生物药工艺验证

30ChurchillPlace●CanaryWharf●LondonE145EU●UnitedKingdomAnagencyoftheEuropeanUnionTelephone+44(0)2036606000Facsimile+44(0)2036605555Sendaquestionviaourwebsite©EuropeanMedicinesAgency,2016.Reproductionisauthorisedprovidedthesourceisacknowledged.28April2016EMA/CHMP/BWP/187338/2014CommitteeforMedicinalProductsforHumanUse(CHMP)Guidelineonprocessvalidationforthemanufactureofbiotechnology-derivedactivesubstancesanddatatobeprovidedintheregulatorysubmissionDraftAgreedbyBiologicsWorkingPartyApril2014AdoptionbyCHMPforreleaseforconsultation25April2014Startofpublicconsultation1May2014Endofconsultation(deadlineforcomments)31October2014BWPDraftingGroupreviewofcommentsNovember2014-January2016AgreedbyBWPFebruary2016AdoptionbyCHMP28April2016Dateforcomingintoeffect1November2016Keywordsactivesubstance,biologics,processvalidation,processevaluation,processverification,lifecycleGuidelineonprocessvalidationforthemanufactureofbiotechnology-derivedactivesubstancesanddatatobeprovidedintheregulatorysubmissionEMA/CHMP/BWP/187338/2014Page2/13Guidelineonprocessvalidationforthemanufactureofbiotechnology-derivedactivesubstancesanddatatobeprovidedintheregulatorysubmissionTableofcontentsTableofcontents.........................................................................................21.Introduction............................................................................................32.Scope.......................................................................................................43.Legalbasis..............................................................................................44.Processcharacterisation.........................................................................44.1.Processdevelopment............................................................................................44.2.Processevaluation................................................................................................55.Processverification.................................................................................65.1.Approachestoprocessverification..........................................................................65.2.Ongoingprocessverificationduringlifecycle............................................................76.Pointstoconsiderinprocesscharacterisationandverification...............86.1.Upstreamprocess.................................................................................................86.1.1.Evaluationofupstreamprocess...........................................................................86.1.2.Verificationofupstreamprocess..........................................................................96.1.3.Generalissuesrelatedtosingleuseequipment.....................................................96.1.4.Generalissuesrelatedtomultipleharvests...........................................................96.2.Downstreamprocess............................................................................................96.2.1.Evaluationofdownstreamprocess.....................................................................106.2.2.Verificationofdownstreamprocess....................................................................106.2.3.Reprocessing..................................................................................................106.2.4.Holdtime,storageandtransportation................................................................116.3.Multifacilityproduction........................................................................................11Definitions.................................................................................................12References................................................................................................13Guidelineonprocessvalidationforthemanufactureofbiotechnology-derivedactivesubstancesanddatatobeprovidedintheregulatorysubmissionEMA/CHMP/BWP/187338/2014Page3/13ExecutivesummaryTheguidelinecoversprocessvalidationwhichincludesprocesscharacterisationandprocessverificationofbiotechnology-derivedactivesubstancesinthemanufactureofmedicinalproducts.Thisguidelineaddressesthedatarequirementsforprocesscharacterisationandverificationforsubmissionofamarketingauthorisationapplicationorvariation.•Processcharacterisationcanbebasedonatraditionalorenhancedapproachtoprocessdevelopment.Traditionalandenhancedapproachesarenotmutuallyexclusive.•Processverificationcanbeperformedinatraditionalwayregardlessoftheapproachtodevelopmenttaken.However,thereisalsothepossibilitytoimplementcontinuousprocessverificationifanenhancedapproachtodevelopmenthasbeenperformedorwhereasubstantialamountofproductandprocessknowledgeandunderstandinghasbeengainedthroughhistoricaldataandmanufacturingexperience.Currentexperienceshowsthatacompanycanuseatraditionaloranenhancedapproachtoprocessvalidation,oracombinationofboth.Regardlessoftheapproachfollowed,thevalidationdatatobeincludedintheregulatorysubmissionshouldcoverinformationrelatingtotheevaluationandth