mp-vol4-chap4-consultation-guideline-en-EUGMP-第四章文件管理

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1Chapter4:Documentation

2Reasonsforchanges:TheGMP/GDPInspectorsWorkingGroupandthePIC/SCommitteejointly

3recommendedthatthecurrentversionofChapter4,ondocumentation,isrevisedtoreflectchangesin

4regulatoryandmanufacturingenvironments.Therevisedguidelineclarifiesrequirementsandexpecta-

5tionsfromRegulatoryAuthoritieswithregardstodocumentationandtakesintoaccountrelatedchanges

6forAnnex11oftheGMPGuide.

Documentmap

Principle

Datagovernancesystems

Riskmanagement

Generalrequirementsfordocumentation

MasterDocuments

GenerationandControlofDocumentation

Gooddocumentationpractice

SignaturesinGMPrelevantdocumentation

Retentionofdocuments

DataIntegrityindocumentation

HybridSystems

Glossary

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7PRINCIPLE

84.1.Documentationconstitutesanessentialpartofthequalityassurancesystemandiskeytoop-

9eratingincompliancewithGMPrequirements.Thevarioustypesofdocumentsandmeans

10usedshouldbefullyunderstoodanddefinedintheregulateduser'spharmaceuticalquality

11system.

124.2.Itshouldbedeterminedbytheregulateduserwhichlegalprovisionsapplytodocumentation

13consideringnewtechnologies,hybridsolutionsandservicesused.

144.3.Appropriatedocumentationpracticesshouldbeappliedwithrespecttothetypeofdocument

15regardlessoftheappliedtechnologyorserviceused.

164.4.Thepresentdocumentwassupplementedbyrequirementsregardingnewtechnologies,hybrid

17solutionsandnewservices,wherebyarisk-basedapproachaselementofadatagovernance

18systemisconsideredpivotalforscalabilityofintegritycontrolmeasures.

194.5.Qualityriskmanagementprinciplesshouldbeappliedtoensurethatthepharmaceuti-

20calqualitysystemincludessufficientinstructionaldetails.Itshouldfacilitateacommon

21understandingoftherequirements.Inadditiontoprovidingforrecordingofthevariouspro-

22cessesandrisk-basedevaluationofanyobservations,itshoulddemonstratetheongoingappli-

23cationofallrequirements.

244.6.Suitablecontrolsshouldbeimplementedusingarisk-basedapproachtoensuretheaccuracy,

25integrity,availability,andlegibilityofdocuments.Documentsshouldbefreefromerrorsand

26availableinhumanreadableform.

274.7.Documentationmayexistinavarietyofforms,includingpaper-based,electronic,orother

28means(e.g.photography,imagery,videoandaudiorecordings).Themainobjectiveofthe

29documentationsystemistoestablish,control,monitorandrecordallactivitieswhichdirectly

30orindirectlyimpactonallaspectsofthequalityandsafetyofmedicinalproducts,usingarisk-

31basedapproach.

324.8.Whetherdocumentsarecreated,stored,andmanagedelectronically,paperbased,byother

33meansorthroughahybridsystem,theymustmeetthesameGMPrequirementsforlegibility,

34accuracy,integrity,andcompletenessthroughoutthewholelifecycle.Thisalsoapplieswhen

35documentationisoutsourced.

364.9.TherearetwoprimarytypesofdocumentationusedtomanageanddemonstrateGMPcompli-

37ance:

38i.instructions(directions,requirements)and

39ii.records/reports.

40DATAGOVERNANCESYSTEMS

414.10.Regardlessofhowdocumentsarecreated,handled,stored,andmanaged(i.e.,usingelec-

42tronic,paper-based,orhybridsystems),theregulatedusershouldestablishadatagovernance

43systemintegraltothepharmaceuticalqualitysystemtodefine,prioritiseandcommunicate

44theirdataintegrityriskmanagementactivities.Arrangementsfordatagovernanceshouldbe

45documentedandreviewedregularly.

464.11.Regulatedusersshoulddesignandoperateadatagovernancesystemwhichprovidesanac-

47ceptablestateofcontrolbasedontheriskassessment,whichisdocumentedwithsupporting

48rationale.Adatagovernancesystemshouldbeconsistentwiththeprinciplesofqualityrisk

49management.

504.12.Toensureintegrityofdatathegovernancesystemshouldcovertheentiredatalifecycleand

51ensurecontrolscommensuratewiththeprincipleofqualityriskmanagement.Thedatalifecy-

52cleshouldreferto:

53i.Creationandrecordingofdata.

