PDA TECHNICAL REPORT NO. 13
REVISEDFUNDAMENTALS OF AN ENVIRONMENTALMONITORING PROGRAM
技术报告13：环境监测
T able of Contents 目录
1.0 INTRODUCTION 简介. . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    1
2.0ENVIRONMENTAL CLASSIFICATIONS 环境分级. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..1
3.0SURVEILLANCE SUPPORT 监视支持. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . .    6
3.1Cleaning and Sanitization/Disinfection 清洗和杀菌/消毒. . . . . . . . .. . . . . . . . . . . . . 6 3.2Sample Site Selection取样位置选择 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3.3Sampling Frequency 取样频率. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . 7 3.4Alert and Action Levels 报警和行动等级. . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . 8 3.5Data Management (Data Collection, Analysis, Approach, and Interpretation) 数据管理（数据收集，分析，处理方法和解释）. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . 9 3.5.1Data Collection 数据收集. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.5.2Data Analysis 数据分析. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . 9 3.5.3Data Approach 数据处理方法.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.5.4Data Interpretation 数据解释. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3.6Characterization of Isolates 分离株识别. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.7Investigations/Corrective Actions 调查/纠正措施. . . . . .. . .. . . . . . . . . . . . . . .. . . . . . 11
3.8Documentation 记录. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . 12
4.0SYSTEM SURVEILLANCE 系统监视 . . . . . . . . . . . . . . . . . . . . . . . . .  . . . . . . . . . 14 4.1Introduction简介. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 14 4.1.1Terminal Sterilization 最终杀菌. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4.1.2Aseptic Filling无菌灌装. . . . . . . . . . . . . . .. . . . . ... . . . . . . . . . . . . . . . . . . . 14
4.1.3Isolation Technology 隔离技术. . . . . . . . . . . . . .. . . . . . . . . . .. . . . . . . . . . . . . 14 4.2Water Monitori
ng水质监测. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4.3Compressed Gas Monitoring 压缩气体监测. . . . . . .. . . . . . . . . . . . . . . . . . . . . . 15
4.4Air Monitoring 空气监测. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 15 4.4.1Non-Viable Monitoring 非活性生物监测. . . . . . . . . . . . .. . . . . . . . . . . . . . . 16
4.4.2Viable Monitoring活性生物监测 . . . . . . . . . . . . . . . . . . .. . . . . . . . . . ... . . . . . . 16 4.4.3Surface Monitoring 表面监测. . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . 19 4.5Personnel Monitoring 人员监测. . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . 21
4.5.1Description 说明 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4.5.2Training/Certification of Personnel for Aseptic Manufacturing Area 无菌生产区人员培训/证书. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .. . . . . . . . . . . . . . . . 21 4.5.3Retraining 再培训. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 21 4.6Product or Component Bioburden 产品或部件生物负荷. . .. . . . . . . . . . . . . . . . . 21
4.6.1Determination of Product or Component Bioburden 产品或部件生物负荷确认. . . . . . . . 22 4.6.2Parametric Release and Bioburden 参数放行和生物负荷. . . . . . . .. . . . . ... . . . . . 22 4.6.3In-Process Testing 过程中培训. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . 23 4.7Environmental Mo
nitoring During Routine Sterility Testing 常规无菌测试过程中的环境监测25
5.0VALIDATION/QUALIFICATION OF ENVIRONMENTAL MONITORING SYSTEMS 环境监测系统验证/确认. . . . . . . . . . . . . . . . .. . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .. 25 5.1Environment/HVAC Systems 环境/HVAC系统. . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 5.2Utilities 公用工程 . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 5.3Validation of Aseptic Processes – Media Fills (Process Simulation Tests) 无菌工艺验证- 培养基填充（工艺模拟测试）. . . . . . . . . . . . . . . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . .. 26
6.0CONCLUSION 总结. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .. . . . 26
1.0 INTRODUCTION 简介
The purpose of this document is to identify microbiological and particulate control concepts and princip
les as they relate to the manufacture of sterile pharmaceu tical products. It expands substantially upon the first edition of Technical Report No. 13, Fundamentals of a Microbiological Environmental Monitoring Program, published by PDA in 1990. While this publication cannot possibly supplant the wealth of information published on this subject, it provides summary information and appropriate references for the reader to consult, if necessary. The objective was to contemporize the first edition through the utilization of current definitions, recognition of improved environmental moni toring procedures, and equipment. 本文件目的是确定微生物和微粒控制的概念和原则，因为这涉及到无菌药品的生产。文件全称为第13号技术报告第一版，微生物的环境监测计划基础，PDA于1990年出版。尽管本出版物不可能取代题目的信息价值，它提供了读者查阅必要的主要信息及相关参考。其目的是通过使用当前定义，改善后的环境监测程序和设备来与第一版同步。
This document should be considered as guidance; it is not intended to establish any mandatory or implied standard. 此文件应作为指南；而不是建立任何强制或隐含的标准。
