fda inspections - lessons learnt
TRANSCRIPT
FDA Inspections – Lessons Learnt
How does FDA decide who to inspect?
• Registration database identifies who manufacturers devices for distribution in the U.S.
• Listing database identifies what devices they distribute
• FDA prioritizes inspections by risk and gives higher risk devices/situations a higher priority
FDA Inspections – Lessons Learnt
How does FDA choose ?
• Mandated by law, every 2 years for class II and class III device manufacturers
• Risk• Follow up inspections to a regulatory action• Complaints (public & industry) and Recalls
FDA Inspections – Lessons Learnt
Investigator Tools
• Federal Food, Drug, and Cosmetic Act• 21 Code of Federal Regulations (800-
1299)• Quality Systems Manual: A Small Entity
Compliance Guide on-line
FDA Inspections – Lessons Learnt
Investigator Tools
• Compliance Policy Guides• Quality System Inspection Techniques
(QSIT)• Compliance Program Guidance Manual• CP 7382.845 Inspection of Medical Device
Manufacturers available on-line
FDA Inspections – Lessons Learnt
Investigator Tools
• Investigations Operations Manual• 5.2.1.1 Preannouncements• 5.6.2 Medical Device Quality System/
GMP• 5.6.9 Device Inspection Reports• 5.10.4.3.9 Manufacturing/Design
Operations Specific Instructions for medical device EIRs
• 5.10.4.3.16 Additional information Specific Instructions for medical device EIRs
FDA Inspections – Lessons Learnt
Investigator Tools
• Previous Establishment Inspections Reports
• Training Courses• Other investigators or FDA Labs• DSMICA
FDA Inspections – Lessons Learnt
Investigator Tools
• Guidance Documents (can be accessed from www.FDA.gov website under Medical devices CDRH Device Advice)
• Internet • Other Federal, State and Local agencies• FDA Recognized Consensus Standards
FDA Inspections – Lessons Learnt
What is high priority for an inspection?
• Make Class III or Class II devices • Make implantable devices and life
supporting and life sustaining devices• Recently introduced a new device to the
market• Have had significant violations and
complaints in the past• Have had a recall
FDA Inspections – Lessons Learnt
Does FDA notify the manufacturer of an upcoming inspection?
• FDA calls domestic manufacturers up to 5 calendar days before the inspection
• FDA contacts foreign manufacturers 2 - 3 months in advance to schedule inspection
• Manufacturer may be requested to send Quality System Manual or equivalent for pre-inspection review
FDA Inspections – Lessons Learnt
Does FDA notify the manufacturer of an upcoming inspection?
• FDA calls domestic manufacturers up to 5 calendar days before the inspection
• FDA contacts foreign manufacturers 2 - 3 months in advance to schedule inspection
• Manufacturer may be requested to send Quality System Manual or equivalent for pre-inspection review
FDA Inspections – Lessons Learnt
WhathappenswhentheFDAinvestigatorarrivesatthesite?
• Asktoseethetopmanagement(”mostresponsibleperson”atthefirm.
• Presentcredentials(identificationasanauthorizedFDAinvestigator)
• IssueFDA-482“NoticeofInspection”(explainsFDA’slegalauthoritytoinspect)
FDA Inspections – Lessons Learnt
Can you refuse an inspection?
• Under section 704 of the FD&C Act, FDA is authorized to enter establishments.
• They are further authorized to inspect “at reasonable times and within reasonable limits and in a reasonable manner”.
• FDA can also seek an Administrative Inspection Warrant from a United States District Court.
FDA Inspections – Lessons Learnt
Whathappensnext?
• Gatherinformationaboutsizeandstructureofcompany,whoaretheresponsibleofficials,whatproductsaremanufacturedthere.
• Evaluatethemanufacturer’sQualitySystemusingtheQualitySystemInspectionTechnique(QSIT)
FDA Inspections – Lessons Learnt
What happens during the inspection?
• Investigator may tour the facility to get an idea of layout, workflow, and areas that may need closer inspection. (Start Big, Get Small)
• This helps the investigator decide how to organize the inspection
FDA Inspections – Lessons Learnt
Whathappensduringtheinspection?
• TheInvestigatormayrequesttointerviewemployees,takesamples(484ReceiptforSample)andmakecopiesofdocuments.
• TheInvestigatormayalsorequesttotakedocumentsandpicturesduringtheinspection
FDA Inspections – Lessons LearntWhatisQSIT?
