who验证指南版.docx

who验证指南版.docx

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who验证指南版

who验证指南2016年版

1.INTRODUCTION

简介

1.1Validationisanessentialpartofgoodpracticesincludinggoodmanufacturingpractices（GMP）（4）andgoodclinicalpractices（GCP）.Itisthereforeanelementofthepharmaceuticalqualitysystem.Validation,asaconcept,incorporatesqualificationandshouldbeappliedoverthelifecycleof,e.g.theapplicableproduct,process,system,equipmentorutility.

验证是包括GMP和GCP在内的良好规范的必要部分。

因此是制药质量体系的组成部分。

验证这个概念包括确认并且应该在产品、工艺、系统、设备或设施的整个生命周期中被使用。

1.2Theseguidelinescoverthegeneralprinciplesofvalidationandqualification.Inadditiontothemainpart,appendicesonvalidationandqualification（e.g.cleaning,computerandcomputerizedsystems,equipment,utilitiesandsystems,andanalyticalmethods）areincluded.

这个指南包括验证和确认的一般原则。

除了主体部分外，还包括确认和验证附件（如清洁、计算机和计算机化系统、设备、设施和系统以及分析方法）。

1.3Thefollowingprinciplesapply:

适用的原则如下:

theexecutionofvalidationshouldbeincompliancewithregulatoryexpectations;

验证的执行应该符合监管预期

quality,safetyandefficacymustbedesignedandbuiltintotheproduct;

质量、安全和效力应该被设计和构建到产品中

qualitycannotbeinspectedortestedintotheproduct;

质量不能通过检查或测试赋予产品

qualityriskmanagementprinciplesshouldbeappliedindeterminingtheneed,scopeandextentofvalidation;

应该应用质量风险管理规则来决定验证的需求、范围和程度

ongoingreviewshouldtakeplacetoensurethatthevalidatedstateismaintainedandopportunitiesforcontinuingimprovementareidentified.

应该进行持续的回顾来确保维持验证状态并识别持续改进的机会

1.4Theimplementationofvalidationworkrequiresconsiderableresourcessuchas:

验证工作的完成需要大量资源，例如

time:

generallyvalidationworkissubjecttorigoroustimeschedules;

时间：

一般验证工作需要有一个严密的时间表

financial:

validationoftenrequiresthetimeofspecializedpersonnelandexpensivetechnology.

资金：

验证经常需要专业人员和昂贵的技术

human:

validationrequiresthecollaborationofexpertsfromvariousdisciplines（e.g.amultidisciplinaryteam,comprisingqualityassurance,engineering,informationtechnology,manufacturingandotherdisciplines,asappropriate.）.

人员：

验证需要不同学科专家的协作（例如一个多学科小组，视情况可能包括QA、工程、信息技术、生产以及其他学科人员）

2.SCOPE

范围

2.1Theseguidelinesfocusmainlyontheoverallconceptofvalidationandarenotintendedtobeprescriptiveinspecificvalidationrequirements.Thisdocumentservesasgeneralguidanceonlyandtheprinciplesmaybeconsideredusefulinitsapplicationinthemanufactureandcontrolofstartingmaterialsandfinishedpharmaceuticalproducts（FPPs）,aswellasotherareas.Validationofspecificprocessesandsystems,forexample,insterileproductmanufacture,requiresmuchmoreconsiderationandadetailedapproachthatisbeyondthescopeofthisdocument.

这些指南主要关注验证的整体概念，无意规定具体的验证要求。

用作GMP检查官和生产商的基本指南，本文件仅作为一个一般指南，其原则在其应用于起始物料及制剂的生产和控制时会比较有用，也应用于其他领域。

特定工艺和产品的验证，例如无菌产品生产，需要考虑更多内容，和更详细的方法，不在本文件范围之内。

2.2Therearemanyfactorsaffectingthedifferenttypesofvalidationanditis,therefore,notintendedtodefineandaddressallaspectsrelatedtooneparticulartypeofvalidationhere.

