论药品生产验证总计划(英文版)

PharmacyManufacturingUnitValidationMasterPlan(VPM).

GeneralNotes

AimsofQualificationandValidation

Anysignificantchangesto,premises,equipmentorprocesses,whichmayaffectthequalityofthefinalproduct,directlyorindirectly,shouldbequalifiedandvalidated.

ThekeyelementsofaqualificationandvalidationprogramshouldbeclearlydefinedanddocumentedinaValidationMasterPlan.Theprocessshouldestablishandprovidedocumentaryevidencethat:premises,supportingutilities,equipmentandprocesseshavebeendesignedinaccordancewiththerequirementsofGMP.ThisnormallyconstitutestheDesignQualificationor‘DQ’andincludesconfirmationthatthepremises,supportingutilitiesandequipmenthavebeenbuiltandinstalledincompliancewiththeirdesignspecifications(thisconstitutesInstallationQualificationor‘IQ’)andthattheyoperateinaccordancewiththeirdesignspecifications(thisconstitutesOperationalQualificationorOQ).

Aspecificprocesswillconsistentlyproduceaproductmeetingitspredeterminedspecificationsandqualityattributes(thisconstitutesProcessValidationorPV.ThetermPerformanceQualificationorPQmaybeusedalso).

Purpose

TheVMPisintendedtobea‘live’documentthatsupportsthedesignandconstructionofanyproductionfacility,itssubsequentoperation,maintenanceandchangestothefacilityforitslifespan.TheVMPshouldpresentanoverviewoftheentirevalidationoperation,itsorganisationalstructure,itscontentandplanning.ThecoreoftheVMPisthelist/inventoryofitemstobevalidatedandtheplanningschedule.

TheVMPshouldprovideyourorganisationwiththebasisforvalidationandqualitysystemactivitiesrequiredforcGMPcompliance.Thiswillenableanysterileornon-sterilemedicinalproductthatisproduced,processed,storedordistributed,bythemanufacturingunit,tobevalidatedunderthecontrolofanappropriatequalitysystem.

TheVMPshouldprovideacross-referencetootherdocuments,suchasSOP’s,validationprotocols,validationreports,anddesignplans.Arationalefortheinclusionorexclusionofvalidations,fromtheapproachadoptedshouldbeincluded.

VMPDocument

TheVMPtemplateisattachedforcompletionasappropriatethedocumentshouldbecross-referencedwithdesignspecifications,designplansandotherrelevantdocumentation.AppendicesshouldcontainalltherelevantdocumentationreferencedorstatedintheVMP.

CompanyLogo

CompanyName

VALIDATIONMASTERPLAN

DocumentReference:

ReferenceNumber

Revision:

DraftNumberorRevisionNumber

DateofIssue:

____/____/____

Page:

PAGE

2

of___

Approvedby:

Name:

Signature:

Date:

ProductionTeamLeader

QualityControlOfficer

SeniorEngineer

Compiledby

Title:

Name:

Signature:

Date:

ValidationEngineer

CONTENTS

TOC\o"1-3"

