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Conceptual DesignFor Bioprocess SolutionsTo start click here

IntroductionPROCESSDesigning a New Manufacturing Facilityfor BiopharmaceuticalsBusinessThe planning and designing of a new biopharmaceuticalproduction facility is a complex process. A new facility mustfulfill all regulatory requirements and the production capacitymust be sufficient and flexible enough to meet ever changingdemands.Drivers:l Singleor multiproductfacility?l Capacity requirement?At Sartorius we have extensive experience in designing facilitiesthat fulfill all these requirements. We can help you with thecreation of a facility concept and quickly find answers tofundamental questions in order to meet demanding timelines.Our conceptual design services deliver comprehensive processreviews, process layout studies, process scale-up designs, as wellas process automation concepts.vers:ss Drich?Procepproaangiid?mpar hybrol Caesuglelly sinl FuRegulatory Drivers:l W hich room classification doI need in which area?l What kind of room segregationfits best to my needs?IntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackageSUCCESS

IntroductionPROCESSConceptual Design2 MonthsProcess Feasibility Study12 MonthsProcess Conceptual DesignBasic DesignDetail DesignProductionT esting of feasibility and taking key-decisions onthe manufacturing strategy and design conceptl Creation of mass balancesl Equipment Listl Process Schedulingl S election of theautomation conceptl Process Flow Diagraml Process layoutIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackageC&QSUCCESS

IntroductionPROCESSSUCCESSProject Schedule Time ScheduleLevel A time schedule based on Deliverables ActivitiesIntermediateMeetingWeek 1Week 2Kick OffWorkshop #1IntroductionMass BalanceReviewIntermediateMeetingWeek 3Week 4Workshop #2IntermediateMeetingWeek 5Week 6Week 7Workshop #3Mass Balance ApprovalFacility Design Approval– Optimized Scenario– Process Solution– Process Flow Diagram– Buffer Concept– Equipment List– Automation ConceptProcess FlowDiagramProcessLayoutAutomationStandardCD PackageCD HandoverWeek 8Workshop #4

Mass Balance ReviewPROCESSSUCCESSProcess DescriptionProcess ModellingN-3 Shake FlaskBased on your process information we calculate the mediaand buffer requirements as well as the time scheduling ofBased on your processyour processes.N-2 RockingN-3 MotionShakeFlaskN-2TankRockingMotionN-1 StirredReactorinformation we calculate theN-1 Stirred Tank ReactorProduction BioreactorBy modelling differentscenarioswe can selectthe mostmediaand bufferrequirementsoptimal parameters for your facility.2 Stage Depth Filtration2 Stage Depth FiltrationOur experiences with both single-use and stainless steelequipment will helpByyoumodellingto find the differentbest solutionscenariosfor allyour processes.we can select the most optimalProtein A Affinity chromatographyProtein A Affinity chromatographyLow pH Virus InactivationLow pH Virus Inactivationfor your echromatographyOur experiences with bothsingle-use and stainless steelequipment will help you to findthe best solution for all changeMembraneAdsorberFiltrationNano NanoFiltrationFinal UF DFFinal UF/DFBulk Fill and FinishBulk Fill and Finish03 January 2018Mass BalanceReview(MBR)Production Bioreactorand durations of your processes.IntroductionMass Balance ReviewMassBalance ReviewPage 6Process FlowDiagramProcessLayoutAutomationStandardCD Package

Mass Balance ReviewPROCESSSUCCESSProcess Modelling1. D escription ofthe processesthat need tobe modelled3. E valuation andoptimizationof the processesProcess 1N-3 Shake Flask5. Process andequipmentschedulingbased on MBRoutputN-2 Rocking MotionN-1 Stirred Tank ReactorProduction Bioreactor2 Stage Depth FiltrationProcess Modelling2. Descriptionof the processparametersas input forthe modellingtoolIntroductionBinding capacityColumn heightScenario 1Scenario 250 g/L50 g/L20 cm20 cmColumn Diameter45 cm60 cmFlow rate320 cm/h320 cm/hEquilibration5 CV5 CVPost Load Wash 110 CV10 CVElution Buffer5 CV5 CVRegeneration buffer 5 CV5 CV4. Process flowdiagram incl.equipment6. Advanced options- Economic Modelling- Detailed SchedulingBuffersMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD Package

