Millipore Filtration Selection Guide L PDF
Millipore Filtration Selection Guide L PDF
Millipore Filtration Selection Guide L PDF
Lenntech
[email protected] Tel. +31-152-610-900
www.lenntech.com Fax. +31-152-616-289
Filtration
Selection
Guide
Choosing the Right Filter
for Your Application
Copyright 2004 Millipore Corporation, Billerica, MA 01821 U.S.A. All rights reserved.
Lit. No. SG1500EN00 Rev. A Printed in U.S.A. 12/04 04-204 Photography, Robert Fraher.
SelGuideCov 1/3/05 3:32 PM Page 2
Application Guide
This tool is intended to give you an overview of key applications and the recommended Millipore filtration solutions.
Understanding that every process stream is different, we recommend that scaling and optimization testing be
conducted in-house or utilizing Millipore’s Access Services team. Use this information as a starting point for
development or optimization.
Buffer Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Cell Culture Media Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Microbial Cell Culture Clarification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Mammalian Cell Culture Clarification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Protein and Antibody Downstream Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Serum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Plasma Fractionation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Mammalian Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Viral Vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Plasmid DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Conjugates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Final Aseptic Filling (SVP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Large Volume Parenterals (LVP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Ophthalmic Solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Facilities Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Tank Venting and Air Filtration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
No tool will replace the need to conduct process development and No specific performance is guaranteed. Visit our on-line catalogue
optimization experiments. The unique nature of every process stream at www.millipore.com for individual product specifications and
combined with application and regulatory requirements play a part in complete ordering information. For personal guidance on
determining the optimum filtration train. Use this filtration selection understanding the wide variety of options available please consult
guide as a starting point for selecting and sizing the most appropriate your local applications specialist or technical service.
Millipore filter.
SelGuide p01-13 12/27/04 5:02 PM Page 2
C l a r i f i c a t i o n a n d P r e f i l t r a t i o n
®
Clarigard • • • •
®
Milligard • • • • • • • • •
Polysep II
™
• • • • • • • • •
®
Polygard CR • • • •
Polygard DF •
®
Durapore 4 4 4 4 4
0.45 µm • • • • • • •
F i n a l F i l t r a t i o n
Durapore
0.1 µm • • • • • • • • • •
Durapore
0.22 µm • • • • • • • • • •
Filter Format Quick Reference Guide
Multilayer
Durapore • • • • •
Multimedia
Durapore • •
Charged
Durapore •
Durapore CBR •
Millipore
®
Express SHC • • • • • • •
Millipore
Express SHF • • • • • • •
Millipore
Express SHR • • • • • • •
V i r a l C l e a r a n c e
®
Viresolve NFP • 1
•2 • • • •
Viresolve NFR •1 •2 • • • •
T a n k V e n t i n g a n d A i r F i l t r a t i o n
®
Aervent • 3
• • • •
1 2
Viresolve membranes are sold in the smaller OptiScale-25 Device format. Available in original Opticap Capsules.
Millistak+ DE
•
•
•
• 5
•
•
•
•
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900 Millistak+ CE • • 5
• •
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289 Viresolve Prefilter •6 •5 •
5 6
Coming in 2005 Viresolve prefilter available in OptiScale-40 device format.
* These tables only includes items mentioned in
this selection guide. Visit our on-line catalogue
at www.millipore.com for details on other fil-
tration products. See connections on page 6.
2
SelGuide p01-13 12/27/04 5:02 PM Page 3
• • • •
• • • •
• • • •
• • • •
• • • •
• • • • •
• • • • • • • • • •
• • • • • • • • • • •
• • •
• • •
• • • •
• • • • • • • • • •
• • • • • • • • • • •
• • • • • • • • • •
• • •
• • •
• • • • •
3 4
Aervent membrane is sold in the larger Aervent-50 Capsule format. Single-layer filters only.
Microfiltration (MF)
™
Prostak Modules • • • •
®
Pellicon Cassettes • • • •
Ultrafiltration (UF)
®
Pellicon Cassettes • • • •
Millipak
Unit
OptiScale OptiScale-25
Capsules Capsule
4
SelGuide p01-13 12/27/04 5:02 PM Page 5
Opticap XL and XLT Disposable Opticap XL disposable capsule filters have Charged Depth Filters
Capsule Filters a unique design to minimize hold-up volume The ultimate in charged depth technology,
Disposable capsule filters save you time and reduce production losses and are Millistak+ filters utilize unique membranes
and resources. They eliminate the need to available in a range of sizes for easy and high quality materials. Choose any
sanitize between cycles and reduce the scale-up. Millistak+ media type; HC, DE, CE or A
associated validation effort. Capsules are Opticap XLT disposable T-line capsule filters and be confident that it will perform in a
commonly used in processes where fast are available with or without a pressure reliable manner .
turnover between cycles is required and to gauge port for ease in monitoring process
minimize worker exposure to hazardous conditions. The T-line design accommodates Millistak+ Mini Small-scale
process fluids. Capsule filters, depending series or parallel filtration to match your Disposable Capsules
upon the materials of construction, are application needs. A specially-designed Millistak+ Mini capsules offer 23 cm2 of
autoclavable or gamma-compatible. stand enables quick and easy integration effective surface area and are ideally suited
Capsule filters have the unique advantage into your existing process. for process development, screening and
of being able to be coupled with small-scale trials.
disposable biocontainers into process Millipak Disposable Filter Units
Millipak sterilizing-grade units have a Opticap Disposable Capsule Filters
assemblies that can be irradiated prior to
unique stacked filter design that allows Original Opticap capsule filters with
use, thus assuring sterility.
minimal hold-up volume and no particle Millistak+ medias are ideal for pilot-scale
Opticap capsules are available in a and small-scale manufacturing.
wide range of sizes, filter medias and shedding, making Millipak filters ideally
inlet/outlet connections (See pg. 6). They suited for high value-added applications Stacked Lenticular Disc Filters
are proven performers in the industry. No such as sterile finish and fill. Millipak filters Ideal for large-scale processing, stacked
matter what your application need Millipore are available in a range of filtration areas depth filters are available in 12- and
has the right configuration. from 100 cm2 to 1,000 cm2, and have 16-inch diameters and various surface
adjustable upstream vents and drain valves areas to accommodate a range of process
Sterile Options with O-ring seal and several connections volumes.
Filter Options
Millipore Express and Durapore sterilizing- for easy process control (See pg. 6).
grade membranes are offered in 2 capsule The Millistak+ Pod
options. Gamma-compatible capsules are Sterile Options This new patented modular disposable filter
designed to be sterilized by gamma Millipak Gamma Gold units are available format was designed for greater flexibility
irradiation prior to use and disposed of gamma-compatible and can be easily and productivity. Each Pod consists of
after use. Sterile Opticap XL or XLT capsules sterilized by gamma irradiation prior to use one, five or ten 0.1 m2 filter cells in a
are gamma irradiated by Millipore and and disposed of after use. self-contained disposable enclosure. The
delivered sterile to your facility. Pods are lightweight and modular, and do
not require housings. Multiple Pods can be
configured up to 30 m2 to match process
volumes.
Millistak+
Mini Capsule
Pod
Opticap XLT
Capsule
Opticap XL
Capsule
Stacked
Disc Filter
5
SelGuide p01-13 12/28/04 3:29 PM Page 6
Sanitary flange 38 mm Sanitary flange 19 mm Hose barb 14 mm Sanitary flange 38 mm Sanitary flange 19 mm
(11/2 in.) inlet/outlet (3/4 in.) inlet/outlet (9/16 in.) inlet/outlet (1 1/2 in.) inlet and hose barb (3/4 in.) inlet and hose barb
14 mm (9/16 in.) outlet 14 mm (9/16 in.) outlet
Sanitary flange 38 mm Sanitary flange 38 mm Hose barb 16 mm Hose barb 25 mm Opticap XLT
(1 1/2 in.) inlet/outlet (1 1/2 in.) inlet and hose barb (5/8 in.) inlet/outlet (1 in.) inlet/outlet full view
16 mm (5/8 in.) outlet
6 mm (1/4 in.) 38 mm (1 1/2 in.) 19 mm (3/4 in.) 14 mm (9/16 in.) 6 mm (1/4 in.) hose barb
NPTM inlet/outlet sanitary flange inlet/outlet sanitary flange inlet/outlet hose barb inlet/outlet inlet/outlet with filling bell
19 mm (3/4 in.) sanitary flange 6 mm (1/4 in.) stepped 19 mm (3/4 in.) 14 mm (9/16 in.) stepped
inlet/6 mm (1/4 in.) stepped hose barb inlet/outlet sanitary flange inlet/outlet hose barb inlet/outlet
hose barb inlet/outlet
14 mm (9/16 in.)
hose barb inlet/outlet
1- Cell Pod with 38 mm (11/2 in.) 5- Cell Pod with 38 mm (11/2 in.) 10- Cell Pod with 38 mm (11/2 in.) 19 mm (3/4 in.)
sanitary flange fittings sanitary flange fittings sanitary flange fittings sanitary flange inlet/outlet
Cartridge Configurations
Code 0 Style Cartridges Code 7 Style Cartridges 2-226 O-ring Code M Style Cartridges Optiseal Cartridges
2-222 O-ring outlet locking outlet with spear assembly 2-118 O-ring 2-123 O-ring
* Inlet and outlet connections can be configured to meet your needs. Some connections are size and media/membrane dependant.
Contact Millipore for details.
6
SelGuide p01-13 12/27/04 5:02 PM Page 7
Filter Options
volume per square meter of membrane 100 L and linearly scale to Pellicon Maxi
cassettes.
Biomax Series 5, 8, 10, 30, 50, 100, 300 High flux hydrophilic 1 – 14 at 25 °C Low
500 and 1,000 kD polyethersulfone
®
Ultracel PLC Series 5, 10, 30, 100, 300 Composite regenerated 2 – 12 at 25 °C Very low
and 1,000 kD cellulose
*
This table includes only products mentioned in this selection guide.
Visit our on-line catalogue at www.millipore.com for details on other available TFF membranes.
Prostak
Modules
Pellicon Standard
Cassette
Pellicon XL 50
Cassette
Pellicon Maxi
Cassette
Pellicon Mini
Cassette
7
SelGuide p01-13 12/27/04 5:03 PM Page 8
Mobius Flexible
Bioprocessing Solutions
We bring together unmatched expertise and
disposable technologies to offer a complete,
ready-to-process solution.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
8
SelGuide p01-13 12/27/04 5:03 PM Page 9
Container Systems
Millipore offers HyClone HyQ® CX5-14 and CX3-9 BioProcess Container™ (BPC®) systems as a part of integrated Mobius assembly solutions.
A wide range of flexible, scalable containers are available from small volume 2-D configurations starting at 50 mL to large volume 3-D
configurations up to 1,500 L.
Two-dimensional Systems* Applications Size
2-D Small Volume Process development, QC sampling, 50, 100, 250, 500 mL; 1, 2 L
End-Ported Hanging bulk product storage, transfer and
Pillow collection
2-D Large Volume Formulation and filling of sterile 5, 10, 20, 50, 100, 200, 300 L
Face-Ported media, buffers and other process
3-D Rectangular Formulation and filling of sterile 50, 100, 200, 500, 900, 1,000,
media, buffers and other process 1,500 L
liquids; bioreactor and fermentation
feed and harvest; waste collection;
transportation and storage of bulk
intermediate product
Tank Liner Media hydration, non-sterile mixing, 50, 100, 200, 300, 500, 1,000,
refiltration of process intermediates 1,500 L
Mixtainer™ Mixing System Stirring, suspending, holding and 50, 100, 200 L
storing sterile fluids
* Bioprocessing containers are only available as an integrated part of Mobius assemblies. Containers are not sold individually.
Other container systems, configurations and accessories are available. Contact your Millipore Application Specialist.
9
SelGuide p01-13 12/27/04 5:03 PM Page 10
Connectology
®
Disposable Lynx connectors, clamps and reliable Lynx connectors enable fluid
valves provide the critical link between transfer while maintaining sterility. Tubing
disposable fluid paths and the various steps and manifolds are also available in a range
in your process. The easy to use and of sizes and materials to fit your application.
