ProductionPlanning,Schedulingand

CapacityAnalysisofMicrobial
BiopharmaceuticalProcesseswith
SchedulePro

INTELLIGEN,INC.
Simulation,Design,andSchedulingTools
fortheProcessManufacturingIndustries
www.intelligen.com
Intelligen,Inc. 1

Introduction
ThisbioprocessingexampleillustratestheuseofScheduleProforcapacityanalysisandschedulingofa
biopharmaceuticalprocess.TheScheduleProfeaturescoveredinclude:

Basicrecipeconstruction
Useofequipmentinmultiplefacilities
Useofmultiple(similar)equipmentlineswithinafacility
Sharingequipmentbetweenprocesses
Equipment/facilitydowntimeduetoworkshiftrestrictions
Buildingflexibilityintotherecipe
Cleanoutcampaignsscheduledafterproductioncampaigns
Settingprioritizationforspecificcampaigns
Facilitiesandsuites
Resourceconstraints
Buffersolutionpreparationandstorage(withinarecipeandasaseparaterecipewhose
schedulingisdrivenbyinventorylevelinastorageunit)
Mobileequipmentarearequirements
Materialsupplysystems,includingcascadingflowofmaterials(i.e.,materialsupplysystems
beingusedtofeedothermaterialsupplysystems)
UseofaCleaning/Changeovermatrixtoautomaticallydeterminewhenadditionalvessel
cleaningisrequired,basedonthelengthofidletimebetweenbatches(maxcleanhold)

Thisexampleincludesthefollowingcases:

A. CaseArepresentsthebaserecipeandithasthesimplestproductionschedule.CaseA1usesasingle
linetoproduceasingleproduct.Itscycletimeisbasedonthecycletimelimitingunit,whichisthe
fermentor.Thereisnobufferpreparationassociatedwiththisrecipe.CaseA2isthesameasCase
A1,exceptthatalonger(72hour)batchcycletimehasbeenspecified.CaseA3assumesonlytwo(8
hour)shiftsperdayareavailableforthedownstreamprocessingoperations.Asaresult,certain
operationareshiftedsincenewoperationscannotbeginduringthenightshift.CaseA4usestwo
upstreamlinesandasingledownstreamline,inordertodoublethethroughputoftheplantwhile
addingminimalequipment.

B. CaseBrepresentstwosimilarproductsrunningwithinamultiproductplant.CaseB1assumesboth
productsusethesameequipmentlineforalloperations.CaseB2assumestwodifferentequipment
linesareusedforthetworecipes,andonlyafewequipmentitems(centrifugeandCIPskids)are
sharedbytheprocesses.

C. CaseCaddsbufferpreparationandholdingactivitiestotherecipes.InCaseC1,thepreparedbuffers
areeachusedwithinasinglebatch.Thebufferpreparationactivitiesarescheduledrelativetothe
chromatographyoperationsoftherecipe.CaseC2showshowtoprepareanduseasinglebatchof
buffermaterialformultipleproductionbatches.Thisisaccomplishedbyusingaseparaterecipefor
thebufferpreparationandholdingactivities.Additionalbatchesofbufferareautomatically
scheduledwhenevernecessary(basedontheinventorylevelofastorageunit).CaseC3assumesthe

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 buffersarepreparedandthenstoredinmobileunitsuntilnecessary.Thiscasedescribeshowto
accountforthefloorspacerequiredformobileunits.

D. CaseDshowshowtodeterminetheinstantaneousandtimeaveragedrequirementsforaresource
suchaswaterforinjection(WFI)andhowtosizeutilitysystems.Italsoshowshowcascaded
materialsupplysystemsmaybeusedtotrackproductionofmaterials.InCaseD1,ROwater
(purifiedbyreverseosmosis)isfurtherpurifiedintoWFI.Inadditiontobeingtherawmaterialfor
WFI,theROwaterisusedalsowithintheprocessitself.Thematerialsupplysystemstrackthe
generationanduseofeachofthesematerials.InCaseD2,aweeklyoutageisaddedtotheWFI
systemtoaccountforloopsanitizationandtheimpactonthescheduleisanalyzed.

E. CaseEdemonstrateshowtoautomaticallyaccountforcleaningwhichmayberequiredifcertain
equipmentsitsidleforanextendedperiodoftime(maxcleanhold).Thiscanbemodeledusing
ScheduleProsEquipmentChangeoverMatrixfunctionality,whichallowsanextracleaningoperation
toautomaticallybeaddedtotheproductionscheduleincaseswhereauserdefinedmaxtime
betweenequipmentusesisexceeded.

Eachofthesecasesisdescribedingreaterdetailinthefollowingsections.

ProcessBackground
Biopharmaceuticalproductsaretypicallyproducedbymammaliancellcultureorbymicrobial
fermentation.Ingeneral,cellcultureisreservedforlargeglycosylatedproteinsincludingmonoclonal
antibodies.Whenpossible,microbialfermentationisoftenapreferredplatformforfastergrowthwith
lessexpensivemedia.Improvementsinmetabolicengineeringandtechnologiessuchashigh
throughputanalysishavehelpedimprovetheconformationandsecretionofproteinproductsfrom
microbes.

Theexamplesthatfollowarebasedonasomewhatsimplifiedprocessinwhichaproductisproducedby
batchmicrobialfermentation.Theproductissecretedinthefermentationbroth.Theupstreamprocess
consistsoffermentationdoneinasmallscaleseedfermentorandaproductionfermentor.Thecontents
oftheproductionfermentoraretransferredtoaharvestvesselbeforecentrifugation.Thedownstream
processconsistsofcentrifugationforbiomassremoval,followedbyionexchangechromatography,
hydrophobicinteractionchromatography,ultrafiltrationdiafiltration(UFDF)andbulkfilling.Thescaleof
theprocessisbasedona5000Lproductionfermentorwithatiterof5g/L.Theaveragerecoveryis80%,
givinganaverageproductionof20kg/batch.

AsimplifiedviewofthisprocessisshowninFigure1.Thisdiagramrepresentsthesimplecasesdescribed
inthisexample(e.g.,CasesA1,A2,A3).Othercasesinthisexampleexpanduponthisprocessto
incorporateadditionalupstreamlines,additionalproducts,preparationandholdingactivitiesfor
fermentationmediaandbuffers,etc.Forthesakeofsimplicity,additionalactivitiessuchasinoculum
preparation,wastetreatment,etc.areignored.

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Figure1:BasicProcessOverview

CaseA:RecipeDefinitionandBaseCase

RecipeDescription
AScheduleProrecipeisadescriptionofabatchprocess.ItisanalogoustotheMasterBatchinbatch
controlormanufacturingexecutionsystems(MES).AScheduleProrecipeisorganizedintosections,unit
procedures,andoperations.Asectionreferstoaseriesofprocessstepsthatareconceptuallyor
physicallyassociated.Aunitprocedureorprocedureisaprocessactivitythatrequirestheuseofamain
pieceofequipment.Eachprocedureincludesatleastoneoperation.Thetimingandresourcesother
thanmainequipmentaredefinedintheoperations.Table1outlinesthebasecaserecipeforthis
example.

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Table1:BioprocessRecipe
Section Procedure Operation Duration(h)
Upstream SeedFermentation Setup 3.0
ChargeMedia 1.0
SterilizeMedia 3.0
FermentationOps 32.0
TransfertoProductionFermentor 0.5
CIP 1.5
Fermentation Setup 4.0
ChargeMedia 0.5
SterilizationCycle(incl.cool) 4.0
Inoculationfromseed 0.5
Fermentation 48.0
ToHarvestTank 1.0
CIP 1.0
Downstream HarvestTank Setup 2.0
BrothFromFermentor 1.0
PumpToCentrifuge 4.0
CIP 1.0
Centrifuge Setup 1.0
Centrifuge 4.0
CIP 3.0
PoolSupernatant Setup 2.0
ReceiveSupernatantFromCentr. 4.0
LoadINXcolumn 8.0
CIP 2.0
IonExchange Setup 3.0
Chromatography Columnoperations 8.0
Clean/Store 2.0
PoolINXeluent Setup 2.0
ReceiveEluentFromINXCol. 8.0
LoadHICCol. 6.0
CIP 1.5
Hydrophobic Setup 3.0
Interaction ColumnOperations 6.0
Chromatography CIPChromSkid 2.0
UFDF Setup 2.0
ReceiveHICEluent 6.0
UFDF 4.0
ToFreezeDryer 0.5
CIP 1.5
FreezeDrying Setup 4.0
TransferFromUFDF 0.5
FreezeDry 24.0
CIP 1.5

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Notethatforthesakeofsimplification,themainchromatographyoperations(e.g.,equilibration,
loading,washing,elution,etc.)havebeencombinedintoasingleColumnOperationsoperationfor
boththeIonExchangeandHydrophobicInteractionprocedures.Itwouldbepossibletobreakthese
operations(andotheroperations)intosmallersuboperationsifadditionaldetailwasrequiredforthe
schedule.

CreatingaRecipeinSchedulePro
CreateSections,ProceduresandOperations
Thestepsinrecipecreationmaybedoneinalmostanyorder.Generallyitiseasiesttocreatearecipe,
addsectionstoit,addprocedurestothesections,andfinallyaddoperationstotheprocedures.

TocreatetherecipeinSchedulePro,createanewScheduleProproject,andselecttheRecipesitemin
theexplorertreeontheleft.ThenselecttheCreateNewRecipe( )buttoninthepaneontheright.
EnterMicrobialAasthenamefortherecipe.Selectthesizetab,andenter20kgastherecipebatch
size.Itisnotnecessarytomakeamaterialselection.SelectOKtocreatetherecipe.ExpandtheRecipes
nodeinthetreeandexpandMicrobialA.ThesectionentitledMainSectioniscreatedautomatically
asshowninFigure2.

