WHO GuidelinesSamplingPharmProducts TRS929Annex4.docx

WHO GuidelinesSamplingPharmProducts TRS929Annex4.docx

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WHOGuidelinesSamplingPharmProductsTRS929Annex4

©WorldHealthOrganizationWHOTechnicalReportSeries,No.929,2005

Annex4WHOguidelinesforsamplingofpharmaceuticalproductsandrelatedmaterials

1.Introduction61

1.1Generalconsiderations61

1.2Glossary61

1.3Purposeofsampling64

1.4Classesandtypesofpharmaceuticalproductsandrelatedmaterials65

1.5Samplingfacilities65

1.6Responsibilitiesforsampling66

1.7Healthandsafety67

2.Samplingprocess67

2.1Preparationforsampling67

2.2Samplingoperationandprecautions68

2.3Storageandretention69

3.Regulatoryissues70

3.1Pharmaceuticalinspections71

3.2Surveillanceprogrammes71

4.Samplingonreceipt（foracceptance）72

4.1Startingmaterials72

4.2Intermediatesinthemanufacturingprocessandbulkpharmaceuticalproducts73

4.3Finishedproducts73

4.4Packagingmaterials（primaryandsecondary）74

5.Samplingplansforstartingmaterials,packagingmaterialsandfinishedproducts75

5.1Startingmaterials76

5.2Packagingmaterials77

5.3Finishedproducts78

Bibliography78

Appendix1Typesofsamplingtools80

Appendix2Samplecollectionform85

Appendix3Stepstobeconsideredforinclusioninastandardoperatingprocedure87

1.Introduction

Theseguidelinesareprimarilyintendedforusebygovernmentalorganizations,suchasdrugregulatoryauthorities（includinginspectorates）,qualitycontrollaboratoriesandcustomsandpoliceofficials,butsomeofthegeneralprinciplesmayalsobeappropriateforapplicationbyprocurementagencies,manufacturersandcustomers.

Theseguidelinesshouldbeusefulwhensurveyingthenationalmarketsforthequalityofdrugproductsinaccordancewithnationaldrugqualitysurveillanceprogrammesformarketedproducts,whetherregisteredforsaleorcompoundedinpharmacies.

Thechoiceofasamplingplanshouldalwaystakeintoconsiderationthespecificobjectivesofthesamplingandtherisksandconsequencesassociatedwithinherentdecisionerrors.ThebibliographyattheendofthisAnnexshouldbeconsultedwhenjustifyingasamplingplanforagivenpurpose.

1.1Generalconsiderations

Samplingcomprisestheoperationsdesignedtoselectaportionofapharmaceuticalproduct（fordefinition,seeglossary）foradefinedpurpose.Thesamplingprocedureshouldbeappropriatetothepurposeofsampling,tothetypeofcontrolsintendedtobeappliedtothesamplesandtothematerialtobesampled.Theprocedureshouldbedescribedinwriting.

Alloperationsrelatedtosamplingshouldbeperformedwithcare,usingproperequipmentandtools.Anycontaminationofthesamplebydustorotherforeignmaterialisliabletojeopardizethevalidityofthesubsequentanalyses.

1.2Glossary

Thedefinitionsgivenbelowapplytothetermsasusedintheseguidelines.Theymayhavedifferentmeaningsinothercontexts.

Availablesample

Whatevertotalquantityofsamplematerialsisavailable.

Batch

Aquantityofanydrugproducedduringagivencycleofmanufacture.Ifthemanufacturingprocessiscontinuous,thebatchoriginatesinadefinedperiodoftimeduringwhichthemanufacturingconditionsarestableandhavenotbeenmodified.

Combinedsample

Sampleresultingfromcombiningallorpartsoftwoormoresamplesofthematerial.

Consignment

Thequantityofabulkstartingmaterial,orofadrugproduct,madebyonemanufacturerorsuppliedbyanagent,andsuppliedatonetimeinresponsetoaparticularrequestororder.Aconsignmentmaycompriseoneormorelot-identifiedpackagesorcontainersandmayincludematerialbelongingtomorethanonelot-identifiedbatch.

Finalsample

Samplereadyfortheapplicationofthetestprocedure.

Homogeneity

Amaterialisregardedashomogeneouswhenitisallofthesameorigin（e.g.fromthesamebatch）andasnon-homogeneouswhenitisofdifferingorigins.

Originalsample

Samplecollecteddirectlyfromthematerial.

Pharmaceuticalproduct

Anymaterial1orproductintendedforhumanorveterinaryusepresentedinitsfinisheddosageformorasastartingmaterialforuseinsuchadosageform,thatissubjecttocontrolbypharmaceuticallegislationintheexportingstateand/ortheimportingstate.

