Model Quality Assurance

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a model quality assurance

system for procurement

agencies

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a model quality assurancesystem or procurement

agencies

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World HealtH organization

United nations CHildrens FUnd

United nations development programme

United nations popUlation FUnd

World Bank

WHO/PSM/PAR/2007.3


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AcknowledgementsT w v bh Ax 6 h 40h R h WHO ExC Sf Ph P (WHO h R S

N. 937, Gv, W Hh Oz, 2006). WHO h Cb h kw h h R.

World Health Organization 2007

A h v. Pb h W Hh Oz b b WHO P, WHh Oz, 20 Av A, 1211 Gv 27, Swz (.: +41 22 791 3264; x: +41 22 7914857; -: bk@wh.). R WHO b whh b h b WHO P, h bv (x: +41 22 791 4806; -: @wh.).

T h h h b h x whv h h W Hh Oz h , , h, h b.

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A b hv b k b h W Hh Oz v h h b. Hwv, h bh b b wh w k, h x . T b h h wh h. I v h h W Hh Oz b b .

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Contents

Introduction.5

Glossary. .9

Module.I.General.requirements.or.procurement.agencies.15

Introduction.15

I.1 Physicalresources................................................................................................15

I.1.1 Premises..................................................................................................15

I.1.2 Equipment..............................................................................................16

I.1.3 Materialsandconsumables......................................................................17

I.1.4 Financialsystems.....................................................................................17

I.1.5 Humanresources.....................................................................................18

I.2 Documentationopoliciesandstandards............................................................19

I.2.1 Qualitymanual.......................................................................................20

I.2.2 Standardoperatingprocedures................................................................20

I.2.3 Changecontrolpolicy.............................................................................22

I.2.4 Codeoconduct......................................................................................22

I.2.5 Guidelinesonconictointerest.............................................................23 I.2.6 Listoprequaliedproductsandmanuacturers......................................23

I.2.7 Maintenanceorecords...........................................................................24

Module.II.Prequalifcation 25

Introduction. .. 25

II.1 Principlesorprequalication.............................................................................25

II.1.1WHOModelListoEssentialMedicines................................................26

II.2 Standardsorprequalication.............................................................................26

II.3 Keypersonsandresponsibilities..........................................................................26

II.3.1 Staresponsibleorprequalication........................................................26

II.3.2 Staresponsibleorevaluationoproductinormation...........................27

II.3.3 Staresponsibleorinspectionomanuacturingsites.............................27

II.4 Keystepsinprequalication...............................................................................28

II.4.1 Step1:solicitandreceiveexpressionsointerest......................................28

II.4.2 Step2:receiveproductinormation.........................................................32

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A model quality assurance system for procurement agencies

II.4.3 Step3:screenproductinormation..........................................................33

II.4.4 Step4:evaluateproductinormation.......................................................33

II.4.5 Step5:plan,prepareandperorminspections.........................................35

II.4.6 Step6:nalizeassessmentprocessandupdateprequalicationlist..........38

II.5 Requalicationandmonitoring..........................................................................40

II.6 Monitoringocomplaints...................................................................................40

II.7 Costrecovery......................................................................................................40

Module.III.Purchasing. 41

Introduction. .. 41

III.1Strategiesorhealthsystems................................................................................41

III.2Procurementmethods.........................................................................................42 III.2.1Restrictedtender.....................................................................................43

III.2.2Competitivenegotiation..........................................................................43

III.2.3Directprocurement.................................................................................43

III.2.4Opentender............................................................................................43

III.3Qualityassuranceinpurchasing..........................................................................43

III.4Keyactivitiesinpurchasing.................................................................................44

III.4.1Productselectionandspecication..........................................................44

III.4.2Productquantication.............................................................................44

III.4.3Selectionosuppliers...............................................................................45

III.4.4Adjudicationotenders...........................................................................45

III.5Organizationandresponsibilities........................................................................46

III.5.1Procurementagencystructure..................................................................46

III.5.2Responsibilities........................................................................................47

III.6Monitoringoperormanceoprequaliedmanuacturers..................................48

III.7Patents .........................................................................................................48

III.8Donations.........................................................................................................49

Module.IV.Receipt.and.storage.o.purchased.products 50

Introduction. .. 50

IV.1 Pre-shipmentqualitycontrol...............................................................................50

IV.2 Receiptostock..................................................................................................50

IV.3 Post-procurementqualitycontrol........................................................................51


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IV.3.1Sampling.................................................................................................51

IV.3.2Rejectedmaterials....................................................................................51

IV.4 Storageomaterialsandproducts........................................................................52

IV.4.1Sta.........................................................................................................52

IV.4.2Storageareas............................................................................................52

IV.4.3Storageconditions...................................................................................52

IV.4.4Labellingandcontainers..........................................................................53

IV.4.5Miscellaneousandhazardousmaterials....................................................54

IV.4.6Stockcontrol...........................................................................................54

IV.4.7Documentation:writteninstructionsandrecords....................................55

Module.V.Distribution. 56Introduction. .. 56

V.1 ransportconditions...........................................................................................56

V.2 Coldchain.........................................................................................................56

V.3 emperaturemonitoringandrecords..................................................................56

V.4 Deliveryorder.....................................................................................................56

V.5 Dispatchproceduresandpolicies........................................................................57

V.6 Dispatchcontainers............................................................................................57

V.7 Dispatchrecords.................................................................................................57

V.8 raceability.........................................................................................................57

V.9 Portoentry.......................................................................................................57

V.10Packagingoproductsandmaterials...................................................................57

Module.VI.Reassessment. 58

Introduction. .. 58

VI.1Re-evaluationomanuacturers...........................................................................58

VI.2Re-evaluationoproducts...................................................................................58

VI.3Monitoringocontracted-outservices.................................................................59

VI.3.1Storageanddistribution..........................................................................59

VI.3.2Qualitycontrollaboratories.....................................................................60

VI.3.3Contractresearchorganizations...............................................................60

Conclusion.. .. 60

Reerences. . .. 62

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Appendix1 Exampleoacodeoconduct.............................................................65

Appendix2 Exampleoaguidelineoncondentiality...........................................71

Appendix3 Exampleoaguidelineonconictointerest.....................................72

Appendix4 Exampleoastandardoperatingprocedure(SOP)

orwritinganSOP.............................................................................78

Appendix5 Exampleoaninvitationorexpressionointerest..............................83

Appendix6 Pharmaceuticalproductquestionnaire................................................88

Appendix7 Exampleoastandardoperatingprocedureorscreening andassessingproductinormation......................................................93

Appendix8 echnicalquestionnaireorpharmaceuticalmanuacturers...............106

Appendix9 Exampleoastandardoperatingprocedureorplanning oinspections...................................................................................114

Appendix10Exampleoastandardoperatingprocedureorpreparing oraninspection..............................................................................120

Appendix11Exampleoastandardoperatingprocedure orperorminganinspection............................................................125

Appendix12Exampleoachecklistorgoodmanuacturingpractices..................131

Appendix13Guidanceongoodmanuacturingpractices:inspectionreport.........133

Appendix14Goodstoragepractice.......................................................................134

Appendix15Goodtradeanddistributionpractices...............................................135

Appendix16Qualitysystemrecommendationsorpharmaceutical inspectorates.....................................................................................136


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Introduction

TeWorldHealthOrganization (WHO), theUnitedNationsChildrens Fund(UNICEF) and many other organizations are involved in the procurement opharmaceuticalproducts.Inparticular,thesupplyopharmaceuticalproductsused

in the treatmentohuman immunodeciencyvirus/acquired immunodeciencysyndrome(HIV/AIDS),malariaandtuberculosishasbecomeamajorconcernatboththeinternationalandcountrylevels.CommitmentsbytheEuropeanCommissionandG8countries, amongothers, oer the potential or signicant increases inunding or eorts to combat communicablediseases.Low-cost pharmaceuticalproductsoassuredqualityhavethegreatestpotentialormaximizingtheimpactotheseeorts.

The need or a model quality assurance system

Eortsto accelerate access topharmaceuticalproductsused in the treatment oHIV/AIDS through negotiation and generic competition have highlighted theimportanceoqualityassuranceorprocurementopharmaceuticalproductsanddiagnostics.Considerablesumsomoneyareinvestedinprocuringpharmaceuticalproductsromvariousmanuacturersindierentcountries.However,evaluationoproduct-specicdataandinormationonqualityisotenlacking,andinspectionsatmanuacturing sitesare not routinely perormedto a consistent standard. Atpresent,someorganizationsinvolvedinprocurementopharmaceuticalproductsdohavequalitysystemsorthedierentactivitiesinplace.However,thesesystemsvarygreatlybetweenorganizations.Someprocurementagenciesrequestmanuacturerstosubmitachecklistorquestionnairecontainingproductinormationorassessment.

In some cases, these checklists ail to address important aspects that should beevaluatedaspartoprequalication.Othersusedetailedquestionnairesorrequestproduct dossiers or evaluation. Someprocurement agencies contract inspectorstoperorminspectionsattheplaceomanuacture,buttheextentandqualityotheseinspectionsmayvaryaccordingtotheresourcesavailable.Moreover,mutualrecognitionandcoordinationosuchinspectionsisanexceptionratherthantherule.

Without a quality assurance system, organizations risk sourcing substandard,countereitorcontaminatedpharmaceuticalproducts,leadingtocomplaintsabout

productsandproductrecalls,wastageomoneyandserioushealthriskstopatients.Suchproblemsaectthecredibilityoprocurementagencies,causenanciallossesandputpatientssaetyindanger.

Background

Apreparatorystudycarriedoutbyateamoexpertsemphasizedthesubstantialdierencesbetweenprequalicationovaccinesandpharmaceuticals.Apilotprojecttostudytheeasibilityoprequaliyingmanuacturersoessentialpharmaceuticalproductsortreatingprioritydiseaseswasrecommended.TeaccumulatedexperienceoexpertsromUNICEF,theUnitedNationsPopulationFund(UNFPA),WHO

andtheWorldBankhasidentiedthenecessaryelementstoensureappropriateproceduresorprocurement.

