Application Note
USD 2999
Allegro™ Single-Use TFF System Integrating
Cadence™ Single-Use TFF Modules
Authors
Pall Life Sciences:
Engin Ayturk, Ph.D., BioPharm Applications R&D (AR&D)
Gregor Kalinowski, Ph.D., Scientific Laboratory Services (SLS)
Pauline Nicholson, Ph.D., Global Product Manager, Allegro Single-use Systems
Nathalie Pathier, Global Product Manager, Single-Use TFF
Rentschler Biotechnologie GmbH:
Sven Heimann, Process Engineer DSP Production
Markus Laukel, Ph.D., Associate Director DSP Production
Thomas Leanyvari, Process Engineer DSP Production
Peter Rogge, Vice President USP Production
Stefan Schmidt, Ph.D., Vice President DSP Production
Daniel Schiessel, Process Engineer, DSP Development
Table of Contents
Abstract/Summary ...........................................................................................................................................3
1. Introduction ..................................................................................................................................................3
2. Experimental ................................................................................................................................................4
2.1 Materials, Equipment and Methods..........................................................................................................4
2.1.1 Feedstock ....................................................................................................................................4
2.1.2 TFF Consumables Breakdown per Test ..........................................................................................4
2.1.3 Allegro Single-use TFF System ......................................................................................................5
2.2 Test Method Summary ............................................................................................................................6
3. Results and Discussion..............................................................................................................................7
3.1 Assembly, Installation and Systems Integration ........................................................................................7
3.2 Minimum Working Volume ......................................................................................................................7
3.3 Pre-use Conditioning ..............................................................................................................................7
3.3.1 TOC and Conductivity Trends ........................................................................................................7
3.3.2 Endotoxin and Bioburden Analysis ................................................................................................8
3.4 Performance Evaluation ..........................................................................................................................9
3.4.1 Process Optimization and Benchmark ..........................................................................................9
3.4.2 Comparability, Scalability and Reproducibility of Test Results..........................................................9
3.4.3 Product Recovery ........................................................................................................................11
3.5 Post-Use Decontamination and Disassembly ........................................................................................12
4. Conclusions................................................................................................................................................12
5. Acknowledgements ...................................................................................................................................12
6. References .................................................................................................................................................13
2
Abstract/Summary
Performance evaluation of Pall Cadence™ Single-Use Tangential Flow Filtration (SUTFF) modules with Omega™
polyethersulfone membrane have been conducted in collaboration with Rentschler Biotechnologie GmbH.
Focus of these tests was to assess the comparative performances of the SUTFF modules against regular Pall
Omega T-Series cassettes, and to evaluate the compatibility and usability features with disposable flow paths
when integrated into the Allegro™ single-use TFF system. Further parameters investigated were working volume,
water for injection (WFI) flush requirements, product recovery, installation and ease of use.
Performance evaluation tests conducted at a transmembrane pressure of 1 bar and varying feed channel pressure
drops or Delta P (0.5 – 2 bar) over the concentration range of 10 – 100 g L-1 monoclonal antibody product confirmed reproducible (0.4 – 6.9 %) and scalable flux performance (4 - 11 %) and comparable product recoveries
between 0.5 m2 Cadence SUTFF modules and 186 cm2 standard Omega T-Series TFF cassettes.
Furthermore, integrating gamma-irradiated Cadence SUTFF modules into Rentschler’s existing Allegro™ singleuse TFF system with the utilization of gamma-irradiated ½ in. flow paths resulted in minimal and/or negligible
total organic carbon (< 1 ppm) and endotoxin values (<0.01 EU mL-1) when run under recommended operating
conditions, achieved within low WFI flush-out volumes. In addition, the absence of detectable bioburden
suggested that the sanitization and post-sanitization WFI flush steps could therefore be eliminated from the
pre-use conditioning protocol for additional cost savings realized in terms of buffer volume requirements,
preparation time and associated labor, when compared to conventional TFF cassettes.
1.
Introduction
Single-use technology is widely accepted in bioprocessing, with key benefits being the elimination
of cross contamination and cleaning, and greater flexibility in manufacturing.