Lynx S2S Sterile To Sterile 1/2 in. x 1/2 in. hose barb SSCSHB2N01
Tubing
10
SelGuide p01-13 12/27/04 9:07 PM Page 11
Millipak-60
Filter Unit
1,000 L
3-D Container
Opticap XL10
Capsule
Lynx Connectors
20 L Hanging
Pillow Container
Opticap XL4 Mixtainer™
Capsule Mixing System
Opticap XL4
Capsule
12
SelGuide p01-13 1/3/05 4:25 PM Page 13
Access Services
A C C E S S C O N S U LT I N G offers guidance in a variety of areas. From development,
scaling and optimization strategies to system and plant design and regula-
tory compliance Millipore experts partner with you to ensure success.
13
SelGuide p14-72 1/4/05 10:37 AM Page 14
Buffer Preparation
Buffer solutions are required for a number
of purification steps and are critical to
1
process efficiency and final product quality. Typical Process Flow
Buffer filtration is critical to protect the life
of chromatography columns, downstream
2 Vent
UF steps and to ensure an endotoxin-free Filter
final product. Buffer solutions are typically
filtered using sterilizing-grade membrane
filters. Depending on the salt concentration
and buffer properties, prefiltration may
be needed.
For details on Tank Venting 2 , see page 70. 1
2
Understanding the Options
Sterile Filtration
• Utilize a sterilizing-grade membrane 1 Single-layer • Sterilizing-grade PES membrane providing broad chemical
to remove contaminants and ensure Millipore Express SHF compatibility across a wide pH range (1–14)
sterility 0.2 µm Filters • Robust construction validated for multiple SIP cycles
• Must work with a variety of process • 100% integrity tested to ensure quality
fluids across a range of pH levels • Asymmetric pore structure delivers extremely high flow rates
• Preserve product purity at low pressure drop
• Able to withstand demanding • Can be integrity tested on-site
steam-in-place requirements
• Depending on salt concentration
and fluid properties, prefiltration
may be needed
1 Double-layer • Sterilizing-grade PES membrane with an additional PES prefilter
Millipore Express SHC layer all in one pleated device
0.5 µm + 0.2 µm Filters • Double-layer construction provides excellent capacity even in
high salt conditions >1M
• PES membrane provides broad chemical compatibility across
a wide pH range (1–14)
• Robust construction validated for multiple SIP cycles
• 100% integrity tested to ensure quality
• Asymmetric PES pore structure delivers extremely high flow rates
at low pressure drop
• Can be integrity tested on-site
ALTERNATIVE: If a PVDF membrane is needed, Millipore’s Durapore Family of Filters have been
a proven performer for decades.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
14
SelGuide p14-72 1/4/05 10:38 AM Page 15
3
Filter Quick Reference Guide
Recommended Filters
Volume Filter Format Area/Filter Catalogue No.
Buffer Preparation
Opticap XLT20 Capsule 1.08 m2 KGEPA2TTT1
1,600 – 3,200 L Opticap XLT20 Gamma-compatible Capsule 1.14 m2 KGEPG2TTT1
20-inch Cartridge 1.08 m2 CGEP72TP3
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
15
SelGuide p14-72 12/27/04 4:35 PM Page 16
1
Typical Process Flow
Cell Culture Media Preparation
4 Tank
Venting
1
3
2
2
Understanding the Options
ALTERNATIVE: If PVDF or low protein binding membrane is needed please include Durapore 0.1 µm filters in your
small-scale trials.
16
SelGuide p14-72 12/27/04 4:35 PM Page 17
Prefiltration
(If sterile filter capacity is <1,000 L/m2 1 Triple-layer • Triple-layer configuration includes a membrane bottom layer to enhance
then a prefilter should be considered.) Millistak+ HC Filters filter loading capacity and retention
• Protect sterilizing-grade filters by • Higher filtrate quality allows smaller size requirements for downstream
effectively removing lipids, colloids (Grade A1HC) sterilizing-grade filtration step
and particles without binding • Unique design enables the compression of multiple process steps into
vital media constituents one, lowering overall filtration costs
• Cost effectiveness and timely
separation
• Needs to work irrespective of
variation from batch to batch ALTERNATIVE: If media stream is less plugging, Millipore suggests testing single-layer Grade 75DE Millistak+ Filters in your
• Preserve cell growth properties small-scale trials.
2 Triple-layer Polysep II Filters • Designed for the protection of downstream 0.1 µm sterilizing-grade filters
• Triple layer construction ensures high particle loading and capacity
(Grade W1, 1.0 µm + • Validated for multiple sanitization and SIP cycles
0.2 µm + 0.1 µm) • Higher filtrate quality allows smaller size requirements for downstream
sterilizing-grade filtration step
• Non-fiber releasing structure preserves product purity
• Cell growth studies confirm growth properties are preserved
ALTERNATIVE: If a PVDF or low protein binding membrane is needed please include Durapore 0.22 µm Filters in your
small-scale trials.
Prefiltration
(Not normally required for 1 Triple-layer • Triple-layer configuration includes a membrane bottom layer to enhance
serum-free media) Millistak+ HC Filters filter loading capacity and retention
• Protect sterilizing-grade filters by • Higher filtrate quality allows smaller size requirements for downstream
effectively removing lipids, colloids (Grade A1HC) sterilizing-grade filtration step
and particles without obstructing the • Unique design enables the compression of multiple process steps into
flow of vital media constituents one, lowering overall filtration costs
• To ensure cost effectiveness and
timely separation filters should have
high flow rates and consistently high
throughput ALTERNATIVE: If media stream is less plugging, Millipore suggests testing Grade 75DE Millistak+ Filters in your small-scale trials.
• Needs to work irrespective of
variation from batch to batch 2 Double-layer • Designed for the protection of downstream 0.22 µm sterilizing-
• Filter should have low extractables Polysep II Filters grade filters
and low binding of key nutrients • Reliable prefilter for concentrated solutions across a full range of
(Grade W3, 1.0 µm + flow rates
0.2 µm) • Robust construction ensures high particle loading and capacity
• Validated for multiple sanitization and SIP cycles
• Higher filtrate quality allows smaller size requirements for downstream
sterilizing-grade filtration step
• Non-fiber releasing structure preserves product purity
• Cell growth studies confirm growth properties are preserved
17
SelGuide p14-72 12/27/04 4:35 PM Page 18
3
Filter Quick Reference Guide
Filter Format Area/Filter Catalogue No. Filter Format Area/Filter Catalogue No.
Bacterial and Mycoplasma Bacterial
OptiScale Capsules OptiScale Capsules
Single-layer Millipore Express SHR 0.1 µm membrane SVEPA47FF3 Double-layer Millipore Express SHC
Double-layer Millipore Express SHR 0.5 µm + 0.2 µm membrane SHGEA47FF3
0.1 µm + prefilter layer 13.8 cm2 SHVEA47FF3 Durapore 0.22 µm membrane 23 cm2 SVGLA47FF3
Durapore 0.1 µm membrane SVVLA47FF3 Double-layer Polysep II Grade W3 media SGW3A47FF3
Triple-layer Polysep II Grade W1 media SGW1A47FF3
Millistak+ Mini Capsules Millistak+ Mini Capsules
Triple-layer Grade A1HC MA1HC23HH3 Triple-layer Grade A1HC MA1HC23HH3
23 cm2 23 cm2
Single-layer Grade 75DE M75DE23HH3 Single-layer Grade 75DE M75DE23HH3
Recommended Filters
Range Range Gamma-
No Prefiltration With Prefiltration Standard compatible
Media/Membrane Area/Filter Volume Volume Cartridge Capsule Capsule
Bacterial and Mycoplasma Retention
Cell Culture Media Preparation
Standard
Media/Membrane Area/Filter Low Range High Range Cartridge Capsule
Triple-layer Polysep II
Grade W1 (1.0 µm + 0.2 µm + 0.1 µm) Filters
Opticap XL5 Capsule
or 4-inch Cartridge 0.19 m2 95 L 380 L CGW1M4S03 KGW1A05TT1 –
Opticap XL10 Capsule
or 10-inch Cartridge 0.46 m2 230 L 920 L CGW171S03 KGW1A10TT1 –
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
18
SelGuide p14-72 12/27/04 4:35 PM Page 19
Standard
Media/Membrane Area/Filter Low Range High Range Cartridge Capsule
Double-layer Polysep II
Grade W3 (1.0 µm + 0.2 µm) Filters
Opticap XL5 Capsule
or 4-inch Cartridge 0.19 m2 95 L 380 L CGW3M4S03 KGW3A05TT1 –
Opticap XL10 Capsule
or 10-inch Cartridge 0.46 m2 230 L 920 L CGW371S03 KGW3A10TT1 –
Standard
Media/Membrane Area/Filter Low Range High Range Stack Capsule Pod
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
19
SelGuide p14-72 1/4/05 10:38 AM Page 20
1
antibiotics, hormones, enzymes, amino Typical Process Flow
acids, blood substitutes and alcohol. The
product of interest may be expressed by
microbial cells or be intracellular (cytoplasmic Expressed Protein
or periplasmic in the case of bacterial cells). Vent 4
To obtain the desired product, it must 2
first be separated from the cells and other
debris in the fermentation broth. In the
case of intracellular products, the cells must 3
be lysed and the lysate must be clarified
to remove the cell debris and other con-
taminants. Depending on the process,
1
additional clarification steps may be
needed. Filtration is also used to process Fermentation Whole Cell Bioburden
fermentation additives such as nutrients Removal Reduction
and pH adjusters prior to addition into
the fermenter.
Microbial Cell Culture Clarification
Inclusion Bodies
9 3
20
SelGuide p14-72 12/27/04 4:36 PM Page 21
2
Understanding the Options
2 Prostak Open-Channel • Open-channel design ideal for fluids containing high cell densities
Modules with 0.22 µm or and solids
ALTERNATIVE: For small volumes with low cell densities, Pellicon V Screen Cassettes with 0.22 µm or 0.1 µm Durapore
Membrane should be tested in your small-scale trials.
ALTERNATIVE: For small volumes with low cell densities, Pellicon V Screen Cassettes with 0.22 µm or 0.1 µm Durapore
Membrane should be tested in your small-scale trials.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
21
SelGuide p14-72 12/27/04 4:36 PM Page 22
• Feed stream quality can vary • Selection of 0.22 µm or 0.1 µm membrane depends on particle
depending on cell type and culture size distribution in feed solution. Choice should be based upon
conditions small-scale testing.
Lysate Clarification
Primary Clarification – TFF with Microfiltration Membrane
• Removal of debris, particles and
colloids generated during the 8 Prostak Open-Channel • Open-channel design ideal for fluids with high solids levels
lysis step, and product recovery Modules with 0.22 µm or • High flux at low transmembrane pressure
in filtrate fluid 0.1 µm Durapore Membrane • Robust construction allows multiple use
• Feed stream quality can vary • Validated for multiple SIP cycles
depending on cell culture type and • Selection of 0.22 µm or 0.1 µm membrane depends on particle
lysis conditions size distribution in feed solution. Choice should be based upon
• Challenging separation due to small-scale testing.
large amount of particles and
wide range in size
• Typically requires several process
steps in series (primary clarification 8 Pellicon V Screen Cassettes • More suited for lower cell density and solid content fluids
then polishing filtration) with 0.22 µm or 0.1 µm • Suspended screen in feed channel allows higher turbulence enhancing
• Centrifugation is a viable option as Durapore Membrane, or separation process
first separation step, but still requires 1,000 kD Biomax Membrane • Complete range of devices for easy scale-up
downstream polishing filtration • Selection of 0.22 µm, 0.1 µm or 1,000 kD membrane depends on
particle size distribution in feed solution. Choice should be based
upon small-scale testing.
22
SelGuide p14-72 12/27/04 4:36 PM Page 23
Sterile Filtration
Bioburden Reduction
• Reduces bioburden 3 Single-layer Durapore • Sterilizing-grade PVDF membrane won’t bind valuable protein
• Protects downstream chromatography 0.22 µm PVDF Filters • 100% Integrity tested to ensure proven performance
and UF/DF steps • Can be integrity testable on-site
• Maintains yield of dilute protein and • Although 0.22 µm is typical for this application, Durapore filters
preserves purity are available in several pore sizes and, in single-layer or multi-layer
• Sterilizing-grade filtration required configurations to accommodate the needs of each user, the degree of
protection required for the downstream process and the plugging char-
acteristics of the fluid. Choice should be based on small-scale testing.
