Guidance on the GMP clearance of overseas medicine 對國外藥品GMP間隙的指導(dǎo)

TherapeuticGoodsAdministration

Copyright

?CommonwealthofAustralia2011

Thisworkiscopyright.ApartfromanyuseaspermittedundertheCopyrightAct1968,nopartmaybereproducedbyanyprocesswithoutpriorwrittenpermissionfromtheCommonwealth.RequestsandinquiriesconcerningreproductionandrightsshouldbeaddressedtotheCommonwealthCopyrightAdministration,AttorneyGeneral’sDepartment,NationalCircuit,BartonACT2600orpostedat.au/cca

GMPClearanceforOverseasManufacturers,17thEdition

Version1.0,May2011

Pagei

AustralianRegulatoryGuidelinesGoodManufacturingPractice(GMP)ClearanceforOverseasManufacturers

17thEdition

Version1.0May2011

AbouttheTherapeuticGoodsAdministration(TGA)

TheTGAisadivisionoftheAustralianGovernmentDepartmentofHealthandAgeing,andisresponsibleforregulatingmedicinesandmedicaldevices.

TGAadministerstheTherapeuticGoodsAct1989(theAct),applyingariskmanagementapproachdesignedtoensuretherapeuticgoodssuppliedinAustraliameetacceptablestandardsofquality,safetyandefficacy(performance),whennecessary.

TheworkoftheTGAisbasedonapplyingscientificandclinicalexpertisetodecision-making,toensurethatthebenefitstoconsumersoutweighanyrisksassociatedwiththeuseofmedicinesandmedicaldevices.

TheTGAreliesonthepublic,healthcareprofessionalsandindustrytoreportproblemswithmedicinesormedicaldevices.TGAinvestigatesreportsreceivedbyittodetermineanynecessaryregulatoryaction.

Toreportaproblemwithamedicineormedicaldevice,pleaseseetheinformationontheTGAwebsite.

TherapeuticGoodsAdministration

GMPClearanceforOverseasManufacturers,17thEdition

Version1.0,May2011

Page

of

NUMPAGES

40

Versionhistory

Version

Descriptionofchange

Author

Effectivedate

V1.0

NewDocument

OfficeofManufacturingQuality

12/05/11

Contents

TOC\o"1-3"

Introduction

6

TGAContactDetails

8

Regulatoryinformation

8

1. ResponsibilitiesofAustraliansponsorsofmedicinesmanufacturedoverseas

9

2. GMPClearanceprocess

11

Figure1-OverviewoftheGMPclearanceprocess

11

2.1. GMPClearanceapplicationrequirements

12

GMPClearance

12

RenewingaGMPClearance

12

ChangestoaGMPClearance

12

ExtensionofaGMPClearance

13

2.2. PathwaysforobtainingGMPClearance

13

GMPClearancesissuedunderaMutualRecognitionAgreements(MRA)

14

GMPClearancesissuedthroughGMPComplianceVerification(CV)

14

TGAon-siteaudit

14

2.3. Identifyandobtaintherequireddocumentation

15

Table1(a)–Requiredassessmenttype

15

Table1(b)–Documentaryevidencerequirements

16

Generaldocumentaryrequirements

17

GMPCertificates

18

Manufacturer’sdeclarationsforActivePharmaceuticalIngredients

19

DocumentsforaTGAon-siteaudit

19

Sharingofdocumentaryevidencebetweensponsorsandmanufacturers

19

2.4. Submitapplicationandpayfees

20

LodginganapplicationforclearancebyMRAandComplianceVerification

20

FailuretoprovideadequateGMPevidence

21

Paymentofapplicationfees(forMRAandCV)

21

LodginganapplicationforaTGAon-siteaudit

21

FeesforTGAon-siteaudit

21

Scheduleoffees

21

2.5. TGAassessment

22

Targettimeframes

22

2.6. OutcomesofTGAassessment

22

Clearanceapproval

22

ConditionalClearance

22

Rejectionofanapplication

22

3. MaintenanceofaClearance

23

Clearanceexpiry

23

4. Revocationorreductioninscopeofaclearance

24

Appendices

25

AppendixA-Glossaryofterms

25

AppendixB–Internationalagreements

29

AppendixC-Explanatorynotesfordocumentaryevidence

31

GMPAgreementswithmanufacturers

31

Procedure(s)forReleaseforSupplyofFinishedProducts/APIs

31

ProductQualityReviews

31

SiteMasterFile(SMF)

