0.2 µm-rated Filter Cartridges and Filter Capsules with ...

USTR2611Validation Guide

Pall 0.2 µm-rated Filter Cartridges and Filter Capsules with Fluorodyne® II Grade DFL Membrane

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Table of Contents

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

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

1.2 Summary of Conclusions ........................................................................................................................6

1.2.1 Microbial Retention Validation Tests ................................................................................................6

1.2.2 Resistance to in situ Steam and Autoclave Conditions ..................................................................7

1.2.3 Determination of Water Flow Characteristics ..................................................................................8

1.2.4 Extractables Testing using Water ..................................................................................................8

1.2.5 Biological Reactivity Tests ..............................................................................................................9

1.2.6 Evaluation of Shelf Life (Pre-sterilized Capsules)..............................................................................9

2. Microbial Retention Validation Tests for 254 mm (10 in.) Fluorodyne II Grade DFL Filter Cartridges ...........................................................................................................................................9

2.1 Introduction..............................................................................................................................................9

2.1.1 The Forward Flow Integrity Test ....................................................................................................10

2.2 Summary of Methods ............................................................................................................................10

2.3 Results ..................................................................................................................................................11

2.4 Conclusions ..........................................................................................................................................12

3. Microbial Retention Validation Tests of Other Styles of Fluorodyne II Grade DFL Filters.....................13

3.1 Introduction............................................................................................................................................13


3.3 Results ..................................................................................................................................................14

3.4 Conclusions ..........................................................................................................................................21

4. Resistance of 254 mm (10 in.) Fluorodyne II Grade DFL Filter Cartridges to in situ Steam................21

4.1 Introduction............................................................................................................................................21


4.3 Results ..................................................................................................................................................22

4.4 Conclusions ..........................................................................................................................................23

5. Resistance of Fluorodyne II Grade DFL Filter Capsules to Autoclave Sterilization...............................24

5.1 Introduction............................................................................................................................................24


5.3 Results ..................................................................................................................................................24

5.4 Conclusions ..........................................................................................................................................26

6. Determination of Water Flow Characteristics ..........................................................................................27

6.1 Introduction............................................................................................................................................27


6.3 Results ..................................................................................................................................................27

6.4 Conclusions ..........................................................................................................................................32

7. Extractables Testing .................................................................................................................................33

7.1 Introduction............................................................................................................................................33


7.2.1 Preparation of Filter Samples ........................................................................................................33

7.2.2 Extraction Procedure for Filter Cartridges......................................................................................33

7.2.3 Extraction Procedure for Filter Capsules ......................................................................................34

7.3 Results ..................................................................................................................................................34

7.4 Conclusions ..........................................................................................................................................36

8. Biological Reactivity Tests on the Materials of Construction .................................................................36

8.1 Introduction............................................................................................................................................36


8.2.1 Acute Systemic Injection Tests......................................................................................................37

8.2.2 Intracutaneous Tests ....................................................................................................................37

8.2.3 Implantation Tests ........................................................................................................................37

8.3 Results ..................................................................................................................................................37

8.4 Conclusions ..........................................................................................................................................37

9. Evaluation of Shelf Life..............................................................................................................................38

9.1 Introduction............................................................................................................................................38


9.3 Results ..................................................................................................................................................38

9.3.1 Integrity of Packaging ..................................................................................................................38

9.3.2 Forward Flow Integrity Test and Bacterial Challenge Test..............................................................38

9.3.3 Burst Pressure Testing ..................................................................................................................40

9.4 Conclusions ..........................................................................................................................................40

10. Validation of Sterilization by Gamma Irradiation of Pall Pre-sterilized Filter Capsules .........................................................................................................................................41

10.1 Principles of Gamma Irradiation ..........................................................................................................41

10.2 Validation ............................................................................................................................................41

10.3 Dose Verification and Dose Auditing ..................................................................................................41

10.4 Dose Mapping ....................................................................................................................................41

10.5 Dosimeter Release..............................................................................................................................42

www.pall.com/biopharm 3

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1. Overview

1.1 IntroductionThis guide contains validation data applicable to 0.2 µm microbially rated Fluorodyne II gradeDFL filter cartridges and filter capsules. It consolidates data previously published in Pallpublications USTR1548 (Validation Guide for Pall 0.2 µm rated Fluorodyne II MembraneCartridges) and USTR2018 (Validation Guide for Pall Kleenpak™ Filter Capsules ['S' and 'G'option] with Fluorodyne II Membrane). It may be used in complement to Pall publications USTR1666 (Validation Guide for Novasip™ Filters) and USTR2099 (Validation Guide for Pall KleenpakNova Filter Capsules).

These filters have been designed as sterilizing-grade liquid filters. The removal rating of 0.2 µmis based on challenges with Brevundimonas diminuta (ATCC 19146). The filter cartridges arecomprised of two layers of Pall polyvinylidene fluoride (PVDF) filter membrane withpolypropylene support and drainage materials. The core, cage and end caps of the filters are allpolypropylene, and thermal bonding sealing technology is used throughout the construction.

Fluorodyne II grade DFL filter capsules with an ‘S’ designation in the part number are suppliedpre-sterilized. Following manufacture, sterilization is achieved by gamma irradiation using aminimum dose of 25 kGy (maximum dose 50 kGy). These conditions ensure a minimum SterilityAssurance Level of 10-6. The sterilization process is validated and routinely controlled incompliance with the following standards:

• ISO 11137-1:2006 ‘Sterilization of health care products - Radiation - Part 1 - Requirementsfor development, validation and routine control of a sterilization process for medical devices.

• ISO 11137-2:2006 ‘Sterilization of health care products - Radiation - Part 2 - Establishing thesterilization dose’.

• AAMI TIR 33:2005 ‘Sterilization of health care products- Radiation. Sustantiation of a selectedsterilization dose - Method VDmax.’.

Fluorodyne II grade DFL filter capsules with a ‘G’ designation in the part number may begamma irradiated by the user. The ‘G’ option products have identical structures to the ‘S’option capsules, and both are manufactured using the same gamma-tolerant hardware. The ‘G’option product is designed for gamma irradiation by the user, with doses up to 50 kGy.

