GMPEu-Annex1-2008_中英文

ANNEX 1
附录Ⅰ
MANUFACTURE OF STERILE MEDICINAL PRODUCTS
无菌药品的生产
Principle
原则
The manufacture of sterile products is subject to special requirements in order to minimize risks of microbiological contamination, and of particulate and pyrogen contamination. Much depends on the skill, training and attitudes of the personnel involved. Quality Assurance is particularly important, and this type of manufacture must strictly follow carefully established and validated methods of preparation and procedure. Sole reliance for sterility or other quality aspects must not be placed on any terminal process or finished product test.
为将微生物、微粒和热原污染的风险降低至最小限度，无菌药品的生产应有各种特殊要求。

这在很大程度上取决于生产人员的技能、所接受的培训及其工作态度。

质量保证极为重要，无菌药品的生产必须严格按照精心制订并经验证的方法及规程进行。

产品的无菌或其它质量特性绝不能仅依赖于任何形式的最终操作或成品检验。

Note:
注：
This guidance does not lay down detailed methods for determining the microbiological and particulate cleanliness of air, surfaces etc. Reference should be made to other documents such as the EN/ISO Standards.
本指南没有制定详细的空气和物体表面等的微生物和微粒的测定方法，相关事项可以参照其他文件，诸如欧洲/国际标准。

General
总则
1.The manufacture of sterile products should be carried out in clean areas entry to which should be through airlocks for personnel and/or for equipment and materials. Clean areas should be maintained to an appropriate cleanliness standard and supplied with air which has passed through filters of an appropriate efficiency.
2.The various operations of component preparation, product preparation and filling should be carried out in separate areas within the clean area. Manufacturing operations are divided into two categories; firstly those where the product is terminally sterilised, and secondly those which are conducted aseptically at some or all stages.
3.Clean areas for the manufacture of sterile products are classified according to the required characteristics of the environment. Each manufacturing operation requires an appropriate environmental cleanliness level in the operational state in order to minimise the risks of particulate or microbial contamination of the product or materials being handled.
1.无菌药品的生产必须在洁净区内进行，人员和/或设备以及物料必须通过缓冲室进入洁净区。

洁净区应当保持适当的洁净度，洁净区的送风须经具有一定过滤效率过滤器的过滤。

2.原料配制、产品加工和灌装等不同操作必须在洁净区内彼此分开的单独区域内进行。

生产工艺可分为两类：一类是最终灭菌工艺；第二类是部分或全部工序为无菌操作的工艺。

3.生产无菌产品的洁净区按所需环境的特点划分其级别。

为了尽可能减少产品（或原料）受微粒或微生物污染的风险，每一步生产操作都应达到适当的动态洁净度。

In order to meet “in operation” conditions these areas should be designed to reach certain specified air-cleanliness levels in the “at rest” occupancy state. The “at-rest” state is the condition where the installation is installed and operating, complete with production equipme nt but with no operating personnel present. The “in operation” state is the condition where the installation is functioning in the defined operating mode with the specified number of personnel working.
为了符合“动态”的洁净度要求，这些洁净区的设计必须符合相应的“静态”洁净度。

“静态”是指安装已经完成并已运行，但没有操作人员在场的状态。

“动态”是指生产设施正按照指定的工艺模式运行并有规定数量的操作人员进行现场操作的状态。

The “in operation” and “at rest” states should be defined for each clean room or suite of clean rooms.
每个洁净室或是一套洁净室都必须定义其“动态”和“静态”状态。

For the manufacture of sterile medicinal products 4 grades can be distinguished.
无菌药品生产所需的洁区一般可分为4个级别：
Grade A: The local zone for high risk operations, e.g. filling zone, stopper bowls, open ampoules and vials, making aseptic connections. Normally such conditions are provided by a laminar air flow work station. Laminar air flow systems should provide a homogeneous air speed in a range of 0.36 –0.54 m/s (guidance value) at the working position in open clean room applications. The maintenance of laminarity should be demonstrated and validated.
A级区
高风险操作区，如：灌装区，放置胶塞桶、敞口安瓿瓶、敞口西林瓶的区域及无菌装配/连接操作的区域。