1.0 LISTOFABBREVIATIONS

5

2.0 DocumentRevisionHistory

6

3.0 ValidationSteeringCommittee

7

3.1 MembershipofValidationSteeringCommittee

7

3.2 Responsibilities

8

3.2.1 PharmacyProductionTeamLeader

8

3.2.2 PharmacySeniorProductionTechnician

8

3.2.3 TrustSeniorEngineer

8

3.2.4 PharmacyQualityControlOfficer

8

3.2.5 ValidationEngineer

8

4.0 Introduction

9

4.1 PurposesofVMP

9

4.2 OverviewofProject

9

4.3 ValidationPhilosophy

9

5.0 RegulatoryStandardsAndGuidelines

10

6.0 DescriptionofProductsandProcesses

11

6.1 Introduction

11

6.2 ProductGroups

11

6.3 Processes

11

6.4 ProductStorageandDistribution

11

7.0 PROJECTDESCRIPTION

12

7.1 SiteLocation

12

7.2 FacilityDesignandLayout.

12

7.3 ProductionSuites

12

7.3.1 Zone1,Non-SterileManufacturing

12

7.3.2 Zone2,PreparationofCytotoxicProductsandParentalNutritionProducts

12

8.0 EquipmentandservicestobeValidated

14

8.1 ImpactAssessment

14

8.2 RiskAssessment

14

8.3 ValidationMatrix

14

9.0 ValidationActivities

15

9.1 ValidationActivities

15

9.1.1 UserRequirementSpecification(URS)

15

9.1.2 TechnicalSpecification

15

9.1.3 ImpactAssessment

15

9.1.4 DesignReview/Qualification

15

9.1.5 FactoryAcceptanceTests

15

9.1.6 Commissioning

16

9.1.7 InstallationQualification

16

9.1.8 Calibration

16

9.1.9 OperationalQualification

17

9.1.10 StandardOperatingProcedures

17

9.1.11 PerformanceQualification

18

9.1.12 CombinedQualifications(I/OQ&O/PQ)

18

9.1.13 ProcessValidation(PV)

18

9.1.14 CleaningValidation

18

9.1.15 AnalyticalMethodandLaboratoryEquipmentValidation

19

9.1.16 ProductStorageandDistributionValidation

19

9.1.17 RelocatedEquipment

19

9.1.18 ComputerValidationTesting

20

9.1.19 ComputerOperationalQualification

错误！未定义书签。

9.2 ValidationReports

20

9.3 ValidationHistoryFile

20

10.0 CHANGECONTROL

21

10.1 VMPRevisions

21

10.2 ChangeControlInitiation

21

10.3 DefinitionofChange

21

10.4 ChangeControlProcedure

21

11.0 QUALITYMANAGEMENT

22

12.0 SCHEDULEOFSTANDARDOPERATINGPROCEDURES

23

13.0 PREVENTATIVEMAINTENANCE

24

14.0 SCHEDULEOFWORKPACKAGES

25

15.0 TRAINING

26

16.0 ResponsibilitiesandAPPROVALOFProtocolsandDOCUMENTATION

27

16.1 ProtocolResponsibility

27

16.2 ApprovalofProtocolsandReports

27

16.3 ApprovalOfValidationDocumentation

27

Appendices

Annex1 Cleaningvalidationmasterplan

Annex2 Analyticalmethodvalidationmasterplan

LISTOFABBREVIATIONS

AHU

AirHandlingUnit

NHS

NationalHealthService

BP

BritishPharmacopoeia

O&M

OperationandMaintenance

BS

BritishStandard

OQ

OperationalQualification

CFR

CodeofFederalRegulations

P&ID

PipingandInstrumentationDiagram

cGMP

CurrentGoodManufacturingPractice

PCA

PatientControlledAnalgesia

CIP

CleanInPlace

PFD

ProcessFlowDiagram

CIVA

CentralisedIntravenousAdditives

PID

ProportionalIntegralandDerivative

Comm.

Commissioning

plc

Programmablelogiccontroller

CPU

CentralProcessingUnit

PQ

PerformanceQualification

DC

DirectCurrent

PV

ProcessValidation

DCC

DesignChangeControl

QA

QualityAssurance

DQ

DesignQualification

QC

QualityControl

DR

DesignReview

QMS

QualityManagementSystem

EDR

EnhancedDesignReview

RA

RiskAssessment

EP

EuropeanPharmacopoeia

Rev.

Revision

EU

EuropeanUnion

SAT

SiteAcceptanceTest

FAT

FactoryAcceptanceTest

SIP

Sterilise/SanitiseInPlace

FDA

FoodandDrugAdministration

SOP

StandardOperatingProcedure

FDS

Functional;DesignStatement

SVA

SmallVolumeAmpoules

GA

GeneralArrangement

TPN

TotalParenteralNutrition

GAMP

GoodAutomatedManufacturingPractice

URS

UserRequirementStatement

GCP

GoodCleaningPractice

VCC

ValidationChangeControl

GEP

GoodEngineeringPractice

VMP

ValidationMasterPlan

GLP

GoodLaboratoryPractice

VSC

ValidationSteeringCommittee

HACCP

HazardAndCriticalControlPoint

VTF

ValidationTechnicalFile

HS&E

HealthSafetyAndEnvironment

WFI

WaterForInjection

HTM

HealthTechnicalMemorandum

HVAC

Heating,VentilationandAirConditioning

IA

ImpactAssessment

IQ

InstallationQualification

ISO

InternationalStandardsOrganisation

ISPE

InternationalSocietyofPharmaceuticalEngineers

LVF

LargeVolumeFluids

MCA

MedicinesControlAgency

DocumentRevisionHistory

Revision

Details

Date

Author

Draft1

Initialdraft

__/__/__

Draft2

__/__/__

Draft3

__/__/__

Revision00

Originalissue.