Figure2:NewRecipe

RightclickonMainSectionandselectProperties.RenameMainSectiontoUpstreamandclickOK.
RightclickontheMicrobialArecipe,selectAddSectionandaddasectionentitledDownstream.
SelecttheUpstreamsectioninthetree.Intheprocedurelistviewontheright,clicktheAdd
Procedure( )buttontoaddanewprocedure.AddproceduresforSeedFermentationand
Fermentation.FortheDownstreamsection,addtheremainingprocedureslistedinTable1.
SelectandexpandtheUpstreamsectioninthetree.SelecttheSeedFermentationprocedure.Thefirst

operation,op1iscreatedautomatically.Selectop1andclicktheproperties( )buttontoeditthe
operation.EnterthenameSetUpfortheoperation.Usetheadd( )buttontoaddtheremaining
operationsinTable1associatedwiththeSeedFermentationprocedure(e.g.,ChargeMedia,Sterilize
Media,etc).ThenaddtheoperationsfortheremainingproceduresintheUpstreamandDownstream
sections.

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SpecifyOperationDetails
Afteraddingtheoperationsassociatedwitheachprocedure,thedetailsofeachoperationshouldbe
specified.Todothis,firstselecttheSeedFermentationprocedureintheexplorertree.Selectthe

Setupoperationandclicktheproperties( )buttonasshowninFigure3.

Figure3:EditingOperations

Theoperationdetailsdialoghastabsforgeneralproperties,duration,schedulingandthevarious
resourcesthatmightbeusedfortheoperation.Thedurationtaboffersthefollowingfourbasicoptions
forsettingtheduration:

Fixedorratebasedentereitherthedurationoranamountandrate
Tiedtootheroperationsenteranotheroperationorsequence
Inventorybaseddurationoperationcontinuesuntilaspecifiedinventorylevelisreached
Basedonchangeovermatrixtakethedurationfromtheequipmentchangeovermatrix

Inthiscase,thedurationoftheSetupoperationisfixedat1h.Since1hdurationisthedefaultoperation
durationinSchedulePro,nochangesarenecessaryhere.
TheSchedulingtabdefinesthetimingoftheoperationwithrespecttootheroperationsinthebatch
(seeFigure4).Thefollowingschedulinglinksareavailable:

Startswiththebatchstart.Notethebatchstartisnotrequiredtobethefirstoperationlisted
intherecipe.
Withrespecttoanotheroperationinthisprocedure

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 Withrespecttoanotheroperationinanotherprocedure

Forthelattertwooptions,thelinkrelationshipsincludestarttostart,finishtostart,starttofinishand
finishtofinish.Thelinksarespecifiedintheformreferenceoperationstart/endtimerelativeto
currentoperationstart/endtime.Timeshiftsoroffsetsrelativetothereferenceoperationmayalsobe
addedasfixedorflexibleshifts.Apositiveshiftisadelaywithrespecttothelink.Anegativeshiftisa
leadtime.Inotherwords,ifthereisanoperationwithastarttostartspecificationandafixedshiftof5
hours,theoperationwillstart5hoursbeforethereferenceoperationstarts.Aflexibleshiftspecifiesa
maximumshiftthatmaybeappliedbyScheduleProinordertoavoidoverallocatingresources
associatedwiththeoperation(suchaslabor,rawmaterials,auxiliaryequipment,etc.).Operationsin
whichtheproductissufficientlystabletoallowforadelaymayhaveaflexibleshift.Addingflexible
shiftstotherecipeallowsScheduleProtoautomaticallymoveoperationswhenconflictsarise,inorder
tomeetequipmentandresourceconstraints.Whenaflexibleshiftisspecified,itisalsonecessaryto
specifywhichcriteriatousewhendeterminingwhethertheshiftcantakeplace(e.g.,shiftforfacility
closure,equipmentavailability,etc.)

NotethattheSchedulingtabalsoallowsanoperationtobeinterrupteduptoacertainmaximumtime
(anduptoacertainnumberofbreaks).Thispermitsanoperationtobestoppedandthenlater
restarted.Forinstance,letsassumeanoperationcanonlybeperformedduringthedayshiftandmay
bestartedandstopped.Ifthatoperationisstartedduringthedaytimeanditdoesnothaveenoughtime
tobecompletedpriortotheendofthedayshift,theoperationcanberestartedagain(atthepoint
whereitwaspreviously)thenextmorning.Notethatitisalsopossibletoallowoperationstorunduring
plantdowntimes,ifdesired.ThisisspecifiedatthebottomoftheSchedulingtab.

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Figure4:TheSchedulingTab

Oncetheschedulingrelationshipsareset,therecipeGanttchartcanbeusedtovalidatethescheduling
links.ToviewtheGanttchart,selecttherecipeintheexplorertreeandclicktheGanttchartbutton(
).TheGanttchart(Figure5)showstheactivitiesandtheirrelativetiming.Thisinformationisshownin

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tabularformat(ontheleft)andgraphicalformat(ontheright).Thetanbaratthetopofthegraphical
portionshowsthetimingforthefullrecipe,whereasthedarkbluebarsandlightbluebarsrepresentthe
unitproceduresandoperations,respectively.Theproceduresmaybeexpandedtoshowtheirindividual
operationsbyclickingthe+buttonoftherelevantprocedure(s)undertheTaskscolumnofthetable.
Alternatively,thefullprocesscanbeexpanded/collapsedbyusingtheDetailLevelmenuitemofthe
toolbarabovethetable.

Figure5:RecipeGanttChart

Another way to view the recipe is with the Recipe Block Diagram (see Figure6). This can be generated

by selecting the recipe in the Explorer Tree and clicking the View Recipe Block Diagram button ( )
in the right hand pane. Each rectangle in the recipe block diagram represents a procedure. The blue
arrows that connect the various operations of the procedures indicate scheduling links among those
operations. If the recipe includes information on consumption and generation of materials, those are
indicated by black horizontal arrows linked to operations. The recipe Gantt chart and Block Diagram
facilitate editing in addition to visualization of a batch process. For instance, double-clicking on an
operation in the Recipe Block Diagram will bring up that operations Properties dialog. If the recipe is not
already scheduled, the specifications within the Properties dialog will be editable. (If the recipe is already
scheduled, it will need to be un-scheduled before modifications can be made to it.)

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Figure6:TheRecipeBlockDiagram

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DefineResources
Thisexampleillustratestheuseofequipment,materialsandlabor.Asaresult,theseresourceswere
definedandassignedtorelevantprocedures/operationswithintherecipe.

Todefinematerialresources,firstselectthematerialsitem( )intheexplorertree.ThenclicktheAdd
( )buttonandentertherelevantspecificationsforthatmaterial.Thebasecase(MicrobialA1)has
twomaterials:reverseosmosiswater(ROWater)andwaterforinjection(WFI).

Allresourcesotherthanmaterialsaredefinedwithinfacilities.Facilitiesrepresentplantsorlocations
withinaplant.Toaddafacility,selecttheFacilitiesnodeintheexplorertree( )andusetheAdd( )
button.Thisbasecase(MicrobialA1)hasonefacilitynamedBiotechFacility.Toviewtheresource
categorieswithinthisfacility,clickthe+buttontoexpandit.Notethattheequipmentitems
associatedwitheachprocedurearetheonlyresourcesrequiredbyarecipe.Furthermore,theminimum
requiredinformationforeachequipmentitemisauniquenameandatype;allotherequipment
specificationsareoptional.

Otherresources(includingauxiliaryequipmentsuchaspumps,etc.)mayoptionallybedefinedand
associatedwithoperationsoftherecipe.Inthisexample,laborhasbeendefinedinordertotrack
and/orlimitthetotalamountoflaboravailableforscheduledactivitiesatagivenpointintime.Toadda
laborclassification,selecttheLaboritemintheexplorertree( )andclicktheAddbuttoninthelabor
list.Theminimumrequiredinformationforlaborisauniquename.Thisexamplehasasinglelabortype,
namedOperator.

AssigningMainEquipmenttoProcedures
Aftertheresourceshavebeendefined,theycanbeassignedtotherecipe.Forexample,Main
Equipmentmustbeassignedtoeachoftheprocedures.Todothis,selectaprocedureintheexplorer
treeandclicktheEditProcedurebutton( ).TheproceduresequipmentisassignedintheMain
EquipmentPooltab.Inthebasecase(MicrobialA1),FermentorFR1hasbeenassignedtothe
FermentationprocedureintheUpstreamsectionoftheprocess(seeFigure7).

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Figure7:AssigningMainEquipment

AssigningAuxiliaryEquipment
Sometimesanindividualoperationwillrequireadditionalequipment.Equipmentassignedatthe
operationlevelisreferredtoasauxiliaryequipment.Inthisexample,theCIPskid(assignedtoCIP
operationsattheendoftheSeedFermentationandotherprocedures)andtheUFDFmembraneunit
(assignedtotheUFDFoperationintheUFDFprocedure)areauxiliaryequipmentitems.Auxiliary
equipmentisassignedintheAuxiliaryEquipmenttaboftherelevantoperation(s).

AddingandSchedulingaCampaign
Afterallthemainequipmenthasbeenadded,ScheduleProcanestimatethethroughputbasedonthe
minimumcycletime.Toseethis,selecttherecipeintheexplorertree.Thefollowinginformationis
displayedontherightside:

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 EstimatedBatchTime:136.50h.Thisisthetimerequiredtomakeonebatchfromstarttofinish.
Inotherwords,itisthetimefromthebeginningofthefirstoperationinabatchtotheendof
thelastoperationinthatsamebatch.
EstimatedCycleTime59.50h.Thisistheminimumtimebetweenstartsofconsecutivebatches.
Thismeansthattheplantcantheoreticallyproduceabout2.8batchesperweek,assuming24x7
operationofthefacility.Howeversincethisestimateonlyaccountsforthemainequipment,
resourceconflictscouldreducetheactualnumberofbatchesperweek.
Bottleneck:Fermentation.Thisisthecycletimelimitingprocedure.

Toactuallydeterminetheamountofeachproductthatcanbeproducedinamultiproductfacilitywithin
agiventimeframe,campaignsshouldbeaddedtotheProductionSchedule.ScheduleProcampaignsare
similartoproductionorders;theyspecifyanumberofbatchesofaparticularrecipe.Toaddacampaign,
selecttheProductionScheduleitem( )intheexplorertree.Thenclicktheaddbutton( )inthe
CampaignSequencewindow.Thecampaigndialog(Figure8)allowsthespecificationofthenumberof
batchesortheamounttobeproducedbythecampaign.FileMicrobialA1.scpcontainsasixbatch
campaignofProductA.