The task force consisted of members representing global companies, to ensure that the methods, terminology, and practices reflect the procedures utilized globally. Technical reviews were performed by some of the more prominent environmental monitoring scientists in the world today. 工作团队由代表全球性公司的成员组成，以确保方法，术语和规程反映了全球范围内使用的程序。技术审查由一些全球
重要的环境监测科学家进行。
This document serves as a source on clean room envi ronmental test methods, and although some non-viable particulate and endotoxin testing data are included, its primary focus is microbiological control. The concepts for sterile product manufacturing are the most stringent application, but these concepts can also be applied to non-sterile product manufacture. The focus is environmental monitoring as it relates to facility control and compliance. This document was compiled to aid in setting up a program that is meaningful, manageable, and defendable.这份文件作为洁净室环境测试方法的来源，虽然包括一些非活性微粒和内毒素检测数据，其主要目的是微生物控制。无菌产品生产的概念是最严格的应用程序，但这些概念也适用于非无菌产品的生产。重点是环境监测，因为它涉及到设施的控制和遵守。编写本文件是为了协助建立一个有意义，易于管理且合理的程序。
In order to ensure    a consistently acceptable production environment,    a comprehensive environmental control program should be supported by: (a) sound facility design and maintenance, (b) documentation systems, (c) validated/qualified sanitization/disinfection procedures, (d) reliable process controls, (e) good housekeeping practices, (f) effective area access controls, (g) effective training, certification/qualification and evaluation programs and (h) quality assurance of materials and equipment. 为了确保持续可接受的生产环境，全面的环境控制计划应当得到以下支持：（a）合理的设
施设计和维修，（b）文件系统，（c）经验证/合格的杀菌/消毒程序，（d）可靠的工艺控制，（e）良好的车间管理规程，（f）有效面积的访问控制，（g）有效的培训，认证/确认和评价程序和（h）材料和设备的质量保证。
Environmental surveillance is a tool utilized to evaluate the effect of controls on the manufacturing environment. A process to assess the clean room and other controlled environments of a pharmaceutical facility can serve as an adjunct to the sterility
assurance program for the microbial quality of drugs. The items addressed in this document include definitions, standards, surveillance support systems, system surveillance, validation systems, appendices of definitions and typical frequen cies and levels, and a bibliography. 环境监测是用于评价对生产环境控制效果的工具。评估洁净室和其他制药设备受控环境的工艺可作为对药物的微生物质量无菌性保证的辅助方法。本文件涉及的项目包括定义，标准，监督支持系统，系统监控，验证系统，定义和典型频率和等级附录和参考书目。
2.0 ENVIRONMENTAL CLASSIFICATIONS 环境分级
The environmental monitoring program should be designed and implemented based on sound scientific principles, the need for and the utility of the collected data, and in conformance with the regulatory requirements of the government agencies regulating the manufacturing site. Personnel administering environmental moni-toring programs should be familiar with a variety of regulatory schemes if they are to be successful in serving the United States and International product markets. Efforts at harmonization are underway, and it is possible that many of the differences in the requirements for monitoring programs may disappear as the coun-tries and organizations involved come to some agreement on the overall approach to be taken. Therefore, it is important to keep up to date on the requirements for the different countries in which the product will be sold. 环境监测程序应根据合理的科学原则，收集到的数据的需求和使用进行设计和执行，符合政府机构监管生产现场的要求。如果人事管理环境监测计划能够成功服务于美国和国际产品市场，应熟悉不同的管理计划。目前正在努力协调，检测计划的要求的差异可能会消失，因为涉及的国家和组织正在协调获得统一的方法。因此，应及时更新产品销往国的要求。
This will ensure that the established program meets the monitoring requirements of each country. If the intent is to serve both the United States and the International markets, the most stringent requirements should be evaluated as the basis of an environmental monitoring program. 这将确保既定的程序符合每
include中文个国家的监测要求。如果目的是为服务美国和国际市场，最严格的要求应作为环境监测计划的基础进行评估。
This section compares published environmental classi fications for environmental monitoring in the United States and the European Union. Although these publi cations are similar in many respects, there are impor tant differences among them in terms of the information each provides. 本节比较公布的美国和欧盟环境检测的分级。虽然这些刊物在许多方面是相似的，其提供的信息仍有重大分歧。
Federal Standard 209E establishes airborne particulate cleanliness classes categorized as Class M 1 through M 7 (SI names). All of the classifications can be ap-plied to particles > 0.5μm, while other particle sizes, e.g., 0.1, 0.2, 0.3 and 5μm, utilize only some of the classifications. In the United States, the pharmaceuti cal industry classifies production areas as Class 100, 10,000 and 100,000 (M 3.5, M 5.5 and M 6.5, respectively) based on particles > 0.5μm, the classification reflecting the number of particles per cubic foot. It should be noted that the Institute for Environmental Sciences and Technology (IEST) has recommended that Federal Standard 209E be retired by the end of 2001 as a result of the publication of the ISO 14644-1 and 14644-2 documents. 美国联邦标准209E规定空气中微粒洁净度M1到M7级。所有分级适用于> 0.5μm的粒子，其他粒子，如0.1、0.2、0.3和5μm，仅使用某些分级。在美国，制药行业根据> 0.5μm的粒子将生产区分为100级，10,000级和100,000级（分别为M3.
