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Doc. No. VGWA2012REV1.0
VALIDATION GUIDE
for WaterSep Hollow Fiber Cartridges
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2 WaterSep Validation Guide
Terms of Sale
WaterSep sells all goods and services per the terms and conditions of sale as specified by the WaterSep sales agreement.
To receive a copy of these terms and conditions, or to comment on our products, contact us at:
WaterSep Technology Corporation
420 Maple Street, Suite 1
Marlborough, MA 01752
USA
Telephone: +1–508–970–0089, extension 204
Fax: 508-970-0146
Email: Contact@WaterSep.net
All third party trademarks are the property of their respective owners.
© 2013 by WaterSep Bioseparations. All rights reserved.
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WaterSep Validation Guide 3
CONTENTS
List of Tables 5
List of Figures 5
Chapter 1—Overview
How this Validation Guide Can Help You 6
Intended Audience 6
Getting Help 7
What is Process Validation? 7
Chapter 2—Product Information
Lab-, Pilot- and Production-Scale Hollow Fiber Cartridges 9
Intended Applications 9
Cartridge Design 10
Cartridge Labeling and Catalog Numbers 11
Materials of Construction 14
Packaging 14
Product Specifications 15
Void Volume of Hollow Fiber Cartridges 15
Membrane Performance 20
Cartridge Performance 20
Storage of New and Used Cartridges 22
Preparing Your Cartridge for Use 22
Chapter 3—Validation Information
Membrane Water Flux 23
Membrane Solute Rejection 24
Cartridge Integrity Test 25
Non-Destructive Testing 25
Integrity test - Pressure Hold Test 25
Reference Values for WaterSep Factory Membrane diffusion test 27
Cartridge Water Flux 27
Cartridge Crossflow 30
Cartridge Chemical Compatibility Study 33
Cartridge Rinsing and Buffer Equlibration Study 35
Hollow Fiber Cartridge Scalability Studies 36
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4 WaterSep Validation Guide
Chapter 4—Product Safety
Biocompatibility Studies 39
Chapter 5—Quality Assurance Information
Certificate of Compliance 40
Appendices
Appendix I—Additional Documentation 41
Appendix II—Test Procedures and Reports 42
Index
Index 43
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WaterSep Validation Guide 5
LIST OF TABLES
Table 1. Overview of the hollow fiber cartridges described in this validation guide 9
Table 2. Physical characteristics of MiniDiscover Green, Discovery Green, and Explorer
Green HF Cartridges 16
Table 3. Physical characteristics of Investigator and BioProducer cartridges 17
Table 4. Void volumes of WaterSep Green hollow fiber cartridges 18
Table 5. Air flow specifications for WaterSep Green single use hollow fiber cartridges 21
Table 6. Water permeability of WaterSep membranes 23
Table 7. Results of solute passage through WaterSep membrane (% P – percent passage)
24
Table 8. Results of membrane integrity tests for Investigator12 Cartridges 27
Table 9. Water flux results for an Investigator12 hollow fiber cartridges 28
Table 10. Chemical compatibility list for WaterSep cartridges (R = recommended, L =
limited exposure, NR = not recommended, U = unknown) 33
Table 11. Results from the E. Coli lysate clarification scalability study 37
Table 12. Helpful information available at www.WaterSep.net 41
Table 13. Test reports available from www.WaterSep.net 42
LIST OF FIGURES
Figure 1. Main parts of a WaterSep hollow fiber cartridge 10
Figure 2. Cartridge showing hollow fibers encapsulated in the hollow fiber housing 11
Figure 3. Typical hollow fiber cartridge label show information helpful to users 12
Figure 4. Identifying cartridge properties by catalog number 13
Figure 5. Clean water flux for an Investigator12 Green, 30K MWCO, 1.0 mm ID 28
Figure 6. Clean Water flux for an Investigator12 Green, 300K MWCO, 1.0 mm ID 29
Figure 7. Clean Water flux for an Investigator12 Green, 0.2 um, 1.0 mm ID 29
Figure 8. Delta P versus crossflow with water for Producer12/24/41 Green cartridges 31
Figure 9. Delta P versus crossflow with water for Investigator12/24/41 Green cartridges 32
Figure 100. Results of Extractables Level vs. Volumetric Throughput of Purified Water
(Liters per m2) 35
Figure 111. Pressure and permeate flux profiles for the Explorer12 cartridge 36
Figure 122. Pressure and permeate flux profiles for the Explorer24 cartridge 37
Figure 133. Optimization results of scalability study using Explorer12 and Investigator12
cartridges 38
Figure 144. Example of a cartridge certificate of compliance 40
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Overview
6 WaterSep Validation Guide
CHAPTER 1—OVERVIEW
HOW THIS VALIDATION GUIDE CAN HELP YOU
WaterSep created this validation guide to help scientists and engineers use our hollow
fiber cartridges properly and efficiently. You can benefit many ways from reading
and understanding the information in this validation guide:
You can save considerable time when setting up and using your hollow fiber cartridge.
You can obtain consistent results and extend the service life of your cartridge.
You can find the information you need to help validate your hollow fiber cartridge
system to meet FDA regulations.
WHAT YOU WILL LEARN
Designing and validating a hollow fiber cartridge system to meet FDA requirements
involves applying technical knowledge in an organized fashion. While the path to system
design and validation can take many directions, the performance and specifications of the
hollow fiber cartridge remain constant. You will need the following information to
validate your WaterSep cartridges within your application:
Product labeling, materials of construction, cartridge physical characteristics, and
product performance specifications
Results of our cartridge integrity, performance, compatibility, and scalability studies
Results of extractable, USP, hemolysis, and cytotoxicity tests performed by
independent testing laboratories
Operational, quality control, and regulatory support documents
INTENDED AUDIENCE
This validation guide was written for scientists and engineers who have laboratory
operation and process engineering skills. If you need assistance, or do not fully
understand the information in this guide, contact WaterSep Bioseparations for support.
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Overview
WaterSep Validation Guide 7
GETTING HELP
WaterSep engineers are membrane filtration experts. If you have questions or need
specific product or application information, please contact our technical support team.
WaterSep Technology Corporation
420 Maple Street, Suite 1
Marlborough, MA 01752
USA
Telephone: +1–508–970–0089 x204
Fax: 508–970–0146
Email: Contact@WaterSep.net
WHAT IS PROCESS VALIDATION?
