固体车间清洁验证方案

-1-上海金冀商务咨询有限公司,ShanghaiJinjiBusinessConsultingCo.,Ltd文件编号：固体车间清洁验证方案CleaningvalidationMasterPlanforSolidDosageWorkshop立项部门：质量保证部InitiationDepartment:QualityAssuranceDepartment工艺验证小组负责人：Leaderofvalidationteem:方案制订日期：年月日Date:YearMonthDay第2页共41页目录ListofContent一.验证概述OVERVIEWOFVALIDATION二.验证组织机构及人员安排VALIDATIONORGANIZAGIONANDMEMBERS三.应用范围AREASOFAPPLICATION四.风险评估RISKEVALUATION五验证方案表格VALIDATIONMATRIX六清洁溶剂CLEANSINGAGENTS七.可接受标准的确定ACCEPTANCECRITERIA八.清洁验证取样CLEANINGVALIATIONANDSAMPLING九清洁验证的实施IMPLEMENTATIONOFCLEANINGVALIDATION十.偏差、变更DEVIATIONSANDCHANGES十一.再验证RE-VALIDATION第3页共41页一.验证概述OverviewofValidation1.验证目的根据GMP的要求，在口服固体制剂生产结束后，要对生产设备及操作间进行彻底清洁，以避免造成不同批号或不同品种产品之间的污染和交叉污染。根据各生产设备的《操作、清洁及维护保养》标准操作规程，进行风险分析，选出最坏情况产品。为了验证清洁方法的稳定性与可靠性，对所选的最坏产品进行三次清洁验证。每批产品生产结束后，对所有在生产中使用的生产设备及容器具进行清洁，清洁后取样检测化学残留及微生物残留，要求残留量低于设定的残留限度要求。AccordingtorequirementsofGMP,themanufacturingequipmentsandroomsmustbecompletelycleanedtoavoidcontaminationofdifferentbatchesofsameproductsorcross-contaminationofdifferentproductsaftermanufacturingoforalsoliddosage.TherearetwotypesofcleaningmethodbasedonSOPsofOperation/Cleaningandmaintenanceforindividualequipments:implementtheriskanalysisassessmenttochoosetheworstcaseproducts.Threeconsecutivecleaningvalidationwillbeconductedtovalidatethestabilityandreliabilityofcleaningmethod.Allequipmentsandutensilsusedinmanufacturingmustbecompletelycleanedonceeverybatchoftheworstcaseproductsarefinished,thensampletotestchemicalresidualandmicrobialresidual,therequirementisthelevelofresidualislessthanthelimitofresidual..二.验证组织机构及人员安排ValidationOrganizationandTeamMembers2.1制造部/ProductionDept.组织清洁验证方案及报告的起草；Preparethecleaningvalidationprotocol/report确定设备表面积、清洁方法、取样部位；Determinethesurfaceareaofequipments,cleaningmethodandsamplinglocations制定清洁操作规程；Establishcleaningprocedure按清洁操作规程清洁设备和容器具；Cleanequipmentsandutensilsaccordingtocleaningprocedure确保清洁记录填写完整；Makesurethecompletenessofcleaningrecords将完成的清洁验证文件提交给QA审查；SubmitthefinalizedcleaningdocumentationtoQAreview2.2质量保证部/QADept.QC审核清洁验证方案/报告；Reviewthecleaningvalidationprotocol/report制定清洁验证取样方法和检测方法；Establishsamplingmethodandanalyticalmethodofcleaningvalidation对清洁后设备、容器具进行取样和检测，报告检验结果；Sampleandtestcleanedequipmentsandutensils,thenreportthetestingresults.使用在校验有效期内的仪器设备进行检测。UsethoseinstrumentswithincalibrationexpireddateQA制定清洁验证计划及验证编号；EstablishcleaningvalidationplanandNo.负责组织审核清洁验证的方案/报告；Organizethereviewthecleaningvalidationprotocol/report组织清洁验证相关部门进行清洁验证方案的培训并记录；Organizethetrainingandrecordforcleaningvalidationprotocol负责验证实施过程的协调，保证验证项目实施进度；第4页共41页Coordinatetheactivitiesofcleaningvalidationtoensuretheperformance.