QuantaSep ® Scale Up Sanitary Automated Chromatography Systems.

QuantaSep ®

Scale Up Sanitary Automated Chromatography Systems

Sepragen Corporation

Why Automate your Chromatographic process

• Decrease down time• Increase productivity• Decrease time to market• Consistency in performance• Complete documentation• GMP and GLP Regulations• Economics

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Sepragen Corporation3

System Specifications


Lab Quantasep Product Line

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0Quantasep 100

(100ml/min max flow)

Quantasep 1000

(1000ml/min max flow)

Hardware Feature Set:

•Two Pumps (Rotating Piston, positive displacement)

•12 inlets and 10 fractions

•3 columns

•Forward flow, reverse flow and bypass

•UV, pH, temp and Conductivity detection

• Sensors for pressure, air, leak and rpm check

•Stainless Steel Fluid-handling compartment

•Biocompatible materials of construction

•Outputs for remote data logging

•Fraction collector interface trigger

•Emergency pause

Integrated, bench top, rugged, sanitary- Roche, Amgen, Lonza, SAFC, Hyclone, Invitrogen, Siemens


cGMP Pilot and Production QuantaSep Sanitary, Bio-compatible Systems at Schering Plough, Teva, Baxter, Dyax

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QuantaSep® 100

QuantaSep® 1800

QuantaSep® 5000QuantaSep® 1000LX

QuantaSep 1800: 1800 ml/min

QuantaSep 5000: 5L/min

QuantaSep 1000 LX: 2 in one

100ml/min & 1000ml/min

QuantaSep 10000: 10L/min

Compact foot print; no metals;removal tubing; low system volume

Sepragen CorporationCustom, Sanitary, 10-40 Liter per minute Class 1 Div 2 Skids

Custom Quantasep Process Chromatography Skids 5LPM & 30 LPM SKIDS at Human Genome Sciences


• Gradient 2 Pump 10-40 Liter per minute per pump, 5-95% Gradient

• 10 Inlets, 2 Outlets, Filter, Bubble Trap, Column fwd, Rev & Bypass

• Pre and post column pH and Cond sensors, Multi wavelength UV

• Sanitary 316L SS Piping, 304 SS Moblie Ex Proof Skid

• Air sensor, Auto air removal and Bubble Trap with control system

• Leak sensor, Pressure Sensor• Filter, Flow through and Bypass• CE, BASEEFA (class 1 Div1, T4)

Certified ATEX explosion proof skid

Quantasep Process Chromatography Skids at GSK, Novartis, Neose


Dramatic Space savings with Quantasep

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QuantaSep

GE Bio-Process3mm skid


10 25 50 75 100 150 200 250 300 400 500

10 1 2 3 3 4 5 7

15 1 1 3 4 6 7 9 12 15

25 4 6 8 12 16 20 25 33 41

35 2 4 8 12 16 24 32 40 48 64 80

50 3 8 16 25 33 49 65 82 98 131 164

70 6 16 32 48 64 96 128 160 192 257 321

100 13 33 65 98 131 196 262 327 393 524 654

140 26 64 128 192 257 385 513 641 770 1,026 1,283

180 42 106 212 318 424 636 848 1,060 1,272 1,696 2,121

200 52 131 262 393 524 785 1,047 1,309 1,571 2,094 2,618

250 82 205 409 614 818 1,227 1,636 2,045 2,454 3,272 4,091

280 103 257 513 770 1,026 1,539 2,053 2,566 3,079 4,105 5,131

Linear flow rate cm hr-1Column

Diameter (mm)

System Size

Maximum Flow mL/min

PKL6 100PKL60 1,000

PK series >1000

System Selection vs. Column Size


Purification of MAb onQuantasep100

A simple, load, wash elute and strip Ab isolation using Protein A Column


Critical Software features

Intuitive method builder

Dashboard Control

Comprehensive run documentation and report

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Quantasep Software Feature Set

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Win XPbased computer control

