watersep validation guide steamer line auvg rev 2 · results of extractables level vs volumetric...

Doc. No. AUVG Rev2

VALIDATION GUIDE for WaterSep Steamer Line Hollow Fiber Cartridges

2 WaterSep Steamer Line Validation Guide, Rev. 2

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 BioSeparations Corporation 450 Donald Lynch Boulevard Marlborough, MA 01752 USA Telephone: 508–970–0089, extension 204 Fax: 508-970-0146 Email: [email protected] All third party trademarks are the property of their respective owners. © 2019 by WaterSep BioSeparations. All rights reserved.

Contents

WaterSep Steamer Line Validation Guide, Rev. 2 3

CONTENTS

List of Tables 5 List of Figures 5

Chapter 1—Introduction 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 Hollow Fiber Cartridge Design 10 Hollow Fiber Cartridge Labeling and Catalog Numbers 11 Materials of Construction 14 Packaging 14 Product Specifications 14 Operating Limits of Hollow Fiber Cartridges 15 Void Volume of Hollow Fiber Cartridges 15 Membrane Performance 20 Cartridge Performance 20 Storage of New and Used Steamer Line Hollow Fiber Cartridges 23 Preparing Your Steamer Line Hollow Fiber Cartridge for Use 23 Autoclaving Procedure for Steamer Line Hollow Fiber Cartridges 24

Chapter 3—Validation Information Hollow Fiber Membrane Water Flux 25 Membrane Solute Rejection 26 Cartridge Integrity Test 27 Non-Destructive Testing 27 Integrity test - Pressure Hold Test 27 Hollow Fiber Cartridge Water Flux 29 Hollow Fiber Cartridge Crossflow 31 Hollow Fiber Cartridge Chemical Compatibility Study 34 Hollow Fiber Cartridge Rinsing and Buffer Equilibration Study 36 Hollow Fiber Cartridge Scalability Studies 37

Chapter 4—Product Safety Biocompatibility Studies 40

Contents


Chapter 5—Quality Assurance Information Certificate of Analysis 41

Appendices Appendix I—Additional Documentation 42 Appendix II—Test Procedures and Reports 43

Index Index 44

Contents


LIST OF TABLES

Table 1. Overview of the hollow fiber cartridges described in this Steamer Line validation guide 9 Table 2. Operating Limits for WaterSep Hollow Fiber Cartridges 15 Table 3. Physical characteristics of Discover™ Steamer, Explorer™ Steamer, and Researcher™ Steamer HF

Cartridges 16 Table 4. Physical characteristics of Investigator™ Steamer, mini-BioProducer™ Steamer, and BioProducer™

Steamer HF cartridges 17 Table 6. Void volumes of Discover™ Steamer, Explorer™ Steamer, Researcher™ Steamer, and Investigator™

Steamer HF Cartridges 18 Table 7. Void volumes of mini-BioProducer™ Steamer, BioProducer™ Steamer HF cartridges 19 Table 8. Air flow specifications for WaterSep Steamer Line HF ultrafiltration cartridges 21 Table 9. Air flow specifications for WaterSep Steamer Line HF microfiltration cartridges 22 Table 10. Water permeability of WaterSep Steamer Line HF membranes 25 Table 11. Results of solute passage through WaterSep membrane (% P – percent passage) 26 Table 12. Water flux results for an Investigator™12 Steamer hollow fiber cartridges 29 Table 13. Chemical compatibility list for WaterSep Steamer Line cartridges (R = recommended, L = limited

exposure {≤12 hours at room temperature}, NR = not recommended) 34 Table 14. Results from the E. coli lysate clarification scalability study 38 Table 15. Helpful information available at www.WaterSep.net 42 Table 16. Test reports available from www.WaterSep.net 43

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 Steamer Line hollow fiber cartridge label show information helpful to users 12 Figure 4. Identifying Steamer Line hollow fiber cartridge properties by catalog number 13 Figure 5. Process Diagram for Pressure Hold Integrity Test 28 Figure 6. Clean water flux for an Investigator™12 Steamer, 30K MWCO, 1.0 mm ID 29 Figure 7. Clean Water flux for an Investigator™12 Steamer, 300K MWCO, 1.0 mm ID 30 Figure 8. Clean Water flux for an Investigator™12 Steamer, 0.2 µm, 1.0 mm ID 30 Figure 9. Delta P versus crossflow with water for BioProducer™12/24/41 Steamer cartridges 32 Figure 10. Delta P versus crossflow with water for Investigator™12/24/41 Steamer cartridges 33 Figure 12. Results of Extractables Level vs Volumetric Throughput of Purified Water (Liters per m2) 36 Figure 13. Pressure and permeate flux profiles for the Explorer™12 cartridge 37 Figure 14. Pressure and permeate flux profiles for the Explorer™24 cartridge 38 Figure 15. Optimization results of scalability study using Explorer™12 and Investigator™12 cartridges 39 Figure 16. Example of a Steamer Line cartridge certificate of analysis 41

Introduction


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 Steamer Line 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.