31

ValidationMasterPlan(VMP)

32

AppendixD-Manufacturer’sdeclarationforAPIs

33

AppendixE-ElectronicapplicationoneBusiness

34

AppendixF-Electronicapplicationchecklist

35

ForGMPClearancesbasedonaMutualRecognitionAgreement

35

ForGMPClearancestobeassessedbyComplianceVerification

35

AppendixG–FlowChartforGMPclearance

36

AppendixH–ManufacturerProfiles

37

Whattheyare

37

Whatinformationtheywillcontain

37

Howitwillwork

37

AppendixI–TargetTimeframes

38

On-SiteAudits

38

Introduction

TheseguidelineshavebeendevelopedtoprovideinformationabouttheprocessofobtainingandmaintainingGoodManufacturingPractice(GMP)clearancesforthemanufacturingstepsofmedicinalproductsincludingActivePharmaceuticalIngredients(APIs)thatarecarriedoutoverseas.TheydescribetheapproachoftheTherapeuticGoodsAdministration(TGA)tograntingGMPclearancesinrelationtothesemanufacturingstepsandthedocumentationrequiredfortheassessmentofapplications.

ThemainobjectiveoftheTherapeuticGoodsAct1989(theAct)istoensurethesafety,quality,efficacyandtimelysupplyoftherapeuticgoodsforAustralianconsumers.Withtheincreasingnumberofoverseassuppliersandthegrowingcomplexityinsupplychains,AustralianconsumersareentitledtobeconfidentthatmanufacturerslocatedoutsideAustraliaaresubjecttoequivalentqualitystandardsofoversighttothoseapplyingtoAustralianmanufacturers.

Therapeuticgoodsthataremedicines(medicinalproducts)suppliedinAustraliaarerequiredtobeincludedontheAustralianRegisterofTherapeuticGoods(ARTG)byaprocessofregistrationorlistingNote:UndertheTherapeuticGoodsAct1989sometherapeuticgoodsarenotrequiredtobeincludedontheARTG.

.TheOfficeofMedicinesAuthorisation(OMA)intheTGAissuesamarketingauthorisationforamedicinalproductwhenitisenteredintheARTG.

Undersections25(1)(g)and26A(3)oftheActasponsorseekingregistrationorlistingofamedicinalproductmustsupplyevidencethateachoverseasmanufacturerinvolvedinthemanufactureoftheproducthasacceptablemanufacturingandqualitycontrolproceduresinplaceTherequirementsintheActvary,basedonwhetherthefinalproductsarerequiredtoberegisteredorlistedintheRegister.Forregisteredgoods,section25(1)(g)states:

25 Evaluationandregistrationoftherapeuticgoods

(1) …theSecretarymustevaluatethegoodsforregistrationhavingregardto:

...

(g) ifastepinthemanufactureofthegoodshasbeencarriedoutoutsideAustralia-whetherthemanufacturingandqualitycontrolproceduresusedinthemanufactureofthegoodsareacceptable;

...

Forlistedgoods,section26A(3)states:

26A Listingofcertainmedicines

(3) Subjecttosubsection(7),ifastepinthemanufactureofthemedicinehasbeencarriedoutoutsideAustralia,theSecretarymusthavecertified,priortotheapplicationbeingmade,thatthemanufacturingandqualitycontrolproceduresusedineachsuchstepareacceptable.

