sharing experiences of heatmarker vaccine vial monitor … · dcvmn-medigen workshop ... (adt ). in...
TRANSCRIPT
1
DCVMN-MedigenworkshoponGlobalRegistra:onandSupplyShortagesfrom6thto10thMarch2017,Taipei
Leo Wang Director Asia Business Development 泰坦公司中国,北京代表 Tel: 86-010-5920-4209 Cell: 86-138-101-64918 Fax: 86-010-5920-4222 email:[email protected] ; www.temptimecorp.com 北京市朝阳区建国路79号 中心写字楼2座9楼 951 100025; 9F, Tower 2, China Central Place, No.79 Jianguo Road, Chaoyang District, Beijing China, 100025 莫里斯平原,新 西州,美国’116 American Rd Morris Plains, NJ 07950
2016
SharingExperiencesofHEATmarker®VaccineVialMonitor
forWHOPQ
2007UNICEF/WHOJointPolicyStatementUrgingMemberStates,DonorAgenciesandNGOstoIncludeVVMsAsMinimumRequirementforPurchaseofVaccine
2012WHOIncludesVVMsAsCri:calCharacteris:cforVaccine
Prequalifica:on
UNICEF/WHOPoliciesonCri:calityofHEATmarkers(VVMs)
2
Vaccine vial monitor (VVM)
All vaccines Proof of feasibility and intent to apply a VVM to the proposed vaccine, as defined below. The vaccine presented for prequalification presents data confirming that it has a thermostability profile that will enable it to be matched to a current WHO-approved VVM type (VVM2, VVM7, VVM14 orVVM30) or a future VVM type approved by WHO(WHO/V&B/99.187, WHO/IVB/07.048). Signed declaration, as part of the cover letter submitted along with the file for prequalification confirming that the manufacturer will apply a VVM to the vaccine, and has the technical capacity to do so if requested by the purchasing specifications.
2
3
MonitorCumula:veHeatwithHEATmarkerVVM
Ac'veSquare
ReferenceCircle
• TheAc'veSquareisthecolorchangingreac'vepor'on• Itislightatthestartandprogressivelyandirreversibly
darkens• Thecolorchangeisfasterathighertemperatures• EndpointisreachedwhenthecoloroftheAc'veSquare
areaisequaltotheReferenceCircle
4
TheHEATmarkerTTIIsEasyToRead
ü
û
TheAc'veSquareislighterthantheReferenceCircle.
Iftheexiprydateisnotpassed,USEthevaccine.
TheAc'veSquarematchesorisdarkerthantheReferenceCircle.
DONOTUSEthevaccine.
ü
û
USE USE DONOTUSE
DONOTUSE
5
HEATmarkerVVMCategories
_____30days@37°C_____14days@37°C_____7days@37°C_____2days@37°C
TheVVM(VaccineVialMonitor)istheTTIusedbyWHO/UNICEFintheglobalimmuniza'onprogram.Temp'mehasmorethan17differentcategoriesofTTIsavailablefromdaysatrefrigeratedtemperaturetoyearsatroomtemperature.
HEATmarker VVM for Use on Vaccines
6
Pharmaceu:calProduct
Indica:on Customer Temp:meProduct
ValueDelivered
Children’sImmuniza'onCampaignsforarangeofcontagiousdiseases:• BCG• Diphtheria• Tetanus• Pertussis• DTP• HepB• HiB• MeningococcalAandC• Measles• Mumps,Pneumococcal• OPV• Rotavirus• Rubella• TetanusToxoid• YellowFever
OtherCampaigns:• HPV• IPV• Rabies• Typhoid
GSK,SanofiPasteur,Merck,Crucell,Pfizer,Novar's,SerumIns'tuteofIndia,Biofarma,JapanBCG,BB-NCIPD,BharatBiotech,StatensSerumIns'tute,BiologicalE,BharatSerumsandVaccines,Hagine,plusothers
VVM2,VVM7,VVM14,VVM30
• Preventsimmuniza'onwithheatdamagedvaccines
• Expandsreachofimmuniza'onprogramstoremotepopula'ons
• Increasesimmuniza'onprogramsefficiency
7
StepstoVVMImplementa:on
1. VaccineManufacturerSubmitsDossiertoWHOforPrequalifica'onwhichIncludesVaccineStabilityData
2. WHOIden'fiestheApprovedCategoryofVVMbasedontheStabilityDataoftheVaccine
3. VaccineManufacturerValidatestheVVMReac'vity&Performance
4. Determina'onofVVMType(DotorFullLabel)andPlacementontheVial(ArtworkApprovalNecessaryforFullLabels)
5. SOPsatManufacturerforVVMReceipt,StorageandUse
6. Installa'onandValida'onofVVMApplica'onEquipment
● GOAL− AcceleratedstabilitydatamustbegeneratedthatallowsthechoiceofthehigheststabilityVVMcategorypossible.