5，M5.5和M 6.5），分类反映了每立方米微粒数量。应当指出，环境科学与技术（IEST）研究所建议，ISO 14644-1和14644-2文件出版后，美国联邦标准209E可于2001年底暂停使用。
FDA's 1987 "Guideline on Sterile Drug Products Produced by Aseptic Processing" discusses environmental requirements for critical areas (Class 100), in which sterile drugs are exposed to the environment. This document also includes specifications for viable airborne monitoring for Class 10,000 and Class 100,000 areas. Viable and non-viable guidance is provided. FDA的1987年“关于无菌加工生产的无菌药品指南”讨论了关键区域（100级）的环境要求，其中无菌药物暴露于环境。本文件还包括了10,000级和100,000级区域的活性空气的监测说明。提供了活性和非活性监测指南。
USP general information chapter <1116> "Microbial Evaluation and Classification of Clean Rooms and Other Controlled Environments" proposes limits for clean room levels, including air, surfaces, and personnel work ing within the clean area. The chapter includes three classifications that would supplement the current cat egories based on non-viable particulate limits. 美国药典的一般信息章节“1116”“微生物评估和洁净室分级及其他受控环境”提出了洁净室级别的限制，包括洁净区空气，表面和人员工作。本章包括三个分类，将根据非活性颗粒极限补充现行分级。
In the European Union, The Rules Governing Medicinal Products in the European Union, (Vol. IV: Good manufacturing practice for medicinal products) include an air classification system in Annex 1 under the heading "Manufacture of Sterile Medicinal Products." Air quality is classified alphabetically as Grade(s) A through D, with Grade A being the cleanest. Associated with each respective grade is the maximum allowab le num-ber of particles per cubic meter. 在欧盟，欧盟药品细则（第四卷：药品良好生产质量管理规范），包括附件1“无菌产品生产”中的空气分级系统。空气质量按字母顺序分为A级D级，A 级洁净度最高。与每个等级相关的是每立方米微粒最大允许数量。
In addition to these publications, additional guidance is available through the International Organization for Standardization (ISO) which is a world-wide federa-tion of national standard bodies. The work of preparing international standards is normally carried out through ISO technical committees. ISO/TC 198 pro vides Guidance for Sterilization of Health Care Products and ISO/TC 209 provides Guidance for the Classification of Airborne Particulate for Clean Rooms and Associated Controlled Environments. Copies of these documents can be obtained from American National Standards Institute (ANSI). 除了这些出版物，国际标准化组织（ISO）有更多的指南，ISO 是一个世界标准机构的联盟。制订国际标准的工作通常由ISO的技术委员会进行。ISO/ TC 198提供保健品无菌性指南，ISO/ TC 209提供洁净室和相关受控环境中空气粒子分级指南。这些文件的副本可从美国国家标准学会（ANSI）获得。
It should be noted that all classifications have a direct counterpart in the documents prepared by other international groups. Tables 1 through 3 summarize and com pare these specifications. 应当指出，所有分级在其他国际组织编写的文件中有直接对应。表1至3总结并比较了这些规范。
3.0SURVEILLANCE SUPPORT 监视支持
The data should be collected in a manner that is in con formance with Current Good Manufacturing Practices (CGMP). CGMP states that the personnel supervising the environmental monitoring program should be competent in the scientific discipline and have appropriate training and authority. Equipment used should be cali brated, systems should be appropriately validated, media should be properly prepared, and all operational procedures should be written and followed. 这些数据应当按照现行良好生产规范（CGMP）进行收集。CGMP规定，监督环境监测计划的人员应有科学学科的能力，

版权声明：本站内容均来自互联网，仅供演示用，请勿用于商业和其他非法用途。如果侵犯了您的权益请与我们联系QQ:729038198，我们将在24小时内删除。