Prequalification

Theactivitiesundertakenindefiningaproductorserviceneed,seekingexpressionsofinterestfromenterprisestosupplytheproductorservice,andexaminingtheproductorserviceofferedagainstthespecification,andthefacilitywheretheproductorserviceispreparedagainstcommonstandardsofgoodmanufacturingpractice（GMP）.Theexaminationoftheproductorserviceandofthefacilitywhereitismanufacturedisperformedbytrainedandqualifiedinspectorsagainstcommonstandards.Oncetheproductisapproved,andthefacilityisapprovedforthedeliveryofthespecifiedproductorservice,otherprocurementagenciesareinformedoftheapproval.Pre-qualificationisrequiredforallpharmaceuticalproductsregardlessof

1“Material”isusedinthedocumentfor“pharmaceuticalproductsandrelatedmaterials”.

theircompositionandplaceofmanufactureorregistration,buttheamountandtypeofinformationrequestedfromthesupplierforuseintheassessmentbytheprocurementagencymaydiffer.

Production

Alloperationsinvolvedinthepreparationofapharmaceuticalproduct,fromreceiptofmaterials,throughprocessing,packagingandrepackaging,labellingandrelabelling,tocompletionofthefinishedproduct.

Randomsample

Sampleinwhichthedifferentfractionsofthematerialhaveanequalprobabilityofbeingrepresented.

Representativesample

Sampleobtainedaccordingtoasamplingproceduredesignedtoensurethatthedifferentpartsofabatchorthedifferentpropertiesofanon-uniformmaterialareproportionatelyrepresented.

Retentionsample

Samplecollectedaspartoftheoriginalsamplingprocessandreservedforfuturetesting.Thesizeofaretentionsampleshouldbesufficienttoallowforatleasttwoconfirmatoryanalyses.Insomecasesstatutoryregulationsmayrequireoneormoreretentionsamples,eachofwhichshouldbeseparatelyidentified,packagedandsealed.

Sample

Aportionofamaterialcollectedaccordingtoadefinedsamplingprocedure.Thesizeofanysampleshouldbesufficienttoallowallanticipatedtestprocedurestobecarriedout,includingallrepetitionsandretentionsamples.Ifthequantityofmaterialavailableisnotsufficientfortheintendedanalysesandfortheretentionsamples,theinspectorshouldrecordthatthesampledmaterialistheavailablesample（seeSamplingrecord）andtheevaluationoftheresultsshouldtakeaccountofthelimitationsthatarisefromtheinsufficientsamplesize.

Sampler

Personresponsibleforperformingthesamplingoperations.

Samplingmethod

Thatpartofthesamplingproceduredealingwiththemethodprescribedforwithdrawingsamples.

Samplingplan

Descriptionofthelocation,numberofunitsand/orquantityofmaterialthatshouldbecollected,andassociatedacceptancecriteria.

Samplingprocedure

Thecompletesamplingoperationstobeperformedonadefinedmaterialforaspecificpurpose.Adetailedwrittendescriptionofthesamplingprocedureisprovidedinthesamplingprotocol.

Samplingrecord

Writtenrecordofthesamplingoperationscarriedoutonaparticularmaterialforadefinedpurpose.Thesamplingrecordshouldcontainthebatchnumber,dateandplaceofsampling,referencetothesamplingprotocolused,adescriptionofthecontainersandofthematerialssampled,notesonpossibleabnormalities,togetherwithanyotherrelevantobservations,andthenameandsignatureoftheinspector.

Samplingunit

Discretepartofaconsignmentsuchasanindividualpackage,drumorcontainer.

Selectedsample

Sampleobtainedaccordingtoasamplingproceduredesignedtoselectafractionofthematerialthatislikelytohavespecialproperties.Aselectedsamplethatislikelytocontaindeteriorated,contaminated,adulteratedorotherwiseunacceptablematerialisknownasan

extremesample.

Uniformity

Astartingmaterialmaybeconsidereduniformwhensamplesdrawnfromdifferentlayersdonotshowsignificantdifferencesinthequalitycontroltestswhichwouldresultinnon-conformitywithspecifications.Thefollowingmaterialsmaybeconsidereduniformunlesstherearesignstothecontrary:

organicandinorganicchemicals;purifiednaturalproducts;variousprocessednaturalproductssuchasfattyoilsandessentialoils;andplantextracts.Theassumptionofuniformityisstrengthenedbyhomogeneity,i.e.whentheconsignmentisderivedfromasinglebatch.

1.3Purposeofsampling

Samplingmayberequiredfordifferentpurposes,suchaspre-qualification;acceptanceofconsignments;batchreleasetesting;in-processcontrol;specialcontrols;inspectionforcustomsclearance,deteriorationoradulteration;orforobtainingaretentionsample.

Theteststobeappliedtothesamplemayinclude:

verifyingtheidentity;

performingcompletepharmacopoeialoranalogoustesting;and

performingspecialorspecifictests.

1.4Classesandtypesofpharmaceuticalproductsandrelatedmaterials

Thematerialstobesampledmaybelongtothefollowingclasses:

startingmaterialsforuseinthemanufactureoffinishedpharmaceuticalproducts;

intermediatesinthemanufacturingprocess（e.g.bulkgranule）;

pharmaceuticalproducts（in-processaswellasbeforeandafterpackaging）;

primaryandsecondarypackagingmaterials;and

cleaningandsanitizingagents,compressedgasesandotherprocessingagents.

1.5Samplingfacilities

Samplingfacilitiesshouldbedesignedto:

preventcontaminationoftheopenedcontainer,thematerialsandtheope