If you are new to process validation, the FDA offers the following introduction as quoted
from CPG Sec. 490.100 Process Validation Requirements for Drug Products and Active
Pharmaceutical Ingredients Subject to Pre-Market Approval.
"Validation of manufacturing processes is a requirement of the Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals (21 CFR 211.100 and 211.110), and is considered an enforceable element of current good manufacturing practice for active pharmaceutical ingredients (APIs) under the broader statutory CGMP provisions of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. A validated manufacturing process has a high level of scientific assurance that it will reliably produce acceptable product. The proof of validation is obtained through rational experimental design and the evaluation of data, preferably beginning from the process development phase and continuing through the commercial production phase. Refer also to the Guideline of General Principles of Process Validation (May 1987, originally published by CDER, CBER, and CDRH and presently recognized by CDER, CBER, and CVM)1. (Note: The guideline is under revision as of the date of this CPG.) Before commercial distribution begins, a manufacturer is expected to have accumulated enough data and knowledge about the commercial production process to support post-approval product distribution. Normally, this is achieved after satisfactory product and process development, scale-up studies, equipment and system qualification, and the successful completion of the initial conformance batches. Conformance batches (sometimes referred to as "validation" batches and demonstration batches) are prepared to demonstrate that, under
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Overview
8 WaterSep Validation Guide
normal conditions and defined ranges of operating parameters, the commercial scale process appears to make acceptable product. Prior to the manufacture of the conformance batches the manufacturer should have identified and controlled all critical sources of variability."
Guidelines for validation of biological systems and processes can be found in publications
from the FDA.
This validation guide provides you with information that can facilitate validation of your
WaterSep products and systems. In addition, WaterSep can provide you with additional
membrane and product information specific to your particular needs. For assistance,
contact WaterSep at +1–508–970–0089, extension 204.
As you begin to validate your system, it is helpful to know that you must accomplish
three qualifications: 1—An installation qualification (IQ) that verifies that the hollow fiber
membrane process and supporting equipment can consistently operate within established
limits and specifications. 2—An operating qualification (OQ) that verifies that the process
can consistently reproduce operating results and that the process is effective.
3—A performance qualification (PQ) that verifies, through operational testing and data,
that the finished product produced by the specific process meets and conforms
to the product release specifications for functionality and safety.
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Product Information
WaterSep Validation Guide 9
CHAPTER 2—PRODUCT
INFORMATION
LAB-, PILOT- AND PRODUCTION-SCALE HOLLOW FIBER
CARTRIDGES
WaterSep manufactures hollow fiber cartridges for lab-, pilot- and production-scale
separation operations (Table 1). The cartridges are designed for linear scale-up, offering
consistency in design elements such as materials of construction, fiber configuration, and
fiber length. Other product benefits include low fouling performance and easy cleaning.
This Validation Guide covers WaterSep’s Green Line, the single use glycerin free hollow
fiber product line.
Table 1. Overview of the hollow fiber cartridges described in this validation guide
Cartridge Type Applications Range of
Surface Areas
Range of Sample Volumes/Cartrid
ge Lengths (Inches)
MiniDiscovery Green Lab 0.019–0.038 ft2 (17.3–35.6 cm2)
10–125 ml 12 and 24
Discover Green Lab 0.056–0.115 ft2
(51.8–106.9 cm2) 10–400 ml 12 and 24
Explorer Green Lab 0.16–0.62 ft2
(155–580 cm2) 150–3000 ml 12, 24, and 41
Investigator Green Pilot 1.4–5.5 ft2
(0.13–0.50 m2) 1–25 L 12, 24, and 41
BioProducer Green Production 13.5–54 ft2
(1.25–5.0 m2) 10–300 L 12, 24, and 41
Maximizer Green Production 54–110 ft2
(5.0–10.0 m2) > 300 L 24 and 41
INTENDED APPLICATIONS
The intended applications in the biopharmaceutical/bioindustrial sectors include
crossflow microfiltration and ultrafiltration for:
Primary recovery/clarification
Vaccine purification and
concentration
Cell washing
Cell harvesting
Bacteria separation
in fermentation broths
Debris removal post-centrifugation
Primary recovery of recombinant
biopharmaceuticals
Macromolecule concentration
and diafiltration (enzymes, antibodies,
proteins, and viruses)
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Product Information
10 WaterSep Validation Guide
CARTRIDGE DESIGN
Hollow fiber cartridges consist of a housing with an inlet port for feed, an outlet port
for retentate, and two outlet ports for the permeate (Figure 1).
The housings contains hollow fiber membrane made from an antifouling modified
polyethersulfone (PES) composition (Figure 2).
Fluid flows into the feed port, through the lumens of the hollow fibers and out of the
retentate port, returning to the feed tank. Fluid and solutes that pass through the walls
of the hollow fiber membrane are flow out the two permeate ports.
Cartridge size, port size, port type, and the number and size of hollow fibers vary
according to the cartridge type.
Figure 1. Main parts of a WaterSep hollow fiber cartridge
Outlet (retentate)
Inlet (Feed)
Outlets (permeate)
Housing
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Product Information
WaterSep Validation Guide 11
Figure 2. Cartridge showing hollow fibers encapsulated in the hollow fiber housing
CARTRIDGE LABELING AND CATALOG NUMBERS
WaterSep hollow fiber cartridges include labels that provide useful information (Figure 3).
Cartridge labels include the following information:
Company name
Cartridge name
Membrane material and pore size
Inside diameter of the fibers
Membrane surface area
Cartridge nominal dimensions
Bar code
Maximum operating temperature
Maximum operating pressure
Catalog (part) number
Lot number
Encapsulated fibers Housing
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Product Information
12 WaterSep Validation Guide
When ordering cartridges, the catalog number enables you to identify the cartridge
properties (Figure 4). The bar code enables you to identify each cartridge using a universal
bar code scanner. The lot number is also unique to each cartridge to ensure traceability.