Tangential Flow Filtration (TFF) is more complex than many other unit operations for which single-use
approaches have been adopted. The product is recirculated during its concentration and key parameters
such as the transmembrane pressure, the differential pressure (Delta P) and the recirculation flow rate
are controlled and monitored. In addition, the system working volume and hold-up volume are key to
ensuring optimal product recovery.
The Allegro Single-Use TFF (SUTFF) system is an automated system designed for the ultrafiltration and
the diafiltration of proteins, recombinant molecules, potent biological and cytotoxic drugs, and vaccines [1].
This system integrates a fully disposable flowpath with all the sensors required to run and control the TFF
process. The flowpath sub-sets are delivered gamma-irradiated.
During this study, Rentschler’s customized Allegro single-use TFF system was tested in conjunction with
Pall Cadence single-use TFF modules with Omega polyethersulfone (PES) membrane. These modules
are pre-assembled, pre-flushed and gamma irradiated modules, providing ease-of-use and readiness
of use compared to standard TFF cassettes used in a single-use mode.
The tests were performed on a monoclonal antibody (mAb) solution and the main objectives of this
study were:
• Evaluate comparative performances of Cadence single-use TFF modules (i.e., flux, product recovery,
etc.) against standard Omega T-Series cassettes.
• Assess installation, assembly and ease-of-use features of the Cadence SUTFF modules integrated in
the Allegro SUTFF system utilizing ½ in. gamma-irradiated flow paths.
www.pall.com/biopharm
3
2.
Experimental
Pall Cadence SUTFF modules with 30 kDa Omega membrane (Figure 1[b]) were tested in 0.5 m2
formats. The tests were conducted in duplicate in combination with a ½ in. single-use flow path in
Rentschler’s Allegro single-use TFF system.
Figure 1
[a] Cadence single-use TFF modules [b] Cadence SUTFF module with 0.5 m2 membrane area.
[a]
[b]
Preliminary process characterization for the mAb product, which was established as the performance
benchmark for the SUTFF modules evaluated in this study, was conducted by Rentschler with a Pall
Centramate™ T-Series cassette (186 cm2) with Omega membrane (Part Number OS030T02).
Main parameters investigated in this study consisted of an operational window of system pressure and
cross-flow flux (CFF), permeate flux, product recovery, assembly and ease-of-use attributes. Additional
data was collected for the assessment of WFI flush performance, quantitative evaluation of total organic
carbon (TOC), endotoxins, and bioburden levels, as well as the estimation of minimum working volume
for the different installations. Details of materials and consumables breakdown per test, utilized equipment
and followed methodology are discussed next.
2.1
Materials, Equipment and Methods
2.1.1
Feedstock
The feedstock used for the SUTFF feasibility tests is a mAb product. Product
characteristics are considered representative for typical feed materials processed in
TFF unit operations. The tests were planned according to a mAb standard production
(final concentration drug substance between 10 and 80 g L-1).
The process characterization for the product and the generation of process
development (PD) data was conducted with a Pall Omega membrane
Centramate T-Series cassette (OS030T02).
2.1.2
TFF Consumables Breakdown per Test
• Pall Omega membrane Centramate T-Series cassette – 186 cm2 (OS030T02)
– Test series conducted in-house by Rentschler on ÄKTAcrossflow* TFF system
(GE Healthcare)
• Cadence Single-use TFF module #1 - 0.5 m2 (30 kDa) – gamma irradiated
– ½ in. manifold – gamma irradiated
– 50 L disposable biocontainer
– Installation: performed under laminar flow to accommodate the single-use module
and assembly of subsets
– Test setup: Pall Allegro Single-use TFF system
4
• Cadence Single-use TFF module #2 - 0.5 m2 (30 kDa) – gamma irradiated
– ½ in. manifold – gamma irradiated
– 50 L disposable biocontainer
– Installation: performed under clean room (class D) conditions to accommodate
single-use module and assembly of subsets
– Test Setup: Pall Allegro single-use TFF system
2.1.3
Allegro Single-use TFF System
The Allegro single-use TFF System, shown in Figure 2, utilized for the tests is owned
by Rentschler [2], with features and key attributes summarized in Table 1.