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Figure8:CampaignDialog

TheTime/Sequencingtaballowstheusertosetthereleasedate,whichistheearliestallowablestartfor
thecampaign.Thistabalsoallowsotheroptionssuchasaduedatetarget,astartthatisrelativeto
anothercampaign,oraconditional(inventorybased)start.

Oncethecampaignisscheduled(byclickingtheScheduleCampaignbutton: ),theproduction
schedulecanbeviewedbyclickingtheequipmentoccupancychartbutton( )onthemainmenu
(Figure9).

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Figure9:EquipmentOccupancyChart

Thischartdisplaystheusageofeachequipmentitem(theyaxis)versustime(thexaxis).Thedifferent
batchesareshownusingdifferentcolors.Thestyleofthechartmaybeeditedbyrightclickinganopen
areaofthechartandchoosingEditStyle.Figure9representsthesimplestcaseinthisexample
(associatedwithMicrobialA1.scp).Thiscaseassumesthatasingleproductisproducedintheplant,and
asingleequipmenttrainisusedfortheprocess.Subsequentcaseswillillustratehowtoaccountfor
bufferpreparationandholding,materialresourcerequirements,aswellasfacilityandequipment
downtime.

SchedulingaCampaignwithSlackTime(CaseA2)
CaseA2issimilartoCaseA1,exceptthata72hourcycletimehasbeenspecified(seeFigure10).This
meansthereare72hoursbetweenconsecutivebatchstarts.Asaresult,thereare12.5hoursofidle
(slack)timebetweenbatchesofthecycletimebottleneckprocedure(fermentationinthiscase).The
specificationofslacktimebetweenbatchesallowstheplanttoabsorbsmallprocessingdelayswithout
impactingtheoverallproductionschedule.

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Figure10:SpecificationoftheBatchCycleTime

TheEquipmentOccupancyChart(EOC)associatedwithCaseA2isshowninFigure11.Itisclearfrom
thischartthatthereisidletimebetweenbatches,whereasinthepreviouscase(Figure9)fermentorFR
1wasusedcontinuously.

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Figure11:EOCforCaseA2

ConsideringFacilityOutages(CaseA3)
CaseA3isthesameasCaseA2,exceptthatitassumesonlytwo(8hour)shiftsperdayareavailablefor
thedownstreamprocessingoperations.Thissetupwasaccomplishedbyfirstseparatingtheequipment
intotwofacilities,theUpstreamFacilityandtheDownstreamFacility.Notethatequipmentcaneasilybe
movedtoadifferentfacilitybyrightclickingtheappropriateequipmentitemandchoosingMoveTo
(thisassumestheotherfacilityhasalreadybeencreated).Next,theDownstreamFacilitywasgivennight
shiftdowntimebyselectingthatfacilityintheexplorertreeontheleftandthenclickingtheEdit
Outagesbutton( )inthepaneontheright.Thenightshiftdowntimewasthenaddedbyright
clickingonthecalendar,selectingAddaNewEntry,andspecifyingtheappropriateinformationas
showninFigure12.ThisensuresthattheequipmentwithintheDownstreamFacilitywillbeunavailable
from11PMto7AMeachdayoftheweek.ThenewEOCisshowninFigure13.

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Figure12:FacilityCalendarDialog

AsyoucanseeinFigure13,severaloperationshavehadtheirstarttimesshiftedautomaticallyinorder
toaccommodatethenightshiftdowntime.Forinstance,inthefirstbatchthestarttimesofcertain
operationsinTK2,C1,andTK3areallshiftedtoTuesdaymorning(seeredarrowsinFigure13)since
thoseoperationscouldnotbecompletedpriortotheendoftheworkdayonMonday.Theseoperations
areshiftedinsubsequentbatchesaswell.Theautomaticshiftingwasaccomplishedbecauserelevant
operationsintheDownstreamportionoftheProductArecipewereassignedflexibleshifts,asdescribed
intheSpecifyOperationDetailssectionearlierinthisdocument.Thespecificoperationswithinagiven
procedurewhichhaveflexibleshiftscanbeeasilydeterminedbyclickingonthatprocedureandlooking
attheFlex.Shiftcolumninthepaneontheright.Figure14displaystheoperationsintheCFPool
procedurethathavebeenassignedflexibleshifts.Toviewthespecificationsforaflexibleshift
associatedwithaparticularoperation,youcandoubleclickthatoperationandvisititsSchedulingtab.

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Figure13:EOCShowingNightShiftDowntimeforCaseA3

Figure14:FlexibleShiftsAssignedtoOperationsintheCFPoolProcedure

Inadditiontoallowingcertainoperationstarttimestobeshiftedautomaticallyinordertoavoid
schedulingconflicts,ScheduleProcanallowspecificoperationstorunduringperiodsof
facility/equipmentoutages.Inthisexample,theFreezeDryoperationinLYO1isallowedtorunduring
periodsoffacility/equipmentoutages(aslongasitisstartedduringnormalworkinghours),asshownby

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thecircledprocedureinFigure13.ThespecificationswhichallowtheFreezeDryoperationtocontinue
duringthenightshiftareshowninFigure15.

Figure15:SpecificationAllowingFreezeDryingtoContinueDuringFacilityOutages

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ReducingCycleTimeswithEquipmentPools(CaseA4)
InCasesA1A3,thefermentor(FR1)hasthelongestcycletimeandisthereforetheproduction
bottleneck.CaseA4addsanotherupstreamline(i.e.,anextraseedfermentorandmainfermentor)to
therecipe,inordertoremovethisproductionbottleneck.ThisallowsFR1tobeusedforthe
fermentationinthefirstbatch,FR2tobeusedforthefermentationinthesecondbatch,FR1tobe
usedagainforthefermentationinthethirdbatch,etc.Byswitchingbackandforthbetweentwo
fermentors,thecycletimeoftheprocesscanbecutinhalf.Thisdoublestheproductioncapacityofthe
plantwhileonlymodestlyincreasingthetotalcapitalcostofthefacility.Toassigntheadditional
fermentor,theUpstreamsectionoftherecipewasselectedintheExplorerTree,theFermentation
procedurewasselectedinthepaneontheright,andtheEditProcedurebuttonwasclicked( ).Next
theMainEquipmentPooltabwasselectedandFR2wasaddedtotheequipmentpool(seeFigure16).
Notethateachentrywithinanequipmentpoolrepresentsanalternativeequipmentunitthatcanbe
usedbytheprocedure.Ineachbatch,onlyoneoftheequipmentunitswillbeassigned.Theorderin
whichtheequipmentappearsinthelististhepriorityinwhichtheywillbeassigned,assumingall
equipmentunitsareavailable.Theprioritizationmaybechangedwiththemoveup/movedown
buttonsimmediatelyabovethelist.

Figure16:TheTwoFermentorEquipmentPoolforCaseMicrobialA4

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ThesameprocessdescribedabovewasfollowedtoaddtheextraseedfermentortotheSeed
Fermentationprocedure.

Withtheadditionofasecondequipmentline,thebatchcycletimecanbereducedfrom72hoursto36
hourswhilestillallowingforslacktimebetweenbatches.TheEOCforthisscenarioisshowninFigure
17.Notethatthebatchstartsalternatebetweenthetwoseedfermentors(SFR1andSFR2)and
betweenthetwoproductionfermentors(FR1andFR2),soeachindividualfermentorisonlyusedthree
timesoverthecourseofsixbatches.Alsonotethatforthesakeofsimplicity,thenightshiftdowntime
describedinCaseA3wasremovedfromthisfileandfromsubsequentfiles.

Figure17:EOCforCaseA4,with2UpstreamEquipmentLines

CaseB:MultiproductFacilityModeling

CaseBrepresentstwosimilarproducts(ProductAandProductB)runningwithinamultiproductplant.
RatherthancreatingtheProductBrecipefromscratch,therecipeforproductBwasgeneratedby
selectingtheRecipesitemintheexplorertree,selectingtheProductArecipeinthepaneontheright,
clickingthecopybutton( ),andclickingthepastebutton( ).Thenthenameofthenewlypasted
recipewaseditedbyselectingitinthelistandclickingtheeditrecipebutton( ).Inthedialogbox
thatappeared,thenameoftherecipewaschangedtoProductB.Finally,certainoperationsinRecipeB
weremodified(e.g.,thedurationsofthefermentationoperationswithintheSeedFermentation
procedureandtheFermentationprocedurewerereduced,thecentrifugationtimewaschanged,the
durationsofcertainchromatographyoperationswerechanged,theFreezeDryprocedurewasreplaced
withaBulkFillprocedure,etc.)ItisassumedthatthesolutionofProductBisfilledintoplastic

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containersthatarestoredinafreezer.Thismethodofcopyingandpastingfollowedbyeditingofthe
newrecipeistherecommendedmethodforgenerationofrecipesthataresimilartooneanother.

MultiProductFacilityUtilizingaSingleProductionLine(CaseB1)
InCaseB1,itisassumedthatbothproductsusethesameequipmentlineforalloperations.Asaresult,
athoroughcleaningoftheequipmentisrequiredbetweencampaignsofthetwoproducts.Thisis
specifiedontheAdvancedtaboftheProductAcampaigndialog,whichmaybeaccessedbyselecting
theProductionScheduleitemintheexplorertree,selectingtheProductA1campaigninthepaneon
theright,clickingtheeditcampaignbutton( ),andclickingtheAdvancedtab(seeFigure18).

Figure18:SpecifyingCleaningthatfollowsaProductionCampaign

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ByclickingtheSetupbuttoninFigure18,apostcampaigncleaningtimemaybespecified(inthiscase,
thecleaningtimeisfixedat24hours,althoughitisalsopossibletohavethecleaningtimecalculated
automaticallybasedonequipmentrequirementsorachangeovermatrix.)