通常用层流操作台/罩来维护该区的环境状态。

层流系统在其工作区域必须均匀送风，风速为0.36-0.54m/s（指导值）。

应有数据证明层流的状态并须验证。

A uni-directional air flow and lower velocities may be used in closed isolators and glove boxes.
封闭式的隔离器和手套式操作箱内，可能使用单向流或是更低的风速。

Grade B: For aseptic preparation and filling, this is the background environment for the grade A zone.
B级区：指无菌配制和灌装A级区所处的背景区域。

Grade C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products.
C级和D级区：指生产无菌产品过程中重要程度较次的清洁操作区。

Clean room and clean air device classification
洁净室和洁净空气设备分类
4. Clean rooms and clean air devices should be classified in accordance with EN ISO 14644 1. Classification should be clearly differentiated from operational process environmental monitoring. The maximum permitted airborne particle concentration for each grade is given in the following table.
4. 洁净室和洁净空气设备必须根据EN ISO 14644-1进行分类。

以上各级别空气悬浮粒子的标准如下表：
5. For classification purposes in Grade A zones, a minimum sample volume of 1m 3 should be taken per sample location. For Grade A the airborne particle classification is ISO 4.8 d ictated by the limit for particles ≥5.0 μm. For Grade B (at rest) the airborne particle classification is ISO 5 for both considered particle sizes. . For Grade C (at rest & in operation) the airborne particle classification is ISO 7 and ISO 8 respectively. For Grade D (at rest) the airborne particle classification is ISO 8. For classification purposes EN/ISO 14644-1 methodology defines both the minimum number of sample locations and the sample size based on the class limit of the largest considered particle size and the method of evaluation of the data collected.
5. 对A级洁净区进行分类时，每个取样点只少要有1立方米的取样容积；A级洁净区≥5.0μm的悬浮粒子限度标准是ISO 4.8。

B级洁净区（静态）两个限度标准都是根据ISO 5。

C级洁净区（静态和动态）限度标准分别是根据ISO 7和ISO 8。

D级洁净区（静态）限度标准是ISO 8。

作为分类目的，EN/ISO 14644-1体系规定了各级别最大粒子的最少取样点和取样量，以及采集来的数据的评估方法。

6. Portable particle counters with a short length of sample tubing should be used for classification purposes because of the relatively higher rate of precipitation of particles ≥5.0μm
in remote sampling systems with long lengths of tubing. Isokinetic sample heads shall be used in unidirectional airflow systems.
6.分类时，应该使用带有短的取样管的便携式粒子计数器；因为在远程取样系统的长取样管中的≥5.0μm的粒子的沉降率相对较高。

单向流系统中应该等速取样探头。

7. “In operation” classification may be demonstrated during normal operations, simulated operations or during media fills as worst-case simulation is required for this. EN ISO 14644-2 provides information on testing to demonstrate continued compliance with the assigned cleanliness classifications.
7.对“动态”进行分类时，必须在正常操作、模拟操作或是培养基填充时模拟最差情况下进行。

EN ISO 14644-2提供了检测的相关信息，以便符合指定的洁净度分类。

Clean room and clean air device monitoring
洁净室和洁净空气设备监控
8. Clean rooms and clean air devices should be routinely monitored in operation and the monitoring locations based on a formal risk analysis study and the results obtained during the classification of rooms and/or clean air devices.
8.必须对洁净室和洁净空气设备进行常规动态监控；监控点必须基于正式的风险分析研究，以及从洁净室和/或洁净空气设备分类时所得到的结果。

9. For Grade A zones, particle monitoring should be undertaken for the full duration of critical processing, including equipment assembly, except where justified by contaminants in the process that would damage the particle counter or present a hazard, e.g. live organisms and radiological hazards. In such cases monitoring during routine equipment set up operations should be undertaken prior to exposure to the risk. Monitoring during simulated operations should also be performed. The Grade A zone should be monitored at such a frequency and with suitable sample size that all interventions, transient events and any system deterioration would be captured and alarms triggered if alert limits are exceeded. It is accepted that it may not always be possible to demonstrate low levels of ≥5.0 μm particles at the point of fill when
filling is in progress, due to the generation of particles or droplets from the product itself.
9.除非工艺中的污染物会损坏粒子计数器或是带来诸如活体微生物和放射线的危害，否则包括设备安装在内的A级洁净区的关键工艺必须全程对粒子进行监控。