Figure 2
Test Setup: Rentschler’s Allegro single-use TFF system (Photo courtesy of Rentschler
Biotechnologie GmbH).
Table 1
Features and key attributes of Rentschler’s Allegro SUTFF system
Features
Key Attributes
Automated
Recipe control
½ in. tubing
1000 L h-1 feed flow
0.5 - 2.5 m2 area
Good engineering design
Open Architecture
Ease of use
Ease of access to components
Gamma irradiated manifolds
The system is equipped with ½ in. flow path manifolds as shown in Figure 3 [a] and
[b]. The installation of the 0.5 m2 Cadence SUTFF module into the system holder is
also shown in Figure 4.
Figure 3
SUTFF Manifolds [a] open architecture flow path and [b] manifold design.
[a]
[b]
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5
Figure 4
Installation of Cadence SUTFF module into the holder in the Allegro system.
2.2
Test Method Summary
Test protocol followed for the performance evaluation of Cadence SUTFF modules is summarized
as follows:
• Installation
– Assembly under laminar flow hood - for module #1
– Assembly under clean room (Class D) – for module #2
• Pre-use Conditioning
– Determination of feed/retentate hold up volume with WFI via feed biocontainer weight drop
utilizing Allegro system load cells.
– WFI Flush (Samples for TOC and conductivity, endotoxins and bioburden)
– SUTFF module integrity test
– Sanitization with 0.5 N NaOH
– Buffer equilibration (Sample for endotoxins and bioburden)
• Optimization and Processing
– Delta P excursion at constant TMP of 1 bar to simulate variation in cross-flow flux
(CFF in L m-2 h-1) at product feed concentrations of 10, 20, 40 and 80 g L-1.
• Post-use Conditioning
– Product recovery – no flush – by gravity and pumping through recovery line
– Decontamination with 0.5 N NaOH
– WFI Flush
– Disassembly and disposal
The recommended flush-out volumes for SUTFF modules are a minimum of 20 L m-2 (2 L ft-2)
deionized (DI) water to waste until a desired TOC, conductivity or neutral pH is achieved. Also
note that the actual required volumes might vary, depending on the application requirements.
6
3.
Results and Discussion
3.1
Assembly, Installation and Systems Integration
Assembly and installation of Cadence SUTFF modules into the Allegro SUTFF system requires
manual compression at a nominal torque setting of 900 in-lbs (102 N m) in the system holder.
Installation and assembly of the ½ in. flow path with gamma-irradiated SUTFF modules was
carried out according to both laminar flow hood assembly and Class D clean room protocols.
During system integration the pre-assembled Cadence SUTFF modules provide improved
handling, compared to the integration of conventional TFF cassettes, gaskets and single-use
distribution plates. Featuring a containment design, supplied pre-flushed and stored in water,
the SUTFF modules enhance operator safety.
3.2
Minimum Working Volume
The system minimum working volume consists of the volume in the feed/retentate loop, plus
the minimum volume in the retentate biocontainer before the system draws air into the loop.
In correspondence to the Allegro SUTFF system specification, a minimum working volume of
<0.7 L, was confirmed for both tests conducted with 0.5 m2 Cadence Single-use TFF modules
in combination with a ½ in. single-use flow path. As summarized in Table 2, system minimum
working volume estimate was based on the measurement of the weight difference on the Allegro
SUTFF system load cells. Minimum working volume is of great importance to achieve high
protein recovery and process yields.
Table 2
Minimum working volume during two replicates
3.3
0.5 m2 SUTFF Module
#1
#2
Feed/Retentate Hold up [L]
Minimum Retentate Biocontainer Volume [L]
(for a 50 L Biocontainer)
Minimum Working Volume [L]
0.45
0.11
0.54
0.12
0.56
0.66
Pre-use Conditioning
3.3.1
TOC and Conductivity Trends
Cadence single-use TFF modules with Omega membrane are delivered pre-flushed,
stored in water and gamma irradiated. They can be considered as ready to use. In
order to better assess the effectiveness of the flush-out performance, the Cadence
single-use TFF modules were assayed for TOC and conductivity of the flush media
(WFI) for the initial flush.