__/__/__

Revision01

__/__/__

ValidationSteeringCommittee

MembershipofValidationSteeringCommittee

ThisValidationMasterPlanhasbeencompiledbyaValidationSteeringCommittee(VSC)whowillalsomanageitsexecution.ThemembersoftheVSCarelistedbelowandbytheirsignaturesacknowledgetheirresponsibilitiestoensurethatallvalidationactivitiesarecarriedoutasdescribedinthisValidationMasterPlan(VMP)anditsannexes.

ItisrecommendedthatthemembersoftheVSCshouldinclude,butisnotlimitedtothefollowingareasofresponsibilityandexpertise:

PharmacyProductionTeamLeader

PharmacySeniorProductionTechnician

TrustSeniorEngineer

PharmacyQualityControlOfficer

cGMPConsultant

ValidationSpecialist

Additionalmembersco-optedontotheVSCshallalsosignbelowbeforeundertakinganyactivitiesassociatedwiththisVMP.

Name(Print)

Position/Company

Initial

Signature

Date

Responsibilities

WithrespecttotheactivitiesoutlinedinthisVMPanditsAnnexes,includingcleaning,manufacturingpracticesandanalyticalmethods,theresponsibilitiesofkeyVSCmembersareoutlinedbelow.Theirresponsibilitieswithrespecttotheoveralloperationareincludedwherethismayhaveanimpactuponvalidationactivities.

Approvalofneworamendeddocumentationshouldbeaccomplishedwiththeminimumofdelay,ideallywithin2workingdays,tofacilitatetheefficientoperationofthefacility

PharmacyProductionTeamLeader

Thepharmacyproductionteamleaderisresponsiblefor:

Ensuringthatappropriatelyqualifiedpersonnelareappointed.

EnsuringproductionprocessesareinaccordancewithcGMPrequirements.

Facilitatingvalidationactivities.

Trainingandmanagementofpersonnel.

Approvalofuserfunctionalaspectsofvalidationprotocols

Approvalofworkingproductiondocumentsforoverallcontent.

PharmacySeniorProductionTechnician

Thepharmacyoperationsrepresentativeisresponsiblefor

Completionofbatchrecords.

Operatingprocedures.

Trainingofpersonnel.

TrustSeniorEngineer

Ensuringthatsystems/equipmentareappropriatefortheirpurpose.

Maintenanceofsystems/equipment.

Maintenanceprocedures.

Calibrationpolicyandprocedures.

RevisionofO&Mmanualsforequipment/systems.

Approvalofvalidationprotocolsforcontentrelatingtoengineeringcontent.

PharmacyQualityControlOfficer

EnsuringappropriateQualityControl(QC)proceduresareinplace

Provisionandmaintenanceofauditabledocumentstoragesystems.

Approvalofvalidationprotocolsforqualityaspects.

ApprovalofallworkingQCandproductiondocuments

ValidationEngineer

Identifyandplanappropriatevalidationactivities.

Providevalidationtechnicalsupportandtraining.

Ensureappropriatevalidationproceduresareinplace.

Introduction

PurposesoftheVMP

ThepurposesoftheVMPareto:

IdentifythemembersoftheValidationSteeringCommittee.

IdentifyRegulatoryrequirements.

Identifyanddescribethefacility,systemsandequipmenttobevalidated.

Identifyanddescribeproductsandprocessestobevalidated.

Identifythevalidationactivitiesthatwillbeundertaken.

Identifythemethodsbywhichtheseactivitieswillbeundertaken.

Identifythedocumentationrequirementstosupporttheaboveactivities.