● RATIONALE− Atelevatedtemperatures,thehighestcategoryVVMwhichreachesitsendpointbeforethevaccinestoredatthesametemperaturebecomessub-potentshouldbechosen.ThisensuresthattheproductissHllsuitabletousewhileminimizeswastagethroughprematurediscardofvaccinethatissHllpotent.
AcceleratedStabilityStudiesforWHOPrequalifica:on
8
Thetemperaturesensi'vityofvaccinecharacteris'cs,par'cularlypotency,hasamajorimpactonthesuccessofglobalimmuniza'onprogrammes.WHOhasacknowledgedtheimportanceofclearlydefiningthestabilitycharacteris'csofavaccine.
Chapter10.Labelingstates:“IfVaccineVialMonitors(VVM)aretobeused,adequatestabilitydatashouldbegeneratedtosupportselec'onofappropriateVVMforavaccineinques'on.FurtherdetailsontheuseofVVMfordifferenttypesofproductsareavailableelsewhere.”2
1hnp://www.who.int/biologicals/publica'ons/trs/areas/vaccines/stability/Microsoo%20Word%20-%20BS%202049.Stability.final.09_Nov_06.pdf
2WHOTemperatureSensiHvityofVaccines(WHO/IVB/06.10)hnp://whqlibdoc.who.int/hq/2006/WHO_IVB_06.10_eng.pdf
WHOGuidelinesonStabilityEvalua:onofVaccines1
9
● ThebasisforchoosingaVVMcategoryforagivenvaccineistheAcceleratedDegrada'onTest(ADT).
● Inthistestsamplesaresubjectedtoarangeofelevatedtemperaturesatwhichsignificantandreadilydetectabledegrada'onisinducedinarela'velyshort'me.Therateatwhichdegrada'onoccursismeasuredandanalyzedinaccordancewiththeArrheniusequa'on.
● Vaccinesshouldbetestedtofailureattheseacceleratedtemperatures.
● VaccinesdonotneedtofollowtheArrheniusequa'onexactlytohaveasuitableVVMapplied.
3hnp://whqlibdoc.who.int/hq/2006/WHO_IVB_06.10_eng.pdf
WHOTemperatureSensi:vityofVaccines3
10
● Chapter7inthisGuidelineprovidesspecificrequirementsforinclusionintheproductdossiersubmissionregardingstability.
● Chapter7.2addressesacceleratedstabilitytes'ngofthefinalproducttodefinetheVVMcategorytobeusedwiththespecificvaccine:
“TablesofacceleratedstabilitydataarerequiredtodefinetheVVMcategorytobeusedwiththespecificvaccine(stabilityat2differenttemperaturesarerequiredandtheseareusually2-8°Cand37°Cor45°C),HoweverrealHmedataestablishestheexpirydaHng.Conclusionsonstabilityandtheclaimedshelflifeofthevaccine(s)shouldbepresented.”
• Manufacturersarestronglyencouragedtoinclude25°Casoneoftheacceleratedtesttemperatures.
4hnp://whqlibdoc.who.int/hq/2006/WHO_IVB_06.16_eng.pdf
GuidelineForthePrepara:onoftheProductSummaryFileforVaccinePrequalifica:on4
11
Category (Vaccines) No. of days to end point at +37°C
No. of days to end point at +25°C
Time to end point at +5°C
VVM 30: High Stability 30 193 > 4 yearsVVM 14: Medium Stability 14 90 > 3 years
VVM 7: Moderate Stability 7 45 > 2 years
VVM 2: Least Stable 2 N/A* 225 days
VVMReac:onRates
● ThefourcategoriesofVVMareVVM2,VVM7,VVM14andVVM30.
● Thenumberfollowing“VVM”correspondstotheupperlimitindaysat37°Cforatleast95%ofVVMstoreachtheendpoint.