3 Millipore Express SHC • Sterilizing-grade PES membrane providing broad chemical compatibility
0.5 µm + 0.2 µm PES Filters across a wide pH range (1–14)
• Robust construction validated for multiple SIP cycles
• 100% integrity tested to ensure quality
• Asymmetric pore structure delivers extremely high flow rates at low
pressure drop
• Can be integrity tested on-site
• Although double-layer 0.5 µm + 0.2 µm (SHC) is typical for this
application, single-layer 0.2 µm (SHF) is also available. The degree
3
Filter Quick Reference Guide
23
SelGuide p14-72 12/27/04 4:36 PM Page 24
Durapore 0.22 µm membrane Mini Cassette (0.1 m2) P2GVPPV01 Maxi Cassette (2 m2) P2GVPPV20
Cassette (0.5 m2) P2GVPPV05
Biomax 1,000 kD membrane Mini Cassette (0.1 m2) P2B01MV01 Maxi Cassette (2 m2) P2B01MV20
Cassette (0.5 m2) P2B01MV05
Durapore 0.1 µm membrane 2-stack (0.17 m2) PSVVAG021 10-stack (0.84 m2) PSVVAG101
4-stack (0.33 m2) PSVVAG041 20-stack (1.7 m2) SK2P127E1
Depth Filtration
Triple-layer Millistak+ HC Filters
Grade A1HC 1-cell Pod (0.1 m2) MA1HC01FS1 10-cell Pod (1 m2) MA1HC10FS1
5-cell Pod (0.5 m2) MA1HC05FS1
10-inch Opticap (650 cm2) KA1HC10FF1
2-cell 16-inch stack (0.45 m2) LA1HCH6S6 8-cell 16-inch stack (1.8 m2) LA1HCG6S2
Microbial Cell Culture Clarification
Grade B1HC 1-cell Pod (0.1 m2) MB1HC01FS1 10-cell Pod (1 m2) MB1HC10FS1
5-cell Pod (0.5 m2) MB1HC05FS1
10-inch Opticap (650 cm2) KB1HC10FF1
2-cell 16-inch stack (0.45 m2) LB1HCH6S6 8-cell 16-inch stack (1.8 m2) LB1HCG6S2
Millipore Express SHC Opticap XL3 Capsule (0.13 m2) KHGEA03TT3 Opticap XL10 Capsule (0.49 m2) KHGEA10TT1
0.5 µm + 0.2 µm PES Filters Opticap XL5 Capsule (0.24 m2) KHGEA05TT1 Opticap XLT10 Capsule (0.49 m2) KHGEA1TTT1
5-inch Cartridge (0.24 m2) CHGE75TS3 Opticap XLT20 Capsule (0.98 m2) KHGEA2TTT1
Opticap XLT30 Capsule(1.47 m2) KHGEA3TTT1
10-inch Cartridge (0.49 m2) CHGE71TS3
20-inch Cartridge (0.98 m2) CHGE72TS3
30-inch Cartridge (1.47 m2) CHGE73TS3
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
24
SelGuide p14-72 12/27/04 4:36 PM Page 25
1
low protein expression levels (<100 mg/L) Typical Process Flow
and are typically grown to low cell viabilities
(<30%) which complicates the harvest
operation.
Vent 5
Cell Culture Media Types
2
Cell culture medium typically contains amino
acids, vitamins, electrolytes and may contain
hormones, growth factors, plant hydrolysates,
animal serum, antibiotics, antioxidants, anti-
3 4
foams, cell stabilizers and other components.
Types of media include serum based,
serum free, animal free, and protein free or
chemically defined. Serum based and serum
1
free media are widely used since they can
be used to grow a broad range of cell types
Bioreactor Primary Secondary Bioburden
and cell lines such as CHO or NS0 cells. Clarification Clarification Reduction
For details on Tank Venting 5 , see page 70.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
25
SelGuide p14-72 12/27/04 4:36 PM Page 26
2
Understanding the Options
Primary Clarification
• Removes whole cells and solids 1 Double-layer • For bioreactors volumes up to 1,000 L or larger volumes with low
from bioreactor fluid and recover Millistak+ HC Filters usage rates of less than 10 batches/year
product in filtrate • Double layer design enhances loading capacity and filtrate quality
• Requires high capacity (Grade D0HC or C0HC) • Unique configuration allows compression of multiple process steps into
• Wide feed stream variability one, lowering overall filtration costs.
depending on cell culture type • Selection of C0HC or D0HC media grade depends on particle
and conditions size distribution in feed solution. Choice should be based upon
• If solid content is too high, small-scale testing.
centrifugation becomes preferred
technology
2 Prostak Open-Channel • Best suited for large bioreactors >1,000 L or bioreactors with
Modules with 0.22 µm or high usage rates of more than 10 batches/year
0.65 µm Durapore • Open-channel design accommodates fluids containing low to medium
Membrane cell density and solids
• High flux at low transmembrane pressure
• Robust construction allows multiple use
Mammalian Cell Culture Clarification
ALTERNATIVE: If the cell culture has high cell viability and relatively low cell counts, all polypropylene
Polygard-DF depth filter cartridges is a viable option for bioreactors up to 1,000 L.
ALTERNATIVE: If process hardware dictates the use of pleated cartridge filters, Millipore suggests testing Polysep II multi-layer
prefilters in your small-scale trials.
Bioburden Reduction
• Reduces bioburden 4 Single-layer • Sterilizing-grade low-protein binding PVDF membrane
• Protects downstream chromatogra- Durapore 0.22 µm Filters • 100% Integrity testing to ensure performance
phy and UF/DF steps • Can be integrity testable on-site
• Maintains yield of dilute protein and • Although 0.22 µm is typical for this application, Durapore filters are
preserves purity available in several pore sizes and, in single-layer or multi-layer
• Sterilizing-grade filtration configurations to accommodate the degree of protection required for
recommended the downstream process and the plugging characteristics of the fluid.
Choice should be based on small-scale testing.
26
SelGuide p14-72 12/27/04 4:36 PM Page 27
3
Filter Quick Reference Guide
0.22 µm Membrane 2-stack (0.17 m2) PSGVAG021 10-stack (0.84 m2) PSGVAG101
4-stack (0.33 m2) PSGVAG041 20-stack (1.7 m2) SK2P484E0
Depth Filtration
Triple-layer Millistak+ HC
Grade A1HC 1-cell Pod (0.1 m2) MA1HC01FS1 10-cell Pod (1 m2) MA1HC10FS1
5-cell Pod (0.5 m2) MA1HC05FS1
10-inch Opticap (650 cm2) KA1HC10FF1
2-cell stack (0.45 m2) LA1HCH6S6 8-cell stack (1.8 m2) LA1HCG6S2
Grade D0HC 1-cell Pod ( 0.1 m2) MD0HC01FS1 10-cell Pod (1 m2) MD0HC10FS1
5-cell Pod (0.5 m2) MD0HC05FS1
10-inch Opticap (650 cm2) KD0HC10FF1
2-cell stack (0.45 m2) LD0HCH6S6 7-cell stack (1.6 m2) LD0HCG6S2
Sterilizing-grade Filtration
Durapore 0.22 µm PVDF Filters Opticap XL2 Capsule (0.09 m2) KVGLA02TT3 Opticap XL10 Capsule (0.69 m2) KVGLA10TT1
Opticap XL4 Capsule (0.19 m2) KVGLA04TT3 Opticap XLT10 Capsule (0.69 m2) KVGLA1TTT1
Opticap XL5 Capsule (0.35 m2) KVGLA05TT1 Opticap XLT20 Capsule (1.4 m2) KVGLA2TTT1
5-inch Cartridge (0.35 m2) CVGL75S01 Opticap XLT30 Capsule (2.9 m2) KVGLA3TTT1
10-inch Cartridge (0.69 m2) CVGL71TP3
20-inch Cartridge (1.4 m2) CVGL72TP3
30-inch Cartridge (2.1 m2) CVGL73TP3
Millipore Express SHC Opticap XL3 Capsule (0.13 m2) KHGEA03TT3 Opticap XL10 Capsule (0.49 m2) KHGEA10TT1
0.5 µm + 0.2 µm PES Filters Opticap XL5 Capsule (0.23 m2) KHGEA05TT1 Opticap XLT10 Capsule (0.49 m2) KHGEA1TTT1
5-inch Cartridge (0.23 m2) CHGE75TS3 Opticap XLT20 Capsule (0.98 m2) KHGEA2TTT1
Opticap XLT30 Capsule(1.47 m2) KHGEA3TTT1
10-inch Cartridge (0.49 m2) CHGE71TS3
20-inch Cartridge (0.98 m2) CHGE72TS3
30-inch Cartridge (1.47 m2) CHGE73TS3
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
27
SelGuide p14-72 1/4/05 10:38 AM Page 28
1
Typical Process Flow
6 Vent
Filter
2
2
1 1
2 2 3 4 5
1
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
28 www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
SelGuide p14-72 12/27/04 4:36 PM Page 29
2
Understanding the Options
Column Protection
• Reduces bioburden levels 2 Durapore PVDF Filters • Sterilizing-grade filters assure reduction of contaminating microorgan-
• Protects and extends the life of isms that shorten the life of costly chromatography media
downstream chromatographic media (0.22 µm or Multilayer • Low-binding PVDF membrane assures protein yeld
• Preserves product purity 0.45 µm + 0.22 µm) • 100% Integrity testing ensures quality
• Although 0.22 µm is typical for this application, Durapore filters
are available in several pore sizes and in single-layer or multi-layer
configurations to accommodate the needs of each user, the degree of
protection required for the downstream process and the plugging char-
acteristics of the fluid. Choice should be based on small-scale testing.
• Can be integrity testable on-site
2 Millipore Express SHF • Sterilizing-grade PES membrane providing broad chemical compatibility
Viral Clearance
(Optional for mammalian cell 4 Viresolve NFP PVDF Filters • >4 log removal of parvovirus and other small viruses
expression systems) • Robust PVDF membrane
• Ensure product safety against viruses 3 • >98% recovery of protein up to 160 kD
• Highly validated and reliable • 100% Integrity testing assures performance
technology • Can be integrity tested on-site
• Maximize product recovery • To enhance filter performance and capacity, Millipore suggests using
• Preserves product purity the Viresolve Prefilter 3 in series
4 Viresolve NFR PES Filters • >6 log removal of retroviruses (80–120 nm)
• >98% recovery of protein (IgG)
• 100% Integrity testing assures performance
• Can be integrity tested on-site
Ultrafiltration
• Concentration, buffer exchange and 1 Pellicon C Screen Cassettes • Low feed flow requirement minimizes pumping, working and hold up
final formulation with Ultracel PLC volumes
• Maximize product recovery Membranes • Highly retentive regenerated cellulose membranes offer good permeate
• Fast, robust process able to flux and withstand process upsets
accommodate feed fluid variations • Robust low binding void-free membranes provide excellent repeat
• Wide chemical compatibility with performance
cleaning agents • Choose a membrane molecular weight cut-off 3–5X smaller than the
• Easily scalable from lab to protein to be retained. Choice should be based on small-scale testing.
manufacturing scale
ALTERNATIVE: Consider using chemically resistant Biomax membranes when harsh cleaning and/or decontamination
chemicals are required.
29
SelGuide p14-72 1/4/05 10:38 AM Page 30
Sterile Filtration
• Sterilizing-grade step to reduce 5 Durapore 0.22 µm PVDF • Sterilizing-grade PVDF membrane won’t bind valuable protein
bioburden Filters • 100% Integrity testing and thousands of existing applications assure
• Highly validated and reliable proven performance
technology • Although 0.22 µm is typical for this application, Durapore filters are
• Preserves product purity available in several pore sizes and in single-layer or multi-layer
• Ensures product safety configurations to accommodate the needs of each user, the degree of
protection required for the downstream process and the plugging char-
acteristics of the fluid. Choice should be based on small-scale testing.
• Integrity testable on-site
5 Millipore Express PES Filters • Sterilizing-grade PES membrane providing broad chemical compatibility
across a wide pH range (1–14)
• Robust construction validated for multiple SIP cycles
• 100% integrity tested to ensure quality
• Asymmetric pore structure delivers extremely high flow rates at low
pressure drop
Protein & Antibody Downstream Processing
3
Filter Quick Reference Guide
30
SelGuide p14-72 12/27/04 4:36 PM Page 31
Recommended Filters
Small-Scale Processing <100 L Large-Scale Processing >100 L
Media/Membrane Device (area/filter) Catalogue No. Device (area/filter) Catalogue No.
