Supor® EX Grade ECV Filters,Supor® EX Grade ECV Filters · 2021. 1. 6. · Supor EX grade ECV filters have been designed as liquid sterilizing filters for use within the pharmaceutical

USTR 2838Validation Guide

Supor® EX Grade ECV Filters

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Table of Contents

1. Overview.......................................................................................................................................................4

1.1 Introduction ............................................................................................................................................4

1.2 Summary of Conclusions ........................................................................................................................5

2. Microbial Retention Validation Tests for AB Style Supor EX Grade ECV Cartridges...............................7

2.1 Introduction ............................................................................................................................................7

2.2 Summary of Methods ..............................................................................................................................8

2.3 Results ....................................................................................................................................................9

2.4 Conclusions ..........................................................................................................................................11

3. Microbial Validation Tests of Other Styles of Supor EX Grade ECV Filters............................................11

3.1 Introduction ..........................................................................................................................................11

3.2 Summary of Methods ............................................................................................................................11

3.3 Results ..................................................................................................................................................12

3.4 Conclusions ..........................................................................................................................................12

4. Endurance to In-Situ Steam Sterilization and Autoclaving .....................................................................13

4.1 Introduction ..........................................................................................................................................13


4.3 Results ..................................................................................................................................................14

4.4 Conclusions ..........................................................................................................................................16

5. Determination of Water Flow Characteristics ..........................................................................................17

5.1 Introduction ..........................................................................................................................................17


5.3 Results ..................................................................................................................................................17

5.4 Conclusions ..........................................................................................................................................17

6. Determination of Water Flow Characteristics for Other Styles of Supor EX Grade ECV Filters ...........18

6.1 Introduction ..........................................................................................................................................18


6.3 Results ..................................................................................................................................................18

6.4 Conclusions ..........................................................................................................................................19

7. Extractables Testing Using Water ............................................................................................................19

7.1 Introduction ..........................................................................................................................................19


7.3 Results of NVR and FTIR ......................................................................................................................21

7.4 Conclusions ..........................................................................................................................................23

8. Extractables Testing of Other Supor EX Grade ECV Filters Using Water...............................................23

8.1 Introduction ..........................................................................................................................................23


8.3 Results of NVR and FTIR ......................................................................................................................24

8.4 Conclusions ..........................................................................................................................................26

9. Biological Safety Tests on the Materials of Construction .......................................................................26

9.1 Introduction ..........................................................................................................................................26

9.2 Summary of Tests ..................................................................................................................................27

9.3 Results ..................................................................................................................................................28

9.4 Conclusions ..........................................................................................................................................28

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1. Overview

1.1 IntroductionThis guide contains validation data for 0.2 micron microbially rated Supor EX grade ECV filtersin sanitary “AB style” filter cartridge format and Supor EX grade ECV filters in Kleenpak™ Novacapsule filter format.

Regulatory guidelines for the pharmaceutical industry comprise many well-defined andestablished quality and safety standards for manufacturers to consider when qualifying their processes (and components thereof) to ensure the output of reliable and reproduciblymanufactured finished goods.

Sterilizing grade filters incorporating advanced membrane filtration technology play an importantrole as key components in these manufacturing processes. They are a significant contributor tothe successful accomplishment of stringent quality and safety objectives where in accordancewith Current Good Manufacturing Practices (cGMP), microbial and particulate contamination of process fluids must be carefully negated.

Supor EX grade ECV filters have been designed as liquid sterilizing filters for use within thepharmaceutical industry and can satisfy the safety and quality requirements of the end-useracross a range of fluids. These can include either those essential to the functioning of a unitoperation (buffers, growth media and bioreactor additives used in biological drug manufacturing)or those containing active pharmaceutical ingredients in either intermediate or final delivery form(topical, oral, or injectables).

The 254 mm (10 inch) sanitary AB style filter is manufactured using a patented laid-over pleatconstruction. This pleat configuration maximizes membrane area in order to increase flow ratesand optimizes filter life.

The removal rating of Supor EX grade ECV filters of 0.2 micron is based on the proven retentionof Brevundimonas diminuta (ATCC 19146) under challenge conditions correlated to standard testmethod ASTM 838-05. Supor EX grade ECV filters feature a novel construction, being comprisedof two layers of polyethersulfone (PES) membrane. The combination of the asymmetric upstreammembrane layer with the symmetric downstream membrane layer provides excellent flow andthroughput while enabling sterilizing grade bacterial removal performance.

As part of Pall’s commitment to delivering the highest quality sterilizing grade filters to thepharmaceutical manufacturer, Supor EX grade ECV filters have been rigorously tested andqualified by Pall’s R&D division to an appropriate performance specification. In addition, Supor EX grade ECV filters are also systematically tested for quality during and after production to confirm the maintenance of this specification from batch to batch.

This guide specifically documents the product qualification tests performed to establish SuporEX grade ECV filter’s performance specification.

The purpose of the guide is to support the selection and qualification of Supor EX grade ECVfilters for a manufacturing process.

The qualification test program for Supor EX grade ECV filters included:

• Microbial retention validation tests correlated to standard test method ASTM 838-05

• Endurance to in-situ steam sterilization and autoclaving under water wet conditions

• Determination of water flow characteristics

• Extractables testing using water

• Biological safety tests on filter components (after sterilization) – Compliance with UnitedStated Pharmacopoeia (USP) Biological Reactivity Tests (in vivo) for Class VI-121 °C plastics


This guide may be combined with other documentation for Supor EX grade ECV filters, namely the technical product datasheet and Pall’s pharmaceutical Certificate of Test for a comprehensive package that substantiates the product specification and quality control standards applied to Supor EX grade ECV filters.

Following an appropriate risk assessment and in reference to FDA’s Guidance for Industry:Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice(September 2004), Pall advises that, where necessary, Supor EX grade ECV filters are subjectto a process-specific test program that considers the end-user’s own operating conditions andacceptance criteria.

Note: The units of pressure quoted in this document are “bar” and “pounds force per square inch (psi)”. The following figures can be used to convert these units ofpressure to Pascals (Pa):

• 1 bar = 1 x 105 Pa

• 1 psi = 6.89476 x 103 Pa

1.2 Summary of Conclusions

Microbial Retention Validation TestsSupor EX grade ECV filter cartridges in AB style were tested for bacterial retention ofBrevundimonas diminuta (ATCC 19146) using bacterial challenge tests correlated to ASTMStandard Test Method F838-05, and in accordance with the FDA’s Guidance for Industry –Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice(September 2004).

The Forward Flow integrity test was shown to be a suitable non-destructive integrity test forSupor EX grade ECV filter cartridges, and test parameters have been set as follows for 254 mm(10 inch) filters (part number AB1UECV7PH4). These test parameters are also applicable to 254 mm (10 inch) capsule filters in Kleenpak Nova capsules, part number N*UECVP#G (*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).

Table 1Forward Flow Integrity Test Parameters for 254 mm (10 inch) Supor EX Grade ECV Filter Elements,Part Numbers AB1UECV7PH4 and N*UECVP#G

* T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).** During the test period the temperature of the filter assembly should not vary more than ± 1 °C (2 °F).