Introduction


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 BioSeparations Corporation 450 Donald Lynch Boulevard Marlborough, MA 01752 USA Telephone: +1–508–970–0089 x204 Fax: 508–970–0146 Email: [email protected]

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). (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 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 Steamer Line products and systems. In addition, WaterSep can provide you with additional membrane and product

Introduction


information specific to your particular needs. For assistance, contact WaterSep at 508–970–0089, extension 204, or email WaterSep at [email protected] 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; and

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.

Product Information


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 Steamer Line, the autoclavable hollow fiber product line.

Table 1. Overview of the hollow fiber cartridges described in this Steamer Line validation guide

Cartridge Type Applications Range of

Surface Areas Range of Sample

Volumes/Cartridge Lengths (Inches)

Discover™ Steamer Lab 0.056–0.208 ft2

(51.8–193 cm2) 10–850 mL 12, 24, and 41

Explorer™ Steamer Lab 0.17–0.62 ft2

(155–579 cm2) 150–3,000 mL 12, 24, and 41

Researcher™ Steamer Lab/Pilot 0.48–1.85 ft2

(0.0444–0.1716 m2) 400-8,000 mL 12, 24, and 41

Investigator™ Steamer Lab/Pilot 1.4–5.4 ft2

(0.13–0.51 m2) 1–25 L 12, 24, and 41

mini-BioProducer™ Steamer Pilot/Production 6.6–26.9 ft2

(0.61–2.50 m2) 5 – 250L 12, 24, and 41

BioProducer™ Steamer Production 13.1–53.8 ft2

(1.21–5.00 m2) 25–500 L 12, 24, and 41

INTENDED APPLICATIONS

The intended applications in the biopharmaceutical/bioindustrial sectors include crossflow microfiltration and ultrafiltration for:

§ Perfusion § Cell harvesting § Cell washing § Bacteria separation in fermentation broths § Debris removal post-centrifugation § Primary recovery/clarification § Vaccine purification and concentration

§ Primary recovery of recombinant biopharmaceuticals

§ Macromolecule concentration and diafiltration (viruses, antibodies, recombinant proteins, enzymes, peptides, and oligomers

Product Information


HOLLOW FIBER 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 (m-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

Product Information


Figure 2. Cartridge showing hollow fibers encapsulated in the hollow fiber housing

HOLLOW FIBER CARTRIDGE LABELING AND CATALOG NUMBERS

WaterSep Steamer Line 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 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.

Encapsulated fibers

Housing

Product Information


Figure 3. Typical Steamer Line hollow fiber cartridge label information

Product Information


Figure 4. Identifying Steamer Line hollow fiber cartridge properties by catalog number

AU 910 10 DIS 12 LD

Product Code Designator AU = Modified PES Membrane Autoclavable

Fiber Lumen Diameter (mm) 05 = 0.5 mm 10 = 1 mm 20 = 2 mm (special production)

MWCO 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

Cartridge Type DIS = Discover™ Steamer EXP = Explorer™ Steamer RES = Researcher™ Steamer INV = Investigator™ Steamer MPR = mini-BioProducer™ Steamer PRO = BioProducer™ Steamer

Fiber Length 12 = 12 inches 24 = 24 inches 41 = 41 inches

Type of Connector (Discover™ ® BioProducer™) L = Luer Lok (Discover™) S = Sanitary

1/2-inch TC (Explorer™) 3/4-inch TC (Researcher™) 1-inch TC (Investigator™) 1.5-inch TC (mini-BioProducer™, BioProducer™)

Catalog number

Package Size Discover™ ® BioProducer™ 6 = 6/pack Discover™ ® Explorer™ D = 12/pack Researcher™ ® BioProducer™ 3 = 3/pack

Product Information


MATERIALS OF CONSTRUCTION

The materials of construction (and wetted components) of WaterSep Steamer Line hollow fiber cartridges include these:

§ Membrane—modified polyethersulfone (m-PES) composition § Encapsulant—USP Class VI compliant medical grade epoxy § 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.