LiketheProductAcampaign,theProductBcampaignincorporatessomeslacktimebetweenbatches.
Asbefore,thisisspecifiedontheOptionstaboftheAddNewCampaigndialog.TheEOCforatwo
campaignproductionplan(eachofwhichhas6batches)isshowninFigure19.

Figure19:EOCforTwoProductsUsingtheSameEquipmentLine

NoticethatFigure19showsallbatchesoftheProductA1campaigningreenandallbatchesofthe
ProductB1campaigninorange.ThisisachangefromthepreviousEOCs,whichshowedeach
individualbatchwithadifferentcolor.ModificationstotheEOCcolorschemecanbemadebyright
clickinganopenareaofthechartandchoosingEditStyle(seeFigure20).Hereyoucanspecifythatthe
chartcolorschemeshouldbebasedonbatches,recipes,orcampaigns(notethattherearealsotabs
whichallowyoutochangethebarstyleandthetimescaleatthebottomofthechart.Itisalsopossible
tochangethetimescaletocalendarbasedratherthanarelativebasisstartingatDay1.)

AlsonoticethatthereisagapbetweenthetwocampaignsinFigure19,representedbywhitebars.This
isthe24hourcleaningtimeforeachequipmentitemthatwasspecifiedontheAdvancedtabofthe
ProductA1campaigndialog.

Finally,noticethattheProductA1campaignusesthefreezedryer(LYO1)foritsfinalprocedure,
whereastheProductB1campaignusesthebulkfiller(FL1).Allotherequipmentisusedbyboth
processes.

Intelligen,Inc. 25


Figure20:TheEOCStyleDialog

MultiProductFacilityUtilizingTwoProductionLines(CaseB2)
CaseB2issimilartoCaseB1,exceptthatinCaseB2theProductBrecipeusesitsownequipmentline.
Thisrequirestheadditionoftwonewseedfermentors(SFR3andSFR4),twonewproduction
fermentors(FR3andFR4),twonewchromatographycolumns(C3andC4),etc.Asaresult,new
equipmentfortheProductBrecipewasaddedtoboththeUpstreamfacilityandtheDownstream
facility.

NextthenewequipmentitemswereassignedtotheProductBrecipebyselectingtherelevant
proceduresintheProductBrecipeandupdatingtheequipmentspecificationsfortheirMainEquipment

Intelligen,Inc. 26

Pools(asdescribedearlier).Forinstance,theMainEquipmentPoolfortheFermentationprocedureof
theProductBrecipewasupdatedtocontainfermentorsFR3andFR4ratherthanfermentorsFR1and
FR2.

AlthoughProductsAandBgenerallyusedifferentequipmentunitsinthisexample,someequipment
unitsweresharedbetweenthetworecipes.TheseincludetheCentrifuge(CF1)andtheCIPskids(CIP1
andCIP2).Furthermore,sincebothrecipesusethesamecentrifugeandCIPskids,theMainEquipment
PoolintheCentrifugeprocedureandtheAuxiliaryEquipmentspecificationsrelatedtoCIPoperations
werenotchangedineitherrecipe.TheresultingEOCisshowninFigure21.

Figure21:TwoProductswithSeparateLinesbutSharedCentrifugeandCIP

Oneimportantpointtomentionaboutcampaignsisthattheorderinwhichtheyappearinthe
CampaignSequencelist(circledinFigure22)representstheprioritizationofthosecampaigns.Notethat
thiscampaignprioritizationdoesnotmeanthatthehighestprioritycampaignmustbecompletedprior
tothecommencementofthelowerprioritycampaigns(inFigure21bothcampaignsbeginatthesame
time).Campaignprioritizationsimplymeansthatcampaignsatthetopofthelisthaveahigherpriority
forresourceallocationthancampaignsbelowthem.Asaresult,ifmultiplecampaignsrequirethesame
resource(e.g.,anequipmentitem,astaffmember,etc.)atagiventime,thetopcampaignwillbe
assignedthatresourceuntilitisnolongerrequired.Thentheresourcewillbeassignedtotheother
campaign.Inotherwords,operationswithinahigherprioritycampaignwillneverbedelayedinorderto

Intelligen,Inc. 27

waitforresourcesbeingusedbyalowerprioritycampaign;resourcesareassignedtothehigherpriority
campaignfirst.TheclearestexampleofthisinFigure21isthegapbetweenoperationsinTK5atthe
endofDay7intheProductB1campaign(circledinblue).Atthistime,boththeProductA1campaign
andtheProductB1campaignrequiretheuseofcentrifugeCF1.However,sincetheProductA1
campaignhashigherpriority,thecentrifugeisassignedtoitfirst,andthematerialinbatch4ofthe
ProductB1campaignisheldintankTK5untilthecentrifugeisavailable.Thisholdingtimeis
representedbythegapbetweenoperationsinTK5attheendofDay7.Asbefore,theautomatic
shiftingoftheoperationthattransfersmaterialtothecentrifugeisdonebyassigningaflexibleshiftto
thatoperationwithintheProductBrecipe.

Figure22:CampaignPrioritization

Finally,ifyouwishtoensurethatentirecampaignsarenotdelayedexcessivelyduetoveryhighuseofa
particularsharedresource,youcanscheduleveryshortcampaignsorevenscheduleeachplannedbatch
asanindividualcampaign(i.e.,alternatingbetweensinglebatchcampaignsofProductAandProduct
B).Thisensuresthattheplantwillnotrun6(or10or20)batchesofProductAbeforeasinglebatchof
ProductBisproduced,eveniftheybothrequireuseofthesameheavilyusedresource.Notethatthe
prioritizationofcampaignsmayalsobemodifiedbyselectingaspecificcampaignandclickingonthe
MoveUp/MoveDownbuttons( )ontheCampaignSequencelist.

Intelligen,Inc. 28

CaseC:IncorporatingBufferPreparationandHolding

Thissetofcasesincorporatesbufferpreparationandholdingactivitiesintotheproductionschedule.Itis
assumedthateachproductrequireseightdifferentbuffersolutions(5buffersfortheoperationsofthe
INXand3buffersfortheoperationsofHICchromatographyprocedures,respectively).

InCaseC1,thebuffersareproducedandconsumedwithinasinglebatch.CaseC2explainshowto
modelprocessesinwhichabatchofacertainbuffersuppliesmaterialtomultiplebatchesofthemain
processorevenmultiplemainprocesses.CaseC3explainshowtomodelprocessesthatutilize
disposablebags(supportedbymobileskids)forstorageofbuffersandhowtoestimateandvisualizethe
floorspacerequirementforstagingsuchmobiletanks(skids).

IntraBatchBufferPreparationandConsumption(CaseC1)
InCaseC1,thepreparedbuffersareeachusedwithinasinglebatch.Asaresult,anewBufferPrep
sectionhasbeenaddedtotheProductArecipe(seeFigure23).Withinthissection,eachofthebuffers
ispreparedinablendingtankandthentransferredtoaholdingtank.Notethatsincethebufferprep
andstorageactivitieswilltakeplaceindifferentequipmentfromthemainprocessingoperations,an
additionalFacilitycalledBufferPrepAreahasbeenadded(seethebottomofFigure23),andthe
preparationandholdingtankshavebeenaddedtoit.

Figure23:TheBufferPrepSectionanditsAssociatedProcedures

Intelligen,Inc. 29

Althoughthereareeightdifferentbufferprepprocedures,onlytwobufferpreptanksareused(TP1
andTP2).Inotherwords,eachpreptankisusedformultiplebufferprepprocedures,andtherefore
thesetanksarereusedmultipletimesoverthecourseofasinglebatch.Thepreptankassignmentscan
beseenbyvisitingtheMainEquipmentPooltabassociatedwitheachbufferprepprocedure.For
instance,theMainEquipmentPooltaboftheProcedureDetailsdialogfortheINXEqPrepprocedureis
showninFigure24.HereyoucanseethatbufferpreptanksTP1andTP2arebothlistedastanksthat
couldpotentiallybeusedforthisprocedure.BothtanksarealsolistedastheMainEquipmentPoolfor
theotherbufferprepprocedures.ThisallowsScheduleProtochoosewhicheverpreptankisavailableat
agiventimeinordertoprepareabuffer,aslongasthattankmeetstheprocesscapacityrequirements.
Notethatinthisexample,thebufferpreptankshavedifferentsizes:TP1is2500LandTP2is4500L.
Sincecertainbuffersaremorethan2500L,thosebufferscanonlybepreparedinthelargertank(TP2).
NoticethatinFigure24,tankTP1isgreyedout.Thismeansthatforthisparticularbufferprep
procedure,TP1isnotcompatiblewiththeprocedurerequirements.Inthiscase,theprocedurebatch
sizeis3600L(thiscanbeseenontheScalingtaboftheProcedureDetailsdialog).ThereforeonlyTP2
canactuallybeusedforthisprocedure.Inotherbufferprepprocedures,eitherbufferpreptankcanbe
used.ScheduleProautomaticallydetermineswhetheranequipmentunithasanappropriatecapacityfor
agivenprocedure,aslongastheprocedurebatchsizeandtheequipmentcapacityhavebeenspecified
andtheConsiderEquipmentSizeLimitsboxontheScalingtaboftheProcedureDetailsdialogis
selected.

Figure24:MainEquipmentPoolTabfortheINXEqPrepProcedure

Intelligen,Inc. 30


TheEOCassociatedwithCaseC1isshowninFigure25.Aswasnotedpreviously,multiplebufferprep
proceduresutilizeeachpreptank(TP1andTP2)duringeachbatch.Thereasonthatonlytwobuffer
preptanksareusedisthatthebufferpreparationactivitiesarerelativelyquick,soreusingthesetanks
doesnotcreateschedulingbottlenecks.Unlikethebufferprepprocedures,eachofthebufferholding
procedureshasitsowndedicatedholdingtank(THA1,2,3,etc.).Furthermore,noticethatthebuffer
holdingtanksaretypicallyidleforextendedtimeperiodsbetweentheirReceiveBufferoperationsand
theirUseBufferoperations.ThisisseenclearlyinthezoomedinviewoftheEOCshowninFigure26.