Figure 3. Typical hollow fiber cartridge label show information helpful to users
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Product Information
WaterSep Validation Guide 13
Figure 4. Identifying cartridge properties by catalog number
SU 910 05 DIS 12 LL
Product Code Designator
SU = Modified PES Membrane Glycerin Free
Fiber Lumen Diameter (mm)
20 = 2 mm (special production)
10 = 1 mm
05 = 0.5 mm
NMWC
001 = 1 K
003 = 3 K
005 = 5 K
010 = 10 K
030 = 30 K
050 = 50 K
100 = 100 K
300 = 300 K
500 = 500 K
750 = 750 K
910 = 0.1 µm
920 = 0.2 µm
945 = 0.45 µm
965 = 0.65 um
Cartridge Type
DIS = Discover Green
EXP = Explorer Green
INV = Investigator Green
PRO = BioProducer Green
MAX = Maximizer Green
Fiber Length
12 = 12 inches
24 = 24 inches
41 = 41 inches
Type of Connector
ML = Luer Lok (Mini Discover)
LL = Luer Lok (Discovery)
SO = 3/4-inch TC (Explorer)
SO = 1-inch TC (Investigator)
SG = 1.5-inch TC (BioProducer)
SH= 2-inch TC (Maximizer
SK = 3-inch TC (BioProducer)
Catalog number
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Product Information
14 WaterSep Validation Guide
MATERIALS OF CONSTRUCTION
The materials of construction (and wetted components) of WaterSep hollow fiber
cartridges include these:
Membrane—modified glycerin free polyethersulfone (PES) composition
Encapsulant—FDA-compliant urethane
Housing—white polysulfone
Polypropylene Screen—made from 100% virgin polypropylene resin.
PACKAGING
New hollow fiber cartridges are packaged in a sealed polyethylene bag. The feed,
retentate, and permeate ports are double capped to retain moisture and prevent
contamination from external sources.
Depending on the cartridge size, packaging consists of different types of foam and
cardboard boxes. A label—similar to the label affixed to the cartridge—is affixed to the
upper-left side of each box.
The finished goods package also includes a certificate of analysis, operating instructions,
and an application guide.
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Product Information
WaterSep Validation Guide 15
PRODUCT SPECIFICATIONS
You can purchase WaterSep Green Single Use hollow fiber cartridges in a variety of sizes
from lab scale to production scale (Table 2 and Table 3). By design, WaterSep Single Use
hollow fiber cartridges provide a linear and predictive scale-up process—from laboratory
to pilot-scale to manufacturing scale—by using matching materials, fluid-path length, and
performance characteristics. A typical scale-up path includes these products and volumes:
PRODUCT VOLUME
MiniDiscover/Discover Green 10–400 ml
Explorer Green 150–3000 ml
Investigator Green 1–25 L
BioProducer Green > 10 L
Maximizer Green > 300 L
For additional scale-up information, contact WaterSep at +1–508–970–0089,
extension 204, or email WaterSep at Experttalk@WaterSep.net
VOID VOLUME OF HOLLOW FIBER CARTRIDGES
The design of WaterSep hollow fiber cartridges maximizes surface area and minimizes
hold-up volume and system working volume. The design elements increase efficiency and
enable the highest possible concentration factors.
Void volumes and other product characteristics for MiniDiscover/Discover, Explorer,
Investigator, BioProducer Green and Maximizer Green hollow fiber cartridges are
presented in Table 2, Table 3, and Table 4.
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Product Information
16 WaterSep Validation Guide
Table 2. Physical characteristics of MiniDiscover Green, Discovery Green, and Explorer
Green HF Cartridges
MiniDiscover Green HF Cartridges
Characteristic 12 Inch 24 Inch —
Dimensions in inches (mm) 3/8 x 12 (9.4 x 30) 3/8 x 24 (9.4 x 60) —
Membrane surface area in ft2 (cm2) 0.019 (17.3) 0.038 (35.6) —
Recommended batch volume per cartridge (mL) 10–80 10–125 —
Recommended permeate flow rate (mL/hr) Up to 70 Up to140 —
Membrane cut-off (k) NMWC 1, 3, 5, 10, 30, 50, 100, 300, 500, 750
Membrane pore size (µm) 0.1, 0.2, 0.45, 0.65
Feed/retentate connectors Luer Lok
Permeate connector Luer Lok
Discover Green HF Cartridges
Characteristic 12 Inch 24 Inch —
Dimensions in inches (mm) 3/8 x 12 (9.4 x 30) 3/8 x 24 (9.4 x 60) —
Membrane surface area in ft2 (cm2) 0.056 (51.8) 0.115 (106.9) —
Recommended batch volume per cartridge (mL) 10–250 50–400 —
Recommended permeate flow rate (mL/hr) Up to 200 Up to 400 —
Membrane cut-off (k) NMWC 1, 3, 5, 10, 30, 50, 100, 300, 500, 750
Membrane pore size (µm) 0.1, 0.2, 0.45, 0.65
Feed/retentate connectors Luer Lok
Permeate connector Luer Lok
Explorer Green HF Cartridges
Characteristic 12 Inch 24 Inch 41 Inch
Dimensions in inches (mm) 0.5 x 12.3 (13 x 312) 0.5 x 23.8 (13 x 605) 0.5 x 41.8 (13 x 1062)
Membrane surface area in ft2 (cm2) 0.16 (155) 0.34 (320) 0.62 (580)
Recommended batch volume per cartridge (mL) 150–175 250–1,500 300–3,000
Recommended permeate flow rate (mL/hr) Up to 600 Up to 1,280 Up to 2,300
Membrane cut-off (k) NMWC 1, 3, 5, 10, 30, 50, 100, 300, 500, 750
Membrane pore size (µm) 0.1, 0.2, 0.45, 0.65
Feed/retentate connectors ½-inch TC