PRODUCT SPECIFICATIONS

You can purchase WaterSep Steamer Line hollow fiber cartridges in a variety of sizes from lab scale to production scale. By design, WaterSep 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 Discover™ Steamer 10–850 mL Explorer™ Steamer 150–3,000 mL Researcher™ Steamer 400–8,000 mL Investigator™ Steamer 1–25 L mini-BioProducer™ Steamer 5–250 L BioProducer™Steamer 25–500 L For additional scale-up information, contact WaterSep at 508–970–0089, extension 204, or email WaterSep at [email protected]

Product Information


OPERATING LIMITS OF HOLLOW FIBER CARTRIDGES

The maximum operating limits for WaterSep’s hollow fiber cartridges are presented in Table 2.

Table 2. Operating Limits for WaterSep Hollow Fiber Cartridges

Pore Sizes/MWCO

Operating Limits

Maximum Feed

Pressure

Maximum Transmembrane Pressure (TMP)

Maximum Temperature pH Range

bar psi bar psi °C °F 0.45µm – 0.2µm 1.0 15 0.7 10 40 104 2 to 13.5

0.1µm 1.4 20 1.0 15 40 104 2 to 13.5

750K MWCO 1.7 25 1.4 20 50 122 2 to 13.5

500K – 300K MWCO 2.1 30 1.7 25 50 122 2 to 13.5

100K – 3K MWCO 2.8 40 2.4 35 60 140 2 to 13.5

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 Discover™ Steamer, Explorer™ Steamer, Researcher™ Steamer, Investigator™ Steamer, mini-BioProducer™ Steamer, and BioProducer™ Steamer hollow fiber cartridges are presented in Table 3, Table 4, Table 5, and Table 6.

Product Information


Table 3. Physical characteristics of Discover™ Steamer, Explorer™ Steamer, and Researcher™ Steamer HF Cartridges

Discover™ Steamer HF Cartridges

Characteristic 12 Inch 24 Inch 41 Inch

Dimensions in inches (cm) 0.38 x 12.88 (0.95 x 32.72) 0.38 x 24.38 (0.95 x 61.93)

0.38 x 41.8 (0.95 x 106.2)

Membrane surface area in ft2 (cm2) 0.056 (52) 0.115 (107) 0.208 (193)

Recommended batch volume per cartridge (mL) 10–250 50–400 80–850

Recommended permeate flow rate (mL/hr) Up to 310 Up to 640 Up to 1,160

Molecular weight cut-off (K) MWCO 3, 5, 10, 30, 50, 100, 300, 500, 750

Membrane pore size (µm) 0.1, 0.2, 0.45

Feed/retentate connectors Luer Lok

Permeate connector Luer Lok

Explorer™ Steamer HF Cartridges



0.5 x 41.8 (1.3 x 106.2)

Membrane surface area in ft2 (cm2) 0.17 (155) 0.35 (321) 0.62 (579)

Recommended batch volume per cartridge (mL) 150–175 250–1,500 300–3,000

Recommended permeate flow rate (mL/hr) Up to 930 Up to 1,900 Up to 3,500



Feed/retentate connectors 1/2-inch TC

Permeate connector 3/16-inch Hose Barb

Researcher™ Steamer HF Cartridges



0.75 x 41.8 (1.91 x 106.1)

Membrane surface area in ft2 (cm2) 0.48 (444) 1.01 (940) 1.85 (1,716)

Recommended batch volume per cartridge (mL) 400–2,000 700–4,000 1,000–8,000

Recommended permeate flow rate (mL/hr) Up to 2.7 Up to 5.6 Up to 10



Feed/retentate connectors 3/4--inch TC

Permeate connector 1/4-inch Hose Barb

Product Information


Table 4. Physical characteristics of Investigator™ Steamer, mini-BioProducer™ Steamer, and BioProducer™ Steamer HF cartridges

Investigator™ Steamer HF Cartridges



1.32 x 41.5 (3.34 x 105.4)

Membrane surface area in ft2 (m2) 1.4 (0.13) 3.0 (0.28) 5.4 (0.51)

Recommended batch volume per cartridge (L) 1–6 2–12 3–25

Recommended permeate flow rate (L/hr) Up to 7.8 Up to 17 Up to 31



Feed/retentate connectors 1.5-inch TC

Permeate connector 1/2-inch TC

mini-BioProducer™ Steamer HF Cartridges



2.70 x 44.5 (6.86 x 113)



Recommended permeate flow rate (L/hr) Up to 37 Up to 81 Up to 150




Permeate connector 1-inch TC

BioProducer™ Steamer HF Cartridges



3.50 x 44.49 (8.89 x 113)



Recommended permeate flow rate (L/hr) Up to 73 Up to 161 Up to 300




Permeate connector 1-inch TC

Product Information


Table 5. Void volumes of Discover™ Steamer, Explorer™ Steamer, Researcher™ Steamer, and Investigator™ Steamer HF Cartridges