Test pressure 2760 mbar (40 psi)Wetting liquid WaterTemperature 20 °C ± 5 °C (68 °F ± 9 °F)Test gas AirMaximum allowable Forward Flow limit** 21.0 mL/min

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Endurance to In-Situ Steam Sterilization and Autoclaving Supor EX grade ECV filter cartridges have been demonstrated to be capable of withstandingmultiple in-situ steam sterilization and autoclave cycles under various standard steamingconditions. Tests performed demonstrate that the Supor EX grade ECV filter cartridges arerobust and capable of withstanding differential pressures up to 300 mbar (4.35 psi) in theforward direction during steaming.

The data presented in this report support the following product claim for in-situ steaming andautoclaving 254 mm (10 inch) Supor EX grade ECV filters in sanitary AB style cartridges:

The autoclave resistance of the Kleenpak Nova capsules has been investigated separately and is documented in the Pall document USTR 2099 “Validation Guide for Pall ‘Kleenpak’ Nova Filter Capsules”. The product claim for autoclave resistance of Kleenpak Nova capsules is three (3) autoclave cycles at 125 °C (257 °F). Kleenpak Nova capsules must not be subject to in-situ steaming.

The following product claim for autoclaving is therefore applicable to 254 mm (10 inch) SuporEX grade ECV filter cartridges in Kleenpak Nova G-grade capsules:

*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).

The above claims are supported by data with a 100 % safety margin.

Determination of Water Flow CharacteristicsDifferential pressure measurements at set water flow rates have been determined. The typicalclean water flow rate for a 254 mm (10 inch) filter (part number AB1UECV7PH4) is 17 L/min at a pressure drop of 100 mbar (1.45 psi) at 20 °C (68 °F). These data are also applicable to the 254 mm (10 inch) Supor EX grade ECV filters in Kleenpak Nova capsules and can thus be usedto assist users in sizing filter systems employing any 254 mm (10 inch) Supor EX grade ECV filters.

Extractables Testing using WaterThe typical amount of non-volatile residue (NVR) extracted from Supor EX grade ECV filtercartridges in sanitary AB1 style has been determined using water as the extraction fluid. For the254 mm (10 inch) filter cartridges tested (part number AB1UECV7PH4) the aqueous extractablesvalues were 4.8-139.9 mg per cartridge in the first extraction without pre-flushing, and werealways much reduced in the second (consecutive) extraction (1.0-19.1 mg per cartridge),demonstrating depletion of the extractables. The data justify the following product claim forSupor EX grade ECV filter cartridges in AB1 style, part number AB1UECV7PH4: NVR < 150 mg.

The typical amount of non-volatile residue (NVR) extracted from Supor EX grade ECV filters ofother styles has also been determined using water as the extraction fluid. For the 254 mm (10 inch) filters cartridges tested in Kleenpak Nova capsules after autoclaving (part numberNP6UECVP1G), the aqueous extractables values ranged from 48.5 to 118.9 mg. For the 254 mm(10 inch) filter cartridges tested in Kleenpak Nova capsules after gamma sterilization with anirradiation dose of 50 ± 5 kGy the aqueous extractables values ranged from 11.5 to 15.2 mg.

Filter Part Number Steaming Conditions Maximum Steam Life ClaimAB1UECV7PH4 In-situ steam cycles at

125 °C (257 °F)5 one-hour cycles

AB1UECV7PH4 In-situ steam cycles at135 °C (275 °F)

1 one-hour cycle

AB1UECV7PH4 Autoclave cycles at125 °C (257 °F)

5 one-hour cycle

Filter Part Number Steaming Conditions Maximum Steam Life ClaimN*UECVP#G Autoclave cycles at



The data justify that the above product claim for 254 mm (10 inch) Supor EX grade ECV filter cartridges in AB1 style, part number AB1UECV7PH4: NVR < 150 mg is also applied to254 mm (10 inch) Supor EX filters in Kleenpak Nova capsules in G and S-grade.

The FTIR spectra of all extracts indicate the presence of compounds typical for these materialsof construction, i.e. the copolymer used to render the polyethersulfone membranes hydrophilic,and oligomers associated with polypropylene. The latter were not detected in the extracts ofthe Supor EX grade ECV filters in Kleenpak Nova capsules in S-grade (i.e. after gammasterilization) with the methods applied.

Actual service in pharmaceutical applications will impose different conditions, such as differentsteaming conditions, exposure times, temperature, liquid type, etc. Evaluation under processconditions is therefore also recommended.

Biological Safety TestsAll of the materials used in Supor EX grade ECV filters in AB style cartridges and in KleenpakNova capsules meet the requirements of the United States Pharmacopoeia (USP) BiologicalReactivity Tests (in vivo) for Class VI-121 °C plastics. The tests included the Systemic Injectiontest, the Intracutaneous test and the Implantation test.

Copies of the test reports are available by contacting Pall Corporation.

2. Microbial Retention Validation Tests for AB Style Supor EX Grade ECV Cartridges

2.1 IntroductionThe FDA’s Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing –Current Good Manufacturing Practice (September 2004) states: ‘A sterilizing filter should bevalidated to reproducibly remove viable microorganisms from the process stream, producing a sterile effluent’. The guideline also states ‘the microorganism Brevundimonas diminuta(ATCC 19146), when properly grown, harvested and used, is a common challenge organism for 0.2 micron rated filters because of its small size (0.3 µm mean diameter).’

In accordance with the requirements of this guideline, liquid challenge tests usingBrevundimonas diminuta (ATCC 19146) were performed with Supor EX grade ECV filtercartridges using a minimum of 1 x 107 colony forming units (CFU)/cm2 of effective filtration area.

The FDA guideline further states: ‘After a filtration process is properly validated for a givenproduct, process and filter, it is important to ensure that identical filters (e.g. of identical polymerconstruction and pore size rating) are used in production runs… Integrity testing of the filter(s)can be performed prior to processing, and should be routinely performed post-use… Forwardflow and bubble point tests, when appropriately employed, are two integrity tests that can beused. A production filter’s integrity test specification should be consistent with the datagenerated during bacterial retention validation studies.’

The correlation between microbial retention and a non-destructive integrity test is an importantaspect of the validation of sterilizing grade filters. The Forward Flow test was the integrity testused during this study.

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The Forward Flow TestIn the Forward Flow test, a filter is wetted with an appropriate test liquid and a pre-determinedgas pressure is applied to the upstream side of the filter assembly. After a stabilization period,the gas flow through the wetted membrane can be measured on the upstream side, usingsensitive flow measurement equipment such as the Palltronic® Flowstar filter integrity testinstrument, see Figure 2.1.

Figure 2.1The Automated Integrity Test

The aim of this study was to demonstrate the microbial removal efficiency of typical Supor EX grade ECV filter cartridges in liquid challenge tests using Brevundimonas diminuta(ATCC 19146) and to document the correlation of the integrity test parameters to the microbial removal efficiency.

2.2 Summary of MethodsSupor EX grade ECV filter cartridges, part number AB1UECV7PH4 (membrane area 1.04 m2

[11.2 ft2]), were subjected to standard microbial challenge tests using an aqueous suspensionof Brevundimonas diminuta (ATCC 19146). Filter manufacturing and sampling consideredpossible variation in the filter manufacturing conditions. The filter samples represent 4 differentsub-batches (A-D) with respect to the combination of different membrane rolls used in themanufacture of these sub-batches.

