洁净室区环境监控SOP0510.docx

1、洁净室区环境监控SOP0510Author作者：Date日期：赵春丽，QA Vice President Assistant/QA副总经理助理Approved by批准人：Date日期：李红坤，Production Dept. Associate Director /生产部副主管Approved by批准人：Date日期：于立慧，QA Site Vice President/QA厂区副总经理Change修改内容：1.The acceptance criteria of mold were added for the microbe test./增加了微生物测试合格标准中霉菌的要求。2.It w

2、as added that during the daily monitoring of pressure difference, the designated environment monitoring personnel should fully open the door according to the related procedure requirement to check and confirm the reading of the corresponding differential manometer return to zero, and then close the

3、door to check the reading of pressure difference and to confirm whether its within the standard requirement. /增加了日常压差监测时，指定的环境监测人员需按照规程要求将门打开，检查并确认压差表示数归零，然后关上门并检查压差计读数并确认是否符合标准要求。3.It was added that check and confirm the pipe for air pressure differential connected with the air pressure meter is in

4、 good condition and replace it if necessary during installation of the pressure meter after each time of calibration./增加了每次压差表校正后安装时检查与压差表相连的导气管是否完好无损，必要时进行更换的要求。Objective/Scope目标/范围：Objective: Establish the general environment monitor and control procedure for cleaning rooms/areas and regulate the

5、method of monitor and control temperature, humidity, pressure difference, airborne particles and airborne viable particles to ensure they meet the cGMP requirement of the product running in the room/area.目标：建立洁净室/区环境监控规程，规范洁净室/区温度、湿度、静压差、悬浮粒子和微生物的监控操作，使其满足相应区域内生产的产品应符合GMP的要求。Scope: It applies air mo

6、nitoring and controlling all the controlled area for processing, warehousing, testing.范围：本规程适用于所有用于工艺操作，储存和检测的洁净室/区的环境监控。Definitions术语定义：Clean room/area: area/room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introducti

7、on, generation, and retention of particles inside the room, and in which other relevant parameters, e.g. temperature, humidity, and pressure, are controlled as necessary.洁净室/区：空气悬浮粒子浓度受控的房间，房间的建设和使用方式要尽可能减少室内引入、产生和滞留粒子，室内其它相关参数如温度、湿度和压力按要求进行控制。At rest test: Test carried out in the condition that the

8、 HVAC system is in normal operational statement, and the clean room (area) is in normal production, technical equipment is installed and there are no operating personnel in the clean room (area).静态测试：洁净室（区）净化空调系统已处于正常运行状态，工艺设备已安装，洁净室（区）内没有生产人员的情况下进行的测试。Operational test: Test carried out in the condi

9、tion that the clean room (area) is in normal production.动态测试：洁净室（区）已处于正常生产状态下进行的测试。RSM: Registered Starting Material. Starting Material that is included in the drug registration documents (such as DMF).在药品注册文件（如DMF）中体现的起始原料。API (Active Pharmaceutical Ingredient): Any substance or mixture of substanc

10、es intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treat

11、ment, or prevention of disease or to affect the structure and function of the body.活性药用成分（原料药）或药物：旨在用于药品制造中的任何一种物质或物质的混合物，而且在用于制药时，成为药品的一种活性成分。此种物质在疾病的诊断，治疗，症状缓解，处理或疾病的预防中有药理活性或其它直接作用，或者能影响机体的功能和结构。Drug Substance: Active pharmaceutical ingredient (API) intended for use as a component of a sterile or

12、 non sterile drug product. Drug substances can be manufactured by chemical synthesis, fermentation, recombinant DNA or other biotechnology methods, isolation / recovery from natural sources or any combination of these processes.药物：用于无菌或非无菌药品成分的活性药用成分。它可以通过化学合成，发酵，DNA重组或其他生物技术、自然物质分离/回收以及以上方法的组合等方式来制

13、造。Applicable to适用对象：Site: All Asymchem sites厂区：所有凯莱英厂区Dept.: cGMP facility, High potency facility, Formulation facility, GMP Key Material Warehouse, GMP Product Warehouse, Engineering Dept.部门：cGMP车间，活性药物车间，制剂车间，原料库，成品库，GMP主原料库，GMP成品库，工程设备部Related Documents相关文件和记录:Attachment A Classification of air c

14、leanness/附件A空气洁净度等级Attachment B Air flow testing method of Clean room/area/附件B 洁净室/区风量检测方法QF03006 Pressure difference recording table /压差记录表QF03007 Temperature and humidity recording table /温湿度记录表QF03036 Air flow test recording table/风量检测记录表ReferenceStandards参考标准:GB50243-2002 Ventilation and air con

15、ditioning engineering construction quality inspection specifications Appendix B Clean room test/通风与空调工程施工质量验收规范 附录B 洁净室测试ISO14644 Cleanrooms and associated controlled environments/洁净室及相关控制环境国际标准Chinese GMP standard(2010 revise)/中国药品生产质量管理规范（2010修订）GMP-042 /悬浮粒子测试GMP-108 /区域和表面环境监控规程QA-010 /偏差汇报QA-01

16、9 /重大偏差调查EHS-053 /灾后恢复和重建SOPProcedure程序：Responsibility执行人Step步骤Action执行内容1Classification of clean room/area洁净等级划分The clean room/area in Asymchem facility is established reference to Chinese GMP standard (2010 revise) and ISO14644; there are two classes clean room/area, Class D and ISO 9. The clean c