Permeate connector Barbed hose
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Product Information
WaterSep Validation Guide 17
Table 3. Physical characteristics of Investigator and BioProducer cartridges
Investigator Green HF Cartridges
Characteristic 12 Inch 24 Inch 41 Inch
Dimensions in inches (mm) 1.3 x 12 (33.4 x 305) 1.3 x 23.5 (33.4 x 597) 1.3 x 41 (33.4 x 1054)
Membrane surface area in ft2 (m2) 1.4 (0.13) 2.3 (0.27) 5.5 (0.50)
Recommended batch volume per cartridge (L) 1–6 2–12 3–25
Recommended permeate flow rate (L/hr) Up to 5.2 Up to 11 Up to 20
Membrane cut-off (k) NMWC 1, 3, 5, 10, 30, 50, 100, 300, 500, 750
Membrane pore size (µm) 0.1, 0.2, 0.45, 0.65
Feed/retentate connectors 1-inch TC
Permeate connector ½-inch TC
BioProducer Green HF Cartridges
Characteristic 12 Inch 24 Inch 41 Inch
Dimensions in inches (mm) 3.5 x 15.0 (89 x 381) 3.5 x 13.5 (89 x 344)
3.5 x 26.5 (89 x 673) 3.5 x 25.0 (89 x 636)
3.5 x 44.5 (89 x 1130) 3.5 x 43.0 (89 x 1093)
Membrane surface area in ft2 (m2) 13.5 (1.25) 29.3 (2.72) 54.0 (5.0)
Recommended batch volume per cartridge (L) 10–60 20–140 50–300
Recommended permeate flow rate (L/hr) Up to 50 Up to 110 Up to 200
Membrane cut-off (k) NMWC 1, 3, 5, 10, 30, 50, 100, 300, 500, 750
Membrane pore size (µm) 0.1, 0.2, 0.45, 0.65
Feed/retentate connectors 1.5-inch TC or 3-inch TC
Permeate connector 1-inch TC
Maximizer Green HF Cartridges
Characteristic 24 Inch 41 Inch
Dimensions in inches (mm) 4.62 x 28.5
(117.3 x723.9) 4.62 x 46.5
(117.3 x 1181.1)
Membrane surface area in ft2 (m2) 54.0 (5.0) 110 (10)
Recommended batch volume per cartridge (L) > 300 > 300
Recommended permeate flow rate (L/hr) Up–200 Up–400
Membrane cut-off (k) NMWC 1, 3, 5, 10, 30, 50, 100, 300, 500, 750
Membrane pore size (µm) 0.1, 0.2, 0.45, 0.65
Feed/retentate connectors 2-inch TC
Permeate connector 1-inch TC
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Product Information
18 WaterSep Validation Guide
Table 4. Void volumes of WaterSep Green hollow fiber cartridges
Product
Performance Properties Hold Up Volume
Fiber ID
(mm) No. of Fibers
Surface Area (cm2)
Feed Side Holdup Volume
(ml)
Permeate Side Holdup Volume
(ml)
MiniDiscover12 Green
0.5 4
17
0.34 2.42
1.0 2 0.57 2.13
2.0 1 1.04 1.69
MiniDiscover24 Green
0.5 4
36
0.56 4.93
1.0 2 1.03 4.35
2.0 1 1.96 3.35
MiniDiscover41 Green
0.5 4
64
0.92 8.87
1.0 2 1.75 7.82
2.0 1 3.39 6.01
Discover12 Green
0.5 12
52
0.81 6.19
1.0 6 1.51 5.33
2.0 3 2.93 3.87
Discover24 Green
0.5 12
107
1.49 12.79
1.0 6 2.89 11.04
2.0 3 5.68 8.04
Discover41 Green
0.5 12
193
2.57 23.12
1.0 6 5.04 19.96
2.0 3 9.98 14.56
Explorer12 Green
0.5 36
155
2.7 14.4
1.0 18 4.8 11.8
2.0 9 9.1 7.4
Explorer24 Green
0.5 36
321
4.8 28.0
1.0 18 9.0 24.2
2.0 9 17.3 15.2
Explorer41 Green
0.5 36
579
8.0 50.5
1.0 18 15.4 43.5
2.0 9 30.3 27.3
Investigator12 Green
0.5 320
1,316
20 94
1.0 160 39 79
2.0 80 76 41
Investigator24 Green
0.5 320
2,785
38 204
1.0 160 75 171
2.0 80 150 93
Investigator41 Green
0.5 320
5,083
67 376
1.0 160 133 315
2.0 80 265 173
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Product Information
WaterSep Validation Guide 19
Product
Performance Properties Hold Up Volume
Fiber ID
(mm) No. of Fibers
Surface Area (cm2)
Feed Side Holdup Volume
(ml)
Permeate Side Holdup Volume
(ml)
BioProducer12 Green
0.5 3200
12,514
348 94
1.0 1600 537 79
2.0 800 914 41
BioProducer24 Green
0.5 3200
27,198
532 204
1.0 1600 904 171
2.0 800 1,647 93
BioProducer41 Green
0.5 3200
50,183
819 376
1.0 1600 1,478 315
2.0 800 2,796 173
Maximizer24 Green
0.5 6400 51,842
1,194 3,126
1.0 3200 1,937 2,502
2.0 1600 51,868 3,425 1,032
Maximizer41 Green
0.5 6400 97,811
1,768 5,701
1.0 3200 3,086 4,522
2.0 1600 97,837 5,722 1,769
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Product Information
20 WaterSep Validation Guide
MEMBRANE PERFORMANCE
The WaterSep Green single use hollow fiber membranes are manufactured using a
unique combination of modified polyethersulfone (PES) and a proprietary spinning
process that results in an asymmetric, void free low binding hollow fiber membrane with
narrow pore size distribution and excellent antifouling and process flow properties.
The manufacturing process for the Green single use hollow fiber membrane is free of
glycerin or any other humectant, which guarantees a very low level of extractables.
CARTRIDGE PERFORMANCE
The exceptional uniformity of WaterSep hollow fiber membrane and the precision of the
hollow fibers cartridge assembly process results in hollow fiber cartridges that perform
consistently and show high lot-to-lot consistency (Table 5)
INHERENTLY SUPERIOR CHARACTERISTICS
WaterSep Green Line hollow fiber cartridges are characterized by:
Antifouling modified glycerin free polyethersulfone (m-PES) composition for
regulatory satisfaction
Void-free structure for sustained reliable performance
Optimization for specific applications
Glycerin free membrane for very low extractables level.
Ready to use with no pre-rinse required. Just a low volume buffer equilibration.