Prior to the challenge tests the filter cartridges were installed in an appropriate housing, flushed with deionized (DI) water at a flow rate of a minimum of 8 L/min for 10 minutes with 1 bar (14.5 psi) back pressure. A Forward Flow integrity test was performed using a PalltronicFlowstar integrity test instrument with an air test pressure of 2760 mbar (40 psi). The filterswere autoclaved at 121 °C (250 °F) for 60 minutes. The filter assembly was asepticallyconnected to the pre-sterilized challenge apparatus, as shown in Figure 2.2.

An aqueous suspension of Brevundimonas diminuta was passed through the filter to achieve achallenge level of > 1 x 107 colony forming units (CFU) per cm2 of effective filtration area.

During the challenge test the entire filter effluent was passed through a 0.2 micron-ratedanalysis disc on the downstream side of the test filter assembly. The filter disc was incubatedon agar and, following incubation, the disc was examined to determine if any colonies hadgrown, indicating whether or not bacteria had passed through the test filter during thechallenge. The titer reduction (TR) for each filter was determined as follows:

Wetted filter(in housing)

Outlet open toatmosphericpressureUpstream

isolated

Calibrated pressureindicator upstream of

filter assembly

Regulatedcompressedgas supply

Palltronic Flowstarintegrity test instrument

TR = Total number of bacteria influent to the filter

Number of colonies recorded on the downstream analysis disc

When no colonies were detected downstream, the titer reduction was expressed as:

> Total number of bacteria influent to the filter (e.g. > 1 x 1010)

On completion of the challenge test the filter assemblies were autoclaved and then flushed and Forward Flow integrity tested as described previously.

Figure 2.2Microbial Challenge Apparatus

2.3 ResultsThe Forward Flow and Brevundimonas diminuta retention results are shown in Table 2.1. The higher of the two Forward Flow values (pre- and post-challenge) is presented and the data are arranged in order of increasing Forward Flow value.

All of the filter cartridges gave sterile effluent when challenged with > 1 x 107 CFU per cm2

of filtration area using Brevundimonas diminuta.


Challengefilter

Analysis membrane filter

Drain

Pressure vesselwith bacterialsuspension

Regulated air inlet

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Table 2.1Results of Forward Flow and B. diminuta Retention for Typical Supor EX Filter Cartridges, Part Number AB1UECV7PH4

* Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C (68 °F ± 9 °F), maximum allowable limit value 21.0 mL/min.

Pall CartridgeSerial Number Sub-Batch

Forward Flow*(mL/min) Sterile Effluent Titer Reduction

IR1311237 D 14.7 yes >1.10 x 1012

IR1311054 A 15.0 yes >2.97 x 1011

IR1311162 C 15.0 yes >4.99 x 1011

IR1311004 A 15.1 yes >3.00 x 1011

IR1311001 A 15.2 yes >1.78 x 1011

IR1311049 A 15.2 yes >2.13 x 1011

IR1311113 B 15.2 yes >2.17 x 1011

IR1311194 D 15.3 yes >2.97 x 1011

IR1311219 D 15.3 yes >4.12 x 1011

IR1311055 A 15.4 yes >1.37 x 1011

IR1311193 D 15.5 yes >1.18 x 1012

IR1311075 B 15.6 yes >2.20 x 1011

IR1311157 C 15.7 yes >1.50 x 1012

IR1311149 C 15.8 yes >1.96 x 1011

IR1311230 D 15.8 yes >1.43 x 1012

IR1311090 B 15.9 yes >5.32 x 1011

IR1311104 B 15.9 yes >2.10 x 1012

IR1311069 B 16.1 yes >2.17 x 1011

IR1311034 A 16.2 yes >9.25 x 1011

IR1311165 C 16.2 yes >2.33 x 1011

IR1311229 D 16.3 yes >2.79 x 1011

IR1311179 C 16.4 yes >2.40 x 1011

IR1311248 D 16.7 yes >2.47 x 1011

IR1311029 A 16.8 yes >2.38 x 1011

IR1311028 A 16.9 yes >1.98 x 1012

IR1311107 B 17.0 yes >9.91 x 1011

IR1311066 B 17.2 yes >2.64 x 1011

IR1311150 C 18.0 yes >1.93 x 1012

IR1311118 B 18.3 yes >2.40 x 1011

IR1311168 C 18.6 yes >1.83 x 1011

IR1311128 C 24.6 yes >2.27 x 1011

IR1311208 D 98.3 yes >2.75 x 1011

2.4 ConclusionsSupor EX grade ECV filter cartridges (part number AB1UECV7PH4) were found to providesterile effluent when subjected to aqueous microbial challenge tests using Brevundimonasdiminuta at a challenge level of > 1 x 107 CFU/cm2.

Forward Flow integrity test parameters have been defined for Supor EX grade ECV filtercartridges based on the above results of the microbial challenge tests and additionalconsiderations and parameters. Data showing that filters with a Forward Flow value >21.0 mL/min were still bacterially retentive demonstrate an adequate safety margin for the established limit value. Capability of the Forward Flow test to distinguish non-retentive filters has been demonstrated in other Filter Validation Guides.

Table 2Forward Flow Integrity Test Parameters for Supor EX Grade ECV Filter Cartridges, Part Number AB1UECV7PH4*

* See Section 2.2 for test procedure.** During the test period the temperature of the filter assembly should not vary more than ± 1°C (2 °F).

3. Microbial Validation Tests of Other Styles of Supor EX Grade ECV Filters

3.1 IntroductionBased on the integrity test parameters set for AB style Supor EX grade ECV filters (see Table 2.1), Forward Flow test parameters were set for other filter styles incorporatingSupor EX grade ECV filter medium. The purpose of this series of tests was to perform Forward Flow and bacteria challenge tests on these other filter styles to demonstrate that filters passing the Forward Flow test provided sterile filtrate during challenge tests.

3.2 Summary of MethodsForward Flow test parameters were set for other filter styles incorporating Supor EX grade ECVfilter medium are shown in Table 3.1:

Table 3.1Forward Flow Test Parameters for Other Styles of Supor EX Grade ECV Filters

Forward Flow values at 20 °C ± 5 °C (68 °F ± 9 °F).During the test period the temperature of the filter assembly should not vary more than ± 1 °C (2 °F).*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).

In order to validate the performance and to confirm the integrity test limit values, relevantsamples of these filter styles from three different production batches were subjected to Forward Flow and liquid bacterial challenge tests using Brevundimonas diminuta according to the procedures described previously in Section 2: Microbial Validation Tests for AB StyleSupor EX Grade ECV cartridges.


Test pressure 2760 mbar (40 psi)Wetting liquid WaterTemperature 20 °C ± 5 °C (68 °F ± 9 °F)Test gas AirMaximum allowable Forward Flow limit** 21.0 mL/min

Part Number Wetting Liquid Air Test PressureMaximum Allowable FF (mL/min) Test Limit

N*6UECVP#G Water 2760 mbar (40 psi) 21.0N*6UECVP#S Water 2760 mbar (40 psi) 21.0

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N*6ECVP#G Kleenpak Nova capsules are sterilizable by autoclaving and incorporate filtercartridges directly comparable to AB1UECV7PH4 filter cartridges. Filters of this type aretherefore fully covered by the bacterial challenge testing of AB1UECV7PH4 filter cartridges,which were also autoclaved prior to bacterial challenge testing. S-Grade Kleenpak Novacapsules (part number N*6ECVP#S) are sterilized by gamma irradiation (max. dose: 50 kGy).Representative sample of N*6ECVP#S filters were therefore sterilized by gamma irradiation at a target dose of 50 kGy (variation of irradiation process: ± 5 kGy) and submitted to bacterial challenge testing to verify their bacteria retention capabilities.

