The document proposes a concept for purifying monoclonal antibody protein (MabP) using a biotech plant. Key aspects of the concept include:
1) The process uses various equipment like harvest tanks, centrifuges, filters, chromatography columns, and ultrafiltration to purify 60% of the MabP from whole cell broth in 31.7 hours per batch.
2) A plant layout places the equipment within the purification hall in a way that optimizes space and minimizes piping while meeting the batch time requirement.
3) An economic analysis estimates the breakeven selling price of the purified MabP would be $19,830/kg to recoup the $20.065 million
1. AVERAGE MABP PROCESS
Mini Design Project: Goal 1
Luke Boustred, JasmineIreneTabatabai, Travis Van De Veer
CHEN 4520
December 04, 2015
2. 1
Contents
Executive Summary ............................................................................................................................2
Introduction.......................................................................................................................................3
Concept.............................................................................................................................................4
Equipment List................................................................................................................................4
Plant Layout...................................................................................................................................5
Process Narrative............................................................................................................................6
Process Flow Diagram.....................................................................................................................8
Equipment Occupancy Chart ...........................................................................................................9
Discussion of Concept.......................................................................................................................10
Additional Assumptions.................................................................................................................10
5th, 95th, average values ..............................................................................................................10
% Occupancy................................................................................................................................11
DFC table/method ........................................................................................................................12
Unit Operating Cost......................................................................................................................12
Sensitivity of Break Even Price.......................................................................................................13
References.......................................................................................................................................15
Appendix..........................................................................................................................................16
A: Monte Carlo Histograms...........................................................................................................16
B: Economic Evaluation Data.........................................................................................................18
3. 2
ExecutiveSummary
The major goal of thisprojectwasto appropriatelysize andmodel the purificationprocessorMabP.
SizingwascalculatedusingMonte Carlosimulationandthe simulationwascreatedinSuperPro. The
layoutof the purificationhall,includinggreyspace,wasprovidedandthe teamplacedall necessary
piecesof equipmentwithinthe givenarea.The necessaryequipmentneededtopurifythe wholecell
broth wasspecified,while anyspecificinformationregardingequipmentwasdetermined,eitherfrom
Monte Carloor the data basesin SuperPro. Informationwasgivenregardingthe cell culture process
aheadof the purificationhall,includingthe total volume leavingthe cell culture hall andthe costs
involvedinthe culture hall.
The concept the teamproposesisable toretain60%, or 36.02 kg/batch,of the total MabP that is
broughtintothe purification hall.The total processtakes31.70 hours perbatch, notincludingthe
change outs of the diafiltermembraneandcolumnpackingresinevery50 batches.The plantthat
housesthe purificationhall canbe purchasedforbetween$70MM-100MM and the teamdetermined
the breakevensellingprice forthe MabPin orderto breakevenin15 years.The breakevenprice
determinedwasapproximately$19,830/kg of antibody.
In the reportthat follows,the specificpiecesof equipmentare listed.The purchase costsandinstallation
costs were determinedfromSuperProbasedonsizinginformationcalculatedandinputtedbythe team.
Alsoincludedisato-scale layoutof the purificationhall witheachpiece of equipmentplaced inthe
appropriate locations.The teamdraftedaprocessnarrative tolayout the specificvaluesassociatedwith
each stepinthe purificationprocess.Thisisaccompaniedwithaprocessflow diagramof the entire
purification,startingwiththe harvesttankthe whole cell brothsitsinafteritisculturedandendingwith
the ultrafiltrationpool tank.
The schedulingforthe processwassetup withthe specificationthatthe purificationprocessmusttake
lessthan48 hours as the bioreactorsproduce new batchesevery2days;the purificationhall mustbe
able to keepupwiththe culture hall withoutbackingupthe entire process. Inconsiderationof this,the
calculatedbatchtime was31.7 hrs,allowingfora5 hr slack period.