● ThisTableliststheupperlimitindaysat25°Cfor95%ofeachVVMcategorytoreachtheendpoint,exceptforVVM2.
● Thecri'caltemperaturesforVVM2are37°Cand5°C.VVM2isonlyusedforOralPolioVaccineandisnotincludedinfurtherdiscussion.
5 hnp://www.who.int/immuniza'on_standards/vaccine_quality/who_pqs_e06_in05_rev_july2011.pdf
WHO PQS Performance Specification – Vaccine Vial Monitor (WHO/PQS/E06/IN05)5
12
● Thesetest'mesarecoincidentwiththeupperlimit'mesintheVVMPerformanceSpecifica'on.
● Thesetest'messhouldbeconsideredastheminimumrequirement.
● Addi'onaltes'ngisencouraged.● Testsshouldbecon'nuedun'lproductfailure,ifpossible.
− Forexample,donotstopthetestaoer7daysat37°C,con'nuetes'ngat14daysand30days.
− Donotstopthetestifasingleassayisbelowtheproductspecifica'on.
● Somevaccineformula'onsareverystabletowardsheatexposure.Manufacturersshouldconsiderextendingtestsat37°Cto45and60daysorlongerasappropriate.Similarlyextendedtestperiodsat25°Cshouldalsobeconsidered.
MinimumTestTimesat25°Cand37°CTest Temperature
(°C)Test Times
(days)
37 7, 14 and 30
25 45, 90 and 193
Minimum Stability Data to Support Choice of VVM Category (except OPV)
13
ProductAStabilityDataandVVMCategories
051015202530353740
1
10
100
1000
10000
100000
DegreesC
DAYS
VVM30 VVM14 VVM7 VVM2
CHOOSEVVM7
14
• VVMisacri'calcharacteris'cforWHOprequalifica'on
• SufficientstabilitydataneedstobeincludedintheProductSummaryFiletosupportthechoiceofthelongestVVMcategoryavailable
• Accelerateddegrada'onstudiesmustbecarriedoutforsufficientdura'ontoreachendofproductlifeattheacceleratedtemperature
• StabilitydataandVVMcategoryrequestsubminedtoWHOinProductSummaryFile
• WHOapprovestheVVMcategoryforapar'cularvaccine
• No'fica'onofVVMcategoryisprovidedtomanufacturerandTemp'me
Summary–VaccineStabilityandVVMCategory
15
16
VVMsarenormallyshippedinanLD3containerwiththeVVMspackagedonawoodenpallet,
Thereceivinginspec:onprocessbeginsonthedaytheHEATmarkerVVM’saredelivered.
Alterna:vely,VVMsaresentininsulatedshipperscontainingVVMspackagedwithdryice.
ReceiptandInboundInspec:on
SOPsforIQAmustbedeveloped
• Physicalcondi'onandVVMcolor
17
• VVMsshouldbestoredatorbelow-24°Ctominimizeanymeasurablechangeinini:alstar:ngop:caldensity.– Careshouldbetakenwhenselec'ngastorageareawithinthefreezer.– TheVVMsshouldbekeptawayfromthedoorsoastominimizetemperature
varia'onsthatcanbeashighasseveraldegreesCelsiusandcauseprematurecolordevelopment.
– Temperaturesduringfrozenstorageshouldbemaintainedandrecorded.
FrozenStorage
StorageVolume
• 10,000VVMsperroll
• 20rolls/carton(200,000VVMs)
• Cartonsize:23x25x41cm
18
• VVMsarereleasedbylot• ACer'ficateofAnalysisisincludedeachlot• Eachreceivedlotshouldbesampledandtestedaccordingtotheestablished
procedureshouldbesampledandtestedat37°CandcolorofVVMmeasuredwithdensitometer
ControlofVVMEndPointat37°C
SOPsforsampling,controltestandreleasemustbedeveloped
19
• VVMscanbeappliedmanuallyorbyautoma:clabelapplica:on– ChengduIns'tuteofBiologicalProductsapplied10millionVVMsmanually
duringtwoyears– StudiesbyChengdushowednodifferenceinadhesionbetweenmanualor
automa'capplica'on
• NoVVMrequiredtemperature/humiditycontrolofenvironmentduringlabelapplica:onbyanymanufacturer– VVMsarenormallyappliedduringfinallabelingprocess– Somemanufacturershavevalidatedcoldstorageinfinallabelingarea
Applica:onofVVMtoVial
20
Loca:onofVVMonVaccine5
Theloca'onoftheVVMonthevialdependsuponwhetherthevaccinemustbediscardedattheendoftheimmuniza'onsessioninwhichitisopened,orwhetheranyremainingcontentsinanopenedvialcanberetainedforuseinsubsequentsessions.Thefollowingcasesapply:
•Formul:-dosevialscontainingavaccinethatcanbeusedinsubsequentsessions:
Regardlessofthevaccinepresenta'on(liquid,freeze-driedortwovialcombina'onsofliquidandfreeze-dried),theVVMmustbepermanentlyanachedtothelabelofthevaccinevialandmustremainreadilyobservablebefore,during,andaoeruse,un'ltheen'recontentsofthevialhavebeenused.