3.3 ResultsThe Forward Flow and Brevundimonas diminuta retention results for Supor EX grade ECV filters tested are shown in Table 3.2. The Forward Flow value of the filter type NP6UECVP1Spresented is the result of the Forward Flow test out-of-box prior to challenge, after the filtercapsules have been flushed with DI water at a flow rate of minimum 4 L/min for 10 min with a 2 bar (29 psi) back pressure.

All of the filter cartridges gave sterile effluent when challenged with > 1 x 107 CFU per cm2 offiltration area using Brevundimonas diminuta.

Table 3.2Results of Forward Flow and B. diminuta Retention for Typical Pre-Sterilized (Irradiated) SuporEX Grade Filters in Kleenpak Nova Capsules

* Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C (68 °F ± 9 °F).

3.4 ConclusionsSupor EX grade ECV filters incorporated in Kleenpak Nova capsules and sterilized by gamma-irradiation were found to provide sterile effluent when subjected to aqueous microbial challengetests using Brevundimonas diminuta at a challenge level of > 1 x 107 CFU/cm2. The resultsconfirm that the Forward Flow limit value for 254 mm (10 inch) Supor EX grade ECV filters insanitary AB-style (21.0 mL/min) is also applicable to 254 mm (10 inch) Supor EX grade ECVfilters incorporated in Kleenpak Nova capsules (part number N*6UECVP#S).

Part NumberIrradiation Dose(kGy)

Pall FilterSerial Number

Forward Flow*(mL/min) Sterile Effluent Titer Reduction

NP6UECVP1S 48.3 – 49.9 IR4931 69588 15.6 yes >2.29 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69590 14.2 yes >3.34 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69592 15.4 yes >2.0 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69593 15.9 yes >1.76 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69596 15.1 yes >2.53 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69599 17.1 yes >1.94 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69602 15.6 yes >1.95 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69598 15.3 yes >2.11 x 1011

NP6UECVP1S 48.3 – 49.9 IR4931 69622 15.3 yes >2.65 x 1011

NP6UECVP1S 48.3 – 49.9 IR4932 69612 16.8 yes >2.45 x 1011

NP6UECVP1S 48.3 – 49.9 IR4932 69616 15.5 yes >2.33 x 1011

NP6UECVP1S 48.3 – 49.9 IR4932 69619 15.7 yes >3.00 x 1011

NP6UECVP1S 48.3 – 49.9 IR4932 69621 15.6 yes >3.25 x 1011

NP6UECVP1S 48.3 – 49.9 IR4932 69623 15.8 yes >2.27 x 1011

NP6UECVP1S 48.3 – 49.9 IR4932 69624 16.4 yes >3.62 x 1011

NP6UECVP1S 48.3 – 49.9 IR4932 69627 15.6 yes >2.69 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 005 11.8 yes >3.65 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 036 14.7 yes >2.48 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 042 17.0 yes >2.94 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 079 14.6 yes >3.82 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 114 15.7 yes >2.37 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 118 14.7 yes >2.24 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 128 17.1 yes >3.12 x 1011

NP6UECVP1S 47.3 – 47.6 IS0534 132 14.7 yes >2.27 x 1011

4. Endurance to In-Situ Steam Sterilization and Autoclaving

4.1 IntroductionThe purpose of these tests was to determine the effects of repeated exposure to in-situ steamcycles and autoclaving on filter integrity and water wettability using Supor EX grade ECV filtercartridges. The tests were used to qualify the steam exposure claims for Supor EX grade ECVfilter cartridges.

4.2 Summary of Methods

In-Situ Steaming at 125 °C (257 °F) Under Water Wet Steaming ConditionsSupor EX grade ECV filters part number AB1UECV7PH4 were used for the tests. Filter manufacturing and sampling considered possible variation in the filter manufacturing conditions.

Twenty four (24) filter cartridges were flushed with DI water for 10 minutes and then ForwardFlow integrity tested using an air test pressure of 2760 mbar (40 psi). The wet filter cartridgeswere then subjected to a one-hour in-situ steam cycle at 125 °C (257 °F).

During the initial stages of the steam cycles, the wet filter membrane caused the differentialpressure to increase across the filter cartridge as steam was introduced. The steam inlet valvewas controlled so that the differential pressure across the wetted filter cartridge did not exceed300 mbar (4.35 psi).

Immediately after each one-hour steam cycle had finished, dry compressed air was flushedacross the upstream side of the filter cartridge surface for 30 minutes in order to replace thesteam and cool the assembly. The cartridges were then flushed with water prior to ForwardFlow integrity testing between steaming cycles and also prior to starting the next steam cycle.

This test sequence was repeated until each filter cartridge had been exposed to 10 one-hoursteam cycles. The filters were Forward Flow integrity tested after steam cycle 1, cycle 2, cycle 3, cycle 4, cycle 5, cycle 8, and cycle 10.

In-situ Steaming at 135 °C (275 °F) Under Water Wet Steaming ConditionsSupor EX grade ECV filters part number AB1UECV7PH4 were used for the tests. Filter manufacturing and sampling considered possible variation in the filter manufacturing conditions.

Twenty four (24) filter cartridges were flushed with DI water for 10 minutes and then ForwardFlow integrity tested using an air test pressure of 2760 mbar (40 psi). The wet filter cartridgeswere then subjected to a one-hour in-situ steam cycle at 135 °C (275 °F).

During the initial stages of the steam cycles, the wet filter membrane caused the differentialpressure to increase across the filter cartridge as steam was introduced. The steam inlet valvewas controlled so that the differential pressure across the wetted filter cartridge did not exceed300 mbar (4.35 psi).

Immediately after each one-hour steam cycle had finished, dry compressed air was flushedacross the upstream side of the filter cartridge surface for 30 minutes in order to replace thesteam and cool the assembly. The cartridges were then flushed with water prior to ForwardFlow integrity testing between steaming cycles and also prior to starting the next steam cycle.

This test sequence was repeated until each filter cartridge had been exposed to 3 one-hoursteam cycles. The filters were Forward Flow integrity tested after steam cycle 1, cycle 2, and cycle 3.


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Autoclaving at 125 °C (257 °F) Under Water Wet Autoclave ConditionsSupor EX grade ECV filters part number AB1UECV7PH4 were used for the tests. Filter manufacturing and sampling considered possible variation in the filter manufacturing conditions.

Twelve (12) filter cartridges were flushed with DI water for 10 minutes and then Forward Flowintegrity tested using an air test pressure of 2760 mbar (40 psi). The wet filter cartridges werethen subjected to five (5) autoclave cycles at 125 °C (257 °F) (slow exhaust). After the autoclavehas cooled down to ambient temperature, the filter cartridge was removed from the autoclave,flushed with DI water for 10 minutes and then Forward Flow integrity tested using an air testpressure of 2760 mbar (40 psi). This test sequence was repeated so that each filter cartridgehad been exposed to 10 autoclave cycles.