PROVEN PERFORMANCE ADVANTAGES
Low fouling and anti-dead spot design
High flow rate and total capacity
High batch-to-batch consistency
Low cost of ownership and better economics due to no pre-treatment or post cleaning
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Product Information
WaterSep Validation Guide 21
Table 5. Air flow specifications for WaterSep Green single use hollow fiber cartridges
Product Name Membrane NMWC
Air Flow per Cartridge ml/min/7 barg
(ml/min/10 psig)
MiniDiscover12 Green
1, 3, 5, 10, 30, 50, 100, 300,
500, 750 KD
< 0.2
MiniDiscover24 Green < 0.4
Discover12 Green < 0.6
Discover24 Green < 1.1
Explorer12 Green < 1.6
Explorer24 Green < 3.4
Explorer41 Green < 6.2
Investigator12 Green < 14
Investigator24 Green < 30
Investigator41 Green < 55
BioProducer12 Green < 135
BioProducer24 Green < 293
BioProducer41 Green < 540
Maximizer24 Green < 540
Maximizer41 Green < 750
Product Name Membrane
Air Flow per Cartridge ml/min/0.35 barg (ml/min/5 psig)
MiniDiscover12 Green
0.1, 0.2, 0.45, 0.65 µm
< 0.2
MiniDiscover24 Green < 0.4
Discover12 Green < 0.6
Discover24 Green < 1.1
Explorer12 Green < 1.6
Explorer24 Green < 3.4
Explorer41 Green < 6.2
Investigator12 Green < 14
Investigator24 Green < 30
Investigator41 Green < 55
BioProducer12 Green < 135
BioProducer24 Green < 293
BioProducer41 Green < 540
Maximizer24 Green < 540
Maximizer41 Green < 750
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Product Information
22 WaterSep Validation Guide
STORAGE OF NEW AND USED CARTRIDGES
NEW CARTRIDGES
Store new hollow fiber cartridges unopened in their original packaging in a protected
location and out of direct sunlight. The temperature of the storage area should remain
between 4°C to 37°C (39°F to 99°F). Under these conditions, a new cartridge can be stored
for 24 months without influencing performance or leading to product alterations.
PREPARING YOUR CARTRIDGE FOR USE
The WaterSep Green Line single use hollow fiber cartridges require a minimum of pre-
conditioning, prior to use.
Extractables are approximately 80X less than a conventional glycerin conditioned hollow
fiber or cassette product. Prior to use there is no need for any extensive rinsing of the
hollow fiber membrane with WFI or purified water. A quick buffer equilibration is all that
is needed. This is a significant saving of WFI/purified water, cleaning chemicals and
valuable facility time.
Because the Green Line hollow fiber cartridges are all single use there is no need for
developing cleaning regimen or cleaning validation documentation.
WaterSep recommends integrity testing of the hollow fiber cartridges pre – and post use.
The preferred method is a pressure hold test at either 10 or 5 psi, (see ….
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Validation Information
WaterSep Validation Guide 23
CHAPTER 3—VALIDATION
INFORMATION
The various product lines of WaterSep hollow fiber cartridges are constructed of the same
materials and use identical design elements and fluid path length. Hence hollow fiber
cartridge performance is scalable, and validating a cartridge at one size normally suffices
for validating cartridges of other sizes.
MEMBRANE WATER FLUX
A common way to measure clean membrane performance and determine the level
membrane recovery after cleaning is to measure the water permeability of the membrane
under controlled conditions. [However, membrane water flux does not necessarily have a
direct correlation to process flux in a biological fluid stream.]
The water permeability of WaterSep membranes, normalized to water viscosity at the
testing temperature, are provided in Table 6.
Table 6. Water permeability of WaterSep membranes
Ultrafiltration Membrane
NMWL Normalized Water Permeability (LMH/psi) 1
3 K 0.1–1
5 K 0.5–3
10 K 7–13
30 K 12–30
50 K 15–40
100 K 18–40
300 K 20–50
500 K 20–50
750 K 25–60
Microfiltration Membrane
0.1 um > 30
0.2 um > 100
0.45 um > 200
1 These numbers are based on Explorer-size quality control cartridges.
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Validation Information
24 WaterSep Validation Guide
MEMBRANE SOLUTE REJECTION
WaterSep’s hollow fiber membranes have very well defined and narrow
retention/passage specifications. Every manufacturing batch is tested for quality
with known solutes and must conform to highly-defined limits for rejection and passage.
Each membrane cut-off is tested with two to three solutes (membrane markers).
Table 7 lists the retention passage data for different membrane cut-offs.
A narrow pore size distribution, guarantees consistent membranes batches over time
and minimizes membrane batch-to-batch variations. Note that there are no overlap
in retention/passage specifications, for various cut-offs/pore sizes.
If a membrane does not have a clear cut-off point between particle retention and
passage, the membrane may pass your product of interest or provide low product yield.
There will be also significant performance variations between membrane batches (wide
lot-to-lot variations).
By testing the retention and passage of known solutes through the membrane under
controlled conditions, and measuring the concentration of the solute in the retentate
and permeate in comparison to the concentration of the original sample, you can
determine the performance of the membrane.
Table 7. Results of solute passage through WaterSep membrane (% P – percent passage)
NMWL
PVP-K15
PVP-K30
PVP-K60S PVP-K90
Blue Dextran Bubble Point
MW = 9700
MW = 66,800
MW = 396,000
MW = 1,570,000
MW = 2,000,000 IPA H2O
%P %P %P %P %P psig
3 K < 20
5 K 20–40
10 K 40–75 < 20
20 K > 70 < 25
30 K > 85 20–40
50 K > 90 40–70 < 10
100 K
> 70 < 20
300 K
20–35 < 20
500 K
35–65 < 30
750 K
> 65 25–50 < 10 > 60
0.1 um
> 50 10–50 35–60 60–100
0.2 um
> 50 22–35 45–60
0.45 um
> 75 10–22 30–45
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Validation Information
WaterSep Validation Guide 25
CARTRIDGE INTEGRITY TEST
NON-DESTRUCTIVE TESTING
Non-destructive integrity testing can be completed on hollow fiber cartridges pre-
and post-operation in order to prevent process failure and product loss. Detecting a failed
hollow fiber cartridge can eliminate process delays and allow for rapid re-processing
of the batch. There are two types of non-destructive testing: the bubble point test
and the diffusion test.
WaterSep recommends using bubble point test for both UF and MF membranes.
(1K – 750K and 0.1 um – 0.65 um)
Pressure hold, forward flow, and pressure decay are variations of the diffusion test.
INTEGRITY TEST - PRESSURE HOLD TEST
The pressure hold test, also known as pressure decay or pressure drop test, is an
alternative to the diffusion test and is based on similar principles. In the pressure hold
test, an accurate pressure gauge is used to monitor upstream pressure changes due to gas
diffusion through the wetted hollow fiber membrane.
The pressure hold value is dependent on the diffusional flow and upstream volume. It can
be calculated using the following equation:
Where:
D = diffusion rate (cc/min)
T = time (minutes)
Pa = atmosphere pressure (1 Atm. or 14.7 psi)
Vh = upstream volume of apparatus (cc)
DP = pressure drop (bar or psi)
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Validation Information
26 WaterSep Validation Guide
PROCEDURE
1. Circulate water through the hollow fiber cartridge for 10 minutes. Ensure fluid
flows from both permeate ports.