The significant5and 95% valuesfromthe Monte Carlosimulationaswell asthe average valuesare
listedinthe report.These valueswereusedtoensure thatthe equipmentdidnotexceeditsspecified
turndown. Onlythe chromatographycolumnfailedtomeetthe requiredturndown,andtoavoid
nonuniformflow,twocolumnsare recommended.
Lastly,thisreportcontains an economicevaluationof the proposedprocess. The calculateddirectfixed
cost was$20.065 MM, and breakevenata $0 netpresentvalue after15 years,the MabP shouldbe sold
at $19,834/kg. A sensitivityanalysiswasconductedtodeterminethe effectthe directfixedcost,
productionrate,andplantpurchase price have on the breakevenprice given15yearsto breakeven. The
resultsshowedthatthe numberof batches harvested peryearhadthe biggestimpactof the breakeven
price of the MabP.
4. 3
Introduction
The purpose of thisinvestigationistodetermine whetherornotto purchase a biotechplant, PlantB,
usedto make recombinantprotein.While the cellculture hall andutilitiesbuildingof PlantBare usable,
the purificationhall containsobsolete equipment,includingsolutionholdtanks.These deviceswillneed
to be replacedinorderto produce the protein.The plantwill be usedtoproduce MabP.In orderto
determine the feasibilityof equippingandrunningthe plant,specificallythe purification hall,a
simulationwasdeveloped.Equipment,economics,andschedulingwere alsoexaminedtodetermine
profitabilityusingthe plant.ItisexpectedthatplantacquisitiontoMabP productionwill take 24
months.
In the followingreport,we identifiedthe neededequipmentandeachfunctioninthe purificationhall.
The cell culture hall containsseven15000L bioreactors.One bioreactorwillbe harvestedforpurification
every48 hours. The culture istransferredfromthe culture hall toa harvesttank inthe purificationhall.
The culture goesthroughthe followingpurificationsteps:centrifugation,inlinefiltration,
chromatographycolumn,anddiafiltration.
There are three specificationsthatmustbe metin orderfor the proposedprocesstobe viable.In terms
of MabP coverage,atleast90% of the processesinthe purificationhall mustbe accommodatedbythe
proposedconcept.Extreme large orsmall processeswouldrequire additionalcapital,engineering,and
technology.The equipmentforthe purification processmustall fitinthe hall,which includeshaving
sufficientextraspace formaintenance andwheelingcolumns,aswell as the pipingthatconnectsthe
tanksand the purificationequipment. Equipmentmustnotbe packedintothe hall fromwall towall and
each piece shouldbe placed tominimize the pipingbetweenequipment. All equipmentinthe proposal
can be foundinthe purificationhall exceptforsolutiontanks.Finally,the characteristicturndownmust
not be exceededforeachpiece of equipment.If aprocessdoesexceedthe specifiedturndown,then
more than one piece of equipmentmaybe needed.
Full capacityfor thisplantmeansrunning24 hours a day,7 daysa week,for300 daysa year.This
correlatestoa yieldof 150 bioreactorharvestsperyear. In termsof cost projection,thereisnonew
capital neededforthe bioreactorhall.Non-WFIutilitiesandwaste treatmentcostsare negligible
comparedto othercosts.An estimated40staff membersare requiredforthe culture hall.
The purificationhall is8000 ft2
total.This includesthe mechanical (grey)space.Greyspace isusedfor
solutiontanks,whilethe purificationroomholdsall processingequipment.
