CVTHigh-speed inspection machinesfor parenterals quality control

Machine Types

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Type Container Inspections Outlets

CVTfc Cartridge Multiple Multiple

CVTcc Cartridge Limited cosmetic inspections Max. 3 outlets plus 1 dump

CVTfv Vial Multiple Multiple

CVTcv Vial Limited cosmetic inspections Max. 3 outlets plus 1 dump

CVTfa Ampoule Multiple Multiple

CVTca Ampoule Limited cosmetic inspections Max. 3 outlets plus 1 dump

CVTcs Syringe Multiple Standard 3 outlets plus 1 dump

All types can be delivered as both an in-line or off-line machine.

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Machine Features• Highestspeedcapacity–+600/min• Robustinspectionmethods&algorithms-proveninspectionconceptforyears.• DR>Humaninspection-withindustry'slowestFRR-proven.• Suppressionofmicro-airbubblesandfoaminginfluenceonFRR• Designedforcleanliness&line-clearance• Flexible&gentlehandlingsystem: • Clips=Min.containertometalcontact • Siliconerubberlinedspin-cups • Min.no.oftransitions(7onlyin“greenpath”)• Strongfocusonergonomics• Noaccidentaloperatoraccesstocameras,optics&lightsources• Novacuumorcompressedairrequired–lowinstallation,runningandmaintenancecost.• Noheavyoscillatingmechanicalmasses• Minimumno.ofcameras–lowercomplexity• Auto-calibrationoflightsettingsformaximumreproducibilityandstability• Self-monitoringofcriticalprocessfunctions• Recirculationoftest-setsthroughtheentiremachineinvalidationrun-mode• Clip-belteasilyaccessibleforinsertionoftest-sets

Aminimumconfigurationmachinerequirestwooutletsfor"goodproducts"toallowanoperatorsuffi-cient time to empty one cassette before the other fills.Inadditionanoptionalrejectdumpisshownasthelastpositionontheoutletclipbelt.

LikewiseitrequirestwooutletsforrejectsifanexactnumberofcontainersmustbeensuredineachcassettewithoutstoppingthemachineforemptyingaRejectoutlet.

OtheroutletsmaybeconfiguredforSPCsampling,Rejectsorforseparatehandlingof“Grey”orUninspected containers.

Optional:• Chips&Cracksmajorstationonthein-feedwheelincludingimmediatedump• Automaticreturnof“grey”/uninspected• Formatchange-2mlto100ml• In-lineoroff-linewithfillingmachine• Carouselsizetosecure100%homogenisationofhardsedimentedsuspensionat600/min.• Mediafillinspection(turbidity)• Outletmodulecustomisation-numberoftrays,patternpackingetc.• Completequalificationdoc.fordirectvalidationuse

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ProductsSolutions Clearorcoloured.Theinfluenceofmicro-airbubblesandfoamingonFalseReject Ratescanbesuppressedbyinvokingspecialmethodsinherentintheinspection concept.

Suspensions Thepatentedinspectionmethodsurpassesanyothermethodwhenopaqueorsemi- opaqueproducttypesmustbeinspected.Containermayhaveintegralmixerbead. Carousel provides re-homogenisation before inspection.

Emulsions As above.

Media fill Additional turbidity measurement station based on laser diffraction may be installed whichtogetherwiththeparticleinspectionsprovidesaverysensitiveinspectionof growthmedia.Detectionof0,5McFarlandstandardisguaranteedat600/min.

Lyophilised Also broken cake.

Powder Specialhandlingmaypresentpowdersurface“rolling”forinspection.

ContainersAmpoules,vials,cartridgesandsyringes.Capacityto660/min.

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Machine LayoutThemachineisavailablewithanynumberofoutlets.