• Identifies4majorsubsystemstoevaluateandstatesthepurposeandimportanceofeachsubsystem
• CAPA• DesignControls• Management• ProcessControl
• Providesflowchartsandinspectionalobjectivestocoverduringinspection
• Offersadviceoninspection• Providestablesforstatisticalsamplingofrecordsfor
review
FDA Inspections – Lessons Learnt
WhatisQSIT?
http://www.fda.gov/downloads/ICECI/Inspections/InspectionGuides/UCM085938.pdf
FDA Inspections – Lessons Learnt
SubsystemsoftheQualitySystem
http://www.fda.gov/ICECI/Inspections/Inspect ionGuides/ucm074883.htm
FDA Inspections – Lessons Learnt
DoesFDAconductdifferenttypesofinspections?
• Investigationmayconduct1of4typesofinspectionformedicaldevices:
• Level1– AbbreviatedQSIT• Level2– BaselineQSIT(Comprehensive)• Compliancefollow-up• ”Forcause”
FDA Inspections – Lessons Learnt
WhatisaLevel2baseline(comprehensive)inspection?
• Coversall4mainsubsystems• IsconductedwhenthefirmhasneverhadLevel
2inspectionandevery6yearsthereafter,resourcespermitting
• Providesanoverallevaluationofthefirm‘squalitymanagementsystem
FDA Inspections – Lessons Learnt
WhatisaLevel1abbreviatedinspection?
• IsconductedafterfirmhashadaLevel2inspection,andqualitysystemwasincompliancewithrequirements
• CoversCAPAplusoneothermajorsubsystem• Coversadifferentsubsystemeachtime
FDA Inspections – Lessons Learnt
Whatisa“ForCause”inspection?
• InitiatedattherequestofCDRH,ORAHeadquarters,RegionalorDistrictDirective
• DictatedbythesourceofinformationandmaydifferfromtypicalQSITapproach
• TheseinspectionsaregenerallymoreindepthinparticularareasthantypicalQSITinspections
• ConductedastheneedarisesImportantnoteinCP,iftheInvestigatorencountersaseriouspublichealthriskduringtheQSITinspectiontheinvestigatormayswitchtoaforcauseinspection
FDA Inspections – Lessons Learnt
Whatisacompliancefollow-upinspection?
• Isconductedtoverifyadequatecorrectionofpreviousviolationsordocumentcontinuingviolationstosupportpossibleregulatoryaction
• Isconductedtofollowuponinformationindicatingseriousproblemsatfirm
• MayincludeelementsofQSIT
FDA Inspections – Lessons Learnt
Whathappensattheendoftheinspection?
• Meetwithmanagementtodiscusstheinspection• PresenttheFDA483“ListofObservations”ofany
significantobservations• Discusstheobservations
FDA Inspections – Lessons Learnt
ThisisanexampleoftheFDAForm483,InspectionalObservations.Theheaderidentifies theFDAdistrictofficethatperformed theinspection,thedate(s)ofinspection,nameandaddressofthefacilitythatwasinspected,thenameandtitleoftheindividualtowhomthe483isissuedto(usuallythemostresponsibleindividualphysicallypresentinthefacility),abriefdescriptionofthetypeoffacility,andthefacility'sFEI(FDAEstablishmentIdentification)number.
FDA Inspections – Lessons Learnt
FDA– 483“InspectionalObservation”
• Thecontentofa483maybehandwritten,typed,completedinaPDFfileandprinted,orcompletedviatheFDA'scomputersystemcalledTurboEIR.
• Theobservations listedonthisformdonotrepresentafinalagencydeterminationregardingyourcompliance.Anadditionalstatementonlyincludedformedicaldevicesisthattheobservationsarenotanexhaustivelistingofobjectionableconditions.Underlawyourfirmisresponsible forconductinginternalself-audits toidentifyandcorrectanyandallviolationsofthequalitysystemrequirements.”
• Ifthefirmhaspromisedand/orcompletedacorrectiveactiontoanFDA483priortothecompletionoftheinspection,theFDA483shouldbeannotated.
FDA Inspections – Lessons Learnt
FDA-483“InspectionalObservations”TurboEIR(EstablishmentInspectionReport)?