5. 4
Concept
Equipment List
Table 1: Equipment SizingandCost
ID Number Type Size Construction
Material
Purchase
Cost ($)
Installation
Cost ($)
Comments
001 Harvest Tank 16666.67 L SS316 264,000 79,200
002 Disk-Stack
Centrifuge
15000 L/h SS316 186,000 93,000
003 Centrate Pool
Tank
14654 L SS316 256,000 72,000
004 InlineFilter 17 m2 SS316 59,000 29,500
005 Column
System
1870 L SS316 1,835,000 91,750 2 columns are
needed to ensure
solution meets
minimum height in
col
006 Column Pool
Tank
8220 L SS316 244,000 73,200
007 Ultrafiltration
System
53 m2 SS316 114,000 44,500
008 UF Pool Tank 562 L SS316 167,000 50,100
009 Solution C
Tank
25560 L SS316 293,000 87,900 One solution C tank
is used to fed all
processes that
require cleaning
010 Solution D
Tank
6269 L SS316 235,000 70,500
011 Solution E
Tank
14542 L SS316 256,000 70,500
012 Solution Q
Tank
14542 L SS316 256,000 70,500
013 InlineFilter
Cartridge
17 m2 Polypropylene 1,250 N/A
014 Diafilter
Membrane
59 m2 Polysulfone 114,000 N/A Must be replaced
every 50 batches
015 Resin A 583.30 L Agarose 5,249,700 N/A Must be replaced
every 50 batches
The purchase costs fromTable (1) were determinedfromSuperProbasedonthe sizinginformationthe
teamcalculatedandinputtedinthe simulation.The type of eachpiece of equipmentwasspecifiedin
the problemstatement. SuperProrecommendedSS316stainlesssteelforall tanksandprocessing
equipment.
6. 5
Plant Layout
Figure 1: Purification Hall Layout
The layoutof the plantwas designedtooptimize movingspace inbothrooms,aswell asto minimize the
lengthof pipingrequiredtoconnectthe differentprocesses.Ithadbeenrecommendedthatthe
solutionCtank(number13) be on wheels,asitisdistributedtomanydifferenttanksthroughoutthe
process.However,due toitssheersize (2.21m diameter,6.64 m height) relocatingthispiece of
equipmentthroughoutthe processiscumbersomeatbest,anddangerousat worst. Consequently,itis
recommended thatpipingisrunfromthe solutionCtankto all the processesthatrequire the cleaning
agent. Thissetupsavestime asthe tankneednotbe relocated betweenprocesses,anditcan be
distributedtomultiple tankssimultaneously,thusmeetingschedulinggoalsinFigure (3).Tothisendthe
solutionCtankwas centrallylocated. Lastly, atleast1 meterof space was leftbetweenequipment
pieces,permittingbothoperatingspace andrepair/servicingspace asnecessary.
7. 6
Table 2: Equipment in Plant Layout
Number Name Height(meters) D (meters)
1 HarvestTank 5.76 1.92
2 Centrifuge Flow:1500 L/hr Sigma= 32450 m2
3 Centrate Pool Tank 5.52 1.84
4 DeadEnd Filter 2 x 5 FilterArea:17 m2
5 SolutionETank 5.50 1.83
6 SolutionQTank 5.50 1.83
7 Chromatography
Column
BedHeight=0.5 2.18
8 ColumnPool Tank 4.55 1.52
9 SolutionDTank 4.16 1.39
10 WFI Tank 3.35 1.115
11 DiafiltrationSystem Area= 59 m2
Dimensions=7.5 x 8
Volume =350 m3
12 MicrofiltrationPool 1.86 0.62
13 SolutionCTank 6.64 2.21
Basedon the sizinginformationof all the equipmentandato-scale sample tank,all solutiontankswere
placedinthe grey space of the purificationhall ascan be seeninFigure (1), while all otherpiecesof
equipmentwereplacedinthe purificationroom.There is ample roomwithall the equipmentinthe hall
to ensure thatthe appropriate wiringandpipingcanbe accommodated.
ProcessNarrative
Referringtothe plantlayout guide, Table (2),the whole cellbrothwill travel fromthe bioreactorhall
and be fedto HarvestTank (001) at 15000 L/batch, or 1500 L/hr. The WCB has an average concentration
of 4 g/L. The centrifuge (002) isflushedwith1500 L of WFI for1 hour. The WCB is thencentrifugedfor
10 hours.The solidsstreamissenttowaste,while the productstreamistransferredtothe Centrate
Pool Tank (003) for holding.The centrifugeisthenflushedwith750L of PW for 0.5 hours.The centrifuge
iscleanedwith200 L of cleaningsolutionCfor1 hour,and there isa final WFIflushwith750 L for0.50
hour.A total of 13071 kg of buffersolutionand52 kgof MabP leave the centrifuge.