Ultrafiltration/Diafiltration
Pellicon C Screen Cassettes
Ultracel PLC 30 kD membrane Mini Cassette (0.1 m2) P2C030C01 Maxi Cassette (2.5 m2) P2C030C25
Cassette (0.5 m2) P2C030C05
Ultracel PLC 10 kD membrane Mini Cassette (0.1 m2) P2C010C01 Maxi Cassette (2.5 m2) P2C010C25
Cassette (0.5 m2) P2C010C05
Bioburden Reduction and Sterile Filtration
Single-layer Durapore 0.22 µm Filters Opticap XL2 Capsule (0.09 m2) KVGLA02TT3 Opticap XL10 Capsule (0.69 m2) KVGLA10TT1
Opticap XL4 Capsule (0.19 m2) KVGLA04TT3 Opticap XLT20 Capsule (1.4 m2) KVGLA2TTT1
Opticap XL5 Capsule (0.35 m2) KVGLA05TT1 Opticap XLT30 Capsule (2.9 m2) KVGLA3TTT1
5-inch Cartridge (0.35 m2) CVGL75S01 10-inch Cartridge (0.69 m2) CVGL71TP3
20-inch Cartridge (1.4 m2) CVGL72TP3
30-inch Cartridge (2.1 m2) CVGL73TP3
Viresolve NFP Prefilter* Opticap (850 cm2) KSPV01FF1 Opticap (850 cm2) KSPV01FF1
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
Millipore offers a comprehensive line of chromatography columns, systems and media. Contact Millipore for details.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
31
SelGuide p14-72 12/27/04 4:36 PM Page 32
Serum
Animal sera contain important growth porcine, etc) tend to have high concen-
factors necessary for the effective culture of trations of colloids and thus require
mammalian cells. Serum can vary signifi- filtration. For difficult serum, a robust
cantly, depending on the species and age clarification step using Millistak+ depth
of the donor animal, seasonal changes and filter can be added. Depending on the
animal diet. Fetal bovine sera tends to be nature and volume of the serum stream
relatively easy to filter while calf and adult filters may need to be run in series to
bovine sera requires prefiltration or greater assure proper contaminant removal.
filtration area. Non-bovine sera (equine, For details on Tank Venting 6 , see page 70.
1
Typical Process Flow
Vent 6
3 4 5 5
2
Serum
2
Understanding the Options
2 Clarigard Filters • Polypropylene prefilter for robust particle and colloid removal
• Validated for multiple sanitization and SIP cycles
(0.5 µm, 1.0 µm or 3.0 µm) • Higher filtrate quality allows smaller size requirements for downstream
sterilizing-grade filtration step
• Non-fiber releasing structure preserves product purity
• Available in a wide-range of pore sizes to accommodate the needs of
each user. Choice should be made based on small-scale testing.
32
SelGuide p14-72 12/27/04 4:36 PM Page 33
3 Polysep II Filters • Depth filter consisting of a borosilicate glass layer and a layer of mixed
esters of cellulose membranes
(Grade W3, 1 µm + 0.2 µm) • Robust prefilter for concentrated solutions across a full range of flow rates
• High particle-loading capacity and retention
• Able to withstand multiple SIP or hot water sanitization cycles
• Non-fiber releasing
Final Filtration
• Reduce bacteria and mycoplasma 4 Durapore CBR 0.1 µm • Low protein-binding PVDF membrane
to ensure long term storage and Filters • Retentive membrane reduces bioburden
stability • Low extractables and non-fiber releasing PVDF chemistry preserve
• Eliminate the risk of adventitious product purity and yield
infectious agents • High flow rate at low pressure drop for reliable economic processing
Serum
• Operate consistently at high • 100% integrity testing ensures quality
differential pressures and flow rates • Validated for multiple SIP and hot water sanitization cycles
• Must be able to withstand multiple • Although 0.1 µm is typical for this application, Durapore CBR
steam-in-place or hot water 0.2 µm filters are also available. Choice should be based on
sanitization cycles small-scale screening.
• Run efficiently to ensure process
economics
5 Durapore 0.1 µm Filters • Sterilizing-grade PVDF membrane will assure bioburden and
mycoplasma clearance
• 100% Integrity testing and thousands of existing applications assure
proven performance
• Integrity testable on-site
• Although 0.1 µm is typical for this application, Durapore filters are
available in several pore sizes and in single-layer or multi-layer
configurations to accommodate the needs of each user, the degree of
protection required for the downstream process and the plugging char-
acteristics of the fluid. Choice should be based on small-scale testing.
5 Millipore Express SHR • Designed to remove high levels of mycoplasma and bacteria over a
0.1 µm Filters range of moderately plugging to highly fouling streams
• Asymmetric pore structure delivers extremely high flow rates at low
(with or without pressure drop
prefilter layer) • Sterilizing-grade PES membrane provides broad chemical compatibility
across a wide pH range (1–14)
• 100% integrity tested to ensure quality
• Robust construction validated for multiple SIP cycles
• Can be integrity tested on-site
• Available in single-layer 0.1 µm or double-layer 0.1 µm with prefilter
layer 0.1 µm configurations. The degree of protection required for the
downstream process and the plugging characteristics of the fluid will
guide this selection. Choice should be based on small-scale testing.
33
SelGuide p14-72 1/4/05 10:38 AM Page 34
3
Filter Quick Reference Guide
Recommended Filters
Grade A1HC Grade B1HC
Triple-layer Millistak+ HC Filters Area/Filter Catalogue No. Area/Filter Catalogue No.
2 2
1-cell Pod 0.1 m MA1CH01FS1 0.1 m MB1HC01FS1
5-cell Pod 0.5 m2 MA1HC05FS1 0.5 m2 MB1HC05FS1
10-cell Pod 1.0 m2 MA1HC10FS1 1.0 m2 MB1HC10FS1
Opticap Capsule 650 cm2 KA1HC10FF1 650 cm2 KB1HC10FF1
2-cell Stack 0.45 m2 LA1HCH6S6 0.45 m2 LB1HCH6S6
Serum
Grade SS Grade SC
Milligard Filters Area/Filter Catalogue No. Catalogue No.
Grade W3
Polysep II Filters Area/Filter Catalogue No.
34
SelGuide p14-72 12/27/04 4:36 PM Page 35
Millipore Express SHR Sterilizing-grade Filters* Area/Filter 0.1 µm Area/Filter 0.1 µm + Prefilter
Opticap XL3 Capsule 0.14 m2 KVEPA03TT3 0.12 m2 KHVEA03TT3
Opticap XL3
Gamma-compatible Capsule 0.14 m2 KVEPG03TT3 0.12 m2 KHVEG03TT3
Opticap XL5 Capsule 0.27 m2 KVEPA05TT1 0.22 m2 KHVEA05TT1
Opticap XL5
Gamma-compatible Capsule 0.27 m2 KVEPG05TT1 0.22 m2 KHVEG05TT1
5-inch Cartridge 0.27 m2 CVEP75TS3 0.22 m2 CHVE75TS3
Opticap XL10 Capsule 0.54 m2 KVEPA10TT1 0.5 m2 KHVEA10TT1
Opticap XLT10 Capsule 0.54 m2 KVEPA1TTT1 0.5 m2 KHVEG10TT1
Opticap XL10
Gamma-compatible Capsule 0.54 m2 KVEPG10TT1 0.5 m2 KHVEA1TTT1
Opticap XLT10
Gamma-compatible Capsule 0.54 m2 KVEPG1TTT1 0.5 m2 KHVEG1TTT1
10-inch Cartridge 0.54 m2 CVEP71TS3 0.5 m2 CHVE71TS3
Opticap XLT20 Capsule 1.07 m2 KVEPA2TTT1 1 m2 KHVEA2TTT1
Serum
Opticap XLT20
Gamma-compatible Capsule 1.07 m2 KVEPG2TTT1 1 m2 KHVEG2TTT1
20-inch Cartridge 1.07 m2 CVEP72TS3 1 m2 CHVE72TS3
Opticap XLT30 Capsule 1.6 m2 KVEPA3TTT1 1.5 m2 KHVEA3TTT1
Opticap XLT30
Gamma-compatible Capsule 1.6 m2 KVEPG3TTT1 1.5 m2 KVEPG3TTT1
30-inch Cartridge 1.6 m2 CVEP73TS3 1.5 m2 CHVE73TS3
*Millipore Express SHR Filters are in final development. Specifications may change. Consult technical services for details.
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
35
SelGuide p14-72 12/27/04 4:36 PM Page 36
Plasma Fractionation
Human plasma is the source of over 700 increasingly employs chromatography to labile proteins. A critical step, viral clear-
proteins of considerable therapeutic value make higher purity and better activity prod- ance, ensures the removal of viruses known
such as albumin, clotting factors, immuno- ucts. Contamination of plasma compounds to have contaminated source plasma such
globulins, fibrinogen and others. The can cause product instability as well as as parvovirus, hepatitis and HIV. Specialty
process used to extract and purify these plugging downstream filters and should antibodies such as hyper-immune globulin
proteins is known as plasma fractionation. be removed via prefiltration. Clarification typically include a viral clearance filtration
Classical fractionation employs selective is used to remove contaminants prior to step in their manufacturing process.
precipitation of proteins by manipulation chromatography or UF steps, while steriliz- For details on Tank Venting 17 , see page 70.
of solution pH, ionic strength, temperature ing-grade filtration is a final step used to
and ethanol content. Modern fractionation reduce bioburden and to sterilize heat
1
Typical Process Flow
Albumin
Vent 17
1
3 4 5
Plasma Fractionation
IgG Hyperimmune
Vent 17
6
18 8 9 10 11
Clotting Factors
12 18 13 14 15 16
36
SelGuide p14-72 12/27/04 4:36 PM Page 37
2
Understanding the Options
Albumin
Clarification and Prefiltration
• Remove colloids, aggregated and 2 Single-layer Millistak+ DE • Better suited for large volumes >500 L
non-product proteins, lipids and Filters • High internal surface area for maximum particle capture loading
particles prior to downstream • Graded density matrix allows retention of particle range
purification (Grade 55DE) • High porosity provides low pressure drop
• Protect downstream sterilizing-grade • Although Grade 55DE is typical for this application, Millistak+ filters
filters, chromatography media and are available in several pore sizes and in single-layer or multi-layer
TFF membranes configurations to accommodate the needs of each user, the degree of
• Must be able to withstand multiple protection required for the downstream process and the plugging char-
steam-in-place or hot water acteristics of the fluid. Choice should be based on small-scale testing.
sanitization cycles
• Run efficiently to ensure process
economics
1 Double-layer Millistak+ HC • Better suited for volumes <500 L or with low usage rates of less than
Filters 10 batches/year
• Double-layer design enhances loading capacity and filtrate quality
(Grade C0HC) • Unique configuration allows compression of multiple process steps so
prefiltration may not be required. This can lower overall filtration costs.
• Although Grade C0HC is ideal for this application, Millistak+ filters
are available in several pore sizes and in single-layer or multi-layer
configurations to accommodate the needs of each user, the degree of
protection required for the downstream process and the plugging char-
Plasma Fractionation
acteristics of the fluid. Choice should be based on small-scale testing.
4 Double-layer Polysep II Filters • Borosilicate glass top layer enhances particle and loading capacity
• Mixed esters of cellulose membrane bottom layer ensures high retention
(Grade W3, 1.0 µm + and filtrate quality
0.2 µm) • Robust construction validated to withstand multiple SIP or hot water
sanitization cycles
• Non-fiber releasing structure preserves product purity
• 100% integrity tested to ensure quality
• Available in a variety of pore sizes to accommodate the needs of each
user. Grade W3 is commonly used to protect downstream 0.22 µm
membrane filters. Choice should be made based on small-scale testing.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
37
SelGuide p14-72 12/27/04 4:36 PM Page 38
Ultrafiltration
• Reduce batch volumes and 3 Pellicon Cassettes with • Biomax void-free membrane has exceptional caustic stability and
exchange buffer systems for Biomax 10 kD Membrane excellent repeat performance
efficient column operation and • Low feed flow requirement minimizes pumping, working and hold up
final formulation volumes.
• Run efficiently to ensure process • Higher product recovery and flux
economics • Suspended screen in feed channel allows higher turbulence enhancing
the separation process
• Complete range of Pellicon devices allow for easy scale-up
ALTERNATIVE: If a PES membrane or broad chemical compatibility is a requirement Millipore suggests testing Millipore Express
SHF 0.2 µm Filters in your small-scale trials.
Plasma Fractionation
ALTERNATIVE: If adsorption is a concern, or a robust bioburden reduction is needed before the final filter Millipore suggests
running Durapore 0.45 µm filters in your small-scale trials.