4.3 Results

In-situ Steaming at 125 °C (257 °F) Under Water Wet Steaming ConditionsThe Forward Flow integrity test results for Supor EX grade ECV filter cartridges (part numberAB1UECV7PH4) before and after exposure to one-hour in-situ steam cycles are shown in Table 4.1. All of the filter cartridges retained integrity following exposure to ten (10) one-hourcycles at 125 °C (275 °F).

Table 4.1Effects of Wet In-Situ Steam Exposure at 125 °C (257 °F) on Filter Integrity for Supor EX Grade ECV AB1UECV7PH4 Filter Cartridges

* Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C (68 °F ± 9 °F),maximum allowable limit value 21.0 mL/min.

Forward Flow* (mL/min) test results before and after exposure to 10 in-situ steam cycles at 125 °C (257 °F):

Pall CartridgeSerial Number

FF (mL/min)pre steaming

FF (mL/min)post steaming

IP5325001 15.1 12.2

IP5325002 15.8 14.4

IP5325014 16.7 13.8

IP5325019 14.4 13.4

IP5325031 14.9 13.2

IP5325035 13.9 16.8

IP5325039 14.0 14.8

IP5325048 15.8 13.3

IP5325060 14.8 11.8

IP5325067 15.4 13.0

IP5325073 15.2 12.1

IP5325090 15.1 12.0

IP5325112 16.1 18.9

IP5325124 15.9 15.7

IP5325134 Not Tested 14.6

IP5325137 16.6 12.6

IP5325146 18.5 16.4

IP5325153 15.0 13.3

IP5325154 15.2 13.2

IP5325167 16.1 13.3

IP5325173 15.2 13.1

IP5325178 16.2 14.2

IP5325183 17.4 15.6

IP5325187 16.2 14.4

In-situ Steaming at 135 °C (275 °F) Under Water Wet Steaming ConditionsThe Forward Flow integrity test results for Supor EX grade ECV filter cartridges (part numberAB1UECV7PH4) before and after exposure to one-hour in-situ steam cycles are shown in Table 4.2. All of the filter cartridges retained integrity following exposure to three (3) one-hourcycles at 135 °C (275 °F).

Table 4.2Effects of Wet In-Situ Steam Exposure at 135 °C (275 °F) on Filter Integrity for Supor EX GradeECV AB1UECV7PH4 Filter Cartridges




Forward Flow* (mL/min) test results before and after exposure to 3 in-situ steam cycles at 135 °C (275 °F):FF (mL/min)pre steaming

FF (mL/min)post steaming

IR1311007 17.5 12.4IR1311008 15.8 12.0IR1311009 12.3 9.29IR1311012 16.7 12.1IR1311032 16.1 12.2IR1311035 15.3 12.6IR1311056 17.0 12.7IR1311070 16.9 12.3IR1311087 16.9 14.7IR1311094 16.6 12.1IR1311106 16.9 13.8IR1311116 16.4 15.1IR1311119 16.6 15.1IR1311131 16.3 12.8IR1311140 17.6 13.6IR1311167 14.3 13.6IR1311180 17.1 14.3IR1311185 15.6 11.1IR1311186 17.3 14.5IR1311196 15.7 12.5IR1311203 16.1 12.7IR1311222 15.4 13.4IR1311225 17.0 13.4IR1311234 15.7 12.1

16

Autoclaving at 125 °C (257 °F) Under Water Wet Autoclave ConditionsThe Forward Flow integrity test results for Supor EX grade ECV filter cartridges (part numberAB1UECV7PH4) before and after exposure to one-hour autoclave cycles are shown in Table 4.3. All of the filter cartridges retained integrity following exposure to ten (10) one-hourcycles at 125 °C (257 °F).

Table 4.3Effects of Wet Autoclave Exposure at 125 °C (257 °F) on Filter Integrity for Supor EX Grade ECVAB1UECV7PH4 Filter Cartridges for Integrity Testing


4.4 ConclusionsSupor EX grade ECV filter cartridges have been demonstrated to be capable of withstandingmultiple in-situ steam and autoclave sterilization cycles, while water wet prior to steaming. The filter cartridges will fully wet for integrity testing both before and after exposure to wet in-situ steam cycles.

The data presented in this section support the following product claims for in-situ steaming andautoclaving of 254 mm (10 inch) Supor EX grade ECV filter cartridges in AB style:

The data also support the autoclave resistance of Supor EX grade ECV filters in Kleenpak Nova configuration (G-grade), as they incorporate 254 mm (10 inch) Supor EX grade ECV filter cartridges.

The autoclave resistance of the Kleenpak Nova capsules has been investigated separately and is documented in the Pall document USTR 2099 “Validation Guide for Pall ‘Kleenpak’ Nova Filter Capsules”. The product claim for autoclave resistance of Kleenpak Nova capsules is three (3) autoclave cycles at 125 °C (257 °F).

Forward Flow* (mL/min) test results before and after exposure to 10 autoclave cycles at 125 °C (257 °F):


FF (mL/min)pre autoclaving

FF (mL/min)post autoclaving

IP5325015 15.3 11.5IP5325027 14.4 12.4IP5325029 13.9 12.5IP5325058 14.0 12.3IP5325070 13.7 10.2IP5325087 13.2 10.1IP5325158 15.7 13.7IP5325161 15.0 14.1IP5325169 14.5 12.0IP5325174 14.0 12.6IP5325189 16.8 12.4IP5325195 15.6 14.3

Filter Part Number Steaming Conditions Maximum Steam Life ClaimAB1UECV7PH4 In-situ steam cycles at


AB1UECV7PH4 In-situ steam cycles at135 °C (275 °F)

1 one-hour cycle

AB1UECV7PH4 Autoclave cycles at125 °C (257 °F)

5 one-hour cycle

The following product claim for autoclaving is therefore applicable to 254 mm (10 inch) Supor EX grade ECV filter cartridges in Kleenpak Nova G-grade configuration:

*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).

The above claims are supported by data with a 100 % safety margin.

5. Determination of Water Flow Characteristics

5.1 IntroductionThe aim of these tests was to determine the typical differential pressure across Supor EX gradeECV filter cartridges at set water flow rates.

5.2 Summary of MethodsThe tests were performed on twenty four (24) Supor EX grade ECV filter cartridges part numberAB1UECV7PH4. Filter manufacturing and sampling considered possible variation in the filtermanufacturing conditions. The filters represent four (4) different sub-batches with respect to the combination of different membrane rolls used in the manufacture of these sub-batches.

Pre-filtered DI water was pumped through the filters in the normal flow (‘out to in’) direction.Pressure readings from transducers on the upstream and downstream sides of the testassembly were monitored to calculate the differential pressure at set water flow rates.

The results were corrected for a standard temperature of 20 °C (68 °F).

5.3 ResultsFigure 5.1 shows the clean water flow rates of the twenty four (24) Supor EX grade ECV filtercartridges, part number AB1UECV7PH4, that were tested.

Figure 5.1Water Flow/Differential Pressure Values of Supor EX Grade ECV Filter Cartridges, Part Number AB1UECV7PH4

5.4 ConclusionsWater flow rates at set differential pressures have been determined. The results support that the typical clean water flow rate for a 254 mm (10 inch) Supor EX grade ECV filter cartridge(part number AB1UECV7PH4) at 100 mbar (1.45 psi) pressure drop is 17 L/min at 20 °C (68 °F). These data can be used to assist users in sizing filter systems employing Supor EX grade ECV filter cartridges.