Figure25:EOCforCaseC1

Intelligen,Inc. 31


Figure26:CloseUpoftheBufferHoldProceduresforBatch1

Notes:
1) ThecalendartimeunitsoftheEOCinFigure26weresetbyrightclickinganopenareaoftheEOC,
choosingEditStyle,switchingtotheTimeScaletab,selectingtheAbsolute(Calendarbased)option
forTimeBasis,andfinallyselectingtheappropriateMinorandMajorTimeunits.
2) ThezoomleveloftheEOCinFigure26wassetbydeselectingtheFittoWindowbutton, ,inthe
topleftportionofthechartandselectingadifferentzoomlevelwiththemagnifyingglassbutton,
.
3) InCaseC1itwasassumedthatCIP1(skid1)isdedicatedtocleaningtheequipmentofthemain
processandCIP2isdedicatedtocleaningthetanksutilizedforbufferpreparationandholding.A
moreevenutilizationofthetwoskidscanbeachievedbysharingthemthroughouttheprocesses.

ThereasonthereisextendedidletimebetweenthepreparationanduseofthebuffersinFigure26is
thatitisprudenttopreparethebufferswellinadvanceoftheirplannedusageintheprocess.This
ensuresthatbufferavailabilitydoesnotbecomeaschedulingbottleneck,evenifaspecificpreparation
activitytakeslongerthanexpectedorallbufferpreptanksarealreadyoccupiedatthescheduledbuffer
prepproceduresstarttime.TospecifywithinScheduleProthatthesebuffersmaybepreparedwellin
advanceoftheiruseinthemainprocess,thefirstoperationineachbufferprepprocedurewasgivena
negativefixedtimeshiftaswellasaflexibleshift.Forexample,theschedulingspecificationsforthe
PrepBufferoperationintheINXEqPrepprocedureareshowninFigure27.Noticethatthisoperation
hasbeengivenaFixedTimeShiftof12hoursrelativetothestartoftheColumnOperationsreference
operationintheINXprocedureoftheDownstreamsectionofProductA.Furthermore,a10hour
FlexibleShifthasalsobeenapplied.ThissetofFixedTimeShiftandFlexibleShiftspecificationswill
causeScheduleProtoattempttofinishthisPrepBufferoperation12hourspriortotheexpecteduseof
thebuffer.Ifthereisafacility/equipmentconflictthatwillnotallowthePrepBufferoperationtofinish
12hoursinadvance,itsfinishtimecanbedelayedbyupto10hours.Inotherwords,theoperationwill
bescheduledasearlyaspossiblewithinthe10hourwindowof12to2hourspriortouse.

Intelligen,Inc. 32


Figure27:TimeShiftsforBufferPreparationCommencement

Notethatforthesakeofsimplicity,thedifferentchromatographyoperationstypicallyrequiredwithina
chromatographyprocedure(i.e.,equilibration,loading,washing,elution,regeneration,etc.)wereall
combinedintoasinglelongoperationcalledChromatographyOperationswithintheserecipes.Asa
result,allbuffersforagivenchromatographyprocedureappeartobefedintothecolumnatthesame
time.Inanactualproductionfacility,thedifferentbufferswouldbefedsequentiallyintothe

Intelligen,Inc. 33

chromatographycolumn.Furthermore,thebufferswouldbepreparedsequentially,withtheearliest
neededbufferspreparedbeforethelatestneededbuffers.Thereareseveralwaystoaccomplishthis:
buffersrequiredlaterintheprocesscanbeexplicitlylinkedtootherbufferpreparationoperationsusing
theOperationSchedulingWithRespecttoanOperationinAnother(BufferPrep)Procedureoption,
buffersrequiredlaterintheprocesscanbegivensmallernegativeFixedTimeShifts,andbuffers
requiredlaterintheprocesscanbelinkedtootherbufferpreparationoperationswithAdvancedLinks.
Figure28displaysthelocationsforspecifyingtheserelationshipsforthePrepBufferoperationinthe
INXRegPrepprocedure.Sinceexplicitoperationschedulingwithrespecttooperationsinother
procedureshasalreadybeendiscussed,onlythesecondandthirdmethodsabovewillbedescribed
here.

Inthisexample,sincetheINXRegPrepbufferisnotneededuntillateintheINXchromatography
procedure,itisgivenaFixedTimeShiftofonly8hour,ratherthanthe12hourshiftappliedtothefirst
operationintheINXEqPrepprocedure.Furthermore,itisapparentbythe1nexttotheAdditional
Links(Advanced)buttonthatthereisoneadditionallinkspecified(inadditiontothespecificationthat
thisoperationshouldfinishwithashiftrelativetothestartoftheColumnOperationsoperationin
procedureINX.)ClickingontheAdditionalLinks(Advanced)buttonrevealsthatthisoperationshould
notstartuntilaftertheINXEIPrepproceduresCIPoperationhasfinished(seeFigure29).Thisensures
thebufferpreptankwillnotbeusedtopreparetheRegbufferpriortopreparingtheEIbuffer.

Incasessuchasthis,wheremultipleconstraintsarespecifiedforagivenoperationsstartorendtime,
ALLofthoseconstraintsmustbemet.Inthisexample,thePrepBufferoperationintheINXRegPrep
procedurecannotbecompletedmorethan8hourspriortothestartoftheColumnOperations
operationinprocedureINX,anditcannotbeginbeforetheINXEIPrepproceduresCIPoperationhas
finished.

Intelligen,Inc. 34


Figure28:SchedulingSpecificationsforthePrepBufferOperationintheINXRegPrepProcedure

Intelligen,Inc. 35


Figure29:TheAdditionalLinksDialog

BufferSchedulingBasedonInventoryControl(CaseC2)
CaseC2representsascenariowhereasinglebatchofINXRegeneration(regen)bufferisusedfor
multipleproductionbatches(theotherbuffersassociatedwithProductAareallstillpreparedforsingle
batchusage.)Tomodelthepreparationofasinglebatchofbufferthatwillbeusedinmultiple
productionbatches,anewINXRegenPreprecipewascreated.ThisrecipeisthesameastheINXReg
PrepprocedureincludedintheProductArecipeofCaseC1.However,movingthisprocedureintoits
ownrecipeallowsustorunfewerRegenbufferprepbatchesthanProductAbatches.Inaddition,it
allowsustousethesameRegenbufferformanydifferentproductionrecipes,ifdesired.

ThereareseveralwaystospecifywhentheINXRegenPreprecipeshouldberun.Thesimplestwayisto
scheduleindividualcampaignsoftheINXRegenPreprecipewheneveradditionalbufferisexpectedto
beneededbytheproductioncampaigns.Forinstance,ifonebufferprepbatchcanfeedtwobatchesof
theproductionrecipe,asinglebufferprepbatchcouldbescheduledpriortoeverytwoproduction
batcheswithintheCampaignSequenceareaoftheProductionSchedule.Anotheroptionistolink
productionandconsumptionofamaterialsuchasabufferbyusingastorageunit.Thiscanallow
additionalbatchesofbuffertobescheduledautomaticallywhenevermorebufferisrequiredbythe
mainprocess.ThissecondmethodistheoneisusedinCaseC2anddescribedhere.

InordertostorethebuffergeneratedbytheINXRegenPreprecipe,severaladditionalresourceshadto
becreated.First,anewmaterialcalledINXRegenBufferwasaddedtothelistofmaterials.Next,an
IntermediateStorageunitwascreatedwithintheBufferPrepAreafacility(seeFigure30).ThenewINX
RegenBuffermaterialwasthenassociatedwiththisunit(seebottomofFigure31),andtheunitwasset
upasbulkvolumetricstorageofIntermediates(seerightsideofFigure31).

Intelligen,Inc. 36


Figure30:TheINXRegenStorageTank

Figure31:INXRegenBufferStorageUnitProperties

Intelligen,Inc. 37


Next,theStorageunitwassetuptotracktheinventorywithintheunit(seeFigure32).Furthermore,the
unitwasassociatedwithholdingtanksTHA1andTHA2(seeFigure33).Inotherwords,multiplevessels
arebeingusedtoserveasingleStorageUnitinthiscase.Furthermore,thesetanksweregiven
capacitiesof5500Leach(specifiedthroughtheBufferPrepAreafacilitysEquipmentlist).Asaresult,
thetotalstoragecapacityforthisbufferis11000L.

Figure32:TheInventoryDataSpecificationsfortheBufferStorageUnit

Intelligen,Inc. 38


Figure33:TheEquipmentTaboftheBufferStorageUnit

Finally,itwasnecessarytoedittherecipesinordertoensuretheappropriateamountofmaterialwould
beproduced/consumedbyeachbatch.Tospecifyanappropriatequantityofbuffergenerationper
batchoftheINXRegenPreprecipe,theTransfertoHoldoperationwithinthisrecipewasedited,as
showninFigure34.First,anewmaterialoutputstreamnamedInxRegBuffertoSTGwasaddedtothe

Intelligen,Inc. 39

MaterialOutputstabofthisoperation(seeitemcircledinredinFigure34).Thenthespecificationsfor
thisstreamweresetbyselectingthecircleditemandclickingtheEditbutton( ).Thisbringsupthe
StreamInformationdialogshownatthefrontofFigure34.Herethecompositionandamountofthe
materialcanbespecified,andtheStorageUnitcanbeassigned.Inthiscase,5000LofINXRegenBuffer
willbeproducedandstoredintheINXRegenstorageunit.

Figure34:SpecifyingtheGenerationofINXRegenBuffer

Next,theColumnOperationsoperationwithintheINXprocedureintheDownstreamsectionofthe
ProductArecipewaseditedinordertoensurethat2400LofINXRegenBufferwouldbeconsumed
duringeachbatchofProductA(seeFigure35).

Intelligen,Inc. 40


Figure35:SpecifyingtheConsumptionofINXRegenBuffer

ThespecificationofINXRegenbuffermaterialconsumptionwasmadeontheMaterialInputstabofthe
ColumnOperationsoperation(withintheINXprocedure).Aswasdonepreviously,thedetailsofthe
consumptioncanbeviewedbyselectingtheInxRegenBufferstreamontheMaterialInputstab(circled
inred)andclickingtheEditbutton( ).ThisbringsuptheStreamInformationdialogshownatthe
frontofFigure35.Herethecompositionandamountoftheinputmaterialcanbespecified,andthe
StorageUnitcanbeassigned.