Introduction


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WHOthereoreundertookaprojectwiththeabove-mentionedUnitedNationspartners, which was supported in principle by the World Bank. Te projectocusedontheprequalicationoproductsandmanuacturersoHIVandAIDS-relatedproducts,andthedratingoamodelqualityassurancesystem(hereaterreerredtoastheModel).TisModelisintendedtoassistorganizationspurchasing

pharmaceutical products, vaccines, or other health sector goods or which areotherwise involved in the prequalication, purchasing, storage and distributionosuchproducts,hereaterreerredtoasprocurementagencies,toprocuresae,eectivepharmaceuticalsosuitablequality.

Goal and objectives

Telong-termgoalotheserecommendationsisthedesignandimplementationoauniormandharmonizedsystemthatwillensureprocurementopharmaceuticalproductsodenedqualityorsupplytopatients,basedonamutuallyrecognizedprocess oprequalication o productsandmanuacturers bymeansoproductdossier evaluation and inspection o manuacturing sites. Such a process, asdenedintheGlossaryanddescribedinModuleII,willhereaterbereerredtoasprequalication.

Establishing, harmonizing and implementing a quality assurance system orprequalication,purchasing,storageanddistributionopharmaceuticalsisa taskoconsiderablemagnitude,whichshouldbeundertakeninstages.Teollowingobjectiveswereidentied:

creation o amodel qualityassurance system (MQAS)tobeadopted and

implementedbyprocurementagencies;

creationoguidelinestoharmonizetheevaluationodataandinormationonproductsaspartotheprequalicationprocedure;and

creationouniedstandardsorinspectionomanuacturersandsupplierstoassesscompliancewithgoodmanuacturingpractices(GMP).

Quality assurance in procurement

Qualityassuranceisawide-rangingconceptwhichcoversallmattersthatindividually

orcollectivelyinuencethequalityoaproduct.Itisthetotalityothearrangementsmadetoensurethatpharmaceuticalproductsareothequalityrequiredortheirintendeduse.Qualityassurancethereoreincorporatesseveralactorsanditisanintegralpartoallkeyactivitiesinprocurement.

Te implementation o a quality assurance system in procurement, includingsystemsorprequalication,storageanddistribution,mayaectcosts.However,thebenetsoensuringqualityoutweighthecostinvestmentbecausetheyreducethepossiblelossescausedbythepurchaseandsupplyosubstandardproducts.

Prequalicationoproductsandmanuacturers,purchasing,storageanddistribution

arecomplexprocessesthatmayinvolvemanyofces,procurementagencies,sections


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ordepartmentsandseveralstagesoadministration,nanceandtechnicaldecisions.Pharmaceuticalproductsarenotordinarycommoditiesotradeandrequirespecialattention.Supportromtheofcesresponsibleorqualityassuranceiscrucial.Teefciencyotheproceduresdependsingreatpartontheuseoaprovenmethodinaconsistentmanner.Teuseoastandardapproachwillensureconsistencyinall

activitiesinvolvedinprocurementopharmaceuticalproductsodenedacceptablequality.

TisModelocusesontheollowingourkeyactivitiesoprocurementagencies:

prequalicationopharmaceuticalproductsandmanuacturers;

purchaseopharmaceuticalproducts;

storageopharmaceuticalproducts;and

distributionopharmaceuticalproducts.Procurementagenciesareultimatelyresponsibleortheoutcomesoallourkeyactivities. In some cases, one or more o the activitiesmay be contracted out.Wherethisoccurs,awrittencontractwhichdescribestheresponsibilitiesobothpartiesshouldbeagreeduponbetweenthetwoparties.Tecontract-giverremainsresponsibleorensuringthatthecontract-acceptormeetsthenormsandstandardsreectedinthisModel.

Recommendations

Itisrecommendedthatprocurementagenciesinvolvedinanyothekeyactivitiesoprocurementdevelopandimplementtheirowninternalqualityassurancesystemsonthebasiso theModel,includingtheelementsdescribedandtechnicaldetailsspecied.Itisimportanttoensurethatthesystemisadaptedtoreecttheactivitiesoeach specicprocurementagency.Tesystem should cover all aspectso theagencysactivitiesandshouldbecomprehensiveenoughtoensurethatinterrelatedactivitieswhichimpactonthequalityopharmaceuticalproductsarelinked.

TisdocumentprovidesguidelinesorUnitedNationsprocurementagencies,buttheymayalsobeusedbyotherprocurementagenciestoestablishqualityassurancesystemsortheirownactivities.

Teseguidelinesaredesignedorprocurementopharmaceuticalproducts.Teymayalsobeapplicabletotheprocurementodiagnostickitsormedicaldevices.

Overview

Tis document is divided into six modules. Module I addresses the generalrequirements or the quality assurance system that should be in place at allprocurement agencies, irrespective o the number o key activities perormed.ModuleIIsetsoutrecommendationsthatprocurementagenciesshouldimplementwhen evaluating their product needs, assessing the products oered and themanuacturingandsupplyarrangementsprovidedbythemanuacturers.Module

Introduction


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IIIdescribesprinciplesopurchasingpharmaceuticalproducts.ModuleIVcontainsrecommendationsonhowtoreceiveandstorepurchasedproducts.InModuleV,gooddistributionpracticesaredescribedandModuleVIdealswithmonitoringandreassessmentoproductsandcontracted-outactivities.Tisdocumentalsoincludesdocumentation examples o elements o thisModel aswell as relevant existing

WHOguidelines.

Troughout this document, reerence will be made to existing WHO norms,standards, guidelines and texts. An eort has been made to avoid duplicationwhereverpossible.Whererelevant,reerenceismadetorelateddocuments.

TestandardtextManaging drug supply(1)providesacompleteanddetailedoverviewotechnicalaspectsopharmaceuticalsmanagement,includingallthekeyactivitiesoprocurement.


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Glossary

accountability

Teobligationtoaccountoronesconductandactions,usuallyto anindividualorgroup,butultimatelytothepublic.Bothindividualsandorganizationsmaybeaccountable.Tereissomeoverlapbetweenaccountabilityandtransparency(seebelow).

active pharmaceutical ingredient (API)

Asubstanceorcompoundintendedtobeusedinthemanuactureoapharmaceuticalproductasatherapeuticallyactivecompound(ingredient).

aordabilityTeextenttowhichpharmaceuticalproductsareavailabletothepeoplewhoneedthematapricetheycanpay.

authorized personAperson(amongkeypersonneloamanuacturingestablishment)responsibleorthereleaseobatchesonishedproductsorsale.Insomegoodmanuacturingpractice(GMP)guidesandlegaltexts,thetermqualiedpersonisusedtodescribeanalogousunctions.

bioequivalencewo pharmaceutical products are bioequivalent i they are pharmaceuticallyequivalentorpharmaceuticalalternativesandtheirbioavailabilities,intermsopeak(C

maxand

max)andtotalexposure(areaunderthecurve(AUC)),ateradministration

inthesamemolardoseunderthesameconditions,aresimilartosuchadegreethattheireectscanbeexpectedtobeessentiallythesame.

bioavailabilityTerateandextentatwhichtheactivepharmaceuticalingredientoractivemoietyisabsorbedromapharmaceuticaldosageormandbecomesavailableatthesite(s)oaction.

competitive tenderA procedure or procuring pharmaceutical products which puts a number osuppliersintocompetition.Purchasingisdoneonthebasisoquotationssubmitted

bythesuppliersinresponsetoapublicnotice.

drugAnysubstanceorpharmaceuticalproductorhumanorveterinaryusethatisintendedtomodiyorexplorephysiologicalsystemsorpathologicalstatesorthebenetotherecipient.Inthisdocument,thetermsdrug, medicineandpharmaceutical product(seebelow)areusedinterchangeably.

drug legislation

Telegalconditionsunderwhichpharmaceuticalactivitiesshouldbeorganized.

(Seealsolegislationbelow.)

Glossary


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drug regulatory authority

Anationalbodythatadministerstheullspectrumodrugregulatoryactivities,includingatleastallotheollowingunctionsinconormitywithnationaldruglegislation:

marketingauthorizationonewproductsandvariationsoexistingproducts;qualitycontrollaboratorytesting;

monitoringoadversedrugreactions;

provisionodruginormationandpromotionorationaldruguse;

good manuacturing practice(GMP)inspectionsandlicensingo manuacturers,wholesalersanddistributionchannels;

enorcementoperations;

monitoringodrugutilization.

eectiveness

Anexpressionothedegreetowhichactivitieshaveproducedtheeectsplanned.

eciency

Te relationship between the results o activities and the corresponding eortexpendedintermsomoney,resourcesandtime.

essential pharmaceutical products

Tosepharmaceuticalproductsthatsatisythehealthcareneedsothemajorityothepopulation.WHOsExpertCommitteeontheSelectionandUseoEssentialMedicinesupdatestheWHO Model List o Essential Medicinesattwo-yearintervals.Eachcountrymayusethismodeltogenerateitsownlistoessentialpharmaceuticalproducts.

generic products

Tetermgeneric producthassomewhatdierentmeaningsindierentjurisdictions.Teuseothistermisthereoreavoidedasaraspossible,andthetermmultisource

pharmaceutical product(seebelow)isusedinstead.Genericproductsmaybemarketedeither under the approved nonproprietary nameorunder a brand(proprietary)

name.Tey may bemarketed in dosage orms and/or strengths dierent romthoseotheinnovator products(seebelow).Wherethetermgeneric productisused,itmeansapharmaceuticalproduct,usuallyintendedtobeinterchangeablewiththeinnovatorproduct,whichisusuallymanuacturedwithoutalicenceromtheinnovator companyandmarketedaterexpiryo thepatent orotherexclusivityrights.TetermshouldnotbeconusedwithgenericnamesorAPIs.

generic substitution

Practiceosubstitutingaproduct,whethermarketedunderatradenameorgenericname,withanequivalentproduct,usuallyacheaperone,containingthesameactive

ingredient(s).


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good manuacturing practice (GMP)

Tatpartoqualityassurancewhichensuresthatproductsareconsistentlyproducedandcontrolledtothequalitystandardsappropriatetotheirintendeduseandasrequiredbythemarketingauthorization.

indicatorCriterionusedtomeasurechanges,directlyorindirectly,andtoassesstheextenttowhich the targetsor objectivesoa programmeorprojectarebeingattained.Indicatorsshouldmeetthecriteriao clarity,useulness,measurability,reliability,validity(seebelow)andacceptancebykeystakeholders.

innovator pharmaceutical product

Generally the pharmaceuticalproductwhichwas rst authorized ormarketing(normallyasapatentedproduct)onthebasisodocumentationoefcacy,saetyandqualityaccordingtorequirementsatthetimeotheauthorization.Whena

substancehasbeenavailableormanyyears,itmaynotbepossibletoidentiyaninnovatorpharmaceuticalproduct.

interchangeability

Aninterchangeablepharmaceuticalproductisonethatistherapeuticallyequivalenttoacomparator(reerence)product.

