欧盟清洁验证方案(带风险分析)

Subject/主题LovastatinTablets20mgCleaningValidationProtocol鲨鱼软骨片清洁验证方案文件编号：Tableofcontents目录1.Responsibility职责2.Purpose目的3.Frequency周期4.RelevantSOP’s相关的SOP’s5.Equipment设备6.TestMethod测试方法7.AcceptanceCriteria接受限度8.RiskAnalysis风险分析9.SamplingPlan抽样计划10.Actiontakenwhenout-of-limitresultfound对不符合接受限度的测试结果所采取的措施12.Revalidation再验证13.CleaningValidationExecutiveRecord清洁验证过程记录14.Conclusion结论Attachments附件Writtenby:制订者：Date:日期：Reviewedby:复核者：Date:日期：Approvedby:批准者：Date:日期：Approvedby:批准者：Date:日期：1.Responsibility职责QAisresponsibleforplanthecleaningvalidation.QA负责整个清洁验证的安排QCisresponsibleforsamplingandanalysis.QC负责抽样及测试ProductionDepartmentisresponsibleforperformingcleaningproductionequipment.生产部负责设备的清洁.2.Purpose目的ThepurposeofthiscleaningvalidationprotocolistodemonstratethatthecleaningprocedureusedtocleanJHZ-250Bhighshearmixer/granulator,three－dimensionalmixer，CT-C-2HotAirCirculatingDrier，JZF-400granulators&millKorschPH300-36TabletPress，BGD-150Dhigh-efficiencycoatingmachineandDPP-250BblisterpackagingmachinecaneffectivelyremoveresiduesoftheproductsmanufacturedinZS-650VortexOscillator/CompactSieve，JHZ-250Bhighshearmixer/granulator,three－dimensionalmixer，CT-C-2HotAirCirculatingDrier，JZF-400granulators&millKorschPH300-36TabletPress，BGD-150Dhigh-efficiencycoatingmachineandDPP-250Bblisterpackagingmachinetoapredeterminedlevelthatdoesnotraiseanysafetyconcerns.清洗验证方案的目的是证明JHZ-250B高效湿法制粒机、HLD-1000B型料斗式混合机清洁操作规程、CT-T-II型热风循环烘箱、JZF-400型整粒、粉碎机、KorschPH-300-36旋转式压片机、BGD-150D型高效包衣机和DPP-250B型多功能自动铝塑包装所使用的清洗程序能够有效地除去产品残留，达到预先确定的限度，从而达到对下批产品无影响。3.Frequency周期ThecleaningvalidationstudyisperformedafterthreeconsecutivemajorcleaningsofZS-650VortexOscillator/CompactSieve，JHZ-250Bhighshearmixer/granulator,three－dimensionalmixer，CT-C-2HotAirCirculatingDrier，JZF-400granulators&millKorschPH300-36TabletPress，BGD-150Dhigh-efficiencycoatingmachineandDPP-250BblisterpackagingmachineafterthemanufactureofLovastatinTablets.连续三批生产后，进行清洗验证研究。4.RelevantSOP’s相关的SOP’sSOP-PD-304-00CleaningprocedureforHLSG-300HighSpeedMixer/GranulatorHLSG-300型高效湿法混合制粒机清洁操作规程SOP-PD-304-00CleaningprocedureforLF120E-Bairpillow-dryGranulatorLF120E-B型沸腾干燥制粒机清洁操作规程SOP-PD-310-00CleaningprocedureforZP43HighSpeedrotarytabletpress高效ZP43旋转式压片机清洁操作规程SOP-PD-307-00CleaningprocedureforHLD-1000BHoppertypeofblenderHLD-1000B型料斗式混合机清洁操作规程SOP-PD-306-00CleaningprocedureforYK-160granulatorsYK-160整粒机清洁操作规程SOP-PD-311-00CleaningprocedureforBG-300Ehigh-efficiencycoatingmachineBG-300E型高效包衣机清洁操作规程SOP-PD-313-00CleaningprocedureforDPH-130、DPP-250BblisterpackagingmachineDPH-130、DPP-250型铝塑袍罩包装机清洁操作规程ESS-VD007Validationguideline–cleaning验证指南－清洁验证ESS-VD011Surfacesamplingforcleaningvalidation清洗验证设备表面取样ESS-VD014Selectionoftheworstcaseincleaningvalidation清洁验证中最坏情况的选择SOP-QC-1075检验操作规程ESS-GM066MicrobeTest微生物限度检测法5.Equipments设备5.1ListofEquipment设备清单ThelistofEquipmentusedinthemanufactureofLovastatinTablets:有关鲨鱼软骨片生产线的所有机器列出如下：1．HLSG-300highspeedmixer/granulatorHLSG-300高效湿法混合制粒机2.LF120E-Bairpillow-dryGranulatorLF120E-B沸腾干燥制粒机器3.ZP43TabletPressZP43TabletPressZP43旋转式压片机4.METALDETECTOR金属探测仪5.HLD-1000BHLD-1000BHoppertypeofblenderHLD-1000B型料斗式混合机6.YK-160granulatorsYK-160型整粒机7.DPH-130\DPP-250blisterpackagingmachineDPH-130、DPP-250型多功能自动铝塑包装机8.BG-300Ehigh-efficiencycoatingmachineBG-300E型高效包衣机No.序号EquipmentNo.设备编号EquipmentName设备名称ProductContactSurfaceArea与产品接触面积(m2)1HLSG-300highspeedmixer/granulatorHLSG-300高效湿法混合制粒机2.81LF120E-Bairpillow-dryGranulatorLF120E-B沸腾干燥制粒机器5.903ZP43TabletPressZP43旋转式压片机64METALDETECTOR金属探测仪0.35HLD-1000BHLD-1000BHoppertypeofblenderHLD-1000B型料斗式混合机5.256YK-160granulatorsYK-160型整粒机0.377DPH-130\DPP-250blisterpackagingmachineDPH-130、DPP-250型多功能自动铝塑包装机1.08BG-300Ehigh-efficiencycoatingmachineBG-300E型高效包衣机8.43TotalProductContactSurfaceArea(m2)与产品接触面积总和(m2)99.62Table1表1:5.2ValidationScope验证范围HLSG-300highshearmixer/granulatorHLSG-300高效湿法制粒机LF120E-Bairpillow-dryGranulatorLF120E-B沸腾干燥制粒机器ZP43TabletPressZP43旋转式压片机METALDETECTOR金属探测仪HLD-1000BgranulemixerHLD-1000B型料斗式混合机YK-160granulatorsYK-160型整粒机DPH-130、DPP-250blisterpackagingmachineDPH-130、DPP-250型多功能自动铝塑包装机BG-300Ehigh-efficiencycoatingmachineBG-300E型高效包衣机6.TestMethod测试方法Thecleaningvalidationstudiesarebasedontheswabbingtechniqueandrinsingsampling.Theselectedswabsshouldbecharacterizedfortheirsuitabilityandarecoverytestshouldbeperformedpriortothevalidationstudies.Thevalidationstudiesincludeswabbingofthemainsurfaceareaaswellasthehard-to-cleanlocations.Swabbingandringingiscarriedoutfortheactiveingredient.清洁验证研究用擦拭取样法和最终淋洗水取样。验证研究之前，选择的棉签的特性应适合并进行回收率研究。验证研究包括主要表面积和难清洁部位的擦拭。对活性成分擦拭取样和淋洗水取样。SamplingMethod抽样方法SwabSampling擦拭法Ringingsampling最终淋洗水取样法7.AcceptanceCriteria接受限度VisualInspection目测检查AcceptanceCriteria接受限度Thereisnovisibleresidueinequipmentsurfaceaftercleaning.设备在清洁后，无可见的物质残留在设备表面AcceptanceCriteriaofmicrobe微生物测试接受限度-Forswabsamples对擦拭样品：Microbes微生物含量:2CFU/cm2，即50CFU/25cm2-Forrinsingsamples/对冲淋样品：Microbes微生物含量:100CFU/mlAcceptanceCriteriaofassay化学测试接受限度ActiveIngredient(seeAttachment26)活性成分(见附件26)MC(mg/swab)=____0.0843_______(Active)Forrinsingsamples对冲淋样品：MC(mg/L)=