Oncetheprecedingspecificationshavebeencompleted,theINXRegenPrepbatchesmaybescheduled
intheProductionSchedule.Asbefore,6batchesofProductAwillbescheduled.However,unlikeCase
C1,CaseC2includesasecondcampaignofINXRegenPrepbatches.Furthermore,thestarttimeofthese
batchesisEventBased(i.e.,eachbatchbeginswhennecessary,baseduponthebufferinventorylevel)
ratherthanbeingbasedonaspecifictimeorbatchsequence.ThisisspecifiedontheTime/Sequencing
taboftheINXRegenPrepcampaign(seeFigure36).

Intelligen,Inc. 41

Figure36:TheTimingSpecificationfortheINXBufferPrepBatches

ClickingtheEventbuttoninFigure36willbringupthedialogshowninFigure37.Herethecriteriaare
specifiedforinitializationofINXRegenPrepbatches.Inthiscase,anewbatchwillbeinitiatedwhenever
thetotalamountofINXRegenBuffermaterialininventorydropsto201Lorless.Inordertoensure
thatsufficientINXRegenPrepbatchesarescheduledtomeetallprocessingdemands,asufficient
maximumnumberofbatchesshouldalsobespecifiedintheAmountsectionoftheID/Amounttabof
theINXRegenPrepcampaign.Inthiscase,3batcheswillbesufficienttomeetallscheduleddemands
fromtheProductAcampaign.

Intelligen,Inc. 42


Figure37:CampaignInitializationBasedonInventoryLevel

Withthecampaignspecificationscomplete,thecampaignscannowbescheduledandtheEOCcanbe
viewed(seeFigure38*).NoticethatthefirstINXRegenPrepbatchstartsatthebeginningofthesecond
day.ThisisbecausetheReleaseDatefortheINXRegenPrepcampaignisonedaylaterthantherelease
datefortheProductAcampaign(thiswasspecifiedontheirrespectiveTime/Sequencingtabsduring
campaignsetup.)Asaresult,thisbufferprepcampaigncanbeginnoearlierthan24hoursafterthestart
oftheProductAcampaign.Furthermore,sincetheinitialinventoryintheINXRegenstorageunitis
zero,theEventBasedcampaigninitializationspecifiedinFigure36andFigure37forcesthefirstbatchof
thiscampaigntobeginasearlyaspossible,whilestillrespectingtheReleaseDayconstraint.Asaresult,
thecampaignstartsattheverybeginningofDay2.Notice,however,thatthethreebufferprepbatches
arenotevenlyspaced.Instead,thesecondandthirdbatchesofthiscampaigndonotbeginuntilthe
bufferhasfallenbelowits201Lthreshold.ThiscanbeseenmoreeasilybyclickingtheOpenInventory
Chartbutton( )onthetoolbaroftheEOC,selectingStorageInventory,selectingtheINXRegen
storageunitandclickingthePlotbutton.NotethatthischartcanbelinkedtotheEOCbyclickingthe
Linkbutton( ).TheresultingplotsareshowninFigure39.ThestorageinventorychartinFigure39
clearlyshowsthatanew5000Lbatchofbufferispreparedeachtimethevolumeinthestorageunit
approacheszero.EachbatchofbufferisthenusedtosupplytwobatchesofProductA,resultinginthe
twodropsininventorypriortothesubsequentbatchofbufferprep.

*NotethatthecontentsofthisEOChavebeenmodifiedsothatonlycertainequipmentitemsare
visible.ThiswasdonebyrightclickinganopenareaoftheEOCandchoosingEditContents/Ordering.
Ontherightsideofthedialogthatappears,specificequipmentitemscanbechecked(orunchecked)in
ordertoinclude(orexclude)themonthechart.

Intelligen,Inc. 43


Figure38:AutomaticSchedulingoftheINXRegenBufferPrepBatches(CaseC2)

Figure39:EOCandINXRegenBufferStorageInventoryChart(CaseC2)

AnotherwaytoviewtheINXRegenbufferinventoryistoclicktheOpenInventoryChartbutton( )
onthetoolbaroftheEOC,selectHoldingEquipmentInventory(MaterialBased),chooseoneofthe

Intelligen,Inc. 44

holdingtanks(THA1orTHA2),andclickthePlotbutton.Thisproducesaplotoftheinventorylevel
withinthatparticulartank.TheseplotscanbelinkedtotheEOCusingtheLinkbutton( ).Figure40
showstheinventorylevelswithintheindividualholdingtanks,linkedwiththeEOC.Hereyoucansee
thattankTHA1isusedtoholdbatches1and3ofthebuffer,whiletankTHA2isusedtoholdbatch2of
thebuffer.Notethatitispossibletocontrolhowthestorageunitswillbeusedwithinaproductionplan
byspecifyingwhetherornotbatchintegritymustbemaintained(i.e.,batchesofbuffercannotbe
mixed),specifyingwhethermaterialcanbesimultaneouslydepositedintotheunitanddischargedfrom
it,specifyingwhethermaterialshouldbedropped(i.e.,drainedtowaste)ifthelevelinthetankgets
verylow,etc.(referbacktoFigure33).

Figure40:INXRegenBufferHeldinEachTank(CaseC2)

StorageofBuffersinDisposableBags(CaseC3)
CaseC3issimilartoCaseC1,exceptthatCaseC3assumesthebuffersarepreparedandthenstoredin
mobileunits(disposablebags)untilnecessary.Thiswasaccomplishedbyeditingthepropertiesof
variousbufferholdingunitsintheBufferPrepAreafacility.Forinstance,thespecificationsforholding
unitTAINXEqHoldweremodifiedtoincludea4.5m2floorspacerequirementontheSizetab(see
Figure41.)Thisspacerequirementincludesthespaceforthestorageskid,plusanyadditionalspace
aroundtheunitrequiredforhandling/connections/etc.Similarmodificationsweremadetoother
holdingtanks,althoughdifferentfloorspacerequirementswereassignedtovariousunits.

Intelligen,Inc. 45


Figure41:SpecifyingtheFloorSpaceRequirementforaMobileEquipmentUnit

Afterenteringthenewmobileequipmentspecifications,thetotalfloorspacerequiredbytheseunits
duringthecourseofacampaignmaybetrackedbychoosingView/ResourceProfiles/Mobile
EquipmentArea.ThischartcanalsobegenerateddirectlyfromtheEOCbyclickingtheOpenResource
Chartbutton( )andselectingMobileEquipmentArea.Figure42displaystheMobileEquipment
chartlinkedtotheEOCfora6batchcampaignofProductAanda6batchcampaignofProductB.The
EOCinthiscaseshowstheutilizationoftheproductionbioreactorsandthebufferprepandholdtanks,
whereastheMobileEquipmentAreachartshowsthetotalamountofopenfloorspacethatwillbe
requiredwithinastagingareaofthefacilityinordertosupportthemainprocess.

Intelligen,Inc. 46


Figure42:MobileEquipmentSpaceUtilizationChart

NoticethatinFigure42,thefirstuseofmobileequipmentoccursattheendofDay2.Thisiswhenunits
TBINXEqHoldandTBINXEIHoldarefirstused.Theseunitsrequireatotalof5.4m2offloorspace.As
processingproceeds,additionalmobileunitsrequiringextrafloorspacearerequired.

CaseD:UtilitySystemSizing
CasesD1andD2demonstratehowtomodelandsizepurifiedwatersupplysystems.CaseD1
incorporatesMaterialSupplySystemstomodeltheproductionandconsumptionofROwater(whichis
purifiedbyreverseosmosis)andWFI(whichisROwaterthatisfurtherpurifiedbydistillation).Thisisan
exampleofcascadedmaterialsupplies,sincetheROwaterisusedtoproducetheWFI.Notethatin
additiontobeingtherawmaterialforWFI,ROwaterisusedalsowithintheprocessitself.TheMaterial
SupplySystemstrackthegenerationanduseofeachofthesematerials.

ThenewROandWFIMaterialSupplySystemswerecreatedwithintheUpstreamFacility.Thesesystems
canbeviewedbyclickingontheMaterialSupplySystemsitemwithintheUpstreamFacilityinthe
explorertree,selectingoneoftheitemsinthepaneontheright,andclickingtheEditbutton( ).The
PropertiestabfortheROSupplysystemisshowninFigure43.Hereitisclearthatthematerialsupplied
bythissystemisROWater,whichwasdefinedpreviouslyduringspecificationoftheprojectsMaterials.
AlsonoticethattheCanServeMultipleParallelMaterialDrawingsboxischecked,sinceROwater
couldbeusedbymultiplebatches(orformultipleoperationswithinagivenbatch)simultaneously.

Intelligen,Inc. 47

Figure43:ThePropertiesoftheROMaterialSupplySystem

TocompletethedefinitionoftheROSupplysystem,additionalinformationwasaddedtotheInventory
Datatab(seeFigure44.)Herethe50,000Lopeninginventoryandthe100,000Lcapacitywerespecified.
Inaddition,aContinuousReceiptstrategywaschoseninordertoreplenishthestoragevessel.Clicking
ontheOn/OffbuttoninthelowerrightquadrantofFigure44bringsupthedialogshowninFigure45.

Intelligen,Inc. 48


Figure44:InventoryDatafortheROSupplySystem

Figure45:ReplenishmentSpecificationsfortheROSupplySystem

Intelligen,Inc. 49


Figure45showsthatwhenthelevelintheROSupplysystemdropsto50%ofitscapacity(50,000Lin
thiscase),theproductionofROwaterisrestartedandnewROsupplyisaddedtothesystematarate
of7,000L/huntilthesystemreaches95%ofitscapacity(95,000Linthiscase).