38
SelGuide p14-72 12/27/04 4:36 PM Page 39
Viral Clearance
• Critical step to ensure removal of 8 Viresolve NFR Filters • >6 log removal of retroviruses (80–120 nm)
viruses known to have contaminated • >98% recovery of protein (IgG)
source plasma such as parvovirus, • 100% Integrity testing assures performance
hepatitis viruses and HIV • Robust PES membrane
• Following current regulatory guide- • Can be integrity tested on-site
lines, 2 orthogonal methods are
normally utilized to remove or
inactivate viruses
• Validated log removal of viruses is
a dedicated process step 8 Viresolve NFP Filters • >4 log removal of parvovirus and other small viruses
• Filtration products should easily • >98% recovery of protein up to 160kD
scale-up and down for simple 18 • Robust PVDF membrane
validation • 100% Integrity testing assures performance
• Can be integrity tested on-site
• To enhance filter performance and capacity, Millipore suggests using
the Viresolve Prefilter 18 in series.
Ultrafiltration
• Reduce batch volumes and 9 Pellicon Cassettes with • Low feed flow requirement minimizes pumping, working and hold
exchange buffer systems for Biomax 30 kD Membrane up volumes
efficient column operation and or Ultracel PLC 30 kD • Higher product recovery and flux
final formulation Membrane • Highly retentive void-free membranes offer good permeate flux and
• Run efficiently to ensure process withstand process upsets
economics • Robust low binding void-free Ultracel PLC membranes provide excellent
Plasma Fractionation
repeat performance
• Choose a membrane molecular weight cut-off 3–5X smaller than the
biomolecule. Choice should be based on small-scale testing.
Sterile Filtration
(Also see Aseptic Filling page 60) 11 Durapore 0.22 µm Filters • Sterilizing-grade PVDF low-binding membrane is ideal when adsorption
• Sterilizing-grade filters reduce is a concern
bioburden and sterilize heat labile • 100% Integrity testing and thousands of existing applications assure
proteins proven performance
• Must be able to withstand multiple • Although 0.22 µm is typical for this application, Durapore filters are
steam-in-place or hot water available in several pore sizes and in single-layer or multi-layer
sanitization cycles configurations to accommodate the degree of protection required for
• Run efficiently to ensure process the downstream process and the plugging characteristics of the fluid.
economics Choice should be based on small-scale testing.
• Integrity testable on-site
11 Millipore Express PES Filters • Sterilizing-grade PES membrane providing broad chemical compatibility
across a wide pH range (1–14)
• Robust construction validated for multiple SIP cycles
• 100% integrity tested to ensure quality
• Asymmetric pore structure delivers extremely high flow rates even with
clogging streams
• Can be integrity tested on-site
• Available in single-layer 0.2 µm (SHF) or double-layer 0.5 µm +
0.2 µm (SHC) configurations. The degree of protection required for the
downstream process and the plugging characteristics of the fluid will
guide this selection. Choice should be based on small-scale testing.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
39
SelGuide p14-72 12/27/04 4:37 PM Page 40
Clotting Factors
Clarification and Prefiltration
• Remove colloids, aggregated and 12 Single-layer Millistak+ DE • Better suited for large volumes >500 L
non-product proteins, lipids and Filters • High internal surface area for maximum particle capture loading
particles prior to downstream • Graded density matrix enables retention of a wide range of
purification (Grade 65DE) particle sizes
• Protect downstream sterilizing-grade • High porosity provides low pressure drop
filters, chromatography media and • Although Grade 65DE is typical for this application, Millistak+ filters
TFF membranes are available in several pore sizes and in single-layer or multi-layer
• Must be able to withstand multiple configurations to accommodate the needs of each user, the degree of
steam-in-place or hot water protection required for the downstream process and the plugging char-
sanitization cycles acteristics of the fluid. Choice should be based on small-scale testing.
• Run efficiently to ensure process
economics
ALTERNATIVE: If adsorption is a concern, or a robust bioburden reduction is needed before the final filter Millipore suggests
running Durapore 0.45 µm filters in your small-scale trials.
Viral Clearance
• Critical step to ensure removal of 13 Viresolve NFR Filters • >6 log removal of retroviruses (80–120 nm)
viruses known to have contaminated • >98% recovery
source plasma such as parvovirus, • Utilizes size exclusion technology
hepatitis viruses and HIV • Robust PES membrane
• Following current regulatory • 100% integrity tested to ensure performance
guidelines, 2 orthogonal methods • Can be integrity tested on-site
are normally utilized to remove or
inactivate viruses
• Validated log removal of viruses is
a dedicated process step
• Filtration products should easily 13 Viresolve NFP Filters • >4 log removal of parvoviruses and other small viruses
scale-up and down for simple • >98% recovery of protein up to 160 kD
validation 18 • Utilizes size exclusion technology
• Robust PVDF membrane
• 100% integrity tested to ensure performance
• Can be integrity tested on-site
• To enhance filter performance and capacity, Millipore suggests using
the Viresolve Prefilter 18 series.
40
SelGuide p14-72 12/27/04 4:37 PM Page 41
Ultrafiltration
• Reduce batch volumes and 14 Pellicon Cassettes with • Low feed flow requirement minimizes pumping, working and hold up
exchange buffer systems for Biomax or Ultracel PLC volumes
efficient column operation and Membranes • Higher product recovery and flux
final formulation • Highly retentive void-free membranes offer good permeate flux and
• Run efficiently to ensure process withstand process upsets
economics • Robust low binding Ultracel PLC void-free membranes provide excellent
repeat performance
• For sera with caustic stability constraints Millipore suggests Biomax
membranes. For low adsorption utilize Ultracel PLC membranes.
• Choose a membrane molecular weight cut-off 3–5X smaller than the
biomolecule. Choice should be based on small-scale testing
Sterile Filtration
(Also see Aseptic Filling page 60) 16 Durapore 0.22 µm Filters • Sterilizing-grade filters assure reduction of contaminating microorgan-
• Sterilizing-grade filters reduce isms that shorten the life of costly chromatography media
bioburden and sterilize heat labile • Low-binding PVDF membrane assures protein yield
proteins • 100% Integrity testing ensures quality
• Must be able to withstand multiple • Although 0.22 µm is typical for this application, Durapore filters are
steam-in-place or hot water available in several pore sizes and in single-layer or multi-layer
sanitization cycles configurations to accommodate the degree of protection required for
• Run efficiently to ensure process the downstream process and the plugging characteristics of the fluid.
economics Choice should be based on small-scale testing.
• Integrity testable on-site
Plasma Fractionation
ALTERNATIVE: For broad chemical compatibility and high flow rates or if PES membranes are required, Millipore suggests
testing Millipore Express SHF filters in your small-scale trials.
41
SelGuide p14-72 12/27/04 4:37 PM Page 42
3
Filter Quick Reference Guide
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
42
SelGuide p14-72 12/27/04 4:37 PM Page 43
Recommended Filters
Small-Scale Processing Large-Scale Processing
Media/Membrane Device (area/filter) Catalogue No. Device (area/filter) Catalogue No.
Clarification and Prefiltration
Single-layer Millistak+ DE
Grade 55DE 10-inch Opticap Capsule (930 cm2) K55DE10FF1 12-inch, 6-cell stack (0.63 m2) L55DEF2S3
16-inch*, 16-cell stack (3.47 m2) L55DET6S1
Grade 65DE 10-inch Opticap Capsule (930 cm2) K65DE10FF1 12-inch, 6-cell stack (0.63 m2) L65DEF2S3
16-inch*, 16-cell stack (3.47 m2) L65DET6S1
Grade 75DE 10-inch Opticap Capsule (930 cm2) K75DE10FF1 12-inch, 6-cell stack (0.63 m2) L75DEF2S3
16-inch*, 16-cell stack (3.47 m2) L75DET6S1
Grade SC (1.2 µm + 0.5 µm) Opticap XL2 Capsule (0.07 m2) KWSCA02TT3 Opticap XL10 Capsule (0.7 m2) KWSCA10TT1
Opticap XL4 Capsule (0.16 m2) KWSCA04TT3 Opticap XLT10 Capsule (0.7 m2) KWSCA1TTT1
Opticap XL5 Capsule (0.28 m2) KWSCA05TT1 10-inch Cartridge (0.7 m2) CWSC71S03
4-inch Cartridge (0.28 m2) CWSCM4S03 Opticap XLT20 Capsule (1.4 m2) KWSCA2TTT1
20-inch Cartridge (1.4 m2) CWSC72S03
Opticap XLT30 Capsule (2.1 m2) KWSCA3TTT1
Plasma Fractionation
30-inch Cartridge (2.1 m2) CWSC73S03
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
43
SelGuide p14-72 1/4/05 10:38 AM Page 44
Viresolve Prefilter* Opticap (850 cm2) KSPV01FF1 Opticap (850 cm2) KSPV01FF1
Viresolve NFR Filters 4-inch Opticap Capsule (0.093 m2) KZRV04TC3 Opticap XL10 Capsule (0.54 m2) KZRVA10TT1
Opticap XLT10 Capsule (0.54 m2) KZRVA1TTT1
10-inch Cartridge (0.54 m2) CZRV71TP1
Opticap XLT20 Capsule (0.86 m2) KZRVA2TTT1
20-inch Cartridge (0.86 m2) CZRV72TP1
Opticap XLT30 Capsule (1.29 m2) KZRVA3TTT1
30-inch Cartridge (1.29 m2) CZRV73TP1
Millipore suggests using multiple cartridges or capsules for values >3,600 L.
Sterilizing-grade Filtration
Durapore 0.22 µm Filters Opticap XL2 Capsule (0.09 m2) KVGLA02TT3 Opticap XL10 Capsule (0.69 m2) KVGLA10TT1
Opticap XL4 Capsule (0.19 m2) KVGLA04TT3 Opticap XLT10 Capsule (0.69 m2) KVGLA1TTT1
Opticap XL5 Capsule (0.35 m2) KVGLA05TT1 Opticap XLT20 Capsule (1.4 m2) KVGLA2TTT1
5-inch Cartridge (0.35 m2) CVGL75S01 Opticap XLT30 Capsule (2.1 m2) KVGLA3TTT1
10-inch Cartridge (0.69 m2) CVGL71TP3
20-inch Cartridge (1.4 m2) CVGL72TP3
30-inch Cartridge (2.1 m2) CVGL73TP3
Millipore Express SHF 0.2 µm Filters Opticap XL3 Capsule (0.16 m2) KGEPA03TT3 Opticap XL10 Capsule (0.54 m2) KGEPA10TT1
Opticap XL5 Capsule (0.29 m2) KGEPA05TT1 Opticap XLT10 Capsule (0.54 m2) KGEPA1TTT1
Plasma Fractionation
5-inch Cartridge (0.29 m2) CGEP75TP3 Opticap XLT20 Capsule (1.08 m2) KGEPA2TTT1
Opticap XLT30 Capsule (1.62 m2) KGEPA3TTT1
10-inch Cartridge (0.54 m2) CGEP71TP3
20-inch Cartridge (1.08 m2) CGEP72TP3
30-inch Cartridge (1.62 m2) CGEP73TP3
Millipore Express SHC Opticap XL3 Capsule (0.13 m2) KHGEA03TT3 Opticap XL10 Capsule (0.49 m2) KHGEA10TT1
0.5 µm + 0.2 µm PES Filters Opticap XL5 Capsule (0.24 m2) KHGEA05TT1 Opticap XLT10 Capsule (0.49 m2) KHGEA1TTT1
5-inch Cartridge (0.24 m2) CHGE75TS3 Opticap XLT20 Capsule (0.98 m2) KHGEA2TTT1
Opticap XLT30 Capsule (1.47 m2) KHGEA3TTT1
10-inch Cartridge (0.49 m2) CGEP71TS3
20-inch Cartridge (0.98 m2) CGEP72TS3
30-inch Cartridge (1.47 m2) CGEP73TS3
*Viresolve Prefilter will be available in Millipore’s Pod technology late 2005.
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
Millipore offers a comprehensive line of chromatography columns, systems and media. Contact Millipore for details.
