GuidanceforIndustry:

ProductQualityReview

Version1.0

DrugOffice
DepartmentofHealth

Contents

1. Introduction..............................................................................................................................3

2. Purposeofthisdocument.........................................................................................................3

3. Scope........................................................................................................................................3

4. Schedulingproductqualityreviews.........................................................................................3

5. GroupingProducts....................................................................................................................4

6. Preparingproductqualityreviews...........................................................................................4

7. ConductinganddocumentingaPQR........................................................................................5

8. EvaluatingPQRresults.............................................................................................................7

9. PQRresponsibilitieswithcontractmanufacturing...................................................................8

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1. Introduction
ThisguidelineisintendedtoprovidegeneralguidanceontheinterpretationofthePIC/SGuideto
Good Manufacturing Practice for Medicinal Products (PIC/S Guide to GMP) with respect to
implementingProductQualityReview(PQR).
There may beother acceptable approaches thatprovide an equivalent level of quality assurance.
This guideline is not intended to create additional requirements and is not intended to form the
basisforGMPinspections.

2. Purposeofthisdocument
ToprovideguidancetoindustryonhowtoimplementProductQualityReviews(PQRs).

3. Scope
PQRsarearequirementinPIC/SGuideforGMP,Clause1.4.
Regular periodic or rolling quality reviews of all registered pharmaceutical products, including
exportonly products, should be conducted to highlight any overall trends (not necessarily visible
with other quality systems) and to identify product/process improvements by verifying and
identifying:
theconsistencyoftheexistingprocess(es);
trendsinproductdata;
the appropriateness of current specifications for starting materials, intermediates and
finishedproducts;
to verify compliance of the registered particulars of pharmaceutical products (Marketing
Authorisation);
deficienciesnotdetectedbyroutinetesting,monitoringorperformancemetrics;and
identifyopportunitiesforproductandprocessimprovements.

4. Schedulingproductqualityreviews
PQRsshouldtypicallybe:
carriedoutforeachproductmanufacturedinthepreviousyear;
takeintoaccountreviewsfrompreviousyears;and
useariskbasedapproach,refertoPIC/SGuidetoGMPAnnex20:QualityRiskManagement.
A PQR schedule is documented (typically annually) for each product/group of products within a
PQRregister(orequivalentmanagementtool).

Manufacturing
PQR scheduling requirements
circumstances
Lowbatchnumbers Ifveryfewbatches(forexample,lessthanthree)aremanufacturedwithin12
months,aPQRcouldbeconductedeverytwoyears.
In this case the justification should also consider the risk associated with the
typeofmedicineandshouldbedocumented.1
Prioritisingspecific Considerthefollowingtoassistwiththeprioritisationofproductsforreview:
PQRs recurringdeviationsoncriticalparameters;
recalls,complaintsandreturns;and
processchanges.

1
http://www.tga.gov.au/industry/manufmedicinescgmpqa.htm#ch1Question20.

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5. GroupingProducts
PQRmaybecompletedbygroupingproductsbyaparticularcharacteristic/type.
Product groupings must be scientifically justified. For example, products selected within a group
must be similar enough so that the parameters being reviewed in the PQR are representative of
thegroup.Manufacturersshouldrevieweverybatchwithinthegrouping.
The justification for the groupings selected must be documented in the PQR report, or
alternatively, within the PQR procedure if groupings/approach will remain the same across
successivePQRs.
Important:Groupingsshouldnotbejustifiedbasedoncommercialfactors.
The grouped products should be of the same pharmaceutical form containing the same or very
similaractiveingredientsandexcipients,andmanufacturedusingthesametypeofequipment.

Example of appropriate groupings: Example of inappropriate groupings:

Groupingsrelevanttothefacilitysfinished Thefollowinggroupingsareunlikelytobe
productscouldinclude: appropriatebecauseoffactorssuchas
finalpresentationsarethesamebutdifferent significantlydifferentexcipients,chemical/physical
packsizeordifferentbrandname; interactions,differenttypeofequipmentusedto
manufactureetc.:
ingredientsandprimarypackagingisthe
same,butdifferentstrengths;and productswiththesameAPIbutverydifferent
excipients;and
finalpresentationsarethesamebutdifferent
marketedregionsand/orproduct liquidvs.solidpreparationsofthesameAPI
registrations. (e.g.creamvs.topicalointment,tabletvs.
gelcapvs.capsule).

The number and name of all finished products manufacturedwillvary from yearto year and as
newlicensedproductscomeontothemarket.Therefore,thenumberandnameofeachproduct
manufactured during the period of review for the PQR must be included within the PQR report
andwithinthePQRregister.