Flexible machine layout

Compact machine layout

Syringe machine layout

Line Handling

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Inspections

Content Parameters:particulate matter - micro-air bubbles suppression.fill level - foaming suppressionpresenceofmixerbead(non-solutions)turbiditycolour

Container Parameters: chips&cracksintheglass.scratchesburns,marksandinclusionstip deformationsring codepresence of grind mark and dotfinger flange defects

Cap Parameters: diameterheight of sideangle of cap-roof height/widthofbeading(crimp)irregularitiesonbeadingedge(earlobes)presence of rubber stopperheaped(crowned)caprubberconcentricity of cap to glass bodyconcentricity of piercing hole to glass bodydents,scratchesanddirtonsurfacesflip-cappresence,positioncolourneedle shield defects

Plunger Parameters (cartridges/syringes): plungerpresence/numberrelativepositiontotop/bottomorientationliquidbetweenribsdeformed ribsdirt and inclusions on all surfacescolour

Optionalinspectionscanbeprovidedasrequested.

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Inspection Processes

Particle InspectionsThe patented particle inspection method combines electronically controlled spinning motors to rehomo-genizesuspensions/emulsionsbeforespinningthecontainerandliquid(includinganyincludedcontamination)toahighspeed.

Precise stopping of container rotation and scanning by a line-scan camerapresentsacontinuoussurfaceimageoftheliquidstillrotatingon the inside glass-surface of the container.

Amixerbeadrotatingwiththeliquid,willnotbedetectedasforeignmatterandwillnotrequireblindingoffofanareaaroundit.

Correlateddoubleinspectionbyinstallingtwostationsincreasesthedetectionprobabilitywithretainedlowfalserejectrate-FRR.

Theprocessisrealizedinacarouselmovingcontinuouslywhilespin-ning and scanning is performed.

Thisrequirestheprojectedcamerascan-lineandlightingtotrackthecontainerwhiletheliquidrotates,asthecontainermoveslaterallywiththecarouselincombinationwiththispatentedlinescanningandlinebasedimageprocessing,thelight-stripeprojectionachievestheunsurpassedworldleadingyieldthroughverylowFRR.

The tracking is done by high precision electro-optical image trackers that have virtually no mass com-pared to common oscillating mechanical drives.

Thisconceptallows+10items/sectobescannedwithoutanydoublingorquadruplingofcamerasystems!

LED transmission light modules inside carousel.

Light-stripe projector and imaging station outside carousel.

Completely sealed inspection station.

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Unfold InspectionsSome inspections are best realised by unfolding the cylindrical surface of the contai-ner.Backlighting,reflexorscatteringmaybeapplied.

Againtheprinciplereliesonprecisecontrolofthespinningofthecontainerwhileitmoveswiththecarousel.

Theimageisgeneratedbyaxiallyline-scanningtherotatingcontainerwhilstatthesame time tracking its lateral movement in the carousel.

Scanningonefullrevolutionofthecontainersurfaceeffectivelygeneratesan“unfol-ded”imageofitsentiresurface.

Precisedetectionofaircontent,presenceofmixerbeads,someside-viewparameters,beading/crimpwidthandsomeneckdefectsarebestobtainedinthisstation.

Cosmetic and Functional InspectionsInspectionsofsidewall,heel,bottom,plunger,cap,stopperetc.areallperformedwithaunifiedinspectionconceptbasedonhighresolutioncamerascombinedwithspecialoptics and lighting.

Inspection results from one station may be used as refe-renceforanotherstationsinspectionduetothenetworkedoperation.

The handling and feeding of containers for inspection is basedonalinearclip-beltalongwhichthecylindricalinspection stations are placed.

Theinspectiondividesintoanupperhalfandalowerhalfofthecontainers.Betweenentranceandexitoftheclip-belt the containers are displaced vertically thereby also exposing the surface covered by the clip.

Duetotheopticaldesignonlyonecameraisrequiredtoacquire4side-viewsand1end-viewofthecontainercombinedinonesinglecameraimage.Imageprocessingisperformedat10items/s.

Theencapsulationensuresnocameras,lightingetc.isleftexposedwiththepotentialofbeingdisplacedordamagedduringhandlingorcleaning.

Unfolded transmissi-on image of cartridge with suspension and mixer glass bead.

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Chips & Cracks InspectionThisinspectiondividesintoatop-halfandabottom-halfstationtocovertheentiresurface.Duetothe4overlappingside-viewsanincreasedprobabilitytodetectcracksisachievedastheseareviewedunder different angles.

The lighting principle relies on the glass container acting as a light-guide. This principle is superior for detecting cracks in suspension filled containers.