54ii.Processingof(raw)datatoreported(derived)data.

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55iii.Verificationofcompleteness,consistencyandaccuracyofalldata(rawandderived

56data).Forderiveddatathetraceabilitywhichallowsreconstructionofalldatapro-

57cessingactivitiesshouldbemaintained.

58iv.Decisionmakingrelyingondata(orderiveddata).

59v.Retaining,archivingandretrievalofdata.Toprotectitfromlossorunauthorisedal-

60terationitshouldbecommensuratewiththeprinciplesofqualityriskmanagement.

61vi.Retirementordestructionofdataattheendofthelifecycleinacontrolledmanner.624.13.Datagovernancesystemsshouldrelyonariskmanagementapproachandconsider:

63i.Datacriticality(impacttodecisionmakingandproductquality)and

64ii.Datarisk(opportunityfordataalterationanddeletion,andlikelihoodofdetection/

65visibilityofchangesbytheregulateduser’sroutinereviewprocesses).

664.14.Datagovernancesystemsshouldrelyontheincorporationofsuitablydesignedsystems,the

67useoftechnologiesanddatasecuritymeasures,combinedwithspecificexpertisetoensure

68thatdataintegrityiseffectivelycontrolledoverthedatalifecycle.

694.15.Datagovernancesystemsshouldaddressdataownershipthroughouttheentirelifecycle.

704.16.Datagovernancesystemsshouldconsiderthedesign,operationandmonitoringofprocesses

71andsystemstocomplywiththeprinciplesofdataintegrity.

724.17.Datagovernancesystemsshouldconsiderriskmitigation.Theeffectivenessofriskmitigation

73measuresshouldbereviewedregularly,regardlessofwhethertheyaretemporaryorperma-

74nent.Residualrisksshouldbereviewedperiodicallyandcommunicatedtomanagement.

754.18.Datagovernancesystemsshouldconsiderandensuretheperiodicreviewofserviceprovider’s

76datamanagementpoliciesandriskcontrolstrategiesintendedtominimisepotentialrisksto

77dataintegrity.Thefrequencyofsuchreviewsshouldbebasedonthecriticalityoftheservices

78provided,usingriskmanagementprinciples.

79RISKMANAGEMENT

804.19.Theregulatedusershouldadoptarisk-basedapproachindocumentationthroughouttheentire

81lifecycleofdata,regardlessofthetechnology,hybridsolutionorserviceusedandshould

82demonstrateanunderstandingfordatacriticality,datariskanddataquality.

834.20.Controlsoverthedatalifecycleshouldbeestablishedwhicharecommensuratewiththeprin-

84ciplesofqualityriskmanagement.Thedepthofdatagovernanceandriskmanagementactiv-

85itiesshouldbejustifiedandcommensuratewiththeriskstoproductqualityandpatientsafety.864.21.Decisionsontheextentofmeasurestoensuredataintegrityshouldbebasedonadocumented

87rationaleanddocumentedriskassessmenttakingintoconsiderationdatacriticalityanddata

88risk.

894.22.Irrespectiveofprocessesusedtogenerateelectronicdata,theymustbeincludedinthere-

90quirementsforthequalificationorvalidationoftherelevantcomputerisedsystemsaccording

91toAnnex11.

92GENERALREQUIREMENTSFORDOCUMENTATION

934.23.Thepharmaceuticalqualitysystemshoulddescribealldocumentsrequiredtoensureproduct

94qualityandpatientsafety.Documentsmaybecreated,recorded,provided,approved,commu-

95nicated,stored,andarchivedelectronically,paperbasedorinahybridsystem.Thereliance

96onelectronic,paper-basedordifferentmeans,hybridsolutionsorhostedservicesinmainte-

97nanceandretentionofdocumentationrequiresthecompliancewithallEUGMPprovisions

98includingAnnex11ifdecisionmakinginmanufacturing(e.g.batchreleasebasedonin-pro-

99cesscontrolsandprocessanalyticaltechnologies)issupportedbyautomaticvalidationscripts

100orartificialintelligence(Annex22).

1014.24.Theaccountabilityfortheintegrityofdocuments,recordsor(raw)dataproducedorprocessed

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withartificialintelligenceoranyotherautomaticmeans(e.g.validationscripts)restswiththeregulateduser.

4.25.Thesupportbyanyautomaticmeans(e.g.validationscriptsorartificialintelligence)shouldbeincludedinapharmaceuticalqualitysystemregardlessoftheservicelocatedonpremiseorasahostedservice.Therecordscreatedelectronicallyshouldenableatrendanalysisofquality-criticaldata.