•Forvaccinesthatmustbediscardedattheendofthesessionorwithin6hours,whichevercomesfirst:TheVVMmustbeanachedtothevaccinevialorampouleandmustremainreadilyobservableun'lthevialorampouleisopened,butnotobservableaoeropening.Inordertoachievethisrequirement,theVVMmustbelocatedontheflip-offtopofavialorontheneckofanampoule.
Onaproductbyproductbasis,WHOwilladviseboththevaccineandtheVVMmanufacturerwheretheVVMistobelocated.
Loca'ngtheVVMonthebonomofavialorampouleisneveracceptable–itmustalwaysbeinavisibleloca'on.
5 hnp://www.who.int/immuniza'on_standards/vaccine_quality/who_pqs_e06_in05_rev_july2011.pdf
24
VVMsareAppliedDuringFinalLabeling
● PreferredtoapplyVVMinlineduringfinallabelingopera'on
● PossibletoapplyVVMasasecondaryprocess
● Ambienttemperatureandligh'ng(avoidexcessivelightexposure)
● SomemanufacturershavelocalcoldstorageofVVMinlabelingarea
PLAYKartoglu-WHO
25
• VVMs Dots are normally applied to the cap of the vial
YouTube Link to Serum Institute of India Video
http://www.youtube.com/watch?v=ytpS1SB_qGY
• VVM Dot rectangles are applied to the neck of ampoules
VVMDotApplica:ontoCapofVialorNeckofAmpoule
26
● VVM applied with existing equipment● Speeds over 400/minute in routine operation
Applica:onofFullLabelVVMtoVial
PLAY
27
VVMApplica:ononPrintedLabel
ThevaccinemanufacturercandecidetoapplytheVVMdotontothe
commonlabel(printedlocally)athisfacilitybeforetheviallabeling.
Pre-printedLabel
VVMDot
PrintedLabelwith
VVM
28
VVMApplica:ononPrintedLabel
1)VVMdotisappliedtopre-printedcommonlabelwithnoVVM
2)CommonlabelwithVVMisappliedtovaccinevial
CrucellCrucell
2StepProcess
29
Automa:cLabelApplica:onEquipmentSuppliers
SeveralcompaniesthatarefamiliarwithVVMapplica:onare:
• Accraply(Barry-WehmillerGroup)• Bausch&Strobel• Herma(Labelworx)• Neri• MaharshiUdyogand• PharmaPack
30
LessonLearned
AdhesionofVVMtocapstronglydependentoncapcomposi:onandtexture• FieldcomplaintofpooradhesionofVVMtocap–VVMslioingorcomingoff
• Raisedleneringonplas'ccapandmanefinishshouldbeavoided• Bestsurfaceisflatandglossy(shiny)
• 2ndfieldcomplaintwithdifferentmanufacturer• Capchangedandnotestofadhesionperformedpriortouse
• Noreportedproblemswithmetalcaps.Nootheradhesionproblemsreported.
31
Conclusions
• SuccessfulGMPimplementa'onofVVMatlargeandsmallvaccinemanufacturersaroundtheworld
• independentofsizeofmanufacturer• VVMimplementa'onbylocalmanufacturersforlocaldistribu'oninIndiaandIndonesia
• SOPs(includingtraining)mustbeputinplaceforreceipt(IQA),storageandapplica'onofVVM
• AdhesionofVVMtocapmustbeverified
• Applica'onofVVMtovialscanbeaccomplishedatroomtemperaturebyhandorbyautoma'cequipment