OverviewofProject

ThisVMPrelatestoanewfacility,tobeknownasthe_______________________.InlinewithcurrentGMPstandardsthenewpharmacywillprovideasepticallydispensedintravenousproductsandmanufacturedsterileandnon-sterileproductsto______________Hospitalpatients.

ValidationPhilosophy

TheVMPisintendedtobea‘live’documentthatinitiallysupportsthedesignandconstructionofthefacilityandsubsequentlytheoperation,maintenanceandchangeofthefacilityforitsentirelife.ItwillprovidethebasisforvalidationandqualitysystemactivitiesrequiredforcGMPcompliance.Thiswillenablethevalidatedproduction,processing,storageanddistributionofarangeofsterileandnon-sterilemedicinalproductsunderthecontrolofanappropriatequalitysystem.

TheVMPmayberevisedasappropriatetoincorporatechangesand/oradditionstothefacilityand/orproducts.

Usingcurrentpharmaceuticalindustryguidelines,thevalidationstepsandactivitieswillbedesignedtoaddressallcriticalproductattributesandprocessstepswhilstminimisingun-necessarywork.ThiswillbeachievedbyemployingtechniquessuchasImpactAssessmentandriskassessment,inordertofocusvalidationactivityontothosesystemscriticaltoproductquality.

Thevalidationprocesswillfollowthesebasicgroupheadings:

QualityPlan

DesignReviews

FAT/Commissioning

InstallationQualification

SAT/Operational/PerformanceQualification

ProcessValidation

CleaningValidation

AnalyticalMethodValidation

Thevalidationactivitieswillbeincorporatedintoprojectdesign,constructionprogramsandproductionschedules.Theobjectiveofthisistointegratesimilaractivities,e.g.SATwithOQ,andthusreduceduplicationoftestsandcheckstoaminimum.AppendixDillustratestherelationshipbetweenprojectandvalidationstages.

RegulatoryStandardsAndGuidelines

Thefollowingisalistofstandardsandguidelinesdeemedtobeappropriateforthisproject.Thislistisnotexhaustiveandfurtherregulationsandguidelineswillbeusedwhereappropriate.ThelistwillbereviewedandrevisedasnecessarywheneveranewrevisionoftheVMPisissued.

NewZealandCodeofGoodManufacturingPracticeforManufactureandDistributionofTherapeuticGood,Part1–ManufactureofPharmaceuticalProducts,1993.

NewZealandCodeofGoodManufacturingPracticeforManufactureandDistributionofTherapeuticGood,Part3–CompoundingandDispensing,1993.

NewZealandCodeofGoodManufacturingPracticeforManufactureandDistributionofTherapeuticGood,Part3,Annex1–CompoundingofSterilePharmaceuticalProducts,1995.

PIC/SGuidetoGoodManufacturingPracticeforMedicinalProducts,15thJan02

MCARulesandGuidanceforPharmaceuticalManufacturersandDistributors,2002.

AS/NZSISO14644.1:2002:Cleanroomsandassociatedcontrolledenvironments–Part1:Classificationandaircleanliness

AS/NZS14644.2:2002:Cleanroomsandassociatedcontrolledenvironments–Part2:SpecificationsfortestingandmonitoringtoprovecontinuedcompliancewithISO14644.1

AS/NZSISO14644.4:2002:Cleanroomsandassociatedcontrolledenvironments–Part4:Cleanroomsandassociatedcontrolledenvironments-Design,constructionandstart-up

ISOEN14644.5:2004,CleanroomsandAssociatedControlledEnvironments–Part5:CleanroomOperations.

ISO14644-7:2004:Cleanroomsandassociatedcontrolledenvironments-Part7:Separativedevices(cleanairhoods,gloveboxes,isolatorsandmini-environments)

AS/NZS4273(INT):1995A1:Guidelinesforthedesign,installationanduseofpharmaceuticalisolators.

PharmaceuticalIsolators,1stedition,2004.

ISPEBaselineGuideVolume3,SterileManufacturingFacilities

ISPEBaselineGuideVolume4,WaterandSteamSystems

ISPEBaselineGuideVolume5,CommissioningandQualification

BS5295EnvironmentalCleanlinessinEnclosedSpaces

EuropeanPharmacopeia

BritishPharmacopeia

TheQualityAssuranceofAsepticPreparationServices,3rdedition,2001.

