1) A new D screen cassette for tangential flow filtration was tested and shown to reduce pressure drop by 50% compared to a standard C screen cassette while maintaining high flux performance. 2) The D screen cassette was able to reach final protein concentrations up to 25% higher than the C screen cassette due to its lower pressure drop at high viscosities. 3) The D screen cassette provides a better balance of low pressure drop and high flux compared to other screen types, allowing for processing of solutions with viscosities over 40 cP.

1. Introduction
Formulating a highly concentrated product that is
suitable for subcutaneous delivery is key to achieving
injectable volumes, typically around 1 mL.
Newly designed TFF cassettes capable of processing
high viscosity product streams were tested using human
IgG (Seracare) as a model feed. The results showed that
the pressure drop along the feed channel was reduced
by more than 50% compared with regular TFF devices
while only sacrificing 15% of the flux and the mass
transfer coefficient. Compared with more open channel
TFF devices with a suspended feed screen, the new
high viscosity TFF cassettes can reach the same final
concentration with nearly double the mass transfer
coefficient over the course of the process.
In this poster, we focus on the various screens that are
available in the Pellicon® cassette family, especially the
D screen which was developed to achieve formulations
with a viscosity higher than 15 cP within an acceptable
pressure drop and with a high flux. A robust, scalable
comparison trial between the different screens was
performed in order to compare these screens.
Ultrafiltration/Diafiltration Process Development
of High Concentration/Viscosity Applications
As the viscosity increases, so does pressure drop with a proportional
relationship. It has been verified that in a well designed TFF UF system the
component that has the greatest effect on overall system resistance (pressure
drop) is the TFF cassette itself. (Figure 1).
The pressure drop of ultrafiltration cassettes (module resistance) due to
the increased viscosity of the protein solution during concentration, is the
most important factor affecting the ability to achieve high final product
concentrations in TFF UF applications for protein.
Different module designs exhibit different pressure drops; Figure 2
demonstrates how utilizing a conventional screen (C screen) and a suspended
screen (V) impact on cassette resistance to fluid flow.
Taking into account the typical maximum inlet pressure for module, by simple
interpolation, the maximum protein concentration achievable for a process
utilizing a V screen device is expected to be much higher than C screen. When
dealing with materials at a high concentration/viscosity, the selection of the
most appropriate screen for the UF cassette is critical for process success.
The mass transfer coefficient and Cw
was determined by calculating absolute
slope of permeate flux versus bulk concentration as described by the stagnant
film model equation taking into account data range before pump turn down:
The D screen flux along the concentration step is similar to the C screen one at
feed flow higher than 5 L/min/m², but D screen was able to reach a 20% higher
final concentration.
D screen average flux is 75% compared to C screen at 3L/min/m², but still a
10% higher final concentration was reached.
In all the experiments, D screen was able to reach a higher final concentration
than C screen.
Where
J = normalized permeate flux
Cw
= protein concentration at the membrane
Cb
= protein concentration in the bulk
Cp
= Protein concentration in the permeate (considered = 0)
k = mass transfer coefficient
Initial and final protein concentration was determined by UV measurement.
Experimental results are summarized in the following table, comparing D versus
C screen performances:
From internal and external experience, the D screen is suitable for high
concentration TFF ultrafiltration applications and can process 2 to 3 higher
viscosities than the C screen at typical process cross flow rates.
In addition, the D screen is consistently able to achieve 4-25% higher final
product concentrations compared to the C screen at the processing limits.
It showed a 0-24% reduction in mass transfer compared to the C screen. In
addition, the D screen required 5-25% more membrane area (or process time)
compared to the C screen for a similar process (Significant improvement over V
screen which requires 2 times more area).
The new D screen cassette has a pressure drop about 50% of the C screen
pressure drop. A comparative concentration step was also run at 3 different
feed flows (3 – 5 and 7 L/min/m²) post flux vs. TMP excursion with a 20 g/L
solution of human IgG to determine the optimum working parameters for this
specific product.
The IgG solution was concentrated as much as possible according to the
following process strategy:
• Maintain the TMP set-point as long as possible by opening the back
pressure valve until retentate pressure reached 2 – 3 psig;
• Next, maintain the feed flow rate set-point as long as possible until a max
Pinlet = 60 psig is reached;
• Slowly ramp down the feed pump to maintain Pfeed at the max Pinlet =
60 psig until the minimum achievable flow is reached (the pump cannot be
turned down any further) or the flux drops to zero;
Screen Selection
We currently offer four different screens: (A, C, D and V) in the Pellicon®
cassette format range.