44
SelGuide p14-72 12/27/04 4:38 PM Page 45
Vaccines
Vaccines are biologically active products Application Requirements
designed to stimulate the immune system • Vaccine broths have moderate to high solids
against future invasion of a pathogen by concentrations that require effective removal
before downstream purification. Millipore
inducing memory to specific antigens.
products are designed for high yield,
Vaccines may be produced from viral throughput and efficiency
pathogens such as those causing polio, • Highly purified vaccines are often required to
influenza and Lyme Disease, or from bac- minimize adverse reaction.
terial pathogens such as pertussis, tetanus, • Injectable vaccines require sterilization.
diphtheria and anthrax. Recombinant
fermentation techniques such as those
used for hepatitis vaccine, produce highly
purified antigen-specific subunits that stimu-
late immunity without concern of pathogen Vaccines Batch Volumes
infection. Vaccine production typically uses Mammalian Cell . . . . .<2,000 L . . . . 45
several filtration and purification steps. Viral Vectors . . . . . . . .<500 L . . . . . 48
To obtain a purified vaccine the selected Plasmid DNA . . . . . . .<5,000 L . . . . 50
microorganism must first be grown then Conjugates . . . . . . . . .<1,000 L . . . . 52
the selected antigen must be separated, Polysaccharides . . . . . .<2,000 L . . . . 54
purified, formulated and sterilized prior Filter Quick Reference Guide . . . . . . . . 56
to delivery.
Vaccines
Vaccines: Mammalian Cell
1
Typical Process Flow
Vent 9
2
6 7 8
45
SelGuide p14-72 12/27/04 4:38 PM Page 46
2
Understanding the Options
Cell Harvesting
(In place of TFF/Centrifuge,
post fermentation) 2 Prostak Open-Channel • Best suited for large bioreactors >1,000 L or bioreactors with high
• Remove heavy solid loads from Modules with Durapore usage rates of more than 10 batches/year
bioreactor fluid and recover product 0.22 µm Membrane • Open-channel design accommodates fluids containing low to medium
in filtrate density and solids
• Requires high capacity • High flux at low transmembrane pressure
• Wide feed stream variability • Robust construction allows multiple use
depending on cell culture type and • Validated for multiple SIP cycles
conditions • Although Durapore 0.22 µm membrane is typical for this application,
• If solid content is too high, centrifu- Prostak Modules are available in with a wide range of membranes to
gation becomes preferred technology accommodate the degree of protection required for the downstream
process and the plugging characteristics of the fluid. Choice should
be based on small-scale testing.
1 Double-layer Millistak+ HC • For bioreactor volumes up to 1,000 L or larger volumes with low usage
Filters rates of less than 10 batches/year
• Double layer design enhances loading capacity and filtrate quality
(Grade D0HC or C0HC) • Unique configuration allows compression of multiple process steps into
one, lowering overall filtration costs
Vaccines: Mammalian Cell
ALTERNATIVE: For smaller batch sizes where no centrifuge or TFF step is required Millipore suggests using Clarigard 0.3 µm or
Double-layer Milligard 0.5 µm + 0.2 µm (Grade SS) Filters in your process. Choice should be based on small-scale testing.
Clarification or Polishing
(Post TFF or Centrifuge)
• Remove cell debris, small particles 3 Triple-layer Millistak+ HC • Ideal solution post-centrifuge for medium and small volume bioreactors
and colloids passed through the Filters with <2,000 L volume
primary clarification step • Triple-layer configuration includes a membrane bottom layer to enhance
• Potential for variations in fluid (Grade B1HC) filter loading capacity and retention
particle size distribution • High filtrate quality allows smaller size requirements for downstream
• Must have high capacity and sterilizing-grade filtration step
protect downstream sterilizing- • Unique design enables the compression of multiple process steps into
grade filters one, lowering overall filtration costs.
4 Double-layer Milligard Filters • Ideal solution post-TFF when additional clarification of whole cells and
colloids is needed
(Grade SS, 0.5 µm + • Double-layer pleated configuration increases particle and colloid
0.2 µm) loading capacity
• Mixed esters of cellulose filter material with low protein-binding
characteristics
• Low extractables and non-fiber releasing
• High flow rate at low pressure drop
• Validated for multiple SIP cycles
• Decades of proven performance protecting membrane filters
• 100% integrity tested to ensure quality
46
SelGuide p14-72 12/27/04 4:38 PM Page 47
Bioburden Reduction
• Reduces bioburden at intermediate 5 Double-layer Millipore • Sterilizing-grade PES 0.2 µm membrane with an additional 0.5 µm
process step Express SHC 0.5 µm + prefilter layer all in one pleated device
• Protects downstream filters, media 0.2 µm Filters • Designed for bulk intermediate processing where fluids may be fouling
and equipment in batch sizes ranging from 100 to 20,000 L.
• Preserves product purity • PES membrane provides broad chemical compatibility across a wide
• Sterilizing-grade filtration required pH range (1–14)
• Robust construction validated for multiple SIP cycles
• 100% integrity tested to ensure quality
• Asymmetric pore structure delivers extremely high flow rates at low
pressure drop
• Can be integrity tested on-site
Sterile Filtration
• Sterilizing-grade step to reduce 8 Durapore 0.22 µm Filters • Low protein-binding sterilizing-grade PVDF membrane
bioburden or sterilize heat labile • Low extractables preserve product purity and yield
products • High flow rate at low pressure drop for reliable economic processing
• Highly validated and reliable • 100% integrity testing and thousands of applications assure proven
technology performance
• Preserves product purity • Validated for multiple SIP and hot water sanitization cycles
• Ensures product safety • Available in Millipak stacked disc format which allows minimal
hold-up volume
• Although 0.22 µm membrane is typical for this application, Durapore
filters are available in several pore sizes and in single-layer or
multi-layer configurations to accommodate the needs of each user.
Choice should be based on small-scale testing.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
47
SelGuide p14-72 12/27/04 4:38 PM Page 48
1
Typical Process Flow
Vent 8
1 2 3 4 5
6 7
2
Understanding the Options
Virus Barrier
• Removes adventitious viruses 2 Viresolve NFP Filters • >4 log removal of parvovirus and other small viruses
• Ensures product safety without compromising flow rate or removing vital media nutrients
• Requires a highly validated and 1 • Robust PVDF membrane
reliable technology • >98% protein recovery up to 160 kD
• Maximizes product recovery • Available in multiple formats for easy scale-up and scale-down
• Preserves and ensures product purity • 100% Integrity testing assures performance
• Can be integrity tested on-site
• To ensure performance and capacity, Millipore suggests using in series
with the Viresolve Prefilter 1 .
Clarification
• Removes cell debris, small particles 3 Single-layer Millistak+ CE • Better suited for volumes <2,000 L
and colloids after the cell lysis step Filters • High internal surface area for maximum particle capture loading
• Must have high throughput capacity • Filter matrix exhibits positive charge properties to enhance filtration
• Protects downstream sterilizing- (Grade 40CE, 45CE, or • High porosity provides low pressure drop
grade membrane filters 50CE) • Available in several media grades to accommodate the degree of
protection required for the downstream process and the plugging char-
acteristics of the fluid. Choice should be based on small-scale testing.
48
SelGuide p14-72 12/27/04 4:38 PM Page 49
Bioburden Reduction
• Reduces bioburden 4 Double-layer Durapore • Low protein-binding PVDF membrane with prefilter layer
• Protects downstream chromatography 0.45 µm Filters • Highly retentive membrane reduces bioburden
and UF/DF steps • Low extractables and non-fiber releasing PVDF chemistry preserves
• Preserves product purity (with 0.5 µm prefilter layer) product purity and yield
• High flow rate at low pressure drop for reliable economic processing
• 100% integrity testing and thousands of applications assures proven
performance
• Validated for multiple SIP and hot water sanitization cycles
Sterile Filtration
• Sterilizing-grade step reduces 7 Durapore 0.22 µm Filters • Low protein-binding sterilizing-grade PVDF membrane
bioburden • Low extractables preserve product purity and yield
• Highly validated and reliable • High flow rate at low pressure drop for reliable economic processing
technology • 100% integrity testing and thousands of applications assure proven per-
• Preserves and ensures product purity formance
• Ensures product safety • Validated for multiple SIP and hot water sanitization cycles
• Available in Millipak stacked disc format which allows minimal
hold-up volume
• Although 0.22 µm membrane is typical for this application, Durapore
filters are available in several pore sizes and in single-layer or
multi-layer configurations to accommodate the needs of each user.
Choice should be based on small-scale testing.
49
SelGuide p14-72 1/4/05 10:38 AM Page 50
1
Typical Process Flow
Vent 6
1 2 3
4 5
2
Understanding the Options
50
SelGuide p14-72 12/27/04 4:38 PM Page 51
ALTERNATIVE: In case of high concentrations (>5 g/L) Pellicon V Screen cassettes are recommended.
Sterile Filtration
• Sterilizing-grade step removes 5 Double-layer Millipore • Sterilizing-grade PES 0.2 µm membrane with an additional 0.5 µm PES
bacteria prior to aseptic fill Express SHC prefilter layer all in one pleated device
• Ensures product safety 0.5 µm + 0.2 µm Filters • Double-layer construction provides excellent capacity even in high salt
• Highly validated and reliable conditions
technology • PES membrane provides broad chemical compatibility across a wide
• Preserves product purity pH range (1–14)
• Robust construction validated for multiple SIP cycles
NOTE: Membrane chemistries other than • 100% integrity tested to ensure quality
PES are known to cause gel formation • Asymmetric PES pore structure delivers extremely high flow rates at low
at the membrane surface. We strongly pressure drop
recommend a PES filter for this step. • Can be integrity tested on-site
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
51
SelGuide p14-72 1/4/05 10:39 AM Page 52
Vaccines: Conjugates
1
Typical Process Flow
Vent 5
1 2 3 4
2
Understanding the Options
Vaccines: Conjugates
Bioburden Reduction
• Reduces bioburden 2 Double-layer Multilayer • Sterilizing-grade PVDF 0.22 µm membrane with an additional
• Protects downstream chromatography Durapore 0.45 µm + 0.45 µm prefilter layer all in one pleated device
and UF/DF steps 0.22 µm Filters • Low-binding membranes assure product yield and sterility
• Preserves product purity • 100% Integrity testing ensures quality
• Double-layer construction provides excellent capacity and protection
of downstream equipment
• Can be integrity tested on-site
52
SelGuide p14-72 12/27/04 4:38 PM Page 53
ALTERNATIVE: For applications where organic solvents are used, Millipore suggests utilizing a Prostak UF Module with
Ultracel membrane.
Sterile Filtration
• Sterilizing-grade step reduces 4 Durapore 0.22 µm Filters • Low protein-binding sterilizing-grade PVDF membrane
bioburden • Low extractables preserve product purity and yield
• Highly validated and reliable • High flow rate at low pressure drop for reliable economic processing
technology • 100% integrity testing and thousands of applications assure proven
• Preserves product purity performance
• Ensures product safety • Validated for multiple SIP and hot water sanitization cycles
• Available in Millipak stacked disc format which allows minimal hold-up
volume
• Although 0.22 µm membrane is typical for this application, Durapore
Vaccines: Conjugates
filters are available in several pore sizes and, in single-layer or
multi-layer configurations to accommodate the needs of each user.
Choice should be based on small-scale testing.
53
SelGuide p14-72 12/27/04 4:38 PM Page 54
Vaccines: Polysaccharides
1
Typical Process Flow
Vent 7
2 3 4
5 6
Vaccines: Polysaccharides
2
Understanding the Options
Primary Clarification
• Remove whole cells and solids from 1 Prostak Open-Channel • Best suited for large bioreactors >1,000 L or more than
bioreactor fluid and recover product Modules with Durapore 10 batches/year
in filtrate 0.22, 0.45 or 0.65 µm • Open-channel design to accommodate high cell density and high solids
• Requires high capacity Membrane cell culture fluids
• Wide feed stream variability • High flux at low transmembrane pressure
depending on cell culture type • Allows volume reduction as fluid is concentrated
and conditions • Robust construction enables multiple use
• If solid content is too high, • Validated for multiple SIP cycles
centrifugation becomes preferred • Selection of Durapore membrane depends on particle size distribution
technology in feed solution. Choice should be based upon small-scale testing.
• Membrane selection will depend
upon the size of the polysaccharide
Secondary Clarification
• Cell recovery from the fermenter 2 Triple-layer Millistak+ HC • Triple-layer configuration includes a membrane bottom layer to
broth, elimination of waste fluid Filters enhance filter loading capacity and retention
in the filtrate • Unique design enables the compression of multiple steps to one,
• High solids content in feed stream (Grade B1HC) lowering overall filtration costs.