17、lass of Class D is equivalent to ISO8. The cleanness requirement and application of clean room/area shows in the following table.本公司洁净室/区是采用中国药品生产质量管理规范（2010修订）和ISO 14644的级别标准，本公司洁净室有D级和ISO 9级两种，其中D级相当于ISO14644中的ISO8级。各洁净室/区的分级和应用如下表所Item项目Class D/D级ISO9Applicable to适用对象Manufacturing of non-sterile

18、drug substance(API), GMP intermediate, High potency product (intermediate and API), including process steps, primary packaging and storage/非无菌药物（API），GMP中间体，高活性产品（中间体和API）的生产：包括工艺步骤，初包装，储存等。Manufacturing of RSM/在注册文件中体现的起始物料的生产（工艺步骤，初包装，储存等）Item项目Class D/D级ISO9Applicable to适用对象Storage of GMP key raw

19、 material/GMP主原料储存Note: Manufacturing of non-sterile drug substance for sterile products based on client requirement of appropriate sterilization and microbe testing and monitoring./注：基于客户要求，经过适当的消毒和微生物监测后，可以进行无菌药品的非无菌部分的生产。Background environment for Class D room/area/D级洁室/区的背景环境Item项目Class D/D级ISO9

20、Airborne particles(at rest test, (particles/m3)/悬浮粒子（静态测试） 0.5m：3,520,0005m：29,0000.5m：35,200,0005m：293,0002Monitoring method and frequency监测方式和监测频率Designated environment monitoring personnel/指定环境监测人员2.1The following items should be controlled and monitored to keep it meets the clean class requireme

21、nt. 对洁净室/区进行以下项目的控制和监测，使其环境持续符合相应洁净级别的要求。Item/监测项Frequency/频率Comment备注Class DISO 9Airborne particles悬浮粒子(particles/m3)Twice a year(at-rest test and operational test in term every six month)每年两次（每6个月一次，静态测试和动态测试交替进行）In-house test or contractor test公司内部检测或委托检测Airflow气流Once a year每年一次Once a year每年一次Air

22、 change rates换气次数Once a year每年一次Once a year每年一次Room relative pressure相对压差Once a day每天一次Once a day每天一次In-house monitor/公司内部监测Temperature温度Twice a day每天2次Twice a day每天2次Relative Humidity相对湿度Twice a day每天2次Twice a day每天2次Item/监测项Frequency/频率Comment备注Class DISO 9Microbe微生物Airborne microbe and sedimental

23、 viable particle: based on risk assessment and the frequency of open operation in the room/area, quarterly test the processing areas/rooms for production, and semi-annually test for material storage warehouses, /浮游菌和沉降菌：基于风险评估和房间/区域内开放性操作的频率，工艺操作的生产房间/区域每季度一次，物料储存库房每半年一次。Surface microbe: Based on pr

24、oduct spec. and characteristics and also client requirement, and will use sampling plan based on size of room and risk assessment. /表面微生物：基于产品标准和特性以及客户要求，并基于房间面积和风险评估确定的取样方案来进行。N/AContractor test/委托检测2.2The acceptance criteria is following标准要求如下：Item项目Class D/D级ISO9Airborne particles悬浮粒子(particles/m

25、3)At-rest test/静态测试0.5m：3,520,0005m：29,000At-rest test/静态测试0.5m：35,200,0005m：293,000Operational test: Not required/动态测试：不作规定Airflow气流Velocity: 0.45 0.09m/s/风速：0.45 0.09m/sVolume: ensure 40m3/h fresh air for each one in the rooms/风量：室内每人新鲜空气量不应小于40m3/hAir change rates换气次数15 times/h（次/h）Room relative

26、pressure/相对压差No less than 10Pa between clean room and non-classified area/room./ 洁净区与非洁净区之间10Pa。No less than 10Pa between different clean-classified rooms/areas./不同洁净级别洁净室（区）之间10Pa。Appropriate pressure difference should be maintained between the adjacent rooms of the same clean classification based

27、on final product flow and risk of open operation/相同洁净等级的相邻房间之间，基于终产品流向和开放性操作的风险，应该保持适当的压差梯度。Item项目Class D/D级ISO9Temperature温度Process steps, primary packaging/工艺步骤和初包装：225Warehouse for storage/储存库房：20251826Relative Humidity相对湿度Production room/area/生产房间/区域：4515%Material storage warehouses/物料储存库房：4515%

28、4515%Microbe微生物Airborne microbe/浮游菌(cfu/m3)：Total aerobic microbial count/mold: 200/40总菌数/霉菌：200/40Not required/不作规定Sedimental viable particle(4h)/沉降菌：100cfu/plate(90mm)Surface microbe/表面微生物：Total aerobic microbial count/mold: 50/10总菌数/霉菌：50/10 cfu/plate(55mm)2.3The monitoring data should be retaine

29、d保留监测数据The temperature and humidity should be monitored by hygrothermograph which installed in the rooms, and recorded in (QF03007). /温度和湿度采用各区域安装的温湿度计监测，并记录于温湿度记录表(QF03007)。The pressure difference should be monitored by differential manometer installed in the rooms and should be recorded in (QF0300

30、6). During the daily monitoring of pressure difference, the designated environment monitoring personnel should fully open the door according to the related procedure requirement to check and confirm the reading of the corresponding differential manometer return to zero, and then close the door to check the reading of pressure difference