International Nonproprietary Name

Teshortenedscienticnamebasedontheactiveingredient.WHOisresponsibleorassigningINNstopharmaceuticalsubstances.

legislation

Terststageothelegislativeprocess,inwhichlawsarepassedbythelegislativebodyogovernmentwithregardtoasubjectmatter,e.g.controlopharmaceuticals.Lawsdenetheroles,rightsandobligationsoallpartiesinvolvedinthesubjectmatteringeneralterms(seealsoregulationsbelow).

licensing system

National legal provisions on who should manuacture, import or supplypharmaceuticalproducts,whatqualicationspeopleinthesupplyingagencyshouldhave,andwhoshoulddispenseandsellpharmaceuticalproducts.

manuacture (manuacturing)

Alloranyoperationsopurchaseomaterialsandproducts,production,qualitycontrol, release, storage and distribution o nished products and the relatedcontrols.

marketing authorization

Alegaldocumentissuedbythecompetentdrugregulatoryauthorityorthepurposeomarketingorreedistributionoaproductaterevaluationorsaety,efcacyandquality.Itmustsetout,interalia,thenameotheproduct,thepharmaceuticaldosage

orm,thequantitativeormula(includingexcipients)perunitdose(usingINNsornationalgenericnameswheretheyexist),theshel-lieandstorageconditions,and

Glossary


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packagingcharacteristics.Itspeciestheinormationonwhichauthorizationisbased(e.g.Teproduct(s)mustconormtoallthedetailsprovidedinyourapplicationand asmodied in subsequent correspondence.). It also contains the productinormationapprovedorhealthproessionalsandthepublic,thesalescategory,thenameandaddressotheholderotheauthorization,andtheperiodovalidity

otheauthorization.Onceaproducthasbeengivenmarketingauthorization,itisincludedonalistoauthorizedproductstheregisterandisotensaidtoberegisteredortohaveregistration.Marketauthorizationmayoccasionallyalsobereerredtoasalicenceorproductlicence.

medicine

Seedrug.

multisource (generic) pharmaceutical product

Pharmaceuticallyequivalentorpharmaceuticallyalternativeproductsthatmayor

maynotbetherapeuticallyequivalent.Multisourcepharmaceuticalproductsthataretherapeuticallyequivalentareinterchangeable.

national list o essential pharmaceutical products

Telistoessential pharmaceutical products(seeabove)thathasbeendened,adoptedandpublishedatcountrylevel.Itisnormallyusedbyallhealthacilities,includingthemainhospitals.

pharmaceutical product

Seedrug.

prequalicationTeactivitiesundertakenindeningaproductorserviceneed,seekingexpressionsointerest romenterprisesto supply theproductorservice,andexamining theproduct or service oered against the specication and the acility where theproductorservice ispreparedagainst common standards ogood manuacturing

practice(GMP).Teexaminationotheproductorserviceandotheacilitywhereitismanuacturedisperormedbytrainedandqualiedinspectorsagainstcommonstandards.Oncetheproductisapproved,andtheacilityisapprovedorthedeliveryo the speciedproduct or service,otherprocurementagenciesare inormedothedecision.Prequalicationisrequiredorallpharmaceuticalproductsregardless

otheircompositionandplaceomanuacture/registration,buttheamountandtypeoinormationrequestedromthesupplierorassessmentbytheprocurementagencymaydier.

procurement

Teprocessopurchasingorotherwiseacquiringanypharmaceuticalproduct,vaccine,ornutraceuticalsorhumanuse.Forthepurposeothisdocument,procurementmeans the pre-selection o productsandmanuacturers through a procedure oqualication, includingprequalication (see above) and continuous monitoringthereater,purchaseo theprequaliedproductsromprequaliedmanuacturers

(linkedtothespecicproduct)throughdenedpurchasingmechanisms,storageanddistribution.


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procurement agency

Anyorganizationpurchasingorotherwiseacquiringanypharmaceuticalproduct,vaccineornutraceuticalorhumanuse.Inthecontextotheseguidelinesitwillnormallybeanot-or-protorganization,anongovernmentalorganization(NGO)or a UnitedNations organization. A procurement agency in the context o this

document is dened as any organization purchasing pharmaceutical products,vaccines,orotherhealthsectorgoodsorotherwiseinvolvedintheirprequalication (seeabove),purchasing,storageanddistribution.

product inormation

In the context o this document, product inormation means inormation onpharmaceuticalproducts submittedbymanuacturersor suppliers in anyo theormats specied in the procurement agencys guidelines (including productdossiers,productquestionnairesorotherormats)toobtainprequalicationortheproducts.

qualication

Action oproving and documenting that any premises, systemsand equipmentare properly installed and/or work correctly and lead to the expected results.Qualication is oten apart (the initial stage) o validation, but the individualqualicationstepsalonedonotconstituteprocessvalidation.Inthecontextothisdocumentitistheworkdonetoprovethatthesupplysystemwilldeliverproductsothequalityrequiredandspeciedonaroutinebasis,meetingalltheapplicablequalityrequirements.

quality assurance

Qualityassuranceisawide-rangingconceptcoveringallmattersthatindividuallyorcollectivelyinuencethequalityoaproduct.Itisthetotalityothearrangementsmadewiththeobjectoensuringthatpharmaceuticalproductsareothequalityrequiredortheirintendeduse.

quality control

Qualitycontrolisconcernedwithsampling,specicationsandtesting,andwiththeprocurementagencysdocumentationandacceptance/rejectionprocedureswhichensurethatthenecessaryandrelevanttestsareactuallycarriedoutandthatstartingmaterials, intermediates and nished products are not accepted oruse, sale or

supplyuntiltheirqualityhasbeenjudgedtobesatisactory.

regulations

Tesecondstageothelegislativeprocess(therststagebeinglegislation,seeabove).Regulationsarespecicallydesignedtoprovidethelegalmachinerytoachievetheadministrativeandtechnicalgoalsolegislation.

reliability

Anexpressionothedegreetowhichameasurementperormedbydierentpeopleatdierenttimesandunderdierentcircumstancesproducesthesameresults(see

alsovalidity).

Glossary


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Module I

General requirements or procurement agencies

Introduction

Procurementagenciesotenhavetopurchaseandsupplypharmaceuticalproductsusing scarce resources. In many cases, product quality is compromised whenproducts areobtained romunqualiedsources.Procurementagencieswilldealwithvarioustypesosuppliersandcustomers,includingdrugregulatoryauthorities,manuacturers, quality control laboratories, contract manuacturers, contractlaboratories, traders, brokers, distributors and pharmacies. A quality assurancesystemwillassistinensuringthattransactionswiththesepartnersultimatelyresultinprocuringpharmaceuticalproductsothebestpossiblequality.

Tismoduleaddressesthegeneralrequirementsorsuchasystem,includingphysicalresourcessuchaspremises,equipmentandpersonnel,aswellasthedocumentedpolicies, standards and procedures required to ensure consistency inall the keyactivitiesoprocurement.Tegeneralrequirementsdescribedinthismodulearethereoreapplicabletoalltheactivitiescoveredinsubsequentmodules.

I.1 Physical resources

I.1.1 Premises

Oces

Teprocurementagencyshouldhavesufcientofcespacetoaccommodatethepersonnelrequiredandtheactivitiestobeperormed.

Storage

Teprocurementagencyshouldhavesufcientspaceorstorageandretentiono

commodities,includingproductdocumentation,productsamples,stock,reports,lesandotherrecordsrelatingtoallkeyactivitiesoprocurement.

Samplesandproductsshouldbestoredundersuitableconditionswhicharespecied,e.g.withregardtotemperature,humidityorprotectionromlight.DetailsostoragerequirementsaregiveninModuleIV.

Tere should be sufcient space or storage o equipment, stationery andmaterialsorproperdistribution.DetailsodistributionrequirementsaregiveninModuleV.

Module 1


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I.1.2 Equipment

Computers

Te use o computers can acilitate, but not replace, efcient procedures inpharmaceuticalprocurement.Whenimplementedappropriately,computerizationwillspeedupcomplextasks,increaseaccuracyandautomaterepetitivetasks.Stamustbetrainedadequatelyintheuseocomputerizedsystems.

Manyaspectsoprocurementaresuitableorcomputerization,includingplanningorequirements,budgetmanagement,nancialanalysis,preparationodocumentationandreportsandinventorycontrol.Hardcopies(printouts)shouldbeproducedasrequiredtoprovidedocumentedevidenceotheactivities.

Wherecomputersystemsarenotused,manualsystemsshouldprovidedocumentedevidenceotheactivitiesperormed.

Sotware

Tesotwareselectedshouldbesuitableortheintendeduse.Teprogrammesusedshouldbeabletoprovidetherequiredqualityandmanagementinormationreliablyandaccurately.Teyshouldbeuser-riendlyandstashouldbetrainedadequatelyintheiruse.Wherepossible,dierentprogrammesusedshouldbecompatiblesothatdatacanbetranserredbetweenthemwithouthavingtoberetyped.

Where inormation is exchanged between the procurement agency and themanuacturer(s)byelectronicmeans,appropriateprogrammesshouldbeinplace.

Suitable security systems should be in place to prevent unauthorized access orchanges to computer records and reports.Back-up systemsmust be inplacetopreventlossodata.Agood-qualityvirusprotectionprogrammeandrewallmustbeinstalled,congured,usedandupdatedregularlytopreventunauthorizedaccessandlossodata.

echnicalsupportshouldbeavailabletoensurethatsotwareandsecuritysystemsarekeptunctionalanduptodate.

Hardware

Tehardwareselectedwhichshouldbeabletohandletherequiredsotwareefciently.Tesystemshouldhavesufcientcapacityandmemoryortheintendeduse,aswellasadequateinputandoutputdevices,includinggoodqualityprinters.AccesstotheInternetandpossiblytoaninternalnetwork(LAN)shouldbeprovidedtoacilitateexchangeoinormation.