•Easy point & click interface

•Auto & manual operation

•Method builder and editor

•Chromatogram and analysis

•Event and alarm log

•Easy software calibration

•GMP Reports

•Part 11 Compliance


Software module for Quantasep Systems

Capabilities• Real time

point& click process control

• Data acquisition

• Analysis• FDA compliant

Reports reports


Manual gradient


Qsep Auto Gradient Run


P&ID with pre-column filter and sensor options

Active Air Trap

Multimode detector

Pre column Multimode detector

Advanced Gradient System

Pre column filter

Positive displacement pump

Fraction Collection valves

Column hookup with forward and reverse flow capability

Column Pressure

Filter pressure

Inlet Buffers


Chromatogram Manipulation And Instant Data Analysis

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Gradient

Overlays

Instant Data Analysis(buffer consumption etc.during elution


Chromatogram and data analysis

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Peak Identification and analysis


Intuitive Method Builder

Tabular format - eliminates the hassle of programming Pick and choose method steps for unprecedented control Automatic method validation 20


Software FeaturesEasy operation, monitoring& control

• Operation from graphical P&ID screen

• Manual or Automated Modes

• Real-time Chromatogram• Programmable based on

time, volume or sensor values

• Real time event log• Real time alarms

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Reports

Validation track alarms, events, notes and

any manual changes Automatic analysis report Calibration Report

Calibration data Time between calibrations

Method and column information

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Calibration History and Report

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More Software Features

• Password controlled security system• Chromatogram replay and zoom capabilities• Linear or step gradient programmability• Generic file formats for easy export• Settable alarm conditions• Built-in audit tracking capability

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Product Features and Benefits


Differentiating Features

Hardware

–Fully Integrated system

–Compact foot-print

–Real time air ejection

–Leak Detect

– multimode detector

–Pump stall feed-back

Software

–Intuitive method builder

–Easy P&ID Control

–Comprehensive reports

–Chromatograms & analysis


Precision Rotary piston pumps with stepper motor control

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•Positive displacement

•Stepper motor control

•No check valve for good clean-ability

•Low pulsation

•Small displacement/ rev= even flow


PKL60 System Gradient Range (10 to 1000 mL/min pump range)

0

10

20

30

40

50

60

70

80

90

100

0 100 200 300 400 500 600 700 800 900 1000

Flow Rate (mL/min)