Product

Cartridge Characteristics Hold Up Volume

Fiber ID (mm)

No. of Fibers

Surface Area (cm2)

Feed Side Holdup Volume

(mL)

Permeate Side Holdup Volume

(mL)

Whole Cartridge

Holdup Volume (mL)

Discover™12 Steamer

0.5 12

52

0.81 6.89 7.70

1.0 6 1.51 6.05 7.56

2.0 3 2.93 4.61 7.53


0.5 12

107

1.49 14.21 15.71

1.0 6 2.89 12.48 15.37

2.0 3 5.68 9.50 15.18


0.5 12

193

2.57 25.67 28.24

1.0 6 5.04 22.54 27.58

2.0 3 9.98 17.16 27.14

Explorer™12 Steamer

0.5 36

155

2.7 14.1 16.9

1.0 18 4.8 11.6 16.5

2.0 9 9.1 7.3 16.4


0.5 36

321

4.8 27.9 32.6

1.0 18 9.0 24.0 33.0

2.0 9 17.3 15.0 32.4


0.5 36

579

8.0 50.3 58.3

1.0 18 15.4 43.3 58.7

2.0 9 30.3 27.2 57.4

Researcher™12 Steamer

0.5 108

444

7.1 36.4 43.4

1.0 54 13.4 29.2 42.6

2.0 27 26.1 16.8 42.9


0.5 108

940

13.2 73.0 86.2

1.0 54 25.8 61.6 87.4

2.0 27 50.9 35.4 86.3


0.5 108

1,716

22.9 133.1 156.0

1.0 54 45.2 112.4 157.6

2.0 27 89.7 64.5 154.2

Investigator™12 Steamer

0.5 320

1,300

20 95 114

1.0 160 39 79 118

2.0 80 76 45 121


0.5 320

2,800

38 206 244

1.0 160 75 173 249

2.0 80 150 97 247


0.5 320

5,100

67 381 448

1.0 160 133 320 453

2.0 80 265 180 445

Product Information


Table 6. Void volumes of mini-BioProducer™ Steamer, BioProducer™ Steamer HF cartridges

Product

Cartridge Characteristics Hold Up Volume

Fiber ID (mm)

No. of Fibers

Surface Area (m2)

Feed Side Holdup Volume

(L)

Permeate Side Holdup Volume

(L)

Whole Cartridge

Holdup Volume (L)

mini-BioProducer™12 Steamer

0.5 1,600

0.61

0.214 0.492 0.706

1.0 800 0.308 0.419 0.727

2.0 400 0.497 0.249 0.746


0.5 1,600

1.35

0.306 1.088 1.394

1.0 800 0.492 0.926 1.418

2.0 400 0.864 0.552 1.415


0.5 1,600

2.50

0.449 2.021 2.470

1.0 800 0.779 1.720 2.499

2.0 400 1.438 1.025 2.463

BioProducer™12 Steamer

0.5 6400

1.21

0.338 0.820 1.158

1.0 3200 0.527 0.674 1.201

2.0 1600 0.904 0.337 1.241


0.5 6400

2.69

0.522 1.815 2.337

1.0 3200 0.894 1.492 2.386

2.0 1600 1.637 0.746 2.383


0.5 6400

5.00

0.809 3.374 4.183

1.0 3200 1.468 2.773 4.241

2.0 1600 2.786 1.385 4.170

Product Information


MEMBRANE PERFORMANCE

The WaterSep Steamer Line hollow fiber membranes are manufactured using a unique combination of modified polyethersulfone (m-PES) and a proprietary spinning process that results in glycerin free, autoclavable hollow fiber membrane.

CARTRIDGE PERFORMANCE

The exceptional uniformity of WaterSep Steamer Line hollow fiber membrane and the precision of the hollow fibers cartridge assembly process results in hollow fiber cartridges that perform consistently through five autoclave cycles, with excellent antifouling and process flow properties, and show high lot-to-lot consistency (Table 7 and Table 8).

