QA of Q8Q9Q10 CHENWord下载.docx

QA of Q8Q9Q10 CHENWord下载.docx

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ICH

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FoodandDrugAdministration食品药品管理局

CenterforDrugEvaluationandResearch（CDER）药品评审中心

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May2010年5月

TABLEOFCONTENTS

I.INTRODUCTION

（1）4

II.QUESTIONSANDANSWERS6

A.ForGeneralClarification（1.1）6

B.QualitybyDesign（QbD）Topics

（2）6

1.DesignSpace（2.1）6

2.Real-TimeReleaseTesting（2.2）9

3.ControlStrategy（2.3）11

C.PharmaceuticalQualitySystem（3）12

D.ImpactofNewICHQualityGuidanceonGMPInspectionPractices（4）14

E.KnowledgeManagement（5）15

F.SoftwareSolutions（6）17

GuidanceforIndustry1

工业指南Q8,Q9和Q10问答

ThisguidancerepresentstheFoodandDrugAdministration’s（FDA’s）currentthinkingonthistopic.ItdoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindFDAorthepublic.Youcanuseanalternativeapproachiftheapproachsatisfiestherequirementsoftheapplicablestatutesandregulations.Ifyouwanttodiscussanalternativeapproach,contacttheFDAstaffresponsibleforimplementingthisguidance.IfyoucannotidentifytheappropriateFDAstaff,calltheappropriatenumberlistedonthetitlepageofthisguidance.

I.INTRODUCTION

（1）概述

SincetheQ8,Q9,andQ10guidancesweremadefinal,experiencesimplementingtheguidancesintheICHregionshavegivenrisetorequestsforclarification.Thisquestionandanswer（Q&

A）documentisintendedtoclarifykeyissues.TheguidancereflectsthecurrentworkingprocedureoftheICHQualityImplementationWorkingGroup（Q-IWG）forimplementingtheQ8,Q9,andQ10guidances.

ThebenefitsofharmonizingtechnicalrequirementsacrosstheICHregionscanberealizedonlyifthevariousqualityICHguidancesareimplementedandinterpretedinaconsistentwayacrossthethreeregions.TheQ-IWGistaskedtodevelopQ&

Astofacilitateimplementationofexistingqualityguidance.

TheQ&

AsreferencethefollowingICHguidancesavailableontheInternetathttp:

//www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htmunderInternationalConferenceonHarmonisation—Quality:

Q8（R2）PharmaceuticalDevelopment（includestheQ8parentguidance（PartI）andtheannex（PartII）,whichprovidesfurtherclarificationoftheQ8parentguidanceanddescribestheprinciplesofqualitybydesign）

Q9QualityRiskManagement质量风险管理

Q10PharmaceuticalQualitySystems药品质量体系

FDA’sguidancedocuments,includingthisguidance,donotestablishlegallyenforceableresponsibilities.Instead,guidancesdescribetheAgency’scurrentthinkingonatopicandshouldbeviewedonlyasrecommendations,unlessspecificregulatoryorstatutoryrequirementsarecited.TheuseofthewordshouldinAgencyguidancesmeansthatsomethingissuggestedorrecommended,butnotrequired.

II.QUESTIONSANDANSWERS问答

A.ForGeneralClarification（1.1）一般问题

Q1:

Istheminimalapproachacceptedbyregulators?

A1:

Yes.TheminimalapproachasdefinedinQ8（R2）（sometimealsocalled“baseline”or“traditional”approach）istheexpectationthatistobeachievedforafullyacceptablesubmission.However,the“enhanced”approachasdescribedinICHQ8（R2）isencouraged（Ref.Q8（R2）Annex,appendix1）.（ApprovedJune2009）

Q2:

WhatisanappropriateapproachforprocessvalidationusingICHQ8,Q9,andQ10?

A2:

TheobjectivesofprocessvalidationareunchangedwhenusingICHQ8,Q9,andQ10.Themainobjectiveofprocessvalidationremainsthataprocessdesignyieldsaproductmeetingitspredefinedqualitycriteria.ICHQ8,Q9,andQ10provideastructuredwaytodefineproductcriticalqualityattributes,designspace,themanufacturingprocess,andthecontrolstrategy.Thisinformationcanbeusedtoidentifythetypeandfocusofstudiestobeperformedpriortoandoninitialcommercialproductionbatches.Asanalternativetothetraditionalprocessvalidation,continuousprocessverification（seedefinitioninICHQ8R

（2）glossary）canbeutilizedinprocessvalidationprotocolsfortheinitialcommercialproductionandformanufacturingprocesschangesforthecontinualimprovementthroughouttheremainderoftheproductlifecycle.（ApprovedOctober2009）

Q3:

HowcaninformationfromriskmanagementandcontinuousprocessverificationprovideforarobustcontinualimprovementapproachunderICHQ8,Q9andQ10?

