EUGMP中英文对照1.docx

1、EUGMP中英文对照1 EU GMP ANNEX 1MANUFACTURE OF STERILE MEDICINAL PRODUCTS（中英文对照） 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

2、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 pr

3、ocess or finished product test.无菌药品的生产，必须符合一些特殊的要求，以防止微生物、微粒和热源的污染。这很大程度上要取决于相关人员的技术水平、培训和工作态度。在这方面质量保证显得特别重要，这种类型的生产，必须严格按照完善的和经过验证的生产方法和工作程序。仅基于产品的最终灭菌或产品检验结果来相信其无菌性和其他质量指标是不可靠的。Note:This guidance does not lay down detailed methods for determining the microbiological and particulate cleanliness of

4、 air, surfaces etc. Reference should be made to other documents such as the EN/ISO Standards.注：本指南没有详述测定洁净区内微生物和尘埃粒子、表面的详细方法，请参阅EN/ISO中相关标准。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 equipmen

5、t 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.无菌产品的生产要在洁净区域内进行，进入这些区域内的人员、设备或物料，必须通过气闸室。洁净区必须保持一定的洁净级别，空气必须通过适宜效率的过滤器2. The various operations of component preparation, prod

6、uct 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.各种成分的制备、产品的制备和灌装，必须在

7、洁净区的不同区域进行。生产操作分为两类，一是产品最终灭菌型，二是部分过程或全过程的无菌操作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 m

8、inimize the risks of particulate or microbial contamination of the product or materials being handled. 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 wh

9、ere the installation is installed and operating, complete with production equipment 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. The “in operation

10、” and “at rest” states should be defined for each clean room or suite of clean rooms. For the manufacture of sterile medicinal products 4 grades can be distinguished.无菌生产的洁净区，按照产品对环境的要求分级，每一步生产操作，在操作状态，对环境有相应的洁净级别的要求，以防止对所处理的物料或产品造成的粉尘或微生物污染最小。为满足操作的要求，这些区域在设计上要达到“静态”的洁净标准。“静态”指设备已经安装并运行，生产设备就位但是没有操

11、作人员在场。“动态”是指在设备正常运转状态下和有规定数量的工作人员在场的情况下。每个或每套房间都要分别确定“静态”和“动态”。无菌药品的生产有4个环境级别：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

12、 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 uni-directional air flow and lower velocities may be used in closed isolato

13、rs and glove boxes.A级：用于高风险的生产操作，如灌装区、加盖区、安瓿与瓶开口区、和进行无菌连接的地方。通常这种情况是带有层流罩的工作点。在开放的洁净区内的工作点上，层流罩应该能产生风速为0.36 0.54米/秒的均匀气流。层流罩的维护，必须有充分的证明和经过验证。密封隔离箱和手套箱内，可采用单向低速气流。Grade B: For aseptic preparation and filling, this is the background environment for the grade A zone.B级：对于无菌制备和灌装，B级区域是A级区域的背景环境。Grade C

14、 and D: Clean areas for carrying out less critical stages in the manufacture of sterile products.C级和D级：无菌产品非关键生产步骤的洁净区。Clean room and clean air device classification洁净室及洁净空气装置分类4. Clean rooms and clean air devices should be classified in accordance with EN ISO 14644-1. Classification should be clear

15、ly differentiated from operational process environmental monitoring. The maximum permitted airborne particle concentration for each grade is given in the following table.洁净室及洁净空气装置应符合EN ISO 14644-1 。应根据生产操作环境监测明确地加以区分。最大允许尘埃粒子浓度应符合下表要求。Maximum permitted number of particles per m3 equal to or greater

16、 than the tabulated sizeAt restIn operationGrade0.5 m5.0m0.5 m5.0mA3 520203 52020B3 52029352 0002 900C352 0002 9003 520 00029 000D3 520 00029 000Not definedNot defined大于等于表中尺寸尘埃粒子最大允许数/ m3静态动态Grade0.5 m5.0m0.5 m5.0mA3 520203 52020B3 52029352 0002 900C352 0002 9003 520 00029 000D3 520 00029 000Not de

