A P P L I C A T I O N

N O T E

Pellicon 2 vs. Hollow Fiber

Filter Cartridge

Millipore recommends Pellicon 2 cassettes over Hollow Fiber filter

modules for ultrafiltration of biopharmaceutical solutions

Figure 1. Hollow fiber module and Pellicon 2 device. Both devices in the photo reveal a
large difference in length and size. However the membrane area is almost identical.

The Hollow Fiber (HF) design was

developed over 35 years ago by the
early pioneers in Ultrafiltration (UF)
technology. Long and straight hollow
fibers, typically polyethersulfone,
were bundled into a housing and
used for concentration of beverages,
cutting oils, water and even wastewater. Hollow Fiber modules are also
used for low-pressure applications
such as hemo-filtration (dialysis) and
in some early pharmaceutical applications.
Scientists soon started to optimize
processes, which spurred development of UF devices specifically aimed
for production of pharmaceuticals.
The cassette format (Pellicon 2) is a
result of this ongoing development.
It offers the highest level of optimization to address improved separation
efficiency, processing speed, linear
scalability, pressure capability,
robustness and reliability. You will
find guidelines for conversion from
Hollow Fiber cartridges to Pellicon 2
cassettes in the following sections.

Hollow Fiber vs. Pellicon 2 Summary

Feature

Hollow Fiber

Pellicon 2

Robustness and reliability

Fibers are prone to stress failure

Very robust

Pressure capability

Low

High

Membrane choices

1. Polyethersulfone

1. Polyethersulfone
2. Regenerated Cellulose
3. PVDF (for MICRO filtration)

Flow rate required to operate TFF processes

High flow rate resulting in

High energy consumption
Large piping
Compromised concentration ratio
Increased demand for floor space

Low flow rate resulting in

Low energy consumption
Small piping
High concentration ratio
Compact system size

Linear scale-up

Compromised by differences in the length

of the flow channel in laboratory vs.
process scale cartridges

Identical length of flow channel length in

all cartridge sizes to facilitate predictable
scaling results

Consistency of retention relative to

retentate channel design

Compromised consistency due to

Open flow channels. No internal mixing

High consistency due to

Build-in static mixer efficient internal mixing

Consistency of retention relative to

the retentate flow channel length

Compromised consistency due to

Long flow channels

High consistency due to

Very short flow channels

Flat membrane devices have higher

pressure-ratings than HF modules and
have considerably higher tolerance to
pressure excursions. Typical pressure
limitations of HF modules range from
23 bar (29 43 PSI) inlet pressure
compared to 5.56.9 bar (80 100
PSI) for Pellicon 2 cassettes (Figure 2).
As a general rule and within limitations, filtrate rate or flux increase with
pressure. Optimum UF process conditions
typically require 3 to 5 bar pressure
(40 70 PSI), however, pressure limitations of HF modules prevent users from
operating in this area. Consequently
processing with HF modules will be
slower or the system and membrane
area will be larger than necessary.
As a result, users tend to operate
HF modules at the upper limit of the
fibers pressure capability, elevating the
risk of fiber damage. Fibers may
break or burst during processing
which can create a leak area similar
to the cross section of the fiber diameter (typically 0.5 to 1.1 mm) and
allow passage of valuable protein
through this opening.
Operating history indicates that
fiber failures are prone to occur at the
interface points between the fiber and
potting compound that bonds each
end in place. The risk of failure must
be based on two interfaces per fiber

Pressure Capability
7

100

6
5

70

PSI

Pressure Capability

Processing of pharmaceutical products

requires a much higher degree of
equipment reliability than equipment
used for removal of turbidity in apple
juice or for concentration of wastewater. Each lot of pharmaceutical
product is very valuable and the consequences of a manufacturing failure,
either due to Hollow Fiber failure or
production of an ineffective product,
are severe.
In HF modules, the long narrow
fibers are self-supporting so each
fiber must withstand the internal pressure required for processing. To the
contrary, in a cassette each sheet of
membrane is supported by the device
itself combined with self-balancing
pressures from parallel flow channels.