6. Preparingproductqualityreviews
A PQR report should be preparedfor every scheduled review using a controlled reporttemplate
toensureastandardiseddocumentationapproach.Thereportshouldincludethefollowing:
productname(s);
batchsize(s)andpresentation(s);
reviewdate;
referencestosourcedata;
comparisonofthereviewfrompreviousPQRs;
datethatthenextreviewisrequired;
groupingsandscientificjustification;
identificationofissuesortrends;
summaryoffindings,conclusionsandrecommendations;
proposedactions;and
names and signatures (with date) of the persons responsible for preparing, reviewing and
approvingthereport.

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7. ConductinganddocumentingaPQR
PIC/SGuidetoGMP(Clause1.4)requiresthefollowingparameters(atminimum)tobeassessed
whenconductingPQR.

Parameter Examples of information to be reviewed

Startingmaterials: Identifyallstartingandpackagingmaterialsreceivedinthe
Areviewofstartingmaterials yearandusedinproductmanufacture
includingpackagingmaterialsused Nameofthesuppliers/manufacturersofthematerials
intheproduct,especiallythose SuppliersCertificateofAnalysis(CoA)orCertificatesof
fromnewsources. Compliance(CoC)oranalyticalresults
Significantdeviationsortrends
Inspectionrejectionrate
Changestoproductionprocessorspecificationsby
suppliers
Resultsofanalyticaltests
Inprocesscontrolsandquality TrendinprocesstestresultsandQCtestresultsinthe
controltesting: manufacturingandpackagingprocessfrombothchemistryand
Areviewofcriticalinprocess microbiologyaspects:
controlsandfinishedproduct Trendingmaytakeintoconsideration:
results. Physicalvariationse.g.weight/dimension,friability,
hardness,disintegrationtime,fillvolume/overage,
uniformityofcontent
Chemicalvariationse.g.assay,related
substances/manufacturingrelatedimpurities,pH,residual
solvents
Rejectedunitse.g.breakages,particulates,etc.
Yieldreconciliationfromstagesofthemanufacturingprocess
usingdatafromtheassociatedbatchrecords.
Manufacturedbatches Listdeviationsandnonconformancesassociatedwiththe
(intermediates,bulk,finished productunderreview
productsandcampaign Identifydeviation/CAPAreportsandtheassociatedbatches
batches):
Identifycurrentstatusofinvestigationsprovidinga
Areviewofallbatchesthatfailedto summaryofthe:
meetestablishedspecification(s)
- reasonforthefailure
andtheirinvestigation.
- completedinvestigations
- correctiveactionstaken
- effectivenessoftheaction
DeviationsandCAPA: Listthefollowingrelatingtosignificantdeviationsandnon
Areviewofallsignificantdeviations conformances:
ornonconformances,theirrelated - reasonforthefailure
investigations,andtheeffectiveness - completedinvestigations
ofresultantcorrectiveand
- correctiveactionstaken
preventiveactionstaken.
Assesscorrectiveactionsforsignificantdeviationsandnon
conformancesfrompreviousPQRs,indicatingthestatusof
eachofthecorrectiveactions,andtheireffectiveness

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Parameter Examples of information to be reviewed

Processortestingchanges: Changesassessedshouldconsiderboththoseclosedduring
Areviewofallchangescarriedout thereviewperiodandapprovedtocommencebutnotyet
totheprocesses,oranalytical implemented.Thechangestatusshouldbeidentifiede.g.
methods. approvedtocommence,closedandassociateddates
Categorisethechangetypee.g.component,labelling
packagingmaterials,manufacturingprocess,analytical
methodsetc.andassessfortrendsandoverallimpacton
quality
Identifythebatchesaffected
Provideajustificationforthechange
Reviewtheeffectiveness/impactofthechangeonthe
batchunderreview
Marketingauthorisations: ListandreviewtheMarketingAuthorisationvariations(include
AreviewofMarketingAuthorisation thirdcountry/exportonlydossiers):
variationssubmitted/granted/ numberofproductssubmittedandgranted/refused
refused,includingthoseforthird numberofproductsregisterslocallyandoverseas
country(exportonly)dossiers.
anychangesmadetotheproductthatrequiresubmission
ofavariationtotheMarketingAuthorisation
fortheabove,variationsthathavebeensubmitted.Ifnot
submitted,thereasonsthereforeshouldbeinvestigated
andaconclusiondocumented
forvariationssubmitted,whetherornottheyhavebeen
grantedorrefused.Ifrefused,theimpactshouldbe
assessedanddocumented
Stabilityprogramme: Listthenumberofbatchesofproductinreviewincludedin
Areviewoftheresultsofthe stabilitystudiesduringthereviewperiod
stabilitymonitoringprogrammeand Reviewtheresultsofanylongtermandongoingstability
anyadversetrends. ofthebulkandmarketedproduct
Includeproductinformationsuchasmanufacturingdate,
referencetotheassociatedmethod,shelflife,etc.
Reviewanyoutofspecificationresults
Returnedproduct: Batchnumber(s)
Areviewofallqualityrelated Reasonforreturnandclassificationofreasonfortrending
returnsandtheinvestigations Associatedinvestigationreportnumber
performedatthetime.
Actionstakenandbatchesaffected
Complaintsand/oradverse Batchnumber(s)
events: Reasonforcomplaintandclassificationfortrending
Areviewofallqualityrelated Previousinstancesoveradesignatedtimeperiod
complaintsandtheinvestigations
Associatedinvestigationreportnumber
performedatthetime.
Actionstakenandbatchesaffected
Currentstatus
Recalls: Batches/productrecalled
Areviewofallqualityrelatedrecalls Reasonforrecallandclassificationfortrending
andtheinvestigationsperformedat Regulator(s)notifiedandrequiredregionalresponses
thetime.
Associatedinvestigationreportnumber
Actionstakenandbatchesaffected
Currentstatus