The inline filter(004),before receivingthe centrate,isflushedwith340 L of WFI for2 hours. The
volumetriccapacityof the filteris3000 L witha surface areaof 2.5 m2
.None of the proteinislost
throughthe filter, asit removestrace impurities.Once all of the MabPsolutionpassesthrough,the filter
iscleanedwith170 L of SolutionCfor1 hour.This isfollowedbyasecond340 L WFI flush.
Aheadof receivingthe MabPsolution, the twopackedbedadsorptionchromatographycolumns(005)
are equilibratedwith7486 L/hof solutionCfor74 minutes. Note that,forsimplicity’ssake,the two
columnsare modeledasone largercolumn. The columnsare thenloadedwithMabPsolution.The
maximumloadingof the columnis45 g of MabP fedto the columnperpackedL of column.Underthese
specifications,each columnis938 L. When runningatthe average processflowrate,bothcolumnsare
required. The columnisthenflushedwith7486 L/hr of solutionQfor30 minutestoremove any
nonbindingimpurities.The MabP boundto the columns iselutedwith13087 L of solutionEoverthe
course of 1.17 hours.The average volume of elutantinthe productstreamis3.5 L inthe columnpool
8. 7
perL of column,givingavolume of 4000 L. The columnpool is collectedinthe columnpool tank(006).
Once the MabP solutionleavesthe column,the columniscleanedwith9403 L/h of solutionCfor 1 hour.
The ultrafiltrationsystem(007) isinitiallyflushedwith1200 L for 30 minuteswithWFI;bothretentate
and permeate are senttowaste.Next,itisequilibratedwith588.6 L of solutionDfor 30 minutes.The
MabP is concentratedbycirculatingfromthe columnpool tankthroughthe UF system;retentate is
circledback tothe tank. To achieve the desiredconcentrationof MabP,a concentrationfactorof 13 is
used. The max membrane loadingis58858 g of MabP for 58.858 m2
of membrane areaof the
membrane.Once the targetconcentrationof 85 g/L is met,the MabP is diafilteredfor3.4hours.
SolutionDisfedto the ColumnPool tankto keepthe concentration constantaspermeate leaves. The
antibody istransferredoutof the UF systemat 25⁰C intothe UF Pool Tank (008). The UF systemis
flushedwith70629 L forof WFI 30 minutesthencleanedwith294.3L of solutionCfor 1 hourintotal
recycle mode;bothpermeate andretentate returntoUFcirculationtank.
9. 8
ProcessFlowDiagram
Figure 2: Process Flow Diagram
The flowof MabP inthe purificationhall isseeninthe processflow diagramin Figure (2).SolutionTanks
will be heldinthe mechanical areawhile all otherequipmentwillbe usedinthe purificationareaasper
Figure (1).
10. 9
Equipment Occupancy Chart
Figure 3: Equipment Occupancy Chart (EOC)
The total time fromforeach batch is31.70 hours,as seeninFigure (3).Fromthe problemstatement,48
hoursmust be allottedafterevery50batchesfor the unpacking,packing,andintegritytestingof the
chromatographycolumn.Removingandinstallingthe columntakes8hours.RemovingoldUF
membrane cassettes,installingnewcassettes,testingthe integritytesting,andsystemcleaningrequires
24 hours andmust to be done every50 batches. Aftereverybatch,2 hoursmust be spentremovingthe
inline filtercartridgesandcleaningthe system. Toillustrate the usage of twochromatographycolumns,
a staggeredsetupwasimplementedforscheduling.Thisisnotentirelyreflectiveof the actual process
however,asbothcolumnscan be usedsimultaneouslyif there isahighflowrate tothe column.