ThespecificationsfortheWFISupplysystemaresimilartothespecificationsfortheROSupplysystem,
withthefollowingexceptions:
1) ThematerialsuppliedbythissystemisWFIratherthanROWater.
2) TheOpeningInventoryandCapacityaresmaller.
3) TheSupplyRateislower,andtherawmaterialforthissystemisdrawnfromtheROSupply
materialsupplysystemthatwascreatedearlier(seeFigure46.)Inaddition,ascalingfactorof
1.1isspecifiedtoaccountforthefactthatnotalloftheROwaterisconvertedintoWFI(thereis
a10%loss).

Figure46:ReplenishmentSpecificationsfortheWFISupplySystem

Next,additionalmaterialswerespecifiedthroughtheMaterialsitemintheexplorertree.Theseinclude
CIPsolutionandvariouschromatographybuffersolutions.Eachofthenewmaterialswasassigneda
composition(throughtheStockMixture/EditMixtureCompositionbuttonoftheirMaterialProperties
dialogs).Forthesakeofsimplicity,allthebuffersinthisprojectwereassignedcompositionsof100%
WFIsincethismaterialisbyfarthelargestcomponentofthesetypesofbuffers,anditisthematerial
thatwewishtotrackinthisexample.

Oncetheadditionalmaterials/mixtureshavebeenaddedtotheprojectsMaterialslist,theymustbe
assignedtothespecificoperationswhichrequirethem.Notethattoseewhereagivenitemisused
withintheprocess,youcanselectthatitemfromitslistandclicktheViewUsesbutton( ).For
instance,selectingtheWFImaterialandclickingtheViewUsesbuttonproducesthedialogshownin
Figure47.HereitisclearthatWFIisusedwithinmanydifferentstreams(inallthreerecipes.)Notethat
tonarrowdownthelistontheright,aspecificrecipecanbechosenontheleft,andthenspecific
SectionsandProcedurescanbeselected.

Intelligen,Inc. 50

Figure47:StreamsthatuseWFI

BasedonFigure47,itisapparentthatWFIisusedintheUFDFDilstreamoftheUFDFProcedurewithin
theDownstreamsectionoftheProductBrecipe(thisisthestreamlistedattheverybottomofFigure
47.)Tovieworeditthisstream,firstnavigatetotheUFDFProcedureintheDownstreamsectionofthe
ProductBrecipeintheexplorertree.ThenselecttheUFDFoperation,clicktheEditbuttonandswitch
totheMaterialInputstab.ByselectingthestreamlistedhereandclickingtheEditbutton,itisapparent
that2000LofWFIisrequiredbythisoperation(seeFigure48).Similarmaterialusagespecifications
wereassignedtootheroperationswithintherecipesofthisproject.

Intelligen,Inc. 51


Figure48:WFIUsageduringtheUFDFoperationintheProductBRecipe

Basedonthesespecifications,itispossibletotracktheprocessrequirementsforROWaterandWFI,as
wellastracktheirinventorylevels.Forinstance,thedemandofWFIfromallscheduledbatchescanbe
viewedbyclickingtheOpenResourceChartbutton( ),selectingRawMaterials,clickingthe
Materialstab,andchoosingWFIinthePlotSingleMaterialdropdownmenu(seeFigure49).Toensure
allWFIusageisaccountedfor,makesurethecheckboxesrelatedtoincludingstockmixturestreamsand
utilityusagearechecked(seebottomofFigure49).

Intelligen,Inc. 52


Figure49:ResourceChartSpecificationforWFIConsumptionintheSchedule

TheresultingWFIusageplotisshownatthebottomofFigure50.HereyoucanseetheWFI
requirementsatanygivenpointintheproductionschedule.Thischartincludesenoughinformationfor
sizingallthreeelementsofaWFIsystem.Forinstance,theredlines(correspondingtotheyaxisonthe
leftsideoftheWFIchart)representtheinstantaneousdemandforWFIinallscheduledcampaigns.
Thereforethetallestredpeak(roughly13,000L/hr)providesusefulinformationforsizingthecirculation
loop,sincethepumpsandthepipediameteroftheloopmustbeabletoaccommodatethehighest
instantaneousflowrate.Furthermore,thegreenpeaks(correspondingtotheyaxisontherightsideof
theWFIchart)represent12hourcumulativedemandofWFI.Therefore,thetallestgreenpeakprovides
usefulinformationforsizingastoragetankthatiscapableofsupplyingtheprocessforany12hour
periodwithoutadditionalWFIproduction.Inthiscase,astoragetankofaround60,000Lwouldbe
required.ThebluelinesrepresenttheaverageWFIrequirementduringeach12hourperiod.This
providesusefulinformationforsizingthestill.Inthiscaseastillcapableofproducingaround5,000L/hr
wouldbesufficient.Notethattheaveragingintervalforthecumulativeandtimeaverageddemandscan
bechangedbyrightclickingablankareaoftheWFIchart,selectingEditStyle,andchangingthe
AverageovervaluesfortheRateAverageLineandtheCumulativeAmountLine.Alsonotethatthere
isatradeoffbetweentanksizeandstillratewhentheaveragingintervalischanged;iftheaveraging
intervalisincreased,therequiredtanksizewilltendtoincreasesincethemaximumcumulative
consumptionperintervalwillusuallyincreaseaswell.However,thestillratewilltendtodecreaseasthe
averagingintervalisincreasedsincehigheruseandlowerusetimeperiodswillbeaveragedtogether,
resultinginalowermaximumstillrate.

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Figure50:WFIUtilizationChartLinkedtotheEOC(CaseD1)

Inadditiontodisplayingtheinstantaneous,cumulative,andratebaseddemandforWFI(andother
materials),ScheduleProcandisplaytheinputflows,outputflows,andinventorylevelsofeachMaterial
Supplysystem.Figure51displaysthisinformationfortheWFIandROWatersupplysystems,linkedto
theEOC.RecallthatROWaterisusedasarawmaterialforWFIproduction,aswellasbeingused
directlywithinvariousoperations.Asaresult,ithasgreaterconsumptionthanWFI.

Figure52providesacloseupoftheROWatersupplysystem.Inthisfigure,thepreviouslydefinedupper
andlowerlimitsof100,000L(100,000Lx100%)and0L(100,000Lx0%)areshownbythegreen
horizontalbars.ThesebarscorrespondtotheyaxisontherighthandsideofFigure52.Thedarkblue
lineonthisfigurerepresentstheamountofROWaterininventory,anditalsocorrespondstotheyaxis
ontherighthandside.ThelightblueandmaroonlinesrepresentthesupplyrateofadditionalROWater
tothesystemandthedischargerateofthatROWatertotheproductionprocesses,respectively.These
linescorrespondtotheyaxisonthelefthandside.Asyoucansee,theROWatersupplysystemishalf
fullwhentheproductionprocessbegins.However,assoonastheschedulestarts,additionalROWater
isproducedandaddedtothesupplysystem.Thiscontinuesuntilthesystemreaches95%ofcapacity(as
wasspecifiedearlier).EarlyonDay2,thefirstprocessdemandsforROWateroccur.Asaresult,the
inventorylevelbeginstodrop.Whenthesupplyinventoryfallsbelow50%ofcapacity,additionalRO
Waterproductionbeginsandeventuallytheinventorylevelreaches95%ofcapacityagain.Notethatif
theprocessesrunningintheplanthavesufficientdemand(morethan7,000L/hinthiscase),itis
possiblethatthelevelwithintheROSupplysystemwillfallwellbelowthe50%ofcapacitytriggerpoint
beforeultimatelyincreasingto95%ofcapacity.ThiscanbeseenclearlyonDay7,whentheinventory
levelfallstoroughly30%ofcapacityduetoveryhighsimultaneousdemandsforROWaterintheplant.

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Figure51:MaterialSupplySystemsforWFIandROWater

Figure52:CloseupViewoftheROWaterMaterialSupplySystem

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ConsideringWFILoopSanitization(CaseD2)
Thefinalcaseassociatedwiththisexample(CaseD2)issimilartoCaseD1,exceptthatdowntimehas
beenaddedtotheWFIsystemtoaccountforloopsanitization.ThisisspecifiedbyselectingtheMaterial
SupplySystemsitemintheUpstreamFacility,selectingtheWFISupplyiteminthepaneontheright
handside,clickingtheEditbutton( ),andthenclickingthecalendarbutton( )ontheProperties
tab.ThisbringsuptheOutagesviewfortheWFIMaterialSupplySystem(seeFigure53).Fromthis
dialog,youmayaddoreditoutagesbyrightclickingonaspecificdayandchoosingAddaNewEntryor
EditEntries.Forinstance,rightclickingonJuly27thandchoosingEditEntriesbringsupthedialogshown
inFigure54.HereitisapparentthattheSanidowntimeentrytakesplacefrom8amtonoonevery
Saturday.

Figure53:WFISupplySystemOutages

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Figure54:SpecificationsforWeeklyWFILoopSanitization

AftertheWFIloopsweeklysanitizationdowntimehasbeenscheduled,theEOCandtheMaterialSupply
InventorychartforWFIcanberegenerated.ThelinkedchartsareshowninFigure55.TheEOCchartin
thisfigureshowsacloseupviewoftheWFIsupplyoutage,circledinred.Theoutageisdisplayedwitha
greybar.Thisoutagebeginson7/27/2013at8amandlastsfor4hours.(NotethattheWFIsystemis
frequentlysupplyingmanyoperationssimultaneously,whichiswhytherearemanyrowsintheEOC
associatedwiththesingleWFISupplysystem.Recallthatthisbehaviorwasdescribedearlier,whenthe
MaterialSupplySystemsettingentitledServeMultipleParallelMaterialDrawingswasmentioned.)
Furthermore,noticethattherearenoWFIsystemdischargeactivitiesallowedduringthis4hour
downtime.Thislackofactivityduringthe4hourdowntimeisevidentinthecircledareaoftheWFI
SupplychartatthebottomofFigure55.