Flush-out data for the Cadence single-use TFF module #2 (0.5 m2) operated under
recommended flush-out conditions, resulted in low TOC values (<1 ppm) at low flush
volumes (<20 L m-2). TOC flush-out curve with subsequent conductivity trends for the
0.5 m2 Single-use TFF module #2 is shown in Figure 5.
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Figure 5
SUTFF flush-out curve with TOC (left y-axis) and conductivity (right y-axis) trends.
Single-Use TFF Modul
e # 2 - 0.5 m2
Module
5
TOC
TOC [mg L -1]
6
Retentate T
OC
TOC
TOC
Permeate T
OC
Conductivity
Retentate Conductiv
ity
Permeate Conductiv
Conductivity
ityy
4
5
4
3
3
2
2
1
1
0
0
0
3.3.2
Conductivity [µS cm-1]
6
10
20
30
WFI Flush V
olume [L m-2]
Volume
o
40
50
Endotoxin and Bioburden Analysis
In addition to the TOC and conductivity testing, Cadence SUTFF modules were
further assayed for endotoxin levels and bioburden for the initial and post-sanitization
flush. As summarized in Table 3, samples from the SUTFF system integrating singleuse TFF modules showed no bioburden and the endotoxin levels were ≤0.01 EU mL-1
without pre-use sanitization.
Thus a pre-use sanitization step for gamma irradiated single-use TFF modules might
not be required, if the user’s processing requirements are met. This will save time,
sanitization solutions and shorten the turnaround times for TFF processes utilizing Pall
single-use TFF modules. The modified pre-use conditioning steps with the utilization
of SUTFF modules are depicted in Figure 6.
Table 3
Endotoxin and bioburden data before and after pre-use sanitization
SUTFF 0.5 m2 Module #1
Endotoxin [EU mL ]
Bioburden [cfu mL-1]
-1
Endotoxin [EU mL ]
Bioburden [cfu mL-1]
-1
8
Before Sanitization
After Sanitization
Retentate
Permeate
Retentate
Permeate
< 0.01
0
< 0.01
0
< 0.10
0
< 0.10
0
SUTFF 0.5 m2 Module #2
Before Sanitization
After Sanitization
Retentate
Permeate
Retentate
Permeate
0.01
0
< 0.01
0
< 0.10
0
< 0.10
0
Figure 6
Steps for pre-use conditioning Cadence single-use TFF modules
with Omega membrane.
Install
Modules
Flush
Step 1
Step 2
Step 3
Flush
Determine
Hold-up Volume
Integrity
Test
Santitization
Step 4
Buffer
Conditioning
Optimization
or
Processing Mode
Flush
Optional
After confirming system and module integrity, conducted at a feed pressure of 2 barg
(30 psig), pre-use conditioning of the modules was completed via buffer conditioning
for a total duration of 15 - 30 minutes.
3.4
Performance Evaluation
3.4.1
Process Optimization and Benchmark
Performance evaluation consisted of generating a control experiment adopting
Rentschler’s process optimization protocol, which assesses the impact of cross-flow
for a constant TMP processing of the mAb feedstock between 10 and 100 g/L. In this
respect, benchmark data for standard cassette performance was generated with a
Pall Omega membrane Centramate T-Series cassette (OS030T02, 186 cm2) with the
same mAb solution utilized for the SUTFF tests at the 0.5 m2 scale.
Permeate flux vs. concentration at constant TMP of 1 bar and varying Delta P to
simulate the impact of cross-flow on process flux is shown in Table 4.