2. Attach an external pressure source to the feed/retentate side of the hollow fiber
system.
3. Close the permeate side and open feed and retentate ports.
4. Pressurize the system slowly to the specified pressure. 10 psi for UF membranes,
5 psi for MF membranes.
5. Drain the system of any liquid upstream.
6. Close the retentate valve
7. Open the permeate valve.
8. Let the system equilibrate for 5 minutes, while any remaining liquid will pass
through the HF cartridge.
9. Close the feed port, and monitor any pressure decay in the system.
10. The system/cartridge is integral if the pressure gauge reads a positive upstream
pressure after 1 minute.
Average Integrity Test Results Delta P/min @ 0.7 barg (10 psig)
Membrane NMWC (KD) Batch 1 Batch 2 Batch 3
1
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Validation Information
WaterSep Validation Guide 27
REFERENCE VALUES FOR WATERSEP FACTORY MEMBRANE DIFFUSION
TEST
Table 8. Results of membrane integrity tests for Investigator12 Cartridges
CARTRIDGE WATER FLUX
Cartridge water flux for a specific cartridge and molecular weight cut off can provide
valuable information when it is compared to membrane water flux data. The correlation
factor for water flux between a membrane and a specific hollow fiber cartridge can also
be used to correlate water flux for other sizes of hollow fiber cartridges.
A cartridge water flux study was conducted on membranes with different molecular
weight cut off values. Included in the study were multiple cartridges for each molecular
weight cut-off. The goal was to determine the average water flux values for the cartridge.
Average Airflow Integrity Test Results cc/min/ft2 @ 0.7 barg (10 psig)
Membrane NMWC (KD) Batch 1 Batch 2 Batch 3
1
10
10
10
3
5
10
30
50
100
300
500
750
Average Airflow Integrity Test Results ml/min/ft2 at 0.35 barg (5 psig)
Membrane NMWC (µm) Batch 1 Batch 2 Batch3
0.1
10
10
10
0.2
0.45
0.45
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Validation Information
28 WaterSep Validation Guide
Table 9 shows the average water flux for Investigator12 cartridges with different
molecular weight cut off values (membrane pore size). All the cartridges had 1,300-cm2
of membrane surface area.
The cartridge water flux results are normalized to surface area and reported as LMH
(liter/m²/hour)/psig (
Figure 5, Figure 6, and Figure 7).
Table 9. Water flux results for an Investigator12 hollow fiber cartridges
Membrane Type
Average Water Flux LMH/psi at .68 barg (10 psig) of TMP
m-PES 30K MWCO 17.4
m-PES 300K MWCO 36.3
M-PES 0.2 um 333.7
Figure 5. Clean water flux for an Investigator12 Green, 30K MWCO, 1.0 mm ID
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Validation Information
WaterSep Validation Guide 29
Figure 6. Clean Water flux for an Investigator12 Green, 300K MWCO, 1.0 mm ID
Figure 7. Clean Water flux for an Investigator12 Green, 0.2 um, 1.0 mm ID
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Validation Information
30 WaterSep Validation Guide
CARTRIDGE CROSSFLOW
The crossflow rate is a critical process parameter for crossflow filtration processes. An
optimized crossflow rate minimizes gel layer formation on the membrane surface, leading
to optimum process flux and maximum transmission of ions and low molecular weight
substances. Optimized crossflow, in combination with low transmembrane pressure
(TMP), is particularly important for cell clarification processes where transmission of
proteins, antibodies, and other high-molecular-weight target products is crucial.
Insufficient crossflow can lead to increased gel layer formation. The result is a decrease
in process flux and an increase in the rejection of low molecular solutes, both of which
lower yield.
The crossflow rate of a hollow fiber cartridge is proportional to the differential pressure
(delta P) along the cartridge (i.e. the pressure difference between the feed and retentate
port). The optimum crossflow rate is a function of the number of fibers in a hollow fiber
cartridge, the inside diameter of the fibers, and the fluid stream characteristics.
While the optimum cross flow rate for a family of hollow fiber cartridges does not vary
with path length, the delta P needed to achieve the optimum cross flow rate can vary.
For example, the optimum crossflow for a BioProducer12/24/41 is the same, although
the delta P to achieve that flow rate varies as a function of the path length of the hollow
fiber cartridge.
WaterSep hollow fiber cartridges are designed for intra-cartridge consistency for delta P
and the crossflow rate, and this design feature ensure consistent performance. Intra-
cartridge inconsistency between delta P and crossflow results in process variances and
potential product yield decay.
Figure 8 and Figure 9 show the measured crossflow vs. delta P forBioProducer12/24/41
Green and Investigator12/24/41 Green HF cartridges.
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Validation Information
WaterSep Validation Guide 31
Figure 8. Delta P versus crossflow with water for Producer12/24/41 Green cartridges
Delta P vs. Cross Flow for Producer24
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
20 25 35 40 50
Delta P (psi)
Delta P
Cross FlowL/min
Delta P vs. Cross Flow for Producer12
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
20 25 35 40 50
Delta P (psi)
Delta P
Cross FlowL/min
Delta P vs. Cross Flow for Producer41
0
0.5
1
1.5
2
2.5
3
3.5
20 25 35 40 50
Delta P (psi)
Delta P
Cross FlowL/min
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Validation Information
32 WaterSep Validation Guide
Figure 9. Delta P versus crossflow with water for Investigator12/24/41 Green cartridges
Delta P vs. Cross Flow for Investigator12
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
2 2.5 3.5 4 5
Delta P (psi)
Delta P
Cross FlowL/min
Delta P vs. Cross Flow for Investigator24
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
2 2.5 3.5 4 5
Delta P (psi)
Delta P
Cross FlowL/min
Delta P vs. Cross Flow for Investigator41
0
0.5
1
1.5
2
2.5
3
3.5
2 2.5 3.5 4 5
Delta P (psi)
Delta P
Cross FlowL/min
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Validation Information
WaterSep Validation Guide 33
CARTRIDGE CHEMICAL COMPATIBILITY STUDY
GENERAL CONSIDERATIONS
Certain chemicals can damage and degrade the membrane structure, or ultimately
dissolve the membrane polymer. It is therefore important to be aware of the
membrane’s chemical compatibility and use compatible process and cleaning chemicals.
