PDA TECHNICAL REPORT NO.34第34号PDA技术报告 DESIGN AND VALIDATION OF ISOLATOR SYSTEMS FOR THE
MANUFACTURING AND TESTING OF HEALTH CARE PRODUCTS
卫生保健产品生产和测试的隔离器系统的设计和验证
Table of Contents内容列表
1.0INTRODUCTION概述
1.1Preface绪言 (1)
1.2Scope范围 (1)
超导量子比特芯片1.3Key Definitions关键词定义 (1)
1.4Purpose目的 (2)
2.0TYPES OF ISOLATORS隔离器的类型
2.1Closed Isolators封闭式隔离器 (2)
2.1.1Closed Isolators Intended for Aseptic Applications无菌应用的封闭式隔离器 (2) 2.1.2Closed Isolators Intended for Containment Applications抑制应用的封闭式隔离器 (2)
2.1.3Closed Isolators Intended for Asepsis and Containment无菌和抑制应用的封闭式隔离器 (2)
2.2Open Isolators开放式隔离器 (3)
2.2.1Open Isolators Intended for Aseptic Applications无菌应用的开放式隔离器 (3)
2.2.2Open Isolators Intended for Asepsis and Containment无菌和抑制应用的开放式隔离器 (3)
3.0ISOLATOR DESIGN AND GENERAL CONSTRUCTION隔离器设计和总体结构
3.1Materials of Construction构造材料 (3)
3.1.1Polyvinyl Chloride(PVC)聚氯乙烯（PVC） (3)
3.1.2Stainless Steel不锈钢 (4)
3.1.3Glazing Materials玻璃质材料 (4)
3.1.4Other Materials其他材料 (4)
3.2Operator Interface操作界面 (4) 3.2.1Gloves/Sleeves手套/套筒 (5)
3.2.2Suits or Half-Suits全身服或者半身服 (5)
3.2.3Air Handling System空气处理系统 (6)
4.0FUNCTIONAL SPECIFICATIONS FOR ISOLATORS隔离器的功能规格
4.1Air Supply Specifications进气规格 (6)
4.1.1Air Change Rate换气率 (7)
4.1.2Air Velocity气流速度 (7)
4.1.3Particulate Air Specification尘埃粒子规格 (7)
微服务开发
4.1.4Recirculation Rate再循环率 (8)
4.1.5Temperature and Humidity温度和湿度 (8)
4.1.6Aeration of the Decontaminating Agent净化剂的曝气 (8)
4.2Leak Testing泄露测试 (8)
4.2.1Pressure Decay Test降压测试 (9)
富硒叶面肥4.2.2Tracer Gas Detection Test探漏气体检测测试 (9)
4.3Ergonomics人体工程学 (10)
4.4Rapid Transfer Ports(RTPs)快速传送接口 (10)
5.0FACILITY REQUIREMENTS设施要求
5.1Classification of the Isolator Room隔离器室的种类 (11)
5.2Temperature and Humidity Control温度和湿度控制 (11)电水壶温控器
5.3Process Utilities公用工程 (11)
6.0USER REQUIREMENT SPECIFICATIONS(URS)用户需求规格
6.1General User Requirement Specifications一般用户需求规格 (11)
6.1.1Sterility Assurance无菌保证 (11)
极化片
6.1.2Cleaning and Cleaning Validation清洁和清洁验证 (14)
6.1.3Containment抑制 (14)
6.1.4Environmental Control环境控制 (16)
6.1.5Leak Testing泄露测试 (17)
6.1.6Monitoring Systems监测系统 (17)
6.1.7Microbiological Monitoring of the Environment对环境的微生物监测 (17)
6.1.8Process Simulation过程模拟 (18)
7.0RE-QUALIFICATION TESTING再确认测试 (18)
8.0CONCLUSION结论 (19)
APPENDIX A:Glossary附录A词汇表 (20)
APPENDIX B:Ljungqvist/Reinmuller(L-R)Method附录B Ljungqvist/Reinmuller(L-R)方法 (20)
APPENDIX C:Test Methods,Pressure Drop Test附录C测试方法，降压测试21 APPENDIX D:Isolators and Sterility Assurance附录D隔离器和无菌保证 (22)
REFERENCES AND TEXT NOTES引用资料和文字附注23
1.0INTRODUCTION绪论
1.1Preface前言
In recent years,isolation technology has rapidly emerged as an alternative to human-scale classified environments for the production and testing of many different types of health care products.The operational characteristics of isolators make them ideally suited for use in the preparation of sterile
materials,as well as in the containment of potent materials.Additional applications can be found in the preparation of clinical supplies,sterile bulk drugs/bio-pharmaceuticals,sterile cytotoxic materials,and in sterility testing.
