Presentation - Sepragen.com

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QuantaSep ®
Scale Up Sanitary Automated
Chromatography Systems
Why Automate your
Chromatographic process
•
•
•
•
•
•
•
Decrease down time
Increase productivity
Decrease time to market
Consistency in performance
Complete documentation
GMP and GLP Regulations
Economics
Sepragen Corporation
2
System
Specifications
Sepragen Corporation
3
Lab Quantasep Product Line
Integrated, bench top, rugged, sanitary- Roche,
Amgen, Lonza, SAFC, Hyclone,
Invitrogen, Siemens
Hardware Feature Set:
•Two Pumps (Rotating Piston, positive
displacement)
•12 inlets and 10 fractions
•3 columns
•Forward flow, reverse flow and bypass
Quantasep 100
(100ml/min max flow)
0
•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
Quantasep 1000
(1000ml/min max flow)
•Emergency pause
Sepragen Corporation
4
cGMP Pilot and Production QuantaSep Sanitary,
Bio-compatible Systems at Schering Plough, Teva, Baxter, Dyax
QuantaSep 5000: 5L/min
QuantaSep 1000 LX: 2 in one
QuantaSep® 100
100ml/min & 1000ml/min
QuantaSep® 5000
QuantaSep®
1800
QuantaSep
1800:
1800 ml/min
QuantaSep® 1000LX
QuantaSep 10000: 10L/min
Compact foot print; no metals;removal tubing; low system volume Sepragen Corporation
5
Custom Quantasep Process Chromatography Skids
5LPM & 30 LPM SKIDS at Human Genome Sciences
Sepragen Corporation
Custom, Sanitary, 10-40 Liter per minute
Quantasep Process Chromatography Skids
at GSK, Novartis, Neose
•
•
•
•
•
•
•
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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
Sepragen Corporation
Dramatic Space savings with Quantasep
QuantaSep
GE Bio-Process
3mm skid
Sepragen Corporation
8
System Selection vs. Column Size
Column
Diameter
(mm)
Linear flow rate cm hr-1
10
25
50
75
10
100
150
200
250
300
400
500
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
System
Size
Maximum Flow
mL/min
PKL6
PKL60
PK series
100
1,000
>1000
Sepragen Corporation
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Purification of MAb onQuantasep100
A simple, load, wash elute and strip Ab isolation using Protein A Column
Sepragen Corporation
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Critical Software features
 Intuitive method builder
 Dashboard Control
 Comprehensive run
documentation and report
Sepragen Corporation
11
Quantasep Software Feature
Set
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
Sepragen Corporation
12
Software module for Quantasep
Systems
Capabilities
• Real time
point& click
process control
• Data
acquisition
• Analysis
• FDA compliant
Reports reports
Sepragen Corporation
Manual gradient
Sepragen Corporation
Qsep Auto Gradient Run
Sepragen Corporation
P&ID with pre-column filter and sensor options
Positive displacement pump
Pre column
filter
Filter pressure
Inlet
Buffers
Advanced
Gradient System
Column
Pressure
Multimode
detector
Fraction Collection valves
Pre column
Multimode
detector
Active
Air Trap
Column hookup with
forward and reverse flow
capability
Sepragen Corporation
16
Chromatogram Manipulation And
Instant Data Analysis
Gradient
Instant Data Analysis
(buffer consumption etc.
during elution
Overlays
Sepragen Corporation
17
Chromatogram and data analysis
Sepragen Corporation
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Peak Identification and analysis
Sepragen Corporation
Intuitive Method Builder
 Tabular format - eliminates the hassle of programming
 Pick and choose method steps for unprecedented control
 Automatic method validation
Sepragen Corporation
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Software Features
Easy 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
Sepragen Corporation
21
Reports
 Validation
track alarms, events, notes and
any manual changes
 Automatic analysis report
 Calibration Report
Calibration data
Time between calibrations
 Method and column information
Sepragen Corporation
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Calibration History and Report
Sepragen Corporation
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More Software Features
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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
Sepragen Corporation
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Product Features and Benefits
Sepragen Corporation
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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
Sepragen Corporation
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Precision Rotary piston pumps with
stepper motor control
•Positive displacement
•Stepper motor control
•No check valve for
good clean-ability
•Low pulsation
•Small displacement/
rev= even flow
Sepragen Corporation
27
Gradient Performance100:1 Turn down ratio on pumps
100
0
90
10
80
20
70
30
60
40
50
50
40
60
30
70
20
80
10
90
0
0
100
200
300
400
500
600
700
800
900
% Mix - Pump B
% Mix - Pump A
PKL60 System Gradient Range
(10 to 1000 mL/min pump range)
100
1000
Flow Rate (m L/m in)
Sepragen Corporation
28
Real- time Air Ejection Vs. Passive Bubble
Traps
Active Air Ejection
 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
Passive Bubble Trap

Causes Dilution of Product

Unwanted Gradient formation
Doesn’t provide complete protection
of column against air