Bar

Robustness and Reliability

40

2
1
0
Pellicon 2
Max
Nominal

Hollow Fiber
Typical pressure range
for Ultra Filtration
applications

Figure 2. Pressure capability of Hollow

Fibers limits process optimization

times the number of fibers in each HF

module (often 3,000 fibers per module). For example, a process system
with 10 HF modules may contain a
total of 30,000 fibers. Consequently
there are 60,000 potential failure
points each ranging from 0.5 mm to
1.1 mm.
Pellicon 2 cassettes do not contain
Hollow Fibers and are not prone to
stress failure due to the self-balancing
construction of the flow channels.
Millipore recommends Pellicon 2
cassettes for BioPharmaceutical
applications.

Membrane Choices
Membrane surface characteristics play
a role in process design and optimization. Some proteins may be best
processed by ultra-low protein binding
membranes such as Regenerated
Cellulose due to the inherent low
fouling characteristics of these membranes. Consequently, it is beneficial
to have more than one choice. Hollow
fibers for Ultrafiltration are only available in Polyethersulfone based materials. (Single-use HF cartridges made of
Cellulose Acetate are commercially
available, however these are seldom
used in BioPharmaceutical production
due to their inability to tolerate NaOH
which is normally used for pre and
post cleaning.)
Pellicon 2 cassettes are offered
with three choices of membrane:
Ultra-low protein binding
Regenerated Cellulose (UltracelTM)
Low protein binding Polyethersulfone (Biomax)
PVDF (Durapore) for Microfiltration
applications.
No matter what the requirements,
Millipore has the right product and
membrane for your process.

Recirculation Rate
Scale

Hollow Fiber Module

Pellicon 2 Cassettes

Laboratory-scale modules

75-500 L/min x m2

4-20 L/min x m2

Production-scale modules

7-98 L/min x m2

4-20 L/min x m2

Table 1. Recommended recirculation rates for hollow fiber modules and Pellicon 2 cassettes

Flow Rate Required to

Operate TFF Processes
Process scale Hollow Fiber modules
are designed with long flow paths in
an effort to minimize pumping requirements and to reduce the heat-input to
the product being processed. Long
flow paths are not feasible for HF
Laboratory scale cartridges thus the
recirculation rate is higher per unit
area of membrane compared to a
Process scale cartridge (Table 1).
Because of the tubular nature of the
flow path in Hollow Fiber modules,
the required recirculation rate is
extremely high. The recirculation rate
for Process scale Hollow Fiber modules is typically 200500% higher
than Pellicon 2 cassettes resulting in
increased capital expense for larger
motors, pumps and piping diameters.
Also, the larger piping required to
transport the high flow rates increases
the internal volume of the system
which limits the concentration ratio
obtainable on HF systems.
The HF Laboratory-scale modules
clearly highlight the inefficiency
with a recirculation requirement
18002500% greater than Pellicon 2
cassettes. The difference in normalized
operating conditions between laboratory and process scale Hollow Fiber
cartridges raises questions about the
reliability of scale-up data derived
from Laboratory Hollow Fiber devices.

Linear Scale-up
The difference in the normalized recirculation rate between laboratory and
production-scale Hollow Fiber modules
(Table 1) will affect the flux and the
separation efficiency of the device
(discussed below). Short laboratory
modules can be expected to perform
better on both fronts, consequently
scale-up data generated on laboratory
size Hollow Fiber modules may be too
optimistic and result in undesired surprises with respect to undersized large
scale systems and lower than expected production yield.
Besides the above, the higher recirculation rate required for Hollow Fibers
will result in a system that is 200500%
bigger than a system required to operate Pellicon 2 cassettes (this without
considering a potentially lower flux will
increase the size of the HF system further). This issue is normally ignored in
the laboratory because of the relative
low cost for lab pumps and tubing.
The higher recirculation rate for
Hollow Fibers require proportionally
higher energy input/electricity to run
the pump but also in the form of cooling. The retentate will heat up as a
result of the energy introduced by the
pump if not cooled. Consequently,
economic considerations for Hollow
Fiber scale-up with respect to capital
and energy prove to be significant
factors resulting in a compromise.
The data (Table 1) clearly indicates
that traditional HF modules are not
linearly scalable from laboratory to production. For the Pellicon 2 cassettes,
the normalized recirculation rate is
independent of module size providing
linearly scalability from 0.1 m2 to hundreds or thousands of m2.