小麦玉米联合收割机
近几年来，隔离器快速成为应用于多种不同类型的卫生保健产品的生产和测试的非传统的
人造级别环境。隔离器本身的操作性能参数使得它很好的适用于无菌材料的制备，也同样适用于对药效较强的原料的抑制，除此之外，它还附加有应用于临床补给的配制剂，无菌原料药，生物制药，无菌细胞毒素原料，和无菌测试的应用。The absence of authoritative implementation and validation guidance for this technology and the considerable confusion that has emerged between"isolators"and"barriers"were prime motivators for PDA to develop this document.It is the product of an international committee made up of representatives of PDA U.S.,PDA's Japan Chapter,A3P,The Parenteral Society,and R3-Nordic.
由于缺少对这项技术的权威性贯彻和验证指导，并且在很大程度上将“隔离器”和“屏蔽”两者混淆的原因，鉴于以上原因，PDA在此基础上提出了这份文件。它是由美国PDA的代表，PDA日本篇，A3P，注射药物科学和R3-Nordic组成的国际委员会的提出并产生的。
This document should be considered as guidance;it is not intended to establish any mandatory or im
plied standard.
这份文件需要将其作为一种指导，并不是为了确定任何强制性的和隐含的标准。
1.2Scope范围
This technical report addresses essential user requirements for the application of isolator technology to a broad range of manufacturing,development,and testing applications in the health care product manufacturing industry.This technical report covers not only product sterility assurance,but also the use of isolators for the containment of hazardous materials.
这篇报告明确说明了隔离器在卫生保健产品的制造行业中所用到的一系列的制造，发展和测试的应用方面的基本用户要求。这篇技术报告不仅仅涵盖了产品的无菌保证，同样包含有隔离器对危险原料的抑制应用。
An important component of this technical report is the glossary(Appendix A).The health care industry has lacked a uniform set of definitions with respect to isolator technology.The committee recognizes that,in order to suggest truly usable technical information,we must ensure that there can be no confusion among readers as to the application of recommendations made within this technical repor t.
词汇表（附录A）是这篇技术报告中一个很重要的组成部分。在卫生保健生产行业里，缺少一套对隔离器技术的统一的定义。委员会认为，为了提出真实可行的技术资料，我们必须要保证使读者不会混淆这篇技术报告中的应用建议标准。
The committee also recognizes that in some regions of the world,processing environments called"isolators"are widely used in the clinical pharmacy setting.These devices have some general features in common with isolators as defined in this document,however,they are distinctly different from the isolator systems currently in use for sterile product manufacturing and testing in the health care product industry.This technical report does not pertain to devices that do not meet the minimum performance criteria defined and explained in this document.
委员会同时认为在世界上某些地区，被称为“隔离器”的加工环境在很大范围上应用于临床药学的环境。这些设备在某种程度上与此文件中提到的隔离器具有相类似的特征。然而，它们无疑不同于目前卫生保健产品工业中应用于无菌制造和测试的隔离器系统。这篇技术报告并未附录那些不符合此文件中定义的最低性能参数指标的设备。
1.3Key Definitions关键词定义
The establishment of a clear distinction between what is and what is not an isolator is essential to un
derstanding this document.PDA suggests the following definition of isolator be adopted by the worldwide health care industry:
为了更好的了理解这份文件，必须要确定隔离器和非隔离器之间的区别。PDA提出了对以下在世界范围的卫生保健工业中应用到的隔离器的定义：
An isolator is sealed or is supplied with air through a microbially retentive filtration system(HEPA minimum)and may be reproducibly decontaminated(1).When closed,it uses only decontaminated(where necessary)interfaces or Rapid Transfer Ports(RTPs)for materials transfer.When open,it allows for the ingress and/or egress of materials
through defined openings that have been designed and validated to preclude the transfer of contamination.It can be used for aseptic processing activities,for containment of potent compounds,or simultaneously for both asepsis and containment.
隔离器是密闭的，或者是通过微生物截留过滤器系统(至少为HEPA)为其提供空气并且可进行重复性净化。当关闭时，仅使用净化排污接口或者专为物料传送用的快速传输接口。当其打开时，它可以允许通过被设计和经过验证的通道进行材料的进入和/或者输出来防止污染的转移。同样它可以用于进行无菌操作的活动，用于对药效较强的化合物的抑制或者同时用于无菌处理和抑制。 In marked contrast to the"isolator"definition above,PDA suggests the following definition for"barrier systems：与上面定义的“隔离器”相比较，PDA对“障碍系统”做出了以下定义：
barrier system is an open system that can exchange contaminants with the surrounding area,and cannot be decontaminated to the extent possible in an isolator.
障碍系统是一个开放式的系统，它可以与周围环境之间产生交叉污染，并且在净化程度和范围上都不能与隔离器相比。
Isolators,whether operated in a closed or open manner,offer significant advantages over barrier systems: isolators can be decontaminated using reproducible and validated methods,do not allow the ingress of airborne contamination from the surrounding environment,and prevent the introduction of personnel borne contamination into the isolator.In contrast,a barrier system is an open system which can exchange unfiltered air with the surrounding environment,can only be manually disinfected,and is directly accessed by gowned personne l.