11. 10
Discussion of Concept
Additional Assumptions
The average MabP processis profitable.
The average MabP processdoesnot change propertiesof the processrelativetothe actual
process.
The maximumworkingtovessel volume ratiois 90%,and wasappliedtoeveryvessel andpool
tank
For goal one,the compositionandconformationof the proteinisnotalteredinanysignificant
way
The MabP wasassumedtobind100% to the ProteinA resininthe chromatographycolumn.
The yieldlossduringthe concentrationand ultrafiltrationstepsisdue toMabP coatingon the
membrane,andisunavoidable.
5th, 95th, average values
Table 3: Monte CarloValues
Process 5% Value 95% Value Average Value
MabP in Centrate (g) 34435 70086 52445
Centrifuge -Sigma(m2
) 26513 32418 29279
Volume of Column(L) 706 1876 1211
Volume ColumnPool
(L)
2038.5 7466.7 4001.9
Inline FilterVolume
(m3
)
1950 4400 2850
MabP ColumnPool (g) 24085 50077 36647
Volume of UF(L) 235 534 372
Table (3) laysoutthe importantMonte Carlovaluesusedinsizingthe equipment. Specificturndown
informationwasgivenforeachpiece of equipment.Thisturndowndataensuredthatthe equipmentis
able to processthe valueswithinthe 5-to-95zone. Again,the lower5% may not be profitable or
worthwhile,andthe upper5%may require large equipment,capital,orengineeringthatisnotfeasible.
Equipment Turndown
It isimportantthat the processequipmentstaywithineach’srespective appropriate operating
conditions.Mostly,thisistoreduce the riskof processfailure, orhavingthe equipmentbreak;reasons
for eachturndownspecificationare includedbelow inTable (4).Topass the equipmentturndown,the
95%/5% ratio of equipmentsize mustbe lessthanthe turndownvalue.Shouldthe equipmentfail the
turndowntest,the equipmentwassplitintotwounitsof equal total size.
12. 11
Table 4: Equipment Turndown Test Requirements
Equipment
Type
Parameter Units Turndown 95%/5%
size
Pass/Fail Remark
DiskStack
Centrifuge
FeedVol.
Flowrate
L/min 10 1.44 Pass
ColumnControl
System
Vol.
Flowrate to
Column
L/min 7 1.44 Pass Limitedbypump&
flow control
ColumnSize Packed
Height
Cm 2.5 2.66 Fail Limitedbyflow
uniformityand
pressure drop.Need
twocolumns.
UF System Membrane
Area
m^2 4 2.27 Pass Limitedby turndown
of feedtopumpto
membrane holder
Centrate Pool
Tank
LiquidVol L 7 3.62 Pass H/D about 1.5
ColumnPool
Tank
LiquidVol L 7 3.61 Pass H/D about 1.5
Microfiltration
Pool Tank
LiquidVol L 7 2.3 Pass H/D about 1.5
Dome-type
filterhousing
FilterArea m^2 10 2.24 Pass Limitedbylow
recoveryof filtrate due
to highfloodedvolume
inhousing
As notedinTable (4) above,the chromatographycolumnisthe onlypiece of equipmenttofail the
turndowntest;everyotherpiece of equipmentpasses byarelativelysignificantmargin.Because of this
failure,the columnmusthave itsrequiredvolume dividedamongsttwosmallercolumns.
% Occupancy
Table 5: Percent Occupancy of each piece of equipment
Equipment % Occupancy
HarvestTank 38.90
Centrate Pool 50.66
Centrifuge 35.18
Inline Filter 16.89
ChromatographyColumn 14.72
ColumnPool Tank 33.86
Diafilter/Ultrafilter 22.57
UF Pool 29.05
The sum of eachequipmentpercent inTable (5) doesnottallyto 100% because some processes(suchas
steaminplace and cleaninplace) couldbe startedwhile the MabPsolutionwasinthe previousstep.