• Feed stream quality can vary
depending on cell type and
culture conditions
54
SelGuide p14-72 12/27/04 4:38 PM Page 55
Bioburden Reduction
• Reduces bioburden at intermediate 3 Millipore Express SHC • Sterilizing-grade PES 0.2 µm membrane with an additional 0.5 µm
process step to reduce the risk 0.5 µm + 0.2 µm Filters prefilter layer all in one pleated device may eliminate the need for a
of pyrogenic contamination and prefilter
damage • Designed for bulk intermediate processing where fluids may be fouling
• Protects downstream filters, media in batch sizes ranging from 100 to 20,000 L.
and equipment • PES membrane provides broad chemical compatibility across a wide
• Preserves product purity pH range (1–14)
• Sterilizing-grade filtration required • Robust construction validated for multiple SIP cycles
• 100% integrity tested to ensure quality
• Asymmetric pore structure delivers extremely high flow rates at low
pressure drop
• Can be integrity tested on-site
ALTERNATIVE: If a PVDF or low-protein binding membrane is required, Millipore suggests testing Multilayer Durapore 0.45 µm
+ 0.22 µm in your small-scale trials.
Vaccines: Polysaccharides
• Easily scalable from lab to processing from batch to batch, have good chemical compatibility and
manufacturing scale are easy to clean
• Complete range of devices for easy scale-up
• Choose a membrane molecular weight cut-off 3–5X smaller than the
biomolecule. Choice should be based on small-scale testing.
Prefiltration
(Bulk intermediate)
• Removes colloidal and particulate 5 Double-layer Milligard Filters • Prefiltration for Durapore 0.22 µm Filters
contaminants and extend the life of • Double-layer pleated configuration of mixed esters of cellulose
final filters (Grade LS, 0.5 µm + 0.2 µm) membranes provide high dirt-holding capacity, and retention efficiency
• Should preserve polysaccharide • Low protein-binding media preserves polysaccharide purity
purity and operate consistently at • High porosity membranes operate at high flow rates and low
high differential pressures and flow pressure drops
rates • Non-fiber releasing structure preserves product purity
• Must be able to withstand multiple • 100% integrity tested to ensure quality
SIP or hot water sanitization cycles • Robust construction validated to withstand multiple SIP or hot water
• Run efficiently to ensure process sanitization cycles
economics • Grade LS is commonly used for this application; Milligard filters are
available in numerous pore sizes and in single-layer or multi-layer
configurations to accommodate the needs of each user, the degree of
protection required for the downstream process and the plugging char-
acteristics of the fluid. Choice should be based on small-scale testing.
ALTERNATIVE: When choosing Multilayer Durapore 0.45 µm + 0.22 µm for Final Filtration, this step is not required.
The prefilter layer is built into the final filter.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
55
SelGuide p14-72 1/4/05 10:39 AM Page 56
3
Filter Quick Reference Guide
56
SelGuide p14-72 12/27/04 4:39 PM Page 57
Vaccines
Ultracel PLC 300 kD membrane P2C300C01
Ultracel PLC 1,000 kD membrane P2C01MC01
Prostak UF 4-stack Modules
Ultracel PL 5 kD membrane PSLCSP041
Ultracel PL 10 kD membrane 0.39 m2 PSLGSP041
Ultracel PL 30 kD membrane PSLTSP041
OptiScale Devices
Durapore 0.22 µm membrane SVGLA47FF3
13.8 cm2
Multilayer Durapore 0.45 µm + 0.22 µm membrane SHGLA47FF3
Polysaccharides
Prostak MF Open-Channel 2-stack Modules
Durapore 0.22 µm membrane PSGVAG021
Durapore 0.45 µm membrane 0.17 m2 PSHVAG021
Durapore 0.65 µm membrane PSDVAG021
OptiScale Devices
Double-layer Milligard LS 0.5 µm + 0.2 µm media SWLSA47FF3
Double-layer Millipore Express SHC membrane SHGEA47FF3
13.8 cm2
Durapore 0.22 µm membrane SVGLA47FF3
Multilayer Durapore 0.45 µm + 0.22 µm membrane SHGLA47FF3
Pellicon 2 C Screen Mini-Cassettes
Ultracel PLC 30 kD membrane P2C030C01
0.1 m2
Ultracel PLC 100 kD membrane P2C100C01
Millistak+ Mini-Capsules
Grade B1HC 23 cm2 MB1HC23HH3
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
57
SelGuide p14-72 12/27/04 4:39 PM Page 58
Recommended Filters
Prostak MF Open-Channel Modules with Durapore Membrane
Area/Filter 0.22 µm 0.45 µm 0.65 µm
Millistak+ HC Filters Area/Filter Grade B1HC Grade C0HC Area/Filter Grade D0HC
2 2
1-cell Pod 0.1 m MB1HC01FS1 MC0HC01FS1 0.1 m MD0HC01FS1
5-cell Pod 0.5 m2 MB1HC05FS1 MC0HC05FS1 0.5 m2 MD0HC05FS1
10-cell Pod 1.0 m2 MB1HC10FS1 MC0HC10FS1 1.0 m2 MD0HC10FS1
Opticap Capsule 650 cm2 KB1HC10FF1 KC0HC10FF1 650 cm2 KD0HC10FF1
2-cell Stack, 16-inch dia. 0.45 m2 LB1HCH6S6 LC0HCH6S6 0.45 m2 LD0HCH6S6
8-cell Stack, 16-inch dia. 1.8 m2 LB1HCG6S2 LC0HCG6S2 1.6 m2 LD0HCG6S2*
58
SelGuide p14-72 1/4/05 10:39 AM Page 59
Viresolve NFP Filters Area/Filter Catalogue No. Viresolve Prefilter Area/Filter Catalogue No.
0.45 µm + 0.22 µm
0.22 µm 0.45 µm + 0.5 µm Sterilizing-grade
Durapore Filters Area/Filter Sterilizing-grade Prefilter Layer Area/Filter Multilayer
2
Opticap XL2 Capsule 0.09 m KVGLA02TT3
Opticap XL4 Capsule 0.19 m2 KVGLA04TT3
5-inch Cartridge 0.35 m2 CVGL75S01
Opticap XL5 Capsule 0.35 m2 KVGLA05TT1
Opticap XL5
Gamma-compatible Capsule 0.35 m2 KVGLG05TT1
Opticap XL10 Capsule 0.69 m2 KVGLA10TT1 KVHLA10TT1 0.55 m2 KHGLA10TT1
Opticap XL10
Gamma-compatible Capsule 0.69 m2 KVGLG10TT1
10-inch Cartridge 0.69 m2 CVGL71TP3 CVHL71TP3 0.55 m2 CHGL71TP3
Opticap XLT10 Capsule 0.69 m2 KVGLA1TTT1 0.55 m2 KHGLA1TTT1
Opticap XLT10
Gamma-compatible Capsule 0.69 m2 KVGLG1TTT1
20-inch Cartridge 1.4 m2 CVGL72TP3 CVHL72TP3 1.1 m2 CHGL72TP3
Opticap XLT20 Capsule 1.4 m2 KVGLA2TTT1 1.2 m2 KHGLA2TTT1
Opticap XLT20
Gamma-compatible Capsule 1.4 m2 KVGLG2TTT1
30-inch Cartridge 2.1 m2 CVGL73TP3 CVHL73TP3 1.65 m2 CHGL73TP3
Opticap XLT30 Capsule 2.1 m2 KVGLA3TTT1 1.75 m2 KHGLA3TTT1
Opticap XLT30
Vaccines
Gamma-compatible Capsule 2.1 m2 KVGLG3TTT1
40-inch Cartridge 2.76 m2 CVGL74TP3 CVHL74TP3
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
Millipore offers a comprehensive line of chromatography columns, systems and media. Contact Millipore for details.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
59
SelGuide p14-72 12/27/04 4:39 PM Page 60
1
include pre-filled syringes, ampules, or Typical Process Flow
lyophilized powder. Sterile filtration is used
after compounding or at the filling head.
For details on Tank Venting 3 , see page 70. 3 Vent
Active
Pharmaceutical
Ingredients
2 1
Other
Formulation
Ingredients
2
Understanding the Options
Final Aseptic Filling
ALTERNATIVE: For high flow applications or if a PES membrane is requested, sterilizing-grade Millipore Express PES Filters
are available.
Prefilter
• Typically needed only for more 2 Milligard Filters • Available in double-layer pleated configurations for increased particle
concentrated solutions (>10 mg/mL) and colloid loading capacity
• Must prevent plugging of down- (Grade SS, 0.5 µm + • Mixed esters of cellulose filter material with low protein-binding
stream sterilizing-grade 0.2 µm) characteristics
• Preserves product purity • Low extractables and non-fiber releasing
• High flow rate • High flow rate at low pressure drop
• Robust construction to withstand SIP • Validated for multiple SIP cycles
• Decades of proven performance protecting membrane filters
• 100% integrity tested
• Although grade SS, 0.5 µm + 0.2 µm is commonly used to protect
downstream 0.22 µm sterilizing-grade membrane filters, Milligard filters
are available in several pore sizes and in single-layer or multi-layer
configurations. Choice should be based on small-scale testing.
60
SelGuide p14-72 12/27/04 4:39 PM Page 61
3
Filter Quick Reference Guide
Recommended Filters
Recommendation table based on filter capacity of approximately 1,000 L/m2
Prefiltration (optional) Final Sterilizing-grade Filtration
Volume Device (area/filter) Catalogue No. Device (area/filter) Catalogue No.
10–50 L Opticap XL2 Capsule (0.07 m2) KWSSA02TT3 Millipak Gold 40 Unit (0.02 m2) MPGL04GF2
Millipak Gold 60 Unit (0.03 m2) MPGL06GF3
Millipak Gold 100 Unit (0.05 m2) MPGL1GCF3
50–300 L Opticap XL2 Capsule ( 0.07 m2) KWSSA02TT3 Opticap XL2 Capsule (0.09 m2) KVGLA02TT3
Opticap XL4 Capsule (0.16 m2) KWSSA04TT3 Millipak Gold 200 Unit (0.11 m2) MPGL2GCL3
Opticap XL5 Capsule (0.28 m2) KWSSA05TT1 Opticap XL4 Capsule (0.19 m2) KVGLA04TT3
4-inch Cartridge (0.28 m2) CWSSM4S03 Optiseal Cartridge (0.18 m2) LAGL04TP6
Opticap XL5 Capsule (0.35 m2) KVGLA05TT1
5-inch Cartridge (0.35 m2) CVGL75S01
300–1,500 L Opticap XL10 Capsule (0.7 m2) KWSSA10TT1 Opticap XL10 Capsule (0.69 m2) KVGLA10TT1
Opticap XLT10 Capsule (0.7 m2) KWSSA10TTT1 Opticap XLT10 Capsule (0.69 m2) KVGLA1TTT1
10-inch Cartridge (0.7 m2) CWSS71S03 10-inch Cartridge (0.69 m2) CVGL71TP3
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
61
SelGuide p14-72 1/4/05 10:39 AM Page 62
1
Typical Process Flow
Vent 4
WFI
1 2 3
Powder
Packaging
2
Understanding the Options
Prefiltration
• Remove colloidal and particulate 1 Double-layer Milligard Filters • Double-layer pleated configuration of mixed esters of cellulose
contaminants membranes remove particles and colloids
• Preserve product purity (Grade SS, 0.5 µm + • High porosity membranes operate at high flow rates and
• Operate consistently at high 0.2 µm, or Grade SC, low pressure drops
differential pressures and flow rates 1.2 µm + 0.5 µm) • Better suited for low-solute concentrations
• Prevent plugging and extend the • Non-fiber releasing structure preserves product purity
life of downstream filters • 100% integrity tested to ensure quality
• Able to withstand demanding • Robust construction validated to withstand multiple SIP or hot water
sanitization cycles sanitization cycles
• Run efficiently to ensure process • Available in a variety of pore sizes to accommodate the needs of
economics each user. Grade SS is commonly used to protect downstream
• Solute concentration impacts 0.22 µm sterilizing-grade filters. Grade SC is better suited to protect
filter selection 0.45 µm membrane filters. Choice should be made based on
small-scale testing.