验证实施中的监控检查；Supervisethevalidationactivities.保证经验证的参数符合预期的标准；Makesurevalidatedparametersmeetpre-determinedcriteria负责组织验证方案中改变控制、偏差处理的调查；Organizetheinvestigationforthechangecontrolanddeviationhandling.负责将完成的清洁验证文件归档。Archivethecompletedcleaningvalidationdocumentation质量保证部经理：QAManager批准清洁验证方案、验证报告。Approvethecleaningvalidationprotocolandreport2.3设备动力部/EngineeringDept.保证清洁验证过程中，所用到的仪器仪表在校验有效期内；Ensuretheinstrumentsandmetersinvolvedinthecleaningvalidationhavebeencalibratedandwithincalibrationduedate.保证验证过程中空调、纯化水、压缩空气、热水等的供应，确保清洁验证的实施。EnsurethenormalworkingorderandoperationofHVAC,purifiedwatersystem,compressedair,hotwaterforthecleaningvalidation.2.4清洁验证小组人员名单/TeamMemberList组长TeamLeader部门Dept.岗位Position姓名Name制造部ProductionDept.业务经理Supervisor小组成员TeamMember部门Dept.岗位Position姓名Name设备动力部EngineeringDept.业务经理Supervisor制造部ProductionDept.工艺质量员Technician制造部ProductionDept.生产协调员ProductionCoordinator制造部ProductionDept.工艺质量员ProductionCoordinator制造部ProductionDept.工段长Teamleader制造部ProductionDept.技术员Technician制造部ProductionDept.工段长Teamleader制造部ProductionDept.技术员Technician制造部ProductionDept.工段长Teamleader制造部ProductionDept.技术员Technician制造部ProductionDept.工段长Teamleader制造部ProductionDept.技术员Technician第5页共41页QCQC主管QCSupervisorQC理化1组组长Leaderofphysicochemicalteam1QC微生物组组长LeaderofMicrobialteamQC微生物检验员AnalyzerQAQA检查员QAinspectorQAQA检查员QAinspectorQAQA检查员QAinspectorQA验证管理员Validationadministrator第6页共41页三应用范围Areasofapplication本清洁验证主计划应用于固体车间所有产品。见产品列表Thevalidationmasterplanisappliedtoalltheproductsinthesolidworkshop.产品名称Productname主成分API规格SpecificationABCDEFGHI第7页共41页四.风险评估RiskEvaluation1.FMEA风险项目Item影响/导致结果Influence/Reslult风险级别RiskLevel预防措施PrecautionaryMeasures是否可以将风险最小化Iftheriskcanbeminimized风险接受(是/否)RiskAcceptance(Yes/No)操作人员对清洁方法不熟悉，清洁操作不规范Operatorsarenotfamiliarwithcleaningmethod;cleaningoperationsdon'tmeetstandard硝苯地平残留超标ResidueofNifedipineisoverspecifications高High培训相关清洁SOP培训；清洁后由生产主管和QA检查确认OperatorsshouldbetrainedforrelatedcleaningSOPs;productionsupervisorandQAshouldcheckaftercleaning是Yes是Yes取样方法及取样工具Samplingmethodsandtools取样方法和工具使用不正确将会影响最终结果Misuseofsamplingmethodsandtoolswillinfluencefinalresult.高High对取样人员进行相关培训，明确取样方法以及取样时间。Samplersshouldbetrainedforsamplingmethodsandtime.是Yes是Yes活性成份残留物检验方法不满足残留限度检测TestingmethodofAPI'sresiduecan'tmeettestofresiduelimit.不能得到准确的检测结果Inaccuratetestingresult高High在本验证实施前进行残留物限度检测方法验证。Performingvalidationoftestingmethodofresiduelimitbeforeperformingthiscleaningvalidation.是Yes是YesQA人员取样错