.ItisalsoaconditionofongoingregistrationandlistingthatsuchevidenceissuppliedonrequestConditionsimposedundersection28oftheTherapeuticGoodsActsponsorsarerequiredtomaintainevidenceofGMPComplianceofanoverseasmanufacturerasastandardconditionofregistrationorlistingofatherapeuticgood.Paragraph23oftheStandardandSpecificConditionsapplyingtoRegisteredorListedTherapeuticGoodsdeterminedundersection28(2)states:

23 GoodsManufacturedOverseas

Wheretheregistered/listedgoodsareimportedgoodswhichifmanufacturedinAustraliawouldberequiredundertheprovisionsoftheActtobemanufacturedinlicensedpremises,thesponsorofthegoodsshall,uponrequestatanytimebytheSecretaryortheSecretary'sdelegateappointedforthepurposesofsection31oftheAct,providetotheNationalManager,TherapeuticGoodsAdministration,anacceptableformofevidencewhichestablishesthestandardofmanufactureofthegoods.Ifthisisnotavailable,thesponsorshallpaythecostsofaninspectionoftheprincipalManufacturerofthegoodsbyAustralianinspectorswherethisisconsiderednecessarybytheSecretaryortheSecretary'sdelegatereferredtointhisparagraph.

.Theserulesapplyif,hadthegoodsbeenwhollymanufacturedinAustralia,theAustralianmanufacturerwouldberequiredtoholdamanufacturinglicenceundertheAct.

TheTGAconsiderswhethertheoverseasmanufacturercomplieswiththeManufacturingPrinciples(orequivalentinternationalstandardsforoverseasManufacturers).On1July2010,theTGAadoptedthePIC/SGuidetoGMPforMedicinalProducts,January2009–PE009-8,forbothMedicinalProductsandAPIs.ThisstandardreplacestheAustralianCodeofGoodManufacturingPracticeforMedicinalProducts16August2002,theICHQ7GuidelineandtheCodeofGoodManufacturingPracticeforSunscreenProducts.

ThisprocessandtheissuingofadocumentthatconfirmscomplianceisknownasGMPClearance.ForthepurposesofundertakingGMPClearance,theTGAconsidersanapplicationbythesponsorandevidencefromanumberofsources.

TheTGAhasestablishedarangeofinternationalagreementstofacilitatetheefficientandeffectivemanagementofitsregulatorycomplianceprogramsandreducetheregulatoryburdenonindustry.Theyinclude:

MutualRecognitionAgreements(MRA)thataretreatiesbetweenAustraliaandothercountriesandareenforceableunderinternationallaw,and

MemorandaofUnderstanding(MOU)thatarearrangementssbetweentheTGAandregulatoryagenciesofothercountriesthatfacilitatetheexchangeofinformation.

ThepartiestoanMRArecogniseandacceptthecertificationissuedbytherelevantregulatoryagencyineachcountryinrelationtomanufacturerslocatedwithinthatcountry.ThecountrieswithwhichAustraliahasMutualRecognitionAgreementsandthescopeoftheproductscoveredbytheseagreementsisincludedinAppendixB.Themutualrecognitionofcertificatesislimitedtomanufacturerswithinthecountryoftheissuingauthority.MRACertificatesformanufacturersoutsidetheregulator’scountrycanbeusedassupportingevidenceinconjunctionwithotherdocumentaryevidenceasoutlinedintables1aand1b.

AnoverseasGMPClearancecanbegrantedbytheTGAtoasponsoronthebasisofGMPComplianceevidencedbyanyoneofthefollowing:

AGMPCertificateissuedbyacountrywithwhichAustraliahasanMRAinrelationtotherelevantoverseasmanufacturingsite.

AComplianceVerificationassessmentofarecentGMPinspectionreportoftherelevantoverseasmanufacturingsitepreparedbyacompetentoverseasregulatoryagencyacceptabletotheTGA,togetherwithsupportingmanufacturingdocumentationsuppliedbythesponsorormanufacturer.

AGMPCertificateissuedbytheTGAfollowinganon-siteauditoftherelevantoverseasmanufacturingsite.

TheTGAreservestherighttoundertakeanauditofanoverseasmanufacturingsite,irrespectiveofanyotherevidencesupplied.Forexample,thismaybewhereTGAhasotherregulatoryinformation,hasconcernsregardingcompliance,orisauditinganadjacentfacility.AnauditmaytakeplacepriortograntinganinitialGMPClearanceforsupplyoftherelevantproductinAustraliaoratanytimefollowingtheissueofaGMPClearance.