Filter Part Number Steaming Conditions Maximum Steam Life ClaimN*UECVP#G Autoclave cycles at


Flow (L/min)

Diff

eren

tial p

ress

ure

at 2

0 ˚C

(mb

ar)

100

0

IP532500IP532500IP532501IP532501IP532503IP532503IP532503IP532504IP532506IP532506IP532507IP532509IP532511IP532512IP532513IP532513IP532514IP532515IP532515IP532516IP532517IP532517IP532518IP532518

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

18

6. Determination of Water Flow Characteristics for Other Styles of Supor EX Grade ECV Filters

6.1 IntroductionThe aim of these tests was to determine the typical differential pressure across other styles ofSupor EX grade ECV filter cartridges at set water flow rates. Table 6.1 shows the additionalstyles of Supor EX grade ECV filters that were tested.

Table 6.1Styles of Supor EX Grade ECV Filters Tested for Water Flow Characteristic

*S-Grade: Pre-sterilized by Gamma irradiation.

6.2 Summary of MethodsThe tests were performed on twelve (12) Supor EX grade ECV filters from three (3) differentproduction batches of each filter style, part numbers NP6UECVP1G and NP6UECVP1S. Pre-filtered DI water was pumped through the filters in the normal flow (‘out to in’) direction.Pressure readings from transducers on the upstream and downstream sides of the testassembly were monitored to calculate the differential pressure at set water flow rates.

The results were corrected for a standard temperature of 20 °C (68 °F).

6.3 ResultsFigure 6.1 shows the clean water flow rates of the twelve (12) Supor EX grade ECV filters, part number NP6UECVP1G that were tested. Figure 6.2 shows the clean water flow rates of the twelve (12) Supor EX grade ECV filters, part number NP6UECVP1S (i.e. after gammasterilization), that were tested.

Figure 6.1Water Flow/Differential Pressure Values of Kleenpak Nova Capsules with Supor EX Grade ECV Filters, Part Number NP6UECVP1G

Part Number Test ConditionNP6UECVP1G Out-of-BoxNP6UECVP1S* Out-of-Box

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24Flow (L/min)

Diff

eren

tial p

ress

ure

at 2

0 ˚C

(mb

ar)

0

100

IR49316958

IR49316958

IR49316958

IR49316958

IR49326960

IR49326961

IR49326960

IR49326960

IS05347186

IS05347186

IS05347186

IS05347186

Figure 6.2Water Flow/Differential Pressure Values of Kleenpak Nova Capsules with Supor EX Grade ECV Filters, Part Number NP6UECVP1S

6.4 ConclusionsWater flow rates at set differential pressures have been determined. The results support that the typical clean water flow rate for a 254 mm (10 inch) Supor EX grade ECV filter cartridge in AB style (part number AB1UECV7PH4) at 100 mbar (1.45 psi) pressure drop, which is 17 L/min at 20 °C (68 °F), is also applicable to the 254 mm (10 inch) Supor EX grade ECVfilters in Kleenpak Nova capsules in G and in S version, part numbers N*6UECV#PG andN*6UECV#PS. These data can thus be used to assist users in sizing filter systems employing 254 mm (10 inch) Supor EX grade ECV filters cartridges in any style.

(*T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).

7. Extractables Testing Using Water

7.1 IntroductionThe aim of this series of tests was to quantify and characterize the material that can beextracted from Supor EX grade ECV filter cartridges using water.

7.2 Summary of MethodsForty four (44) Supor EX grade ECV filter cartridges in AB style (part number AB1UECV7PH4)from five filter batches were used for the tests.

Preparation of Filter SamplesPrior to the extraction tests the Supor EX grade ECV filter samples were autoclaved in order tomaximize the quantity of any extractable material present. The filter cartridges were wrapped in aluminum foil and autoclaved for one hour at 125 °C ± 5 °C (257 °F ± 9 °F), using a slowexhaust cycle. Visible droplets of water remaining on the filter cartridges were allowed toevaporate at room temperature before the extraction was performed.

Extraction Procedure for Filter Cartridges and Determination of Non-volatile Residue (NVR)Dynamic extraction tests were performed in a known volume of water at ambient temperature.The test filters were immersed in the extraction fluid in a clean measuring cylinder, as shown inFigure 7.1. For twenty four (24) hours the filter was gently moved up and down. This movementcreated flow through the filter membrane as a result of the pressure head that was createdeach time the element was partially lifted out of the liquid.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24Flow (L/min)

Diff

eren

tial p

ress

ure

at 2

0 ˚C

(mb

ar)

0

100

IR49316959

IR49316959

IR49316959

IR49316960

IR49326961

IR49326962

IR49326962

IR49326962

IS05347186

IS05347186

IS05347187

IS05347188

20

Some filter cartridges were submitted to a second (consecutive) dynamic extraction cycle under the same extraction conditions as described above. Blank samples were determined as appropriate for method and result controls.

Following the extraction period, a measured volume of the extraction liquid was evaporated todryness and the non-volatile residue (NVR) was determined gravimetrically. A correction wasmade to the NVR value to account for the total extraction volume used.

Analysis by Fourier Transform Infra Red Spectroscopy (FTIR) The dry NVR of some filter cartridges was analyzed by Fourier Transform Infra RedSpectroscopy (FTIR) to provide information on the nature of its organic compounds. The analysis included first and also second (consecutive) extracts.

Figure 7.1

Filter Extraction Apparatus

Motor witheccentric rotor

Filter cartridgein measuringcylinder filled withextraction fluid

Stainless steelweight

7.3 Results of NVR and FTIRTable 7.1 shows the levels of aqueous extractables obtained from the forty four (44) Supor EXgrade ECV filter cartridges, part number AB1UECV7PH, that were tested. The values in the first extraction ranged from 4.8 mg to 139.9 mg and from 1.0 mg to 19.1 mg in the second(consecutive) extraction.

Table 7.1Non-volatile Aqueous Extractables Obtained Using Supor EX Grade ECV Filter Cartridges After Autoclaving at 125 °C ± 5 °C (257 °F ± 9 °F) (24 Hours Extraction Time at Ambient Temperature)


Pall Cartridge Serial Number NVR (mg) 1st Extraction NVR (mg) 2nd ExtractionIP5325003 37.9 9.0IP5325017 26.7IP5325046 26.1IP5325053 26.1IP5325069 28.4IP5325093 50.7IP5325105 32.0 – IR spectrum 7.6 – IR spectrumIP5325125 13.5IP5325144 53.7IP5325149 47.6 10.0IP5325176 26.9IP5325197 14.8IR1311016 7.6IR1311143 13.2 4.7IR1311153 7.9IR1311175 8.2IR4931010 65.9IR4931014 10.8IR4931017 50.2IR4931040 57.2IR4931058 13.3IR4931075 42.1 10.2IR4932016 12.4IR4932042 78.7 19.1IR4932049 61.9IR4932078 108.4IR4932103 8.1IR4932108 137.9IR8002011 121.5IR8002027 20.0 3.7IR8002030 92.7IR8002035 39.9 8IR8002042 36.2 8.1IR8002046 10.0IR8002051 6.9IR8002059 12.0 2.6IR8002063 47.1IR8002082 4.8IR8002099 12.8 2IR8002106 18.1 3.1IR8002110 137.1IR8002118 78.2IR8002122 8.8 1.0IR8002126 18.0 3.9

22

Typical infrared spectra of the aqueous NVRs from Supor EX grade ECV filter cartridges (part number AB1UECV7PH4) are shown in Figure 7.2 and Figure 7.3. Figure 7.2 shows theInfrared spectrum of the NVR from a first extraction of a filter cartridge. Figure 7.3 shows theinfrared spectrum of the NVR from the second (consecutive) extraction of that cartridge.