4.26.Toensuredataintegrity,datawhichisrecordedorprocessedelectronicallyshouldnotbeconvertedtoorstoredinapaperformunlessitmeetstherequirementssetoutinsection13“hybridsystems”ortheconversionisvalidatedorverifiedforaccuracy.

MASTERDOCUMENTS

4.27.Specificallyrequiredmasterdocuments(notexhaustivelist):

i.SiteMasterFile:RefertoEUGMPGuidelines,Volume4“ExplanatoryNotesonthepreparationofaSiteMasterFile”.

ii.ValidationMasterPlan:Adocumentdescribingthekeyelementsofthesitequalifi-cationandvalidationprogram.Masterdocumentsshouldbeevaluatedandreviewedonaregularbasis.

iii.Instructions(directions,orrequirements)type:

-Specification:Refertoglossaryfordefinition

-ManufacturingFormulae,Processing,PackagingandTestingInstruction:Pro-videcompletedetailonallthestartingmaterials,equipment,andcomputerisedsys-tems(ifany)tobeusedandspecifyallprocessing,packaging,sampling,andtestinginstructionstoensurebatchtobatchconsistency.In-processcontrolsandprocessan-alyticaltechnologiestobeemployedshouldbespecifiedwhererelevant,togetherwithacceptancecriteria.

-Procedures:(OtherwiseknownasStandardOperatingProcedures,orSOPs),docu-mentedsetofinstructionsforperformingandrecordingoperations.

-Protocol:definedsetofactivitiestoprovideinstructionsforperformingandrecord-ingcertaindiscreetoperations.

-Technical/QualityAgreement:Writtenproofofagreementbetweencontractgiversandacceptorsforoutsourcedactivities.

iv.Record/Reporttype:

-Record:Provideevidenceofvariousactionstakentodemonstratecompliancewithinstructions,e.g.activities,events,investigations,andinthecaseofmanufacturedbatchesahistoryofeachbatchofproduct,includingitsdistribution.Recordsin-cludetherawdatawhichisusedtogenerateotherrecords.Forelectronicrecordsregulatedusersshoulddefinewhichdataaretobeusedasrawdata.Atleast,alldataonwhichqualitydecisionsarebasedshouldbedefinedasrawdata.

Recordscanalsoexistashybridrecordswhichisacombinationofpaperrecords,electronicrecordsorbyothermeans.Thecompletenessandintegrityofrecords,in-cludingallrelevantrawdataandmetadatashouldbeensuredandprotectedbasedonrisk.

-CertificateofAnalysis:Provideasummaryoftestingresultsonsamplesofproductsormaterials

1

togetherwiththeevaluationforcompliancetoastatedspecification.

1Alternatively,thecertificationmaybebased,in-wholeorin-part,ontheassessmentofrealtimedata(summar-iesandexceptionreports)frombatchrelatedprocessanalyticaltechnology(PAT),parametersormetricsaspertheapprovedmarketingauthorisationdossier.

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-Report:Documenttheconductofexercises,studies,assessments,projectsorinves-tigations,togetherwithresults,conclusionsandrecommendations.

Specifications

4.28.Thereshouldbeapprovedandupdatedspecificationsforstartingandpackagingmaterials,intermediate,bulk,finishedproducts,processaidsandotherqualitycriticalmaterial,asap-plicable.Specificationsshouldincludeallattributeswhicharerelevantforproductqualityoneachstageofmaterialormanufacture.

Specificationsforstartingandpackagingmaterials

4.29.Specificationsforstartingandprimaryorprintedpackagingmaterialsshouldincludetheprod-uctanditsreferencecode,ifapplicable:

i.Adescriptionofthematerials,including:

•Thedesignatednameandtheinternalcodereference.

•Thereference,ifany,toapharmacopeialmonograph.

•Theapprovedsuppliersand,ifapplicable,theoriginalproducerofthematerial.

•Aspecimenofprintedmaterials.

ii.Directionsforsamplingandtesting.

iii.Qualitativeandquantitativerequirementswithacceptancelimits.

iv.Storageconditionsandprecautions.

v.Themaximumperiodofstoragebeforere-examination.

Specificationsforintermediateandbulkproducts

4.30.Specificationsforintermediateandbulkproductsshouldbeavailableforcriticalstepsorifthesearepurchasedordispatched.Thespecificationsshouldbesimilartospecificationsforstartingmaterialsorforfinishedproducts,asappropriate.