INHERENTLY SUPERIOR CHARACTERISTICS

WaterSep Steamer Line hollow fiber cartridges are designed for:

§ Aseptic and cell perfusion applications § Use in an ATFÔ system or crossflow pump operated system § Autoclaving up to five (5) times in a liquid cycle § Glycerin free membrane for very low extractables level

PROVEN PERFORMANCE ADVANTAGES

§ Reuse up to five (5) times § Easy and effective cleaning and autoclaving § Low fouling and anti-dead spot design § High flow rate and total capacity § High batch-to-batch consistency

Product Information


Table 7. Air flow specifications for WaterSep Steamer Line HF ultrafiltration cartridges

Product Name Membrane MWCO

Air Flow per Cartridge mL/min/7 barg

(mL/min/10 psig)


3, 5, 10, 30, 50, 100, 300,

500, 750K

< 5

Discover™24 Steamer < 10


Explorer™12 Steamer < 5



Researcher™12 Steamer < 10



Investigator™12 Steamer < 20



mini-BioProducer™12 Steamer < 60



BioProducer™12 Steamer < 110



Product Information


Table 8. Air flow specifications for WaterSep Steamer Line HF microfiltration cartridges

Product Name Membrane

Air Flow per Cartridge mL/min/0.35 barg (mL/min/5 psig)


0.1, 0.2, 0.45 µm

< 5


















Product Information


STORAGE OF NEW AND USED STEAMER LINE HOLLOW FIBER CARTRIDGES

NEW STEAMER LINE 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 until the expiration date (i.e., 24 months from date of labeling) without influencing performance or leading to product alterations.

USED STEAMER LINE CARTRIDGES

In most cases, you can clean, autoclave, and reuse WaterSep Steamer Line cartridges up to five (5) times. After cleaning your cartridge using the WaterSep Installation and Operating Instructions for Steamer Line Hollow Fiber Cartridges, you can store the cartridge in 0.1N sodium hydroxide solution for reuse at a later time. The maximum storage time depends on the process solutions and conditions to which the cartridge was exposed.

PREPARING YOUR STEAMER LINE HOLLOW FIBER CARTRIDGE FOR USE

The WaterSep Steamer Line HF cartridges contains a glycerin free membrane with very low extractable levels. New WaterSep Steamer Line hollow fiber cartridges are pre-wetted with deionized water and gamma irradiated. Prior to use, please complete the steps below.

§ Remove the storage solutions (from used cartridges) § Connect the Steamer cartridge into a perfusion/crossflow system and re-wet the cartridge (optional)

Prior to autoclaving, the recommended re-wetting volume of deionized water for new HF cartridges is 0.5L/m2 through the permeate for 5 minutes.

§ Autoclave the Steamer cartridge or system, if required for your application § Measure the water flux and normalized water permeability if intended to reuse § Integrity test the Steamer cartridge § Condition the Steamer cartridge with buffer before introducing product § Run the filtration process and recover your product § Clean the Steamer cartridge if intended to reuse § Store the Steamer cartridge

You can learn about preparing cartridges for use by reading the WaterSep’s publication Installation and Operating Instructions for Steamer Line Hollow Fiber Cartridges which is available to download from our website.

Product Information


AUTOCLAVING PROCEDURE FOR STEAMER LINE HOLLOW FIBER CARTRIDGES

For aseptic or sanitary applications including perfusion, the Steamer hollow fiber cartridges can be autoclaved connected to a system using a commercial autoclave and a standard operating procedure. Plastic sanitary clamps should be loose for autoclaving. The cartridge should be autoclaved using a liquid or wet cycle for 35 minutes at 121 degrees Celsius (maximum); do not use a dry or solid autoclave cycle. Once the autoclave cycle is complete, allow the cartridge to cool to ≤50 degrees C prior to handling. The sanitary clamps can be re-tightened after the cartridge has cooled to ≤50 degrees Celsius. WaterSep Steamer Line cartridges can be autoclaved up to five (5) times. For detailed information about autoclaving, contact WaterSep BioSeparations 508 970 0089, Extension 204 or email WaterSep at [email protected]

Validation Information


CHAPTER 3—VALIDATION INFORMATION WaterSep uses dynamically challenging testing strategies to ensure that all products meet WaterSep’s release specifications. 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.

HOLLOW FIBER MEMBRANE WATER FLUX

A common way to measure clean membrane performance and determine the level of membrane recovery after cleaning is to measure the water permeability of the membrane under controlled, dynamic 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 9.

Table 9. Water permeability of WaterSep Steamer Line HF membranes

Ultrafiltration Membrane

MWCO Normalized Water Permeability (LMH/psi) 1

3K 0.2–5

5K 2–9

10K 4–10

30K 10–40

50K 15–50

100K 18–55

300K 20–60

500K 30–80

750K 40–110

Microfiltration Membrane

MWCO Normalized Water Permeability (LMH/psi) 1

0.1 µm > 100

0.2 µm > 250

0.45 µm > 400

1 These numbers are based on Explorer™12 Steamer HF cartridges.



MEMBRANE SOLUTE REJECTION

In addition to water flux testing, WaterSep’s hollow fiber membranes have very well defined and narrow retention/passage specifications, or two-sided 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 10 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 10. Results of solute passage through WaterSep membrane (% P – percent passage)

