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首页 FDA资料汇编美国现行药品生产质量管理规范(cGMP-en)

FDA资料汇编美国现行药品生产质量管理规范(cGMP-en).doc

FDA资料汇编美国现行药品生产质量管理规范(cGMP-en)

longyun918
2018-09-07 0人阅读 举报 0 0 0 暂无简介

简介:本文档为《FDA资料汇编美国现行药品生产质量管理规范(cGMP-en)doc》,可适用于医药卫生领域

CodeofFederalRegulationsTitle,VolumeRevisedasofApril,CITE:CFRTITLEFOODANDDRUGSSUBCHAPTERCDRUGS:GENERAL PARTCURRENTGOODMANUFACTURINGPRACTICEFORFINISHEDPHARMACEUTICALS SubpartAGeneralProvisionsSecScopeLinktoanamendmentpublishedatFR,May,(a)Theregulationsinthispartcontaintheminimumcurrentgoodmanufacturingpracticeforpreparationofdrugproductsforadministrationtohumansoranimals(b)Thecurrentgoodmanufacturingpracticeregulationsinthischapter,astheypertaintodrugproducts,andinpartsthroughofthischapter,astheypertaintobiologicalproductsforhumanuse,shallbeconsideredtosupplement,notsupersede,theregulationsinthispartunlesstheregulationsexplicitlyprovideotherwiseIntheeventitisimpossibletocomplywithapplicableregulationsbothinthispartandinotherpartsofthischapterorinpartsthroughofthischapter,theregulationspecificallyapplicabletothedrugproductinquestionshallsupersedetheregulationinthispart(c)Pendingconsiderationofaproposedexemption,publishedintheFederalRegisterofSeptember,,therequirementsinthispartshallnotbrabrasivesubstancesThetestproceduresshallbeinwritingandshallbefollowed(c)Foreachbatchofcontrolledreleasedosageform,thereshallbeappropriatelaboratorytestingtodetermineconformancetothespecificationsfortherateofreleaseofeachactiveingredientThetestproceduresshallbeinwritingandshallbefollowedSecReservesamples(a)AnappropriatelyidentifiedreservesamplethatisrepresentativeofeachlotineachshipmentofeachactiveingredientshallberetainedThereservesampleconsistsofatleasttwicethequantitynecessaryforalltestsrequiredtodeterminewhethertheactiveingredientmeetsitsestablishedspecifications,exceptforsterilityandpyrogentestingTheretentiontimeisasfollows:()Foranactiveingredientinadrugproductotherthanthosedescribedinparagraphs(a)()and()ofthissection,thereservesampleshallberetainedforyearaftertheexpirationdateofthelastlotofthedrugproductcontainingtheactiveingredient()Foranactiveingredientinaradioactivedrugproduct,exceptfornonradioactivereagentkits,thereservesampleshallberetainedfor:(i)Threemonthsaftertheexpirationdateofthelastlotofthedrugproductcontainingtheactiveingredientiftheexpirationdatingperiodofthedrugproductisdaysorlessor(ii)Sixmonthsaftertheexpirationdateofthelastlotofthedrugproductcontainingtheactiveingredientiftheexpirationdatingperiodofthedrugproductismorethandays()ForanactiveingredientinanOTCdrugproductthatisexemptfrombearinganexpirationdateunder§,thereservesampleshallberetainedforyearsafterdistributionofthelastlotofthedrugproductcontainingtheactiveingredient(b)AnappropriatelyidentifiedreservesamplethatisrepresentativeofeachlotorbatchofdrugproductshallberetainedandstoredunderconditionsconsistentwithproductlabelingThereservesampleshallbestoredinthesameimmediatecontainerclosuresysteminwhichthedrugproductismarketedorinonethathasessentiallythesamecharacteristicsThereservesampleconsistsofatleasttwicethequantitynecessarytoperformalltherequiredtests,exceptthoseforsterilityandpyrogensExceptforthosefordrugproductsdescribedinparagraph(b)()ofthissection,reservesamplesfromrepresentativesamplelotsorbatchesselectedbyacceptablestatisticalproceduresshallbeexaminedvisuallyatleastonceayearforevidenceofdeteriorationunlessvisualexaminationwouldaffecttheintegrityofthereservesampleAnyevidenceofreservesampledeteriorationshallbeinvestigatedinaccordancewith§TheresultsoftheexaminationshallberecordedandmaintainedwithotherstabilitydataonthedrugproductReservesamplesofcompressedmedicalgasesneednotberetainedTheretentiontimeisasfollows:()Foradrugproductotherthanthosedescribedinparagraphs(b)()and()ofthissection,thereservesampleshallberetainedforyearaftertheexpirationdateofthedrugproduct()Foraradioactivedrugproduct,exceptfornonradioactivereagentkits,thereservesampleshallberetainedfor:(i)Threemonthsaftertheexpirationdateofthedrugproductiftheexpirationdatingperiodofthedrugproductisdaysorlessor(ii)Sixmonthsaftertheexpirationdateofthedrugproductiftheexpirationdatingperiodofthedrugproductismorethandays()ForanOTCdrugproductthatisexemptforbearinganexpirationdateunder§,thereservesamplemustberetainedforyearsafterthelotorbatchofdrugproductisdistributedFR,Mar,,asamendedatFR,Jan,SecLaboratoryanimalsAnimalsusedintestingcomponents,inprocessmaterials,ordrugproductsforcompliancewithestablishedspecificationsshallbemaintainedandcontrolledinamannerthatassurestheirsuitabilityfortheirintendeduseTheyshallbeidentified,andadequaterecordsshallbemaintainedshowingthehistoryoftheiruseSecPenicillincontaminationIfareasonablepossibilityexiststhatanonpenicillindrugproducthasbeenexposedtocrosscontaminationwithpenicillin,thenonpenicillindrugproductshallbetestedforthepresenceofpenicillinSuchdrugproductshallnotbemarketedifdetectablelevelsarefoundwhentestedaccordingtoproceduresspecifiedin‘ProceduresforDetectingandMeasuringPenicillinContaminationinDrugs,`whichisincorporatedbyreferenceCopiesareavailablefromtheDivisionofResearchandTesting(HFD),CenterforDrugEvaluationandResearch,FoodandDrugAdministration,PaintBranchPkwy,CollegePark,MD,oravailableforinspectionattheNationalArchivesandRecordsAdministration(NARA)ForinformationontheavailabilityofthismaterialatNARA,call,orgoto:http:wwwarchivesgovfederalregistercodeoffederalregulationsibrlocationshtmlFR,Sept,,asamendedatFR,Mar,FR,Mar,FR,Mar,FR,Nov,FR,Apr,SubpartJRecordsandReportsSecGeneralrequirements(a)Anyproduction,control,ordistributionrecordthatisrequiredtobemaintainedincompliancewiththispartandisspecificallyassociatedwithabatchofadrugproductshallberetainedforatleastyearaftertheexpirationdateofthebatchor,inthecaseofcertainOTCdrugproductslackingexpirationdatingbecausetheymeetthecriteriaforexemptionunder§,yearsafterdistributionofthebatch(b)Recordsshallbemaintainedforallcomponents,drugproductcontainers,closures,andlabelingforatleastyearaftertheexpirationdateor,inthecaseofcertainOTCdrugproductslackingexpirationdatingbecausetheymeetthecriteriaforexemptionunder§,yearsafterdistributionofthelastlotofdrugproductincorporatingthecomponentorusingthecontainer,closure,orlabeling(c)Allrecordsrequiredunderthispart,orcopiesofsuchrecords,shallbereadilyavailableforauthorizedinspectionduringtheretentionperiodattheestablishmentwheretheactivitiesdescribedinsuchrecordsoccurredTheserecordsorcopiesthereofshallbesubjecttophotocopyingorothermeansofreproductionaspartofsuchinspectionRecordsthatcanbeimmediatelyretrievedfromanotherlocationbycomputerorotherelectronicmeansshallbeconsideredasmeetingtherequirementsofthisparagraph(d)Recordsrequiredunderthispartmayberetainedeitherasoriginalrecordsorastruecopiessuchasphotocopies,microfilm,microfiche,orotheraccuratereproductionsoftheoriginalrecordsWherereductiontechniques,suchasmicrofilming,areused,suitablereaderandphotocopyingequipmentshallbereadilyavailable(e)Writtenrecordsrequiredbythispartshallbemaintainedsothatdatathereincanbeusedforevaluating,atleastannually,thequalitystandardsofeachdrugproducttodeterminetheneedforchangesindrugproductspecificationsormanufacturingorcontrolproceduresWrittenproceduresshallbeestablishedandfollowedforsuchevaluationsandshallincludeprovisionsfor:()Areviewofarepresentativenumberofbatches,whetherapprovedorrejected,and,whereapplicable,recordsassociatedwiththebatch()Areviewofcomplaints,recalls,returnedorsalvageddrugproducts,andinvestigationsconductedunder§foreachdrugproduct(f)Proceduresshallbeestablishedtoassurethattheresponsibleofficialsofthefirm,iftheyarenotpersonallyinvolvedinorimmediatelyawareofsuchactions,arenotifiedinwritingofanyinvestigationsconductedunder§§,,oroftheseregulations,anyrecalls,reportsofinspectionalobservationsissuedbytheFoodandDrugAdministration,oranyregulatoryactionsrelatingtogoodmanufacturingpracticesbroughtbytheFoodandDrugAdministrationFR,Sept,,asamendedatFR,Jan,SecEquipmentcleaninganduselogAwrittenrecordofmajorequipmentcleaning,maintenance(exceptroutinemaintenancesuchaslubricationandadjustments),anduseshallbeincludedinindividualequipmentlogsthatshowthedate,time,product,andlotnumberofeachbatchprocessedIfequipmentisdedicatedtomanufactureofoneproduct,thenindividualequipmentlogsarenotrequired,providedthatlotsorbatchesofsuchproductfollowinnumericalorderandaremanufacturedinnumericalsequenceIncaseswherededicatedequipmentisemployed,therecordsofcleaning,maintenance,anduseshallbepartofthebatchrecordThepersonsperforminganddoublecheckingthecleaningandmaintenanceshalldateandsignorinitialthelogindicatingthattheworkwasperformedEntriesinthelogshallbeinchronologicalorderSecComponent,drugproductcontainer,closure,andlabelingrecordsTheserecordsshallincludethefollowing:(a)Theidentityandquantityofeachshipmentofeachlotofcomponents,drugproductcontainers,closures,andlabelingthenameofthesupplierthesupplier`slotnumber(s)ifknownthereceivingcodeasspecifiedin§andthedateofreceiptThenameandlocationoftheprimemanufacturer,ifdifferentfromthesupplier,shallbelistedifknown(b)Theresultsofanytestorexaminationperformed(includingthoseperformedasrequiredby§(a),§(d),or§(a))andtheconclusionsderivedtherefrom(c)Anindividualinventoryrecordofeachcomponent,drugproductcontainer,andclosureand,foreachcomponent,areconciliationoftheuseofeachlotofsuchcomponentTheinventoryrecordshallcontainsufficientinformationtoallowdeterminationofanybatchorlotofdrugproductassociatedwiththeuseofeachcomponent,drugproductcontainer,andclosure(d)Documentationoftheexaminationandreviewoflabelsandlabelingforconformitywithestablishedspecificationsinaccordwith§§(c)and(c)(e)Thedispositionofrejectedcomponents,drugproductcontainers,closure,andlabelingSecMasterproductionandcontrolrecords(a)Toassureuniformityfrombatchtobatch,masterproductionandcontrolrecordsforeachdrugproduct,includingeachbatchsizethereof,shallbeprepared,dated,andsigned(fullsignature,handwritten)byonepersonandindependentlychecked,dated,andsignedbyasecondpersonThepreparationofmasterproductionandcontrolrecordsshallbedescribedinawrittenprocedureandsuchwrittenprocedureshallbefollowed(b)Masterproductionandcontrolrecordsshallinclude:()Thenameandstrengthoftheproductandadescriptionofthedosageform()Thenameandweightormeasureofeachactiveingredientperdosageunitorperunitofweightormeasureofthedrugproduct,andastatementofthetotalweightormeasureofanydosageunit()Acompletelistofcomponentsdesignatedbynamesorcodessufficientlyspecifictoindicateanyspecialqualitycharacteristic()Anaccuratestatementoftheweightormeasureofeachcomponent,usingthesameweightsystem(metric,avoirdupois,orapothecary)foreachcomponentReasonablevariationsmaybepermitted,however,intheamountofcomponentsnecessaryforthepreparationinthedosageform,providedtheyarejustifiedinthemasterproductionandcontrolrecords()Astatementconcerninganycalculatedexcessofcomponent()Astatementoftheoreticalweightormeasureatappropriatephasesofprocessing()Astatementoftheoreticalyield,includingthemaximumandminimumpercentagesoftheoreticalyieldbeyondwhichinvestigationaccordingto§isrequired()Adescriptionofthedrugproductcontainers,closures,andpackagingmaterials,includingaspecimenorcopyofeachlabelandallotherlabelingsignedanddatedbythepersonorpersonsresponsibleforapprovalofsuchlabeling()Completemanufacturingandcontrolinstructions,samplingandtestingprocedures,specifications,specialnotations,andprecautionstobefollowedSecBatchproductionandcontrolrecordsBatchproductionandcontrolrecordsshallbepreparedforeachbatchofdrugproductproducedandshallincludecompleteinformationrelatingtotheproductionandcontrolofeachbatchTheserecordsshallinclude:(a)Anaccuratereproductionoftheappropriatemasterproductionorcontrolrecord,checkedforaccuracy,dated,andsigned(b)Documentationthateachsignificantstepinthemanufacture,processing,packing,orholdingofthebatchwasaccomplished,including:()Dates()Identityofindividualmajorequipmentandlinesused()Specificidentificationofeachbatchofcomponentorinprocessmaterialused()Weightsandmeasuresofcomponentsusedinthecourseofprocessing()Inprocessandlaboratorycontrolresults()Inspectionofthepackagingandlabelingareabeforeandafteruse()Astatementoftheactualyieldandastatementofthepercentageoftheoreticalyieldatappropriatephasesofprocessing()Completelabelingcontrolrecords,includingspecimensorcopiesofalllabelingused()Descriptionofdrugproductcontainersandclosures()Anysamplingperformed()Identificationofthepersonsperforminganddirectlysupervisingorcheckingeachsignificantstepintheoperation()Anyinvestigationmadeaccordingto§()Resultsofexaminationsmadeinaccordancewith§SecProductionrecordreviewAlldrugproductproductionandcontrolrecords,includingthoseforpackagingandlabeling,shallbereviewedandapprovedbythequalitycontrolunittodeterminecompliancewithallestablished,approvedwrittenproceduresbeforeabatchisreleasedordistributedAnyunexplaineddiscrepancy(includingapercentageoftheoreticalyieldexceedingthemaximumorminimumpercentagesestablishedinmasterproductionandcontrolrecords)orthefailureofabatchoranyofitscomponentstomeetanyofitsspecificationsshallbethoroughlyinvestigated,whetherornotthebatchhasalreadybeendistributedTheinvestigationshallextendtootherbatchesofthesamedrugproductandotherdrugproductsthatmayhavebeenassociatedwiththespecificfailureordiscrepancyAwrittenrecordoftheinvestigationshallbemadeandshallincludetheconclusionsandfollowupSecLaboratoryrecords(a)Laboratoryrecordsshallincludecompletedataderivedfromalltestsnecessarytoassurecompliancewithestablishedspecificationsandstandards,includingexaminationsandassays,asfollows:()Adescriptionofthesamplereceivedfortestingwithidentificationofsource(thatis,locationfromwheresamplewasobtained),quantity,lotnumberorotherdistinctivecode,datesamplewastaken,anddatesamplewasreceivedfortesting()AstatementofeachmethodusedinthetestingofthesampleThestatementshallindicatethelocationofdatathatestablishthatthemethodsusedinthetestingofthesamplemeetproperstandardsofaccuracyandreliabilityasappliedtotheproducttested(IfthemethodemployedisinthecurrentrevisionoftheUnitedStatesPharmacopeia,NationalFormulary,AssociationofOfficialAnalyticalChemists,BookofMethods,orinotherrecognizedstandardreferences,orisdetailedinanapprovednewdrugapplicationandthereferencedmethodisnotmodified,astatementindicatingthemethodandreferencewillsuffice)ThesuitabilityofalltestingmethodsusedshallbeverifiedunderactualconditionsofuseCopiesmaybeobtainedfrom:AssociationofOfficialAnalyticalChemists,WilsonBlvd,Suite,Arlington,VA()Astatementoftheweightormeasureofsampleusedforeachtest,whereappropriate()Acompleterecordofalldatasecuredinthecourseofeachtest,includingallgraphs,charts,andspectrafromlaboratoryinstrumentation,properlyidentifiedtoshowthespecificcomponent,drugproductcontainer,closure,inprocessmaterial,ordrugproduct,andlottested()Arecordofallcalculationsperformedinconnectionwiththetest,includingunitsofmeasure,conversionfactors,andequivalencyfactors()Astatementoftheresultsoftestsandhowtheresultscomparewithestablishedstandardsofidentity,strength,quality,andpurityforthecomponent,drugproductcontainer,closure,inprocessmaterial,ordrugproducttested()Theinitialsorsignatureofthepersonwhoperformseachtestandthedate(s)thetestswereperformed()Theinitialsorsignatureofasecondpersonshowingthattheoriginalrecordshavebeenreviewedforaccuracy,completeness,andcompliancewithestablishedstandards(b)CompleterecordsshallbemaintainedofanymodificationofanestablishedmethodemployedintestingSuchrecordsshallincludethereasonforthemodificationanddatatoverifythatthemodificationproducedresultsthatareatleastasaccurateandreliableforthematerialbeingtestedastheestablishedmethod(c)Completerecordsshallbemaintainedofanytestingandstandardizationoflaboratoryreferencestandards,reagents,andstandardsolutions(d)Completerecordsshallbemaintainedoftheperiodiccalibrationoflaboratoryinstruments,apparatus,gauges,andrecordingdevicesrequiredby§(b)()(e)Completerecordsshallbemaintainedofallstabilitytestingperformedinaccordancewith§FR,Sept,,asamendedatFR,Mar,FR,Apr,SecDistributionrecordsDistributionrecordsshallcontainthenameandstrengthoftheproductanddescriptionofthedosageform,nameandaddressoftheconsignee,dateandquantityshipped,andlotorcontrolnumberofthedrugproductForcompressedmedicalgasproducts,distributionrecordsarenotrequiredtocontainlotorcontrolnumbers(ApprovedbytheOfficeofManagementandBudgetundercontrolnumber)FR,Mar,SecComplaintfiles(a)WrittenproceduresdescribingthehandlingofallwrittenandoralcomplaintsregardingadrugproductshallbeestablishedandfollowedSuchproceduresshallincludeprovisionsforreviewbythequalitycontrolunit,ofanycomplaintinvolvingthepossiblefailureofadrugproducttomeetanyofitsspecificationsand,forsuchdrugproducts,adeterminationastotheneedforaninvestigationinaccordancewith§SuchproceduresshallincludeprovisionsforreviewtodeterminewhetherthecomplaintrepresentsaseriousandunexpectedadversedrugexperiencewhichisrequiredtobereportedtotheFoodandDrugAdministrationinaccordancewith§§andofthischapter(b)AwrittenrecordofeachcomplaintshallbemaintainedinafiledesignatedfordrugproductcomplaintsThefileregardingsuchdrugproductcomplaintsshallbemaintainedattheestablishmentwherethedrugproductinvolvedwasmanufactured,processed,orpacked,orsuchfilemaybemaintainedatanotherfacilityifthewrittenrecordsinsuchfilesarereadilyavailableforinspectionatthatotherfacilityWrittenrecordsinvolvingadrugproductshallbemaintaineduntilatleastyearaftertheexpirationdateofthedrugproduct,oryearafterthedatethatthecomplaintwasreceived,whicheverislongerInthecaseofcertainOTCdrugproductslackingexpirationdatingbecausetheymeetthecriteriaforexemptionunder§,suchwrittenrecordsshallbemaintainedforyearsafterdistributionofthedrugproduct()Thewrittenrecordshallincludethefollowinginformation,whereknown:thenameandstrengthofthedrugproduct,lotnumber,nameofcomplainant,natureofcomplaint,andreplytocomplainant()Whereaninvestigationunder§isconducted,thewrittenrecordshallincludethefindingsoftheinvestigationandfollowupTherecordorcopyoftherecordoftheinvestigationshallbemaintainedattheestablishmentwheretheinvestigationoccurredinaccordancewith§(c)()Whereaninvestigationunder§isnotconducted,thewrittenrecordshallincludethereasonthataninvestigationwasfoundnottobenecessaryandthenameoftheresponsiblepersonmakingsuchadeterminationFR,Sept,,asamendedatFR,July,FR,Mar,SubpartKReturnedandSalvagedDrugProductsSecReturneddrugproductsReturneddrugproductsshallbeidentifiedassuchandheldIftheconditionsunderwhichreturneddrugproductshavebeenheld,stored,orshippedbeforeorduringtheirreturn,oriftheconditionofthedrugproduct,itscontainer,carton,orlabeling,asaresultofstorageorshipping,castsdoubtonthesafety,identity,strength,qualityorpurityofthedrugproduct,thereturneddrugproductshallbedestroyedunlessexamination,testing,orotherinvestigationsprovethedrugproductmeetsappropriatestandardsofsafety,identity,strength,quality,orpurityAdrugproductmaybereprocessedprovidedthesubsequentdrugproductmeetsappropriatestandards,specifications,andcharacteristicsRecordsofreturneddrugproductsshallbemaintainedandshallincludethenameandlabelpotencyofthedrugproductdosageform,lotnumber(orcontrolnumberorbatchnumber),reasonforthereturn,quantityreturned,dateofdisposition,andultimatedispositionofthereturneddrugproductIfthereasonforadrugproductbeingreturnedimplicatesassociatedbatches,anappropriateinvestigationshallbeconductedinaccordancewiththerequirementsof§Proceduresfortheholding,testing,andreprocessingofreturneddrugproductsshallbeinwritingandshallbefollowedSecDrugproductsalvagingDrugproductsthathavebeensubjectedtoimproperstorageconditionsincludingextremesintemperature,humidity,smoke,fumes,pressure,age,orradiationduetonaturaldisasters,fires,accidents,orequipmentfailuresshallnotbesalvagedandreturnedtothemarketplaceWheneverthereisaquestionwhetherdrugproductshavebeensubjectedtosuchconditions,salvagingoperationsmaybeconductedonlyifthereis(a)evidencefromlaboratorytestsandassays(includinganimalfeedingstudieswhereapplicable)thatthedrugproductsmeetallapplicablestandardsofidentity,strength,quality,andpurityand(b)evidencefrominspectionofthepremisesthatthedrugproductsandtheirassociatedpackagingwerenotsubjectedtoimproperstorageconditionsasaresultofthedisasteroraccidentOrganolepticexaminationsshallbeacceptableonlyassupplementalevidencethatthedrugproductsmeetappropriatestandardsofidentity,strength,quality,andpurityRecordsincludingname,lotnumber,anddispositionshallbemaintainedfordrugproductssubjecttothissectionAuthority:USC,,,,b,,Source:FR,Mar,,unlessotherwisenote
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