OverseasGMPClearancesaregrantedforaspecifiedtimeperiod.SponsorsmustmonitortheexpirydateofGMPClearancesforalloverseasmanufacturersusedandsubmitfurtherapplicationswitheithersupportingGMPevidenceorarequestforaTGAon-siteauditofrelevantoverseasmanufacturingsitesbeforethecurrentGMPClearanceexpires.

AstheTGAisrequiredtorecoverthefullcostofitsregulatoryactivities,sponsorsarerequiredtopaytohaveanapplicationforGMPClearanceassessed.AuditfeesapplyiftheTGAcarriesoutanoverseason-siteaudit.

Therelevantfeesandcharges,includingthebasisofcalculatingfees,arelocatedontheTGAwebsiteat

.au/about/fees-current.htm

TGAContactDetails

Forfurtherassistance,contacttheTGAGMPClearanceUnit:

Tel-1800446443

Fax-(02)62328426

Email-

gmpclearance@.au

Post:

GMPClearanceUnit

OfficeofManufacturingQuality

TherapeuticGoodsAdministration

POBox100

WODENACT2600

Toarrangeforanauditofanoverseasmanufacturer,contacttheTGALicensingandCertificationUnit

Tel-1800446443

Fax-(02)62328426

Email-

gmp@.au

ThisinformationisalsoavailableontheTGAwebsiteat

.au/industry/manuf.htm

Regulatoryinformation

InformationcanbeobtainedfromtheOfficeofMedicinesAuthorisationaboutthecircumstancesinwhichaGMPClearanceisrequiredforaparticularactivityinvolvedinmanufacturingafinishedproductoranAPI.

Sponsorscanseekinformationoradvicefromanagentorregulatoryconsultantconcerningtherequirementsforsubmittinganapplicationforaclearanceand/orthesuitabilityandcomplianceofanoverseasmanufacturingsite.

TheTGAdoesnotendorseagentsorregulatoryconsultants.FurtherdetailsconcerningagentsorconsultantscanbeobtainedfromvariousindustryassociationsortheAssociationofTherapeuticGoodsConsultantsInc.

LinkstothesebodiesareavailableontheTGAwebsiteat

.au/industry/basics-regulatory-affairs-consultants.htm

ResponsibilitiesofAustraliansponsorsofmedicinesmanufacturedoverseas

ThekeyresponsibilitiesofAustraliansponsorsofmedicinesthatuseoverseasmanufacturersinrelationtoGMPClearancesarelistedbelow.Pleasenotethislistisnotexhaustiveandsponsorsshouldsatisfythemselvesthattheyhavedoneallthattherelevantlegislationandguidelinesrequire.

AsponsorwhoproposestoseekmarketauthorisationforsupplyinAustraliathroughtheregistrationorlistingoftheproductontheARTGorwhohasaproductregisteredorlistedontheARTGisresponsiblefor:

ProvidingtotheTGArelevantevidenceofGMPcomplianceforthepurposesofobtainingthemarketingauthorisationtosupplymedicinalproductsinAustralia;

MaintainingevidenceofGMPcomplianceofalloverseasmanufacturingsitesusedinthemanufactureoftheregisteredorlistedmedicine,andnotifyingtheTGAimmediatelyofanychangesincircumstancesorregulatorycomplianceoftheoverseasmanufacturer.TheTGAisintroducingaPeriodicManufacturerUpdateformtoassistsponsorsinmeetingthisresponsibility.ThisformallowssponsorstoinformtheOfficeofManufacturingQualityofnon-criticalchangessuchaschangesinproductionandproducts,whichensurestheinformationtheTGAholdsofthemanufacturerremainscurrent.TheformwillbeaccessiblefromtheTGAwebsite.AnycriticaleventsshouldbenotifiedimmediatelytoGMP@.au.

SponsorsareresponsibleforalloverseasmanufacturingsitesnominatedintheirClearanceapplicationsatalltimes.

SponsorsarerequiredtoadvisetheTGAofany“significantchanges”tothemanufacturingsite,qualitymanagementsystem(QMS),productsorproductrange(thesearechangesthatcouldpotentiallyaffectGMPcompliance)–changesmayalsorequireavariationapplicationforthesponsor’slistingorregistrationontheARTG.