Mass Balance ReviewPROCESSSUCCESSProcess DescriptionN-3 Shake FlaskN-2 Rocking MotionN-1 Stirred Tank ReactorProduction Bioreactor2 Stage Depth FiltrationProtein A Affinity chromatographyLow pH Virus InactivationCation Exchange chromatographyAnion exchange Membrane AdsorberEvaluate the impact of differenttechnology options on your processl Sartoclear DynamicsModel parameters to optimize bufferrequirements and equipment sizesl 2 Stage Depth Filtrationl Centrifugation Depth Filtrationl IEX resin (bind and elute)Binding capacityl IEX resin (Flow through)l IEX membrane (bind and elute)l IEX membrane (flow through)Column height20 cm20 cm45 cm60 cmFlow rate320 cm/h320 cm/hFinal UF DFBulk Fill and FinishMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationScenario 250 g/LColumn DiameterNano FiltrationIntroductionScenario 150 g/LStandardCD Package

Mass Balance ReviewPROCESSSUCCESSProcess 1N-3 Shake FlaskEvaluate the impact of changing parameterson important factors such buffer demandsand equipment scheduling.Scenario 1Scenario 2Binding capacity35 g/L35 g/LColumn height20 cm20 cmColumn Diameter30 cm45 cmFlow rate320 cm/h320 cm/h5 CV5 CVPost Load Wash 15 CV5 CVElution Buffer2 CV2 CVRegeneration buffer 3 CV3 CVN-1 Stirred Tank ReactorExample:Impact of Protein A column volumeProduction Bioreactor2 Stage Depth FiltrationProtein A Affinity chromatographyLow pH Virus InactivationBuffersEquilibrationN-2 Rocking MotionCation Exchange chromatographyAnion exchange Membrane AdsorberNano FiltrationCycles per BatchProcess time13 h7h14.6 g/L12.9 g/LVolume Out226254Equilibration565636Wash 1565636Elution Buffer226254Regeneration buffer 339382BuffersBulk Fill and FinishMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationScenario 24Concentration OutFinal UF DFIntroductionScenario 18StandardCD Package

Mass Balance ReviewPROCESSBased on the results from the MassBalance detailed time schedules forProcess Schedulingall equipment can be composed inorder Theto resultsstreamlinetheandproductionfrom the MBRthe generated PFDcanbeusedtocreatedetailedscheduling in orderprocess.to streamline the production process.Reasons for process scheduling:l Hourly based process scheduling considering 3 shiftsl Process debottleneckingl Equipment capacity and availability evaluationWhyl Shared equipment strategy DE bottle necking process stepsl Media-Buffer preparation & holding concept to reduce turn around time or cycle timereduction Modelling and Design of Multi-ProductFacilities to calculate number of batches annually output used in room segregation strategyIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutExamplesAutomationfor roomconcept :StandardCD Package Inoculation Cell culture harvestSUCCESS

Mass Balance ReviewPROCESSSUCCESSAdvanced Process SchedulingOn request the advanced Process scheduling withSchedule Pro* can be added to the basic package.l Process debottleneckingl Shift modelling capabilities e.g. 2 shifts,Handles plant down-time, weekend andholiday schedulesl Multi-product campaign schedulingl Cost engineering, optimization of media-bufferpreparation and holdsl Labor, room, facility occupancy capabilities03 January 2018* Schedule Pro is licensed from Intelligen Inc.IntroductionMass BalanceReviewPage 3403 January 2018Process FlowDiagramProcessLayoutAutomationPage 34StandardCD Package

Mass Balance ReviewSUCCESSEconomic ModelingEconomic modelingN-3 canShakehelpFlask you in making better decisions foryour project. Together with our partner Biosolve we can quicklyN-2 Rocking impactMotionevaluate the economicalof process related factors.N-1 Stirred Tank Reactorheentsesses.nariosimalPROCESSMass Balance ReviewMassReview (MBR)Production Bioreactor(MBR)2 Stage Depth FiltrationOpen Questions:Protein A Affinity chromatographyl Single-use or hybrid?Low pH Virus Inactivationl How many bioreactors?Cation Exchange chromatographyAnion exchange Membrane Adsorberelfindur07 June 2018Page 3Nano FiltrationFinal UF/DFBulk Fill and FinishIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationPage 6StandardCD Package

