Latest Advances in TFF

8/8/2019 Latest Advances in TFF

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Advanced Degrees of SeparationAdvanced Degrees of SeparationAdvanced Degrees of SeparationAdvanced Degrees of Separation


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Latest Advances

in

for

Separation and Concentration


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The NCSRT Challenge

Develop novel filtration, separation and

purification technologies to elevate performance

optimization standards in bioprocessing,

development and production.


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The NCSRT SolutionApply a revolutionary NCSRT design enabling bioprocessing

professionals to increase optimum yield, press for greater standards

of purity and achieve:

Higher Permeate Rates Higher Permeate Rates Higher Permeate Rates Higher Permeate Rates

Improved Cleaning Improved Cleaning Improved Cleaning Improved Cleaning

Increased Process Yield Increased Process Yield Increased Process Yield Increased Process Yield

Higher Cell Densities Higher Cell Densities Higher Cell Densities Higher Cell Densities

Finer Separations Finer Separations Finer Separations Finer Separations

Higher Protein Concentrations Higher Protein Concentrations Higher Protein Concentrations Higher Protein Concentrations

Higher Viscosities Higher Viscosities Higher Viscosities Higher Viscosities And Consistent, Repeatable Results And Consistent, Repeatable Results And Consistent, Repeatable Results And Consistent, Repeatable Results


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The NCSRT AdvantageThe NCSRT AdvantageThe NCSRT AdvantageThe NCSRT Advantage

In Downstream ProcessingIn Downstream ProcessingIn Downstream ProcessingIn Downstream Processing

Typical Cell Culture Flow DiagramTypical Cell Culture Flow DiagramTypical Cell Culture Flow DiagramTypical Cell Culture Flow Diagram


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The NCSRT Solution:

OPTISEPSmartFlow

Tangential Flow Filtration (SFTangential Flow Filtration (SFTangential Flow Filtration (SFTangential Flow Filtration (SF----TFF)TFF)TFF)TFF)

The TechnologyThe TechnologyThe TechnologyThe Technology

ProvenProvenProvenProven

To HeightenTo HeightenTo HeightenTo Heighten

TFFTFFTFFTFFProcessing YieldProcessing YieldProcessing YieldProcessing Yield

By 50% To 500%By 50% To 500%By 50% To 500%By 50% To 500%


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Separations of Significance

NCSRT Application # 129:NCSRT Application # 129:NCSRT Application # 129:NCSRT Application # 129:

Protein Concentration / DiafiltrationProtein Concentration / DiafiltrationProtein Concentration / DiafiltrationProtein Concentration / Diafiltration

Concentration Step 0.4 to 4% Solids AverConcentration Step 0.4 to 4% Solids AverConcentration Step 0.4 to 4% Solids AverConcentration Step 0.4 to 4% Solids Average (LMH)age (LMH)age (LMH)age (LMH)

---- Omega 10 kD MaximateOmega 10 kD MaximateOmega 10 kD MaximateOmega 10 kD Maximate 30303030

- GE Amersham 10 kD Hollow FiberGE Amersham 10 kD Hollow FiberGE Amersham 10 kD Hollow FiberGE Amersham 10 kD Hollow Fiber 39393939

- NCSRT OPTISEP RC 10 kDaNCSRT OPTISEP RC 10 kDaNCSRT OPTISEP RC 10 kDaNCSRT OPTISEP RC 10 kDa 70707070

Customer Commentary:Customer Commentary:Customer Commentary:Customer Commentary:

The NCSRT module performs best compared with any other formats used.

Flux was stable at 70 LMH through two hours of concentration and 3X diafiltration.

Omega and Maximate are registered trademarks of Pall Corporation. OPTISEP is a registered trademark of NCSRT, Inc.


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NCSRT Application # 272:NCSRT Application # 272:NCSRT Application # 272:NCSRT Application # 272:

Fungal Culture ProcessingFungal Culture ProcessingFungal Culture ProcessingFungal Culture ProcessingAvg. (LMH)Avg. (LMH)Avg. (LMH)Avg. (LMH)

750 kD GE Amersham750 kD GE Amersham750 kD GE Amersham750 kD GE Amersham 35353535

OPTISEP PES 1000 kDOPTISEP PES 1000 kDOPTISEP PES 1000 kDOPTISEP PES 1000 kD 66666666


Concentration StepConcentration StepConcentration StepConcentration Step

10 kD GE Amersham10 kD GE Amersham10 kD GE Amersham10 kD GE Amersham 10101010


Comparative Data Summary:Comparative Data Summary:Comparative Data Summary:Comparative Data Summary:

Product Yield for GE Amersham 26%Product Yield for GE Amersham 26%Product Yield for GE Amersham 26%Product Yield for GE Amersham 26%

Product Yield OPTISEP 96%Product Yield OPTISEP 96%Product Yield OPTISEP 96%Product Yield OPTISEP 96%


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NCSRT Application #104:NCSRT Application #104:NCSRT Application #104:NCSRT Application #104:

Protein PercipitatesProtein PercipitatesProtein PercipitatesProtein Percipitates(LMH)(LMH)(LMH)(LMH) Avg.Avg.Avg.Avg. ConcentrationConcentrationConcentrationConcentration

Step 0.4 to 4% SolidsStep 0.4 to 4% SolidsStep 0.4 to 4% SolidsStep 0.4 to 4% Solids 0.2 PVDF Millipore Cassette0.2 PVDF Millipore Cassette0.2 PVDF Millipore Cassette0.2 PVDF Millipore Cassette 40404040----5555 22222222

0.2 PVDF Millipore ProStak0.2 PVDF Millipore ProStak0.2 PVDF Millipore ProStak0.2 PVDF Millipore ProStak 30303030----0000 0000

0.1 PVDF NCSRT OPTISEP0.1 PVDF NCSRT OPTISEP0.1 PVDF NCSRT OPTISEP0.1 PVDF NCSRT OPTISEP 350350350350----150150150150 250250250250 RC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEP 200200200200----175175175175 187.5187.5187.5187.5

Diafiltration Step 10XDiafiltration Step 10XDiafiltration Step 10XDiafiltration Step 10X

0.2 PVDF Millipore Cassette 50.2 PVDF Millipore Cassette 50.2 PVDF Millipore Cassette 50.2 PVDF Millipore Cassette 5 5555

RC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEP 186186186186 186186186186

Final Process:Final Process:Final Process:Final Process:RC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEPRC 100 kD NCSRT OPTISEP Concentration from 0.4 to 20% SolidsConcentration from 0.4 to 20% SolidsConcentration from 0.4 to 20% SolidsConcentration from 0.4 to 20% Solids

and 10X Diafiltration with an average flux rate of186 LMHand 10X Diafiltration with an average flux rate of186 LMHand 10X Diafiltration with an average flux rate of186 LMHand 10X Diafiltration with an average flux rate of186 LMH


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NCSRT Application #79:NCSRT Application #79:NCSRT Application #79:NCSRT Application #79:E. coliE. coliE. coliE. coli Lysate ProcessingLysate ProcessingLysate ProcessingLysate Processing

Filter TypeFilter TypeFilter TypeFilter Type Avg. (LMH)Avg. (LMH)Avg. (LMH)Avg. (LMH)

PelliconPelliconPelliconPellicon ZeroZeroZeroZero

CentrasetteCentrasetteCentrasetteCentrasette ZeroZeroZeroZero

3 mm Hollow Fiber3 mm Hollow Fiber3 mm Hollow Fiber3 mm Hollow Fiber 5555

OPTISEP PS 0.2OPTISEP PS 0.2OPTISEP PS 0.2OPTISEP PS 0.2 18181818

OptiSEP PES 1000 kDOptiSEP PES 1000 kDOptiSEP PES 1000 kDOptiSEP PES 1000 kD 30303030

OptiSEP PES 500 kDOptiSEP PES 500 kDOptiSEP PES 500 kDOptiSEP PES 500 kD 70707070

Comparative Data Summary:Comparative Data Summary:Comparative Data Summary:Comparative Data Summary:

Yield from Hollow FiberYield from Hollow FiberYield from Hollow FiberYield from Hollow Fiber 50%50%50%50%

Yield from OPTISEPYield from OPTISEPYield from OPTISEPYield from OPTISEP 94%94%94%94%

Pellicon is a registered trademark of Millipore, Inc. Centrasette is a registered trademark of Pall Corporation.