This report summarizes the tests that were conducted to qualify the performance of FluorodyneII grade DFL filter cartridges and filter capsules under a range of standard test conditions.

The qualification program included:

• Microbial retention validation tests

• Correlation to Forward Flow integrity test limits

• Resistance to in situ steam and steam-autoclave conditions

• Determination of water flow characteristics

• Extractables testing using water and ethanol

• Biological reactivity tests

• Shelf life testing of pre-sterilized filter capsules

The performance parameters and part nomenclature for Fluorodyne II grade DFL filters aredescribed in Pall publication USD2562 (Fluorodyne II Filters).

The units of pressure quoted in this document are bar or millibar (mbar) and pounds force persquare inch (psi). The following formulae can be used to convert these units of pressure toPascals (Pa):

1 bar = 1000 mbar = 1 x 105 Pa

1 psi = 6.89476 x 103 Pa = 0.069 bar = 69.85 mbar


Configurations of Fluorodyne II Grade DFL Filter Cartridges and Filter Capsules Supported bythis Validation Guide:

Part Number Filter Type Style Prefix Primary Use

Pleated membrane Junior Filter Cartridges SBF1DFL For sterile filtration of small volumes of fluid, filter cartridges, for (SBF Style) typically 2 L to 50 Luse in stainless steel filter housings

Junior Filter Cartridges MCY1110DFL For sterile filtration of fluids typically ranging from(MCY Style) MCY2220DFL 20 L to 500 L in volume

MCY4440DFL

Sealkleen Filter SLK7001DFLCartridges SLK7002DFL

Standard (‘AB-Style’) AB05DFL For sterile filtration of fluid, typically from 50 L to Filter Cartridges AB1DFL > 1000 L in volume. Filter assemblies forming

AB2DFL AB-style filter cartridges are also available AB3DFL encapsulated in polymeric filter housings, AB4DFL as Kleenpak Nova filter capsules

Pleated membrane Mini Kleenpak KA02DFL For filtration of small volumes of fluid, typically filter elements in Capsules 2 L to 50 L, for use during research, process polymeric capsule development or manufacturinghousing Kleenpak Capsules KA1DFL For filtration of fluids from 10 L to 500 L in

KA2DFL process development and manufacturingKA3DFLKA4DFL

Novasip Capsules C05DFL For filtration of fluids ranging from 10 L to 500 L. C3DFL Can be sterilized by in-line steaming (SIP).CL1DFL Novasip filters comprise a steam resistant (MCY1110) polymeric filter capsule containing Junior MCY CL2DFL style filter cartridge elements (element size (MCY2220) shown in brackets). Data for Junior MCY style CL3DFL filters in this guide can be used to support the (MCY4440) qualification of a corresponding Novasip

configuration and may be used in conjunction with data in Pall publication USTR1666 (Validation Guide for Novasip Filters)

Kleenpak Nova NP5LDFL For filtration of liquids in medium to large scale Capsules (AB05) GMP production environments (typically for

NP6DFL (AB1) filtration of 50 L to > 1000s L)NP7DFL (AB2) Kleenpak Nova filters comprise a polymeric NP8DFL (AB3) capsule containing filter assemblies used in NT6DFL (AB1) AB- style filter elements (AB element size shown NT7DFL (AB2) in brackets). Data for AB-style filters in this guide NT8DFL (AB3) can be used to support the qualification of a

corresponding Kleenpak Nova configuration andmay be used in conjunction with data in Pall publication USTR2099 (Validation Guide for Pall Kleenpak Nova Filter Capsules)

Process volumes are a guideline – please contact Pall for further assistance

The performance parameters, physical appearance, inlet and outlet adaptor / connection options and part numbersystem for the above formats of Fluorodyne II grade DFL filters are detailed in Pall publication USD2562 (FluorodyneII Filters), and can also be found at www.pall.com

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1.2 Summary of Conclusions

1.2.1 Microbial Retention Validation TestsFluorodyne II grade DFL filter cartridges and filter capsules were tested for bacterialretention of Brevundimonas diminuta (ATCC 19146) using bacterial challenge testsper modified ASTM F838-05 Standard Test Method, and in accordance with the U.S.FDA’s Guidance for Industry — Sterile Drug Products Produced By AsepticProcessing (September 2004).

The Forward Flow integrity test was shown to be a suitable non-destructive integritytest for Fluorodyne II grade DFL filter cartridges and filter capsules.

The test parameters have been set as follows for 254 mm (10 in.) AB-style filtercartridges and Kleenpak Nova filter capsules as indicated in Table 1.

Table 1Forward Flow Integrity Test Parameters for 254 mm (10 in.) Filter elements used in Fluorodyne II grade DFL Filter Cartridges, Part Number AB1DFL7PH4 and KleenpakNova Filter Capsules with Part Number Prefix NP6 and NT6

Test Parameters

Test pressure 2760 mbar (40 psi)

Wetting liquid Water

Temperature 20 °C ± 5 °C

Test gas Air

Maximum allowable Forward Flow limit1 12 mL/min1 During the test period the temperature of the filter assembly should not vary more than +1 °C.

Forward Flow integrity test values have also been set for other filter stylesincorporating Fluorodyne II grade DFL filter membrane, as shown in Table 2. Typical filters from production were subjected to Forward Flow integrity testing andbacterial challenge tests, demonstrating that the filters that pass the Forward Flowintegrity test also provide a sterile effluent.