GoodAutomatedManufacturingPractice.

GoodLaboratoryPractice.

DescriptionofProductsandProcesses

Introduction

Thepharmacyproducesandissuesalargenumberofproductstoin-patients,,out-patientsandothergrouphospitals/clinics.

ThisVMPappliestoallproductionprocessesinthepharmacy.

ProductGroups

Productswithsimilarcharacteristicsand/ormanufacturingprocesseshavebeenplacedintosevengroups.Ageneralprocessflowdiagram(PFD)hasbeengeneratedforeachgroup(foundinAnnexA).Wheresignificantdifferencesoccurwithinagroup,theseareidentifiedinsub-sectionswithinthePFDforthegroup.

Thesevenproductgroupsare:

Cytotoxics(dispensed,unlicensedmanufacture)

TPN(dispensed,unlicensed)

CIVA(dispensed,unlicensed)

Terminallysterilisedproducts(licensedmanufacture)

Non-SterileProducts(unlicensedmanufacture)

Repacking(dispensed)

Other(unlicensedmanufacture)

Pleaserefertoscheduleofproducts,productgroupdescriptionsandassociatedprocessflowchartslocatedinappendixA.

Whenevernewproductsaretobeprocessedbythepharmacy,theneachwillbeassessedforinclusionintoanexistinggroup.Wherethisisinappropriate,e.g.asignificantnewprocessisintroduced,thenanewgroupwillbeadded,withsupportingPFDandprocessdescriptions.

Processes

Foreachproductgroup,themanufacturingprocessesandthespecificequipmentutilisedwillbedescribedindetail.Specifically,thesewillincludeallprocessescriticaltoproductquality.Processesthatinvolve‘standard’operationofequipment,e.g.weighingofproductmaterials,maybesimplylistedandreferencedtoappropriateequipmentSOPs.

ProductStorageandDistribution

Generallyforcompoundedproducts,productstoragetimeisrelativelyshort,asmostproductsaremanufacturedtomeetprescriptionordersandinsomecaseshaveashortshelflife.Whenbatchproductionisemployed,batchsizeismanagedtomeetanticipatedshort-termdemandandhenceavoidtheneedforlong-termstorage.Batchproductswithaprolongedexpiry,rawmaterialsandrepackedproductswillbestoredinaquarantineareabeforereleaseforuse,whichwillbeadesignatedsiteinthecoldroomorstorageareathatisinaccessible.

Productswillbestoredwithinadedicatedstoragearea.Wherenecessary,productswillbestoredinrefrigeratorsoracoldroom.

ThereisapapersystemforInventorycontrol.

Productsaredeliveredbyavarietyofroutesdependantuponproductandintendeduse.Generallytheywillbedeliveredinsmalllots,carriedbyhand,trolley,etc.totheenduser.Returnablecoldboxeswillbeusedwhenacoldchaindeliveryisrequired.

PROJECTDESCRIPTION

Note:AlldrawingsreferencedinthissectionarelocatedinAppendixC.

SiteLocation

Thenewpharmacyislocatedonthesiteofthe__________________.Itspositionwithrespecttootherfacilitiesonthesamesiteisshownonlayoutdrawingno._____________.

FacilityDesignandLayout.

Thefacilityconsistsofa_________________.Pleaserefertodrawingno._____________.

Thefacilitycontainstheproductionarea.Thisisdividedinto2discretecleanroomproductionsuitestermedzones1,2and3accordingtotheHVACzoning.

Zone1_____________.

Pleaserefertodrawingno._____________.

Thereisawalk-onceilinglevelabovethecleanroomswithinwhichpipedservices,HVACductingandelectricalservicesarelocated.

TheplantroomwithinwhichequipmentsuchasAirHandlingUnits(AHUs),WaterforInjections(WFI)generation,storageandcirculationequipment,cleansteamgeneratorandcontrolpanelsissituatedin_____________.Pleaserefertodrawingno._____________.

ProductionSuites

Zone1,Non-SterileManufacturing

AllroomsclassifiedGMPgradeD.PleaserefertoscheduleofroomdatasheetslocatedinAppendixC.ServedbyHVACzone1.Pleaserefertodrawingno._____________.