这种情况下，在暴露于风险前，日常设备的设置操作也要进行监控。

A级洁净区应当以这样的频率进行监控，并且须有合适的取样量，以便捕捉所有干扰、瞬时事件和任何系统恶化，并且在超过警报线时给出警报。

由于产品本身也会产生微粒或是液滴，因而如果灌装正在进行，灌装的那一刻不必显示≥5.0μm粒子的最低线。

10. It is recommended that a similar system be used for Grade B zones although the sample frequency may be decreased. The importance of the particle monitoring system should be determined by the effectiveness of the segregation between the adjacent Grade A and B zones. The Grade B zone should be monitored at such a frequency and with suitable sample size that changes in levels of contamination and any system deterioration would be captured and alarms triggered if alert limits are exceeded.
10.对于B级洁净区，建议使用类似的系统，但是取样频率可以适当减少。

粒子监控系统的重要性应该由A级和B级区相邻处的隔离效果来决定。

B级洁净区应该以这样的频率进行监控，并且须有合适的取样量，以便捕捉多级的污染变化和任何系统恶化，并且在超过警报线时给出警报。

11. Airborne particle monitoring systems may consist of independent particle counters; a network of sequentially accessed sampling points connected by manifold to a single particle counter; or a combination of the two. The system selected must be appropriate for the particle size considered. Where remote sampling systems are used, the length of tubing and the radii of any bends in the tubing must be considered in the context of particle losses in the tubing. The selection of the monitoring system should take account of any risk presented by the materials used in the manufacturing operation, for example those involving live organisms or radiopharmaceuticals.
11.悬浮粒子监控系统应当包括独立的粒子计数器；由管道连接到单个粒子计数器的连续取样点网络；或者是两者的结合。

选择的系统必须适合粒度。

如果使用远程取样系统，
考虑到粒子在取样管中的流失，必须控制管长和曲径。

在选择监控系统时，必须考虑生产操作过程中物料所带来的任何风险，比如涉及到活体微生物和放射药剂的操作。

12. The sample sizes taken for monitoring purposes using automated systems will usually be a function of the sampling rate of the system used. It is not necessary for the sample volume to be the same as that used for formal classification of clean rooms and clean air devices.
12.使用自动化系统，用于监控的取样量，必须成为选用的监控系统的取样率机能。

但是取样容积不需要跟标准分类的洁净室和洁净空气设备一样。

13. In Grade A and B zones, the monitoring of the ≥5.0 μm particle concentration count takes on a particular significance as it is an important diagnostic tool for early detection of failure. The occasional indication of ≥5.0 μm particle count s may be false counts due to electronic noise, stray light, coincidence, etc. However consecutive or regular counting of low levels is an indicator of a possible contamination event and should be investigated. Such events may indicate early failure of the HVAC system, filling equipment failure or may also be diagnostic of poor practices during machine set-up and routine operation.
13.在A级和B级洁净区中，对≥5.0μm微粒的浓度的监控以微粒数（值）表示，因为这是对系统故障提早监测到重要诊断工具。

偶尔读取到的≥5.0μm微粒数值可能是因为电子噪声、杂散光、巧合等带来的错误数值。

但是持续或是经常读到的低数值是污染可能的指示器，应当进行调查。

这些时间可能显示HVAC系统早期的故障，灌装设备故障或是对机器设定和日常操作不符合规范的诊断。

14. The particle limits given in the table for the “at rest” state should be a chieved after a short “clean up” period of 15-20 minutes (guidance value) in an unmanned state after completion of operations.
14.表中的“静态”的微粒限度在操作完成后，短暂“清洁时间”15－10分钟（指导值）无人状态下，必须达到。

15. The monitoring of Grade C and D areas in operation should be performed in accordance
with the principles of quality risk management. The requirements and alert/action limits will depend on the nature of the operations carried out, but the recommended “clean up period” should be attained.
15.对C级和D级洁净区的动态监控必须按照质量风险管理的原则进行。

监控要求和警戒/行动线取决于要进行的操作，但必须有建议的“清洁时间”。

16. Other characteristics such as temperature and relative humidity depend on the product and nature of the operations carried out. These parameters should not interfere with the defined cleanliness standard.
16.其他诸如温度和相对湿度等参数取决于产品和操作的性质。