% M

ix -

Pu

mp

A

0

10

20

30

40

50

60

70

80

90

100

% M

ix -

Pu

mp

B

Gradient Performance- 100:1 Turn down ratio on pumps


Real- time Air Ejection Vs. Passive Bubble Traps

Protects against dilution of Product

No Unnecessary Gradient formation

Provides Protection of Column from any amount of air

Can be used to detect end of sample

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Causes Dilution of Product

Unwanted Gradient formation

Doesn’t provide complete

protection

of column against air

Increases Holdup volumeAir Outlet

Flow InFlow Out

3 way valve

Ultrasonic air sensor

Manual air valve

Air

Flow in Flow Out

Active Air Ejection Passive Bubble Trap


With Active Air Trap0.25L elution volume

With Standard Bubble Trap0.4L elution volume

Active Air Trap reduces Elution Volume by 50%



Down Stream Purification hookup

Mixer

PressureSensor

AirSensor

Air Bypass Valve

Column1

Column2

Column3

ColumnBypass

Pump B

Pump A

2

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5

6

2

34

5

6

UVConduct.pH, TempFlow Cell1

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4

5

7

610

9

8

~~~~~~~~~~~~~~~~~~

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1 Active Air Trap

Multi mode detector

2 Pump Gradient System

Cleaning Validation Sanitization Study

Process:

Inoculate

Incubate

Wash in NaoH

Water Wash

Swab at test points


Results of Microbial challenge study on Quantasep 1000

Location S. Aureus

E.Coli P.Aerg.

C. Albicans

A.niger

Inlet A 0 0 0 0 0

Inlet B 0 0 0 0 0

Pump A 0 0 0 0 0

Pump B 0 0 0 0 0

Manifold A 0 0 0 0 0

Manifold B 0 0 0 0 0

Pressure 0 0 0 0 0

Mixer 0 0 0 0 0

Col Outlet 0 0 0 0 0

Col. Inlet 0 0 0 0 0

Bypass In 0 0 0 0 0

Bypass Out 0 0 0 0 0

UV flow cell 0 0 0 0 0

Cond. sensor 0 0 0 0 0

pH sensor 0 0 0 0 0

pH Ref 0 0 0 0 0

Fraction comm 0 0 0 0 0

Fraction 1 0 0 0 0 0

Air Outlet 0 0 0 0 0

Air Inlet 0 0 0 0 0


Material

Tubing Silicone, polyethylene and polypropylene, 316L ss

Valves Polypropylene, PTFE diaphragms, 316L SS

Pump Head Ceramic, 316LL SS

Pump Body PVDF, 316L SS

Instrumentation glass/quartz/316L stainless steel

Gaskets Silicone, EPDM

Material of Construction


Multimode Detector Vs. Individual Detectors

• UV, pH, Conductivity and Temp. all in one

• Reduce Lag time between detectors• Minimize Hold up / Dead zone• More accurate control of

Chromatography process

• Separate UV, pH, Conductivity and Temp.

• Too much lag time between detectors.• Increases unnecessary Hold up / Dead

Zone.• Harder to control and validate a

process.

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Multimode Detector Separate Detectors

Flow in Flow out

All Sensors are embedded in one unit

Separate detector flow cells connected by tubing

Flow in

Flow out


Chromatography Automation Cost-benefit analysis

• Overall cost with system– Fixed Cost: System and accessories- manual components– Variable Cost: annual maintenance

• Benefits– Direct Saving

• Labor Savings in production: Skilled labor (upto $400/hr fully burdened)• Labor Savings in documentation, report writing and admin

– Indirect Savings• Better time management with 24/7 operation• Lesser skilled labor rate can be applied to production• Improvement in lot-to-lot consistency or quality• Reduced batch failure• Accessible documentation for regulatory compliance

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Cost- Benefit Case Study

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Incremental investment $258K

Savings/run=25 hrs or$400x25= $10K/run=$30K/mo

Payback= 258/ 30 x12 =7 mos


Competitive Analysis


Product Comparison– Qsep 100 vs AKTA Explorer

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System Positioning Solution/ Price

QuantaSep 100 is also positioned as small scale production system (simple, compact, Integrated unit design)

Small scale productionProcess scale up studies

Integrated design with certain optionsSimpler selectionPriced 10-15% lower than competitionBetter features

AKTA Explorer is positioned as “all things to all people” toolSmall scale production toolProcess scale up studiesR&DQC

Price10-15% above Qsep 100Modular design with “mix and match” of different componentsComplex selection criteria


Advantage: QuantaSep 100 over Akta Explorer

Features Qsep 100

AktaExp

Quantasep Advantages

Hardware

Low System Backpressure at max-flow

Yes No Akta generates high pressure at 100 ml/min; Qsep is only 50% of the pressure

Can Run Pump Dry Yes No Pumps need to be primed or doesn’t flow

Pumps don’t siphon Yes No Unintended loss of buffer or sample

Auto Air Eject System Yes No Column protected from air intrusion

Leak detection Yes No Protection from loss of material

Diaphragm valves Yes No Diaphragm valves are more sanitary compared to rotating valves