Process Flow DiagramPROCESSProcess Flow Diagram(PFD). This tool provides the visualization of process relatsionshipsas well as the major equipmentselection based on outputs of themass balance review.Upstream ProcessIntroductionMass BalanceReviewProcess FlowDiagram03 January 2018ProcessLayoutAutomationStandardCD PackageSUCCESS

Process Flow DiagramPROCESSSUCCESSParallel to the PFD preparationa buffer concept will be selectedand visualized.03 January 2018ProcessDownstreamIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutPage 11AutomationStandardCD Package

Process Flow DiagramPROCESSSUCCESSBuffer Distribution ConceptAs most DSP steps require largebuffer volumes, the processlayout is highly impacted bythe buffer preparation anddistribution concept.Single-use technology offersflexible new options for bufferconcepts. Two examples can beseen on the right.Separated preparation ready madeIntroductionMass BalanceReviewPage 407 June 2018Combined preparation and storagel Lower room classification in distribution areal Less traffickingl More challenging with large buffer volumesl Adjacency & wall area requirementProcess FlowDiagramProcessLayoutAutomationStandardCD Package

Process Flow DiagramPROCESSSUCCESSConcept 1:Separated Preparation Ready MadeBuffer preparation is remote from the point of useAdvantages:l High mobility and flexibilityl Distribution area can be reduced to CNC, leads to less operational costl Smaller Buffer Prepl Less movement in Pre Viral & Post Viral areaChallenges:l Adjacency & wall area required for previraland post viral room with distribution corridorl Suitable only for low titer process, challenging for high titer processl Fixed palletanksl High trafficking2018IntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackagePage 4

Process Flow DiagramPROCESSConcept 2:Combined Preparation and StorageLarge volume buffers are prepared and stored in proximityto the point of use.Advantages:l Less traffickingl Suitable for low & high titer processl Less movement in Pre Viral & Post Viral areaChallenges:l Adjacency & wall area required for previraland post viral room with buffer areal Bigger space for preparation & distribution.Extra operational area requiredl Fixed high volume palletanksl Higher Grade D area leads to higher operational costIntroductionMass BalanceReviewProcess FlowDiagram07 June 2018ProcessLayoutAutomationStandardCD PackageSUCCESS

Process LayoutPROCESSSUCCESSFitting Layout Around Process SolutionDepending on the number of product, batches and flexibilityrequirements for the future, a process layout will be drawn.The process layout must full fill cGMP & regulatory principlesand will consider personnel, material, product and waste flows.Color Codes:l Process Areal Supply Corridorl Support AreaDifferent concepts have been generated and optimized forcommon single use and hybrid projects.l Return CorridorSupply to Return ConceptMobile Buffer ConceptFuturistic Dance Floor Ballroom Concept– Unidirectional Flow– Less traffic– Bidirectional flow– High traffic– Reduce walls and airlocks– Operational flexibilityIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD Package

Process LayoutPROCESSSUCCESSPost Viral PurificationSupply to Return ConceptReturn CorridorCharacteristics of thesupply to return concept:Media Prep & DistributionPre Viral Purificationl Unidirectional flowBuffer Prep & Distributionl No transportation of buffers dueto adjacency of buffer prep to preand post viral purificationSupply CorridorCell CultureGuidance for 2 2000 L STRs:l Total process area required:1200 – 1500 m2Harvestl ISO8 Grade C: 175 – 250 m2l ISO9 Grade D: 625 – 750 m2l Grade NC CNC: 400 – 500 m2Support AreaIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD Package

Process LayoutPROCESSAdjacency Bubble DiagramSUCCESSInoculationAdjacency of certain process areas is key for streamlinedprocessing. Static equipment near to next process unit reducesmovement of tanks and the length of tubing’s.Media Prep& DistributionCell CultureFitting the facility around the equipment rather than theequipment around the facilityHarvestPre ViralPurificationPost ViralPurification &Bulk filtrationBuffer Prep& DistributionIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD Package