有很多因素会对不同类型的验证产生影响，因此，这里不会对某个特定类型的验证相关的所有方面进行定义和说明。

2.3Thegeneraltextinthemainpartoftheseguidelinesmaybeapplicabletovalidationandqualificationofpremises,equipment,utilities,systems,processesandprocedures.

这些指南的主体部分的一般内容可能适用于设施、设备、公用设施和系统、工艺和程序的验证和确认。

3.GLOSSARY

术语

Thedefinitionsgivenbelowapplytothetermsusedintheseguidelines.Theymayhavedifferentmeaningsinothercontexts.

本指南使用的术语定义如下。

它们在其它环境中可能有不同的含义

calibration.Thesetofoperationsthatestablish,underspecifiedconditions,therelationshipbetweenvaluesindicatedbyaninstrumentorsystemformeasuring（forexample,weight,temperatureandpH）,recording,andcontrolling,orthevaluesrepresentedbyamaterialmeasure,andthecorrespondingknownvaluesofareferencestandard.Limitsforacceptanceoftheresultsofmeasuringshouldbeestablished.

校准：

changecontrol（includingchangemanagement）.Aformalsystembywhichqualifiedrepresentativesofappropriatedisciplinesreviewproposedoractual

工艺验证

prospectivevalidation.Validationcarriedoutduringthedevelopmentstageonthebasisofariskanalysisoftheproductionprocess,whichisbrokendownintoindividualsteps;thesearethenevaluatedonthebasisofpastexperiencetodeterminewhethertheymayleadtocriticalsituations.

前验证

qualification.Documentedevidencethatpremises,systemsorequipmentareabletoachievethepredeterminedspecificationsproperlyinstalled,and/orworkcorrectlyandleadtotheexpectedresults.Qualificationisoftenapart（theinitialstage）ofvalidation,buttheindividualqualificationstepsalonedonotconstituteprocessvalidation.

确认

revalidation.Repeatedvalidationofapreviouslyvalidatedsystem（orapartthereof）toensurecontinuedcompliancewithestablishedrequirements.

再验证：

对先前已验证的系统（或它的一部分）的重复验证来确保持续符合既定标准。

standardoperatingprocedure.Anauthorizedwrittenproceduregivinginstructionsforperformingoperationsnotnecessarilyspecifictoagivenproductormaterialbutofamoregeneralnature（e.g.equipmentoperation,maintenanceandcleaning;validation;cleaningofpremisesandenvironmentalcontrol;samplingandinspection）.Certainstandardoperatingproceduresmaybeusedtosupplementproduct-specificmasterbatchproductiondocumentation.

标准操作规程

validation.Actionofprovinganddocumentingthatanyprocess,procedureormethodactuallyandconsistentlyleadstotheexpectedresults.

验证

validationmasterplan.Thevalidationmasterplanisahigh-leveldocumentthatestablishesanumbrellavalidationplanfortheentireprojectandsummarizesthemanufacturer’soverallphilosophyandapproach,tobeusedforestablishingperformanceadequacy.Itprovidesinformationonthemanufacturer’svalidationworkprogrammeanddefinesdetailsofandtimescalesforthevalidationworktobeperformed,includingastatementoftheresponsibilitiesofthoseimplementingtheplan.

验证主计划

validationprotocol.Adocumentdescribingtheactivitiestobeperformedduringavalidation,includingtheacceptancecriteriafortheapprovalofaprocessorsystem–orapartthereof–forintendeduse.

验证方案

validationreport.Adocumentinwhichtherecords,resultsandevaluationofvalidationareassembledandsummarized.Itmayalsocontainproposalsfortheimprovementofprocessesand/orsystemsand/orequipment.

验证报告

verification.Theapplicationofmethods,procedures,testsandotherevaluations,inadditiontomonitoring,todeterminecompliancewithestablishedrequirementsandspecifications.