Processesundertakeninthisareainclude:

Non-sterilemanufactureofcreams,ointments,suppositories,oralsuspensions,oralliquidsandcapsules.

Extemporaneouspreparationofcreams,ointmentsandoralsuspensions

PleaserefertoprocessflowdiagramslocatedinAppendixA.

Thezoneisdividedinto3discreteareasandaccessedbydedicatedpersonnelchangeairlocknumber_______.:

Hazardousnon-sterileproductmanufacture,includingDithranol/CoalTar,flammablesandcytotoxics.

Prep1,2and3.Non-sterileproductmanufacture(non-hazardous).

Equipmentandbottlewasharea.Passboxesprovideaccessformaterialstolocalstorageareaswithinpreparationareas.

Pleaserefertotypicalpersonnel,material,productandwasteflowdiagramslocatedinAppendixA.

Zone2,PreparationofCytotoxicandParentalNutritionProducts

RoomsclassifiedEUgradesB,CandDservedbyHVACzone2.Additionallythereisasmallequipmentstore.PleaserefertoscheduleofroomdatasheetslocatedinAppendixC,andtodrawingno._____________.

Processesundertakeninthisareainclude:

Asepticdispensingofparenteralnutritionproductsandasepticdispensingofotherparenteralitems.

Asepticdispensingofcytotoxicchemotherapy

Asepticmanufactureofcytotoxicchemotherapy

PleaserefertoprocessflowdiagramslocatedinAppendixA.

Thezoneisdividedinto4discreteareas:

GradeDcytotoxiccompoundingarea.Accessedbydedicatedpersonnelchangeairlocknumber_______.CompoundingofCytotoxicproductsingradeAisolator.

GradeDcytotoxicmaterialsdisinfectionandfinalcheckarea,access……etc..

GradeDcheckanddisinfectionarea,servinggradeBcompoundingroom.Personnelaccessvia……..Materialsaccessviacorridorandtrolleytransferairlock.

GradeBareaforcompoundingofTotalParenteralNutrition(TPN)productsingradeAlaminarflowcabinet.PersonnelaccessviacascadinggradeBchange.Materialsaccessviahatch.

Pleaserefertotypicalpersonnel,material,productandwasteflowdiagramslocatedinAppendixA.

EquipmentandservicestobeValidated

ImpactAssessment

Inordertosimplifythevalidationandminimiseunnecessaryqualificationactivities,anImpactAssessment(IA)exercisewillbecarriedout,followinganapprovedprocedure.Thiswillencompassallequipmentandservicesinstalledwithinthefacility.Itwilldefinethevalidationrequirementsforequipmentandservicesthatarefoundtobecriticaltoproductqualityandrisktopatient.

Itisexpectedthatequipmentandservicesthataredeemednon-criticalwillbeinstalled,operatedandmaintainedsubjecttoGoodEngineeringPractice(GEP).

DatafromtheIAshouldbeusedtoprovideinformationforuseinthequalificationprotocols,suchascriticalinstrumentlistingsandacceptancecriteria.

IAwillbeconsideredforanychangetoestablishedequipmentand/orservicesinordertohelpdefinevalidationorre-validationrequirements.

ValidationactivitiesappropriatetotheequipmentandservicesmaybeconsideredatIA.

ThelocationoftheIAresultswillberecordedandthedataenteredinavalidationmatrixattachedtothisVMPinappendixB.

RiskAssessment

AppropriateRiskAssessments(RAs)willbecarriedouttoidentifyandchallengeallinstallation,operation,cleaningandmaintenanceprocesses.

ProcessesthatareidentifiedascriticaltoproductqualityandrisktopatientwillbesubjecttoProcessValidation.

SomeprocessesmaybeidentifiedashazardouswithrespecttoHealth,SafetyandEnvironmental(HS&E)considerations.Insuchcases,appropriateHS&Eactivitieswillbecarriedout.Generallythisactivityisoutsidethescopeofthisdocument.Itisrecognised,however,thatsomehazardousprocesseswillinvolvevalidatableprocesses,itemsofvalidatableequipmentand/orservices.Whereitislogicaltodoso,thequalificationprotocolsmayincludeHS&Etests.Asimpleexampleofthisisthequalificationofoperationofemergencystops.