1 Double-layer Polysep II Filters • Borosilicate glass top layer enhances particle and loading capacity in
high solute applications
(Grade W6, 1 µm+ 0.5 µm, • Mixed esters of cellulose membrane bottom layer ensures high retention
or Grade W3, 1 µm + and filtrate quality
0.2 µm) • Ideal for high solute concentration such as 5% Dextrose
• Robust construction validated to withstand multiple SIP or hot water
sanitization cycles
• Non-fiber releasing structure preserves product purity
• 100% integrity tested to ensure quality
• Available in a variety of pore sizes to accommodate the needs of
each user. Grade W3 is commonly used to protect downstream
0.22 µm membrane filters. Grade W6 is better suited to protect
0.45 µm membrane filters. Choice should be made based on small-
scale testing.
62
SelGuide p14-72 12/27/04 4:39 PM Page 63
Bioburden Reduction
• Reduce bioburden prior to terminal 2 Double-layer Durapore • Low protein-binding PVDF membrane with prefilter
sterilization 0.45 µm Filters • Retentive membrane reduces bioburden
• Preserve product purity • Low extractables and non-fiber releasing PVDF chemistry preserve prod-
• Operate consistently at high flow (with 0.5 µm prefilter layer) uct purity and yield
rates • High flow rate at low pressure drop for reliable economic processing
• Able to withstand demanding saniti- • 100% integrity tested to ensure quality
zation requirements • Validated for multiple SIP and hot water sanitization cycles
ALTERNATIVE: If a PES membrane is required, Millipore suggests including Millipore’s Express SHF Filters in your screening trials.
63
SelGuide p14-72 12/27/04 4:39 PM Page 64
3
Filter Quick Reference Guide
Recommended Filters
Prefiltration and Bioburden Reduction used in combination.
Low Solute Concentration (e.g. 5% Dextrose)
Area/Filter Catalogue No. Area/Filter Catalogue No.
Milligard SC (1.2 µm + 0.5 µm) Filters Durapore 0.45 µm Filters + 0.5 µm Prefilter Layer
Opticap XL10 Capsule 0.7 m2 KWSCA10TT1 Opticap XL10 Capsule 0.69 m2 KVHLA10TT1
Opticap XLT10 Capsule 0.7 m2 KWSCA1TTT1 10-inch Cartridge 0.69 m2 CVHL71TP3
10-inch Cartridge 0.7 m2 CWSC71S03 20-inch Cartridge 1.4 m2 CVHL72TP3
Opticap XLT20 Capsule 1.4 m2 KWSCA2TTT1 30-inch Cartridge 2.1 m2 CVHL73TP3
20-inch Cartridge 1.4 m2 CWSC72S03 40-inch Cartridge 2.8 m2 CVHL74TP3
Opticap XLT30 Capsule 2.1 m2 KWSCA3TTT1
30-inch Cartridge 2.1 m2 CWSC73S03
40-inch Cartridge 2.8 m2 CWSC74S03
64
SelGuide p14-72 12/27/04 4:39 PM Page 65
Polysep II W6 (1.0 µm + 0.5 µm) Filters Durapore 0.45 µm Filters + 0.5 µm Prefilter Layer
Opticap XL10 Capsule 0.46 m2 KGW6A10TT1 Opticap XL10 Capsule 0.69 m2 KVHLA10TT1
Opticap XLT10 Capsule 0.46 m2 KGW6A1TTT1 10-inch Cartridge 0.69 m2 CVHL71TP3
10-inch Cartridge 0.46 m2 CGW671S03 20-inch Cartridge 1.4 m2 CVHL72TP3
Opticap XLT20 Capsule 0.92 m2 KGW6A2TTT1 30-inch Cartridge 2.1 m2 CVHL73TP3
20-inch Cartridge 0.92 m2 CGW672S03 40-inch Cartridge 2.8 m2 CVHL74TP3
Opticap XLT30 Capsule 1.38 m2 KGW6A3TTT1
30-inch Cartridge 1.38 m2 CGW673S03
40-inch Cartridge 1.84 m2 CGW674S03
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
65
SelGuide p14-72 12/27/04 4:40 PM Page 66
Ophthalmic Solutions
Ophthalmic solutions range from contact such as NaCl, preservatives, petrolatum for
lens cleaning and storage solutions to eye ointments and thixotropic polymeric sub-
surgery and treatment products. These stances for lubricating agents. Heat-labile
preparations must meet stringent regulatory components are processed via sterile filtra-
requirements and product specifications. tion for particle and bioburden reduction
Though the major component in and microorganism removal.
ophthalmics is water, many contain salts For details on Tank Venting 3 , see page 70.
1
Typical Process Flow
Vent 3
WFI
1 2 2
Powder
2
Understanding the Options
Prefiltration
• Reduce particles and bioburden 1 Double-layer Polysep II Filters • Borosilicate glass top layer enhances particle and loading capacity in
• Extend the life of final filters high solute applications
• Must be robust for high volume (Grade W6, 1 µm + 0.5 µm) • Mixed esters of cellulose membrane bottom layer ensures high retention
processes and filtrate quality
• Run efficiently for optimal process • Robust construction validated to withstand multiple SIP or hot water san-
economics itization cycles
• Non-fiber releasing structure preserves product purity
• 100% integrity tested to ensure quality
• Available in a variety of pore sizes to accommodate the needs of each
user. Grade W6 is commonly used in this application. Choice should
be made based on small-scale testing.
Sterile Filtration
• Sterilizing-grade filter to remove 2 Charged Durapore 0.22 µm • Sterilizing-grade PVDF membrane
microorganisms Filters • Ideal solution when preservative binding is a concern
• Operate consistently at high flow • High flow rates and throughput, low extractables and protein binding
rates • 100% Integrity testing to ensure performance
• Must be robust for high volume
processes
• Run efficiently to ensure process
economics
2 Millipore Express SHF • Sterilizing-grade PES membrane providing broad chemical compatibility
0.2 µm Filters across a wide pH range (1–14)
• Asymmetric pore structure delivers extremely high flow rates at low
preservative binding
• 100% integrity tested to ensure quality
66
SelGuide p14-72 12/27/04 4:40 PM Page 67
3
Filter Quick Reference Guide
Recommended Filters
Small-Scale Processing <100 L Large-Scale Processing >100 L
Media/Membrane Device (area/filter) Catalogue No. Device (area/filter) Catalogue No.
Prefiltration
Double-layer Polysep II Filters Opticap XL2 Capsule (0.06 m2) KGW6M02TT3 Opticap XL10 Capsule (0.46 m2) KGW6A10TT1
(Grade W6, 1.0 µm + 0.5 µm) Opticap XL4 Capsule (0.11 m2) KGW6A04TT3 Opticap XLT10 Capsule (0.46 m2) KGW6A1TTT1
Opticap XL5 Capsule (0.19 m2) KGW6A05TT1 10-inch Cartridge (0.46 m2) CGW671S03
4-inch Cartridge (0.19 m2) CGW674S03 Opticap XLT20 Capsule (0.92 m2) KGW6A2TTT1
20-inch Cartridge (0.92 m2) CGW672S03
Opticap XLT30 Capsule (1.38 m2) KGW6A3TTT1
30-inch Cartridge (1.38 m2) CGW673S03
Sterilizing-grade Filtration
Ophthalmic Solutions
Charged Durapore 0.22 µm PVDF Filters Optiseal Cartridge ( 0.18 m2) LCGL04TP6 10-inch Cartridge (0.69 m2) CCGL71TP1
20-inch Cartridge (1.4 m2) CCGL72TP1
30-inch Cartridge (2.1 m2) CCGL73TP1
Millipore Express SHF 0.2 µm PES Filters Opticap XL3 Capsule (0.16 m2) KGEPA03TT3 Opticap XL10 Capsule (0.54 m2) KGEPA10TT1
Opticap XL5 Capsule (0.29 m2) KGEPA05TT1 Opticap XLT10 Capsule (0.54 m2) KGEPA1TTT1
5-inch Cartridge (0.29 m2) CGEP75TP3 10-inch Cartridge (0.54 m2) CGEP71TP3
Opticap XLT20 Capsule (1.08 m2) KGEPA2TTT1
20-inch Cartridge (1.08 m2) CGEP72TP3
Opticap XLT30 Capsule (1.62 m2) KGEPA3TTT1
30-inch Cartridge (1.62 m2) CGEP73TP3
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
67
SelGuide p14-72 1/4/05 10:39 AM Page 68
Facilities Water
Pharmaceutical grade water is defined as bioburden and contaminant load while
feed water common to process systems maintaining a low pressure drop for
such as washers, autoclaves or secondary extended periods of time. Filters in DI
water purification systems such as WFI systems must maintain low pressure drops
distillation. Filters in central water systems throughout long throughput cycles and may
may be exposed to a variety of contami- be exposed to particle loads for resin beds.
nants. The filter train should reduce the
1
Typical Process Flow
Bioburden
Reduction
Feed Pharmaceutical
Water 1 2 Facilities
Water
Facilities Water
Endotoxin
Prefiltration Removal
Final
Sterile
Filtration
2
Understanding the Options
Prefiltration
1 Clarigard 3.0 µm Filters • All-polypropylene filters have a 99.99% retention rating with high
particle holding capacity and low extractables
Bioburden Reduction
2 Durapore CBR 0.2 µm • An economical solution when only bioburden reduction is required
PVDF Filters
Endotoxin Removal
2 Charged Durapore 0.22 µm • A great choice when endotoxin and bioburden reduction is required
PVDF Filters
68
SelGuide p14-72 1/4/05 10:39 AM Page 69
3
Filter Quick Reference Guide
Recommended Filters
Flowrate Prefiltration Bioburden Reduction Endotoxin Removal Sterilizing Filtration
(Lpm)
Clarigard 3.0 µm Filters Durapore CBR 0.2 µm Filters Charged Durapore 0.22 µm Filters Millipore Express SHF 0.2 µm Filters
1–15 10-inch Cartridge: D03071S01 10-inch Cartridge: CVDI71TPS 10-inch Cartridge: CCGL71TP1 10-inch Cartridge: CGEP71TP3
15–30 20-inch Cartridge: D03072S01 20-inch Cartridge: CVDI72TPS 20-inch Cartridge: CCGL72TP1 20-inch Cartridge: CGEP72TP3
30–45 20-inch Cartridge: D03072S01 20-inch Cartridge: CVDI72TPS 30-inch Cartridge: CCGL73TP1 30-inch Cartridge: CGEP73TP3
Per 45 30-inch Cartridge: D03073S01 30-inch Cartridge: CVDI73TPS 30-inch Cartridge: CCGL73TP1 30-inch Cartridge: CGEP73TP3
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2 for a detailed list.
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
Facilities Water
69
SelGuide p14-72 12/27/04 4:41 PM Page 70
1
Typical Process Flow
Vent
Filter
3
Filter Quick Reference Guide
Recommended Filters
Filter Format Area/Filter Catalogue No.
Aervent Hydrophobic Filters
Aervent-50 capsule 19.6 m2 MTGR15010
Opticap XL2 capsule 0.10 m2 KTGRA02TT3
Optiseal cartridge 0.18 m2 LAGR04TP6
Opticap XL4 capsule 0.21 m2 KTGRA04TT3
Opticap XL5 capsule 0.32 m2 KTGRA05TT1
5-inch cartridge 0.32 m2 CTGR75S01
Opticap XL10 capsule 0.65 m2 KTGRA10TT1
10-inch cartridge 0.65 m2 CTGR71TP1
20-inch cartridge 1.3 m2 CTGR72TP1
30-inch cartridge 1.95 m2 CTGR73TP1
Filters are available in many sizes, configurations and formats. See the quick reference tables on page 2
for a detailed list.
70
SelGuide p14-72 1/3/05 4:21 PM Page 71
Trademark Information
Millipore Corporation.
Mobius™ Solutions
Polysep™ II Filters
Prostak™ Modules
71
SelGuide p14-72 1/4/05 10:40 AM Page 72
Ordering Information
Lenntech
[email protected]
[email protected] Tel.
Tel. +31-152-610-900
+31-152-610-900
www.lenntech.com
www.lenntech.com Fax.
Fax.+31-152-616-289
+31-152-616-289
Contact Millipore
72
SelGuideCov 1/3/05 3:32 PM Page 1
Filtration
Selection
Guide
Choosing the Right Filter
for Your Application
Lenntech
[email protected] Tel. +31-152-610-900
www.lenntech.com Fax. +31-152-616-289
Copyright 2004 Millipore Corporation, Billerica, MA 01821 U.S.A. All rights reserved.
Lit. No. SG1500EN00 Rev. A Printed in U.S.A. 12/04 04-204 Photography, Robert Fraher.