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Parameter Examples of information to be reviewed

ReviewofpastPQRresponses: ThefocusofthisrequirementisonpreviousPQRsandthe
Areviewofadequacyofanyother statusandeffectivenessofassociatedactions:
previousproductprocessor reviewandreportonpreviousPQRCAPAsandchange
equipmentcorrectiveactions. implementationstatus
assesseffectivenessofactionstakingintoaccountthe
currentPQRfindings
Postmarketingcommitments: Countryofcommitment
FornewMarketingAuthorisations Productnameandpresentation
andvariationstoMarketing Descriptionofthecommitment
Authorisations,areviewofpost
Statusofthecommitment
marketingcommitments(ifany).
Equipmentqualification: Listandreviewthefollowingforcriticalequipment/instruments
Thequalificationstatusofrelevant andutilitiesinproductionandlaboratorydepartments
equipmentandutilities,e.g.HVAC, associatedwiththeproductinreview:
water,compressedgases,etc. Qualification/requalificationstatusandthenext
qualificationduedateofequipmentusedintheproduction
processesandQClaboratory
Referencetorelevantqualificationreports
Reviewchangesmadetoequipmentandutilitieswhich
resultedinrequalificationandassessforsubsequent
impacttoproductquality
Contractualagreements: Reviewcontractsforservicesassociatedwiththeproductin
Areviewofanycontractual reviewandreport:
arrangementstoensurethatthey nameandaddressofthecontractacceptor
areuptodate. availabilityanddetailsofthewrittencontract
typeofserviceprovidede.g.testingormaintenanceand
calibrationservices
confirmationthattheservicesprovidedarealignedwiththe
marketingauthorisation
RefertoPIC/SGuidetoGMP,Chapter7foradditional
informationoncontractmanufactureandcontract
requirements.

8. EvaluatingPQRresults
The manufacturer must evaluate the results of the PQR to determine whether actions are
required,including:
correctiveorpreventativeactions;
validationorrevalidation;and

othersiteorprocesschanges.

Processesshouldbedemonstratedtobeincontrolbydeterminingupper/lowerlimitsandtrends.
Preventative actions mustbe implementedfor anyprocesses shown tobe notin control before
deviationsoroutofspecificationsoccur.

8.1Identifyingtrends
Appropriate statistical analysis technique should be used to review the data collected as part of
thePQR.

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Technique Example

Charting Runchart
Controlchart(e.gIandMRcharts)

Processcapability Processcapabilitystudyisastatisticalmethodwhichcanbeusedby
studies manufacturerstoestablishifspecificationlimitsaresetappropriately(eg.
UCLandLCL).Itcomparesprocessinformationtotheupperandlower
specificationlimits
ItisrecommendedthatCp/Cpkvaluesaretargetedat1.33orabove

8.2Interpretingresults
Analysis must be interpreted and documented as this will assist manufacturers to identify
correctiveandpreventativeactionsifrequired.
Proposed actionsandconclusions,includingjustification fornotimplementingactionswhen the
PQR has revealed an adverse trend on product quality must also be documented in the PQR
report.

9. PQRresponsibilitieswithcontractmanufacturing
When manufacturingprocesses are partlyor whollycontractedout,technical agreements should
beinplacebetweenthevariouspartiesthatdefinestheirrespectiveresponsibilitiesinconducting
thePQR.
Refer toPIC/S Guide to GMP,Chapter 7 for additional information on contractmanufacture and
contractrequirements.

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DocumentInformation

Version Date DescriptionofChange

1.0 27Dec2013 Firstversion

References

DocumentTitle

PIC/SGuidetoGoodManufacturingPracticeforMedicinalProductsPE00910:PartIandII

PIC/SGuidetoGMPAnnex20:QualityRiskManagement

HealthSciencesAuthorityRegulatoryGuidance:GuidanceNotesonProductQualityReview

DOCUMENTEND

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