Increases Holdup volume
Manual air valve
Air Outlet
Air
Ultrasonic air
sensor
Flow
Out
Flow In
3 way valve
Flow in
Flow Out
Sepragen Corporation
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Active Air Trap reduces Elution Volume by 50%
With Active Air Trap
0.25L elution volume
With Standard Bubble Trap
0.4L elution volume
Sepragen Corporation
30
Cleaning Validation Sanitization Study
Process:
Down Stream Purification hookup
Inoculate
Incubate
Wash in
NaoH
1
6
Air Bypass Valve
2
5
Pressure
Sensor
3
4
Water
Wash
Swab at
test
points
Column
1
Pump A
Air
Sensor
~~~~~~
~~~~~~
~~~~~~
1
6
Active Air Trap
Mixer
Column
2
2
8
5
4
3
Pump B
2 Pump Gradient System
Column
3
7
9
10
6
5
1
4
3
2
UV
Conduct.
pH, Temp
Flow Cell
Multi mode
detector
Column
Bypass
Sepragen Corporation
Sepragen Corporation
31
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
Sepragen Corporation
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Material of Construction
Material
Tubing
Silicone, polyethylene and
polypropylene, 316L ss
Valves
Polypropylene, PTFE diaphragms, 316L
SS
Pump Head
Ceramic, 316LL SS
Pump Body
PVDF, 316L SS
glass/quartz/316L stainless steel
Instrumentation
Gaskets
Silicone, EPDM
Sepragen Corporation
33
Multimode Detector Vs. Individual
Detectors
Multimode Detector
•
•
•
•
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 Detectors
•
•
•
•
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.
Flow out
Flow in
Flow out
All Sensors are embedded in one unit
Flow in
Separate detector flow cells connected by tubing
Sepragen Corporation
34
•
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
Sepragen Corporation
35
Cost- Benefit Case Study
Incremental investment $258K
Savings/run=25 hrs
or$400x25=
$10K/run=$30K/mo
Payback= 258/ 30 x12 =7 mos
Sepragen Corporation
36
Competitive Analysis
Sepragen Corporation
37
Product Comparison–
Qsep 100 vs AKTA Explorer
System Positioning
Solution/ Price
QuantaSep 100 is also positioned as
small scale production system (simple,
compact, Integrated unit design)
Small scale production
Process scale up studies
Integrated design with certain options
Simpler selection
Priced 10-15% lower than competition
Better features
AKTA Explorer is positioned as “all things
to all people” tool
Small scale production tool
Process scale up studies
R&D
QC
Price10-15% above Qsep 100
Modular design with “mix and match”
of different components
Complex selection criteria
Sepragen Corporation
38
Advantage: QuantaSep 100 over Akta
Explorer
Features
Qsep
100
Akta
Exp
Quantasep Advantages
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
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
Hardware
Software
Sepragen Corporation
Real time superior process control
Get buffer volumes; switch conditions; % areas in 39
real time as opposed to post run
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
Sepragen Corporation
40
Product Positioning –
Sepragen Qsep 1000 vs. GE AKTA Pilot
System Positioning
Solution/ Price
QuantaSep 1000 is also positioned
as small scale production system
(simple,compact,integrated unit
design)
Small scale production
Process scale studies
Integrated design with certain
options
Smaller footprint & more
compact
Priced 10-15%lower than
competition
Better features
AKTA Pilot is positioned more as a
Small scale production
Process scale up studies
AKTA “mix and match" multiple
components
Complex decision making
Integrated system with few
options
Akta priced 15% above Qsep
1000
Sepragen Corporation
41
Advantages QuantaSep 1000 vs
Akta Pilot
Features
Qsep 100
Akta Pilot
Benefits
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
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; Sepragen
lower
losses and increase yields
Hardware
Software
Corporation
42
Advantages of QuantaSep Software vs
Competition
Software
Features
Sepragen
Amersham
Pall
Millipore
Benefits
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
Software
2 operations
for the
Sepragen
Corporation
price of one 43
QuantaSep Skids vs Competition
Sepragen
GE
Pall
Millipore
Hardware
Qsep 1000Qsep 5000
Akta Process
PK Series
KPrime
Series
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/min5000ml/min
600ml/min6000ml/min
100 ml/min3000 ml/min
150ml/min1500ml/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
Sepragen Corporation
44
QuantaSep vs Competition
Sepragen
Amersham
Millipore
Features
Qsep 1000Qsep 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
Sepragen Corporation
45
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
Sepragen Corporation
46
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
Sepragen Corporation
47
Representative Quantasep Users for
Quantaseps
Domestic
Customer
Product
International
Country
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, 1800
Qsep 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/
Sepragen Corporation
1000
48
Summary
 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%
Sepragen Corporation
49
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
Sepragen Corporation
51
Quantasep General Specifications
Quantasep 100
Quantasep
1000
Flowrate
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)
Sepragen Corporation
52
Sensor Specifications
Accuracy
Sensor
Range
Conductivity
0-200 ms
± 2%
pH
1-14 pH
± 0.3
UV (280nm)
0-2 Au
± 2%
UV (260nm)
option
Active Air Trap
0-2 A-u
± 2%
>5mm (0.20")
0.6 x tubing ID
Operating
Pressure
Leak
0-7 bar (0-100 psi)
± 0.07bar (± 1 psi)
5 mL
-
Flow:Qsep100
Qsep1000
Qsep2000
1-100 mL/min
10-1000 mL/min
20-2000 ml/min
± 3%
Operating
Temperature
4 - 30oC
-
Sepragen Corporation
53
Quantasep Flow cell
Sepragen Corporation
54
Quantasep 100- Inside Look
Sepragen Corporation
55
Quantasep 1000- Inside Look
Sepragen Corporation
56
Flow cell and column & fraction manifolds
forQuantasep 1000
Sepragen Corporation
57
Multimode Detector
Flow Cell
pH Ref
pH Probe
UV Lamp
Compact and Zero lag time detector helps minimize footprint
Sepragen Corporation
58
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