A screen: A tight screen that is used for dilute protein solution or low viscosity
solutions. The tight weave is not suitable for highly concentrated protein
solutions as the pressure drop is unacceptably high at greater viscosities.
However, this screen typically provides superior flux performance.
C screen: A coarse screen that is used for product streams with viscosity up
to 15 cP. The C screen provides good flux performance but the pressure drop is
above the limit of usage when the viscosity increases.
V screen: A suspended C screen. The V screen gives lower pressure drops than
the C screen, but the flux performance is much lower compared to C screen.
D screen: This new screen
has a coarser mesh and
altered weave compared
to the standard C screen.
It was designed to offer
lower pressure drop
without the large flux
performance penalty found
when using a suspended
screen technology
Conclusion
High protein concentration by TFF UF is a challenging application. From an
operational point of view, the increase of viscosity and module resistance with
the increase of protein concentration obliges the operator to find a compromise
between pressure drop (module resistance) and flux at final concentration.
A variety of TFF cassette designs exist and the choice of the most appropriate
TFF cassette is key for an efficient and high performance process.
The new Pellicon® 3 cassettes with D screen, when accompanied by the best
working procedure, are able to provide higher final product concentration
with similar flux performance of a tighter screened cassette. This performance
similarity is dependent on being able to provide a reasonable feed flow rate.
A summary of the performances of Pellicon® 3 cassette with D screen in
comparison with C screen is presented in Table 2.
Comparison Study of C and D Screen
at High Protein Concentrations
An internal study was performed in order to evaluate screened module
resistance (or pressure drop or DP) vs. protein (IgG) concentration.
The pressure drop across the feed channel for cassettes with different screens
is shown in Figure 4. At a given feed flow, the pressure drops increase with the
“tightness” of the screen. Since the pressure drop (dark blue and light blue lines)
is related to the protein concentration and its viscosity (green line), the lower
the feed channel resistance the higher the protein concentration that can be
achieved.
Frederic Sengler, Josselyn Haas, Renato Lorenzi
0
5
10
15
20
25
30
35
5 cp
psid
10 cp 15 cp 20 cp
holder
90% elbow
straight pipe
tank return
block valve
retentate valve
cassette
0.0
20.0
40.0
60.0
80.0
100.0
120.0
140.0
0.0 50.0 100.0 150.0 200.0 250.0
dP(psi)
Concentration of BgG (g/L)
V Screen
C Screen
Table 1. Process concentration summary: D and C screen performances
comparison
Table 2. Performances comparison D screen vs. C screen
Figure 5 shows the flux vs. concentration curves for the various screens.
By the stagnant film model, the slopes represent the mass transfer coefficient
for each device.
Figure 5:
Cassettes
permeate flux vs.
IgG concentration
at 3 different
feed flows
Figure 4:
D screen and C
screen cassette
resistance vs. IgG
concentration
(internal data).
Figure 3: Pellicon® Cassette Screens
Figure 1: TFF System components pressure drop
Figure 2: C and V screen modules resistance versus protein
concentration
3 LMM 5 LMM 7 LMM
Screen D C D C D C
k (LMH) 13,21 20,17 33,73 34,4 35,33 36,83
Cgel (g/L) 236 230 230 209 229 217
Max g/L 254 221 275 231 275 226
Product Attribute Performance Outcome
Final viscosity > 40 cP with IgG
Feed channel DP - proteins 50% of C screen at ≥ 25 cP
Mass transfer k ≥ 75% of C screen
Max protein concentration ≈ 1.25 X of C screen
Membrane area ≈ 1.25 X of C screen
0
5
10
15
20
25
30
35
40
45
50
0
10
20
30
40
50
60
70
80
90
0 50 100 150 200 250 300
Viscosity(cP)
Resistance(psi/LMM)
IgG Concentration (mg/mL)
Module resistance and IgG viscosity as a function of
concentration at 25°C - Buffer: Milli-Q® ultrapure water
Viscosity
D screen
C screen
0
10
20
30
40
50
60
70
80
90
10 100 1000
Flux(LMH)
Concentration (g/L)
Flux vs. concentration at different feed flow
D screen 3 LMM
D screen 5 LMM
D screen 7 LMM
C screen 3 LMM
C screen 5 LMM
C screen 7 LMM
A Screen
0.4 mm thick
C Screen
0.53 mm thick
D Screen
0.61 mm thick
V Screen
0.93 mm thick
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