Table 2Forward Flow Integrity Test Parameters for Other Styles of Fluorodyne II grade DFLFilter Cartridges and Capsules

Pall Filter Maximum AllowablePart Number1 Wetting Liquid2 Air Test Pressure Forward Flow Limit3

KA02DFLP* Water 2760 mbar (40 psi) 0.5 mL/min





NP5LDFLP* Water 2760 mbar (40 psi) 6.0 mL/min

C05DFLP* Water 2760 mbar (40 psi) 0.8 mL/min

C(L)1DFLP* Water 2760 mbar (40 psi) 1.6 mL/min


SBF1DFLP Water 2760 mbar (40 psi) 1.0 mL/min

MCY1110DFL Water 2760 mbar (40 psi) 0.8 mL/min


MCY4440DFLP Water 2760 mbar (40 psi) 3.4 mL/min

SLK7001DFLP Water 2760 mbar (40 psi) 2.0 mL/min


AB05DFL2P Water 2760 mbar (40 psi) 6.0 mL/min1 * denotes “blank”, S or G option- see Pall website for detailed part numbering information2 Temperature: 20 °C ± 5 °C3 During the test the temperature of the filter assembly should not vary more than +1 °C

1.2.2 Resistance to in situ Steam and Autoclave ConditionsFluorodyne II grade DFL filter cartridges and Novasip filter capsules have demonstratedthe ability to withstand multiple in situ steam and autoclave cycles, and otherFluorodyne II grade DFL filter capsules have demonstrated the ability to withstandmultiple autoclave cycles. Kleenpak Nova, Kleenpak and Mini Kleenpak capsules withFluorodyne II DFL membrane should not be subjected to steaming in situ.

The data presented in Table 3 of this guide supports the product claims for the in situ steaming of Fluorodyne II grade DFL filter cartridges and Novasip filter capsules.

The physical test conditions for in situ steaming of Fluorodyne II grade DFL filters can be considered as worst case for any sterilization process by steam and therefore include autoclave process conditions with the same temperature exposure and cycle times.

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Table 3Product Claims for in situ Steaming of Fluorodyne II grade DFL Filter Cartridges and Novasip Filter Capsules

Fluorodyne II grade Maximum RecommendedDFL Filter Styles Steaming Conditions Steam Life Claim1

“AB Style” Filter Cartridges in situ steam cycles at 125 °C 30 x 1 hour cyclesin situ steam cycles at 140 °C 10 x 1 hour cycles

Junior Filter Cartridges – in situ steam cycles at 125 °C 30 x 1 hour cyclesMCY Style and Novasip Filter in situ steam cycles at 140 °C 10 x 1 hour cyclesCapsules

Junior Filter Cartridges – in situ steam cycles at 125 °C 30 x 1 hour cyclesSealkleen and SBF Styles1 The above claims are supported by data that incorporates a safety margin.

Table 4Product Claims for Autoclave Sterilization of Fluorodyne II grade DFL Mini Kleenpak,Kleenpak, and Kleenpak Nova Filter Capsules

Maximum RecommendedPall Filter Part Number Sterilization Conditions Autoclave Life Claim

KA02DFLP*G Autoclaving at 125 °C 3 x 1 hour cycles

KA*DFLP* Autoclaving at 125 °C 30 x 1 hour cycles

KA*DFLP* Autoclaving at 140 °C 10 x 1 hour cycles

NP/T*DFLP* Autoclaving at 125 ºC 3 x 1 hour cycles1 The above claim is supported by data that incorporates a safety margin.

1.2.3 Determination of Water Flow CharacteristicsDifferential pressure measurements at set water flow rates have been determined fortypical Fluorodyne II grade DFL filters cartridges and capsules. These data can beused to assist users in sizing filter systems employing Fluorodyne II grade DFL filtercartridges and capsules. See Section 6 for details.

1.2.4 Extractables Testing using Water As the majority of applications for Fluorodyne II filters are with aqueous solutions, the typical amount of non-volatile residue (NVR) extracted from Fluorodyne II gradeDFL filter cartridges and capsules have been determined using water as theextraction fluid.

The data presented in this guide support the following product claims for aqueousextractables for Fluorodyne II grade DFL filter cartridges and capsules as shown inTable 5.

Table 5Product Claims for Aqueous Extractables from Fluorodyne II grade DFL Filter Cartridges and Filter Capsules

Typical Extractables in Water at 20 °CPall Filter Styles After 4 Hours of Extraction

“AB Style” filter cartridges < 5 mg per 10" / 254 mm filter element

Junior filter cartridges, Sealkleen, MCY and SBF styles, < 5 mgand Novasip filter capsules

Mini Kleenpak filter capsule - G option < 1 mg

All other Kleenpak filter capsule styles < 5 mg(includes “Blank”, G and S capsule options)

Actual service in pharmaceutical applications will impose different conditions, such as different steaming conditions, exposure times, temperature and liquid types.Evaluation under process conditions is therefore also recommended.

1.2.5 Biological Reactivity TestsAll of the materials used in Fluorodyne II grade DFL filter cartridges and capsulesmeet the requirements of the Biological Reactivity Tests (in vivo), listed in the currentrevision of the United States Pharmacopeia (USP) chapter <88> for Class VI-121 °Cplastics. The tests included the Systemic Injection test, the Intracutaneous test andthe Implantation test.

1.2.6 Evaluation of Shelf Life (Pre-sterilized Capsules)The data presented in this report demonstrate that pre-sterilized Fluorodyne II gradeDFL filter capsules retain their strength and expected performance after storage forup to 36 months, following irradiation at doses ranging between 25 – 35 kGy.

2. Microbial Retention Validation Tests for 254 mm (10 in.) Filter elements used inFluorodyne II grade DFL Filter Cartridges and Kleenpak Nova filter capsules

2.1 IntroductionThe FDA’s Guidance for Industry — Sterile Drug Products Produced by Aseptic Processing —Current Good Manufacturing Practice (2004) states:

“A sterilizing filter should be validated to reproducibly remove viable microorganisms from theprocess stream, producing a sterile effluent.”

The guideline also states:

“The microorganism Brevundimonas diminuta (ATCC 19146), when properly grown, harvestedand used, is a common challenge organism for 0.2 micrometer rated filters because of its smallsize (0.3 µm mean diameter).”