Process LayoutPROCESSSUCCESSNEUProcess Layout ProcessConcept ILayoutConcept IPersonnel Flowl Uni-directional flow in process areasPersonnelFlowl Bi-directional flow for media & buffer areas with support areas IntroductionUni-directional flow in processareasBi-directional flow for media &buffer areas with support areasMass Balance03January 2018ReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackagePage 21

Process LayoutPROCESSSUCCESSNEUProcessI Layout Concept IProcess Layout ConceptProduct FlowMedia-Buffer FlowProduct Flowl Product streams incl. media and buffer transferMedia-Buffer Flowl Product flow from one room to another via wall penetrationsl Planned room adjacency IntroductionProduct streams incl. media andbuffer transferProduct flow from one room toanother via wall penetrationsPlanned room adjacency03 January 2018MassBalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackagePage 22

Process LayoutPROCESSSUCCESSNEUProcessI Layout Concept IProcess Layout ConceptMaterial FlowMaterial FlowWaste FlowWaste FlowMaterial Flowl Uni-directional flow in critical environmentsMaterial Flowl Risk Based Approach Uni-directional flow in criticalenvironmentsl Temporal Segregation, ProceduralControl Risk Based Approach Temporal Segregation, ProceduralControlWaste Flowl Uni-directional flowWaste Flow soiledUni-directionalflowl Decontamination of GMOsolid & liquidwaste Decontamination of GMO soiledl Risk Based Approachsolid & liquid waste Risk BasedApproachl Temporal Segregation, ProceduralControl Temporal Segregation, ProceduralControlIntroduction03 January 2018Mass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackagePage 23

AutomationPROCESSSUCCESSIntroductionThe automation of your processes and the integration intoexisting networks is a key factor for a successful operation.Depending on the kind of project we can either offer proprietarysolutions or partner with all mayor industrial players such asSiemens (PCS7) and Emerson (DeltaV).Unit operations such as bioreactors and DSP equipment canbe implemented at different levels providing you different levelsof control and flexibility.Our automation expertise covers the full spectrum from basicstand alone units, to fully integrated systems, into DCS networks.AutomationIntroERPEnterprise Level (Level 5)MESPlant Management Level (Level 4)SCADA DCSProcess Management Level (Level 3)PLCConcept 1Controller Level (Level 2)Inputs OutputsConcept 2Concept 3IntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackageField Level (Level 1)

AutomationPROCESSSUCCESSAutomation Concepts OverviewIn general there are 3 different automation concepts that can beapplied in manufacturing facilities. At Sartorius we guide you tothe best approach for your unique situation.Stand Alone Package UnitsPackage-Units withServer Client SCADA SystemPackage-Units integrated intoa Distributed Control -06PU-05l Individual local controll Remote control of groupl Data transfer via OPCl Central Unit Reportsl P lant wide process visualizationwith batch and recipe controll Plug-and-Play capabilitiesIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD Package

AutomationPROCESSStand Alone Package-UnitsAll control, reporting, recipe and unit operations are localizedinto one system called the “package-unit”. This includes allparameter settings for unit-based control loops as well as recipes.ControllerAcquired measurement data can be transferred to a higher levelvia OPC connectivity.ControllerThe autonomous process units, require individual maintenanceand 21 CFR 11 reports are only possible per individual unit.PU-01This basic approach is an ideal solution for a process with alimited set of parameters.IntroductionMass BalanceReviewProcess FlowDiagramPU-02ProcessLayoutAutomationStandardCD PackageSUCCESS

AutomationPROCESSPackage-Units with Server Client SCADA SystemA group of unit operations or clients (e.g. all bioreactors) isconnected to a server with all control functionalities installed onit (SCADA). Control loops and recipes are used for this group only.Additional unit operation groups may use another server systemor use local package unit functionalities.ServerPU-01Measurement data from all individual systems can be transferredto one server which enables centralized data handling.PU-02This classical approach has lower investment costs and is oftenused in pilot plants and small facilities.IntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutPU-03AutomationStandardCD PackageSUCCESS

AutomationPROCESSSUCCESSPackage-Units Integrated into a Distributed Control SystemAll control and data acquisition functionalities are integratedtop to bottom. Parameter settings, recipes, as well as batchmanagement control loops are distributed on a plan-wide level.Implementing a single control platform across all plant applicationsprovides a number of advantages, including more synchronizedprocesses, increased reliability, reduced maintenance efforts andseamless transfer of real-time data for improved decision-makingand increased manufacturing flexibility.Distributed control systems are to those seeking a state of the artautomation system driven by the process state.IntroductionMass BalanceReviewProcess PU-07PU-03PU-04PU-06PU-05AutomationStandardCD Package