这些参数不可以与定义的洁净度标准发生冲突。

17. Examples of operations to be carried out in the various grades are given in the table below (see also paragraphs 28 to 35):
17. 下表列出了各级区内示例性生产操作（也可以参照28－35点）：
18. Where aseptic operations are performed monitoring should be frequent using methods such as settle plates, volumetric air and surface sampling (e.g. swabs and contact plates). Sampling methods used in operation should not interfere with zone protection. Results from monitoring should be considered when reviewing batch documentation for finished product release. Surfaces and personnel should be monitored after critical operations. Additional microbiological monitoring is also required outside production operations, e.g. after validation of systems, cleaning and sanitisation.
18. 为了控制无菌操作区的微生物状况，应频繁地对微生物进行动态监测，监测方法有沉降碟法、定量空气采样法和表面取样法（如：擦拭法和接触碟法）等。

动态取样时不得对洁净区的保护产生干扰。

在成品批档案审核，应同时考虑环境监测的结果，决定是否放行。

表面和操作人员的监测，应在关键操作完成后进行。

除在生产过程中需进行微生物监控外，系统验证、清洁和消毒等操作后，也应进行微生物监控。

19. Recommended limits for microbiological monitoring of clean areas during operation:
19. 各洁净区微生物监控的动态参考标准：
微生物污染限度参考标准(a)
Notes
(a) These are average values.
(b) Individual settle plates may be exposed for less than 4 hours.
注：
（a）表中各数值均为平均值。

（b）单个沉降碟的暴露时间可以少于4小时。

20. Appropriate alert and action limits should be set for the results of particulate and microbiological monitoring. If these limits are exceeded operating procedures should prescribe corrective action.
20.应当对微粒和微生物监控制定适当的警戒和行动线。

操作规程中应详细说明结果超标时应采取的整改措施。

Isolator technology
隔离技术
21. The utilisation of isolator technology to minimize human interventions in processing areas may result in a significant decrease in the risk of microbiological contamination of aseptically manufactured products from the environment. There are many possible designs of isolators and
transfer devices. The isolator and the background environment should be designed so that the required air quality for the respective zones can be realised. Isolators are constructed of various materials more or less prone to puncture and leakage. Transfer devices may vary from a single door to double door designs to fully sealed systems incorporating sterilisation mechanisms.
21.采用能最大限度降地低生产区人员影响的隔离技术，可大大降低无菌生产中环境对产品微生物污染的风险。

隔离操作台和传递装置的设计可以有多种形式。

隔离操作台及其所处环境的设计，应能保证相应区域空气的质量达到设定标准。

隔离操作台所采用的材料在某种程度上易被穿剌或易产生渗漏。

传输装置可设计成单门的、双门的，甚至可以是同灭菌设备相连的全密封系统。

22. The transfer of materials into and out of the unit is one of the greatest potential sources of contamination. In general the area inside the isolator is the local zone for high risk manipulations, although it is recognised that laminar air flow may not exist in the working zone of all such devices.
22.将物品放入隔离操作台或从中取出属污染风险最为严重的操作过程。

尽管人们认为这类隔离操作器的工作区内不一定要有层流，但是，隔离系统通常是用于进行高污染风险操作的场所。

23. The air classification required for the background environment depends on the design of the isolator and its application. It should be controlled and for aseptic processing it should be at least grade D.
23.隔离操作台所处环境的级别取决于它们的设计及其应用。

无菌操作的隔离操作台所处环境的级别应予控制，至少为D级。

24. Isolators should be introduced only after appropriate validation. Validation should take into account all critical factors of isolator technology, for example the q uality of the air inside and outside (background) the isolator, sanitisation of the isolator, the transfer process and isolator integrity.
24.隔离操作台只有经过适当的验证之后方可投入使用。

验证时应当考虑到隔离技术的所有关键性因素，例如，隔离系统内部和外部（所处环境）的空气质量、隔离操作台的消毒、传递操作以及隔离系统的完好性。

25. Monitoring should be carried out routinely and should include frequent leak testing of the isolator and glove/sleeve system.
25.隔离操作器和隔离用袖管/手套系统应进行常规监测，这包括经常进行必要的检漏试验。