TheimageprocessingalsoperformstheC&Cdetectionwheretheplungerdisturbsthebackground!

Exampleofhardlydiscernibleside-wallcrackalsovisibleinmoreviewsduetothespecialopticalarrangement.

Plunger InspectionTheplungerinspectionstationcoversthelowerpartofthecontainer.Againtheinspectionisbasedonfourside-viewsandonebottom-viewacquiredinonecameraimage.Forvialsandampoulesand/orforlyophilizedproductsthisstationcanprovidesupplementaryinspec-tion of the bottom area of the container.

Cap Inspection - CartridgesThecapinspectionissplitontotwostations-cosmeticdefectsandfunctionaldefects.

Thecosmeticinspectionstationcanbeequippedwithtwointernallightingsystemstooptimizetheinspection of both the cap top and the cap side. The lighting may further be based on polarisation to facilitateinspectiononroundededges,wherehighlightswillnormallysaturatethecamera.

Thecosmeticinspectioncanbeperformedonsixviewscapturedinoneimage-fouroverlappingside-viewsandtwoseparatelylightedtop-views.

Thefunctionalinspectionoperatesontwobacklitimagesobtainedat90°tooneanother.Thisstationwouldalsobeusedfortipinspectionofampoules.

Manygeometricalfeaturesaremeasuredinthisimagetoverifytheconsistencyofthecap,cappingprocessandintegrityoftheseal.Forampoulesinclusions,burns,treads,tipshapea.o.canbemeasu-red.

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Cap and Fill Level Inspection - VialsTheunfoldinspectionconsistsofonemeasurementstationbasedonadedicatedimageprocessingPC,whichinspectsthevialfor:• filllevel-toolowortoohighfillinglevel• presenceofflipcap• obligeflipcap• capsideheight-therebythepresenceofoneandjustonediscseal• scratchesanddentsoncapside• variationofcapcrimpseenfromtheside• variationofcapcrimpseenfromunderneaththecap

Thecapturedimageconsistoftwohalf's.

Forthe1sthalfoftheimageitispossibletoviewthevialdirectfromthesideand360°aroundduetolinescantrackingandvialrotation.Belowispicturedtheviewwithoutlinescantrackingandnovialrotation.

Forthe2ndhalfoftheimagethevialflip-off,cap,neckandshoulderscanbeseenfromthesideand360°aroundduetolinescantrackingandvialrotation.Specialopticmakeitalsopossibletoviewcrimpingunderalowerangle.Belowispicturedtheviewwithoutlinescantrackingandnovialrotati-on.

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90°sideview Angledcrimpview

Theimagecapturedduringinspectionwithlinescantrackingandvialrotationispicturedbelow.

Themeasurementmethodisanopticaltransmissionmeasurement,whichcombinedwithacontrolledspinningallowsreliabledetectionofthefillinglevel.

Imagetrackingisdonebyagalvanometermirrorwhichwithaveryhighresolutionthroughdecodingofthecarousel'spositiontrackstherotationwithinapp.2.4degrees.

Thelightisacombinationofabacklightpanelforthefillingandcapheightinspection,andfrontlightfor the other cap inspections.The galvanometer drivers are placed in the lamp rack in the machine frame.

Filllevelmeasurementthroughimageprocessingissupplementedwithanopticalsensor,whichdetectsemptyvials,thatotherwisecannotbereliablydistinguishedfromthe100%filledones.

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Vial heel reference for fill level

(1sthalf)Fillleveldetermination,onone vial rotation revolution

(2ndhalf)One vial rotation revolution

Flip-offcappresence&wobble,alu.capsideheight.Twoormissingmembranes.Scratches&dentsoncapside.

Crimp/Beadingwidthmeasurement&earlobes

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HVLD - High Voltage Leak DetectionTheleakdetectionisbasedonHighVoltage-HighFrequencydetectionprinciple,andallowstodestin-guishbetweensurfacescratchesandpenetratingcracks.