AutomationPROCESSExample of a DCS NetworkDCS with Package Unit integration– Central process Historian– Central batch reporting– Central recipe systemRedundantOS ServerRedundantDCS CPUHistorianTFFSTRIntroductionRedundantBatch & RecipeServerMass BalanceReviewProcess FlowDiagramSIMCAonline ServerDCS ClientFAProcessLayoutAutomationStandardCD PackageSUCCESS

Standard CD PackagePROCESSA concept design study from Sartorius will provide insight toyour process and new production facility within 8 weeks time.IntermediateMeetingWeek 1Week 2At the end of the study a handover package will be generatedcontaining all information needed for a smooth projectexecution.IntermediateMeetingWeek 3Week 4IntermediateMeetingWeek 5Week 6Week 7Week 8Handover Closing MeetingProjectManagementKick OffWorkshop #1IntroductionWorkshop #2SUCCESSWorkshop #3Workshop ain Doc:ProjectDescriptionMain Doc:ProcessDescriptionMain Doc:UtilityDescriptionMain Doc:Process LayoutDescriptionProjectExecution PlanSUSICUtilityRequirementMatrixProcess LayoutPlanProjectOrganogramMass BalanceReportCIP SIP StrategyProcess LayoutClassificationPlanMass Balance ApprovalFacility Design ApprovalProject ScheduleProcessSchedulingProcess LayoutFlow Plan– Optimized Scenario– Process SolutionTotal EquipmentCost*Process FlowDiagramProcessEquipmentArrangement Plan– Process Flow Diagram– Buffer ConceptTotal ConsumableCost*MainEquipment List3D Visualization– Equipment List– Automation ConceptMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationMainConsumable ListStandardCD PackageQualityEngineeringCommissioning& QualificationStrategyAut

Standard CD issioning& QualificationStrategyMain Doc:ProjectDescriptionMain Doc:ProcessDescriptionMain Doc:UtilityDescriptionMain Doc:Process LayoutDescriptionProjectExecution PlanSUSICUtilityRequirementMatrixProcess ass BalanceReportCIP SIP StrategyProcess LayoutClassificationPlanUMETRICSProject ScheduleProcessSchedulingProcess LayoutFlow PlanTotal EquipmentCost*Process FlowDiagramProcessEquipmentArrangement PlanTotal ConsumableCost*MainEquipment List3D VisualizationMainConsumable ListIntroductionAutomationMass BalanceReviewProcess FlowDiagramMain Doc:AutomationDescriptionAdd OnProcessLayoutAutomationStandardCD PackageSUCCESS