Amaintenanceandupgradingplanmustbeinplacetoensurethatthesystemremainsunctional.


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Telecommunications

Tere should be access to telephone and acsimile acilities to ensure instantcommunication. I at allpossible,electronicmailing (e-mail) systemsshouldbeavailable.

Furniture

Suitable ofce urniture should be provided, including desks, chairs, shelves,cupboards,lingcabinetsandotheritemsasrequired.

Oce equipment

Ofce equipment including copyingmachines, staplers and punches should beprovided.

I.1.3 Materials and consumables

Stationery and consumables

Teprocurementagencyshouldprovidestationerytoenablestatoperormtherelevanttasks,includingpaper,letterheads,businesscardsandpre-printedormsasrequired.Computerconsumablestobeprovidedincluderemovablestoragedevices(oppydisks,CDsand/orashmemorysticks),printercartridges,printingpaper,aswellasanyreplacementpartsnotcoveredbyamaintenancecontract.

Vehicles and transport

Ofcialtransportorreimbursementotransportcostsincurredshouldbeprovidedortripstomeetings,visits,inspectionsandperormanceootherofcialduties.

Incaseswheretheprocurementagencyisresponsibleorlocaltransportationanddistributionoproducts,appropriatetransportshouldbeprovidedtoensurethatthequalityotheproductsismaintained.

I.1.4 Financial systems

Teprocurementagencyshouldbeabletoeectnationalandinternationalnancial

transactionsasrequired.Fundsmustbeavailabletoensurecontinuedoperations,whetherornotcostrecoverymechanismsorkeyactivities,e.g.prequalication,areinplace.

Adequatebankingacilitiesmustbeavailable.Signatoriesobankaccountsshouldbeappointedtoensurecontrolononehand,andcontinuityooperationsduringtheabsenceokeypersonnelontheotherhand.

An accounting system should be in place. Regular nancial audits should beperormed.

Itheprocurementagencyispartoalargerorganization,itshouldhavesufcientautonomyand/orsufcientlygoodcommunicationwiththemotherorganizations

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nancialdepartmenttoenableittoconductallitsnancialtransactionswithoutdelay.

I.1.5 Human resources

Personnel

Tere should be a sufcient number o appropriately trained, educated andexperiencedpersonneltoperormthekeyactivities.Tenumberomembersostarequiredinthedepartmentresponsibleorthekeyactivitieswilldependonthevolumeandvalueoproductssourcedandtobesupplied.Sufcientsupportstaorsecretarial,organizationalandaccountingdutiesaswellaslegalsupportshouldalsobeavailable.

Keypersonnelshouldincludethoseresponsibleorprequalication,purchasing,storageanddistribution.Tepersonresponsibleorprequalicationcouldalsobe

responsibleorqualityassurance.Nationallegislationshouldbecompliedwith,e.g.requirementsoraresponsiblepersonorpurchasing,storageanddistributionopharmaceuticalproducts.

Tepersonresponsibleorprequalicationandthepersonresponsibleorpurchasingshouldbeindependentooneanother.Oneshouldnotreporttotheother.

TeresponsibilitiesothestainchargeothedierentkeyactivitiesaredescribedinModulesIItoV.

Qualications and experience

Personnel responsible or prequalication, purchasing, storage and distributionshouldhavesufcientqualications,knowledgeandexperienceotheirrespectiveelds(seeModulesIItoV).

Code o conduct

Allstamembersshouldcomplywithacodeoconductwhichshouldguidealltheirproessional activities.Moredetail oncodes oconduct isgivenin sectionI.2.4.AnexampleoacodeoconductisshowninAppendix1.

Condentiality

It is essential that all inormation obtained by any person working or theprocurementagencyistreatedascondential.Mostotheinormationobtainedromcompaniesandmanuacturersisproduct-specic,maybepatentedandwillbecommerciallysensitive.Teevaluatorsandinspectorsmusttreatallinormationsubmittedandobservedduringtheassessmentoproductdossiersandinspectionsatmanuacturing sites, and otherwise inconnectionwith the discharge o theirresponsibilitiesinregardotheabove-mentionedproject,asstrictlycondentialandproprietarytothepartycollaboratingwiththeprocurementagency.

Condentialityagreementsshouldbesignedbyassessorsandinspectors.Anexample


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osuchanagreementisattachedinAppendix2.AdditionalinormationmaybeoundinAppendix3(exampleoaguidelineonconictointerest).

Confict o interest

Beore undertaking any work, assessors and inspectors (including contractedpersonnel)shouldsignadeclarationointerest.I,basedontheirdeclarationointerest,itisdeemedappropriateorthemtoundertaketheworkspecied,theyagreetocarryouttheirunctionsexclusivelyortheagency.Teyshouldconrmthattheinormationdisclosedbytheminthedeclarationointerestiscorrect,thatnosituationoreal,potentialorapparentconictointerestisknowntothemandthattheyhavenonancialorotherinterestin,and/orrelationshipwithapartywhich:

mayhavevestedcommercialinterestinobtainingaccesstoanycondentialinormation disclosed to them in the course o the evaluation activities

describedinthedeclaration;and/or

mayhaveavestedinterestintheoutcomeotheevaluationactivitiesincluding,but not limited to, parties such as themanuacturerswhoseproductsaresubjecttoevaluationormanuacturersocompetingproducts.

Personnel should undertake to advise the procurementagency promptlyo anychangeintheabovecircumstances,orinstanceianissuearisesleadingtoaconictointerestduringthecourseotheirworkortheprocurementagency.

Job descriptions

Tereshouldbewrittenjobdescriptions,withdenitionsoresponsibilities,orallpersonnel.

Organizational structure

Teprocurementagencyshouldhaveanorganizationchartindicatingthepositions,namesoresponsiblepersonsandreportinglines.

Teorganization chart should reect the responsibilities and reporting lines inaccordancewiththejobdescriptions.

I.2 Documentation o policies and standards

Documentationisacriticalpartoaqualityassurancesystem.Teprocurementagencyshouldhaveacomprehensivedocumentationinrastructure,whichshouldincludepolicies,guidelines, norms, standards,manuals,procedures, records andrelateddocuments.

Allactivitiesoeachsectionordepartmentshouldbeperormedanddocumentedinastandardizedmanner,ollowingapprovedwrittenprocedures.

Te main elements o the documentation system o this Model are describedbelow.

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I.2.1 Quality manual

Teprocurementagency should have a qualitymanual.Tepurpose o suchamanualistodocumentthequalitypolicyasdenedbymanagementinrelationtothevariousactivitiesundertakenbytheprocurementagency.Tereshouldbepolicy

statementsandaqualitypolicyintermsotheagencysactivitiesandobjectives,aswell asdocuments describing the policy o each section ordepartment withregardtoallactivitiesinprequalicationandsubsequentpurchasing,storageanddistribution.

Oncethisqualitypolicyisdened,itshouldbeimplemented,maintained,reviewedandamendedasnecessaryatregularintervalsbytheprocurementagency.

I.2.2 Standard operating procedures

Teprocurementagencyshouldhavewritten,clearanddetailedstandardoperating

procedures(SOPs)oralltheactivitiestobeperormedintheprocurementagency.TecontentoeachSOP,particularlythestep-by-stepdescriptionsoactivitiesandapprovedrecordingorreportingormatsattachedasaddenda(seebelow),shouldreecttheoperationsotheparticularprocurementagency.

SOPsshouldbedratedbythepersonresponsibleortheprocedure.AnSOPorwritinganSOPshouldbeollowedtoensureconsistencyodesign,ormatandlayout.AnSOPonhowtowriteanSOPisattachedasAppendix4.

Style and layout

SOPs should bewritten in the procurement agencys approved ormat, and beormallyapproved(signedanddated)bytheauthorizedperson(s).

SOPsshouldbewritteninclear,unambiguouslanguage.

Tenameand/orlogootheprocurementagencyshouldbeincludedontherontpageoeachSOP.

Elements o standard operating procedures

TeSOPshouldcontainatleasttheollowingelements.

Title and number

EachSOPshouldhaveatitle.Tetitleshouldgiveaclearindicationotheactivitywhichitdescribes.AnumberingsystemisuseultoidentiytowhichactivityordepartmenttheSOPreers.

Objective

Tissectionshoulddescribewhatistobeaccomplishedand/orachievedwiththeSOP.

Scope

Tissectionshoulddescribetowhatlevelordepth,orhowwidely,theSOPisapplicable.


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Policy

Tissectionshouldreecttheprocurementagencyspolicyregardingthisparticularactivity.

Responsibility

Tissectionshouldlisttheperson(s)responsibleorperormingtheactivitieslistedintheprocedure.Itmaybeuseultoreertothepositionratherthanthenameotheperson.

Action

Tissectionshoulddescribethesequenceoactionstepstobeollowed,romthebeginningtotheendotheprocess,toperormtheactivity.

Teactionstepsshouldbewrittenintheimperativeandshouldbenumbered.Itisadvisabletoindicatewhoisresponsibleoreachstep.Tiscouldbedonebyputtingtheposition(jobtitle)otheresponsiblepersoninbracketsnexttoeachstep,orbyindicatingthenumbersotherelevantstepsnexttothepositionslistedundertheheadingResponsibility.

Whereastepleadstoanotherproceduretobeollowed,theapplicableSOPshouldbereerredtointhatparticularstep.

Distribution and retrieval

Documentationshouldbedistributedwithcare.NosupersededorobsoleteSOPsshouldbeavailableatuserpoints.Tesectionsand/orresponsiblepersons(positions)towhomtheSOPwasdistributedshouldbelisted.EachtimetheSOPisreviewedand amended,supersededversionso theSOPs shouldberemoved romall theuserpointslistedandreplacedwiththeupdatedversion;theretrievalshouldbe

documented.

Revisions

InasectionwhichcouldbeheadedHistory,thedateoeachchangetotheSOP,thepersonresponsibleorthereview,thechangeitselandthereasonorthechangeshould be recorded.Tis section will provide the procurementagency with thehistoryotheamendmentstotheSOP.

Addenda

Anyrecordstobecompletedormaintainedaspartotheactivityshouldhaveastandardizedormat.Itisuseultodeneandapprovetheseormatsinadvance.