Hollow Fiber Filter Cartridge

Hollow Fiber
wall/membrane

Feed

Retentate

Hollow Fiber retentate flow channel

Concentration
(gel) layer

Membrane

Concentration
(gel) layer
Pellicon2 Cassette

Feed

Retentate

Pellicon 2 Cassette retentate flow channel

Figure 3. Hollow Fiber. Concentration (gel) layer increase in thickness along the length of the fiber
Pellicon 2 Maxi Cassette. The retentate channel separator/static mixer ensures continuous blending of the solution along the flow
channel and simultaneously minimize the formation of the gel layer.

Consistency of Retention
Relative to Retentate
Channel Design
Pellicon 2 flat plate cassettes offer
superior separation efficiency by incorporating three-dimensional retentate
channel separators to ensure
efficient mixing of the solution and
redirection of the mixed solution to the
membrane surface, compared to a
straight HF cartridge where the concentration layer by nature is laminar
and increasing in thickness along the
length of the fiber until an equilibrium
prevents further increase (Figure 3).

Molecular separation in TFF

devices is governed not only by the
membrane characteristic but also by a
gel layer that is formed by an elevated
concentration of retained molecules at
the membrane surface. This gel layer
acts as a secondary membrane
reducing both the filtrate rate (process
speed) and the consistency of the
retention profile throughout the device.
Without efficient mixing the concentration will increase at the membrane
surface and slow the filtration process
(Figure 4). Also, the concentration
difference along the length of the fiber
will result in an inconsistent retention
profile and capability from inlet to
outlet. (Figure 5).

Filtrate
(permeate)
Figure 4. Hollow Fiber channel. Gel layer increase along the length of the fiber will reduce the filtrate rate (flux) thus negatively affect
the efficiency of the installed membrane area which ultimately will force installation of a larger and more expensive system.

Note 1

Note 1: Osmotic forces and other phenomena can reduce the retention capability of an Ultrafiltration Membrane at
elevated concentrations near the membrane surface. This can negatively affect production yield.

Figure 5. Hollow Fiber channel. Concentration (gel) layer increase in thickness along the length of the fiber negatively affecting the
consistency of the retention profile and the overall retention efficiency. (Few proteins are globular in shape. Globular species are
illustrated for simplicity)

Note 2

Note 2: Efficient gel layer control improves purity and product yield along the entire length of the flow path.

Figure 6. Pellicon 2 Cassette. The combined channel separator and static mixer reduces the gel layer at the membrane surface.
This design ensures efficient mixing along the flow channel and redirects the mixed solution effectively to the membrane surface
thus improving process speed and retention characteristics.

Consistency of Retention
Relative to the Retentate
Flow Channel Length
In any filtration module, the total length
of the retentate flow channel can
affect separation efficiency. The bulk
concentration of retained molecules
along the retentate flow channel
increases in proportion to the filtrate
volume going through the membrane
(Figure 7).
In a flat plate cassette the retentate
channels are short so the bulk concentration and the gel layer formation of
retained molecules is limited and much
more uniform. Production scale Hollow
Fiber modules are designed with
600% longer flow path length than
Pellicon 2 cassettes (1050 mm vs.
165 mm) (Figure 8). Short HF laboratory modules are available, however,
they are limited to processing just a
few liters. In addition, scale up of these
HF modules is based on increasing
flow path length so laboratory and
process scale modules are not linearly
scalable.

Figure 7. Bulk concentration increases along the flow channel reducing the filtrate
rate and creating an inconsistent molecular retention profile between the inlet and
outlet of the cartridge.

Pellicon

Length of flow channels in Process scale Hollow Fiber

Figure 8. Shorter is better. The flow path in Pellicon devices is only 165 mm vs.
1050 mm for a similar process scale Hollow Fiber cartridge, which explains the
higher performance of the Pellicon 2 design.

