JMSZ-MOS-SP-110-A 环氧乙烷灭菌过程控制规范

1、环氧乙烷灭菌过程控制规范EthyleneOxideSterilizationProcessControlSpecification版权所有，注意保密JMSZ-MOS-SP-110RevA第1页共7页版本号VersionNo修改日期ModifiedDate修改内容描述DescriptionaboutmodifiedcontentA2020.3.16首次发布InitialReleased制定：Draft审核：Review批准：Approval签名Sign签名Sign签名Sign发放部门Distributiondepartment研发中心、质量法规、生产运营、物料管理R&D，Qualityregul

2、ation,Operationdepartment,Materialmanagementdepartment.1.0目的Purpose对环氧乙烷灭菌进行控制，保证文件的适用性和有效性。Controlofethyleneoxidesterilizationtoensurethesuitabilityandeffectivenessofthedocumentation.环氧乙烷灭菌过程控制规范EthyleneOxideSterilizationProcessControlSpecification版权所有，注意保密JMSZ-MOS-SP-110RevA第2页共7页2.0范围Scope适用于本公司环

3、氧乙烷灭菌产品控制。Suitableforthecontrolofourcompanysethyleneoxidesterilizationproducts3.0职责Responsibility3.1研发中心：负责提供产品材料所能够承受的灭菌方式，且满足设定的灭菌条件。R&D:Responsibleforprovidingthesterilizationmethodthattheproductmaterialscanwithstandandmeetthesetsterilizationconditions.3.2生产运营：负责准备灭菌的产品。Operationdepartment:Respon

4、sibleforpreparingproductsforsterilization3.3质量法规：负责灭菌供商的审核，灭菌验证；灭菌前、后产品指标的检测，审核灭菌公司提供灭菌报告；Qualityregulations:responsiblefortheauditofsterilizationsuppliers,sterilizationverification;testingofproductindicatorsbeforeandaftersterilization,andinspectionofsterilizationreportsprovidedbythecompany.3.4物料管理：

5、负责外包装后，产品放行前(灭菌前、后)的隔离，灭菌货物的运输、与灭菌公司的灭菌协议签订和沟通。Materialmanagement:Afterbeingresponsiblefortheouterpackaging,theproductisreleasedbeforetherelease(beforeandaftersterilization),thetransportationofthesterilizedgoods,andthesterilizationagreementwiththesterilizationcompany.4.0程序Process4.1定义definition4.1.1

6、灭菌批：在同一灭菌柜内，同一灭菌条件下，满足同灭菌要求的一定量的产品。Sterilizationbatch:acertainamountofproductsthatmeetthesterilizationrequirementsunderthesamesterilizationconditionsinthesamesterilizer.SAL=SterilityAssuranceLevel无菌保证水平，表示已灭菌物品的微生物存活的概率。Asepticassurancelevel,indicatingtheprobabilityofmicrobialsurvivalofsterilizedite

7、ms.BI=BiologicalIndicator生物指示物，对特定灭菌过程具有确定抗力的染菌测试系统。Biologicalindicator,abacterialtestsystemwithdefinedresistancetoaspecificsterilizationprocess.4.2灭菌供商选择及评价Sterilizationsupplierselectionandevaluation4.2.1对供货商的质量管理和生产能力评估(查看供商的资质、现场审核等方式)。Qualitymanagementandproductioncapacityassessmentforsuppliers(

8、checksupplierqualifications,on-siteaudits,etc.)环氧乙烷灭菌过程控制规范EthyleneOxideSterilizationProcessControlSpecification版权所有，注意保密JMSZ-MOS-SP-110RevA第3页共7页4.2.2对灭菌厂商评估的项目：Projectforevaluationofsterilizationmanufacturers确认灭菌设备是经过安装验证和运行验证。Confirmthatthesterilizationequipmentisverifiedbyinstallationandverified

9、byoperation确认灭菌操作员是经过专业培训并持有上岗证。Confirmthatthesterilizationoperatorisprofessionallytrainedandholdsacertificateofemployment.确认质量体系相关文件的建立。Confirmtheestablishmentofrelevantdocumentsofthequalitysystem.灭菌过程是经过确认，并能够提供符合要求的报告。Thesterilizationprocessshouldbeconfirmedandcanprovideareportthatmeetstherequire

10、ments当更换灭菌公司或者出现无菌不合格情况时，需要重新进行灭菌验证。Whenthesterilizationcompanyisreplacedorthesterilityisunqualified,thesterilizationverificationneedstoberepeated.验证前设定Pre-verificationsetting对需要灭菌产品，根据产品风险分析，规定产品的SAL。Productsthatrequiresterilization,accordingtoproductriskanalysis,specifytheSALoftheproduct.对灭菌产品做灭菌的

11、抗性对比。新产品与已确认产品灭菌做抗性对比。使用新产品的短周期与已确认产品进行产品生物负载(BI)评估，即生物指示物(BI)抗性对比。Comparisonofresistancetosterilizationofsterilizedproducts.Thenewproductiscomparedwiththeconfirmedsterilizationoftheproduct.Bioburden(BI)resistancecomparisonusingshort-termcyclesofnewproductsandconfirmedproductsforbioburden(BI).首次验证流程

12、Firstverificationprocess环氧乙烷灭菌过程控制规范EthyleneOxideSterilizationProcessControlSpecification版权所有，注意保密JMSZ-MOS-SP-110RevA第4页共7页短周期循环（确认BI）存活）温度、压力下限，时间一半以，下，加湿上或下限实施1次BI存活吗?NO确认培养条件、培养基性能、BI应设定BI能存活的时间（7天）yes半周期确认（时间：一半）温度、压力、加湿：全下限条件实施3次温度、压力下限、加湿上限实施1次结果设定：温度、压力、E0浓度的下限、湿度上下限值（参考全周期的结果）BI全部灭死吗?yesNO确认