IntroductionIntroductionPROCESSDesigning a New Manufacturing Facilityfor BiopharmaceuticalsMass BalanceReviewMass Balance ReviewSUCCESSPROCESSProcess FlowDiagramSUCCESSProcess Flow DiagramN-2 RockingN-3 MotionShakes:s Driverch?Proces?ign approahybridl Campause orsinglel FullyN-1 Stirred Tank ReactorProduction BioreactorProcess ESSProtein A Affinity chromatographyDetail DesignProductionERPPage 10Process FlowDiagramProcessLayoutAutomationStandardCD PackageIntroductionPROCESS3. Evaluation andoptimizationof the processesProcess 1N-3 Shake FlaskSUCCESSProcess FlowDiagramMass BalanceReviewProcessLayoutAutomationStandardCD PackageSupply to Return ConceptMobile Buffer ConceptFuturistic Dance Floor Ballroom Concept– Unidirectional Flow– Less traffic– Bidirectional flow– High traffic– Reduce walls and airlocks– Operational flexibilityIntroductionProcess Flow DiagramPROCESSMass BalanceReviewProcessLayoutProcess FlowDiagramAutomationl Equipment Listl Selection of theautomation concept2. Descriptionof the processparametersas input forthe modellingtooll Process layoutIntroductionPROCESSMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackageScenario 1Binding capacity50 g/LColumn height20 cm45 cm60 cm320 cm/h320 cm/hPROCESSIntroductionPROCESSEquilibration5 CV10 CV10 CV5 CV5 CVRegeneration buffer 5 CV5 CVIntermediateMeetingKick OffWorkshop #1AutomationCell CultureWeek 3Week 4Workshop #2Week 5Week 6CD HandoverWeek 7IntroductionSUCCESSWorkshop #3l Sartoclear DynamicsMass Balance ApprovalBinding capacityl IEX resin (Flow through)l IEX membrane (bind and elute)l IEX membrane (flow through)50 g/L50 g/LColumn height20 cm20 cmColumn Diameter45 cm60 cmFlow rate320 cm/h320 cm/hProcess FlowDiagramMass BalanceReviewProcessLayoutAutomationProcess FlowDiagramIntroductionPROCESSMass BalanceReviewAutomationStandardCD PackageProcess LayoutSUCCESSPROCESSAdjacency of certain process areas is key for streamlinedprocessing. Static equipment near to next process unit reducesmovement of tanks and the length of tubing’s.07 June 2018UtilityRequirementMatrixCIP SIP StrategyProcessLayoutMain Doc:Process LayoutDescriptionQualityEngineeringCommissioning& QualificationStrategyAutomationMain Doc:AutomationDescriptionProcess LayoutPlanAutomationArchitectureProcess LayoutClassificationPlanUMETRICSProcess LayoutFlow PlanProcessEquipmentArrangement Plan3D VisualizationProcess FlowDiagramProcessLayoutAutomationIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutPage 407 June 2018AutomationAdd OnSUCCESSProcessInterfaceProcessLayoutMain Doc:Process LayoutDescriptionQualityEngineeringCommissioning& chitectureServerCIP SIP StrategyUMETRICSProject SchedulePU-07Mass BalanceReviewProcess FlowDiagramPU-04Total EquipmentCost*PU-06Total ConsumableCost*ProcessSchedulingProcess LayoutFlow PlanProcess FlowDiagramProcessEquipmentArrangement PlanMainEquipment List3D VisualizationAutomationProcessLayoutMainConsumable ListStandardCD PackageIntroductionPROCESSMain Doc:AutomationDescriptionMass BalanceReviewProcess FlowDiagramAdd OnProcessLayoutAutomationStandardCD ntrollerControllerServerPU-01PU-01Implementinga allsinglecontrolplatformacrossall plant applicationsdatafromindividualsystemscanThis basicMeasurementapproachis anidealsolutionfora processwitha be transferredprovidesa numberadvantages,includingmore synchronizedto ofoneserverwhichenables ofcentralizeddatahandling.limited setparameters.processes, increased reliability, reduced maintenance efforts andseamlesstransferreal-timedata forimproveddecision-makingThis classicalapproachhasoflowerinvestmentcostsand is oftenand plantsincreasedused in pilotandmanufacturingsmall U-08PU-03PU-02PU-07Distributed control systems are to those seeking a state of the artautomation system driven by the process state.PU-03PU-04PU-06PU-05Page 4l Less traffickingl Adjacency & wall area requirementStandardCD PackageIntroductionMass BalanceReviewProcess FlowDiagramProcessLayoutAutomationStandardCD PackageIntroductionMass BalanceReviewProcess FlowDiagramMass neeringProcess LayoutPlanPU-08Buffer Prep& DistributionCombined preparation and storageStandardCD PackageProcess LayoutClassificationPlanl Plant wide process visualizationwith batch and recipe controlAutomationAll control, reporting,recipe and unit operations are localizedPackage-Unitswith Server Client SCADA Systeminto one system called the “package-unit”. This includes allparameter settings for unit-based control loops