Figure 7.2Typical Infra Red Spectrum of the Aqueous NVR from Supor EX Grade ECV Filter Cartridgesfrom the First Extraction

AB1UECV7PH4 Serial Number IP5325105 Infrared Spectrum of NVR from 1st Extraction

Figure 7.3Typical Infra Red Spectrum of the Aqueous NVR from Supor EX Grade ECV Filter Cartridges of the Second (Consecutive) Extraction

AB1UECV7PH4 Serial Number IP5325105 Infrared Spectrum of NVR from 2nd Extraction

EU-PA-000791 B1.14000 3500 3000 2500 2000 1750 1500 1250 1000 750

1/cm

100

%T

90

80

70

60

50

40

3325

.28

2870

.08

1724

.36

1450

.47

1350

.17

1246

.0212

69.1

6

1097

.50

1033

.85

997.

2094

7.05

860.

25 746.

45

30

4000 3500 3000 2500 2000 1750 1500 1250 1000 7501/cm

100

%T

90

80

70

60

50

40

3267

.41

2868

.15

1724

.36

1598

.99

1450

.47

1246

.0213

50.1

7

1101

.35

1033

.85

842.

89

947.

0586

0.25

717.

52

30

EU-PA-000791 B1.2

7.4 ConclusionsThe typical amount of non-volatile residue (NVR) extracted from Supor EX grade ECV filtercartridges in AB style has been determined using water as the extraction fluid. For the 254 mm(10 inch) filter cartridges tested (part number AB1UECV7PH4) the aqueous extractable valueswere 4.8 mg -139.9 mg per cartridge in the first extraction but were always much reduced inthe second (consecutive) extraction (1.0 mg - 19.1 mg per cartridge), demonstrating depletionof the extractables. The data justify the following product claim for Supor EX grade ECV filtercartridges in AB style, part number AB1UECV7PH4: NVR < 150 mg.

The FTIR spectra of all extracts indicate the presence of compounds typical for these materialsof construction, i.e. the copolymer used to render the polyethersulfone membranes hydrophilic,and oligomers associated with polypropylene.

Actual service will impose different conditions, such as different steaming conditions,exposure times, temperature, liquid type, etc. Evaluation under process conditions is therefore also recommended.

8. Extractables Testing of Other Supor EX Grade ECV Filters Using Water

8.1 IntroductionThe aim of this series of tests was to quantify and characterize the material that can beextracted from Supor EX grade ECV filters of other styles using water. Table 8.1 shows the filters that have been tested:

Table 8.1Styles of Supor EX Grade ECV Filters Tested for Aqueous Extractables

8.2 Summary of MethodsSix (6) Supor EX grade ECV filters from three (3) different batches of the filter styles to beinvestigated (part numbers NP6UECVP1G and NP6UECVP1S) were used for the tests.

Preparation of Filter SamplesPrior to the extraction test the filter samples of part number NP6UECVP1G were autoclaved in order to maximize the quantity of any extractable material present. The filter samples of part number NP6UECVP1S are supplied pre-sterilized by gamma irradiation and must not be autoclaved prior to use, and were thus used out-of-box, i.e. after gamma-sterilization. The filter samples for autoclaving were wrapped in aluminum foil and autoclaved for one hour at 125 °C ± 5 °C (257 °F ± 9 °F), using a slow exhaust cycle.

Extraction Procedure for Filter Cartridges and Determination of Non-volatile Residue (NVR)The extraction tests were performed in a recirculation mode with a known volume of water atambient temperature using a pump. This method is routinely used at Pall for the extraction ofencapsulated filters. Recirculation was performed for twenty four (24) hours.

Blank samples were determined as appropriate for method and result controls.

Following the extraction period, a measured volume of the extraction liquid was evaporated todryness and the non-volatile residue (NVR) was determined gravimetrically. A correction wasmade to the NVR value to account for the total extraction volume used.


Part Number Test ConditionNP6UECVP1G After 1 autoclave cycle (125 °C, 60 min, 257 °F ± 9 °F)NP6UECVP1S Gamma-sterilized (irradiation dose: 50 ± 5 kGy)

24

Analysis by Fourier Transform Infra Red Spectroscopy (FTIR) The dry NVR of some filter cartridges was analyzed by Fourier Transform Infra RedSpectroscopy (FTIR) to provide information on the nature of its organic compounds.

8.3 Results of NVR and FTIRTable 8.2 shows the levels of aqueous extractables obtained from the six (6) Kleenpak Novacapsules with Supor EX grade ECV filters part number NP6UECVP1G that were tested afterone (1) cycle of autoclaving at 125 °C ± 5 °C (257 °F ± 9 °F) without pre-flushing. The valuesranged from 48.5 mg to 118.9 mg.

Table 8.2Non-volatile Aqueous Extractables Obtained Using Supor EX Grade ECV Filters Part Number NP6UECVP1G After Autoclaving at 125 °C ± 5 °C (257 °F ± 9 °F) (24 Hours Extraction Time at Ambient Temperature)

Table 8.3 shows the levels of aqueous extractables obtained from the six (6) Kleenpak Novacapsules with Supor EX grade ECV filters part number NP6UECVP1S that were tested after out-of-box (i.e. after gamma sterilization at a irradiation dose of 50 ± 5 kGy) without pre-flushing. The values ranged from 11.5 mg to 15.2 mg.

Table 8.3Non-volatile Aqueous Extractables Obtained Using Supor EX Grade ECV FiltersPart Number NP6UECVP1S After Gamma Sterilization (Irradiation Dose: 50 ± 5 kGy)(24 Hours Extraction Time at Ambient Temperature)

Typical infrared spectra of the aqueous NVRs from Kleenpak Nova capsules with Supor EXgrade ECV filters (part number NP6UECVP1G and NP6UECVP1S) are shown in Figure 8.1 and Figure 8.2, respectively.

Pall Cartridge Serial Number NVR (mg)IR493169584 48.5IR493169580 56.2IR493269606 79.9IR493269611 89.3IS053471859 118.9IS053471861 89.9

Pall Cartridge Serial Number NVR (mg)IR493169595 14.6IR493169589 15.1IR493269617 14.1IR493269615 13.3IS053471869 15.2IS053471874 11.5

Figure 8.1Typical Infra Red Spectrum of the Aqueous NVR from Kleenpak Nova Capsules with Supor EX Grade ECV Filters, Part Number NP6UECVP1G After Autoclaving NP6UECVP1G Serial Number IR493169580 Infrared Spectrum of NVR

Figure 8.2Typical Infra Red Spectrum of the Aqueous NVR from Kleenpak Nova Capsules with Supor EX Grade ECV Filters, Part Number NP6UECVP1S After Gamma SterilizationNP6UECVP1S Serial Number IR4932024 Infrared Spectrum of NVR


4000 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 8001/cm

60%T

55

50

45

40

35

30

25

3296

.35

2906

.73

2875

.86

1948

.10

1724

.36

1450

.47

1629

.85

1273

.02

1247

.94

1352

.10

1390

.68

950.

91

20

2140

.99

2125

.56

1099

.43

846.

75

LIR EU-PA-001041;residue from aqueous extract ex capsule SN IR493169580.

4500 4000 3500 3000 2500 2000 1750 1500 1250 1000 751/cmEU-PA-001042 SAMPLE C

97.5%T

90

82.5

75

67.5

60

52.5

45

3302

.13

2914

.44

2873

.94

1604

.77

1722

.43

1319

.31 12

47.9

4

1425

.40

945.

12

1085

.92

806.

25

26

8.4 ConclusionsThe typical amount of non-volatile residues (NVR) extracted from other Supor EX grade ECVfilters has been determined using water as the extraction fluid. For the 254 mm (10 inch) filtercartridges tested in Kleenpak Nova capsules after autoclaving (part number NP6UECVP1G) the aqueous extractable values ranged from 48.5 mg to 118.9 mg. For the 254 mm (10 inch)filter cartridges tested in Kleenpak Nova capsules after gamma sterilization (part numberNP6UECVP1S) the aqueous extractable values ranged from 15.2 mg to 11.5 mg. The datajustify that the product claim for Supor EX grade ECV filter cartridges in AB1 style, part numberAB1UECV7PH4: NVR < 150 mg is also applied to 254 mm (10 inch) filters in Kleenpak Novacapsules in G and S-grade.

The FTIR spectra of the all extracts obtained from NP6UECVP1G filters after autoclavingindicate the presence of compounds typical for these materials of construction, i.e. thecopolymer used to render the polyethersulfone membranes hydrophilic, and oligomersassociated with polypropylene. The presence of some residual water from the extractionprocess is also indicated.

The FTIR spectra of the all extracts obtained from NP6UECVP1S filters after gamma sterilizationindicate the presence of compounds typical for these materials of construction, i.e. the copolymerused to render the polyethersulfone membranes hydrophilic. Oligomers associated with poly -propylene were not indicated with this test.

Actual service will impose different conditions, such as different steaming conditions, exposure times, temperature, liquid type, etc. Evaluation under process conditions is therefore also recommended.

9. Biological Safety Tests on the Materials of Construction

9.1 IntroductionThe aim of this study was to evaluate the biological suitability of the materials of construction of Supor EX grade ECV filter cartridges in AB style and in Kleenpak Nova capsule filterconfiguration. The materials of construction of the filters are as follows:

Table 9.1Materials of Construction for Supor EX Grade ECV Filters in AB style

Membranes Upstream layer: Supor asymmetric hydrophilic polyethersulfone (PES) membraneDownstream layer: Supor symmetric hydrophilic polyethersulfone (PES) membrane

Membrane support and drainage layers PolypropyleneCore and end caps PolypropyleneAdapter Polypropylene with internal reinforcing ringFilter cage Polypropylene with titanium dioxideO-rings Silicone elastomer for ‘H4’ option

Table 9.2Materials of Construction for Supor EX Grade ECV Filters in Kleenpak Nova Capsules

9.2 Summary of TestsThe tests on the respective material of construction were performed in accordance with theBiological Reactivity Tests (in vivo) for Class VI Plastics (121 °C) as described in the currentUnited States Pharmacopeia (USP).

The testing procedures described in the United States Pharmacopeia include:

• Injection of extracts of plastic materials

• Implantation of the solid material into animal tissue

The four extracting media listed in the United States Pharmacopeia simulate parenteralsolutions and body fluids. These include:

• Sodium Chloride Injection

• 1 in 20 Solution of Alcohol in Sodium Chloride Injection

• Polyethylene Glycol 400

• Vegetable Oil (sesame or cottonseed oil)

The United States Pharmacopeia states that extracts may be prepared at one of three standardconditions: 50 °C (122 °F) for 72 hours, 70 °C (158 °F) for 24 hours or 121 °C (250 °F) for 1 hour. The most stringent condition not resulting in physical changes in the plastic isrecommended, therefore the filter materials were extracted at 121 °C (250 °F).

Acute Systemic Injection TestsAn Acute Systemic Injection Test was performed to evaluate the potential of a single injection of an extract to produce systemic toxicity. Sodium Chloride Injection and 1 in 20 Solution ofAlcohol in Sodium Chloride Injection were injected intravenously. Vegetable oil extract andPolyethylene Glycol 400 extract were injected intraperitoneally.

Intracutaneous TestsAn Intracutaneous Test was performed to evaluate the potential of a single injection of an extractto produce tissue irritation. All four of the extracts listed above were used for these tests.

Implantation TestsImplantation tests were also performed, in order to subject the materials of construction to themost stringent conditions included in the United States Pharmacopoeia. Each of the materialsof the Supor EX filters grade ECV was implanted separately.


Membranes Upstream layer: Supor asymmetric hydrophilic polyethersulfone (PES) membraneDownstream layer: Supor symmetric hydrophilic polyethersulfone (PES) membrane

Membrane support and drainage layers PolypropyleneCore and end caps PolypropyleneAdapter Polypropylene with internal reinforcing ringFilter cage Polypropylene with titanium dioxideCapsule components Head: Polypropylene with titanium dioxide

Bowl: PolypropyleneEnd cap gasket Silicone elastomer (white)Weld strand Polypropylene blended with stainless steelValve and connector caps Polyvinylchloride

(Packaging – To be removed prior to product use)O-rings Silicone elastomer for ‘H4’ option

9.3 ResultsNo unacceptable biological response was observed in any of the tests performed and thereforethe materials used in Supor EX filter cartridges passed all of the tests specified.

9.4 ConclusionsThe materials used in Supor EX filters in AB style and in Kleenpak Nova capsule configurationmet the requirements of the United States Pharmacopoeia Biological Reactivity Tests (in vivo)for Class VI-121 °C plastics. The tests included the Systemic Injection test, the Intracutaneoustest and the Implantation test.

Copies of the test reports are available by contacting Pall Corporation.

Corporate HeadquartersPort Washington, NY, USA+1.800.717.7255 toll free (USA)+1.516.484.5400 [email protected] e-mail

European HeadquartersFribourg, Switzerland+41 (0)26 350 53 00 [email protected] e-mail

Asia-Pacific HeadquartersSingapore+65 6389 6500 [email protected] e-mail

International OfficesPall Corporation has offices and plants throughout the world in locations such as:Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India,Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand,Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden,Switzerland, Taiwan, Thailand, the United Kingdom, the United States, and Venezuela.Distributors in all major industrial areas of the world. To locate the Pall office or distributornearest you, visit www.pall.com/contact.

The information provided in this literature was reviewed for accuracy at the time ofpublication. Product data may be subject to change without notice. For currentinformation consult your local Pall distributor or contact Pall directly.

© 2012, Pall Corporation. Pall, , Supor, Kleenpak, and Palltronic are trademarks of Pall Corporation.® indicates a trademark registered in the USA and TM indicates a common law trademark. ENABLING A GREENER FUTURE and Filtration. Separation. Solution. are service marks of Pall Corporation.

6/12, PDF, GN12.5321 USTR 2838

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Supor® EX Grade ECV Filters,Supor® EX Grade ECV Filters · 2021. 1. 6. · Supor EX grade ECV filters have been designed as liquid sterilizing filters for use within the pharmaceutical