WHO_TRS970_annex2(制药用水-对照版)

©WorldHealthOrganizationWHOTechnicalReportSeries,No.970,2012Annex2附件2Page1of20Annex2附件2WHOgoodmanufacturingpractices:waterforpharmaceuticaluseWHOGMP：制药用水1.Introduction介绍1.1Scopeofthedocument文件范围1.2Backgroundtowaterrequirementsanduses水的要求和使用背景1.3Applicableguides适用的指南2.Generalprinciplesforpharmaceuticalwatersystems制药用水系统的一般原则3.Waterqualityspecifications水质量标准3.1General概述3.2Drinking-water饮用水3.3Bulkpurifiedwater散装纯化水3.4Bulkhighlypurifiedwater散装高纯水3.5Bulkwaterforinjections散装注射用水3.6Othergradesofwater其它类型水4.Applicationofspecifictypesofwatertoprocessesanddosageforms不同类型水在工艺和剂型中的应用5.Waterpurificationsystems水纯化系统5.1Generalconsiderations一般考虑5.2Productionofdrinking-water饮用水的制备5.3Productionofpurifiedwater纯化水的制备5.4Productionofhighlypurifiedwater高纯水的制备5.5Productionofwaterforinjection(s)注射用水的制备6.Waterstorageanddistributionsystems水存贮和分配系统6.1General概述6.2Materialsthatcomeintocontactwithsystemsforwaterforpharmaceuticaluse与制药用水系统接触的材质6.3Systemsanitizationandbioburdencontrol系统消毒和微生物控制6.4Storagevesselrequirements贮罐要求6.5Requirementsforwaterdistributionpipework水分配管道要求7.Operationalconsiderations运行时的考虑7.1Start-upandcommissioningofwatersystems水系统开机和运行7.2Qualification确认7.3Continuoussystemmonitoring对系统的持续监控7.4Maintenanceofwatersystems水系统维护7.5Systemreviews系统回顾8.Inspectionofwatersystems水系统检查Furtherreading扩展阅读©WorldHealthOrganizationWHOTechnicalReportSeries,No.970,2012Annex2附件2Page2of201.Introduction介绍1.1Scopeofthedocument文件范围1.1.1Theguidancecontainedinthisdocumentisintendedtoprovideinformationabouttheavailablespecificationsforwaterforpharmaceuticaluse(WPU),guidanceaboutwhichqualityofwatertouseforspecificapplications,suchasthemanufactureofactivepharmaceuticalingredients(APIs)anddosageforms,andtoprovideguidanceongoodmanufacturingpractices(GMP)regardingthedesign,installationandoperationofpharmaceuticalwatersystems.Althoughthefocusofthisdocumentisonwaterforpharmaceuticalapplications,theguidelinesmayalsoberelevanttootherindustrialorspecificuseswherethespecificationsandpracticescanbeapplied.本文件中包括的本指南目的在于提供以下信息，关于制药用水（WPU）的可获得的质量标准，哪种质量的水适用于特定用途，例如活性药用物质（API）生产和制剂生产，提供关于药用水系统设计、安装和运行GMP指南。尽管本文重点在于水在制药行业的应用，如果质量标准和规范适用的话，该指南也可能与其它行业或特定用途相关。Note:Thisdocumentdoesnotcoverwaterforadministrationtopatientsintheformulatedstateortheuseofsmallquantitiesofwaterinpharmaciestocompoundindividuallyprescribedmedicines.注：本文件未包括在配方状态下给病人摄入的水，和少量用于药房单独处方配制的水。1.1.2TheGMPguidanceforWPUcontainedinthisdocumentisintendedtobesupplementarytothegeneralGMPguidelinesforpharmaceuticalproductspublishedbyWHO(WHOExpertCommitteeonSpecificationsforPharmaceuticalPreparations.thirty-seventhreport.Geneva,WorldHealthOrganization,2003(WHOTechnicalReportSeries,No.908),Annex4).本文件中对WPU的GMP指南是对WHO出版的通用药物GMP指南（WHO专家委员会：制剂质量标准，第37号报告，日内瓦，WHO，2003（WHO技术报告系列第908号）附件4）的补充。1.1.3Thisdocumentreferstoavailablespecifications,suchasthepharmacopoeiasandindustryguidancefortheuse,production,storageanddistributionofwaterinbulkform.Inordertoavoidconfusionitdoesnotattempttoduplicatesuchmaterial.本文件引用了可以得到的质量标准，例如药典，和行业中对散装形式水的使用、制备、存贮和分配的指南。为避免混淆，这里没有复制这些内容。1.1.4Theguidanceprovidedinthisdocumentcanbeusedinwholeorinpartasappropriatetotheapplicationunderconsideration.在本文件中给出的指南可以，全部或部分用于认为适用的应用。1.1.5Wheresubtlepointsofdifferenceexistbetweenpharmacopoeialspecifications,themanufacturerwillbeexpectedtodecidewhichoptiontochooseinaccordancewiththerelatedmarketingauthorizationsubmittedtothenationalmedicinesregulatoryauthority.如果在不同药典质量标准间存在很小的差异，生产商应根据其将要提交上市许可的相关的市场的药监当局来决定其选择。1.2Backgroundtowaterrequirementsanduses水的要求和使用的背景1.2.1Wateristhemostwidelyusedsubstance,rawmaterialorstartingmaterialintheproduction,processingandformulationofpharmaceuticalproducts.Ithasuniquechemicalpropertiesduetoitspolarityandhydrogenbonds.Thismeansitisabletodissolve,absorb,adsorborsuspendmanydifferentcompounds.Theseincludecontaminantsthatmayrepresenthazardsinthemselvesorthatmaybeabletoreactwithintendedproductsubstances,resultinginhazardstohealth.水是药品生产、处理和配方中昀广泛使用的物质、原料或起始物料。由于其极性和氢键，它具有独一无二的化学特性。这表示它可能溶解、吸收、吸附或中止许多不同的化合物。这也包括可能会出现的对其自身产生危害的污染物，或可能与想要的产品物质发生反应，对健康产生危害。©WorldHealthOrganizationWHOTechnicalReportSeries,No.970,2012Annex2附件2Page3of201.2.2Controlofthequalityofwaterthroughouttheproduction,storageanddistributionprocesses,includingmicrobiologicalandchemicalquality,isamajorconcern.在制备、存贮和分析过程整个过程中，对水的质量的控制，包括微生物和化学质量，是主要的关注点。Unlikeotherproductandprocessingredients,waterisusuallydrawnfromasystemondemand,andisnotsubjecttotestingandbatchorlotreleasebeforeuse.Assuranceofqualitytomeettheon-demandexpectationis,therefore,essential.Additionally,certainmicrobiologicaltestsmayrequireperiodsofincubationand,therefore,theresultsarelikelytolagbehindthewateruse.不像其它产品和工艺成分，水一般根据需求从系统中抽出，并且不适用于在使用前经过检测和批放行。因此，保证其质量符合预期的要求是必需的。另外，由于某些微生物检测会需要一定的培养周期，因此，其结果可能会在水已经使用了才出来。1.2.3ControlofthemicrobiologicalqualityofWPUisahighpriority.Sometypesofmicroorganismmayproliferateinwatertreatmentcomponentsandinthestorageanddistributionsystems.Itiscrucialtominimizemicrobialcontaminationbyproperdesignofthesystem,periodicsanitizationandbytakingappropriatemeasur