DatafromtheRAshouldbeusedtoprovideinformationforuseintheoperationandmaintenanceSOPs.ThesemustincludesufficientinformationtoensurethatHS&Erequirementsaresatisfied.

DatafromtheRAshouldbeusedtoprovideinformationforuseinthequalificationprotocols,suchascriticalinstrumentoperationallimitsandacceptancecriteria.

RAwillbecompletedforanychangetoestablishedprocesses.

ValidationMatrix

Acomprehensivelistofequipment,servicesandprocesseswillbegeneratedfromIAandRAresults.Appropriatevalidationactivitiesfrom,butnotlimitedto,thelistingsinsection

REF_Ref11150628\r

9.1

willbeenteredagainstallvalidatableentriestocreateamatrixofvalidationactivities.ThismatrixwillbeattachedtothisVMPinappendixBandupdatedasnecessarythroughthelife-cycleofthefacility.

ValidationActivities

ValidationactivitieswillbecarriedoutinaccordancewiththisValidationMasterPlanandthecompleteddocumentationwillbeindexedintheValidationHistoryFiles.

ValidationActivities

Allprospectiveandconcurrentvalidationactivitieswillbeperformedaccordingtopreviouslyagreedprotocols.Anyretrospectivevalidationactivitieswillcompriseofareviewandcollationofexistingdatatodemonstrateconformancetopredeterminedacceptancecriteria.Detailsofthespecifictestsandmethodologythatwillbeusedtodeterminevalidationcompliancewillbefoundinthevalidationprotocolsforeachitem.

Inmostcases,theprotocolsformajornewequipmentwillbeproducedandexecutedbytheequipmentsuppliers,withreviewofthedocumentationandwitnessingofthepracticalactivitiesbeingperformedbyRVIortheiragents.RVIwill,however,produce‘header’protocolsthatwillverifythatprotocolsproducedandexecutedbyothersconformtotherequirementsdefinedinthisVMP.

UserRequirementSpecification(URS)

Anapprovedstatementoftheusers'requirementsintermsoffunction,throughput,operatabilityandapplicablelocalstandardsmustbeobtainedforeachnewitem.

TechnicalSpecification

AnapproveddocumenttranslatingtheURSintoaspecificationdetailinghowtherequirementsaretobeachieved.TogetherwiththeURS,thiswillprovidetheobjectivesandacceptancecriteriaforthesubsequentvalidationprotocols.

ImpactAssessment

Thecriticalityofsystems,equipmentandcomponentswithrespecttoproductqualitywillbeassessedusingappropriatetoolssuchasImpactAssessment(asdescribedintheISPEBaselineGuide,CommissioningandQualification).

Appropriatelyqualifiedpersonnelwillconducttheassessments.Theresultswillbeformallyrecordedandapprovedandwillbeusedtoprovideinformationforthegenerationofappropriatevalidationprotocolsandqualificationtestswithinthevalidationprotocols.

Subsequentactivitiese.g.cGMPReviewwillfocusonthesystemsandequipmentdefinedascriticalandhavingadirectimpactonproductquality.

DesignReview/Qualification

Areviewofthedevelopeddesignswillbeperformedforcriticalorbespokeitemstoensure:

CompliancewiththeUser’sRequirement

ComplianceofdesigndetailswithcGMPrequirements

Practicalvalidationtestswillbepossible

ThefindingsoftheDesignReviewswillberecordedinwrittenreports,whichwillbeincludedinthevalidationreport,togetherwitharecordofanyfollow-upactions.

FactoryAcceptanceTests

Someitemsofneworrefurbishedequipmentmaybesubjecttoacceptancetestsatthesupplier'spremises.Thedatagainedmaybereferencedinsubsequentvalidationdocumentationprovidedthat:

Thesetestsarepre-approvedbytheVSC

WitnessedbytheVSCortheiragents

Criticalinstrumentsarecalibratedtoappropriatestandards

Theequipmentisnotdismantledfortransporttosite

Themanufacturercancertifythatnosubsequentchangeshavebeenmadetotheconstructionorcontrolsystems.SummaryreportsoftheFactor