• Linkscitationstounderlyingregulationsandstatutes
• ProvidesuniformFDA-483sandEIRs• Improvesdataanalysis
FDA Inspections – Lessons LearntWhatareannotationstothe483Asof1997,theFDAestablishedanannotationpolicyformedicaldeviceinspections.Theinvestigator(s)shouldoffertoannotatethe483withoneofthefollowing:
• Reportedcorrected,notverified• Correctedandverified• Promisedtocorrect(maybeappendedwith"byxxxdate"or"withinxxxx daysormonths")• Underconsideration• Noannotation
Theactualannotationofthe483occursduringthefinaldiscussionofthefirm’smanagement;ifthefirmprefersnoannotation,thenannotationwillnotbeperformed.Theannotationsmaybeaftereachobservation,attheendofeachpage,oratthebottomofthelastpagepriortotheinvestigator’ssignature(s).
Theterm„verified”means„toconfirm;toestablishthetruthoraccuracy”.Incase,theinvestigatormustdotheverification.Insomesituations,theywillnotbeabletoverifythecorrectiveactionunlessthereisfurtherdistrictorCenterrevieworuntilthereisanotherinspectionoftheestablishment.Ifthefirmhaspromisedcorrectionandfurnishesadateortimeframeforcompletion,thismaybeaddedtotheannotation.Iftheinvestigatorandfirmhave„agreedtodisagree”aboutthevalidityofanobservation,theobservationmaybeannotatedwith„underconsideration”ornoannotationisused,basedonthefirm’sdecision.
FDA Inspections – Lessons LearntTop10DevicesObservationsUsedinTurboEIR- 2015http://www.fda.gov/ICECI/Inspections/ucm481432.htm#Devices
FDA Inspections – Lessons Learnt
Whatshouldthemanufacturerdoaftertheinspection?
• SendalettertoFDAidentifyinghowtheyhavecorrectedobservationsorwillcorrectthem
• Providedocumentationofanycorrectionsthathavebeencompleted
• Provideatimetableorestimatedcompletiondateforfuturecorrections
FDA Inspections – Lessons Learnt
Whathappensnext?
• Investigatorreturnstoofficetowritean“EstablishmentInspectionReport”orEIR
• Inspectionisclassifiedbasedoninspectionalfindings
• Complianceofficerdecideswhethertorecommendregulatoryaction
FDA Inspections – Lessons Learnt
HowdoesFDAclassifyinspectionreports?• NAI– Noactionindicated• VAI– Voluntaryactionindicated– somedeficiencies
butnotserious• OAI– Officialactionindicated– seriousdeficiencies
identified,andFDAmusttakeactiontoassurecorrection
FDA Inspections – Lessons Learnt
WhatactionscanFDAtaketoaddressOAIinspections?
• WarningLetter• Seizure(Importrestrictions)• Injunction• Civilpenalties• Criminal
FDA Inspections – Lessons Learnt
WarningLetter
• FDAsends“WarningLetter”describingmanufacturer’sviolationsofFDAregulationsandrequestingareplywithin15days
• FDAinspectsthemanufacturer6- 12monthsaftersendingtheWarningLettertoconfirmcorrectionofdeficiencies
FDA Inspections – Lessons Learnt
Preparation
• ConfirmInspectionDatewithFDAprovidetravelandhotelsuggestion
• ReviewpreviousFDAinspectiondocumentation483
• IdentifycompanyprimarycontactandSubjectMatterExperts
• PrepareListofProductsShippedtoUSA• ReviewEstablishmentListing• ReviewUSclearanceandapprovalstatus
FDA Inspections – Lessons Learnt
Preparation
• PerformGapAnalysistoQSR• Focus
• CAPA• DesignChangesandDesignControl• ComplaintsMDRs• Recalls• ProcessValidation• LabelingversusClearance• Audits• Purshasing
FDA Inspections – Lessons Learnt
Preparation
• EstablishrealisticCorrectionPlan• TrainEmployeesonQSRandGeneralBehavior
duringInspection• PrepareListofContacts/SME’sanddeputies• SetUpFrontandBackOffice• PerformSimulatedInspectiontoVerifyWorkFlow
duringInspection• PreparealistofknowGapsnotCorrectedpriorto
Inspection• DiscussopenRisksandGapstoagreeonStrategy
FDA Inspections – Lessons Learnt
DuringInspection
• AskforAgendatoplanfacilitytoursandSME’s• DocumentRequestsfromInspectorandStatus,
informinspectorondelaysinprovidingdocumentation
• TrackDocumentsRequested• TrackInteractionwithEmployees• Incasetheinspectorrequestsdocumentationtobe
sendtoFDAdocumentdocumentstransferred