Sponsorsshouldmonitorregulatoryactionsbyanycompetentoverseasregulatoryagency(i.e.recalls,unacceptableinspectionfindings,warningletters)thatinvolvesanyoverseasmanufacturerusedbythesponsor.

SponsorsmustnotifytheTGAassoonastheoverseasmanufacturingsiteisnolongerusedandisnotintendedtobemaintainedasanalternativemanufacturer.

EstablishingandmaintainingGMPagreementswithmanufacturerswithwhichthesponsorhasadirectrelationship.Wherethemanufacturerisawhollyownedsubsidiaryofthesameparentcompanyasthesponsor,therolesandresponsibilitiesofthepartiesshouldbedocumentedintheabsenceofaagreement.SponsorsarenotexpectedtohaveaGMPagreementwithamanufacturer’ssub-contractorsGMPcontractsbetweenprincipalmanufacturersandsub-contractorsarerequiredbythecodeofGMP

.

EnsuringthatallrequireddocumentsaresubmittedelectronicallywithapplicationsforGMPClearance.

Incompleteapplicationsmayberejected.

RemittingallapplicationfeesatthetimeoflodginganapplicationforGMPClearance(refertoScheduleoffeesat

.au/about/fees-current.htm

).

Initialprocessingofanapplicationwillnotcommenceuntilpaymentoftheapplicationfeehasbeenreceived.

Anyapplicableassessmentfeeinvoicedtothesponsormustalsobepaidbeforeassessmentofanapplicationcancommence.

SubmittingapplicationsforrenewalofaGMPClearanceatleastsixmonthspriortotheexpiryofthecurrentClearance.Thisallowstime:

tosubmitanextensionofaClearancewhereevidenceisnotyetavailable.See3.1;or

todeterminetheneedforarequestthattheTGAattempttoobtainevidencefromtherelevantMRAregulatorSee3.2;or

forschedulinganoverseasauditshoulditappearduringtheassessmentthatsuchanauditisrequired.

PromptlysubmittinganyadditionalinformationrequestedbytheTGAduringanassessment.

FailuretoproviderequireddocumentsinthetimerequestedbytheTGAmayresultintheapplicationbeingrejectedwithoutarefundoffeespaid.

Aseparateapplicationisrequiredforeachoverseasmanufacturingsiteusedinrelationtodosageformsforregisteredorlistedmedicines.

Clearanceextensionsmaybegrantedifsomedocuments(egauditreport)fortheclearanceapplicationarenotyetavailable.

GMPClearanceprocess

Figure1-OverviewoftheGMPclearanceprocess

Aseparateapplicationisrequiredforeachsponsorandforeachoverseasmanufacturingsite.Applicationsarerequiredforrenewals,changestoscope,changestostepsofmanufactureandmajorfacilitychanges.

Assessmentofanapplicationisbasedonthefollowingevidence:

MutualRecognitionAgreements(MRA)

ComplianceVerification(CV)

aTGAon-siteaudit

(ApplicationsforaTGAauditwillnotbeacceptedwhileanMRAorCVassessmentisinprogress.)

Theextentofthereviewprocessincreaseswithproductriskandthecomplexityofmanufacture.

RefertoTables1(a)and1(b).

RefertoAppendixEandthecurrent‘scheduleoffees’at

.au/about/fees-current.htm

.AdditionalfeesmaybepayableiftheTGAisrequestedtoobtainevidencefromanoverseasregulatororiftheapplicationissubjecttoaCV.

TGAmayrequestadditionalinformation.

Applicationmayberejectedifinformationisnotsuppliedwithinduedates.

AssessmenttimeframescanbefoundinappendixI

Iftheapplicationisineffectiveandrequestedinformationcannotbepresented,theTGAwillnotifythesponsorofaproposalnottoissueaclearanceandprovidethesponsortheopportunitytorespond.

SponsorisissuedaGMPClearanceletterfollowingasuccessfulMRAorCVassessmentoraTGAonsiteaudit.ACertificateofGMPCompliancemaybeissuedtothemanufactureronrequestfollowingasuccessfulTGAon-siteaudit.