Table 4
Permeate flux data for Pall Omega membrane Centramate cassette (OS030T02)
Concentration [g L-1]
Delta P 2.0 bar
Delta P 1.5 bar
Delta P 1.0 bar
Delta P 0.5 bar
3.4.2
10.0
20.0
40.2
60.2
80.1
100.2
157.9
145.8
129.4
102.6
107.0
99.2
86.9
67.2
60.9
54.8
46.3
33.8
34.4
30.8
25.9
17.9
20.1
17.7
14.4
10.2
11.7
10.3
8.7
6.5
Flux
[L m-2 h-1]
Comparability, Scalability and Reproducibility of Test Results
Performance evaluation of Cadence SUTFF modules integrated into Allegro SUTFF
system consisted of generating a performance map with similar process parameters
(1 bar TMP at various Delta P set-points) in order to benchmark against the standard
cassette data discussed in Section 3.3.1. As shown in Figure 7, test data for 0.5 m2
Cadence SUTFF modules showed excellent performance, comparable to standard
Omega T-series cassettes tested at smaller scale.
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Figure 7
SUTFF performance evaluation [a] module #1 and [b] module #2.
[a]
Process Optimization and Performance Evaluat
ion
Evaluation
with 0.5 m2 Single-Use TFF Module #1
160
Delta P 0.5 bar (TMP=1 bar)
Delta P 1.0 bar (TMP=1 bar)
Delta P 1.5 bar (TMP=1 bar)
Delta P 2.0 bar (TMP=1 bar)
Flux [L
[L m-2 h-1]
140
120
100
80
60
40
20
0
1
10
100
Concentration [g L-1]
Process Optimization and Performance Evaluat
ion
Evaluation
with 0.5 m2 Single-Use TFF Module #2
[b]
160
Delta P 0.5 bar (TMP=1 bar)
Delta P 1.0 bar (TMP=1 bar)
Delta P 1.5 bar (TMP=1 bar)
Delta P 2.0 bar (TMP=1 bar)
140
Flux [[L
L m-2 h-1]
1000
120
100
80
60
40
20
0
1
10
100
1000
Concentration [g L-1]
At a given Delta P set-point, the average permeate flux between the control cassette
and the SUTFF modules during concentration from 10 to 80 g L-1, differed between
4-11% for SUTFF module #1 and 4-8 % for module #2, favouring SUTFF modules.
While the minor difference in performance was attributed to the changes in CFF as
feed was concentrated, the performance data plotted in Figure 7 and summarized in
Table 5, not only showed comparable performance but also confirmed 27x scalability
(186 cm2 to 0.5 m2) to that of standard Omega T-Series cassettes.
Table 5
Permeate flux data for Pall 0.5 m2 Single-Use TFF modules #1 and #2
SUTFF Module #1
SUTFF Module #2
Concentration [g L ]
Concentration [g L-1]
-1
Delta P 2.0 bar
Delta P 1.5 bar
Delta P 1.0 bar
Delta P 0.5 bar
10
11.0
20.9
40.7
79.5
132.0
115.2
108.0
92.4
98.4
86.4
79.2
63.6
61.2
54.0
46.8
36.0
24.0
21.6
18.0
13.2
Flux
[L m-2 h-1]
10.4
21.0
41.3
83.6
135.6
129.6
112.8
93.6
99.6
91.2
76.8
61.2
58.8
54.0
45.6
32.4
22.8
21.6
19.2
13.2
It is noteworthy to mention that the pressure excursions for different concentration
profiles were performed stepwise from low to high concentrations. In this respect, a
slight increase of the product temperature over processing time might have occurred
and could have also contributed to the observed increase in permeate flux for the
higher feed concentrations. During these experiments, temperature monitoring was
not included as a parameter. Regardless of minor influential factors, the variability in
permeate flux between the control run and the SUTFF modules was minimal.
As shown in Figure 8, processing of 0.5 m2 Cadence SUTFF modules at constant
TMP of 1 bar and various Delta P resulted in identical performance, thus excellent
reproducibility, with minimal variation of 0.4 – 6.9%, over the entire Delta P set-points
and concentration range tested.
