Hospira Takes QbD Approach to Compliance Remediation Efforts While Production Continues.docx
《Hospira Takes QbD Approach to Compliance Remediation Efforts While Production Continues.docx》由会员分享,可在线阅读,更多相关《Hospira Takes QbD Approach to Compliance Remediation Efforts While Production Continues.docx(18页珍藏版)》请在冰豆网上搜索。
HospiraTakesQbDApproachtoComplianceRemediationEffortsWhileProductionContinues
HospiraTakesQbDApproachtoComplianceRemediationEffortsWhileProductionContinues
Hospiraistakingaqualitybydesign-orientedapproachtocomplianceremediationandqualityimprovementatitskeyRockyMount,NorthCarolinainjectablemanufacturingfacility–focusingmoreheavilyonidentifyingandmonitoringcriticalprocessstepsthanonreviewingbatchrecords.
ThedifferenttactthatHospiraistakinginitscomplianceremediationeffortsreflectsthechallengeofkeepingitsoperationsgoingattheRockyMountplantwhileoverhaulingitsqualitymanagementprogram.
TheextentoftheFDAconcernsattheplant,expressedinlengthy483soverthepastfewyearsandunderscoredinawarningletterinApril,2010(IPQ“TheNewsinDepth”August26,2010),wouldtypicallyhaveresultedinaplantclosing,potentiallyunderaconsentdecree,untiltheremediationcouldbeassuredbytheagency.
However,theroleHospiraplaysinsupplyingmedicallynecessaryinjectablesandthethreattothehealthcaresystemifthatsupplyweredisruptedhasleadtheagencytoworkwiththecompanyinachievingtheoverhaulwhileproductioncontinues.
AtFDLI’smid-December“Enforcement,Litigation&Compliance”conferenceinWashington,D.C.,QuintilesConsultingSeniorDirectorMichaelLevittandHospiraGlobalQualitySeniorVPZenaKaufmanprovidedarevealingupdateonHospira’seffortstowalkthistightropeandadvanceitsqualityoversightprogramatthefacilitywiththehelpofQbDconcepts(seeboxbelow).
LevitthasbeendirectingQuintile’sengagementwithHospirainitsremediationefforts.Hereviewedthecompliancecontextinwhichtheeffortsaretakingplaceandtheemphasisbeingplacedonheightenedmonitoringofcriticalprocessstepsratherthanofbatchdocumentation.
Kaufmanexplainedfurtherthe“roadmap”thecompanyisfollowinginitseffortstotaketheRockyMountplantfromremediationtoqualityimprovement,andthemetricsitisusingtomeasuresuccess.
“Hospiraisinauniqueposition”inproducing“probablyalittlemorethan50%ofallthegenericinjectableproductsusedinhospitalsintheUnitedStates,”LevittpointedoutattheFDLIsession.“Anytypeofdisruptionintheirproductstreamandsupplywouldhaveasignificantimpacton[US]healthcare.”
ThenatureoftheFDAobservationsattheRockyMountplantledtointernalconsiderationofwhethertheplantshouldbeshutdownforaperiodoftimetoremediatethem,hesaid.
However,neitherHospiranortheFDA“wantedtotakethattackbecauseoftheimpactthatwouldhavenationally.Soinfact,inourfirstdiscussions…14monthsagowiththeagency,theirrequestwas:
‘Don’tthinkaboutshuttingdown–findalternatives.’AndthatwasthechallengethatwaspresentedtotheHospiramanagementteamandtoQuintilestosupporttheminfiguringoutawaytomaintainsomelevelofproductionwhiletheyinitiatedastrongandcomprehensiveremediationprogram.”
AttentionPlacedonCriticalProcessSteps
Inhispresentation,LevittdiscussedhowQuintilesworkedwithHospiratostructure“analternativetoclassicaloversightthattheagencymightaskfor–becauseinthiscasewehaveafirmthattookanaggressiveposture,recognizedtheneedtochange,recognizedthesituation,andself-imposedwhatwecouldclearlydefineasaconsentdecree,allbeforetheagencymovedinthatdirection.”
Theresulthasbeenthecreationof“anenvironmentformorerapidimprovement,changesintheorganizationandmostimportantly,changesintheculture–thesubstrate,ifyouwill,thatreallyiscriticalforsustainablecompliance.”
LevittcontrastedtheapproachHospirahastakentothatusuallymandatedofbringingin“anarmyofconsultants”whoreviewalargestackofbatchrecordsto“determineifinfacttheproductisreleasable”–anenormoustaskgiventheRockyMountplant’sproductionvolumethatwouldhavesignificantly“impactedthehealthcaresystembecauseoftheholdupinreleasingproducts.”
Thechallengewastofindanalternativeway“toensurethatproductsthatareleavingtheplantaresafeandeffective,whilethereisanextensiveremediationprogramunderway.”
Withcriticaldrugshortageshanginginthebalance,thedecisionwasreachedtodoariskassessmenttodeterminethepointsintheprocesswhereaproductwasmostlikelytobecompromisedandputthird-partyoversightatthosecriticalprocesssteps.
HospiraandQuintilesweretransparentwithFDA,sharingtheirbeliefandapproachthatthequalityassurancecouldbeachievedmoreefficientlywiththisapproachthanbythetypicalthird-party,intensivebatchrecordreview–freeingupresourcesfortheremediationeffortwhileproductioncontinued.