13. 12
The above table laysout the time eachpiece of equipmentisinuse as a percentof the total time a
single batchtakes.
DFC table/method
The estimatedDirectFixedCost(DFC) is$20,565,450. The DFC, as seenin Table (5),isthe sumof the
purchase costsfor all the equipment,the costtomake the equipmentfunctional,the costof
engineeringandconstruction,andthe contractor’sfee.The purchase andinstallationcostsforthe
equipmentinthe purificationhall canbe found inTable (1).
Table 6: Breakdown of Direct Fixed Cost
Element Cost (MM$)
Equipment 5.209
Installation 1.384
Process Piping 1.823
Instrumentation 2.084
Insulation 0.156
Electrical 0.521
Engineering 2.294
Construction 3.912
Contractor’sFee 0.894
Contingency 1.788
TOTAL 20.065
See Appendix(B) forthe EconomicEvaluationfromSuperPro.
Unit Operating Cost
Table 7: Breakdown of Unit Operating Cost
Element Cost ($/harvest)
OperatorLabor/Maintenance(Culture Hall) 26,700
OperatorLabor/Maintenance(PurificationHall) 1,571,900
Capital Depreciation 1,988,100
Raw Materials+ Consumables(Culture Hall) 75,000
Raw Materials(PurificationHall) 6,018,000
Consumables(PurificationHall) 52,110,000
Utilities 13,000
Waste Treatment/Disposal 57,000
Laboratory/QC/QA 236,000
TOTAL 62,095,700
14. 13
The total unitoperatingcost, Table (7),includesthe variablecostsperbatch. Capital Depreciationwas
determinedbymultiplyingthe capital cost($20.93MM) bythe salvage value (5%) andsubtractingthe
salvage costfrom the capital cost.This value wasthenmultipliedbythe depreciationrate (10years
10% depreciation) togeta capital depreciationvalue of $1.99 MM. The raw materialsandconsumables
costs forthe culture hall were giveninthe problemstatementwhile the raw materialsandconsumables
costs forthe purificationhallwere determinedfromSuperProafterinputtingcostsperunitforeach
element,ie $/Lforsolutionsand$/size forconsumables. The costto dispose of all the solutions(C,D,E,
Q, WFI) was $0.003/kg of solution.The total waste was190MM L so the total cost was$57M.
Sensitivityof Break Even Price
From usingthe pricesof equipmentaswell assolutionpricesinSuperPro,itwasfoundthatMabP must
be soldat a cost of $19,834/kg to have a NPV of approximately $0at a 20% interestrate over15 years. It
shouldbe notedthatthe resolutionforall of the followingbreakevenpriceswassuchthat
-$10,000 < NPV < $10,000. The relative sensitivitywasfoundbyvaryingparameterssuchasDirectFixed
Cost,productionrate in termsof harvestperyear,and the cost to purchase plantB all withinthe
Superprosimulation.Itwasfoundthatthe breakeven costwasmostdependentonthe batches peryear
produced. Table (7) showsthe adjustmentsof breakeven price thatmustbe made bychangingthese
variables.
BatchesPer
Year
BreakEven
Price ($/kg)
PlantPurchase
Price ($MM)
BreakEven
Price ($/kg)
DirectFixed
Capital ($MM)
BreakEven
Price ($/kg)
50 36,855 70 18,457 25% = 5.141 18,546
100 23,976 80 19,274 50% = 10.282 18,975
150 19,834 90 20,091 100% = 20.565 19,834
200 17,535 100 20,908 150% = 30.848 20,692
200% = 41.130 21,551
Table (7): Sensitivity Analysis Break Down
Figure (4) showsthe breakevenprice of MabP as a functionof the numberof batchesperyear
produced.Ascan be seen,increasingthe amountof batchesperyeardecreasesbreakevenprice. The
average schedule callsfor150 batchesper year.