Figure 8
Process reproducibility with 0.5 m2 SUTFF modules at [a] Delta P of 0.5 bar (constant
TMP of 1 bar) [b] Delta P of 1 bar (constant TMP of 1 bar) [c] Delta P of 1.5 bar
(constant TMP of 1 bar) and [d] Delta P of 2 bar (constant TMP of 1 bar).
Process Reproducibility
with 0.5 m2 Single-Use TFF Modules
Delta P 0.5 bar (module #1)
Delta P 0.5 bar (module #2)
1
Flux [L
[L m-2 h-1]
3.4.3
1000
Process Reproducibility
with 0.5 m2 Single-Use TFF Modules
[c]
160
140
120
100
80
60
40
20
0
10
100
Concentrati
Concentration
on [g L-1]
Flux [[L
L m-2 h-1]
160
140
120
100
80
60
40
20
0
100
10
Concentrati
on [g L-1]
Concentration
160
140
120
100
80
60
40
20
0
Delta P 1.0 bar (module #1)
Delta P 1.0 bar (module #2)
1
10
100
Concentration
Concentration [g L-1]
[d]
Delta P 1.5 bar (module #1)
Delta P 1.5 bar (module #2)
1
Process Reproducibility
with 0.5 m2 Single-Use TFF Modules
[b]
Flux [L
[L m-2 h-1]
Flux [[L
L m-2 h-1]
[a]
1000
1000
Process Reproducibility
with 0.5 m2 Single-Use TFF Modules
160
140
120
100
80
60
40
20
0
1
Delta P 2.0 bar (module #1)
Delta P 2.0 bar (module #2)
10
100
Concentrati
Concentration
on [g L-1]
1000
Product Recovery
Product recovery was carried out by gravity drain via the low point recovery valve of
the system and subsequent pumping through the drain valve. No additional recovery
flush was performed. As shown in Table 6, the product recovery rates achieved for
0.5 m2 SUTFF modules were >92 %, which was comparable to the values achievable
with standard cassettes. Product recovery could be further improved via a buffer
chase for retentate displacement at the expense of retentate pool dilution.
Table 6
Product recovery for Pall 0.5 m2 single-use TFF modules
SUTFF Module and manifold tested
[%]
0.5 m Module #1
0.5 m2 Module #2
92.5
93.1
2
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3.5
Post-Use Decontamination and Disassembly
Upon completion of the processing and product recovery steps, the Cadence single-use TFF
module and system flow path should be discarded per local codes or standards. This may
include autoclaving or incinerating the disposable products (module and tubing). On the other
hand, post-use decontamination protocols may change depending on the end-user application
and containment requirements and TFF system design.
In this study, the post-use decontamination or inactivation of the whole TFF system was
carried out prior to disassembly via 1 N NaOH recirculation and subsequent DI Water flush-out.
Disassembly of the single-use TFF flow path including the SUTFF modules from the TFF skid to
allow a safe post-use containment has been demonstrated.
4.
Conclusions
Integration of Cadence single-use TFF modules into Allegro single-use system equipped with disposable
flow path was successfully demonstrated during testing at Rentschler Biotechnologie GmbH (Laupheim,
Germany).
Performance evaluation of 0.5 m2 Cadence single-use TFF modules over a concentration range of
10 – 80 g L-1, during constant TMP processing at different Delta P set points, resulted in an excellent
performance that was comparable to that of standard Omega T series cassettes. Benchmark against
186 cm2 standard cassettes, further confirmed scalable performance for the processing of same mAb
feedstock. In addition, the Cadence modules performance map generated over the entire Delta P set-points
and concentration range, was reproducible with minimal variation of 0.4 – 6.9 %, indicating process robustness and reliable operation.
Product recovery for SUTFF modules was carried out by gravity drain only via the low point recovery
valve of the system and resulted in comparable yields to typical values achieved in the SUTFF system
with regular TFF cassettes.