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NCSRT Application #133:NCSRT Application #133:NCSRT Application #133:NCSRT Application #133:

Membrane StabilityMembrane StabilityMembrane StabilityMembrane Stability

Processing Performance SummaryProcessing Performance SummaryProcessing Performance SummaryProcessing Performance Summary

Membrane delivered to bioprocessing customer (1999)

5 years old, 0.875 mm channel, 2.5 kD, 5 square meters

Processed monthly batches for 2 years

During 2002 added second 5 square meter module

Increased process duration to 8 days (24 hours per day)

Membrane cleaned / turned around in 12 hours

Process restarted immediately without change in flux or retention


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NCSRT, Inc. research verifies that fluid distribution is thNCSRT, Inc. research verifies that fluid distribution is thNCSRT, Inc. research verifies that fluid distribution is thNCSRT, Inc. research verifies that fluid distribution is theeee

single most important factor impacting:single most important factor impacting:single most important factor impacting:single most important factor impacting:

flux decayflux decayflux decayflux decay

cleaning validationcleaning validationcleaning validationcleaning validation

and scale upand scale upand scale upand scale up

Key Findings:Key Findings:Key Findings:Key Findings:

Field Data Analysis SummaryField Data Analysis SummaryField Data Analysis SummaryField Data Analysis Summary ::::

Uniform fluid distribution is required for true optimizationof TFF processes.


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Optimal Flow: Hollow Fiber

IdentifyIdentifyIdentifyIdentify

thethethethe

pathpathpathpath

ofofofof

leastleastleastleast

resistanceresistanceresistanceresistance


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Flow Geometry: Hollow Fiber

Fibers in center areFibers in center areFibers in center areFibers in center are

blasted by turbulenceblasted by turbulenceblasted by turbulenceblasted by turbulence

Fibers along theFibers along theFibers along theFibers along the

outer diameter areouter diameter areouter diameter areouter diameter are

stagnantstagnantstagnantstagnant

RedRedRedRed = Optimal Flow (path of least= Optimal Flow (path of least= Optimal Flow (path of least= Optimal Flow (path of least resistance)resistance)resistance)resistance)

PurplePurplePurplePurple = Secondary Flow= Secondary Flow= Secondary Flow= Secondary Flow BlueBlueBlueBlue = Decreasing Flow= Decreasing Flow= Decreasing Flow= Decreasing Flow

GreenGreenGreenGreen = Poor Flow= Poor Flow= Poor Flow= Poor Flow

OrangeOrangeOrangeOrange //// YellowYellowYellowYellow= Poorest Flow= Poorest Flow= Poorest Flow= Poorest Flow


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Flow Dynamics: Conventional FilterRedRedRedRed = Optimal Flow= Optimal Flow= Optimal Flow= Optimal Flow

(path of least resistance)(path of least resistance)(path of least resistance)(path of least resistance)

PurplePurplePurplePurple = Secondary Flow= Secondary Flow= Secondary Flow= Secondary Flow

BlueBlueBlueBlue = Decreasing Flow= Decreasing Flow= Decreasing Flow= Decreasing Flow

GreenGreenGreenGreen = Poor Flow= Poor Flow= Poor Flow= Poor Flow

OrangeOrangeOrangeOrange //// YellowYellowYellowYellow= Poorest Flow= Poorest Flow= Poorest Flow= Poorest Flow


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Retentate Channels: Conventional FilterHow do you validate cleaningHow do you validate cleaningHow do you validate cleaningHow do you validate cleaning

the X areasthe X areasthe X areasthe X areas

between the retentate channels?between the retentate channels?between the retentate channels?between the retentate channels?

RedRedRedRed = Optimal Flow= Optimal Flow= Optimal Flow= Optimal Flow

(path of least resistance)(path of least resistance)(path of least resistance)(path of least resistance)

PurplePurplePurplePurple = Secondary Flow= Secondary Flow= Secondary Flow= Secondary Flow

BlueBlueBlueBlue = Decreasing Flow= Decreasing Flow= Decreasing Flow= Decreasing Flow

GreenGreenGreenGreen = Poor Flow= Poor Flow= Poor Flow= Poor FlowOrangeOrangeOrangeOrange //// YellowYellowYellowYellow= Poorest Flow= Poorest Flow= Poorest Flow= Poorest Flow


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Flow Distribution: Conventional Filter

INLETINLETINLETINLET OUTLETOUTLETOUTLETOUTLET


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The OPTISEP AdvantageThe OPTISEP AdvantageThe OPTISEP AdvantageThe OPTISEP Advantage

SmartFlowSmartFlowSmartFlowSmartFlow TFFTFFTFFTFF Optimizing Fluid Dynamics


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NCSRTs patented rib design creates uniform retentate channelsNCSRTs patented rib design creates uniform retentate channelsNCSRTs patented rib design creates uniform retentate channelsNCSRTs patented rib design creates uniform retentate channels

Produces equal flow rates across the entire membrane surface.Produces equal flow rates across the entire membrane surface.Produces equal flow rates across the entire membrane surface.Produces equal flow rates across the entire membrane surface.