Figure (4) demonstratesthe greatdependencyof breakevenprice onthe numberof batches
harvestedperyear.Of the three variablestested,thisisthe onlyone tonothave a lineardependency.
Althoughthe productioniscappedat150 batchesa yeardue to scheduling, itisnoteworthytosee what
price the MabP wouldhave to be soldfor at 200 batchesa year.
15. 14
Figure 4: Sensitivity of the breakeven price with respect to the number of yearly batches
Figure (5) showsthe dependenceof breakeven price withrespecttoplantpurchase price.Aspurchase
price increases,breakevenincreasedaswell. $85 MM was the average price usedwhenvarying the
othertwo conditions.
Figure 5: Sensitivity of the breakeven price with res pect to the plant purchase cost
Figure (6) showsthe sensitivityanalysisof breakevenprice withrespecttoDirectFixedCost.Asthe DFC
capital increases,breakevenprice alsoincreases. Lastly,the calculatedDFCof $20.065 MM was used
whenvaryingthe othertwoconditions.
$-
$5,000.00
$10,000.00
$15,000.00
$20,000.00
$25,000.00
$30,000.00
$35,000.00
$40,000.00
0 50 100 150 200 250
BreakevenPrice($/kg)
Batches Harvested per Year
$18,000.00
$18,500.00
$19,000.00
$19,500.00
$20,000.00
$20,500.00
$21,000.00
$21,500.00
60 70 80 90 100 110
BreakevenPrice($/kg)
PurchasePriceof Plant
16. 15
Figure 6: Sensitivity of the breakeven price with respect to the Direct Fixed Cost
References
Productand ProcessDesignPrinciples,3rdedition,byW.D.Seider,J.D.Seader,D.R Lewin,andS.
Widagdo,JohnWiley(2009).
CHEN 4520 Customtextbook,JohnWiley(2014).
$18,000.00
$18,500.00
$19,000.00
$19,500.00
$20,000.00
$20,500.00
$21,000.00
$21,500.00
60 70 80 90 100 110
BreakevenPrice($/kg)
PurchasePriceof Plant
17. 16
Appendix
A: Monte Carlo Histograms
0.00%
50.00%
100.00%
150.00%
0
50
100
150
200
250
26.6846…
31.8515…
37.0183…
42.1852…
47.3520…
52.5189…
57.6857…
62.8526…
68.0194…
73.1863…
More
Frequency
Bin
Mass of MabP in Centrate (kg)
0.00%
50.00%
100.00%
150.00%
0
100
200
300
17.153…
21.052…
24.950…
28.849…
32.748…
36.647…
40.546…
44.445…
48.344…
52.243…
56.142…
60.041…
Frequency
Bin
Mass of MabP in Column Pool
(kg)
0.00%
50.00%
100.00%
150.00%
0
100
200
300
455.744…
664.624…
873.504…
1082.38…
1291.26…
1500.14…
1709.02…
1917.90…
2126.78…
2335.66…
More
Frequency
Bin
Volume of Chromatography
Column (L)
0.00%
20.00%
40.00%
60.00%
80.00%
100.00%
120.00%
0
100
200
300
400
999.0404…
2038.489…
3077.938…
4117.387…
5156.835…
6196.284…
7235.733…
8275.182…
9314.631…
10354.08…
11393.52…
12432.97…
Frequency
Bin
Volume of the Column Pool (L)
0.00%
50.00%
100.00%
150.00%
0
100
200
300
152.4…
211.0…
269.7…
328.4…
387.0…
445.7…
504.4…
563.0…
621.7…
680.4…
More
Frequency
Bin
Volume of DiafiltrationSolution
(L)
0.00%
20.00%
40.00%
60.00%
80.00%
100.00%
120.00%
0
50
100
150
26250.40…
26775.30…
27300.21…
27825.11…
28350.02…
28874.92…
29399.83…
29924.74…
30449.64…
30974.55…
31499.45…
32024.36…
32549.27…
Frequency
Bin
Sigma (m2)