Conversion from Hollow

Fiber Cartridges to
Pellicon 2 Cassettes
Select a membrane rating that compares to the Hollow Fiber filter cartridge you are planning to replace. To
convert from HF modules to Pellicon 2
cassettes select a channel configuration according to the characteristics of
the feed fluid as shown in Table 2.
For pharmaceutical applications
the Pellicon 2 cassette offers superior
reliability and efficiency compared to
HF modules. Pellicon 2 cassettes are
available with Ultracel, Biomax, or
Durapore membrane offering a wide
range of molecular weight alternatives.

Recirculation Rate
Fiber

Solution

20 mil (0.5 mm)

Dilute

Channel type
A or C

High concentration or slightly viscous

40 mil (1.1 mm)

Dilute, low viscosity

A or C

High concentration or slightly viscous

C or V

Ultra high concentration, high viscosity,

and suspended solids (cells)

Table 2. Recommendations for converting from hollow fiber cartridges to

Pellicon 2 cassettes.

Example:
I am currently using Amicon Hollow
Fiber cartridges model H10P30-20 in
my process. The process stream is
dilute. I would like to upgrade to
Pellicon 2 cassettes. Which model
should I select?
Hollow Fiber nomenclature
H10P30-20:
H = Hollow Fiber
10 = 10 square feet (0.9 m2)
P = Polysulfone/polyethersulfone
based membrane material
30 = 30 kD (kilo Dalton retention
rating)
20 = 20 mil fiber*
*Fibers are available in 20 and 40 mil
diameters (0.5 and 1.1 mm ID respectively)

Answer:
Since you are operation with a
dilute feed solution you should
select a Pellicon 2 model with an
A-channel
Since the membrane area of the
Hollow Fiber unit is 10 square feet
(approximately 1 m2) you should
select two Pellicon 2, 0.5 m2
cassettes to match the existing
membrane area.
As far as the membrane material,
you can select Biomax (which is
polysulfone and polyethersulfone
based)
Since the membrane rating of the
Hollow Fiber is 30 kD you should
select a 30 kD Biomax membrane.
The current fiber diameter is 20 mil
(0.5 mm) you can therefore select
either A or C channel as listed in
the table above.
The suggested Pellicon 2 model would
be P2B030A05
Pellicon 2 nomenclature P2B030A05
P = Pellicon 2
B = Biomax membrane
030 = 30 kD (kilo Dalton retention
rating)
A = A channel
05 = 0.5 m2
NOTE: The process flux from Pellicon 2 model
may be higher than from the Hollow Fiber.
Consequently you could start out with only
one 0.5 m2 cassette.

Summary
Robustness and reliability
The design of Pellicon 2 cassettes
overcome the integrity problems of
Hollow Fibers by employing a pressure balanced construction and by
elimination of the thousands of interface points that are prone to cause
Hollow Fiber failure.
Efficiency
Pellicon 2 cassettes overcome the
efficiency problems of HF modules by
providing short effective flow channels
with three different static mixer configurations to accommodate viscosity considerations, solid content, and high flux.

To Place an Order or Receive

Technical Assistance

For additional information call your

nearest Millipore office:
In the U.S. and Canada,
call toll-free 1-800-MILLIPORE
(1-800-645-5476)
In the U.S., Canada and Puerto
Rico, fax orders to 1-800-MILLIFX
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Internet: www.millipore.com
E-mail: tech_service@millipore.com

Now you can buy

Millipore products
online @
www.millipore.com/purecommerce

Millipore, Pellicon, Biomax, Durapore, and Amicon

are registered trademarks of Millipore Corporation
or an affiliated company.
Ultracel is a trademark of Millipore Corporation or
an affiliated company.
Lit. No. AN1020EN00
Printed in U.S.A. 5/01 01-033
Copyright 2001 Millipore Corporation or an affiliated company, Bedford, MA. All rights reserved.

Linear scalability
Pellicon 2 cassettes maintain constant
flow path length and type regardless
of the size of the installation to facilitate easy scaleup from the laboratory
to full-scale production.
Membrane choices
Pellicon 2 cassettes offer 3 alternative
membrane materials to facilitate a wider
range of application requirements.
Consistent retention
Pellicon 2 offers short flow channels
with static mixers to enhance the retention consistency, during processing,
along the entire length of the flow
channel

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