USD2941(1)
iCELLis® Bioreactor
Single-use bioreactor for process intensification
Highlights and Benefits
Process simplification, from pre-culture to final product
The first fully-integrated, single-use bioreactor (integrated perfusion with disposable,
pre-installed calibrated probes and no additional oxygen device needed)
Straightforward implementation for faster process development
Linear scalability from R&D to manufacturing
Compact high-cell-density, fixed-bed bioreactor providing a significant increase
in volumetric productivity vs. traditional stirred tanks
Dramatic decrease in operational costs and capital investments
Overview
The iCELLis bioreactor is the world’s first fully-integrated,
high-cell density bioreactor designed to simplify your process
by combining the advantages of single-use technologies with the
benefits of a fixed-bed system. The compact system—designed
for quick implementation and ease-of-use—represents a new
generation of single-use bioreactors.
Central to the iCELLis bioreactor technology is the use of a
compact fixed-bed, filled with custom macrocarriers. This matrix
is made of medical grade polyester microfibers and provides –
in only 25 L volume – up to 500 m2 available area for cell
growth. This is the surface-equivalent of 3,000 Roller Bottles
(at 1700 cm2 each). The iCELLis bioreactor is provided with
pre-packed macrocarriers. Compared to a standard stirred-tank
bioreactor using microcarriers, the iCELLis technology leads to
a dramatic simplification of the cell culture process. It alleviates
delicate and time-consuming manual operations, reducing
the overall process time and making the cell culture process
more robust.
With biomass multiplication occurring in the fixed-bed, iCELLis
bioreactors can be inoculated at very low density. The number
and volume of pre-culture steps are reduced considerably;
20 Roller Bottles (1700 cm2) are sufficient to inoculate an iCELLis
500 bioreactor (with 500 m2 of available surface to the cells). As
a result of this process simplification, manual operations and
associated costs are greatly reduced.
Evenly-distributed media circulation is achieved by a built-in
magnetic drive impeller, ensuring low shear stress and high cell
viability. The cell culture medium flows through the fixed-bed
from the bottom to the top. At the top, the medium falls as a
thin film down the outer wall where it takes up O2 to maintain
high KLa the in the bioreactor. This unique waterfall oxygenation,
together with a gentle agitation and biomass immobilization,
enables the compact iCELLis system to achieve and maintain
high cell densities—equaling the productivity of much larger
stirred-tank units.
Media flow and average media
in the iCELLis 500 bioreactor
(60-70 L)
Features and Configurations
Integrated mixing system for evenly-distributed media
circulation and low shear stress
Specialized carriers specifically adapted to adherent
cell cultures
Unique waterfall media oxygenation for high oxygen transfer
Single-use bioreactor made from USP Class VI rigid plastic to
ensure process reliability
Modular height of fixed-bed – from 2 cm to 10 cm – offering
several configurations of small and large scale
The iCELLis bioreactor is available in two formats:
The iCELLis nano system for feasibility studies and
small-scale production
The iCELLis 500 system for industrial scale manufacturing
(up to 500 m2)
Process simplification, from vial thawing to final product, is at the
heart of the iCELLis platform. As cells are immobilized in the
fixed-bed, and the iCELLis system operates in perfusion mode,
no centrifugation is needed to harvest the cells. This benefit
further simplifies the downstream process.
The iCELLis 500 bioreactor (500 m2) is equivalent to 3,000
Roller Bottles (1700 cm2 each)
2
Microscopy view of MDCK
cells immobilized on
iCELLis system carriers
The iCELLis 500 bioreactor on its
fully-integrated skid
Table 1
Configurations of iCELLis bioreactors at small and manufacturing scale
Bioreactor
Bioreactor
Diameter (mm)
Fixed-Bed
Height (mm)
Fixed Bed
Volume (L)
Bioreactor
Volume (L)
Surface Area (m2)
Low Compaction
High Compaction
iCELLis nano
iCELLis nano
iCELLis nano
iCELLis 500/100
iCELLis 500/200
iCELLis 500/500
110
110
110
860
860
860
20
40
100
20
40
100
0.04
0.08
0.2
5
10
25
1
1
1
70
70
70
0.53
1.06
2.6
66
133
333
0.8
1.6
4
100
200
500
iCELLis 500 Bioreactor Components
Process Control Systems
1 Probe supports (T, pH, D.O.)
Startup Requirements
2 Outer shell, top section with 8 ports (5 IN/3 OUT);
Media IN/OUT, Feed IN/OUT, NaOH, Gas IN/OUT,
Cell/Virus
3 - 5 Fixed-bed support integrating pump housing (5)
and filled with macrocarriers (4). Top grid to retain
carriers (3)
6 - 7 Integrated magnetic-driven impeller (6) and pump housing
ring (7)
8 - 9 Outer shell, bottom section including double-jacket (9)
Bioreactor
iCELLis nano
iCELLis 500
Power Requirement
Power Supply
500 W
100 – 230 VAC
50-60 Hz
3500 W (2)
100 – 230 VAC
50-60 Hz
1 bar
1 bar
N/A
1 bar
2 bar
2 bar
2 bar
2 bar
Gas Requirements
O2
CO2
N2
Air
System Specifications
Bioreactor
1
2
Dimensions (mm)
Docking Station
Controller
Perfusion
Weight
Docking Station
Controller
Instrumentation
pH probes
D.O. probes
Temperature probes
Biomass probes
(single-use)
Pumps
3
4
5
Control System
Architecture
Compliance
iCELLis nano
iCELLis 500
200 x 120 x 200
260 x 300 x 220
200 x 120 x 200
Fully-integrated device
1400 x 1700 x 890
2.5 kg
3.5 kg
~ 300 kg
1 (classical)
1 (classical)
1
1 (classical)
2 (single-use)
2 (single-use)
2
1* (single-use)
1 for NaOH addition
5 – Perf IN/OUT, NaOH
Perfusion module (optional) addition,sampling and
accessories
PC-HMI
GAMP & 21 CFR Part 11
compliant (optional)
PLC-SCADA
GAMP & 21 CFR Part 11
compliant (optional)
6
7
8
9
www.pall.com
3
Startup Requirements
Bioreactor
pH
Range
Regulation
D.O.
Range
Regulation
Temperature
Range
Regulation
Speed
Range
Mixing System
Perfusion
Regulation
Gas Flow Rates
O2
CO2
N2
Air
Data Recording/
Trending
Production
Sequences Mode
and Alarm
Management System
iCELLis nano
iCELLis 500
Detection range =
pH 0 – 14
NaOH/CO2 addition
Detection range =
pH 6 .0– 9.0
Precision = +/– 0.01
@ pH 7.0
NaOH/CO2 addition
0-100%
O2 addition
0-100%
Air/O2/N2 additions
15 to 40 °C
Peltier elements
25 to 40 °C
Double jacket – Cryostat
0-1,500 rpm
Magnetic drive impeller
(integrated)
0-400 rpm
Magnetic drive impeller
(integrated)
External perfusion system
(self-regulated pumping
outflow - automatic and
manual modes)
Perfusion system
integrated
(self-regulated pumping
outflow - automatic and
manual modes)
0-200 mL/min
0-10 mL/min
0-50 mL/min
0-50 mL/min
Available on external
laptop (optional)
NA
0-7 L/min
0-2 L/min
0-1 L/min
0-2 L/min
Optional
Data Management with the iCELLis 500
Bioreactor
The iCELLis 500 bioreactor is operated through a fully-integrated
process control unit designed to fit with GAMP and 21 CFR Part
11 requirements. It operates with a SCADA system (inTouch)
developed by Wonderware which offers maximum functionality
for process control and data acquisition. The data and alarms
generated during the cell culture batch are stored on a local
hard-drive in a secured Wonderware format. An additional
network interface card, as well as an Ethernet port, is included
in the system to connect it to the user’s network and enable
custom data history. In addition, the system allows real-time
alarming (option) by sending the pre-defined user an SMS or
e-mail message in case of an unexpected event. Pall Life
Sciences IT experts can support integration of the iCELLis
process control system in GMP environments.
Performance
The fixed-bed design of the iCELLis system makes it the perfect
solution for process intensification, providing a large cell growth
surface area while keeping the volumes very small. In only 25 L
of volume, iCELLis accommodates up to 500 m2 of growth area,
which, when compared with available surfaces of multitray
systems and roller bottles, corresponds to a huge reduction
in volumes. Table 2 illustrates the iCELLis 500/500 m2 system
is equivalent to 794 cell stacks with 10 trays and 5,882 Roller
Bottles at 850 cm2 each.
