WHO-清洁验证新指南--WHO-TRS-1019-53

WHO在上个月发布新指南WHOTRS1019-53，英文全文303页，本文节选其中清洁验证部分，进行了翻译，供参考。Appendix3Cleaningvalidation清洁验证Thetextofthisappendixwaspreviouslypublishedas:本附录的文本以前以下列形式发表:■■Appendix3:Cleaningvalidation.In:WHOExpertCommitteeonSpecificationsforPharmaceuticalPreparationsfortiethreport.Geneva:WorldHealthOrganization;2006:Annex4(WHOTechnicalReportSeriesNo.937;附录3:清洁验证。在:世界卫生组织药物制剂规范专家委员会第四十次报告。日内瓦世界卫生组织;2006:附件4(世卫组织技术报告系列，第937号;=1).1.Principle原则1382.Scope范围1383.General概述1394.Cleaningvalidationprotocolsandreports清洁验证方案和报告1395.Personnel人员1426.Equipment设备1427.Detergents清洗剂1428.Microbiology微生物1439.Sampling取样14310.Analyticalmethods分析方法14511.Establishingacceptablelimits确定可接受标准1461.Principle原则1.1Theobxxxxjectivesofgoodmanufacturingpractices(GMP)includethepreventionofpossiblecontaminationandcross-contaminationofpharmaceuticalstartingmaterialsandproducts.药品生产质量管理规范(GMP)的目标包括防止可能的污染和药物原料和产品的交叉污染。1.2Pharmaceuticalproductscanbecontaminatedbyavarietyofsubstancessuchascontaminantsassociatedwithmicrobespreviousproducts(bothactivepharmaceuticalingredients[APIs]andexcipientresidues)residuesofcleaningagentsairbornematerialssuchasdustandparticulatematterlubricantsandancillarymaterialsuchasdisinfectantsanddecompositionresiduesfrom:药品可以被各种物质污染如污染物与微生物有关以前的产品(包括原料药(api)和赋形剂残留)残留的清洁剂空气传播的物料如灰尘和颗粒物。润滑剂和辅助材料如消毒剂、和残留降解产物:■■productresiduebreakdownoccasionedbyforexampletheuseofstrongacidsandalkalisduringthecleaningprocess;例如，在清洗过程中使用强酸和强碱会导致产品残渣分解■■breakdownproductsofthedetergentsacidsandalkalisthatmaybeusedaspartofthecleaningprocess.洗涤剂、酸和碱的分解产物，可作为清洗工艺的一部分。1.3Adequatecleaningproceduresplayanimportantroleinpreventingcontaminationandcross-contamination.Validationofcleaningmethodsprovidesdocumentedevidencethatanapprovedcleaningprocedurewillprovidecleanequipmentsuitableforitsintendeduse.适当的清洗程序对防止污染和交叉污染具有重要作用。清洗方法的验证提供文件证明，经批准的清洗程序将提供与其预期用途相适应的清洁设备。1.4Theobxxxxjectiveofcleaningvalidationistoprovethattheequipmentisconsistentlycleanedofproductdetergentandmicrobialresiduestoanacceptableleveltopreventpossiblecontaminationandcross-contamination.清洁验证的目的是证明设备对产品、洗涤剂和微生物残留物的清洗一致并达到可接受的水平，以防止可能的污染和交叉污染。1.5Cleaningvalidationisnotnecessarilyrequiredfornon-criticalcleaningsuchasthatwhichtakesplacebetweenbatchesofthesameproduct(ordifferentlotsofthesameintermediateinabulkprocess)oroffloorswallstheoutsideofvesselsandfollowingsomeintermediatesteps.清洁验证对于非关键性的清洗并不一定是必需的，例如批次相同的产品(或散装过程中相同中间体的不同批次)、地板、墙壁、容器外部以及以下一些中间步骤之间的清洗。1.6Cleaningvalidationshouldbeconsideredimportantinmultiproductfacilitiesandshouldbeperformedamongothersforequipmentsanitizationproceduresandgarmentlaundering.清洁验证应被认为在多产品设施中很重要，并应在设备、消毒程序和服装洗涤等方面进行验证。2.Scope范围2.1Theseguidelinesdescribethegeneralaspectsofcleaningvalidationexcludingspecializedcleaningorinactivationthatmayberequiredforexampleforremovalofviralormycoplasmalcontaminantsinthebiologicalmanufacturingindustry.这些指南描述了清洁验证的一般方面，不包括可能需要的特殊清洗或灭活，例如，在生物制造业中去除病毒或支原体污染物。2.2NormallycleaningvalidationwouldbeapplicableforcriticalcleaningsuchascleaningbetweenmanufacturingofoneproductandanotherofsurfacesthatcomeintocontactwithproductsdrugproductsandAPIs.一般情况下，清洁验证适用于关键的清洗，例如在生产一种产品与另一种产品，与产品、药品和原料药接触的表面之间的清洗。3.General概述3.1Thereshouldbewrittenstandardoperatingprocedures(SOPs)detailingthecleaningprocessforequipmentandapparatus.Thecleaningproceduresshouldbevalidated.应该有书面的标准操作规程(sop)，详细说明设备和仪器的清洗过程。清洗程序应经过验证。3.2Themanufacturershouldhaveacleaningpolicyandanappropriateprocedureforcleaningvalidationcovering:制造商应制定清洗策略和适当的清洁验证程序，包括:■■surfacesthatcomeintocontactwiththeproduct;与产品接触的表面;■■cleaningafterproductchangeover(whenonepharmaceuticalformulationisbeingchangedforanothercompletelydifferentformulation);产品转换后的清洗(当一种药物配方被另一种完全不同的配方替换时);■■betweenbatchesincampaigns(whenthesameformulaisbeingmanufacturedoveraperiodoftimeandondifferentdays);在批次之间的活动(当同一配方是在一段时间内，在不同的日期生产);■■bracketingproductsforcleaningvalidation.(Thisoftenariseswhereproductscontainsubstanceswithsimilarproperties[suchassolubility]orthesamesubstanceindifferentstrengths.Anacceptablestrategyistofirstmanufacturethemorediluteform[notnecessarilythelowestdose]andthenthemostconcentratedform.用于清洁验证的产品组。(这种情况经常发生在产品中含有具有类似性质(如溶解度)或具有不同强度的相同物质的地方。一种可接受的策略是首先制造含量较低的剂型(不一定是最低剂量)，然后是含量较高的形式。Therearesometimes“families”ofproductswhichdifferslightlyastoactivesorexcipients.);有时产品的“组”在活性物质或赋形剂方面略有不同。■■periodicevaluationandrevalidationofthenumberofbatchesmanufacturedbetweencleaningvalidations.定期评估和清洁再验证之间生产的批次数量。3.3.Atleastthreeconsecutiveapplicationsofthecleaningprocedureshouldbeperformedandshowntobesuccessfultoprovethatthemethodisvalidated.至少连续三次应用清洗程序，并证明是成功的，以证明该方法是有效的。4.CleaningvalidationprotocolsandreportsCleaningvalidationprotocols清洁验证方案和清洁验证报告。4.1Cleaningvalidationshouldbedescribedincleaningvalidationprotocolswhichshouldbeformallyapprovedforexamplebythequalitycontrolorqualityassuranceunit.清洁验证应在清洁验证方案中进行描述，该方案应得到正式批准，例如由质量控制或质量保证部门批准。4.2Inpreparingthecleaningvalidationprotocolthefollowingshouldbeconsidered:在制