当隔离器处于密闭或者开放式的操作模式下时，与障碍系统向比它具有明显的优点：隔离器可以通过可再生的和验证的方法进行净化处理，并且不允许周围环境中的空气污染物进入，并且能防止由个人携带的污染物进入隔离器内。相比之下，障碍系统只是一个能与周围环境进行未过经滤空的气的交换
的开放式系统，它只能利用手动消毒，并且允许穿着便装的人员直接进入。
1.4Purpose目的
The increased use of isolators in the health care product industry over the last decade and a half has been remarkable.In fact,isolators now clearly represent the most rapidly growing technology for the production of health care products.In spite of the rapid growth this segment of the industry has enjoyed,very little technical guidance exists for those who work in this field.
过去十年里，随着在卫生保健产品工业当中对隔离器的使用的增加其大多数备受关注。事实上，隔离器技术很明显的成为在卫生保健产品生产中发展最快的技术。尽管这种快速发展的技术在工业生产中得到应用，但是在这方面的技术指导非常缺乏。
It was often said at the beginning of the"isolator era"that isolators could be considered nothing more than small clean rooms.Experience has taught scientists and engineers that functional requirements for isolators are,in fact, distinctly different from those for human scale or"conventional"clean rooms.Although human scale clean rooms and isolators have much in common,they have many important differences and this technical report endeavors to focus on and discuss these differences.
在开始经常提到的“隔离器时代”中，隔离器被认为仅仅是一个小型的洁净室。实际上，经验提醒科学家和工程师，隔离器的功能要求明显不同于人类尺度上的或者传统意义上的洁净室。尽管人类尺度意义上的洁净室与隔离器有很多相似之处，但是它们之间依然有许多明显区别，因此这篇技术报告尝试着将重点关注和论述这些区别。
2.0TYPES OF ISOLATORS隔离器的类型
2.1Closed Isolators密闭式隔离器
Isolators operated as closed systems do not exchange unfiltered air or contaminants with adjacent environments. Their ability to operate without personnel access to the critical zone makes isolators capable of levels of separation between the internal and external environment unattainable with other technologies.Because of the effectiveness of this separation,closed isolators are ideally suited for application in the preparation of sterile and/or toxic material.
当隔离器处于密闭式系统操作时，它和周围相邻环境中没有与未过滤空气或者污染物的交换。隔离器能够在没有人员进入其关键区域进行操作，表明了隔离器在其他技术不能达到的分离其内部环境和外部环境的能力水平。鉴于这种高效的隔离效果，封闭式隔离器能很好的适用于无菌制备和/或者对有毒材料的处理。
There are two types of closed isolators:aseptic and containment.Aseptic isolators are intended to exclude external contamination from the critical zone inside the isolator.Containment isolators are intended to prevent the release of toxic materials processed inside the isolator to the surrounding environment in which personnel are located 这里有两种类型的封闭式的隔离器：无菌的和抑制的。无菌隔离器是用于从隔离器内部的关键区域排除外部污染物。抑制作用的隔离器是用于在隔离器内部进行有毒材料工艺时防止有毒材料被释放到人员所处的周围环境当中。
2.1.1Closed Isolators Intended for Aseptic Applications无菌应用的封闭式隔离器
These units are typically operated under positive pressure and are subject to validatable decontamination procedures prior to use.Isolators intended for the processing of sterile materials adhere to the following general principles:
此设备典型的是在正压情况下进行操作的，并在使用前服从经过验证的净化规程。用于无菌原料工艺的的隔离器遵循以下几点总则：
·They must not exchange air with the surrounding environment except when that air passes through a microbially retentive filter.
除非有高效微生物过滤器系统，它绝对不允许与周围环境发生空气交换。
·They must be decontaminated in a reproducible and quantifiable manner.
必须利用可再生的和可量化的方式对其进行净化处理。
·All work or handling of materials within the isolator enclosure must be accomplished remotely;no human operator or part thereof can directly enter the isolator during operation.
隔离器内部所有对原料进行的加工或者处理都是在远程操作模式下完成的。操作期间操作人员或者其身体的任何部份不允许直接进入隔离器内部进行操作。
·All materials that enter the isolator must be decontaminated or sterilized and must enter either directly through a decontaminating or sterilizing system,or via a rapid transfer port.
所有进入隔离器的原料都是必须经过净化或者灭菌处理的，并且是通过净化或者灭菌系统直接进入，又或者是通过快速传输接口进入的。
2.1.2Closed Isolators Intended for Containment Applications抑制应用的封闭式隔离器
These units generally operate under negative pressure and are cleared of all potentially hazardous materials prior to opening.Isolators intended for containment applications adhere to the following general principles:
这类设备通常是在负压条件下进行操作的并且在将其打开之前已清除了所有潜在的有毒物质的存在，用于抑制作用的隔离器遵循以下几点总则：
•They must not exchange air with the surrounding environment except when that air passes through a filter capable of retaining the materials being processed.
除非通过有能保存加工处理的原料的高效过滤器，它们绝对不允许与周围环境有空气交换发生。
•All work or handling of materials within the isolator enclosure must be accomplished remotely.No human operator or part thereof can directly enter the isolator during operation.
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