To optimize for viscosity and solids content, ribs are availablTo optimize for viscosity and solids content, ribs are availablTo optimize for viscosity and solids content, ribs are availablTo optimize for viscosity and solids content, ribs are availableeee

in multiple channel heightsin multiple channel heightsin multiple channel heightsin multiple channel heights

OPTISEPOPTISEPOPTISEPOPTISEP SmartFlowSmartFlowSmartFlowSmartFlow TFF ModelsTFF ModelsTFF ModelsTFF Models


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Note the clear advantage SmartFlow technology providesNote the clear advantage SmartFlow technology providesNote the clear advantage SmartFlow technology providesNote the clear advantage SmartFlow technology provides

by equalizing flow across 100% of the membrane surfaceby equalizing flow across 100% of the membrane surfaceby equalizing flow across 100% of the membrane surfaceby equalizing flow across 100% of the membrane surface


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NCSRT Retentate Channels

These patented retentate channels, found only in NCSRT filtersThese patented retentate channels, found only in NCSRT filtersThese patented retentate channels, found only in NCSRT filtersThese patented retentate channels, found only in NCSRT filtersalso reduce gel layer buildup and prevent foulingalso reduce gel layer buildup and prevent foulingalso reduce gel layer buildup and prevent foulingalso reduce gel layer buildup and prevent fouling


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Bioprocessing professionals throughout the world continue toBioprocessing professionals throughout the world continue toBioprocessing professionals throughout the world continue toBioprocessing professionals throughout the world continue to

document how the entire line of OPTISEP modules consistentlydocument how the entire line of OPTISEP modules consistentlydocument how the entire line of OPTISEP modules consistentlydocument how the entire line of OPTISEP modules consistentlyprovide:provide:provide:provide:

Protein Recoveries >99%Protein Recoveries >99%Protein Recoveries >99%Protein Recoveries >99%

Cell Mass Concentrates to >80% Solids (wet weight)Cell Mass Concentrates to >80% Solids (wet weight)Cell Mass Concentrates to >80% Solids (wet weight)Cell Mass Concentrates to >80% Solids (wet weight)

and Protein Concentration to >40% Solidsand Protein Concentration to >40% Solidsand Protein Concentration to >40% Solidsand Protein Concentration to >40% Solids

OPTISEP ModulesOPTISEP ModulesOPTISEP ModulesOPTISEP Modules

Exponentially Advance TFF PerformanceExponentially Advance TFF PerformanceExponentially Advance TFF PerformanceExponentially Advance TFF Performance


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OptiSEP 800 is ideal forOptiSEP 800 is ideal forOptiSEP 800 is ideal forOptiSEP 800 is ideal formembrane and processmembrane and processmembrane and processmembrane and processevaluation from 1evaluation from 1evaluation from 1evaluation from 1----20L20L20L20L

Unique flow channels utilizeUnique flow channels utilizeUnique flow channels utilizeUnique flow channels utilize 100%100%100%100%of membrane surfaceof membrane surfaceof membrane surfaceof membrane surface

Autoclavable and can withstandAutoclavable and can withstandAutoclavable and can withstandAutoclavable and can withstandmultiple SIP cyclesmultiple SIP cyclesmultiple SIP cyclesmultiple SIP cycles

Available with channel heights of:Available with channel heights of:Available with channel heights of:Available with channel heights of:! 0.25 mm0.25 mm0.25 mm0.25 mm

! 0.50 mm0.50 mm0.50 mm0.50 mm

! 1.0 mm1.0 mm1.0 mm1.0 mm

! 1.5 mm1.5 mm1.5 mm1.5 mm

OPTISEPOPTISEPOPTISEPOPTISEP

800800800800


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OptiSEP 3000 series filter modules yieldOptiSEP 3000 series filter modules yieldOptiSEP 3000 series filter modules yieldOptiSEP 3000 series filter modules yield

optimum efficiency on a range ofoptimum efficiency on a range ofoptimum efficiency on a range ofoptimum efficiency on a range of

solutions from dilutesolutions from dilutesolutions from dilutesolutions from diluteproteins to viscous cell harvestingproteins to viscous cell harvestingproteins to viscous cell harvestingproteins to viscous cell harvesting

Homogeneous fluid dispersionHomogeneous fluid dispersionHomogeneous fluid dispersionHomogeneous fluid dispersion