“Thebenefitsofthisreallyhaveproventobethatinalargefacility,wewereabletoaccomplishthiswithamuchsmallergroupofpeoplethanwouldhavebeennecessarytodofullbatchrecordreviews,”Levittreported.“Pluswewereabletoputpeopleonthefloorwhonotonlyservedasoversight,butbecamecoachesandmentorstothequalityorganizationthatwasalreadyinplaceandtothemanufacturingpeople–topointoutwhatthecriticalissueswereandhelpthemlearn,andthenmodifybatchrecordstobettercontroltheprocesses.”
Batchrecordreviewswerestillperformed,theQuintilesofficialadded,“butamuchsmallernumber,andwewereabletoeliminateouroversightasbeingacontrollingfactor….So,infact,wedidnotaffectthecycletimeoftheindividualproductsbeingproduced.However,tofreeupresources,Hospiramadethedecisiontoreducethetotalnumberofbatchestheyproduced,andthatallowedthemthentoputafairlyextensiveandcomprehensiveremediationprograminplace.”
FromComplianceRemediationtoQualityImprovement
KaufmanleftAbbotttobecomeheadofglobalqualityforHospirainthefirstpartof2012. Herinitialfocus,sheexplainedattheFDLIconference,wasoncreatinga“roadmap”orstrategy“forlong-termsustainablecompliance”thatwouldtakeHospirafrom“complianceremediation”to“qualityimprovement.”
ThedecisionwasmadetohaveonequalitysystemacrossHospira’soperations,Kaufmansaid,soimprovementsmadeattheRockyMountfacilitywouldhaveglobalimpact.
Infocusingonremediationontheshopfloor,“thefirstelementwastobuild,trainandcertifyamanufacturingqualityorganization”[MQO]–aprocessthathadstartedwellbeforeshejoinedHospira,Kaufmanexplained.
Improvingthedeviationinvestigations–aprimaryareaofconcernduringFDA’sinspectionsofthefacility–hasbeenafocalpointinthefirm’sremediationeffortsontheshopflooroverthepastyear.
HospiraofficialsworkedwithQuintilestocategorizedeviationsintolow,mediumandhighconcern.Forthoseinthemediumandhighcategory,theconsultantsperformedareviewtodetermineiftherootcausehadbeenarrivedat.
TheadditionalMQOstaffhiredbyHospiraiscontinuingtheoversightwiththehelpofan“assessmenttool”designedtoassurethattheinvestigationsarecorrectlyclassifiedandrobustlyperformed.
“Weareintheprocessofimplementingwhatwecalla‘rubric,’whichwillassurethatinvestigationsaredocumentedusingpredeterminedcriteria,”Kaufmanexplained.“Itisreallyatoolforhowtowrite,howtodocumentanddoaninvestigation.Butitisalsoatoolforsomeonetousesothatyouhaveanobjectivereviewoftheinvestigation.”
TheHospiraofficialconcludedherremarksbynotingthatthesamplepopulationofbatchrecordsreviewedbyQuintileshasdemonstratedthatthecompany’sremediationefforts“areprogressingwellandtheyareeffective,”andtherehavenotbeenanyissueswiththefinalproduct.
GMPvs.DrugShortageRisks
Hospira’scomplianceproblemsandremediationchallengesprovideaninterestingcomparisonwiththoseatBenVenue,whichhasproceededdowntheconsentdecreepathwaywithFDA(IPQ“TheNewsinDepth”February4,2013).
BothcompanieshavebeenmajorgenericinjectablesupplierstotheUSmarketasproducersoftheirownproductsandascontractmanufacturers–raisingthestakesforFDAinhowitapproachesenforcementandweighs publichealthriskstheGMPproblemsposeagainstthoseposedbypotentialdrugshortages.
FDA’scurrentengagementwiththeGMPcomplianceproblemsinthegenericinjectablearenaillustratesthetightropetheagencyiswalkingintryingtoprotectpatientsagainstsubstandardproducts–particularlyhigh-riskinjectables–whileatthesametimetryingtoassurethattheyhaveaccesstothecriticalmedicinestheyneed.
InaninsightfulwhitepaperpublishedintheFebruaryissueofClinicalPharmacology&Therapeutics,CenterforDrugEvaluationandResearchDirectorJanetWoodcockandCDERcolleagueMartaWosinskahighlightedthecomplexitiestheagencyfacesinchoosingacourseofcomplianceactionwhendrugshortagesareatrisk(IPQ“TheNewsinDepth”February8,2013).
Inthepaper,theCDERofficialstakeahardlookatdrugqualityandshortageproblemsplaguingthegenericdruginjectablearenaandprovidevaluableinsightintotheircausesandhowtheyarelinked.Theanalysisencompassesthefactorsbehindtheinsufficientinvestmentbytheindustryinquality,howthatismanifestedintheplantsandtheproducts,andwhyqualityproblemsandmanufacturingdisruptionsturnintodrugshortages.
PropofolProblemsAlsoPlagueHospira,TevaandBenVenue
BenVenueandHospira,alongwithanothermajorgenericinjectablemanufacturer–Teva–haveallhadnotablysimilarissueswiththemanufactureofpropofol,includingcontaminationofthefinalproduct.
InHospira’s2010warningletter,visibleparticulatecontaminationofpr