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洁净室区环境监控SOP0510
Author
作者:
Date
日期:
赵春丽,QAVicePresidentAssistant/QA副总经理助理
Approvedby
批准人:
Date
日期:
李红坤,ProductionDept.AssociateDirector/生产部副主管
Approvedby
批准人:
Date
日期:
于立慧,QASiteVicePresident/QA厂区副总经理
Change
修改内容:
1.Theacceptancecriteriaofmoldwereaddedforthemicrobetest./增加了微生物测试合格标准中霉菌的要求。
2.Itwasaddedthatduringthedailymonitoringofpressuredifference,thedesignatedenvironmentmonitoringpersonnelshouldfullyopenthedooraccordingtotherelatedprocedurerequirementtocheckandconfirmthereadingofthecorrespondingdifferentialmanometerreturntozero,andthenclosethedoortocheckthereadingofpressuredifferenceandtoconfirmwhetherit’swithinthestandardrequirement./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.Itwasaddedthatcheckandconfirmthepipeforairpressuredifferentialconnectedwiththeairpressuremeterisingoodconditionandreplaceitifnecessaryduringinstallationofthepressuremeteraftereachtimeofcalibration./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:
Establishthegeneralenvironmentmonitorandcontrolprocedureforcleaningrooms/areasandregulatethemethodofmonitorandcontroltemperature,humidity,pressuredifference,airborneparticlesandairborneviableparticlestoensuretheymeetthecGMPrequirementoftheproductrunningintheroom/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:
Itappliesairmonitoringandcontrollingallthecontrolledareaforprocessing,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:
Cleanroom/area:
area/roominwhichtheconcentrationofairborneparticlesiscontrolled,andwhichisconstructedandusedinamannertominimizetheintroduction,generation,andretentionofparticlesinsidetheroom,andinwhichotherrelevantparameters,e.g.temperature,humidity,andpressure,arecontrolledasnecessary.
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。
Atresttest:
TestcarriedoutintheconditionthattheHVACsystemisinnormaloperationalstatement,andthecleanroom(area)isinnormalproduction,technicalequipmentisinstalledandtherearenooperatingpersonnelinthecleanroom(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。
Operationaltest:
Testcarriedoutintheconditionthatthecleanroom(area)isinnormalproduction.
动态测试:
洁净室(区)已处于正常生产状态下进行的测试。
RSM:
RegisteredStartingMaterial.StartingMaterialthatisincludedinthedrugregistrationdocuments(suchasDMF).
在药品注册文件(如DMF)中体现的起始原料。
API(ActivePharmaceuticalIngredient):
Anysubstanceormixtureofsubstancesintendedtobeusedinthemanufactureofadrug(medicinal)productandthat,whenusedintheproductionofadrug,becomesanactiveingredientofthedrugproduct.Suchsubstancesareintendedtofurnishpharmacologicalactivityorotherdirecteffectinthediagnosis,cure,mitigation,treatment,orpreventionofdiseaseortoaffectthestructureandfunctionofthebody.
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。
DrugSubstance:
Activepharmaceuticalingredient(API)intendedforuseasacomponentofasterileornonsteriledrugproduct.Drugsubstancescanbemanufacturedbychemicalsynthesis,fermentation,recombinantDNAorotherbiotechnologymethods,isolation/recoveryfromnaturalsourcesoranycombinationoftheseprocesses.
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造。
Applicableto
适用对象:
Site:
AllAsymchemsites
厂区:
所有凯莱英厂区
Dept.:
cGMPfacility,Highpotencyfacility,Formulationfacility,GMPKeyMaterialWarehouse,GMPProductWarehouse,EngineeringDept.
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
RelatedDocuments
相关文件和记录:
AttachmentAClassificationofaircleanness/
附件A空气洁净度等级
AttachmentBAirflowtestingmethodofCleanroom/area/
附件B洁净室/区风量检测方法
QF03006Pressuredifferencerecordingtable/压差记录表
QF03007Temperatureandhumidityrecordingtable/温湿度记录表
QF03036Airflowtestrecordingtable/风量检测记录表
Reference
Standards
参考标准:
GB50243-2002VentilationandairconditioningengineeringconstructionqualityinspectionspecificationsAppendixBCleanroomtest/通风与空调工程施工质量验收规范附录B洁净室测试
ISO14644Cleanroomsandassociatedcontrolledenvironments/洁净室及相关控制环境国际标准
ChineseGMPstandard(2010revise)/
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-019/《重大偏差调查》
EHS-053/《灾后恢复和重建SOP》
Procedure
程序:
Responsibility
执行人
Step
步骤
Action
执行内容
1
Classificationofcleanroom/area
洁净等级划分
Thecleanroom/areainAsymchemfacilityisestablishedreferencetoChineseGMPstandard(2010revise)andISO14644;therearetwoclassescleanroom/area,ClassDandISO9.ThecleanclassofClassDisequivalenttoISO8.Thecleannessrequirementandapplicationofcleanroom/areashowsinthefollowingtable.