In accordance with the requirements of this guideline, liquid challenge tests usingBrevundimonas diminuta were performed with Fluorodyne II grade DFL filter cartridges 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 given product, process and filter, it isimportant to ensure that identical filters (e.g. of identical polymer construction and pore sizerating) are used in production runs... Integrity testing of the filter(s) can be performed prior toprocessing, and should be routinely performed post-use... Forward flow and bubble point tests,when appropriately employed, are two integrity tests that can be used. A production filter’sintegrity test specification should be consistent with the data generated during bacterialretention 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 integrity test was theintegrity test used during this study.1

1 Pall, David B., “Quality Control of Absolute Bacteria Removal Filters,” Bulletin of the Parenteral Drug Assoc., 1973.”


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2.1.1 The Forward Flow Integrity TestIn the Forward Flow integrity test, a filter is wetted with an appropriate test liquid anda pre-determined gas pressure is applied to the upstream side of the filter assembly.After a suitable stabilization period, the gas flow through the wetted membrane canbe measured on the upstream side, using sensitive flow measurement equipmentsuch as the Palltronic® Flowstar filter integrity test instrument (Figure 1). This gas flowis comprised of diffusion plus bulk flow through any unwetted pores.

Figure 1The Automated Integrity Test

The aim of this study was to demonstrate the microbial removal efficiency of typical Fluorodyne II grade DFL filter cartridges in liquid challenge tests usingBrevundimonas diminuta and to document the correlation of the integrity testparameters to the microbial removal efficiency.

2.2 Summary of MethodsTypical Fluorodyne II grade DFL filter cartridges, part number AB1DFL7PH4, membrane area0.55 m² (5.9 ft2), from a minimum of three separate manufacturing batches were subjected tostandard microbial challenge tests using an aqueous suspension of Brevundimonas diminuta.

Prior to the challenge tests the filters were installed in an appropriate housing, flushed withdeionized (DI) water at a flow rate of 8 L/min for 5 minutes, and then autoclaved at 121 °C for60 minutes. A Forward Flow integrity test was then performed using an air test pressure of2760 mbar (40 psi). The filter assembly was then aseptically connected to the pre-sterilizedchallenge apparatus, as shown in Figure 2.

An aqueous suspension of Brevundimonas diminuta was passed through the filter cartridge toachieve a challenge level of > 1 x 107 CFU/cm2 of effective filtration area.

During the challenge test the entire filter effluent was passed through a 0.2 µm-rated analysisdisc on the downstream side of the test filter assembly. The filter disc was incubated on agar.The disc was then examined to determine if any colonies had grown, indicating whether or notbacteria had passed through the test filter during the challenge. The titer reduction (TR) for eachfilter (Equation 1) was determined as follows:

Wetted filter(in housing)

Outlet open toatmosphericpressureUpstream

isolated

Calibrated pressureindicator upstream of

filter assembly

Regulatedcompressedgas supply

Palltronic Flowstar instrumentintegrity test

Equation 1Titer Reduction

TR = Total number of bacteria influent to the filterNumber 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 107)

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

Figure 2Microbial Challenge Apparatus

2.3 ResultsThe Forward Flow and Brevundimonas diminuta retention results are shown in Table 6. Thehigher of the two Forward Flow values (pre- and post-challenge) are presented and the data are arranged in order of increasing Forward Flow value.

All of the filter cartridges with Forward Flow values < 12 mL/min gave sterile effluent whenchallenged with > 1 x 107 CFU/cm2 of filtration area using Brevundimonas diminuta.

Table 6Results of Forward Flow Integrity Test and Brevundimonas diminuta Retention for Typical Fluorodyne II grade DFL Filter Cartridges, Part Number AB1DFL7PH4

Pall Cartridge Forward Flow1

Serial Number (mL/min) Sterile Effluent Titer Reduction

IW6080065 8.1 yes > 9.2 x 1010

IW9440064 8.6 yes > 1.2 x 1011

IW9440046 8.6 yes > 1.2 x 1011

IW9820021 8.7 yes > 1.0 x 1011


TestFilter

Analysis Membrane Filter

Drain

Pressure Vesselwith BacterialSuspension

Regulated Air Supply

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Table 6 ContinuedResults of Forward Flow Integrity Test and Brevundimonas diminuta Retention for Typical Fluorodyne II grade DFL Filter Cartridges, Part Number AB1DFL7PH4

Pall Cartridge Forward Flow1

Serial Number (mL/min) Sterile Effluent Titer Reduction

PILF331016 8.9 yes > 1.2 x 1011

PILF331025 8.9 yes > 1.2 x 1011

IW9440030 9.0 yes > 1.2 x 1011

IW6080086 9.0 yes > 9.2 x 1010

IW9820048 9.0 yes > 1.0 x 1011

IW9440112 9.0 yes > 1.2 x 1011

IW6080039 9.0 yes > 9.2 x 1010

IW9820038 9.0 yes > 1.0 x 1011

PILF331022 9.0 yes > 1.2 x 1011

IW6080045 9.1 yes > 9.2 x 1010

IW9820053 9.1 yes > 1.0 x 1011

IW6080021 9.2 yes > 9.2 x 1010

IW9820012 9.2 yes > 1.0 x 1011

IW9820017 9.2 yes > 1.0 x 1011

IW6080021 9.2 yes > 9.2 x 1010

IW6080019 9.3 yes > 9.2 x 1010

IW9440097 9.3 yes > 1.2 x 1011

PILF331024 9.3 yes > 1.2 x 1011

PILF331012 9.4 yes > 1.2 x 1011

IW9440051 10.6 yes > 1.2 x 1011

IY9640005 11.1 yes > 6.1 x 1010

IY6230048 11.8 yes > 5.8 x 1010

PILF331019 12.2 yes > 1.2 x 1011

IY7770003 13.2 no 1.5 x 1010

Recovery = 4 colonies

IW9440074 18.5 yes > 7.3 x 1010

IA0351139 34.1 no 4.0 x 109

Recovery = 24 colonies

IW9440066 57.0 yes > 7.1 x 1010

IY7380241 60.0 yes > 6.1 x 1010

IY7380248 75.0 no 7.2 x 106

Recovery = 8.48 x 103 colonies

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

2.4 ConclusionsBased on the results of this study, the Forward Flow integrity test has been demonstrated to be a suitable non-destructive integrity test for Fluorodyne II grade DFL filter cartridges. Integritytest parameters for Fluorodyne II grade DFL filter cartridges, part number AB1DFL7PH4, andKleenpak Nova filter capsules with the prefix NP6DFL or NT6DFL have been set as shown in Table 7.

