC recommendations on cleaning validation and in the SFSTP Commission report "Validation desprocédés de nettoyage."美国、欧洲及全球其他地区均有制药界清洁作业的通则性指南。

PDA_TR28中英无菌原料药工艺模拟验证（2006年）

PDA_TR28中英无菌原料药工艺模拟验证（2006年）

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。