Sanitary design Yes No Sanitary tubing connections; Bug Challenge study

Software

Easy to use and program

Yes No 2 hrs to learn software as opposed to 2 days

Point & Click P&ID operation

Yes No Easy to run, monitor and change parameters

Real time analysis Yes No Real time superior process controlGet buffer volumes; switch conditions; % areas in real time as opposed to post run

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Similarities between QuantaSep 100 vs Akta Explorer

Features Qsep100 Akta Options

Bench top Yes Yes Similar footprint

Flow rate 0- 100 ml/min 0- 100 ml/min

Similar stated flow range but Akta’s usable flow range is ~40 ml/min

Air detector yes yes Akta uses it to stop flow not remove air dynamically

Gradient 0- 100% 0- 100% Similar

Sample injector yes yes In Quantasep sample loops are standard

Detectors UV, Cond, pH UV, Cond, pH

All 3 sensors standard

Pumps 2 2 2 Pumps but Akta pumps can only run with primiing

Columns 3 1 Quantasep can enable user to do uf/df

Manual & Auto Operation

Yes Yes Buffer selection; Flow setting; switch conditions based on time, volume, UV, pH, Cond, Air, Fraction collection

Security Yes Yes Controlled access

Data Analysis Yes Yes % areas; HETP; buffer usage; switch conditions

Reports Yes Yes Method and batch; chromatogram; alarms & events; access

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Product Positioning – Sepragen Qsep 1000 vs. GE AKTA Pilot

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System Positioning Solution/ PriceQuantaSep 1000 is also positioned as small scale production system (simple,compact,integrated unit design)

Small scale productionProcess scale studies

Integrated design with certain optionsSmaller footprint & more compactPriced 10-15%lower than competitionBetter features

AKTA Pilot is positioned more as aSmall scale production Process scale up studies

AKTA “mix and match" multiple componentsComplex decision makingIntegrated system with few optionsAkta priced 15% above Qsep 1000


Advantages QuantaSep 1000 vs Akta Pilot

Features Qsep 100

Akta Pilot

Benefits

Hardware

Buffers 12 8 Greater versatility- enables all 3 columns to be used without stopping run

Fractions 10 8 More capability for collecting fractions from multi- column run

Low System Backpressure

Yes No Operational over 100% range vs. only 60% for Akta

Auto Air Eject System

Yes No Column protected from air intrusion

Leak detection Yes No Protection from loss of material

Flow rate/ pump

0-1000 ml/min

0- 400 ml/min

Greater dynamic range…..can process large dilute batches faster

No Bubble trap Yes No Better chromatography less dilution

Software

Point & Click software

Yes No Software easy to learn, use and troubleshoot; Akta Software unwieldy to program, train and run overkill for production

Real time Analysis

Yes No Better process control; lower losses

Real time overlays

Yes No Increase run- run consistency; lower losses and increase yields

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Advantages of QuantaSep Software vs Competition

Software Features

Sepragen Amersham

Pall Millipore Benefits

Software

Point and Click Manual Operation

Yes No No No Less training time

Online Data Analysis

Yes No No No Lower failure rate

Ease of Operation

+++ + ++ ++ Ease of Use

Ease of Programming

+++ + ++ + Ease of Use

Real Time Overlays

Yes No No No Improved reliability

Integrate Chrom and UF/ DF

Yes No No No 2 operations for the price of one

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QuantaSep Skids vs CompetitionSepragen GE Pall Millipore

Hardware Qsep 1000-Qsep 5000

Akta Process

PK Series KPrimeSeries

Benefits

Product Range 6 3 3 3 Greater range

Turndown Ratio of Pumps

100:1 10:1 30:1 10:1 Greater dynamic range

Typical Flow Range 50ml/min-5000ml/min

600ml/min-6000ml/min

100 ml/min-3000 ml/min

150ml/min-1500ml/min

Greater dynamic range

Gradient (at 50% FS)

5-95% 10-90% 10-90% 20-80%% Better Chromatography

Online Buffer Dilution

Yes Yes Yes No Save labor, space, time

System Volume 750ml ~2000 ml 2000 ml 2000 ml Better chromatography

Footprint 22”x27”x46” 30”x60”x72” 30’x60’x72” 30”x60”x50” Increased Capacity

Air Ejection Electronic Bubble trap Bubble trap Bubble trap Increased Reliability

Leak Detection Yes No No No Increased Reliability

Leak Sensor Yes No No No Increase reliability

Easy to use software

Yes No No No Easy training; usage and intervention

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QuantaSep vs CompetitionSepragen Amersham Millipore

Features Qsep 1000-Qsep 5000

3-10 mm Bioprocess

K Prime 40+

Benefits

Inlet Valves 6+6, 4+4 4+4 4+4 Greater flexibility

Columns 3,1 1 1 Greater flexibility

Fractions 10,6 4 4 Greater flexibility

Dual wavelength UV

Yes Yes Yes Greater flexibility