Table 7Forward Flow Integrity Test Parameters for 254 mm (10 in.) Filter Elements used in Fluorodyne IIgrade DFL filter cartridges part number AB1DFL7PH4 and Kleenpak Nova filter capsules, partnumber prefix NP6DFL or NT6DFL

Test Parameters

Test pressure 2760 mbar (40 psi)

Wetting liquid Water

Temperature 20 °C ± 5°C

Test gas Air

Maximum allowable Forward Flow limit2 12 mL/min1 See Section 2.2 for test procedure.2 During the test period the temperature of the filter assembly should not vary more than +1 °C.

3. Microbial Retention Validation Tests of Other Styles of Fluorodyne II grade DFL Filters

3.1 IntroductionBased on the integrity test parameters for 254 mm (10 in.) Fluorodyne II grade DFL filtercartridges (Table 7), Forward Flow integrity test parameters were set for other filter stylesincorporating Fluorodyne II grade DFL filter media. The purpose of this series of tests was to perform Forward Flow integrity tests and bacterial challenge tests on typical filters fromproduction to demonstrate that filters passing the Forward Flow integrity test provided sterileeffluent during challenge tests.

3.2 Summary of MethodsForward Flow integrity test parameters were set for other filter styles incorporating Fluorodyne IIgrade DFL filter media as shown in Table 8.

Table 8Forward Flow Integrity Test Parameters for other styles of Fluorodyne II grade DFL Filter Cartridges and Filter Capsules

Pall Filter Maximum AllowablePart Number Wetting Liquid1 Air Test Pressure Forward Flow Limit2

KA02DFLP2G Water 2760 mbar (40 psi) 0.5 mL/min

KA1DFLP Water 2760 mbar (40 psi) 1.0 mL/min




NP5LDFLP* Water 2760 mbar (40 psi) 6.0 mL/min

C05DFLP* Water 2760 mbar (40 psi) 0.8 mL/min



SBF1DFLP Water 2760 mbar (40 psi) 1.0 mL/min



MCY4440DFLP Water 2760 mbar (40 psi) 3.4 mL/min



AB05DFL2P Water 2760 mbar (40 psi) 6.0 mL/min1 Temperature: 20 °C ± 5 °C2 During the test period the temperature of the filter assembly should not vary more than +1 °C.


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In order to validate the integrity test limit value, production samples of the respective filter styleswere subjected to Forward Flow integrity testing and liquid bacterial challenge testing usingBrevundimonas diminuta according to the principles of the procedures described in Section 2.When testing pre-sterilized (irradiated) filter capsules, the samples were aseptically connected tothe bacterial challenge apparatus and no pre-challenge Forward Flow integrity test or autoclavecycle was performed. A Forward Flow integrity test was conducted on completion of thechallenge test.

3.3 ResultsThe bacterial challenge and Forward Flow results for non-irradiated filter cartridges andcapsules (sterilized by autoclaving prior to bacterial challenge) are shown in Table 9. TheForward Flow values that are presented are the higher of the pre- and post microbial challengemeasurements.

The bacterial challenge and Forward Flow results for pre-sterilized (irradiated) filter capsules areshown in Table 10. The Forward Flow values that are presented are the post-microbialchallenge measurements.

All of the filters with Forward Flow values below the limit value provided a sterile effluent whenchallenged. In some cases filters with Forward Flow values above the recommended limit valuealso gave a sterile effluent when subjected to a liquid challenge test.

Table 9Results of Forward Flow Integrity Test and Brevundimonas diminuta Retention for Typical Non-Irradiated (Autoclaved) Fluorodyne II grade DFL Filter Cartridges and Filter Capsules

Pall Filter Pall Filter Forward Flow1

Part Number Serial Number (mL/min) Sterile Effluent Titer Reduction

KA02DFLP2G ID3416098 0.27 yes > 1.3 x 1010

ID4135078 0.28 yes > 1.3 x 1010

ID3416083 0.28 yes > 1.1 x 1010

ID3416032 0.29 yes > 1.1 x 1010

ID3416001 0.29 yes > 9.6 x 109

ID4135193 0.29 yes > 1.4 x 1010

ID4135080 0.30 yes > 1.0 x 1010

ID4135008 0.30 yes > 8.8 x 109

ID4135027 0.30 yes > 1.3 x 1010

ID4135173 0.30 yes > 1.3 x 1010

ID4135043 0.31 yes > 3.8 x 109

ID3416003 0.31 yes > 1.2 x 1010

ID3416037 0.31 yes > 1.0 x 1010

ID3416024 0.31 yes > 1.4 x 1010

ID4135199 0.32 yes > 9.0 x 109

ID3416095 0.32 yes > 1.1 x 1010

ID4135131 0.32 yes > 1.0 x 1010

ID4135084 0.33 yes > 1.2 x 1010

ID3416022 0.33 yes > 9.2 x 109

ID3416048 0.33 yes > 1.6 x 1010

ID3416056 0.33 yes > 1.4 x 1010

ID3416073 0.33 yes > 1.2 x 1010

ID4135129 0.34 yes > 7.5 x 109

ID4135047 0.34 yes > 1.3 x 1010

Table 9 ContinuedResults of Forward Flow Integrity Test and Brevundimonas diminuta Retention for Typical Non-Irradiated (Autoclaved) Fluorodyne II grade DFL Filter Cartridges and Filter Capsules