Specificationsforfinishedproducts

4.31.Specificationsforfinishedproductsshouldincludeorprovidereferenceto:

vi.Thedesignatednameoftheproductandthecodereferencewhereapplicable.

vii.Theformula.

viii.Adescriptionofthepharmaceuticalformandpackagedetails.

ix.Directionsforsamplingandtesting.

x.Thequalitativeandquantitativerequirements,withtheacceptancelimits.

xi.Thestorageconditionsandanyspecialhandlingprecautions,whereapplicable.

xii.Theshelf-life.

ManufacturingFormulaandProcessingInstructions

4.32.Approved,writtenManufacturingFormulaandProcessingInstructionsshouldexistforeach

productandbatchsizetobemanufactured.

4.33.TheManufacturingFormulashouldinclude:

i.Thenameoftheproduct,withaproductreferencecoderelatingtoitsspecification.

ii.Adescriptionofthepharmaceuticalform,strengthoftheproductandbatchsize.

iii.Alistofallstartingmaterialstobeused,withtheamountofeach,described;

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185mentionshouldbemadeofanysubstancethatmaydisappearwhileprocessing,of

186processingaidsneededoranyothermaterialrelevantforproductquality.

187iv.Astatementoftheexpectedfinalyieldwiththeacceptablelimits,andofrelevantin-

188termediateyields,whereapplicable.1894.34.TheProcessingInstructionsshouldinclude:

190i.Astatementoftheprocessinglocationandtheprincipalequipmenttobeused.

191ii.Themethods,orreferencetothemethods,tobeusedforpreparingthecriticalequip-

192ment(e.g.cleaning,assembling,calibrating,sterilising).

193iii.Checksthattheequipmentandworkstationareclearofpreviousproducts,docu-

194mentsormaterialsnotrequiredfortheplannedprocess,andthatequipmentisclean

195andsuitableforuse.

196iv.Detailedstepwiseprocessinginstructions[e.g.checksonmaterials,pre-treatments,

197sequenceforaddingmaterials,criticalprocessparameters(time,tempetc)].

198v.Theinstructionsforanyin-processcontrolswiththeirlimits.

199vi.Wherenecessary,therequirementsforbulkstorageoftheproducts;includingthe

200container,labellingandspecialstorageconditionswhereapplicable.

201vii.Anyspecialprecautionstobeobserved.

202PackagingInstructions

2034.35.ApprovedPackagingInstructionsforeachproduct,packsizeandtypeshouldexist.These

204shouldinclude,orhaveareferenceto,thefollowing:

205i.Nameoftheproduct;includingthebatchnumberofbulkandfinishedproduct.

206ii.Descriptionofitspharmaceuticalform,andstrengthwhereapplicable.

207iii.Thepacksizeexpressedintermsofthenumber,weightorvolumeoftheproductin

208thefinalcontainer.

209iv.Acompletelistofallthepackagingmaterialsrequired,includingquantities,sizes

210andtypes,withthecodeorreferencenumberrelatingtothespecificationsofeach

211packagingmaterial.

212v.Whereappropriate,anexampleorreproductionoftherelevantprintedpackaging

213materials,andspecimensindicatingwheretoapplybatchnumberreferences,and

214shelflifeoftheproduct.

215vi.Checksthattheequipmentandworkstationareclearofpreviousproducts,docu-

216mentsormaterialsnotrequiredfortheplannedpackagingoperations(lineclear-

217ance),andthatequipmentiscleanandsuitableforuse.

218vii.Checksonfunctioningofanyelectroniccodereaders,labelcountersorsimilarde-

219vices.

220viii.Specialprecautionstobeobserved,includingacarefulexaminationoftheareaand

221equipmentinordertoascertainthelineclearancebeforeoperationsbegin.

222ix.Adescriptionofthepackagingoperation,includinganysignificantsubsidiaryopera-

223tions,andequipmenttobeused.

224x.Detailsofin-processcontrolswithinstructionsforsamplingandacceptancelimits.

225BatchProcessingRecord

2264.36.ABatchProcessingRecordshouldbekeptforeachbatchprocessed.Itshouldbebasedon

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227therelevantpartsofthecurrentlyapprovedManufacturingFormulaandProcessingInstruc-

228tions,andshouldcontainthefollowinginformation:

229i.Thenameandbatchnumberoftheproduct.

230ii.Datesandtimesofcommencement,ofsignificantintermediatestagesandofcomple-

231tionofproduction.

232iii.Identification(initials)oftheoperator(s)whoperformedeachsignificantstepofthe

233processand,whereappropriate,identification(initials)ofthepersonwhochecked

234theseoperations.