as well as recipes.A group of unit operations or clients (e.g. all bioreactors) isPackage-UnitsIntegratedinto a DistributedControlto a dataserverwithcontrol functionalitiesinstalled onAcquiredconnectedmeasurementcanbe alltransferredto a higher levelit (SCADA). Control loops and recipes are used for this group only.via OPC connectivity.All control and data acquisition functionalities are integratedtopunitto bottom.Parametersettings,recipes,serveras wellas thersystemThe autonomousprocessunits, requireindividualmanagementcontrolloopsare distributedor uselocalpackageunitfunctionalities.and 21 CFR11 reportsare onlypossibleper individualunit. on a plan-wide level.Post ViralPurification &Bulk filtrationAutomationMain Doc:UtilityDescriptionPU-03l Remote control of groupl Central Unit ReportsIntroductionMass Balance ionStand Alone Package-UnitsMedia Prep& DistributionHarvestSeparated preparation ready madeStandardCD PackageProcess FlowDiagramSUSICAutomationSUCCESSInoculationCell CultureFitting the facility around the equipment rather than theequipment around the facilityl Lower room classification in distribution areaMass BalanceReviewIntroductionMain s FlowDiagramPU-02l Individual local controll Data transfer via OPCIntroductionPre ViralPurificationFinal UF DFStandardCD PackageProcessInterfaceMain Doc:ProcessDescriptionMass BalanceReportMainEquipment ListMainConsumable ListMain Doc:ProcessDescriptionl Plug-and-Play capabilitiesProcessLayoutProcess FlowDiagramAdjacency Bubble DiagramBulk Fill and Finish– Buffer ConceptAutomationStandardCD PackageMass BalanceReviewPU-05As most DSP steps require largebuffer volumes, the processlayout is highly impacted bythe buffer preparation anddistribution concept.– Automation ConceptProcessLayoutProcessEngineeringMass BalanceReportPU-01PU-02PU-03Buffer Distribution Conceptl More challenging with large buffer volumesMass BalanceReviewTotal EquipmentCost*ProjectOrganogramPU-02Nano FiltrationFacility Design Approval– Process Solution– Process Flow Diagram– Equipment ListIntroductionMain Doc:ProjectDescriptionProjectExecution PlanProject SchedulePU-09PU-01HarvestSingle-use technology offersflexible new options for bufferconcepts. Two examples can beseen on the right.Scenario 1 Scenario 2l IEX resin (bind and elute)Low pH Virus InactivationCation Exchange chromatographyAnion exchange Membrane Adsorber– Optimized ScenarioModel parameters to optimize bufferrequirements and equipment sizesl 2 Stage Depth Filtrationl Centrifugation Depth FiltrationProtein A Affinity chromatographyWorkshop #4Handover Closing MeetingTotal ConsumableCost*Main Doc:ProjectDescriptionSupport AreaPage 11Process Flow DiagramEvaluate the impact of differenttechnology options on your processN-1 Stirred Tank ReactorWeek 8Week 8Workshop #4ProjectExecution PlanControllerPU-01l Total process area required:1200 – 1500 m2StandardCD PackagePROCESSN-2 Rocking MotionIntermediateMeetingProduction BioreactorWeek 2ProcessLayoutN-3 Shake FlaskIntermediateMeeting2 Stage Depth FiltrationWeek 1Week 7– Automation ConceptPackage-Units integrated intoa Distributed Control Systeml ISO9 Grade D: 625 – 750 m2Process FlowDiagramProcess DescriptionLevel A time schedule based on Deliverables ActivitiesWeek 6Workshop #3Facility Design Approval– Process Solution– Buffer Concept– Equipment ListProjectManagementPackage-Units withServer Client SCADA SystemControllerl ISO8 Grade C: 175 – 250 m25 CVPost Load Wash 1Mass Balance ReviewSUCCESSProject Schedule Time ScheduleWeek 5– Optimized Scenario– Process Flow DiagramStandard CD PackageSUCCESSIn general there are 3 different automation concepts that can beapplied in manufacturing facilities. At Sartorius we guide you tothe best approach for your unique situation.Stand Alone Package UnitsGuidance for 2 2000 L STRs:6. Advanced options- Economic Modelling- Detailed SchedulingBuffersElution BufferIntroductionAutomation Concepts OverviewMedia Prep & DistributionPre Viral PurificationBuffer Prep & DistributionSupply CorridorServer4. Process flowdiagram incl.equipmentScenario 250 g/L20 cmColumn DiameterFlow rateStandardCD PackageReturn CorridorCharacteri

The process layout must full fill cGMP & regulatory principles and will consider personnel, material, product and waste flows. Different concepts have been generated and optimized for common single use and hybrid projects. Color Codes: cess Automation ay ut Process Flow Diagram Mass Balance