Under normal operating conditions, WaterSep cartridges are resistant to commonly-used
aqueous solutions within ph 1–14, bio-chemicals and most solvents, with the exception of
aromatic compounds. Certain operating conditions and elevated temperature, can affect
the membrane’s compatibility. WaterSep advises you to complete your own chemical
compatibility studies under you specific operating conditions and temperatures
(Table 10).
Table 10. Chemical compatibility list for WaterSep cartridges (R = recommended,
L = limited exposure, NR = not recommended, U = unknown)
Chemical Compatibility
Acetic acid (diluted-5%) R
Acetic acid (med conc-25%) L
Acetic acid (glacial) NR
Acetone NR
Acetonitrile NR
Alconox (1%) R
Ammonium hydroxide R
Amyl acetate NR
Amyl alcohol L
Aniline NR
Benzene NR
Benzyl alcohol NR
Boric acid R
Brine R
Butyl acetate NR
Butyl alcohol R
Butylaldehyde NR
Carbon tetrachloride NR
Chloroacetic acid NR
Chloroform NR
Chromic acid NR
Citric acid (2%) R
Cresol NR
Cyclohexane L
Chemical Compatibility
Cyclohexanone NR
Diacetone alcohol NR
Dichloromethane L
Dimethyl formamide NR
Dimethylsulfoxide (50%) L
1,4 Dioxane L
Ethers NR
Ethyl acetate NR
Ethyl Alcohol R
Ethyl alcohol (15%) R
Ethyl alcohol (95%) L
Ethylene dichloride NR
Ethylene glycol R
Ethylene oxide R
Formaldehyde (2%) R
Formaldehyde (30%) R
Formic acid (25%) R
Formic Acid (50%) R
Freon® R
Gasoline L
Glycerine / Glycerol R
Hexane R
Hexanol R
Hydrochloric acid (diluted- R
http://www.spectrumlabs.com/generic/tms.html?LiFrom=%2Fdialysis%2FCompatibility.html;FrName=Chemical+Compatibility;rtm=Freon;#FREON
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Validation Information
34 WaterSep Validation Guide
Chemical Compatibility
5%)
Hydrochloric acid (conc-25%)
R
Hydrochloric acid (conc-37%)
R
Hydrofluoric acid (25%) L
Hydrogen peroxide (30%) L
Iodine solutions NR
Isobutyl alcohol R
Isopropanol R
Isopropyl acetate NR
Isopropyl alcohol / Isopropanol
R
Isopropyl ether R
Lactic acid R
Methyl acetate NR
Methyl alcohol R
Methyl alcohol (98%) L
Methyl cellosolve R
Methyl chloride NR
Methyl ethyl ketone NR
Methyl formate NR
Methyl isobutyl ketone NR
Methylene chloride NR
N-methyl-2-pyrrolidone NR
Mineral spirits R
Monochlorobenzene NR
NALCON 7647 (
-
Validation Information
WaterSep Validation Guide 35
CARTRIDGE RINSING AND BUFFER EQULIBRATION STUDY
A total of 650 ml of purified water was first flushed through a BioProducer12, hollow fiber
cartridge (1.25 m2, 13.5 ft2 membrane surface area) at a delta P of 0.2 barg (3 psig) from
feed to retentate port with the permeate port closed.
The retentate port was then closed. And an additional 650 ml of purified water was
flushed through the permeate ports at 0.33 barg (5psig) of TMP. Throughout the rinsing,
water samples were collected and analyzed for extractables in PPM.
After rinsing a total of 650 ml saline buffer ml was first flushed through the cartridge at a
delta P of 0.2 barg (3 psig) through the retentate port to drain with the permeate port
closed.
The retentate port was then closed, and an additional 650 ml of saline buffer were flushed
through the permeate port at 0.33 barg (5 psig) of TMP, to equilibrate the Bioproducer12.
Results shows that a minimum of 0.65 liters of purified water (0.5 L/m2 of membrane) was
required for rinsing the hollow fiber lab cartridge (Figure 10). This rinsing volume should
be proportionally adjusted for larger/smaller cartridges. The minimum rinsing volume—
0.65 liters for1.25 m2 (13.5 ft2) cartridges—should be proportionally increased when
larger cartridges with more membrane surface areas are used ( ≈ 0.5 L/m2 of membrane).
Figure 100. Results of Extractables Level vs. Volumetric Throughput of Purified Water
(Liters per m2)
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Validation Information
36 WaterSep Validation Guide
HOLLOW FIBER CARTRIDGE SCALABILITY STUDIES
A key benefit of WaterSep hollow fiber cartridges is the capability to linearly and
consistently scale your process up or down from lab-scale to pilot-scale to production-
scale. Linear and consistent scaling reduces the costs and complexity of product
development and troubleshooting. The similarity in flow geometry between the different
product groups enables this capability.
WaterSep performed these two studies to demonstrate the scalability characteristics of
our cartridges:
1. An E. Coli lysate clarification study with Explorer12 and Explorer24 cartridges
2. A protein concentration study with Explorer12 and Investigator12 cartridges
E.COLI STUDY WITH EXPLORER12 AND EXPLORER24 CARTRIDGES
This study demonstrates cartridge scalability and provides data to assist with scalability.
The E. Coli lysate clarification study was conducted using Explorer12 and Explorer24
cartridges. The results of the study are illustrated in Figure 11, Figure 12, and Table 11.
CONCLUSIONS
The results indicate that TMP and flux data for production Explorer12 and Explorer24
have a scalability factor close to 1.0 in this application.
Figure 111. Pressure and permeate flux profiles for the Explorer12 cartridge
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Validation Information
WaterSep Validation Guide 37
Figure 122. Pressure and permeate flux profiles for the Explorer24 cartridge
Table 11. Results from the E. Coli lysate clarification scalability study
Process Parameter
Explorer12 NMWL = 750 KD
Fiber Diameter = 1 mm
Explorer24 NMWL = 750 KD
Fiber Diameter = 1 mm
Fluid path length (inches) 12 24
Membrane surface area (cm2) 155 321
P feed (psi) 6–8 9.5–11.5
P retentate (psi) 1–2 1
TMP (psi) 3–4 2–4
Flux clarification (LMH) 18–20 21
Flux diafiltration (LMH) 24–31 24–33
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Validation Information
38 WaterSep Validation Guide
PROTEIN CONCENTRATION STUDY WITH EXPLORER12
AND INVESTIGATOR12 CARTRIDGES
This study demonstrates cartridge scalability and provides data to assist with scalability.
A protein concentration study was conducted using Explorer12 and Investigator12
cartridges. The results of the study are illustrated in Figure 13.