235iv.Thebatchnumberand/oranalyticalcontrolnumberaswellasthequantitiesofeach

236startingmaterialweighed(includingthebatchnumberandamountofanyrecovered

237orreprocessedmaterialadded).

238v.Anyrelevantprocessingoperationoreventandmajorequipmentused.

239vi.Arecordofthein-processcontrolsandtheinitialsoftheperson(s)carryingthem

240out,andtheresultsobtained.

241vii.Theproductyieldobtainedatdifferentandpertinentstagesofmanufacture.

242viii.Notesonspecialproblemsincludingdetails,withsignedauthorisationforanydevia-

243tionfromtheManufacturingFormulaandProcessingInstructions.

244ix.Approvalbythepersonresponsiblefortheprocessingoperations.

245Note:Whereavalidatedprocessiscontinuouslymonitoredandcontrolled,thenautomati-

246callygeneratedreportsmaybelimitedtocompliancesummariesandexception/out-of-

247specification(OOS)datareports.

248Withregardstodecisionmakinginmanufacturingsupportedbyautomaticvalidationscripts

249orartificialintelligencerefertoparagraph4ofthisdocument.

250BatchPackagingRecord

2514.37.ABatchPackagingRecordshouldbekeptforeachbatchorpartbatchprocessed.Itshouldbe

252basedontherelevantpartsofthePackagingInstructions.

2534.38.Thebatchpackagingrecordshouldcontainthefollowinginformation:

254i.Thenameandbatchnumberoftheproduct.

255ii.Thedate(s)andtimesofthepackagingoperations.

256iii.Identification(initials)oftheoperator(s)whoperformedeachsignificantstepofthe

257processand,whereappropriate,thenameofanypersonwhocheckedtheseopera-

258tions.

259iv.Recordsofchecksforidentityandconformitywiththepackaginginstructions,in-

260cludingtheresultsofin-processcontrols.

261v.Recordsofchecksthattheequipmentandworkstationareclearofpreviousproducts,

262documentsormaterialsnotrequiredfortheplannedpackagingoperations(lineclear-

263ance),thatequipmentiscleanandsuitableforuse,andthatanyelectroniccoderead-

264ers,labelcountersorsimilardevicesarefunctioningasexpected.

265vi.Detailsofthepackagingoperationscarriedout,includingreferencestoequipment

266andthepackaginglinesused.

267vii.Wheneverpossible,samplesofprintedpackagingmaterialsused,includingspeci-

268mensofthebatchcoding,expirydatingandanyadditionaloverprinting.

269viii.Notesonanyspecialproblemsorunusualeventsincludingdetails,withsigned

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270authorisationforanydeviationfromthePackagingInstructions.

271ix.Thequantitiesandreferencenumberoridentificationofallprintedpackagingmate-

272rialsandbulkproductissued,used,destroyedorreturnedtostockandthequantities

273ofobtainedproduct,toprovideforanadequatereconciliation.Wheretherearevali-

274datedelectroniccontrolsinplaceduringpackagingtheremaybejustificationfornot

275includingthisinformation

276x.Approvalbythepersonresponsibleforthepackagingoperations.

277Receipt

2784.39.Thereshouldbewrittenproceduresandrecordsforthereceiptofeachdeliveryofeachstarting

279material,(includingbulk,intermediateorfinishedgoods),primary,secondaryandprinted

280packagingmaterialsandQC-samples.Therecordsofthereceiptsshouldinclude:

281i.Thenameofthematerialonthedeliverynotesandthecontainers.

282ii.The"in-house"nameand/orcodeofmaterial(ifdifferentfroma).

283iii.Dateofreceipt.

284iv.Supplier’snameand,manufacturer’sname.

285v.Manufacturer’sbatchorreferencenumber.

286vi.Totalquantityandnumberofcontainersreceived.

287vii.Thebatchnumberassignedafterreceipt.

288viii.Anyrelevantcomment.

289ix.Ifapplicable,proofofverificationthattemperatureduringtransportationwerewithin

290theapprovedlimit.

2914.40.Thereshouldbewrittenproceduresfortheinternallabelling,quarantineandstorageofstart-

292ingmaterials,packagingmaterials,QCsamplesandothermaterials,asappropriate.

293Sampling

2944.41.Thereshouldbewrittenproceduresforsampling,whichincludethemethodsandequipment

295tobeused,theamountstobetakenandanyprecautionstobeobservedtoavoidcontamination

296ofthematerialoranydeteriorationinitsquality(referencetoEUGMPGuidelineVolume4,

297Chapter6“QualityControl”).

298Testing

2994.42.Thereshouldbewrittenproceduresfortestingmateria