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Customer Quotes• Human Genome Sciences, Inc.

"We have purchased several QuantaSep Systems and use them routinely in development and manufacturing. They have provided us with the capability to scale-up quickly and reliably. The robust design and compact size has enabled us to add productive capacity without waiting for additional construction.

The QuantaSep software is easy to learn and use. Automated processing and report generation have enabled us to get more done with the same resources. Our quality and consistency have improved, as well. I would highly recommend the QuantaSep® family of products to anyone."

Mark Oelkuct, Purification Manager

• Cohesion Technologies

"At Cohesion we have used a QuantaSep 1000 as a workhorse in both manufacturing and process development. We are quite satisfied with its performance. In our hands the QuantaSep has been a reliable instrument that is also easy to use and maintain. The flow rate range of the 1000 matched out commercial requirement for one process and pilot scale for another. It fits well into smaller processing spaces (critical when working in Palo Alto). Again, we have been happy with our QuantaSep 1000 and would be willing to discuss our experience with others"

Lou Sehl, Ph. D. , Senior Scientist and Team Leader

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Customer Quotes

• Dade Behring"The efficiency of these products, in our hands, provides a significant advantage over other purification equipment we have evaluated for the following reasons:1) The QuantaSep software is easy to use and train.2) The QuantaSep allows us to reduce our standard direct hours, thus reduce our projected costs, by allowing a production chemist to perform multiple purification tasks simultaneously. This system eliminates the need to "baby-sit" all the individual purification steps. With reduced labor costs, the return on investment is easily less than two years for the QuantaSeps.3) This programmable system insures lot-to-lot consistency, resulting in consistent elution profiles vs. the built in variability with more manual operations. A critical advantage for a GMP production process.4) And finally, one unique advantage of this system is its versatility. We can run both our small and large volume production (5 liter to 200 liter) runs with the change over feature. No other systems we have investigated have that volume flexibility."

Dennis Gould, Manager, Antibody Manufacturing

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Representative Quantasep Users for Quantaseps

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Domestic Customer

Product InternationalCountry

Company Product

Siemen’s Diagnostic,Dyax

Qsep 1000 LX Japan Asahi Kasei Qsep 1000

Neovatech Qsep 1000s Germany Baxter Qsep 1000

Dow Pharma

Qsep 1800/ 1000

Switzerland Lonza Qsep 1000

Lonza, Biogen- Idec

Qsep 1000, 1800Qsep 1000

India Cadilla Pharma

Qsep 1000

Amgen, Roche Diagnostics

Qsep 100 Belgium Henogen Qsep 1000

HGS Qsep 1000/ 1800

U.K., Belgium

GSK Qsep 1000, Qsep 40Lpm

Schering Plough

Qsep 1000s, 5000

China, Russia

several Qsep 100/ 1000


Summary

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Reduce Project backlog Improve product backlog Improve product quality and

reliability Reduce Project backlog Unattended clinical Production

24/7 NOW! GMP documentation

automatically Easy scale-up 500X Improved process economic by

50%

QuantaSep ®

Additional Slides


Custom Explosion Proof Chromatography Skids

• 10-40 Liter per minute

• Class 1, Div 1 or 2

• Stainless Steel construction

• Fully drainable

• Multi-wavelength detection

• Diaphragm pumps

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Quantasep 100 Quantasep

1000Flowrate 1 – 100 mL/min 10 – 1000 mL/min

Tubing ID (mm)

1.59(1/16”)

6.35(1/4”)

Connections ¼.28 thread ½” tri-clamp

Hold-up volume

7 mL 120 mL

Dimensions (WxDxH)

660 x 533 x 381(mm) (26"X 21" X15")

660 x 533 x 381(mm)(26"X 21" X15")

Un-crated weight (kg)

57 (125 lbs) 66 (145 lbs)

Quantasep General Specifications


Sensor

RangeConductivity 0-200 ms ± 2%

pH 1-14 pH ± 0.3

UV (280nm) 0-2 Au ± 2%

UV (260nm) option

0-2 A-u ± 2%

Active Air Trap >5mm (0.20") 0.6 x tubing ID

Operating Pressure

0-7 bar (0-100 psi) ± 0.07bar (± 1 psi)

Leak 5 mL -

Flow:Qsep100 Qsep1000 Qsep2000

1-100 mL/min 10-1000 mL/min20-2000 ml/min

± 3%

Operating Temperature

4 - 30oC -

Accuracy

Sensor Specifications


Quantasep Flow cell


Quantasep 100- Inside Look


Quantasep 1000- Inside Look


Flow cell and column & fraction manifolds forQuantasep 1000


pH Ref

pH Probe

UV Lamp

Flow Cell

Multimode Detector

Compact and Zero lag time detector helps minimize footprint

QuantaSep ® Scale Up Sanitary Automated Chromatography Systems.

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