TheHVLDisdividedintwostations;onepositionedonthecarouseltheotherattheInspectionClip-Belt.TheHVLDhasbeenrealisedusingsmallcompactself-containedHVmodulesconnectedtothemachi-nereal-timecontrollerthroughthemachinesCAN-buslink.Eachmodulereceivesset-upparametersand transmits status messages back to its dedicated inspection PC. Timing of inspection is driven by the carousel main encoder.

Forcartridgesthesetwostationscovertheglassandcap/tipareawhereliquidisbehindthesurface:

• Penetratingcracksintheglasswall.• Leakingcap/tipclosure

Sidewall inspectionThe high revolution spin motors in the carousel are used to ensurethatliquidhaswettedtheinteriorofthecontainerwhentheHVinspectionpositionisreached.

Thisallowsinspectingalsosidewallsofcontainersbeingonlypartlyfilledwhenthesearenotlyingdown.

ContainersarethenrotatingatapredefinedlowerspeedduringthetimeslotwheretheactualapplicationofHighVoltageHighFrequencyACtakesplace,wherebytheentire360°oftheglasssidewalliscove-red.EachHVmodulehasasetofpointedelectrodescoveringahorizontalstretchofapp.25mm.AdefinednumberofHVmodulesarerequiredto cover the vertical height of the container.

Cap inspection - Syringe needle piercingLeaking cap inspection may be performed in the carousel by a third module,butwillnormallybedoneinadedicatedstationattheInspection Clip-Belt.

Capinspectionrequiresnorotationsincethemetalcapitselfactsasacircular electrode around the seal disc.Todetectaleakingcapclosurerequiresthataconductivepathisestab-lishedbetweenthemetalcapandthewettedinterior.Aninversionmodulemayberequiredforlowfilllevels.

Tip inspectionAmpouletipinspectionrequirestheinteriorsurfaceoftheglasstipbewetted.Thisisrealisedbyaspecialhandlingmoduleattachedtotheclip-belt,whichinvertsandrotatestheampoules(tipdown)whiletheHVinspectionisperformed.

Inversion module

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Barrel Inspection - SyringesThesidewallunfoldinspectionconsistsofonemeasurementstationbasedonaline-scancamera,LEDlampunitsandadedicatedimageprocessingPC,whichmayinspectthesyringefor:

• filllevel-toolowortoohighfillinglevel• crackedbody-outsideliquidarea• scratches• stains/inclusions• sidewaysplunger• multipleplungers• misshapedplunger• foldedlips• stainsonside• fragments/producton/betweenplungerlips• plungerposition• printonside

The CVTcs machine does not rely on single ended clamping of the flange for spinning in the carousel. Instead syringes are held inbothendsallowingsafehighspeedspinningwithouttheriskofbeingthrownoff.

Themeasurementmethodisanopticaltransmissionmeasurement,combinedwithareflectiveimageoftheplungerside.

Thiscombinedwithacontrolledspinningallowsreliabledetec-tionofdownto25Microlitresofair-(filllevel).

Imagetrackingisdonebyagalvanometermirrorwhich,withaveryhighresolutionthroughdecodingofthecarousel'sposition,tracksthespinningsyringeinthecarouselthroughapp.2.4degrees.The same type of galvanometer is used for both image tracking andlighttrackingwhenlight-stripeprojectionisrequired.

Filllevelmeasurementthroughimageprocessingissupplementedwithanopticalsensor,whichdetects100%emptycontainer,thatotherwisecannotbereliablydistinguishedfromthe100%filledones.

ForsolutionsonlyaLEDbasedlightmoduleisemployed,whereasthepatentedlight-stripeprojectionmethodisusedtogetahighqualityimagefromeventhedensestsuspensionproductwhenrequired.

Unfolded sidewall transmission image of syringe with dark plunger; flange at bottom.

Optical crack detection in unfolded image despite presence of print.

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Needle Shield ShapeConsistsofaninspectionstation,whichinspectstheprotectivecap/luerlockofthesyringe.

Theinspectionisbasedon2pcs.of90°shiftedsideimagesinbacklight.

Thecapshapestationinspectsthesyringefor:

• Missing,wrongorbendcap• Capposition

The cap shape inspection is based on a high-resolution matrixcamera,optics/lightunit,andimageprocessingdirectly in a dedicated PC.

