KOREANMFDS

RegulatoryInspections
Osvaldo Lozada
February 27 2014
1
February 27, 2014
KOREANMFDS
PresentationTopics
The Agency TheAgency
NotificationofInspection
InspectionCosts
Pre Inspection
CulturalAspects
InspectionOpeningMeeting p p g g
FacilityWalkthroughs FocusAreas
GeneralInspectionProceedings
Inspection Closure InspectionClosure
Response
ProductApprovalTimelines
InspectionHighlightsSummary
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KOREANMFDS
h TheAgency
The Korean Ministry of Food and Drug Safety (MFDS) was established in TheKoreanMinistryofFoodandDrugSafety(MFDS)wasestablishedin
1996astheKoreaFoodandDrugSafety
Formerly named as Korean Food and Drugs Administration KFDA FormerlynamedasKoreanFoodandDrugsAdministration KFDA
AgencyvisionandpurposesimilartoUSFDA:
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KOREANMFDS
f f NotificationofInspection
Inspectiontriggeredbyanewproductfiling.
OurRegulatoryAffairscolleagueinKorea g y g
servedasourliaisonwiththeagency.
The agency requested a total of four (4) Theagencyrequestedatotaloffour(4)
inspectiondaysforthePAI.
Inspection dates were discussed and agreed Inspectiondateswerediscussedandagreed.
Inspectorsnames(2)notifiedinadvance.
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KOREANMFDS
f f NotificationofInspection
I i PAI Inspectionpurpose:PAI
InspectionDates:February1821,2013
Two(2)InspectorsofthePharmaceutical
QualityManagementDivision y g
TheLeadInspectorwastheScientificReviewer assignedto
ourNDA
ConsideredanationalexpertinGMPfacilitiesandutilities
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KOREANMFDS
InspectionCosts
InspectionarrangedandcostspaidbyMerck.
Agencyrequiredbudgetlimits:
Travel:Specificflightsselectedbyinspectors
Hotel:105USD/night(w taxes,WIFI,breakfast)
May be up to 123 USD per each inspector Maybeupto123USDpereachinspector
Meals:49USDpereachinspector
DailygroundtransportationwithMerckSecurity y g p y
Dailyallowance:26USDpereachinspector
InspectionfeepaidbyMerck:$10,500
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KOREANMFDS
Pre Inspection
Preinspectionchecklistreceived
Merck employees (2) allowed to serve as Merckemployees(2)allowedtoserveas
translatorsbytheagency
Requested facility tour through the product Requestedfacilitytourthroughtheproduct
mfg.processinoperation
D il d d i i i i d Dailyextendedinspectiontimeperiodrequest
Noinspectionagendaprovided
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KOREANMFDS
Pre Inspection
D il d li f d d b 3 Detailedlistofdocumentsrequestedabout3
monthspriortoinspection
Multipledrawings(facilities,operations,productmfg.
processflow,water/airsystems,labs.,etc.)
Environmental Monitoring Water HEPA filter previous EnvironmentalMonitoring,Water,HEPAfilter previous
yeardata/trendanalysis
Training(Operators,QAandLabs)
Organizationalcharts
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KOREANMFDS
Pre Inspection
D il d li f d d b 3 Detailedlistofdocumentsrequestedabout3
monthspriorinspection(continued)
MultipleSOPs(Environmental,Training,PestControl,
DocumentationMgt.,ChangeControl,Internal/Supplier
Audits,RetentionSamples,Micro,Sampling,Stability, , p , , p g, y,
Deviations,OOS,APR,Complaints,Recall,packaging,
disposition,etc.)