Blow/fill/seal technology
吹气/灌装/密封技术
26. Blow/fill/seal units are purpose built machines in which, in one continuous operation, containers are formed from a thermoplastic granulate, filled and then sealed, all by the one automatic machine. Blow/fill/seal equipment used for aseptic production which is fitted with an effective grade A air shower may be installed in at least a grade C environment, provided that grade A/B clothing is used. The environment should comply with the viable and non viable limits at rest and the viable limit only when in operation. Blow/fill/seal equipment used for the production of products which are terminally sterilised should be installed in at least a grade D environment.
26.吹气/灌装/密封系统是一套专用机械设备，连续操作，从一个热塑性颗粒吹制成容器至灌装和密封，整个过程由一台全自动机器完成。

用于无菌生产的吹气/灌装/密封设备本身装有A级空气风淋装置，在操作人员按A/B级区要求着装的条件下，该设备可以安装在洁净度至少为C级的环境中。

在静态条件下，此环境微粒和微生物均应达到标准，在动态条件下，此环境的微生物应达到标准。

用于生产最终灭菌产品的吹气/灌装/密封设备至少应安装在D级环境中。

27. Because of this special technology particular attention should be paid to, at least the following:
♦equipment design and qualification
♦validation and reproducibility of cleaning-in-place and sterilisation-in-place
♦background clean room environment in which the equipment is located
♦operator training and clothing interventions in the critical zone of the equipment including any aseptic assembly prior to the commencement of filling.
27.因此项技术有其特殊性，以下几方面应予特别注意：
♦设备设计及设备的确认
♦在线清洗和在线灭菌的验证及结果的重现性
♦设备所处的洁区环境
♦操作人员的培训和着装
♦设备关键区域内的影响因素，包括灌装开始前设备的无菌装配。

Terminally sterilised products
最终灭菌产品
28. Preparation of components and most products should be done in at least a grade D environment in order to give low risk of microbial and particulate contamination, suitable for filtration and sterilisation. Where the product is at a high or unusual risk of microbial contamination, (for example, because the product actively supports microbial growth or must be held for a long period before sterilisation or is necessarily processed not mainly in closed vessels), then preparation should be carried out in a grade C environment.
28.原料和大多数产品的准备/配制应当至少在D级区进行，以降低粒子和微生物污染的风险，以适过滤及灭菌操作的要求。

微生物污染风险比较高时，如容易长菌的产品、配制后要等相当长时间方可灭菌的产品或因故主要不在密闭容器内进行配制操作的产品，配制必须在C级环境中进行。

29. Filling of products for terminal sterilization should be carried out in at least a grade C environment.
29.最终灭菌产品的灌装应至少在C级区进行。

30. Where the product is at unusual risk of contamination from the environment, for example because the filling operation is slow or the containers are wide-necked or are necessarily exposed for more than a few seconds before sealing, the filling sho uld be done in a grade A zone with at least a grade C background. Preparation and filling of ointments, creams,
30.当环境对产品污染的风险比较大时，例如灌装速度慢或容器是广口瓶、或是须暴露数秒钟后方可压塞的产品，必须在C级区内局部A级条件下灌封。

软膏、霜剂、悬浊液以及乳剂一般应在C级区配制和灌封，然后作最终灭菌。

Aseptic preparation
无菌配制
31. Components after washing should be handled in at least a grade D environment. Handling of sterile starting materials and components, unless subjected to sterilisation or filtration through a micro-organism-retaining filter later in the process, should be done in a grade A environment with grade B background.
31.清洗后的物料应当至少在D级区进行处理。

除在配制后须灭菌或除菌过滤的产品外，无菌原料、物料的处理应在B级区内局部A级的条件下进行。

32. Preparation of solutions which are to be sterile filtered during the process should be done in
a grade C environment; if not filtered, the preparation of materials and products should be done in a grade A environment with a grade B background.
32. 在生产加工过程中须无菌过滤的药液必须在C级区内配制；配制后不作除菌过滤的产品，药液的配制应在B级区内局部A级的条件下进行。

33. Handling and filling of aseptically prepared products should be done in a grade A environment with a grade B background.
33. 无菌制备的产品，其处理和灌装必须在B级区内局部A级的条件下进行。