TeapprovedstandardormatshouldbepartotheSOPandcanbeattachedasanaddendumtotheSOP.

Activities to be covered by standard operating procedures

TeollowinglistgivesexamplesoactivitieswhichcouldbecoveredbySOPs: howtowriteastandardoperatingprocedure(seeAppendix4); dratingacontractoragreement; amendmentstocontractoragreement; identiyingandreportingcountereitproducts; reportingodeviations;

appointingevaluatorsoproductinormation;

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appointingcontractinspectors; maintainingamasterdocumentationlist; receivingandscreeningoanoerreceived; evaluatingoersreceived; orderingproduct(s)romsupplierormanuacturer;

publishingspecicationsoproductsorprocurement; sendingout,receivingandevaluatingsupplierquestionnaires; handlingrecalls; policyorregularre-inspection; routineollow-upoinspections; inspectionaultcorrection;and standardormatsorinspectionreporting.

I.2.3 Change control policy

Teprocurementagencyshouldhaveapolicyorchangecontrol.Tispolicyshouldbedesignedtomanagechangesintheagencysownproceduresanddocumentation,aswellaschangesindataandinormationonthepharmaceuticalstobeprequalied.

AprocedureorcontrollingchangesthataectAPIs,ormulation,manuacturingprocesses,analyticaltestingmethodsorpackagingoprequaliedproductsisessential.Teprocedureshouldensurethatthesechangesarereportedtotheprocurementagency beore new batches are manuactured or beore they are delivered andreleasedordistribution.DetailsomanagingchangesinproductinormationaregiveninModuleVI.

I.2.4 Code o conduct

Teprocurementagencyshoulddesign,authorizeandimplementawrittencodeoconduct.

Te code o conduct should describe the policy o the procurement agencyregardingtheconductostainrespecttotheiractivities.Itshouldbeollowedbyallpersonnel.

Tecodeoconductshouldgiveguidancetostamembersonappropriateconductinvarioussituations.Teollowingtopicscouldbecoveredinthecode: introductionandobjectives; keyresponsibilities; personalresponsibilities; saety; proessionalcompetence; qualicationsandexperience; conduct; integrityandattitude; attire,healthandhygiene; managementrelationship;

SOPs;


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travelandaccommodation; condentialityandconictointerest; documentationandrecords; contractsandtermsoreerence(OR); productles,evaluationandinspection;

samples; evaluationandinspectionreports;and provisionoinormationandadvice.

I.2.5 Guidelines on conict o interest

Teprocurement agency should have a policy on conict o interestwhich allpersonnelshouldobserve.AnexampleoaguidelineonconictointerestisshowninAppendix3.

Tedocumentshouldaddressatleasttheollowingpoints: introductionandobjectives; denitionsandprinciples; responsibilities; condentiality;and impartiality.

I.2.6 List o prequalifed products and manuacturers

Teprocurementagencyshouldhaveaprocedureordratingandmaintainingalistoprequaliedproductsandmanuacturers,basedontheoutcomeotheevaluation

oproductdataandinormationandmanuacturingsiteinspections.Telistshouldbeproduct-andmanuacturingsite-specic,i.e.sitesareprequaliedoroneormorespeciedproducts,andproductsareprequaliedasmanuacturedatspeciedsites.

Tekeypersonresponsibleorprequalicationshouldberesponsibleoradditiontoand/ordeletionsromthelist.

Once the evaluation o a product dossier is complete, and the inspection hasbeen perormed to assess compliance with goodmanuacturing practices, goodstoragepracticesandgooddistributionpracticesasappropriate,theprocurementagencyshouldpreparealistreectingthestatusotheprequaliedproductsandmanuacturers.

Telistshouldcontainatleasttheollowinginormation: nameotheprocurementagency; authorizationsignatures; reerencenumberandversionothelist; dateopreparationothelist; nameandphysicaladdressomanuacturer,includingtheapprovedsite(s)o

manuacturelinkedtoeachproduct;

contactdetails, includingpostaladdress,telephone,axnumberande-mailaddressothemanuacturerandsupplier;

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productdetails,includingthebrandname,INN,dosageorm,strengthperdoseandpacksize;

dateooriginalprequalication; dateoexpiryotheprequalication;and dateuntilwhichthelistisvalid.

I.2.7 Maintenance o records

Recordsoalloperationsshouldbemaintainedandkeptinasuitablyorganizedmanner.

Sufcient areas or the storage o records, including product inormation,manuacturersinormationandinspectionreports,shouldbeavailable.

Access to these areas should be restricted to authorized personnel only, ascondentialinormationmaybeled(includingrecordsomanuacture,testing

and/orstorage).

Recordsshouldbemaintained or adened periodo time, inaccordancewithnationallegislation.Generallytheyshouldberetainedoratleastoneyearbeyondtheexpirydateothenishedproduct.

Module II. Further guidanceon record-keeping in quality assurance systems isprovidedintheWHOpublicationQuality assurance o pharmaceuticals (2, 3).


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Module II

Prequalication

Introduction

Prequalication isone o the key elements in ensuringpurchase and supply opharmaceuticalproductsoacceptablequality.Teprequalicationprocesscanbesubdividedintotwomajorparts,i.e.product-relatedassessmentandmanuacturer-relatedassessment.

Product-related assessmentshouldensurethatthecorrectproductisspeciedbytheprocurementagency.Teprocurementagencyshouldthenassesswhetherthemanuacturerisoeringaproductthatmeetsthepredeterminednormsandstandardsintermsosaety,qualityandefcacy.

Manuacturer-related assessmentshouldensurethatthemanuacturerisabletomanuacturetheproductasspeciedintheproductinormationpackageandinaccordancewithgoodmanuacturingpractices(GMP)asrecommendedbyWHO.Temanuacturermustbecapableoroutinelycarryingouttheactivitiestothespeciedstandardstoensurebatch-to-batchconsistencyotheproduct.

Assessment o contracted-out services, e.g. by storage and distribution agents,contract research organizations (CROs) and quality control laboratories orcompliancewithGMP,goodclinicalpractices(GCP)andgoodlaboratorypractices

(GLP),areurtherelementsthatmaysupplementtheprequalicationprocess.

TeprocurementagencyisresponsibleorensuringthatallstepsintheprequalicationprocessarecarriedoutinaccordancewiththisModel.Tisshouldensurethatthemanuacturerswillbeprovidingproductsasspeciedthatmeetallpredeterminednormsandstandards.Itwillassistprocurementagenciesinmaximizingtheuseoresourcesandwillavoidduplicationoprequalicationbydierentprocurementagencies.Itshouldalsominimizetheriskoprocurementagenciespurchasingandsupplyingsubstandardproducts.

Tis module sets out recommendations which procurement agencies should

implementwhenevaluatingtheirproductneedsandwhenassessingtheproductsandthemanuacturingandsupplyarrangementsoeredbythemanuacturers.

II.1 Principles or prequalication

Prequalicationproceduresshouldbebasedontheollowingprinciples: reliance on the inormation supplied by the national drug regulatory

authority; evaluation o product data and inormation submitted by manuacturers,

includingproductormulation,manuactureandtestdataandresults;

ageneralunderstandingotheproductionandqualitycontrolactivitiesothemanuacturersandsuppliersandotheircommitmenttotheprinciplesoGMP;

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assessment o consistency in production and quality control throughcompliancewithGMPasdescribedintheWHOpublicationQuality assuranceo pharmaceuticals,Volumes1and2(2,3)andsupplementaryWHOGMPguidelines;

availabilityoappropriatequalitysystemsandSOPs;

randomsamplingandtestingopharmaceuticalproductssupplied; adequatepurchasingmechanisms(seeModuleIII); goodstoragepractices(seeModuleIV); gooddistributionpractices(seeModuleV); monitoringocomplaintsromprocurementagenciesandcountries; adequatehandlingocomplaintsandrecalls;and continuousmonitoringandrequalication.

Te procurement agency should have a document describing the policy andproceduresorprequalication,includingtheassessmentoproductinormationandomanuacturersorcompliancewithstandards.

II.1.1 WHO Model List o Essential Medicines

Procurement agenciesmay nd thatmany o the products they require are onWHOsModelListoEssentialMedicines,whichcontainsmedicinesoprovensaetyandefcacyandisupdatedperiodically(4).ProcurementagenciesshouldocusonprocurementomedicinesreectedintheModelList.Teywillndthislistauseulreerenceorestablishingspecicationsorthemedicinesneededortheirpurposes.

II.2 Standards or prequalication

TeprequalicationprocedureshouldbebasedontheProcedureorassessingtheacceptability,inprinciple,opharmaceuticalproductsorpurchasebyUnitedNationsAgencies (5). Inprinciple, products shouldmeet at least the recommendationsmadebyWHOinMarketing authorization o pharmaceutical products with specialreerence to multisource (generic) products a manual or drug regulatory authorities(6).ManuacturingsitesshouldcomplywithatleastWHOGMP(3).

II.3 Key persons and responsibilities

II.3.1 Sta responsible or prequalifcation

Tepersonresponsibleorprequalicationshouldbeindependentromthepersonresponsibleorpurchasing.

Te key responsibilities o the person responsible or prequalication activitiesshouldincludetheollowing: establishingspecicationsorproducts; publicationoinvitationsorexpressionsointerest(EOI); preparationoaquestionnaireorcollectingproductdataandinormation

and/orguidelinesorthecompilationoproductinormation;


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assessmentoproductdataandinormationorcompliancewithnormsandstandards;

assessmentomanuacturingsites,throughinspection,orcompliancewithWHOGMP;and

preparationothelistoprequaliedproductsandmanuacturers.

II.3.2 Sta responsible or evaluation o product inormation

Tepersonresponsibleorevaluationoproductinormationshouldbeindependentromthepersonevaluatingthemanuacturingsite.Neithershouldreporttotheotherintermsodecision-making.

Tekeyresponsibilitiesothepersonresponsibleorevaluatingproductinormationshouldinclude: preparingandimplementingSOPsandguidelinesorevaluationoproduct

inormation; receiptoproductinormation; screeningoproductinormation; evaluationoproductinormation; inormingmanuacturersotheoutcomeotheevaluationotheproduct

inormation;and communicatingwiththepersonresponsibleorinspectionsomanuacturing

sites.