MWCO

PVP-K15 PVP-K30 PVP-K60S PVP-K90 Bubble Point

MW = ~9700 MW = 66,800 MW = 396,000

MW = 1,570,000 60% IPA H2O

%P %P %P %P psig

3K 12–20

5K 20–40

10K 40–75

30K 20–40

50K 40–65

100K > 65 < 25

300K > 80 20–35 < 20

500K 35–65 < 30

750K > 65 < 50 > 60

0.1 µm > 50 35–60 60–100

0.2 µm 22–35 45–60

0.45 µm 10–22 30–45



CARTRIDGE INTEGRITY TEST

Membrane integrity testing is an important process step to ensure that membrane filtration systems operate to the performance product specification for the membrane and membrane element(s) installed. The integrity test methods described are used to determine the integrity of membrane systems, and are applicable to systems containing any membrane module configurations and both UF and MF membrane classes. Integrity test procedures detect only system or membrane leaks or defects and do not provide a means to determine retention characteristics of the membrane.

The ability of the methods to detect any given defect is affected by the size of the system or portion of the system tested. Selecting smaller portions of the system to test will increase the sensitivity of the test to defects, henceforth; individual element testing will produce the highest accuracy.

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 pressure hold/diffusion test. WaterSep recommends using the pressure hold test for both UF and MF membranes (3K – 750K and 0.1 µm – 0.45 µm, respectively). 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:

𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒𝐻𝑜𝑙𝑑𝑇𝑒𝑠𝑡𝐹𝑜𝑟𝑚𝑢𝑙𝑎 = (𝐷 × 𝑇 × 𝑃4

𝑉6) − ∆𝑃

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)



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 (using either location ① or ② in Figure 5).

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.

Figure 5. Process Diagram for Pressure Hold Integrity Test



HOLLOW FIBER 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. Table 11 shows the average water flux for Investigator™12 Steamer 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 6, Figure 7, and Figure 8).

Table 11. Water flux results for an Investigator™12 Steamer hollow fiber cartridges

Membrane Type Average Water Flux LMH/psi at 0.68 barg (10 psig) of TMP

m-PES 30K MWCO 17.4

m-PES 300K MWCO 36.3

m-PES 0.2 µm 333.7

Figure 6. Clean water flux for an Investigator™12 Steamer, 30K MWCO, 1.0 mm ID

Investigator™12 Steamer 30K MWCO 1mm



Figure 7. Clean Water flux for an Investigator™12 Steamer, 300K MWCO, 1.0 mm ID

Figure 8. Clean Water flux for an Investigator™12 Steamer, 0.2 µm, 1.0 mm ID

Investigator™12 Steamer 300K MWCO, 1mm

Investigator™12 Steamer 0.2 µm, 1mm



HOLLOW FIBER 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 buffer/salt 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 crossflow rate for a family of hollow fiber cartridges does not vary with path length, the delta P needed to achieve the optimum crossflow rate can vary. For example, the optimum crossflow for a BioProducer™12/24/41 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 9 and Figure 10 show the measured crossflow vs. delta P for BioProducer™12/24/41 Steamer and Investigator™12/24/41 Steamer HF cartridges.



Figure 9. Delta P versus crossflow with water for BioProducer™12/24/41 Steamer cartridges

Delta P vs. Cross Flow for Producer24

00.20.40.60.8

11.21.41.61.8

2

20 25 35 40 50

Delta P (psi)

Delta P

Cross FlowL/min


00.10.20.30.40.50.60.70.80.9

1

20 25 35 40 50

Delta P (psi)

Delta P

Cross FlowL/min


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

Delta P vs. Crossflow for BioProducer™12 Steamer





Figure 10. Delta P versus crossflow with water for Investigator™12/24/41 Steamer cartridges

Delta P vs. Cross Flow for Investigator12

00.10.20.30.40.50.60.70.80.9

1

2 2.5 3.5 4 5

Delta P (psi)

Delta P

Cross FlowL/min


00.20.40.60.8

11.21.41.61.8

2

2 2.5 3.5 4 5

Delta P (psi)

Delta P

Cross FlowL/min


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

Delta P vs. Crossflow for Investigator™12 Steamer





HOLLOW FIBER CARTRIDGE CHEMICAL COMPATIBILITY STUDY

GENERAL CONSIDERATIONS

Certain chemicals can damage and degrade the membrane structure, or ultimately dissolve the membrane polymer. It is important to be aware of the membrane’s chemical compatibility and use compatible process and cleaning chemicals. Under normal operating conditions, WaterSep Steamer Line cartridges are resistant to commonly-used aqueous solutions within pH 4–10, and biological reagents with the exception of aromatic solvents. Certain operating conditions greater than ambient 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 12). Recommendations in this publication do not constitute a warranty of performance and do not modify our Standard Warranty as stated in our Terms and Conditions of Sale.