Data for 0.5 m² Cadence SUTFF modules indicate low TOC values even with low flush volumes. Samples
from the SUTFF system integrating gamma-irradiated SUTFF modules showed no bioburden and
endotoxin levels ≤ 0.01 EU mL-1 without pre-use sanitization. This supports elimination of the pre-use
sanitization step. Such an approach could offer significant savings through reduction in buffer/sanitant
volumes and reduces direct labor hours required for solution preparation, and shortens the processing
time for TFF unit operation, with the utilization of Cadence single-use TFF modules. Time saving would
be in the range of 2 - 4 hours. Rentschler typically assembles regular TFF cassettes and conducts
pre-sanitization one day prior to processing their product. Potentially, all processing steps could
be performed on the same day with SUTFF modules, which could also improve overall productivity
and resource allocation.
Easy assembly and sterile connections of Cadence single-use TFF modules to single-use flow path
under a laminar flow hood has been demonstrated. Based on bioburden data gathered, assembly
under clean room (class D) conditions might be sufficient for processing and allow bioburden control.
Further data would need to be collected and a risk assessment performed by Rentschler would be
required to finalize the decision for the further simplification of pre-use conditioning steps.
Finally, disassembly of the single-use TFF flow path including the Cadence single-use modules (post-use
containment) has been demonstrated. This would be a benefit in applications were the operator safety is
a concern post-use (e.g. with cytotoxic or some virus based products).
5.
Acknowledgements
Authors gratefully acknowledge the support provided by the Rentschler team and Pall TFF Product
Development (Rob Ieraci and Rachel Forman) and PASS Engineering team, (Steve Crouch, Aymen
El-Ghezal and Zander Hack).
12
6.
References
1. Nicholson, Pauline and Storm, Erik. "Single-Use Tangential Flow Filtration in Bioprocessing".
BioProcess International (2011).
2. Laukel, Markus; Rogge, Peter and Dudziak Gregor. “Disposable Downstream Processing
for Clinical Manufacturing”. BioProcess International (2011).
About Rentschler:
Rentschler is a biopharmaceutical contract manufacturer with over 35 years proven track record. As an independent
and family-owned company headquartered in Germany our full-service customized solutions range from supporting
drug candidate selection by our TurboCell platform, as well as cell line and process development over production
to analytics and fill & finish.
Focused on the utilization of mammalian cell lines, our experience covers the development and production of
recombinant proteins such as cytokines, enzymes, monoclonal antibodies and fusion proteins in compliance
with international GMP standards (EMA/FDA). Our project management is characterized by proactive and
responsive communication. Successful projects and long lasting client relationships show that we are reliable
and experienced.
State-of-the-art facilities and services comprising batch, fed-batch and perfusion processes allow the production
of material for clinical phases and commercial supplies. Our GMP manufacturing comprises stainless steel bioreactors with total volume from 30 L up to 3,500 L ensuring the flexible and customized production and delivery of
material. As a cost-efficient and fast manufacturing alternative, Rentschler provides also single-use bioreactors
with volumes of up to 1,000 L. Our Fill & Finish facility offers aseptic liquid filling in vials (100 up to 80,000 units),
lyophilization (100 up to 70,000 units) and aseptic liquid filling of prefilled syringes (100 to 15,000 units). Our
experience with international regulatory affairs and authorities complete our services.
In summary, our full-service concept allows us to react with flexibility on the individual project requirements
of our clients.
Visit us on the Web at www.pall.com/allegro
E-mail us at allegro@pall.com
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Pall Corporation has offices and plants throughout the world in locations such as: Argentina, Australia, Austria,
Belgium, Brazil, Canada, China, France, Germany, India, Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico,
the Netherlands, New Zealand, Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden,
Switzerland, Taiwan, Thailand, the United Kingdom, the United States, and Venezuela. Distributors in all major
industrial areas of the world. To locate the Pall office or distributor nearest you, visit www.pall.com/contact.
European Headquarters
Fribourg, Switzerland
+41 (0)26 350 53 00 phone
LifeSciences.EU@pall.com e-mail
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.
Asia-Pacific Headquarters
Singapore
+65 6389 6500 phone
sgcustomerservice@pall.com e-mail
© 2014, Pall Corporation. Pall,
, Allegro, Cadence and Omega 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. ◆ÄKTAcrossflow is a trademark of GE
Healthcare.
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