Figure 133. Optimization results of scalability study using Explorer12 and Investigator12
cartridges
CONCLUSIONS
The Flux vs. TMP curves for an Explorer12 and an Investigator12 are almost identical and
suggest that the scalability factor is close to 1.0 in this application.
-
Product Safety
WaterSep Validation Guide 39
CHAPTER 4—PRODUCT
SAFETY
BIOCOMPATIBILITY STUDIES
WaterSep submitted samples of hollow fiber cartridges to Toxikon for biocompatibility
analyses. The following summarizes the results of the testing.
USP Class VI Test – GLP Compliance
Study Summary: “Therefore, the test article, WaterSep hollow fiber cartridge, meets the
requirements of USP guidelines, for Class VI Plastics – 70°C.”
USP Physicochemical Test for Plastics – GLP Compliance
Study Summary: “The purified water extract of the test article, WaterSep hollow fiber
cartridge, meets the test criteria described in the USP Physicochemical Test for Plastics
guidelines.”
You can review the Toxikon reports cited above by clicking on the links in Table 12.
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Quality Assurance Information
40 WaterSep Validation Guide
CHAPTER 5—QUALITY
ASSURANCE INFORMATION
CERTIFICATE OF COMPLIANCE
WaterSep supplies a Certificate of Analysis with each cartridge. The Certificate of Analysis
verifies that your new cartridge was tested and complied with WaterSep’s quality
assurance standards (Figure 14).
Figure 144. Example of a cartridge certificate of compliance
-
Appendices
WaterSep Validation Guide 41
APPENDICES
APPENDIX I—ADDITIONAL DOCUMENTATION
You can learn more about WaterSep’s standard technology and obtain additional
information such as operating procedures and product sheets by visiting the WaterSep
website or by clicking a link below (Table 12).
Table 12. Helpful information available at www.WaterSep.net
Standard Operating Procedures
Hollow Fiber Cleaning and Storage Procedure
Preconditioning for Use Procedure
Product Sheets
MiniDiscover 12
MiniDiscover 24
Discover 12
Discover 24
Explorer12
Explorer24
Explorer 41
Investigator 12
Investigator 24
Investigator 41
BioProducer 12
BioProducer 24
BioProducer 41
http://www.watersep.net/http://watersep.net/shop/validation/HF%20SOP%20-%20CIP%20&%20Storage%20Procedure.pdfhttp://watersep.net/shop/validation/HF%20SOP%20-%20Preconditioning.pdfhttp://watersep.net/shop/pdf/WaterSep_MiniDiscover12.pdfhttp://watersep.net/shop/pdf/WaterSep_MiniDiscover24.pdfhttp://watersep.net/shop/pdf/WaterSep_Discover12.pdfhttp://watersep.net/shop/pdf/WaterSep_Discover24.pdfhttp://watersep.net/shop/pdf/WaterSep_Explorer12.pdfhttp://watersep.net/shop/pdf/WaterSep_Explorer24.pdfhttp://watersep.net/shop/pdf/WaterSep_Explorer41.pdfhttp://watersep.net/shop/pdf/WaterSep_Investigator12.pdfhttp://watersep.net/shop/pdf/WaterSep_Investigator24.pdfhttp://watersep.net/shop/pdf/WaterSep_Investigator41.pdfhttp://watersep.net/shop/pdf/WaterSep_BioProducer12.pdfhttp://watersep.net/shop/pdf/WaterSep_BioProducer24.pdfhttp://watersep.net/shop/pdf/WaterSep_BioProducer41.pdf
-
Appendices
42 WaterSep Validation Guide
APPENDIX II—TEST PROCEDURES AND REPORTS
You can obtain the reports cited in this validation guide from the WaterSep website by
clicking on the links below (Table 13).
Table 13. Test reports available from www.WaterSep.net
Title of Report
WaterSep Membrane and Cartridge Regulatory and Bio-Compatibility Summary Rev. 0 - AH
Toxikon Final GLP Report: 09-0302-G1 Class VI Test – USP
Toxikon Final GLP Report: 09-0302-G2 Physicochemical Test for Plastics – USP
http://www.watersep.net/http://watersep.net/shop/validation/BioCompatibility%20Summary.pdfhttp://watersep.net/shop/validation/WaterSep%20USP%20Class%20VI%20results%2009-0302-G1.pdfhttp://watersep.net/shop/validation/WaterSep%20USP%20physicochemical%20test%20results%2009-0302-G2.pdf
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Index
WaterSep Validation Guide 43
INDEX
INDEX
Appendices, 41
Applications, 9
Audience for this guide, 6
Biocompatibility, 39
Biocompatibility studies, 39
Cartridge
additional information, 41
biocompatibility, 39
certificate of compliance, 40
chemical compatibility study, 33
cross-flow, 30, 35
design, 10
information, 9
inlets and outlets, 10
materials of construction, 14
packaging, 14
quality assurance, 40
storage, 22
Test procedures and reports, 42
water flux, 27
Cartridge scalability study, 36
Cartridges
Protein concentration, 38
scalablity, 36
Certificate of compliance, 40
Chemical compatibility, 33
Contacting WaterSep, 7
Cross-flow rate, 30
Customer support, 7
Documentation
additional information, 41
E-mailing WaterSep, 7
Extractables, 39
GLP compliance, 39
Help, 7
List of figures, 5
List of tables, 5
Materials of construction, 14
Membrane solute rejection, 24
Membrane water flux, 23
Non-destructive testing, 25
Packaging, 14
Performance
advantages, 20
Performance characteristics, 20
Preconditioning, 22
Pressure and permeate flux profiles, 36
Pressure hold test, 25
Process validation, 7
Protein concentration, 38
Quality assurance, 40
Rinsing
pH and conductivity reduction, 35
Rinsing cartridges, 34
Scalability, 36
Specifications, 15
materialls of construction, 14
physical properties, 15
water flux, 23
Storage, 22
Support, 7
Test procedures and reports, 42
Test reports, 42
USP Class VI Test, 39
USP Physicochemical Test for Plastics, 39
Validation, 7
Validation guide purpose, 6
Validation information, 23
Void volume, 15
Water flux, 27
Water permeability, 23
Website, 7
-
WaterSep Technology Corporation
420 Maple Street, Suite 1
Marlborough, MA 01752
USA
Telephone: 508-970-0089 x204
Fax: 508-970-0146
Email:Contact@WaterSep.net
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