34. Prior to the completion of stoppering, transfer of partially closed containers, as used in freeze drying should be done either in a grade A environment with grade B background or in sealed transfer trays in a grade B environment.
34.用于冻干剂的部分密封的容器有二种传递方式：在完全压塞之前必须在B级区内局部A 级条件下进行；或将其装入密封的周转箱内在B级环境中传递。

35. Preparation and filling of sterile ointments, creams, suspensions and emulsions should be done in a grade A environment, with a grade B background, when the product is exposed and is not subsequently filtered.
35.处于暴露状态而又不再作除菌过滤的软膏、霜剂、悬浊液和乳浊液，必须在B级区内局部A级的条件下配制和灌装。

Personnel
人员
36. Only the minimum number of personnel required should be present in clean areas; this is particularly important during aseptic processing. Inspections and controls should be conducted outside the clean areas as far as possible.
36.洁净区内的人员数应严加控制，这对无菌操作犹为重要。

检查和监督应尽可能在远离洁净区的地方进行。

37. All personnel (including those concerned with cleaning and maintenance) employed in such areas should receive regular training in disciplines relevant to the correct manufacture of sterile products. This training should include reference to hygiene and to the basic elements of microbiology. When outside staff who have not received such training (e.g. building or maintenance contractors) need to be brought in, particular care should be taken over their instruction and supervision.
37.凡在洁净区工作的人员（包括清洁工和设备维修工）都必须定期给予操作方面的纪律教育，以使无菌产品的操作符合要求，培训的内容应包括卫生学知识和微生物方面的基础知识。

没有受过这类培训的外部人员（如按合同施工的建筑工人或维修人员）需进入洁净区时，应对他们进行特别详细的指导和监督。

38. Staff who have been engaged in the processing of animal tissue materials or of cultures of micro-organisms other than those used in the current manufacturing process should not enter sterile-product areas unless rigorous and clearly defined entry procedures have been followed.
38.凡从事动物组织加工处理的人员或者从事与现生产无关的微生物培养的工作人员不应进入无菌产品生产区，除非他们一直严格遵循进入上述操作区标准操作规程的明文规定。

39. High standards of personal hygiene and cleanliness are essential. Personnel involved in the manufacture of sterile preparations should be instructed to report any condition which may cause the shedding of abnormal numbers or types of contaminants; periodic health checks for such conditions are desirable. Actions to be taken about personnel who could be introducing undue microbiological hazard should be decided by a designated competent person.
39.高标准的个人卫生要求及清洁程度是至关重要的。

应当教育从事无菌药品生产的员工随时报告任何可能导致污染风险增大的异常情况，包括种类或数量；应定期进行健康检
查并由指定的称职人员负责对那些可能导致微生物污染风险增大的员工采取适当的措施。

40. Wristwatches, make-up and jewellery should not be worn in clean areas.
40.在洁净区内不得戴手表和首饰，不得涂抹化装品。

41. Changing and washing should follow a written procedure designed to minimize contamination of clean area clothing or carry-through of contaminants to the clean areas.
41.更衣和洗手必须遵循相应的书面规程，以尽可能减少着装对洁净区污染或将污染物带入该区的风险。

42. The clothing and its quality should be appropriate for the process and the grade of the working area. It should be worn in such a way as to protect the product from contamination. 42.工作服及其质量应与生产操作的要求及操作区的洁净级别相适应，其穿着方式应能保护产品免遭污染。

43. The description of clothing required for each grade is given below:
♦Grade D: Hair and, where relevant, beard should be covered. A general protective suit and appropriate shoes or overshoes should be worn. Appropriate measures should be taken to avoid any contamination coming from outside the clean area.
♦Grade C: Hair and where relevant beard and moustache should be covered. A single or two-piece trouser suit, gathered at the wrists and with high neck and appropriate shoes or overshoes should be worn. They should shed virtually no fibres or particulate matter.
♦Grade A/B: Headgear should totally enclose hair and, where relevant, beard and moustache; it should be tucked into the neck of the suit; a face mask should be worn to prevent the shedding of droplets. Appropriate sterilised, non-powdered rubber or plastic gloves and sterilised or disinfected footwear should be worn. Trouser-legs should be tucked inside the footwear and garment sleeves into the gloves. The protective clothing should shed virtually no fibres or particulate matter and retain particles shed by the body.
43.现对各洁净区的着装要求作如下说明：
D级区：应将头发、胡须等相关部位遮盖住。