Tepersonresponsibleortheevaluationoproductinormationmaybeamemberotheexistingstaorappointedorthistask.

Te people assigned to evaluate product inormation should have relevantqualications and experience, including a background in pharmaceuticals,pharmaceutical chemistry and pharmacology. Ideally they should be rom aregulatorybackground,orhaveregulatoryexperience.

II.3.3 Sta responsible or inspection o manuacturing sites

Tekeyresponsibilitiesothepersonresponsibleorinspectionomanuacturingsitesshouldincludetheollowing: preparationandimplementationoguidelinesandSOPs; coordinationoinspectionstobeperormed; recruiting or appointing inspectors with appropriate qualications and

experiencewhennecessary; trainingoinspectors; organizationoinspections; nalizinginspectionreports;and inormingmanuacturersotheoutcomeotheinspection.

Asaminimum,thepersonnelresponsibleorinspectingmanuacturingsitesshouldhave relevant qualications and experience in pharmaceutical manuacturing,

qualityassurance,GMP,perorminginspectionsandaudits,chemistryandqualitycontrol.Ideallytheyshouldhaveaninspectionbackgroundromworkingwitharegulatoryauthority.

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Althoughdecision-makingshouldbeindependent,thereshouldbecommunicationbetween the person responsible or evaluation o product inormation and thepersonresponsibleorinspectionomanuacturingsites,as someinormationontheproductmayhavetobeveriedduringthesiteinspection.

II.4 Key steps in prequalication

TekeystepsinprequalicationaresummarizedinFig.1.Detaileddescriptionsothedierentstepsaregivenbelow.Tepreparatorystepsodratingadocumentationsystem, including condentiality agreements, declaration o conict o interest,SOPsandguidelines,aredescribedinModuleI.

II.4.1 Step 1: solicit and receive expressions o interest

Drat product specications or prequalication

Specicationsortheproduct(s)tobeprequaliedshouldbedratedwithinputromthepersonresponsibleorpurchasing,sothattheproductmeetstherequirementsortheintendedpurpose.

Tespecicationsshouldbedetailed,clearandunambiguoustoavoidunnecessarysubmission and processingodocumentation not relevant to the product tobesourced.

Tespecicationshouldstateatleast: thenameotheactivepharmaceuticalingredient(s); pharmacopoeia reerence (i any), e.g. European Pharmacopoeia,

Japanese Pharmacopoeia, United States Pharmacopeia and InternationalPharmacopoeia;

strengthperdoseanddosageorm; dosageorm(routeoadministration); packsize; packingmaterial;and labellingrequirements.

TespecicationcouldbepublishedaspartotheinvitationorEOIs.

Drat and publish invitation or expressions o interest

Oncethespecicationisnalized,aninvitationorEOIsshouldbepublishedwidelyto reachanymanuacturers thatmay be interested in supplying the product(s).


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Figure 1

Key steps in prequalification

Step 1: solicit and receive expressions of interest (EOIs)

Step 2: receive product information

Step 3: screen product information

Step 5: plan, prepare and perform inspection

Step 6: finalize assessment process and update prequalification list

Draft documentation system, confidentiality agreements,

declaration of conflict of interest, SOPs and guidelines

Make administrative arrangements for transport,

accomodation, etc.

Draft screening form, guidelines for evaluation,

product assessment report format

Draft product specifications and invitation for EOIs

Collate information to plan inspections

Draft documentation, guidelines and SOP for inspections

Plan inspections

Evaluate product information

Step 4: evaluate product information

Write reports

Communicate results to suppliers, requesting additional information if necessary

Perform inspections

Write reports

Communicate contents to manufacturers, requesting additional information if necessary

Review additional information submitted

Inform manufacturers of outcome

Make decision on prequalification

Finalize list of prequalified manufacturers and products

Inform recipients of any changes to the list

Publish revised list periodically

Publish invitation for EOIs

Receive EOIs

Send guidelines for submitting product information to manufacturers

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TeprocessoinvitingallinterestedmanuacturerstosubmittheirEOIorthepharmaceutical products listed should be open and transparent. Invitations orEOIsmaybepublishedorgroupsoproducts,andmayberepeatedasnecessary.

TeinvitationorEOIsshouldbedetailedandshouldstateatleast:

thepurposeotheinvitationorEOIs; theobjectiveotheinvitationorEOIs; thelistoproducts,includingspecicationsoreachproduct; inormationonquantitiesrequired(iavailable); detailsotheinormationtobesubmitted; guidelinesorsubmission,includinginormationondetailstobesubmitted

aspartotheEOI,ontheocalpointorthesubmissionandontheormatorthesubmission;

contact details (name, address, telephone number, ax, e-mail and postaladdress)orsubmissionotheEOI;and

theclosingdateorreceiptotheEOIbytheprocurementagency.

AnexampleoaninvitationorEOIsisshowninAppendix5.

Manuacturers should submit their EOI with the requested inormation abouttheproduct(s)andmanuacturer(s),beorethedatespeciedbytheprocurementagency.

Receive expressions o interest

TeprocurementagencyshouldensurethattherelevantinrastructureexistsorthereceiptandprocessingotheEOIsthroughthesubsequentprequalicationsteps.

Teprocurement agency should have a clearpolicy regarding the acceptanceoEOIs ater the speciedclosingdate.Processingo late submissions should notnormallybeallowed.OnlyinexceptionalinstancesshouldlateEOIsbeconsidered,e.g.whenamanuactureristheonlyonetoexpressaninterestinsupplyingaspecicproduct.

It would be appropriate to express concern at the late arrival o theEOI, andmanuacturersshouldgivereasonsorlatesubmission.

ArecordoalltheEOIsreceivedromeachmanuacturershouldbemaintained.

Send guidelines or submitting product inormation to manuacturers

Manuacturerswho have submitted anEOI beore the closingdate specied intheinvitationshouldbegivenguidelinesorthecompilationandsubmissionoinormationonproductsandmanuacturers.Teguidelines should bepubliclyavailableandaccessible.Incaseswherethisisnotdone,reasonsorthedecisionshouldbegivenanddocumented.

Teguidelinesshouldbewritteninclear,unambiguouslanguage.Guidelinesshouldcontaininormationincludingatleast:

the content and ormat o submission, including the type and ormat o


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inormation required (e.g. the procedure or submission o inormationoraproductregisteredinacountryrecognizedashavinganeectivedrugregulatoryagency,andinstructionsor cross-reerencinganexistingdossierwiththeprescribedsubmissionormat);and

theprocessosubmission,includingtheaddresstowhichthedocumentation

shouldbesentandastatementoanyeespayableorcostrecovery.

Content and format of submission

Foreachproducttobeprequalied,interestedmanuacturersshouldbeaskedtosubmitproductinormation,togetherwithasampleosufcientquantitytoallowanalysesotheproductagainstitsnishedproductspecicationasstatedintheproductinormation,acoveringletter(asrecommendedontheEOI)andachecklistortheproductinormation.

Dependingontheactiveingredients,countryomanuactureandregistrationo

productstobeprequalied,dierentormatsorsubmissionwillberequired.

Detailedinormationshouldbesubmittedorproductsorwhichbioavailabilitymaybealteredbychirality,isomerism,controlledreleaseormulation,polymorphismorotherpropertieswhichmayaectthetherapeuticoutcome.

Inthisdocument,thetermproductinormationreerstoanyotheollowingourormats,inwhichsubmissionsshouldbemade:1. A product dossier, which should be submitted or multisource (generic)

products,orinnovatorproductswhichhavebeenonthemarketorlessthanveyears,andorproductscontainingsubstancesthathavespecicproperties

thatmayhaveexplicitimpactonthesaety,efcacyorqualityotheproduct.TeModel application orm or new marketing authorizations, periodic reviewsand variations, with notes to the applicant (7)may also provide ahelpulexampleoguidelinesorthistypeosubmission.

2. Astandardproductdossieraspreparedoranationaldrugregulatoryauthoritycanbesubmitted,provideditcontainstheappropriateinormationasrequiredintheseguidelines.Insuchcases,thesuppliershouldprovideacoveringletterwhichindicateswheretherequiredinormationcanbeoundinthestandardproductdossier.

3. For products manuactured and registered in countries where regulatory

requirementsareinlinewithinternationalregulationsorassessmentosaety,efcacyandquality,theollowinginormationshouldbesubmitted:

aWHO-typecerticateoapharmaceuticalproduct(CPP)(8)issuedbyoneotheregulatoryauthoritiesoanInternationalConerenceonHarmonisation(ICH)region(EuropeanUnion,JapanortheUSA),togetherwithasummaryoproductcharacteristics(SmPC);

anassessmentreportissuedbytheregulatoryauthority; aWHO-typebatchcerticateromthemanuacturer.

Ithepackagingotheproductisdierentromthatapprovedbyaregulatory

authorityoanICHregion,stabilitytestingdatashouldbesubmitted.Ithe

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ormulation,strengthorotherspecicationsaredierentromtheproductorwhichtheWHO-typeproductcerticate(CPP)wasissued,argumentsand/ordatatosupporttheapplicabilityothecerticatedespitethedierencesshouldbesubmitted.

4. Acompletedquestionnairewithlimitedinormationontheproductshould

besubmittedorproductscontainingonlysubstancesthatdonothavespecicpropertiesthatmayhaveexplicitimpactonthesaety,efcacyorqualityotheproduct.AnexampleoapharmaceuticalproductquestionnaireisshowninAppendix6.

Inormationaboutthesite(s)whereeachproductismanuacturedwillalsoberequiredatalaterstage.Forguidelinesonsubmissionoinormationonmanuacturingsites,seePlanningandpreparationoinspections.

Tesameprocessasoutlinedaboveshouldbeollowedorsupplierswhoperormonlypartothesupplyprocess.Tisisparticularlyrelevantwhereaproductroma

prequaliedmanuactureristobesuppliedthroughanewdistributionchannel.Forexample,aprocurementagencymightwishtoshipanalreadyprequaliedproductto a newcountry usingnew traders, brokers or distributors.Teorganizationsinvolvedinthenewdistributionchannelwillneedtobeappropriatelyprequalied.Dependinguponthenatureothesupplyarrangement,therequirementsorproductinormationandtheGMPinspectionprocessmaybemodied.

Process of submission

Suppliersshouldbeallowedatleast60daysorthecompilationandsubmissionoproductinormation.