13、有无培养问题确认气体有无渗透到BI（有无导管折痕）品温是否太低全周期确认（时间：上限）温度、压力、加湿上限实施3次产品性能评价、残留E0结果设定：温度、压力、上限值各参数确认、性能评价没问题吗？NOyes确认原因（特别是温度、湿度）（若必要应改变条件）结束：完成报告灭菌再验证Re-validation在设备符合性的前提下(即IQ、OQ完成)，进行以下确认：Onthepremiseofequipmentcompliance(ieIQ,OQcompleted),confirmthefollowing灭菌再验证进行短周期、半周期、整周期确认。Sterilizationandre-verificati

14、onforshortcycle,halfcycle,andfullcycleconfirmation.验证过程所使用的产品和装载的灭菌难度与日常灭菌所具备的灭菌难度相同。Thesterilizationprocessoftheproductsandloadsusedintheverificationprocessisthesameasthesterilizationdifficultyofdailysterilization.4.5.3明确说明载荷物品，灭菌验证PQ过程中选择的载荷物品须与日常灭菌产品密度一致。Definingtheloaditemclearly,theloaditemsele

15、ctedduringthesterilizationverificationPQprocessmustbeconsistentwiththedailysterilizationproductdensity.灭菌验证中明确装载模式：包装、装载的密度、装载示意图、装载最大量、包装材料尺寸、托盘尺寸。环氧乙烷灭菌过程控制规范EthyleneOxideSterilizationProcessControlSpecification版权所有，注意保密JMSZ-MOS-SP-110RevA第5页共7页Loadingmodeinsterilizationvalidation:packaging,loadin

16、gdensity,loadingschematic,maximumloading,packagingmaterialsize,traysize.BI放置图，BI应放置于产品最难灭菌位置或难度相当位置。BIplacement:BIshouldbeplacedinthemostdifficultlocationofsterilizationpositionordifficultyposition.至少每年进行一次灭菌再验证。Sterilizationverificationatleastonceayear灭菌再验证流程图常规灭菌控制Conventionalsterilizationcontrol灭

17、菌供应商根据灭菌确认形成的灭菌工艺参数和装载方式等，进行灭菌。Sterilizeaccordingtosterilizationprocessparametersandloadingmethodsconfirmedbysterilization.按照SOP进行日常灭菌装箱操作。灭菌装箱方式如有变动，由质量法规部人员进行评估对灭菌有效性的影响。DailysterilizationandpackingoperationsinaccordancewithSOP.Ifthereisachangeinthesterilizationandpackingmethod,theimpactoftheevalu

18、ationbythequalityandregulationsdepartmentontheeffectivenessofsterilization.采购应与灭菌供方形成灭菌委托协议，在协议中明确灭菌要求和质量责任。Procurementshouldformasterilizationentrustmentagreementwiththesterilizationsupplier,specifyingthesterilizationrequirementsandqualityresponsibilityintheagreement.生产部负责整理灭菌产品清单，并填写委外灭菌单，将灭菌产品运送或

19、快递至灭菌供方，灭菌供方根据灭菌协议进行灭菌。Theproductiondepartmentisresponsibleforsortingthelistofsterilizedproducts,andfillingoutthe“ExternalSterilizationOrder”,transportingnogrthdeelsitevreilriziedproductstothesterilizingsupplier,andthesterilizingsuppliersterilizesaccordingtothesterilizationprotocol.环氧乙烷灭菌过程控制规范Ethyl

20、eneOxideSterilizationProcessControlSpecification版权所有，注意保密JMSZ-MOS-SP-110RevA第6页共7页4.6.5灭菌供方完成灭菌过程和BI检测后返回本公司，同时出具环氧乙烷灭菌报告ThesterilizationsuppliercompletesthesterilizationprocessandsimultaneouslyissuestheEthyleneOxideSterilizationReport.4.6.6质量法规部负责对灭菌后的产品进行检验。Thequalityregulationdepartmentisresponsi

21、bleforinspectingthesterilizedproducts.重新验证Re-verification当灭菌设备或辅助系统有重大变更时需重新进行灭菌验证。比如设备内部结构、加热系统，给蒸系统，控制系统等。Sterilizationverificationisrequiredwhenthereisamajorchangeinthesterilizationequipmentorauxiliarysystem.Suchastheinternalstructureoftheequipment,theheatingsystem,thesteamingsystem,thecontrolsys

22、tem,etc.当发生以下改变，需要重新评估是否需要进行再验证Whenthefollowingchangesoccur,needtore-evaluatewhetherneedtore-verify产品包装材质、装载方式(包括内外包装)变化Productpackagingmaterials,loadingmethods(includinginternalandexternalpackaging)changes装载方式变化Loadingmethodchange生产设备变化Productionequipmentchange原材料供货商Rawmaterialsupplierchange生产工艺变化P

23、roductionprocesschange生产环境变化Productionenvironmentchange新产品增加(包括产品族建立、抗性评估)Newproductadditions(includingproductfamilyestablishment,resistanceassessment)生物负载变化(包括抗性评估)Bioburdenchanges(includingresistanceassessment)不合格品控制Nonconformingproductcontrol在灭菌过程(包括灭菌验证过程)和检测过程中发生不合格，依照不合格品控制程序执行。Nonconformingoccursduri