Optional
General overview from iCELLis 500 software
Split view of iCELLis nano disposable bioreactor with reusable lid
Bioreactor overview from iCELLis 500 software
4
Table 2
Available surface area in an iCELLis 500 system and comparison with multitray cell factory systems (CF)/Roller Bottles (RB).
Equivalent CF10
Equivalent RB
(6,300 cm2)
(850 cm2)
Equipment
Fixed-Bed Volume (L)
Culture Surface Area (m2)
iCELLis nano
Fixed-bed height 10 cm
iCELLis 500/500
Fixed-bed height 10 cm
0.2
4
6
47
25
500
794
5,882
In addition to volume reduction, the use of a filled, fixed-bed in the iCELLis system enables higher specific productivity than in classical
systems. To demonstrate the impact of iCELLis bioreactors on cell densities and productivity, many cultures were performed with
several cell lines (Table 3). Results clearly highlight that the growth matrix inside the iCELLis system is a favored growth environment
which, together with controlled cell culture parameters, can significantly increase the biomass amplification, as well as the number
of viral particles produced by each cell (specific productivity). Additional experiments demonstrated that iCELLis bioreactors require
limited adaptation protocols and enable easy, straightforward scale-up for the majority of mammalian cell lines.
Table 3
Cell densities and specific productivities achieved with iCELLis systems (several mammalian cell lines). Comparison is with
multitray cell factory systems (CF)/Roller Bottles (RB).
Equivalent CF/RB Equivalent CF/RB
Cell Densities in
Specific Productivity (/cm2)
500/500 (500 m2)
Cell Line
Bioproduct
iCELLis Bioreactor
Control
iCELLis
nano 4 m2
Vero Serum-Free
Paramyxovirus
33.7 x 106 cell/mL
A549
rAAV
9 x 104 cell/cm2
HEK293
CGTC102
1.68 x 105 cell/cm2
CEF Serum-Free
30 to 100 cell/mL
3.48 x 106 PFU
MDBK
MVA Virus
(non-lytic infection)
BHV
60 cell/mL
VERO Serum-Free
Influenza
28 cell/mL
VERO
Undisclosed
Human Vaccine
Undisclosed
Human Vaccine
75 to 150 cell/mL
(max)
75 to 150 cell/mL
(max)
VERO Serum-Free
T-Flask
5.67 x 104 TCID50
CS5, 3 x 106
vg/cm2
Hyperflask
7 x 108 TCID50
6.37 x 105
TCID50
5 x 108
vg/cm2
3.8 x 109 TCID50
Undisclosed
2.17 x 106
TCID50
3.75 x 105
TCID50
Undisclosed
71 CF10
527 RB
10 CF10
75 RB
35 CF102
63 RB
5 CF10
38 RB
16 CF10
120 RB
15 CF10
110 RB
10 CF10
8,750 CF10
64,625 RB
1,250 CF10
9,375 RB
4,413 CF10
32,946 RB
625 CF10
4,750 RB
2,000 CF10
15,000 RB
1,875 CF10
13,750 RB
1,238 CF10
Undisclosed
Undisclosed
6 CF10
794 CF10
Visit us on the Web at www.pall.com/bioreactors
E-mail us at bioreactors@pall.com
Corporate Headquarters
Port Washington, NY, USA
+1.800.717.7255 toll free (USA)
+1.516.484.5400 phone
biopharm@pall.com e-mail
European Headquarters
Fribourg, Switzerland
+41 (0)26 350 53 00 phone
LifeSciences.EU@pall.com e-mail
Asia-Pacific Headquarters
Singapore
+65 6389 6500 phone
sgcustomerservice@pall.com e-mail
International Offices
Pall Corporation has offices and plants throughout the world in: Argentina, Australia, Austria,
Belgium, Brazil, Canada, China, France, Germany, India, Indonesia, Ireland, Italy, Japan,
Korea, Malaysia, New Zealand, Norway, Philippines, Poland, Russia, Singapore, South
Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, and Vietnam.
Distributors in all major industrial areas of the world. To locate the Pall office or distributor
nearest you, visit www.pall.com/contact.
The information provided in this literature was reviewed for accuracy at the time of publication.
Product data may be subject to change without notice. For current information consult your
local Pall distributor or contact Pall directly.
© 2015, Pall Corporation. Pall,
, and iCELLis are trademarks of Pall Corporation. ® indicates a trademark
registered in the USA and TM indicates a common law trademark. Filtration. Separation. Solution. is a service
mark of Pall Corporation.
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