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Figure55:EOCandWFIMaterialSupplywithWeeklyOutage(CaseD2)

IncorporatingAutomaticCleaningAfterExtendedIdleTime(CaseE1)
Thefinalcase(E1)demonstrateshowtoautomaticallyaccountforcleaningwhichmayberequiredif
certainequipmentsitsidleforanextendedperiodoftime.Forinstance,letsassumeatankisusedto
preparevariousbuffersoverthecourseofacampaign.Thistankisgivenacleaningaftereachindividual
bufferpreparationactivity.However,ifthetanksitsidleforanextendedperiodoftime,itmaybe
necessarytocleanthetankagainincasethereissomebacterialgrowththathastakenplacewithinthe
tankoritsassociatedpiping.ThistypeofscenariocanbemodeledusingScheduleProsEquipment
ChangeoverMatrixfunctionality,whichallowsanextracleaningoperationtoautomaticallybeaddedto
theproductionscheduleincaseswhereauserdefinedtimebetweenoperationsisexceeded.

Tosetupthisautomaticschedulingofcleaningactivities,itwasfirstnecessarytospecifyoneormore
RecipeTypesintheScheduleProproject.ThiswasdonebyselectingSchedule/RecipeTypesfromthe
mainmenuandthenclickingtheAddNewTypebutton( )inthepaneontheright.Inthisexample,a
recipetypenamedMicrobialwasaddedtotheProductTyperecipecategory(seeFigure56).

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Figure56:RecipeTypeforCaseE1

NexttheMicrobialRecipeTypewasassignedtothespecificrecipeswhichrequiretheuseofthe
changeovermatrix.ThiswasdonebyselectingtheProductAnodeintheExplorerTreeontheleftside
oftheapplication,clickingtheEditRecipeDatabutton( )intherightsidepane,andchoosingthe
MicrobialrecipetypeintheRecipeDatadialog(seeFigure57).TheProductBrecipeandINXRegen
PreprecipewereassignedtheMicrobialtypeinthesameway.

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Figure57:theRecipeDataDialog

NextitwasnecessarytosetuptheChangeoverMatrixthatdetermineswhetheradditionalcleaningis
required.ThiswasdonebyfirstselectingtherelevantequipmentitemintheExplorerTreeontheleft
side.Inthiscase,theTPrep1vesselwithintheBufferPrepAreafacilitywasselected.Thenthe
ChangeoverMatrixwascreatedbyclickingtheEditbutton( )inthepaneontheright,selectingthe
Cleanout/Changeovertab,clickingtheAddNewCleaning/ChangeoverMatrixbutton( ),and
specifyinganameassociatedwiththenewmatrix(seeFigure58andFigure59).Inthiscasethematrix
wasnamedMaxcleanholdtodenotethemaximumholdtimeforwhichtheequipmentisstill
consideredcleanafterthecompletionofaprioruseandcleaning.Alsonoticethatthecategoryinthe
dropdownmenuinFigure59issettobethesameastheClassificationCategoryspecifiedearlierfor
theMicrobialrecipe(i.e.,thecategoryisProductTypeinbothplaces).

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Figure58:TheEquipmentPropertiesDialog'sCleanout/ChangeoverTab

Figure59:CreatingtheChangeoverMatrix

Oncethenewmatrixwasnamedandtheappropriatecategorytypewaschosen,theOKbutton
onFigure59wasclicked.Thenappropriateparametersassociatedwiththecleaning/changeover
requirementswerespecified.Thiswasaccomplishedbyselectingthematrixinthe
Cleaning/ChangeoverMatriceslistandclickingtheEditbutton( ).Theresultingdialogis
showninFigure60.

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Figure60:SpecifyingChangeoverMatrixParameters

InFigure60,therowlabelsrepresenttherecipethatisonthefromsideofthetransition.Thecolumn
headingsrepresentthetoside.Inotherwords,inthiscaseacleaning/changeovertimeof1hourwas
specifiedforanytransitionfromtheIdlestatetoaMicrobialrecipe.Furthermore,aminimumtime
of48hoursbetweenusesisrequiredinorderforthisvesseltobeconsideredIdle.Inotherwords,
withthesespecificationsthemaximumcleanholdtimeis48hours,afterwhichthebufferprepvessel
TPrep1mustberecleanedpriortothesubsequentbatch.Incontrast,sincetheentriesinthe
MicrobialrowinFigure60arebothzero,therewillnotbeanadditionalcleaningactivityscheduled
whentransitioningfromaMicrobialrecipetotheidlestate,orfromaMicrobialrecipetoanother
Microbialrecipe(withinthe48hourwindow).

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WiththeChangeoverMatrixnowdefined,itcanbeappliedtoothervessels,ifdesired.Forinstance,it
wasappliedtobufferprepvesselTPrep2byselectingTPrep2intheBufferPrepAreasequipment
list,clickingtheEditbutton( ),selectingtheCleanout/Changeovertab,clickingtheAddNew
Cleaning/ChangeoverMatrixbutton( ),andselectingtheMaxcleanholdentryintheNamefields
dropdownlist.TheOKbuttonwasthenclickedontheNewChangeoverMatrixandEquipment
Propertiesdialogstoconfirmtheselection.ThissameprocesswasrepeatedtoassigntheMaxclean
holdcleaning/changeovermatrixtobufferprepvesselsTPrep3,TPrep4,andTAINXRegenPrep.

Thefinalstepthatmustbeperformedistoaddprecleaningoperationstoeachprocedurethatuses
equipmentwhichissubjecttothemaxcleanholdrequirement,andassignthecleaning/changeover
matrixtothoseoperations.ThiswasdonebyopeningtheBufferPrepsectionoftheProductArecipe,
selectingtheINXEqPrepprocedure,andinsertingaPrecleaningoperationatthebeginningofthe
procedure.Afterinsertingtheoperation,itwaseditedbyclickingtheEditbutton( ),clickingthe
Durationtab,selectingDurationBasedonMainEquipmentChangeoverMatrix,andchoosingthe
Maxcleanholdmatrixinthedropdownmenu(seeFigure61).Furthermore,inFigure61the
transitionshouldbewithrespecttothetaskbeforesincethiswillcausetheoperationsdurationtobe
setequaltotheentryinthechangeovermatrixthatcorrespondstothepreviousoperation(i.e.,the
previousbufferprepuseinthisvessel)andthisoperation.Inotherwords,ifthereisanidletimegreater
thanorequalto48hoursbetweenthepreviousactivitywhichusedthisvesselandthenewactivity
whichusesthisvessel,thisPrecleaningoperationwillbegivenadurationof1hour.Notethatthevery
firstbatchwithinavesselmayalsobeassignedaPrecleaningoperationifthevesselisidlefor48or
morehourspriortothecommencementofthatbatchontheProductionSchedule.Incontrast,ifthe
idletimebetweenbatchesislessthan48hours,thePrecleaningoperationwillbeassigneditsnominal
durationofzerohours(refertoFigure60forthisspecification).Inotherwords,ifthereislessthan48
hoursofidletimebetweenconsecutiveuses,thePrecleaningoperationisignored.

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Figure61:AssigningtheChangeoverMatrixtoaPrecleaningOperation

TocompletethespecificationsforthisPrecleaningoperation,theSchedulingtabwasclicked,the
operationstarttimewaschangedtoWithRespecttoAnotherOperationinthisProcedure,thePrep
Bufferoperationwasreferenced,andaFinisheswithstartofreferenceoperationspecificationwas
set(seeFigure62).

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SimilarmodificationsweremadebycopyingandpastingthenewPrecleaningoperationintotheother
bufferpreparationproceduresintheProductA,ProductBandINXRegenPreprecipes(andupdating
thelinksontheSchedulingtabforthepastedoperations).

Figure62:UpdatingtheSchedulingTab

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Withthesechangescomplete,thecampaignswerescheduledandthenewEOCwasgenerated(see
Figure63).

Figure63:EOCShowingPrecleaningOperationsinPurple

Asyoucansee,whenthereareshortgaps(lessthan48hours)betweenbatchesinaparticularbuffer
prepvessel(suchasTAINXRegenPrep),noadditionalPrecleaningisscheduled.However,forlonger
gapsinthebufferprepvessels,thechangeovermatrixautomaticallyschedulesaPrecleaningoperation
priortothesubsequentbatch(severalofthePrecleaningoperationsintheTAINXRegenPreptankare
outlinedinredinFigure63).Asmentionedpreviously,ifthereissufficientidletimepriortothestartof
thefirstbatchwithinavessel,aPrecleaningoperationisscheduledjustpriortothatfirstbatch.Thisis
thecasefortheinitialoperationsinallthebufferprepvessels(seethepurpleoperationsinFigure64).

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Figure64:PrecleaningOperationsDuringtheInitialUseofEachBufferPrepVessel

Furthermore,noticethatallthePrecleaningoperationsin theEOC are the same color (purple)

regardless of which campaign an individual Precleaning operation belongs to. This required the
Changeover Operation Type to be assigned to relevant operations in the recipe. This was accomplished
by selecting the Product-A recipe in the Explorer Tree, clicking the Set Operation Types button ( ) in
the pane on the right side, and choosing Changeover as the operation type for the Precleaning
operations (see Figure65). The same process was followed to assign Changeover operation types to the
Product-B and INX Regen Prep recipes.

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Figure65:AssigningOperationTypestoOperationsinaRecipe

After assigning operation types, the EOC was generated. The Changeover-type operations were then
differentiated from other operations on the EOC by right-clicking an open area of the chart, choosing Edit
Style, clicking on the Use Activity Colors for Selected Operation Types checkbox, and clicking on the
Changeover checkbox (see Figure66). Note that this selection overrides the bar color selection on the
left side of this dialog (e.g., Color by Batch/Recipe/Campaign) for the selected operation type(s).

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Figure66:HighlightingthePrecleaningOperationsontheEOC

Thisconcludesthemicrobialbioprocessingexample.Foradditionaldetailsonhowtocreatemodelsin
SchedulePro,pleaserefertotheScheduleProUsersGuideandtheReadMefilesoftheother
ScheduleProexamples(locatedathttp://intelligen.com/schedulepro_overview.html)andwatchthe
onlinetrainingvideosathttp://www.intelligen.com/videos.html.Thefunctionalevaluationversionof
ScheduleProcanbedownloadedfromtheDownloadspageofourwebsite.Presentationdocumentsand
publicationsareavailableatwww.intelligen.com/literature.

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