A:

Liketheproductitself,processvalidationalsohasalifecycle（processdesign,processqualificationandongoingprocessverification）.Ariskassessmentconductedpriortoinitialcommercialvalidationbatchescanhighlighttheareaswhereparticularfocusanddatacollectioncoulddemonstratethedesiredhighlevelofassuranceofcommercialprocessrobustness.Continualmonitoring（e.g.,viacontinuousprocessverification）canfurtherdemonstratetheactuallevelofassuranceofprocessconsistencyandprovidethebasisforcontinualimprovementoftheproduct.QualityRiskManagementmethodologiesofICHQ9canbeappliedthroughouttheproductlifecycletomaintainastateofprocesscontrol.（ApprovedOctober2009）

B.QualitybyDesign（QbD）Topics

（2）

Isitalwaysnecessarytohaveadesignspace（DS）orreal-timerelease（RTR）testingtoimplementQbD?

UnderQualitybyDesign,establishingadesignspaceorusingreal-timereleasetestingisnotnecessarilyexpected（ICHQ8（R2））.（ApprovedApril2009）

1.DesignSpace（2.1）

Isitnecessarytostudymultivariateinteractionsofallparameterstodevelopadesignspace?

No,theapplicantshouldjustifythechoiceofmaterialattributesandparametersformultivariateexperimentationbasedonriskassessmentanddesiredoperationalflexibility.（ApprovedApril2009）

Canadesignspacebeapplicabletoscale-up?

Yes,whenappropriatelyjustified（foradditionaldetails,seeQ8（R2）AnnexsectionII.D.4（2.4.4））.Anexampleofascale-independentdesignspaceisprovidedintheEuropeanFederationofPharmaceuticalIndustriesandAssociations（EFPIA）MockP2document（EFPIAMockP2submissionon“Examplain”:

ChrisPotter,RafaelBeerbohm,AlastairCoupe,FritzErni,GerdFischer,StaffanFolestad,GordonMuirhead,StephanRoenninger,AlistairSwanson,AguidetoEFPIA’s“MockP.2”Document,Pharm.Tech.（Europe）,18,December2006,39-44）.

Thisexamplemaynotreflectthefullregulatoryrequirementsforascale-up.（ApprovedApril2009）

Canadesignspacebeapplicabletoasitechange?

A3:

Yes,itispossibletojustifyasitechangeusingasiteindependentdesignspacebasedonademonstratedunderstandingoftherobustnessoftheprocessandanindepthconsiderationofsitespecificfactors（e.g.,equipment,personnel,utilities,manufacturingenvironment,andequipment）.Thereareregionspecificregulatoryrequirementsassociatedwithsitechangesthatneedtobefollowed.（ApprovedApril2009）

Q4:

Canadesignspacebedevelopedforsingleand/ormultipleunitoperations?

A4:

Yes,itispossibletodevelopadesignspaceforsingleunitoperationsoracrossaseriesofunitoperations（seeQ8（R2）Annex,sectionII.D.3（2.4.3））.（ApprovedApril2009）

Q5Isitpossibletodevelopadesignspaceforexistingproducts?

A5:

Yes,itispossible.Manufacturingdataandprocessknowledgecanbeusedtosupportadesignspaceforexistingproducts.Relevantinformationshouldbeutilizedfrome.g.,commercialscalemanufacturing,processimprovement,correctiveandpreventiveaction（CAPA）,anddevelopmentdata.

Formanufacturingoperationsrunundernarrowoperationalrangesinfixedequipment,anexpandedregionofoperationandanunderstandingofmulti-parameterinteractionsmaynotbeachievablefromexistingmanufacturingdataaloneandadditionalstudiesmayprovidetheinformationtodevelopadesignspace.Sufficientknowledgeshouldbedemonstrated,andthedesignspaceshouldbesupportedexperimentallytoinvestigateinteractionsandestablishparameter/attributeranges.（ApprovedApril2009）

Q6:

Istherearegulatoryexpectationtodevelopadesignspaceforanexistingproduct?

A6:

No,developmentofdesignspaceforexistingproductsisnotnecessaryunlesstheapplicanthasaspecificneedanddesirestouseadesignspaceasameanstoachieveahigherdegreeofproductandprocessunderstanding.Thismayincreasemanufacturingflexibilityand/orrobustness.（ApprovedApril2009）

Q7:

Canadesignspacebeapplicabletoformulation?

A7:

Yes,itmaybepossibletodevelopformulation（notcomponentbutrathercomposition）designspaceconsistingoftherangesofexcipientamountanditsphysicochemicalproperties（e.g.,particlesizedistribution,substitutionde