ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
1
CDER/OPQOfficeofSurveillance
SurveillancePastandFuture
RussellWesdykActingDirectorOfficeofSurveillance
22
Surveillance‐ Past
2
SSM
eDRLS Incidents
EIRReview Recalls
DirtydataSystemsIssuesLimitedintegrated
PIC
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
2
33
Surveillance‐ Planned
SiteSelectionModel(SSM)
eDRLS Incident
EIRReviewRecalls QualityMetricNIPP
QIDossiers
CleanedData,IntegratedSystems,EnhancedReg
Data knowledgeBetterdecisions
VolumeSite&ProductList
4
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
3
5
OfficeofSurveillance
• Whatarethesiteandproductsinourinventory?– Andwhatdotheydo?
• Howwellaretheydoingit?– Granular,atproductorsitelevel
• Whereshouldwego?
• Howshouldweassesswhatwefind?
OSStructureandActivity
QIBKarthik Iyer
DQIRAMBethPhilpy
(RaphaelBrykman)
DQSATeddiLopez
(RosaMotta)
OfficeofSurveillanceRussWesdyk(NeilStiber)
RAMBRezaKazemi
DIBObinnaUgwu‐Oju
QDABEliseMurphy
IAB“Coki”Cruz
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
4
OSStructureandActivity
Sites/Products QualityMetrics
DIB QIB RAMB QDAB IAB
SSM&SSIList
FARs/BPRDsSampling
EIRAssessment
Wheretogo?
Dossiers
ORA
NIPP
Who/whatisoutthere?
Whatshouldwedowhenwegetthere?
Howwellaretheydoing?
RISKBASEDINSPECTIONSCHEDULING
8
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
5
FDASIA705:Risk‐basedInspectionFrequencyFactors
(A)Thecompliancehistoryoftheestablishment.
(B)Therecord,history,andnatureofrecallslinkedtotheestablishment.
(C)Theinherentriskofthedrugmanufactured,prepared,propagated,compounded,
orprocessedattheestablishment.
(D)Theinspectionfrequencyandhistoryoftheestablishment,includingwhether
theestablishmenthasbeeninspectedpursuanttosection704withinthelast4years.
(E)Whethertheestablishmenthasbeeninspectedbyaforeigngovernmentoran
agencyofaforeigngovernmentrecognizedundersection809.
(F)AnyothercriteriadeemednecessaryandappropriatebytheSecretaryfor
purposesofallocatinginspectionresources.”
9
CurrentSurveillanceModelStructure
10
OVERVIEW
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
6
NIPP
11
NewInspectionProtocol– KeyPoints• Whatistherecipeforasuccessfulinspection,onethataddsvalueandencouragesmanufacturingquality?
12
12
Inspectionsshouldyieldsemi‐quantitativeassessmentsonthemanufacturingquality atinspectedfacilities.
Whilecontinuingtodocumentobserveddeficiencies,inspectionsshouldalsoidentifypracticesthatexceedbasiccompliance.
Promoteanoverallbroadassessmentofstateofquality CDERandORAcollaboratethroughteam‐based
inspectionsthatincludereal‐timesharingoffindingsandfeedback.
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
7
QualityMetricsAnotherpartofthequalityintelligencepicture…
13
ClassicCars?• MGBorMazdaMiata?
– Bothareroadlegal– Butinsuranceratesaredifferent!
• GuyVillax says“FDANeedsaDean’sList”– FDAagreestheconcept
• Whichcarislikeasixsigma,ICHQ10embracingsite?– Shouldthatsitebeonthesameinspectioncycle?– Treatedthesameforpostapprovalchangecontrol?
14
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
8
15
GoalsforQualityMetrics
• Forindustry– Promotesresponsiblepracticesandqualitydrivencorporateculture
• Forpublic:– Focusonqualityleadstofewerrecallsandqualityrelatedshortages
• ForFDA All:– Industryachievesandisrewardedforquality,withoutextensiveregulatoryoversight
16
ISPE Pilot Results Wave 1
PDA Metric Conf #2 Survey Results
PDA Journal publishes Metric Definitions
PDA Culture Metrics Survey
FDA Draft Guidance Comment Period
“Metrics of Potential Interest”
•Feb 2013
•May •Aug •Nov•Feb
•2014•May •Aug •Nov
•Feb
•2015
Brookings Stakeholder Meeting
ISPE Pilot Announced
Industry White Papers Published
Initial Industry Responses
FR Notice Requesting Metrics to Prevent Drug Shortages
FDA Metrics Journey 2013- 2015
•May •Aug Nov
PDA Metric Conf #3
PDA Metric Conf #1
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
9
FromScientiststoLawyers…?
…topatientswehope!
17
QMProgram‐ Concept• BIO – Metricsprovideavaluabletooltoquantifyprogresstowarda
specificgoalofcompliancewithcGMP,andultimatelyproductquality.MetricscanprovideavaluabletooltoquantifyproductqualityandcanassisttheAgencyindevelopingarisk‐basedinspectionprogram.
• GPHA – thegoalofGPHAmembersistoproducehighqualitymedicine,andwebelievethatFDA’smetricseffortscanfacilitatethatgoal.FDAhasbeenverycollaborativeandtransparentwithindustryinconsideringmetrics.