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ISO14644的级别标准,本公司洁净室有D级和ISO9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
ClassD/
D级
ISO9
Applicableto
适用对象
∙Manufacturingofnon-steriledrugsubstance(API),GMPintermediate,Highpotencyproduct(intermediateandAPI),includingprocesssteps,primarypackagingandstorage/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。
∙ManufacturingofRSM/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
ClassD/
D级
ISO9
Applicableto
适用对象
∙StorageofGMPkeyrawmaterial/GMP主原料储存
Note:
Manufacturingofnon-steriledrugsubstanceforsterileproductsbasedonclientrequirementofappropriatesterilizationandmicrobetestingandmonitoring./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。
∙BackgroundenvironmentforClassDroom/area/D级洁
∙室/区的背景环境
Item
项目
ClassD/
D级
ISO9
Airborneparticles
(atresttest,(particles/m3))/
悬浮粒子(静态测试)
≥0.5μm:
3,520,000
≥5μm:
29,000
≥0.5μm:
35,200,000
≥5μm:
293,000
2
Monitoringmethodandfrequency
监测方式和监测频率
Designatedenvironmentmonitoringpersonnel/
指定环境
监测人员
2.1
Thefollowingitemsshouldbecontrolledandmonitoredtokeepitmeetsthecleanclassrequirement.
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
ClassD
ISO9
Airborneparticles
悬浮粒子
(particles/m3)
Twiceayear(at-resttestandoperationaltestintermeverysixmonth)
每年两次(每6个月一次,静态测试和动态测试交替进行)
In-housetestorcontractortest
公司内部
检测或
委托检测
Airflow
气流
Onceayear
每年一次
Onceayear
每年一次
Airchangerates
换气次数
Onceayear
每年一次
Onceayear
每年一次
Roomrelativepressure
相对压差
Onceaday
每天一次
Onceaday
每天一次
In-housemonitor/
公司内部
监测
Temperature
温度
Twiceaday
每天2次
Twiceaday
每天2次
RelativeHumidity
相对湿度
Twiceaday
每天2次
Twiceaday
每天2次
Item/
监测项
Frequency/频率
Comment
备注
ClassD
ISO9
Microbe
微生物
∙Airbornemicrobeandsedimentalviableparticle:
basedonriskassessmentandthefrequencyofopenoperationintheroom/area,quarterlytesttheprocessingareas/roomsforproduction,andsemi-annuallytestformaterialstoragewarehouses,/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。
∙Surfacemicrobe:
Basedonproductspec.andcharacteristicsandalsoclientrequirement,andwillusesamplingplanbasedonsizeofroomandriskassessment./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/A
Contractortest/
委托
检测
2.2
Theacceptancecriteriaisfollowing
标准要求如下:
Item
项目
ClassD/
D级
ISO9
Airborneparticles
悬浮粒子
(particles/m3)
At-resttest/
静态测试
≥0.5μm:
3,520,000
≥5μm:
29,000
At-resttest/
静态测试
≥0.5μm:
35,200,000
≥5μm:
293,000
Operationaltest:
Notrequired/动态测试:
不作规定
Airflow
气流
∙Velocity:
0.45±0.09m/s/风速:
0.45±0.09m/s
∙Volume:
ensure40m3/hfreshairforeachoneintherooms/风量:
室内每人新鲜空气量不应小于40m3/h
Airchangerates
换气次数
≥15times/h(次/h)
Roomrelativepressure/
相对压差
∙Nolessthan10Pabetweencleanroomandnon-classifiedarea/room./洁净区与非洁净区之间≥10Pa。
∙Nolessthan10Pabetweendifferentclean-classifiedrooms/areas./不同洁净级别洁净室(区)之间≥10Pa。
∙Appropriatepressuredifferenceshouldbemaintainedbetweentheadjacentroomsofthesamecleanclassificationbasedonfinalproductflowandriskofopenoperation/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
ClassD/
D级
ISO9
Temperature
温度
∙Processsteps,primarypackaging/工艺步骤和初包装:
22±5℃
∙Warehouseforstorage/储存库房:
20~25℃
18~26℃
RelativeHumidity
相对湿度
Productionroom/area/生产房间/区域:
45±15%
Materialstoragewarehouses/物料储存库房:
45±15%
45±15%
Microbe
微生物
∙Airbornemicrobe/浮游菌(cfu/m3):
Totalaerobicmicrobialcount/mold:
200/40
总菌数/霉菌:
200/40
Notrequired/不作规定
∙Sedimentalviableparticle(4h)/沉降菌:
100cfu/plate(φ90mm)
∙Surfacemicrobe/表面微生物:
Totalaerobicmicrobialcount/mold:
50/10
总菌数/霉菌:
50/10cfu/plate(φ55mm)
2.3
Themonitoringdatashouldberetained
保留监测数据
∙Thetemperatureandhumidityshouldbemonitoredbyhygrothermographwhichinstalledintherooms,andrecordedin(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)。
∙Thepressuredifferenceshouldbemonitoredbydifferentialmanometerinstalledintheroomsandshouldberecordedin(QF03006).Duringthedailymonitoringofpressuredifference,thedesignatedenvironmentmonitoringpersonnelshouldfullyopenthedooraccordingtotherelatedprocedurerequirementtocheckandconfirmthereadingofthecorrespondingdifferentialmanometerreturntozero,andthenclosethedoortocheckthereadingofpressuredifference