2.1RequirementforGMPClearanceapplication

Ineffectiveapplication

ClearanceLetterorGMPCertificate

Ifrequestedsubmitadditionalinformation

2.5and2.6

TGA

assessment

2.2PathwaysforobtainingGMPClearance

2.4SubmitelectronicClearanceapplicationandpayapplicationfees

2.3Identifyandobtainrequireddocumentation

GMPClearanceapplicationrequirements

GMPClearance

GMPClearancesarerequiredforallthestepsofmanufactureofregisteredandlistedmedicinalproducts(includingAPIsusedforthemanufactureofregisteredproducts)beforetheproductscanbesuppliedinAustralia.

AlthoughtheTGAdoesnotcurrentlyrequiresponsorstosubmitClearanceapplicationsforAPIsusedinlistedmedicinesorregisteredover-the-counter(OTC)andcomplementarymedicines,sponsorsmustensurethatanystepofmanufactureundertakenoutsideofAustraliaisundertakeninGMPcompliantfacilities.EvidenceoflicensingorapprovalofthemanufactureroftheAPI(s)doesnotneedtobesubmittedtotheTGAunlessitisanintermediateproduct(egpremixes).SeeARGOMsectionX.2.1

RenewingaGMPClearance

GMPClearancesrelatingtooverseasmanufacturersareprovidedforaspecifiedperiodandhaveanexpirydate.Sponsorsmustthereforeapplyperiodicallytorenewtheirclearancesforoverseasmanufacturingsitesforaslongastheycontinuetousethatmanufacturer.ThispermitstheTGAtoreviewthemanufacturingandqualitycontrolsandprovidecontinuousconfidencetothepublicofthemanufacturer’scompliancewithrelevantinternationalGMPstandards.

ChangestoaGMPClearance

TheTGAexpectssponsorstoremainvigilantinensuringtheregulatorycomplianceoftheoverseasmanufacturingsitestheyuse.WhenasponsorbecomesawareofaneedtochangeorrenewaGMPClearance,anewapplicationwithallrequireddocumentationmustbesubmitted,andapplicablefeespaid.

ExamplesofcircumstanceswhereasponsormayneedtoamendorcancelaGMPClearanceinclude:

Ifproductsaretransferredbetweensponsors;anamendmentoftheClearancemustberequestedwithin3monthsfromthedateoftransfer.

WhereproductsontheARTGhavebeentransferredtoanothersponsor,thenewsponsormustprovidethedetailsofallaffectedclearances(products,ManufacturersInformationSystem(MIS)clearancenumbersetc.)andenclosealetterfromthetransferringsponsorindicatingassenttotheclearancetransfers.Acopyofanysale/transferagreementmayalsobeacceptable.

EachsponsormusthaveaGMPagreementwitheachmanufacturerwithwhomtheyhaveadirectrelationship.

Thereisnoneedtosubmitanewclearanceapplicationaslongastheclearancesinquestionarecurrent.

Note:Thereiscurrentlynofeeattachedtothischange.

Achangeinthetradingnameofanoverseasmanufacturerfollowingachangeinownership.

Sponsorsshouldprovideacopyofthecertificateofregistrationoraletterfromtheregistrarinthemanufacturer’scountryconfirmingthechangeofnameIfeitheroftheseisnotavailable,adeclarationfromthemanufactureronitsletterheadstatingthechangeinthemanufacturer’snamemaybeaccepted

.

ChangesinthescopeofmanufactureoftheexistingGMPClearance,forinstancewheretheCurrentGMPClearanceisforthemanufactureofhardcapsulesandthesponsornowwishestoincludesoftgelcapsules.

AnewGMPClearanceapplicationmustbesubmitted.Feesarepayable.

Newmanufacturingsiteoranewmanufacturingfacilityattheexistingsite.

AnewGMPClearanceapplicationmustbesubmittedifmanufactureforsupplytoAustraliaistooccuratthenewsite/facility.Feesarepayable.

Supplyofproductsfromthemanufacturingsiteceases.