• CHPA – Wearesupportiveofrisk‐basedinspectionapproachesandacknowledgethatqualitymetricsshouldbeinvestigatedasonefactorinassessingrisk.Weagreethatcertainmetricsmaybeapplicableasanindicatorofafirm’soverallqualitysystem,qualityculture,andcomplianceprofile…supporttheconceptthatwell‐designedmetricsarecriticalindrivingandmeasuringcontinuousimprovementactivitiesinbothqualitysystemsandimprovingprocesses.
18
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
10
QMProgram– 706Mechanism
• BioWhitePaper – “FDASIA[…]provideFDAwiththeauthoritytorequestcertaininformation,outsideofanon‐siteinspection,fromregulatedcompaniestofurtherinformandrefinetheAgency’sriskbasedinspectionplanningefforts.”
• GPHAWhitePaper– “GPHAwouldliketosuggest[…]ariskbasedapproachintheselectionofsitesforinspectionfrequencyandtargetingusing[…]submissionunderFDASIA.”
• PDAWhitePaper– “FDASIAgaveFDAnewtools[…].Section706allowsFDAtorequest[…]recordsinadvanceorinlieuofaninspection.”
• ISPEWhitePaper– “This‘whitepaper’proposesaninitiallistofqualitymetricswhicharereportabletoFDAtosupportarisk‐basedinspectionprogramasgiveninsections704to706ofUSFoodandDrugAdministrationSafetyandInnovationAct(FDASIA)andassistindustrymovingtowardsthe‘desiredstate’.“
19
QMProgram‐ Scope
• ISPEPilot – FDAcannotparticipateinindustrypilotbutappreciatesISPE’seffortconsistentwithcallsfor“trial,”“pilot,”or“phasedapproach.”
• GPHAWhitePaper– “GPHAwouldliketosuggest[…]mandatoryinformationsubmission.”
• CGA–Medicalgastradeassociationrecommendedsubmissionofspecificmetricsrecognizingthepotentialof“inlieuofinspection”language.
20
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
11
QMProgram‐ ReportingApproach
• AmgenCommentstoDocket– AmgenagreeswithFDA’sproposaltocollectmetricsbyproductsegmentedbysite.
• PDACommentsatPublicMeeting– PDAsupportsFDA’sapproachtocollectmetricsbyproduct,bysiteasdescribedinthedraftguidance.
21
QMProgram‐ Metrics
• FDAMetrics – Limitedsetderivedfromconsensusset(majorityrecommended)andrefinedwithmetricsnotedbysupportedset(multiplerecommendations).
• GPHAWhitePaper– recommendeduseof16factors.
• PhRMAWhitePaper– recommendeduseof17‐ 18factors;7‐8ofwhicharenewandsuggestedforimmediateuse,withanadditional6suggestedforfutureuse.
22
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
12
QMProgram– WhitePaperMetrics
23
Metric /
Org.
Critical
Deviation
Rate
Confirmed
OOS Rate
Batch
Reject
Rate
Product
Quality
Complaint
Rate
Recall
Rate
Stability
Failure
Rate
Rework /
Reprocessing
Rate
Unconfirmed
OOS Rate
% APR
completed
On time
FAR/BPD
Rate
Sterility
Failure
Rate
Drug
Shortage Rate
Bio X X X
Genetech X X X
GPHA X X X X
Mylan X X X X
ISPE X X X X X X
PDA X X X X
PhRMA X X X X X X X
WhatwasFDAdoing?...
Listeningtostakeholdertechnicalinputover2yearsanddevelopinganalignedproposal
24
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
13
InitialImplementationandLearningPeriod
25
ProposedImplementationofQMProgram• Thisisasurveillanceprogram…notanenforcementprogram
• Submissionofmetricswouldnotresultin– 483observationsorotherenforcementactions– Fraud(vs.dataqualityissues)wouldbereferredtoOC
• Submissionofmetricswouldinitiallyresultin– DiminishedriskrankscoreinSSM(routineGMPinspectionscheduling)– Moremetrics=greaterreduction– Metricdataitselfwouldnotinfluencereduction
• Untillearningperiodcompleteandrelationshipsestablished…thiswilltaketime
• Firstprinciple…moreinformationisbetterthanlessinformation
• SignaldetectionleadstoOPQengagingwthefirm
26
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
14
ProposedInitialLearningFocus• Correlations
– Doesnotimplycausation– Likelydifficultytoestablish
• Outcomesdataisvery“dirty”– FARs,Recalls,EIRclassification,evenshortage
• OutlierSignalDetection– Canweidentifybestpractices?– CanweidentifypotentialissuesandengageviaOPQratherthanoverlookandpotentiallyfaceneedforOCenforcementactionslater?
• DataQualityChallengesandSolutions– Whatdefinitionsneedclarification– Whatdataportalsystemsneedrefinement?
27
28
Test The Plumbing
• InformalDataExchange• PotentialDate:Q2/Q32016• Voluntary• Nobenefit• Nodisadvantage• Datawouldnotbeusedforanyotherpurposebuttotesttheinformaticscapabilities
Ifinterested,pleasesendanemailto:[email protected]
ISPE Annual Meeting
8 – 11 November 2015
Philadelphia, PA
15
ThankYou
29