KA02DFLP2G ID3416014 0.34 yes > 1.3 x 1010

ID3416045 0.34 yes > 1.0 x 1010

ID3416088 0.34 yes > 1.2 x 1010

ID3416092 0.34 yes > 1.0 x 1010

ID3416059 0.35 yes > 1.1 x 1010

ID3416060 1.28 yes > 1.6 x 1010

KA1DFLP1 IC1095009 0.5 yes > 1.7 x 1010

IC1095066 0.5 yes > 1.3 x 1010

IC1095027 0.5 yes > 1.8 x 1010

IC1095045 0.5 yes > 2.3 x 1010

IC1095003 0.5 yes > 2.1 x 1010

IC1095013 0.6 yes > 2.3 x 1010

IY7210054 0.6 yes > 1.3 x 1010

IY7210022 0.7 yes > 1.3 x 1010

IY7210031 0.7 yes > 1.3 x 1010

IY7210037 0.7 yes > 1.3 x 1010

IY7210042 0.7 yes > 1.3 x 1010

IY7210028 0.8 yes > 1.3 x 1010

KA2DFLP1 IA0029029 1.2 yes > 2.0 x 1010

IA0029038 1.2 yes > 2.0 x 1010

IA0029040 1.3 yes > 2.0 x 1010

IA0029015 1.3 yes > 2.0 x 1010

IA0029011 1.4 yes > 2.0 x 1010

IY7190018 1.4 yes > 3.8 x 1010

IY7190002 1.5 yes > 3.8 x 1010

IY7190025 1.5 yes > 3.8 x 1010

IY7190049 1.5 yes > 3.8 x 1010

IY7190020 1.6 yes > 3.8 x 1010

IY7190044 1.6 yes > 3.8 x 1010

KA2DFLP2 IA1878013 1.0 yes > 2.9 x 1010

IA1878040 1.4 yes > 2.9 x 1010

IA1878053 1.4 yes > 2.9 x 1010

IA1878058 1.4 yes > 2.9 x 1010

IA1878009 1.4 yes > 2.9 x 1010

IA1878029 1.5 yes > 2.9 x 1010

KA2DFLP6 ID0342004 1.1 yes > 5.8 x 1010

ID0342050 1.1 yes > 5.7 x 1010

ID0342057 1.1 yes > 5.3 x 1010

ID0342045 1.0 yes > 5.8 x 1010


16




KA2DFLP6 ID0342046 1.0 yes > 4.4 x 1010

ID0342058 1.0 yes > 5.3 x 1010

KA3DFLP1 IA4029056 2.3 yes > 1.6 x 1010

IA4029011 2.5 yes > 1.6 x 1010

IA4029053 2.6 yes > 1.6 x 1010

IA4029002 2.8 yes > 1.6 x 1010

IA4029008 2.8 yes > 1.6 x 1010

IA4029033 2.8 yes > 1.6 x 1010

IA2466060 2.9 yes > 2.2 x 1010

IA2466086 2.9 yes > 2.2 x 1010

IA2466014 3.0 yes > 2.2 x 1010

IA2466045 3.1 yes > 2.2 x 1010

IA2466001 4.7 yes > 2.2 x 1010

IA2466084 4.8 yes > 2.2 x 1010

KA3DFLP6 IA3451052 2.5 yes > 4.1 x 1010

IA3451019 2.7 yes > 4.1 x 1010

IA3451060 2.8 yes > 4.1 x 1010

KA4DFLP1 IA6087016 4.8 yes > 1.1 x 1011

IA6087068 4.9 yes > 1.1 x 1011

IA6087021 5.0 yes > 1.1 x 1011

IA2467093 5.9 yes > 4.1 x 1010

IA6087067 6.0 yes > 1.1 x 1011

IA2467107 7.4 yes > 4.1 x 1010

IA2467028 7.6 yes > 4.1 x 1010

IA2467018 8.1 yes > 4.1 x 1010

IA2467029 8.0 yes > 4.1 x 1010

IA2467008 8.5 yes > 4.1 x 1010

IA6087077 28.5 yes > 1.1 x 1011

KA4DFLP6 IB2879066 5.2 yes > 1.1 x 1011

IB2879031 6.4 yes > 1.1 x 1011

IB2879049 6.7 yes > 1.1 x 1011

IB2879063 6.9 yes > 1.1 x 1011

IB2879075 8.1 yes > 1.1 x 1011

IB2879021 10.0 yes > 1.1 x 1011

NT6DFLP1G PB8790001 7.9 yes > 1.0 x 1011

PB8790004 8.4 yes > 1.1 x 1011

PB8790002 8.7 yes > 1.2 x 1011

PB8790003 8.9 yes > 1.2 x 1011

PB8790005 8.9 yes > 1.1 x 1011




SBF1DFLP IA1914016 0.5 yes > 6.2 x 109

IA1914089 0.6 yes > 6.2 x 109

IA1914033 0.6 yes > 6.2 x 109

IA1914095 0.6 yes > 6.2 x 109

IA1914009 0.7 yes > 6.2 x 109

IA1914044 1.3 yes > 6.2 x 109

MCY1110DFL IA4000004 0.6 yes > 3.9 x 1010

IA4000012 0.6 yes > 3.9 x 1010

IA4000013 0.6 yes > 3.9 x 1010

IA4000046 0.6 yes > 3.9 x 1010

IA1912051 0.6 yes > 1.0 x 1010

IA1912088 0.6 yes > 1.0 x 1010

IA1912097 0.6 yes > 1.0 x 1010

IA1912101 0.6 yes > 1.0 x 1010

IA1912078 0.8 yes > 1.0 x 1010

IA1912034 1.0 yes > 1.0 x 1010

IA4000021 1.3 yes > 3.9 x 1010

IA4000041 1.6 yes > 3.9 x 1010

MCY2220DFL IA4267143 1.2 yes > 8.9 x 109

IA4267190 1.2 yes > 8.9 x 109

IA4267239 1.2 yes > 8.9 x 109

IA4267003 1.3 yes > 8.9 x 109

IA4267046 1.3 yes > 8.9 x 109

IA4267004 1.4 yes > 8.9 x 109

MCY4440DFLP IA3449055 2.0 yes > 2.6 x 1011

IA3449024 2.1 yes > 2.6 x 1011

IA3449054 2.2 yes > 2.6 x 1011

IA3449046 2.4 yes > 2.6 x 1011

IA3449096 2.4 yes > 2.6 x 1011

IA3449097 2.6 yes > 2.6 x 1011

IA1913025 2.8 yes > 2.6 x 1010

IA1913088 2.9 yes > 2.6 x 1010

IA1913048 2.9 yes > 2.6 x 1010

IA1913009 2.9 yes > 2.6 x 1010

IA1913002 3.0 yes > 2.6 x 1010

SLK7001DFLP2 IL4284012 1.02 yes > 9.2 x 1010

IK6742096 1.07 yes > 8.6 x 1010

IM5523001 1.19 yes > 8.8 x 1010

IK2787050 1.25 yes > 7.0 x 1010

IM4820058 1.46 yes > 7.7 x 1010


18




SLK7001DFLP1 IM0624060 1.48 yes > 5.8 x 1010

IM2757042 1.48 yes > 5.1 x 1010

IK5696035 1.49 yes > 5.7 x 1010

IK6499040 1.54 yes > 7.0 x 1010

IK4794068 1.57 yes > 6.0 x 1010

IL9525084 1.60 yes > 5.4 x 1010

SLK7002DFLP2 IM8610033 2.31 yes > 8.4 x 1010

IM2615034 2.59 yes > 8.0 x 1010

IM4821076 2.67 yes > 5.5 x 1010

IM9300095 2.68 yes > 6.6 x 1010

IM6798062 2.68 yes > 6.2 x 1010

IM6945010 2.74 yes > 8.8 x 1010

IM0625046 2.74 yes > 7.3 x 1010

IM5304092 2.81 yes > 8.0 x 1010

IM3029016 2.89 yes > 5.1 x 1010

IM2759070 2.90 yes > 5.9 x 1010

IM0144090 2.92 yes > 7.5 x 1010

AB05DFL2P2 IL6286090 2.48 yes > 5.6 x 1010

IM0806014 2.65 yes > 6.8 x 1010

IM2996002 3.10 yes > 5.4 x 1010

IL8369094 3.38 yes > 6.9 x 1010

IM7537442 3.66 yes > 7.4 x 1010

IM5394015 3.98 yes > 3.5 x 1010

IM9308017 4.05 yes > 6.9 x 1010

IM2995085 4.08 yes > 5.1 x 1010

IL9506097 4.55 yes > 6.8 x 1010

IM1609558 4.58 yes > 7.0 x 1010

IM8281085 5.04 yes > 8.2 x 1010

1 Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C, maximum allowable limitvalues presented in Table 8.

2 Pre-challenge Forward Flow values are reported.

Table 10Results of Forward Flow and Brevundimonas diminuta Retention for Typical Fluorodyne II gradeDFL Filter Capsules pre-sterilized by gamma irradiation at no greater than 50 kGy

Pall Filter Pall Filter Forward Flow1 Sterile Titer Part Number Serial Number (mL/min) Effluent Reduction

KA02DFLP2S ID9543043 0.20 yes > 2.1 x 1010

ID9543020 0.24 yes > 6.5 x 109

ID9543050 0.27 yes > 1.7 x 109

ID9543025 0.28 yes > 8.6 x 109

ID9543044 0.28 yes > 8.6 x 109

ID9543009 0.29 yes > 8.0 x 109

ID9543018 0.29 yes > 1.0 x 1010

ID9543029 0.29 yes > 8.2 x 109

ID9543032 0.30 yes > 9.2 x 109

ID9543040 0.34 yes > 1.1 x 1010

ID9280052 0.01 yes > 9.6 x 109

ID9280048 0.21 yes > 1.0 x 1010

ID9280067 0.23 yes > 7.6 x 109

ID9280008 0.23 yes > 9.0 x 109

ID9280017 0.24 yes > 8.8 x 109

ID9280037 0.25 yes > 1.1 x 1010

ID9280040 0.25 yes > 7.8 x 109

ID9280064 0.25 yes > 1.1 x 1010

ID9280063 0.32 yes > 9.4 x 1010

ID8754053 0.17 yes > 1.1 x 1011

ID8754068 0.28 yes > 1.0 x 1011

ID8754022 0.28 yes > 8.8 x 1010

ID8754012 0.29 yes > 9.0 x 1010

ID8754061 0.33 yes > 7.8 x 1010

KA1DFLP1G IC9875004 0.4 yes > 4.0 x 1010

IC9875038 0.4 yes > 3.5 x 1010

IC9875143 0.4 yes > 4.0 x 1010

IC9875158 0.4 yes > 4.0 x 1010

IC9875009 0.5 yes > 4.1 x 1010

IC9875139 0.5 yes > 3.8 x 1010

KA2DFLP2S IC6350029 0.8 yes > 5.9 x 1010

IC6350030 0.9 yes > 5.6 x 1010

IC6350051 0.9 yes > 5.1 x 1010

IC6350146 0.9 yes > 5.1 x 1010

IC6350055 1.0 yes > 5.1 x 1010

IC6350075 1.1 yes > 9.5 x 1010

IC6564020 0.7 yes > 6.2 x 1010

IC6564064 0.7 yes > 6.6 x 1010

IC6564068 0.7 yes > 1.0 x 1011

IC6564102 0.7 yes > 1.0 x 1011


20

Table 10 ContinuedResults of Forward Flow and Brevundimonas diminuta Retention for Typical Fluorodyne II gradeDFL Filter Capsules pre-sterilized by gamma irradiation at no greater than 50 kGy