17、finedNot defined5. For classification purposes in Grade A zones, a minimum sample volume of 1m3 should be taken per sample location. For Grade A the airborne particle classification is ISO 4.8 dictated by the limit for particles 5.0 m. For Grade B (at rest) the airborne particle classification is IS

18、O 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 nu

19、mber 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. 在A级区，每个采样点取样量应不小于1 m3。A级尘埃粒子分类是根据ISO 4.8粒子 5.0 m的数量定义的。B级（静态）尘埃粒子分类根据ISO 5要考虑两种大小的粒子。C级（静态动态）粒子分类分别根据ISO7和ISO8。D级（静态）粒子分类是ISO 8 。分类是根据EN/I

20、SO 14644-1方法论，既明确了最少的取样点数，也规定了取样量和相适应的级别的最大允许颗粒大小和采集数据评价方法。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 5.0m in remote sampling systems with long lengths of tubing. Is

21、o kinetic sample heads shall be used in unidirectional airflow systems. 洁净分级应使用一个带有短取样管的便携式颗粒计数器，因为使用长距离的取样管会采集到远距离猛然落下 5.0 m的粒子的几率相对较高。单向气流系统应使用等动力采样头。7. “In operation” classification may be demonstrated during normal operations, simulated operations or during media fills as worst-case simulation i

22、s required for this. EN ISO 14644-2 provides information on testing to demonstrate continued compliance with the assigned cleanliness classifications.动态是在正常生产条件下定义的，模拟操作或在无菌分装的情况下，需要这方面的规定。EN ISO 14644-2提供了相关测试资料，以证明连续的符合洁净区的分类。Clean room and clean air device monitoring洁净室及洁净空气监测装置8. Clean rooms and

23、 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. 洁净室及洁净空气装置应动态条件下定期监测，监测的位置应基于正式的风险评估和日常监测结果。9. For Grade A zones, particle monitoring

24、 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 eq

25、uipment 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

26、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 m particles at the point of fill when filling is in progress, due to the generation of particles or droplets from the product itself.A级区，粒子监测应覆盖全部的关

27、键操作，包括设备装配，除非有正当理由证明污染物这个进程将损害粒子计数器或具有危险性，例如：活生物体和辐射危害。在这类情况下，日常设定操作的监测应该在暴露之前评估风险，模拟操作期间也应该监测。应该监测A级区域以一定的频率和适当采样量，所有干预、瞬变事件和任何系统恶化都能被捕获，并且如果超出报警限能报警。分装操作过程中，5.0 m微粒可能不总是符合较低的标准要求的，只要证明微粒或小滴是从产品产生的就可以了。10. It is recommended that a similar system be used for Grade B zones although the sample frequen

28、cy 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

29、and any system deterioration would be captured and alarms triggered if alert limits are exceeded.推荐B级区也使用和A级区类似的系统。虽然取样频率可能会减少，重要的是粒子监测系统应取决于有效的毗邻A级和B级区的隔离间。B级区也应以一定的频率和合适的取样量监测，污染程度变化的和任何系统恶化都能被捕获，并且如果超出报警限能警报。11. Airborne particle monitoring systems may consist of independent particle counters; a

30、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 t

31、ubing 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. 尘埃粒子监测系统，可以是独立的颗粒计数器; 也

32、可以是以单个粒子计数器采样点相连的网络，或者两者兼而有之。该系统的选定一定要适合粒子大小。而使用远程取样系统，应考虑取样管的长度及延伸的半径，必须考虑采样管中的粒子损失。选用何种监测系统应考虑当前药品存在的风险，例如那些涉及活生物体或放射性药品。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. 使用自动化系统的采样量通常会和采用速率有一个函数关系