核实

worstcase.Aconditionorsetofconditionsencompassingtheupperandlowerprocessinglimitsforoperatingparametersandcircumstances,withinSOPs,whichposethegreatestchanceofproductorprocessfailurewhencomparedtoidealconditions.Suchconditionsdonotnecessarilyincludeproductorprocessfailure.

最差条件

4.RELATIONSHIPBETWEENVALIDATIONANDQUALIFICATION

验证与确认的关系

4.1Qualificationandvalidationareessentiallythesame.Thetermqualificationisnormallyusedforequipmentandutilities,andvalidationforsystemsandprocesses.Inthissense,qualificationcanbeseenaspartofvalidation.

确认和验证本质上是一样的。

确认通常用于设备和设施，而验证则用于系统和工艺。

在这层意义上，确认可以被看做是验证的一部分。

4.2Wheretheterm“validation”isusedinthedocument,thesameprinciplesmaybeapplicablefor“qualification

在文件中使用术语“验证”的规则同样适用于“确认”

5.VALIDATION

验证

Approachestovalidation

验证的方法

5.1Manufacturersshouldorganizeandplanvalidationinamannerthatwillensureproductquality,safetyandefficacythroughoutitslifecycle.

生产商应该组织和计划验证以保证产品在其生命周期内的质量、安全和有效。

5.2Thescopeandextentofqualificationandvalidationshouldbebasedonriskmanagementprinciples.

确认和验证的范围和程度应该基于风险管理规则。

5.3Statisticalcalculationsshouldbeapplied,whereappropriate,andprovidescientificevidencethattheprocess,systemorotherrelatedaspectisappropriatelyvalidated.

适当时，应该使用统计学计算并提供工艺、系统或其它相关方面有效的科学证据

5.4Qualificationandvalidationshouldbedoneinaccordancewithpredeterminedprotocols,andtheresultsappropriatelydocumented,e.g.inreports.

确认和验证应该按照预定的方案执行并且结果应被适当的记录，如在报告中。

5.5Thereshouldbeanappropriateandeffectivequalitysystemensuringtheorganizationandmanagementofvalidation.

应有适当的和有效的质量体系来保证验证的组织和管理。

5.6Seniormanagementshouldensurethattherearesufficientresourcestoperformvalidationinatimelymanner.Managementandpersonsresponsibleforqualityassuranceshouldbeactivelyinvolvedintheprocessandauthorizationofprotocolsandreports.

高级管理层应该确保充分的资源来及时地执行验证。

管理层和质量保证负责人应该积极参与方案和报告的批准活动中。

5.7Personnelwithappropriatequalificationandexperienceshouldberesponsibleforperformingvalidation.

有适当资质和经验的人员应该对验证的执行负责。

5.8Thereshouldbeaspecificprogrammeorscheduletosupportplanningandexecutionofvalidationactivities.

应有专门的计划或时间表来支持计划和执行验证活动。

5.9Validationshouldbeperformedinastructuredwayaccordingtothedocumentedprotocolsandprocedures.

验证应该按照文件化的方案和规程以一种有组织的方式执行。

5.10Qualificationandvalidationshouldbeperformed:

确认和验证应该被执行：

‒fornewpremises,equipment,utilitiesandsystems,andprocessesandprocedures;

新设施、设备、公用设施和系统，以及新的工艺和程序；

‒whenchangesaremade,dependingontheoutcomeofriskassessment;

当发生变更时，根据风险评估的结果；

‒wherenecessaryorindicatedbasedontheoutcomeofperiodicreview.

基于定期回顾的结果表明需要的

5.11Awrittenreportontheoutcomeofthevalidationshouldbeprepared.

应该对验证的结果准备一份书面报告。

5.12Thescopeandextentofvalidationshouldbebasedonknowledgeandexperience,andtheoutcomeofqualityriskmanagementprinciplesasdescribedintheWorldHealthOrganization（WHO）guidelinesonqualityriskmanagement.Wherenecessaryworst-casesituationsorspecificchallengetestsshouldbeconsideredforinclusioninthevalidation,forexample,stressloadandvolumeverificationincomputersyst