V lid ti M t Pl P V lid ti b t h d ValidationMasterPlan,ProcessValidation,batchrecords,
Bulkproductholdtime
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KOREANMFDS
Cultural aspects Culturalaspects
MFDAInvestigatorsEnglishisverylimited
WesternHandshakeispopularinSouthKorea
BusinessCards:importantpartofintroduction
Give a card so recipient can read without turning Giveacardsorecipientcanreadwithoutturning
Receiveacardwithbothhands,readand
acknowledge contents, keep on desk for duration acknowledgecontents,keepondeskforduration
ofmeeting
Name placards on the inspection table Nameplacardsontheinspectiontable
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KOREANMFDS
l l Culturalaspects
Dietaryhabits:
Didnotrequestanyspecificmeals
Suggesttohavewhitericeandvegetablesinmenu
Hierarchy was obvious between inspectors Hierarchywasobviousbetweeninspectors
InspectionwasfullyledbytheLeadinspector
Second inspector showed very high respect to the Secondinspectorshowedveryhighrespecttothe
inspectionleader,andherrolewaslimitedto
documentreviewandwalkthroughobserver g
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KOREANMFDS
InspectionOpeningMeeting
Openingmeetingagendafollowed:
1. Introductions Ledbythehost y
Exchangebusinesscards
Roundtableintroductions
SiteSr.Mgt.,Translators,ScribeandHost
2. GeneralSitepresentation BysiteGM
3. Productpresentation Byproducttechnicallead
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KOREANMFDS
InspectionOpeningMeeting
4. Noagencypresentationofferedbythe
inspectors
5. Agreedinspectionitemsfor1
st
day:
Reviewofdrawingssentinadvancesuchas:
Productmfg.facilities
Personnelandmaterialsflow
HVAC/PurifiedWatersystems / y
Facilitytour(11:00AM)
Fullproductprocessflow(chronologicalorder)
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KOREANMFDS
l lk h h FacilityWalkthroughs FocusAreas
Warehouse
Externalairparticlescontrols
Pestcontrol
Productmaterialmovementprocess
APIReceiving/Storage/Weighing/Disposition
Qualityincomingsamplingroomcontrols
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KOREANMFDS
l lk h h FacilityWalkthroughs FocusAreas
Manufacturing
Productmfg.stagessegregation
Rooms,equipmentandcorridorscleaning
Material/peopleflowcontrols
Equipment&utilitiesstate
Mfg.Equipment
HEPAfilters
Dustcollectionsystem
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KOREANMFDS
l lk h h FacilityWalkthroughs FocusAreas
Laboratories
API&Rawmaterialsweighing/testingreports
MicrobiologyLabEnvironmentalMonitoring
Bulk product hold time Bulkproductholdtime
ReserveSamplescontrolledcage
/ l Containers,RoomTemperature/RHcontrols
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KOREANMFDS
l lk h h FacilityWalkthroughs FocusAreas
Utilities
PurifiedWater&HVAC
Spentmostofthetourtimeinspectingphysical
conditionsandlabelingofthesesystems g y
SystemsQualifications
HEPA filters verification program HEPAfiltersverificationprogram
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KOREANMFDS
l d GeneralInspectionProceedings
D il d d i i i i d Dailyextendedinspectiontimeperiods
8:30AM arrivaltosite
7:00PM 8:00PMdeparturetime
Mostofthetimeduringthefourinspection
dayswerespentinfacilitywalkthroughs
Inspectorsdidnotsplitduringtours
Noformaldailywrapups
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KOREANMFDS
l InspectionClosure
Briefagencypresentationoffered
Agencygeneralinformation/goals
Reportandresponseprocess
Inspectionreportshouldbereceivedin23weeks
Responsereportmustincludecompletedactionsand
evidences
Once response and actions are reviewed and accepted Onceresponseandactionsarereviewedandaccepted
productapprovalwillthenbedetermined.
Presentationelectronicfilenotshared
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KOREANMFDS
l InspectionClosure
Lead inspector presented the Leadinspectorpresentedthe
observations/concernsinclosuremeeting
V b ll N d ft t id d Verbally Nodraftreportprovided
Fewminorobservationsmostlyrelatedtofacilities
and equipment andequipment
Observationsnotcategorizedwhenmentioned
N t ti f CAPA i di t d NoexpectationsofCAPAsindicated
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KOREANMFDS
Response
Inspection report received 1 month later Inspectionreportreceived1monthlater
TranslatedtoEnglishin2days
Response due date for 2 months after report date Responseduedatefor2monthsafterreportdate
Verylongresponseprocess
Ledbetweensitehost&MerckKoreaLiaison
(Leadtranslator) withtheKFDA
Li i ll d th L d I t l ti d LiaisoncalledtheLeadInspectorseveraltimesand
visitedhimintheKFDAofficestwicetoreview
proposed action plans proposedactionplans
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KOREANMFDS
Response
Leadinspectorrequestedtoreviseresponse
reporttoaddmoreevidenceofcompleted p p
actionsasattachments:
AllBeforeandAfter All efore and After
Pictures,SOPs,drawings,reports
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KOREANMFDS
d l l ProductApprovalTimeline
Action Month # Action Month #
NDAsubmitted to KFDA 0
KFDAinspection 6 p
Originalresponseissued 9
R i d i d 10 Revised responseissued 10
KFDArequestedadditional
evidences
11
Responsefinally accepted 12
NDAapprovedbyMFDS 13
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KOREANMFDS
hl h InspectionHighlightsSummary
I t d ti b i d t l Introductionsbusinesscardsprotocol
Facilitywalkthroughswithproductinoperations
Mf S i Mfg.Stagesroomssegregation
Facilities&equipment
HVAC / Water System HVAC/WaterSystem
Watchfortheinspectorsbodylanguage!
Show your immediate actions to the inspector Showyourimmediateactionstotheinspector
Noformaldailywrapups
Responses with completed actions /evidences Responseswithcompletedactions/evidences
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KOREANMFDS
Thankyou!
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