Suppliersshouldberequestedtosubmitacoveringletter,containingaclearstatementbytheresponsiblepersonthattheinormationsubmittedistrueandcorrect.

Teprocurementagencyshouldreservetherighttoterminatetheprequalicationprocedureoaproductandmanuacturerithemanuacturerailstoprovidetherequiredinormationinaspeciedtimeperiod,oritheinormationsuppliedisinadequatetocompletetheprequalicationeectively.

II.4.2 Step 2: receive product inormation

Teprocurementagencyshouldhavethenecessaryinrastructuretoreceiveandprocess the product inormation submitted by manuacturers. It will requirepersonnel or processing the documentation; written procedures or receiving,identication, marking les, containers and samples, and sufcient space orunpackingandstorage.

Containerswithproductinormationshouldbereceivedatthespeciedaddressbeoreaspecieddateasdeterminedbytheprocurementagency.

Containersshouldbeopenedinthepresenceoatleasttwopeople.Arecordshould

bekeptothenamesothepeoplewhoopenedthecontainersandthecontentsothecontainers.


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Eachproductshouldbeallocatedauniquereerencenumbertoensuretraceabilityotheproductinormation.

II.4.3 Step 3: screen product inormation

Each product inormation package submitted by the manuacturer should bescreenedorcompleteness.Tescreeningshouldbedoneinaccordancewithawrittenprocedure.Itheproductinormationsubmittedailstomeettherequirements,itshouldbeexcludedromtheevaluationprocedureandinspectionprocess.

Ascreeningormshouldbeusedtoensureconsistencyoscreening.Tereshouldbeawrittenrecordothescreeningoeachproductinormationpackage.Inormationtoberecordedshouldinclude:dateoreceipt;nameotheinterestedmanuacturer(s);addressothemanuacturer;nameotheproduct;countryomanuacture;productnumber;andoutcomeothescreening.

AnexampleoanSOPorscreeningandassessingproductinormation,includingasamplescreeningorm,isshowninAppendix7.Incompleteinormationshouldnotbekeptorevaluationpurposes.Temanuacturershouldbeinormedthatanincompleteinormationpackagewasreceived,andberequestedtosupplythemissinginormationwithinaspeciedperiod.Ithisrequestisnotcompliedwith,

theapplicationshouldberejectedongroundsoincompleteness.

Product inormation packages which meet the requirements o the screeningprocedureshouldberetainedorullevaluation.

Asummaryshouldbemadeoeachproductinormationpackagereceived,statingany reerence number allocated to the product by the procurement agency, theINN,strength,dosageormandpacksizeotheproduct,thenameothesupplier,the name and address o themanuacturing site(s),whether a sample has beensubmitted,andiso,thesamplesize.

II.4.4 Step 4: evaluate product inormation

Evaluators

Evaluatorswithsuitablequalicationsandexperienceintheevaluationoproductdataandinormationshouldbeavailabletoconducttheassessment.Suitablyqualiedexternalevaluatorsmaybeappointed.Appointmentoexternalevaluatorsshouldbesubjecttocompliancewiththepolicyotheprocurementagency,regardingaspectssuchascondentiality,conictsointerestandnancialresources.Examinationopotentialconictso interestandcondentialitymustgobeyondthepotentialevaluatorsigningadeclaration.Checksonreerencesshouldalsobemade.

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A ormal agreement or the perormance o work and terms o reerence orcontractedevaluatorsshouldbeinplacebeorecommencementowork.

A summary list o names, addresses, dates o appointment, qualications andexperienceoevaluatorsshouldbemaintained.Copiesosignedagreementsshould

bekeptinacentralle.

Evaluation

imeramesshouldbesetorevaluationoproductinormation.Productinormationshouldbeevaluatedwithin21daysatertheclosingdateorsubmission.

Awrittenprocedureorevaluationshouldbeollowed.AnexampleoanSOPorscreeningandassessingproductinormationisattachedasAppendix7.

Te person responsible or evaluation should monitor the process to ensurethat each product inormation package is evaluated in compliance with theserequirements.Inormationontheproductspatentstatusshouldbeconsideredtoavoidinringementointellectualpropertyrights(seealsoSectionIII.7).

ContractresearchorganizationsshouldbeinspectedaspartotheassessmentprocesstoensurethatbioequivalencestudieshavebeendoneinaccordancewithGCPandGLP,andthattabulateddatasubmittedtoprovebioequivalenceaccuratelyreectthegeneratedrawdata.

Evaluation reports

Eachevaluatorshouldprepareaormalevaluationreportoreachproduct,includinga recommendation oracceptanceor rejection.Teevaluation reportshould becommunicatedtothemanuacturerwithin14daysotheevaluation.

A response should be invited rom the manuacturer in cases where data andinormationareoundtobeincompleteordonotmeettheguidelines.Aperiodoatleast60daysshouldbeallowedorsubmissionoadditionaldataandinormation.

Tis additional inormation should be assessed and the nal outcome o theevaluationshouldbecommunicatedtothemanuacturer.

Teevaluationreportshouldbeledwiththeproductevaluationdocumentationorreerencepurposesandollow-upwhererelevant.

Analysis o samples

Samplessubmittedtogetherwithproductinormationpackagesshouldbeanalysedinaccordancewiththenishedproductspecication.Certicatesoanalysisonalproductsreleasedbythemanuacturershouldbemadeavailabletotheprocurementagencyonrequest.

Te procurement agency should have access to a quality control laboratory toperormtheanalyses.TeWHO Guide or a quality systems manual in a controllaboratory(9)seekstoestablishapracticalbasisorthequalitysystemsmanualoa


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controllaboratorywhicheachcountrycanadoptandadapttoprepareitsownmoredetailedmanualtomeettherequiredlevelospecicityandcomplexity.

A laboratory may be contracted to perorm the analyses. In that case, theprocurementagencyshouldensurethatthelaboratorycomplieswithGMPand

goodpracticesorcontrollaboratories(10).Teuseoanaccreditedlaboratoryisthereorerecommended.Teprocurementagencyshouldveriytheaccreditation.Tereshouldbeawrittencontractoragreementbetweentheprocurementagencyand the contractlaboratory.Tewordingothe contractshouldbeclear and itshouldspeciytheresponsibilitiesothecontract-giverandthecontract-acceptor.

Teprocurementagencyisresponsibleorensuringaccesstorawdata.

Teprocurementagencyshouldhaveaprocedureor investigating,handlingandreportingout-o-specicationresultswhentheseareobtainedromlaboratories.Iasampleailstomeetthespecications,theprocurementagencyshouldinvestigate

theproblemandcommunicatetheoutcometothemanuacturer.

II.4.5 Step 5: plan, prepare and perorm inspections

Each batch o every product procured by a procurement agency should bemanuactured in compliance with GMP to ensure batch-to-batch consistency.Teactualsiteomanuactureotheproductshouldbeknownandspecied.Insomecases,acontractmanuacturermaymanuacturetheproductonbehalothesupplieroragent.EachmanuacturingsitespeciedintheproductinormationshouldbeinspectedtoassesscompliancewithWHOGMP.

Manuacturers o the active pharmaceutical ingredients (APIs) used shouldbe inspected as part o the assessment procedure to ensure that the APIs weremanuacturedinaccordancewithGMP.

Existing certicates

ISO certication is not an assurance o compliance with GMP and is not areplacementorsubstituteorvericationocompliancewithGMP.

Similarly, aCPP is not a guarantee o compliance withGMP. Participation intheWHOCerticationscheme(8)isavoluntaryprocess,andthereisnoormalassessmentorevaluationodrugregulatoryauthoritiesenteringthescheme.Insomecases,relianceontheCPPaloneisthereorenotrecommended.Tecerticationschemeisanadministrativetoolandisreliableonlywheretherelevantnationaldrug regulatory authority has anestablished systemwhich isknown to complywithacceptablestandardsorevaluationandregistration/licensingoproductsandmanuacturers, including products or exportmarkets. Inormation in additiontotheCPP,e.g.acopyotheinspectionreportandcorrectiveactionplanromthe manuacturer, may be requested. Tese documents, in addition to otherdocumentation,maybeconsidereduseulintheprequalicationprocessandinollow-upassessmentorevaluationatalaterstage.

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TeprocurementagencyshouldstillveriycompliancewithWHOGMPaspartotheprequalicationprocedure,andaninspectionothemanuacturingsitemustbeconsideredineverycase.

Inspectors

Inspectionsshouldbeperormedbyasuitablyqualied,experiencedinspectororteamoinspectorswithrelevantqualications,trainingandexperienceinperorminginspectionsinoreigncountries.InspectorsshouldhavesoundknowledgeoqualityassuranceandGMPinpharmaceuticalproductproductionandqualitycontrol.Asufcientnumberoinspectorsshouldbeappointedtocarryoutinspectionswithinpredeterminedtimerames.

Where possible, a representative rom the procurement agency (the personresponsibleorprequalicationwithaknowledgeoGMP)shouldbepartotheinspectionteam.

In exceptional cases, consultants rom the private sector may be appointed toperorm inspections, provided that there is no conict o interests and that allcondentialityundertakingsareagreeduponandmaintained.Forthesereasons,personsworking in amanuacturing companymay not be considered suitable.Interestedexternalinspectorsshouldsubmittheirlettersointerestandcurriculumvitae to the procurement agency.Teagency should reviewthe documentationbeoredecidingtoappointanyinspectors.Aormalagreementortheperormanceoworkandtermsoreerenceshouldbeinplacebeorecommencementoworkbycontractedinspectors.

A summary list o names, addresses, dates o appointment, qualications andexperienceoinspectorsshouldbemaintained.

Planning and preparation o inspections

Inpreparationortheinspection,theprocurementagencyshouldensurethatthemanuacturerswhohavesubmittedEOIstosupplyproductsarelistedinarecordingsystemorinspectionplanningpurposes.

oacilitateplanningandtosavecosts,manuacturersshouldbegroupedtogetherbycountry.Insomecountries,onemanuacturermayhavedierentmanuacturing

sitesinadditiontothesubmittedaddressotheheadquarters.