Table 12. Chemical compatibility list for WaterSep Steamer Line cartridges (R = recommended, L = limited exposure {≤12 hours at room temperature}, NR = not recommended)

Chemical Compatibility

Acetic acid (≤1M or ≤6% v:v) L

Acetic acid (>6% v:v) NR

Acetone NR

Acetonitrile NR

Alconox® (≤2% w:v) R

Ammonium hydroxide NR

Amyl acetate NR

Amyl alcohol (≤3% v:v) L

Aniline NR

Benzene NR

Benzyl alcohol NR

Boric acid (≤2% w:v) R

Brine R

Butyl acetate NR

Butyl alcohol (≤15% v:v) L

Butylaldehyde NR

Carbon tetrachloride NR

Chloroacetic acid NR

Chloroform NR

Chromic acid NR

Citric acid (≤2% w:v) R

Cresol NR

Cyclohexane NR

Cyclohexanone NR


Diacetone alcohol NR

Dichloromethane NR

Dimethyl formamide NR

Dimethylsulfoxide NR

1,4 Dioxane NR

Ethers NR

Ethyl acetate NR

Ethyl alcohol (≤20% v:v) L

Ethyl alcohol (>20% v:v) NR

Ethylene dichloride NR

Ethylene glycol (≤10% v:v) R

Formalin solution NR

Formic acid (≤1M or ≤4% w:v) L

Guanidine Hydrochloride (≤6M) R

Glycerin / Glycerol (≤15% v:v) R

Hexane NR

Hexanol NR

Hydrochloric acid NR

Hydrofluoric acid NR

Hydrogen peroxide NR

Iodine solutions NR

Isobutyl alcohol (≤5% v:v) L

Isopropyl acetate NR




Isopropyl alcohol/Isopropanol (≤20% v:v) L

Isopropyl ether NR

Lactic acid (≤30% v:v or ≤4M) L

Methyl acetate NR

Methyl alcohol (≤15% v:v) L

Methyl alcohol (>15% v:v) NR

Methyl cellosolve NR

Methyl chloride NR

Methyl ethyl ketone NR

Methyl formate NR

Methyl isobutyl ketone NR

Methylene chloride NR

N-methyl-2-pyrrolidone NR

Mineral spirits NR

Monochlorobenzene NR

NALCON® 7647 (≤1% w:v) R

NALCON® 7678 (≤1% w:v) R

NALCON® 7330 (≤1% w:v) R

Nitric acid NR

Nitrobenzene NR

Nitropropane NR

Pentane NR

Peracetic acid NR

Perchloric acid NR


Perchloroethylene NR

Petroleum based oils NR

Petroleum ether NR

Phenol NR

Phosphoric acid (≤5% v:v or ≤1M) L

Potassium hydroxide NR

2-Propanol (≤20% v:v) L

Pyridine NR

Silicone oil R

Sodium hydroxide NR

Sodium hypochlorite (≤200ppm) R

Sulfuric acid NR

Tetrahydrofuran NR

Toluene NR

Trichloroacetic acid (≤6% v:v or ≤0.5M) L

Trichlorobenzene NR

Trichloroethane NR

Trichloroethylene NR

Triethylamine NR

Turpentine NR

Urea (≤ 20% w:v or ≤3.7M) L

Water R

Xylene NR

Product Safety

36 WaterSep Steamer Line Validation Guide

HOLLOW FIBER CARTRIDGE RINSING AND BUFFER EQUILIBRATION STUDY

A new BioProducer™12, hollow fiber cartridge (1.25 m2, 13.5 ft2 membrane surface area) was filled with 650 mL of purified water 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 was 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 BioProducer™12. 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 11). This rinsing volume should be proportionally adjusted for larger/smaller cartridges. The minimum rinsing volume—0.65 Liters for 1.25 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 11. Results of Extractables Level vs Volumetric Throughput of Purified Water (Liters per m2)

Safety Information


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 Explorer™12 and Explorer™24 cartridges 2. A protein concentration study with Explorer™12 and Investigator™12 cartridges

E. COLI STUDY WITH EXPLORER™12 AND EXPLORER™24 CARTRIDGES

This study demonstrates cartridge scalability and provides data to assist with scalability. The E. coli lysate clarification study was conducted using Explorer™12 and Explorer™24 cartridges. The results of the study are illustrated in Figure 12, Figure 13, and Table 13.