Measurementiscarriedoutbyrecordinganimageconsistingoftwo90°shiftedsidesectionsofthecapusingthematrixcamera,optics,andmirrors.

Thecapimageisacquiredintransmission,whichmakesthecapoutlinestanddarkonalightback-ground,providingthebestcontrastforgeometricmeasurements.

Cap Cosmetics InspectionConsistsofaninspectionstation,whichinspectsthecompletesurfaceofthecapofthesyringeforcos-meticand/orfunctionaldefects.

Thecapcosmeticsinspectionisbasedonahigh-resolutionmatrixcamera,optics/lightunits,andimageprocessing directly in a PC.

Measurementiscarriedoutbyrecordinganimageconsistingofthecap'saswellas4sideimagesofthecapusingonehighresolutionmatrixcamera,optics,and4prisms.

Thecapisilluminatedfromabove,thelightingbeingbasedonLEDringlightsplacedconcentricallyabove the syringe.

Dependingonthetypeofcap,differentlightingmaybeemployed.

Thecapinspectioninspectsthesyringecapfor:

• stains• luerlockunbroken• othercap/tipdefects

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Turbidity InspectionTheturbiditystationistypicallyplacedonthecarouselbutmaybepositionedelsewhere.

Themeasuringprinciplehasbeendesignedtoallowhighspeedoperationofthedetectionat600/min.

The measurement is based on detecting the diffraction pattern of a laser beam being transmitted throughtheliquid.

Whenusedforgrowthmediainspectionitshouldbeincombinationwithaparticleinspectionsincesomefungiandbacteriahavegrowthpatternswhichdonotaffecttheturbidityrathertheygeneratelumps.

TheTurbiditymeasuringstationwilldetect:

• 0,5McFarlandstandardwithreprodu- cibilityof0,25McFarlandon11mm diameter containers.

Colour InspectionCamera

Thisinspectioncameramaytakedifferentpositionsbutisgenerallyappliedwheremultiplepointsofinterest have to be inspected for proper colour.

TheinspectionisbasedonamatrixcolourcamerainconjunctionwithastabilisedLEDwhite-lightsource coupled to dedicated inspection PC.

Thecolourinspectionimagesthesideofthecap/container/plungerandidentifiestherespectiveROI(RegionsOfInterest)wherethecolourischeckedagainsta3Dcolourbodywithconfigurabletoleran-ces.

Point sensor

Thecoloursensorisbasedonahighstabilitytriplecolourpointdetectorwhichmayhaveafibre-opticadaptor on the input.

Thesensormaybeimplementedintransmissionmodetodetectdiscolourationofliquidsorbeappliedto check for correct colour of individual parts such as flip cap or stopper in a reflective mode.

IneithercasethesensorisconnectedtoaninspectionPCwhereconfiguration,calibrationandmeasu-rements are handled and presented on screen.

Oneormoresensorsmaybeappliedtocheckthepropercolourofcapand/orplunger.

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Company Profile

InnoScanSødalsparken 118220BrabrandDENMARKPhone: +45/86265677Fax: +45/86265678E-mail:innoscan@innoscan.dkWeb: www.innoscan.dk

Key PersonnelGertNielsen,Manager,InspectionSystems

Company DescriptionInnoScan,foundedin1988,specializesinhigh-techinspectionsystemsandmachinesforautomaticqualitycontrolpharmaceuticalvials,ampoules,cartridgesandsyringes.Dedicatedinspectionsystemsforeasy-openendsandshallowcansforthecanmakingindustryaswellasflatworkscannersforcoiland sheet material.

FacilitiesThirdquarter2004InnoScanmovedintoabrandnewheadquarterwithoffices,laboratories,productionandassemblyfacilitiescoveringanareaof1700sqm.InnoScanhandlesin-housemulti-disciplinarydevelopmentanddesignofmechanics,optics,lightning,electronichardwareandsoftwareaccordingtointernationalqualitycontrolguidelinesdrivenbytheGAMP.

ServicesInnoScanoffersstandardsolutionsaswellascustomerengineeringincludinginstallation,commissio-ningandcomprehensivequalificationdocumentation.World-wideaftersalessupportisguaranteedwithspecifiedreactionpattern.