Available in wide range of membraneAvailable in wide range of membraneAvailable in wide range of membraneAvailable in wide range of membrane

materials and pore sizesmaterials and pore sizesmaterials and pore sizesmaterials and pore sizes

Ideally suited for downstream processing of 2Ideally suited for downstream processing of 2Ideally suited for downstream processing of 2Ideally suited for downstream processing of 2----

50 L bioreactors50 L bioreactors50 L bioreactors50 L bioreactors


3000300030003000


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Homogeneous fluid distributionHomogeneous fluid distributionHomogeneous fluid distributionHomogeneous fluid distribution

Yields optimum efficiency on a range ofYields optimum efficiency on a range ofYields optimum efficiency on a range ofYields optimum efficiency on a range ofsolutions fromsolutions fromsolutions fromsolutions fromdilute proteins to viscous celldilute proteins to viscous celldilute proteins to viscous celldilute proteins to viscous cellharvestingharvestingharvestingharvesting

Multiple channel heights formedMultiple channel heights formedMultiple channel heights formedMultiple channel heights formedby NCSRTs patented distribution ribsby NCSRTs patented distribution ribsby NCSRTs patented distribution ribsby NCSRTs patented distribution ribs

Efficiently utilizesEfficiently utilizesEfficiently utilizesEfficiently utilizes 100%100%100%100% ofofofofthe membrane areathe membrane areathe membrane areathe membrane area

OPTISEPOPTISEPOPTISEPOPTISEP 7000700070007000


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OptiSEPOptiSEPOptiSEPOptiSEP 11000 series filter modules yield11000 series filter modules yield11000 series filter modules yield11000 series filter modules yield

optimum efficiency on a range of solutionsoptimum efficiency on a range of solutionsoptimum efficiency on a range of solutionsoptimum efficiency on a range of solutions

from dilute proteins to viscous cellfrom dilute proteins to viscous cellfrom dilute proteins to viscous cellfrom dilute proteins to viscous cellharvestingharvestingharvestingharvesting


11000110001100011000

Available in wide range of membraneAvailable in wide range of membraneAvailable in wide range of membraneAvailable in wide range of membrane

materials and pore sizesmaterials and pore sizesmaterials and pore sizesmaterials and pore sizes

Production systems processingProduction systems processingProduction systems processingProduction systems processing

50505050 1,400,000 L per day in operation1,400,000 L per day in operation1,400,000 L per day in operation1,400,000 L per day in operation


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PUROSEP LT-1

Designed for dependable laboratory

scale filtration

Evaluate and develop micro and

ultra filtration separation processes

Portable

Countertop system

Shown with

OPTISEP-200filter module


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Dependable laboratoryscale filtration

Evaluate and developmicro and ultrafiltration separationprocesses

Performance levels oflarger units

Compact

Countertop System

Compatible withOPTISEP 200 -3000 filter modules

PUROSEP LT-2


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Provides dependable laboratoryscale filtration to evaluatemicro and ultra filtration

separation processes.Offers performance levels of

larger units.

Precise control of recirculation

flow rate, permeate flow rateand transmembrane pressureensures that test data can bedirectly scaled for production.

Allows easy evaluation ofdifferent filter formats,membrane types andporosities.

Shown withoptional cartShown withoptional cart

PUROSEP LT-2


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PUROSEP PTBuilt-in process tank for totally self-

contained operation.GMP compliant for high value, low

volume feed stocks for clinicalproduction.

Able to handle 100-foldscale up.

Designed for filtration andconcentration of10 to 1,000 L of

feed stock to less than1 L of product.

Allows easy evaluation of differentfilter formats, membrane type

and porosities.


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Designed for a wide range oftangential flow microfiltrationand ultrafiltration

applications.Utilized worldwide for

concentration or purificationof cells, proteins, bloodfractions, diafiltration, andmany other processes in thepharmaceutical andbioprocess industry.

SIP and CIP compatible.

Designed for large scaleproduction using a feed andbleed loop.

Operates with a variety ofmembranes, filters andprocess streams.

PUROSEP PRO


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SYSTEM FEATURES

"Bubble Trap

"

Column Control Valve"CIP and SIP Compatible

"UV

"pH

"Conductivity"Temperature

"Pressure

"Precolumn Filtration

"0-100% Gradient byMetering Pumps

"Isocratic

Chromatography System


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NCSRT Solut ion

Validation Services

Process Development

Process Optimization

Training Seminars

Preventive Maintenance


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Thank You

Rental and Demonstration UnitsAvailable

[email protected]

919-387-8460

Latest Advances in TFF

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