CONCLUSIONS

The results indicate that TMP and flux data for production Explorer™12 and Explorer™24 have a scalability factor close to 1.0 in this application.

Figure 12. Pressure and permeate flux profiles for the Explorer™12 cartridge

Product Safety


Figure 13. Pressure and permeate flux profiles for the Explorer™24 cartridge

Table 13. Results from the E. coli lysate clarification scalability study

Process Parameter

Explorer™12 MWCO = 750 K

Fiber Diameter = 1 mm

Explorer™24 MWCO = 750 K

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

Safety Information


PROTEIN CONCENTRATION STUDY WITH EXPLORER™12 AND INVESTIGATOR™12 CARTRIDGES

This study demonstrates cartridge scalability and provides data to assist with scalability. A protein concentration study was conducted using Explorer™12 and Investigator™12 cartridges. The results of the study are illustrated in Figure 14.

Figure 14. Optimization results of scalability study using Explorer™12 and Investigator™12 cartridges

CONCLUSIONS

The Flux vs. TMP curves for an Explorer™12 and an Investigator™12 are almost identical and suggest that the scalability factor is close to 1.0 in this application.

Product Safety


CHAPTER 4—PRODUCT SAFETY BIOCOMPATIBILITY STUDIES

WaterSep submitted samples of hollow fiber cartridges for biocompatibility analyses. The following summarizes the results of the testing. WaterSep USP Class VI Results 09-0302-G1 Study Summary: “Therefore, the test article, WaterSep hollow fiber cartridge, meets the requirements of USP guidelines, for Class VI Plastics – 70°C.” WaterSep USP Physicochemical Test Results 09-0302-G2 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.” The above reports are available at www.watersep.net

Quality Assurance Information


CHAPTER 5—QUALITY ASSURANCE INFORMATION CERTIFICATE OF ANALYSIS

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 15).

Figure 15. Example of a Steamer Line cartridge certificate of analysis

Appendices


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.

Table 14. Helpful information available at www.WaterSep.net

Standard Operating Procedures

Installation and Operating Instructions for Steamer Line Hollow Fiber Cartridges

Product Data Sheets



















Appendices


APPENDIX II—TEST PROCEDURES AND REPORTS

You can obtain the reports cited in this validation guide from the WaterSep website.

Table 15. Test reports available from www.WaterSep.net

Title of Report

MAR-CAR001 WaterSep Cartridge Integrity Test Procedure

MAR - REG003 WaterSep Membrane and Cartridge Regulatory and Bio-Compatibility Summary

WaterSep USP Class VI Results 09-0302-G1

WaterSep USP Physicochemical Test Results 09-0302-G2

Index


INDEX INDEX

Appendices, 46 Applications, 11 Audience for this guide, 7 Biocompatibility, 44 Biocompatibility studies, 44 Cartridge

additional information, 46 biocompatibility, 44 caustic stability study, 38 certificate of analysis, 45 chemical compatibility study, 36 crossflow, 33 design, 12 information, 10 inlets and outlets, 12 integrity test, 29 materials of construction, 16 packaging, 16 quality assurance, 45 rinsing study, 39 scalability study, 40 storage, 26 Test procedures and reports, 47 water flux, 31

Cartridges Protein concentration, 43 scalability, 40

Certificate of ANALYSIS, 45 Chemical compatibility, 36 Contacting WaterSep, 8 Crossflow rate, 33 Customer support, 8 Documentation additional information, 46 E-mailing WaterSep, 8 Extractables, 44 GLP compliance, 44 Help, 8 List of figures, 6

List of tables, 6 Materials of construction, 16 Membrane solute rejection, 28 Membrane water flux, 27 Non-destructive testing, 29 Operating Limits, 17 Packaging, 16 Performance

characteristics, 23 Performance advantages, 23 Performance characteristics, 23 Preconditioning, 26 Pressure and permeate flux profiles, 41 Pressure hold test, 29 Process validation, 8 Protein concentration, 43 Quality assurance, 45 Rinsing cartridges, 39 Rinsing pH and conductivity reduction, 39 Scalability, 40 Specifications, 16

materials of construction, 16 physical properties, 16 water flux, 27

Storage, 26 Support, 8 Test procedures and reports, 47 Test reports, 47 USP Class VI Results, 44 USP Physicochemical Test Results, 44 Validation, 8 Validation guide purpose, 7 Validation information, 27 Void volume, 17 Water flux, 31 Water permeability, 27 Website, 8

WaterSep BioSeparations Corporation 450 Donald Lynch Blvd. Marlborough, MA 01752 USA Telephone: 508-970-0089 x204 Fax: 508-970-0146 Email:[email protected]

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