应当穿一般性的保护服装和合适的鞋子或鞋套。

应采取适当措施避免将级区外的污染物带入本区。

C级区：必须将头发、胡须等相关部位遮盖住。

应穿手腕处可收紧、领圈比较高的单件式或双件式套装，并配以合适的鞋或鞋套。

它们不应脱落纤维或微粒。

A/B级区：应当用头罩将所有头发以及胡须等相关部位全部遮盖住，头罩应塞进衣领内，应戴口罩以防散发液滴。

应戴经灭菌且未上滑石粉的橡胶或塑料手套，穿经灭菌或消毒的脚套，裤腿管应当塞进脚套内，袖口应塞进手套内。

着装应不脱落纤维或粒子，并能滞留身体散发的粒子。

44. Outdoor clothing should not be brought into changing rooms leading to grade B and C rooms. For every worker in a grade A/B area, clean sterile (sterilised or adequately sanitised) protective garments should be provided at each work session. Gloves should be regularly disinfected during operations. Masks and gloves should be changed at least for every working session.
44.人员的便服不得带进通向B及C级区的更衣室。

对于在A/B级区工作的每一位员工来说，每次操作都须更换一次清洁的无菌（经灭菌或充分消毒）防护服，或一天至少更换一次（但必须由监测结果证明这种方法的可行性）。

操作期间应经常消毒手套，每工作一个阶段即应更换口罩和手套。

45. Clean area clothing should be cleaned and handled in such a way that it does not gather additional contaminants which can later be shed. These operations should follow written procedures. Separate laundry facilities for such clothing are desirable. Inappropriate treatment of clothing will damage fibres and may increase the risk of shedding of particles.
45.洁净区所用工作服的清洗和处理应当确保其不沾有污染物，这些污染物此后脱落，造成污染。

工作服的清洗和处理应遵循书面规程，最好能使用单独的洗衣设备。

工作服处理不当会损坏纤维并由此增加散发粒子的风险。

Premises
厂房
46. In clean areas, all exposed surfaces should be smooth, impervious and unbroken in order to
minimize the shedding or accumulation of particles or micro-organisms and to permit the repeated application of cleaning agents, and disinfectants where used.
46.为了尽可能减少微粒或微生物的散发或积聚、便于清洁剂和消毒剂的重复使用，洁净区内所有外露表面都必须光滑平整、无渗漏性或有裂缝。

47. To reduce accumulation of dust and to facilitate cleaning there should be no uncleanable recesses and a minimum of projecting ledges, shelves, cupboards and equipment. Doors should be designed to avoid those uncleanable recesses; sliding doors may be undesirable for this reason.
47.为了减少尘埃的积聚并便于清洁，洁净区内不应有难以清洁的凹陷处，货架、柜子以及设备应尽可能没有凸出的边缘。

门的设计应避免有难以清洁的凹陷；因此不宜使用移门。

48. False ceilings should be sealed to prevent contamination from the space above them.
48.活动天花板宜作密封处理，防止来自上方的污染。

49. Pipes and ducts and other utilities should be installed so that they do not create recesses,
unsealed openings and surfaces which are difficult to clean.
49.管道、风管以及其它设施的安装不应造成凹陷、不密封的敞口和难以清洁的表面。

50. Sinks and drains should be prohibited in grade A/B areas used for aseptic manufacture. In other areas air breaks should be fitted between the machine or sink and the drains. Floor drains in lower grade clean rooms should be fitted with traps or water seals to prevent backflow.
50.无菌生产的A/B级区内禁止设置水池和地漏。

在其它洁净区内，机器设备或水池与地漏不应直接相连。

在洁净度要求较低级区的地漏应设水封，防止倒流。

51. Changing rooms should be designed as airlocks and used to provide physical separation of the different stages of changing and so minimize microbial and particulate contamination of protective clothing. They should be flushed effectively with filtered air. The final stage of the changing room should, in the at-rest state, be the same grade as the area into which it leads. The use of separate changing rooms for entering and leaving clean areas is sometimes desirable. In general hand washing facilities should be provided only in the first stage of the changing。