Manuacturers should be inormedo tentative inspectiondates, and should berequestedtosubmitinormationabouteachmanuacturingsitetobeinspected.Tisinormationshouldnormallybeprovidedinasitemasterle(SMF).AnexampleoatechnicalquestionnaireorpharmaceuticalmanuacturersisattachedasAppendix8.Tis inormationwillbeused during the preparation or the inspection andduringtheinspectionitseltoveriyinormationsuppliedbythemanuacturertotheprocurementagency.


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AnexampleoastandardoperatingprocedureorplanninganinspectionisshowninAppendix9.

As the manuacturer will be inspected as part o the prequalication processor specic products to the procurement agency, inspectors should prepare or

inspectionsbystudyingtheproductinormationsubmittedbythemanuacturer.Appendix10containsanexampleoanSOPorpreparingoraninspection.

AsitevisitbeoredecidingwhetheraGMPinspectionshouldbeperormedmayinsomecasesbeappropriate.Tisvisitisoptionalanddoesnotleadtotherequirementortheperormanceotheinspectionbeingwaived.

Perorming inspections

Inspections should be perormed in accordance with a written procedure.TeinspectionshouldcoverallaspectsoGMP.AnexampleoanSOPorperorming

aninspectionisshowninAppendix11.

Inormationsubmitted inrelationtothe supply o theAPI, ormulationo theproduct,manuacturingmethodandstabilitydatashouldalsobeveriedduringtheinspection.

Teinspectionshouldcovertheevaluationandassessmentothedocumentation,premises, equipment, utilities andmaterials. It should also cover vericationodataanddocumentationsuchasresults,batchrecords,compliancewithSOPandinormation submitted on the manuacturing method, equipment and aspectsincluding(butnotlimitedto)validationothemanuacturingprocess,validation

outilitiesandsupportsystems,andvalidationoequipment.

I checklists are used, these should be drawn up and agreed upon or use bycollaboratingprocurement agencies implementing thisModel.An example o aGMPchecklistisshowninAppendix12.

Waiving o inspections

Teneedoraninspectionmaybewaivedwhereaninspectionreportisavailablerominspectorsrepresentingnationaldrugregulatoryauthoritiesorthemanuacturingsiteunderconsideration,coveringactivitiesor theproduct(s)beingprequalied,

providedthatthereportsatisestheagencythat: allaspectsoGMPortherelativeproduct(s)havebeencovered; theinspectionreportisnotolderthan24months; thereisastatementromthemanuacturerthatnomajorchangeshavebeen

madetopremises,equipmentandkeypersonnelsincetheinspectionbythemedicinesregulatoryauthority;

thereports o thenationaldrugregulatory authoritydemonstratethat themanuacturerhasahistoryocompliancewithGMP;and

theinspectionreporthasaavourableoutcome.

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Inspection report

Each inspector or inspection team (where inspection teams are perorminginspections)shouldprepareaormalinspectionreportoreachmanuacturingsiteinspected.

TeinspectororinspectionteamshouldmakearecommendationonthestatusothemanuacturerinrelationtocompliancewithGMP.Accordingtothendings,the recommendation ollowing the inspection may or example be one o theollowing: Te manuacturer is considered to be operating at a reasonable level o

compliancewithWHOGMPandaollow-upinspectionisrecommendedto veriy implementation and acceptability o corrective actions prior toparticipationinanytender.

Temanuacturer is considered to be operating at an acceptable level ocompliancewithWHOGMP.

TemanuacturerisconsiderednottobeoperatingatanacceptablelevelocompliancewithWHOGMP.

Te inspector or inspection team(s) will nalize a report according to therecommended ormat. Te WHO Guidance on Good Manuacturing Practices(GMP): inspection report (11)(seeAppendix13)providesinormationonhowtowriteaninspectionreport.

Acopyotheinspectionreportshouldbeledinacentralmanuacturerslethatisuniquetothatmanuacturer.

Teinspectionreportshouldbecommunicatedtothemanuacturer.Wherenon-compliancewasobserved,correctiveactionsandtimelinesorcompletingthemshouldbesuggested.Aresponsewithsupportivedocumentationshouldbeinvitedromthemanuacturer.

Ianyadditionalinormationisrequired,oricorrectiveactionhastobetaken,analrecommendationastotheacceptabilityotheproductandmanuacturershouldbemadeonlyatersuchinormationhasbeenevaluated,or thecorrectiveactionhasbeenveried.

Intheeventoanydispute,astandardprocedureshouldbeollowedordiscussingandresolvingtheissue.

Te ownership o the report should be with the procurement agency, as it isresponsibleortheprequalication.

II.4.6 Step 6: fnalize assessment process and update prequalifcation list

Decision-making process or acceptance or rejection o a manuacturer

Teprocurementagencyshouldollowawrittenproceduretocollatetheoutcomes

otheevaluationoproductinormation,laboratoryresultsorsamplesanalysedandinspectionreports.


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TeSOPshouldalsoidentiythepeopleresponsibleortakingthedecisiontoacceptorrejectaproductand/ormanuacturer,includingthegroundsorthedecision.Itmaybehelpultoreertothepersonbyposition,ratherthanbyname.

Teprocurementagencyshouldinormthemanuacturerinwritingotheoutcome

otheprequalicationoeachproductmanuacturedateachspeciedsite.

Recording o outcomes

Te person responsible or prequalication should record the outcome o theprequalicationprocessinalistoprequaliedproductsandmanuacturers.TelistshouldincludeonlythoseproductsevaluatedasindicatedbythemanuacturerandlistedintheEOI.Itshouldbeproduct-andmanuacturingsite-specic.

Telistshouldbepublishedinthepublicdomainandshouldincludeatleasttheollowinginormation.

General inormation

Normsandstandardsused; reerencetothegeneralprocedureorprequalication; a statement to indicate that the list isnot comprehensive or any disease

category,butincludesonlythoseproductssubmittedbypossiblesuppliersandprequaliedbytheprocurementagency;

astatementtoindicatethatthepurchaseroproductsromthelistshouldensurethatonlyprequaliedproducts(i.e.thesameormula,manuacturingmethods,manuacturingsite,etc.asintheproductinormationsubmitted)willbesuppliedbythesupplierthroughcontractualagreementbetweenthe

buyerandthesupplier; astatementthatbeingonthelistdoesnotguaranteecontractsorsalestothe

suppliers; astatementthatthelistshouldnotbeusedbysuppliersasamarketingtool

togeneratebusiness; dateopublication;and periodovalidity.

Product inormation

Productsandtheirmanuacturingsiteswhereproducts andmanuacturersmeet the standards set or the prequalication, including the ollowingspecications:

INNoactiveingredient(s); strength; dosageorm; packsize; shel-lie; storageconditions; nameosupplier; nameomanuacturerandmanuacturingsite(s).

Teprocurementagencyshouldhaveamechanismorsharinginormationwithotherprocurementagencies.

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Teprocurement agency should have anagreementwith the supplier toensurecompliancewiththeprequalicationprinciplesandthattheproductssuppliedarethesameproductsaswereprequalied(e.g.theyaremanuacturedatthesamesiteandthesameprocessesareadheredto).Telistshouldbereviewedandupdatedatregularintervals,atleasteveryyear.Newlyprequaliedmanuacturersshould

beaddedtothelistastheybecomequalied,andnon-compliantmanuacturersshouldberemovedromthelistassoonastheyarerecognizedassuch.

Wherepossible,morethanonesupplieroaproductshouldbeincludedonthelisttoensureopenandtransparentprocurementthroughcompetitiveprocurementprocedures(seeModuleIII).

II.5 Requalication and monitoring

Requalication should occur at regular intervals. Routine reinspection omanuacturersshouldtakeplaceatleastonceeverythreeyears.Routinere-evaluationoproductinormationorquestionnairesshouldbedoneeverythreeyears.Non-routinere-evaluationand/orinspectionshouldbedonewhennecessary,e.g.whenthemanuacturerimplementsanychangetotheormula,manuacturingmethodormanuacturingsite;ianyproductsuppliedisconsiderednottobeincompliancewiththeagreedspecicationotheproduct;oriaseriouscomplainthasbeenreceived.FormoredetailsonreassessmentseeModuleVI.

Randomsamplesobatchesopharmaceuticalproduct(s)suppliedbyprequaliedmanuacturersshouldbetakenor independenttestingorcompliancewithnalproductspecicationsaspartothecontinuousmonitoringprogramme.

II.6 Monitoring o complaints

Complaintsshouldbehandledinaccordancewithawrittenprocedure.

Awrittenreportothecomplaint,investigation,recommendationsoractionwhererelevant,andoutcomeshouldbeavailabletotheprocurementagency.

Anycomplaintconcerningapharmaceuticalproductorbatchoproductssuppliedbythemanuacturershouldbethoroughlyinvestigated.Tenatureothecomplaintshouldbecommunicatedtothemanuacturer.

II.7 Cost recovery

It is recommended that the costs o prequalication should be covered by theprocurementagency.

Icostsaretoberecovered,denedtransparentproceduresshouldbeestablishedandmanuacturersshouldbenotiedotheseproceduresinadvance.Costrecoveryshouldbebasedonaee-or-servicesstructure.


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Module III

Purchasing

Introduction

Pharmaceuticalproductsshouldbepurchasedwiththeaimoprocuringeective,good-qualitymedicinesatthelowestpossiblecost.PrequalicationoproductsandmanuacturersasdescribedinModuleIIcontributestoensuringinadvancethatmanuacturersandsupplierscandeliverqualityproductsonasustainedbasis.

Tismodulegivesanoverviewothestrategiesandmethodsusedinpharmaceuticalprocurement. Te term procurement in this module relates specically to thepurchaseohealthsectorgoodsrommanuacturersorsuppliers.Temodulegoesontodescribethekeyactivitiesinpurchasingpharmaceuticalproducts,aswellastherecommendedorganizationalstructureotheprocurementagencieswhocarryoutthesekeyactivities.

III.1 Strategies or health systems

Although many health systems are decentralizing, some aspects o the healthsystemareotenhandledmoreefcientlyatacentrallevel.Approvaloralistoessentialpharmaceuticalproductsandregistrationor licensingopharmaceuticalproductsarenormallytheresponsibilityothecompetentauthorityatthenationallevel.Centralizedprocurementopharmaceuticalproductsincreasesthequantityobtainedundereachpurchasecontractandusuallyreducesthecostotheproducts.

Programme ofcials should thereore consider consolidating quality assuranceproceduresatthenat

Model Quality Assurance

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