ThesponsorshouldnotifytheTGAGMPClearanceUnitinwritingandtheclearancewillbecancelled.

Note:Thereiscurrentlynofeeattachedtothischange.

Significantnewmanufacturingsteps,orsignificantlydifferenttechnology,inthemanufactureofanexistingproductontheARTGwheretheoverseasmanufacturerhascurrentGMPClearanceapprovalthatdoesnotincludethenewstepsortechnology.(e.g.fermentationinadditiontochemicalsynthesisforanAPIManufacturer).

AnewGMPClearanceapplicationmustbesubmitted.Feesarepayable.

AreductioninthescopeofaGMPClearancemayberequiredwherethemanufacturingsitedecommissionsfacilities,orhasceasedmanufactureasaresultofregulatoryactionsbyanoverseasagency.SponsorsshouldmonitortheirmanufacturersandcommunicatethesechangestotheTGApromptly.

ThesponsorshouldnotifytheTGAGMPClearanceUnitinwritingandtheclearancewillbeamended.

Note:Thereiscurrentlynofeeattachedtothischange.

ExtensionofaGMPClearance

Ashorttermextension(generally3to6months)toaGMPClearancemaybegrantedundercertaincircumstancesattherequestofasponsor.Thecircumstancesmightincludeforinstancewhenaninspectionhastakenplace(orisscheduledtotakeplace)andthereisadelayintheissuingoftheGMPCertificateand/orinspectionreport.DocumentationindicatingthescopeoftheproposedinspectionisrelevantandshouldbesuppliedtotheTGAwhentheapplicationforextensionismade.

ApplicationsshouldbemadetotheGMPclearanceunit.

Thereasonsfortheextensionmustbeclearlysetoutandrelevantsupportingdocumentationprovided.SponsorsshouldnotexpectthattheTGAwillgrantanextensionwheretheapplicationismadeaftertheClearancehasexpired.

WhereaninspectionreportorotherdocumentationreceivedafteranextensionhasbeengrantedisfoundbytheTGAtobeunacceptable,anyextensiontoaGMPClearancepreviouslygrantedmaybecancelled.

PathwaysforobtainingGMPClearance

AGMPClearanceofanoverseasmanufacturerwillalwaysbebasedontheassessmentofevidenceofGMPCompliancethatincludesarecentinspectionofthemanufacturerbyacompetentregulatoryagency.

TherearethreeproceduresusedtograntaGMPClearance:

underaMutualRecognitionAgreement(MRA);

throughComplianceVerification(CV);or

afteraTGAon-siteaudit.

Theavailableprocedureforassessmentwilldependon:

whethertheTGAhasagreementswiththeregulatoryagencythathasinspectedamanufacturingsite;

wherethesiteislocated;

theTGA’slevelofconfidenceofcompliancewithanequivalentCodeofGMPdemonstratedbytheevidencesubmittedbythesponsor;

thetypeofproduct(s)ormanufacturingstepsundertakenatthesite;and

thetimingoftheinspection.

GMPClearancesissuedunderaMutualRecognitionAgreements(MRA)

Inaccordancewithinternationalagreementswithcertaincountries,theTGAacceptscomplianceofanoverseassitewiththelocalGMPrequirementsbasedonacurrentGMPCertificateissuedbytheregulatoryagencyoftheotherpartytotheMRA.

ClearancemaybegrantedbytheTGAonthebasisofacurrentGMPCertificateissuedwithinthescopeofaMRAagreement.

MRA-basedassessmentsarelimitedtoGMPCertificatesissuedformanufacturingsiteslocatedwithinthebordersoftheotherpartytotheMRA.

ThescopeofthemanufacturingactivitiesforwhichapprovalissoughtintheClearanceapplicationshouldbewithinthescopeoftheactivitiescoveredbytheGMPCertificate.

AlistofcountrieswithwhichAustraliahasanMRAorequivalentiscontainedinAppendixB

GMPClearancesissuedthroughGMPComplianceVerification(CV)

ComplianceVerificationinvolvesadetailedassessmentbytheTGAofspecifieddocumentaryevidencesuppliedbythe