KA2DFLP2S IC6564011 0.8 yes > 6.6 x 1010

IC6564027 0.8 yes > 1.1 x 1011

IC4434025 0.7 yes > 1.6 x 1010

IC4434048 0.7 yes > 1.2 x 1010

IC4434027 0.8 yes > 2.4 x 1010

IC4434077 0.8 yes > 2.8 x 1010

IC4434116 0.8 yes > 1.0 x 1010

IC4434204 0.8 yes > 6.9 x 1010

IC0045055 0.6 yes > 1.8 x 1010

IC0045012 0.6 yes > 3.3 x 1010

IC0045032 0.8 yes > 8.7 x 109

IC0045022 0.8 yes > 1.4 x 1010

KA3DFLP6S IC3218089 1.9 yes > 3.2 x 1010

IC3218127 2.0 yes > 3.2 x 1010

IC3218091 2.0 yes > 2.2 x 1010

IC3218056 2.3 yes > 4.0 x 1010

IC3218078 2.3 yes > 2.3 x 1010

IC3218008 2.4 yes > 3.2 x 1010

ID6008163 1.8 yes > 1.1 x 1011

ID6008028 2.0 yes > 1.2 x 1011

ID6008119 2.0 yes > 8.9 x 1010

ID6008112 2.2 yes > 1.1 x 1011

ID6008128 2.3 yes > 1.0 x 1011

ID6008132 2.3 yes > 1.2 x 1011

KA4DFLP6G IB8101017 3.8 yes > 8.7 x 1010

IB8101028 3.9 yes > 4.9 x 1010

IB8101074 4.0 yes > 6.3 x 1010

IB8101091 4.0 yes > 6.1 x 1010

IC0522006 3.7 yes > 4.2 x 1010

IC0522094 3.8 yes > 7.6 x 1010

IC0522080 3.9 yes > 1.9 x 1011

IC0522120 4.0 yes > 8.0 x 1010

IC0522026 4.8 yes > 1.4 x 1011

IB8101089 5.1 yes > 7.9 x 1010

IB8101065 5.6 yes > 7.9 x 1010

IB8101078 5.7 yes > 8.3 x 1010

IB8101043 7.2 yes > 6.5 x 1010

Table 10 ContinuedResults of Forward Flow and Brevundimonas diminuta Retention for Typical Fluorodyne II gradeDFL Filter Capsules pre-sterilized by gamma irradiation at no greater than 50 kGy


NT6DFLP1S PB8910042 7.3 yes > 2.8 x 1011

PB8910038 8.0 yes > 2.8 x 1011

PB8910040 8.0 yes > 2.8 x 1011

PB8910037 8.1 yes > 2.5 x 1011

PB8910039 8.4 yes > 2.4 x 1011

1 Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C, maximum allowable limitvalues presented in Table 8.

3.4 ConclusionsBased on the validation of the 254 mm (10 in.) Fluorodyne II grade DFL filter cartridges, partnumber AB1DFL7PH4, Forward Flow integrity test values have been set for other filter stylesincorporating Fluorodyne II grade DFL filter membrane. Typical filters from production weresubjected to Forward Flow Integrity Test and bacterial challenge tests using Brevundimonasdiminuta (challenge level of > 1 x 107 CFU/cm2), demonstrating that filters that pass theForward Flow integrity test also produce a sterile effluent under the conditions of test.

4. Resistance of AB-style, Sealkleen Style and Junior Style Fluorodyne IIgrade DFL Filter Cartridges to in situ Steam

4.1 IntroductionThe purpose of these tests was to determine the effects of repeated exposure to in situ steamcycles on filter integrity using standard AB-style, Junior MCY-style, and Sealkleen styleFluorodyne II grade DFL filter cartridges from production. The tests were used to qualify thesteam exposure claims for these types of Fluorodyne II grade DFL filter cartridges, and byrelation Fluorodyne II grade DFL Novasip filter capsules.

4.2 Summary of MethodsTypical Fluorodyne II grade DFL filters from production were used for the tests.

During the tests typical production filters installed in a stainless steel housing were steamed inplace using saturated condensate-free steam. The steam pressure and flow were held constantduring the sterilization period and after each steam in place cycle, the filters were cooled bypassing dry compressed air through the test assembly. The filter cartridges were Forward Flowintegrity tested at appropriate intervals. Steam tests were performed at 125 °C and 140 °C. A summary of the steam exposure tests is shown in Table 11.

Table 11In situ Steaming Tests Performed on Fluorodyne II grade DFL Filter Cartridges

Fluorodyne II DFL Filter Style Steaming Conditions Maximum Steam Exposure

“AB Style” Filter Cartridges in situ steam cycles at 125 °C 60 x 1-hour cyclesin situ steam cycles at 140 °C 20 x 1-hour cycles

Junior Filter Cartridges – in situ steam cycles at 125 °C 60 x 1-hour cyclesMCY Style in situ steam cycles at 140 °C 20 x 1-hour cycles

Junior filter Cartridges – Sealkleenand SBF styles in situ steam cycles at 125 °C 60 x 1-hour cycles


22

4.3 ResultsThe Forward Flow integrity test results for Fluorodyne II grade DFL filters before and afterexposure to one-hour in situ steam cycles at 125 °C and 140 °C are shown in Tables 12 to 16. All of the filter cartridges retained integrity throughout the steam exposure tests.

Table 12Effects of in situ Steam Exposure at 125 °C on Filter Integrity for Fluorodyne II grade DFL FilterCartridges, part number AB1DFL7PH4

Pall Cartridge Forward Flow1 (mL/min) test results Serial Number after following number of cycles at 125 °C

0 4 8 16 30 45 60

IW608068 8.15 8.90 8.50 8.95 8.60 9.00 8.50

IW608097 7.75 8.50 8.42 9.00 9.00 9.00 8.60

IW608075 7.50 7.88 7.65 8.25 8.40 9.00 8.00

IW608003 7.50 8.48 7.85 9.30 9.00 7.20 8.75

IW608012 7.80 8.40 8.88 9.00 8.25 9.00 8.601 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C, maximum allowable limit of 12 mL/min.

Table 13Effects of in situ Steam Exposure at 140 °C on Filter Integrity for Fluorodyne II grade DFL Filtercartridges, part number AB1DFL7PH4


0 5 10 15 20

IW944019 9.50 9.50 8.60 8.50 8.90

IW944077 9.00 9.00 9.00 9.00 9.20

IW944023 9.50 9.00 9.00 9.30 9.00

IW944072 9.50 8.60 8.50 8.50 8.50

IW944012 9.50 9.30 9.50 9.50 9.401 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C, maximum allowable limit of 12 mL/min.

Table 14Effects of in situ Steam Exposure at 125 °C on Filter Integrity for Fluorodyne II grade DFL FilterCartridges in Junior MCY-Style and SBF1 Styles

Pall Filter Pall Cartridge Forward Flow1 (mL/min) test results Part Number Serial Number after following number of cycles at 125 °C

0 15 30 45 60

SBF1DFL IA6322011 0.6 0.1 0.1 0.1 0.5

IA6322023 0.5 0.2 0.1 0.1 0.5

IA6322038 0.1 0.1 0.2 0.4 0.5

MCY2220DFLP IA5589046 1.3 1.6 1.1 1.1 1.0

IA5589047 1.0 1.3 1.0 1.1 0.9

IA5589085 1.2 1.4 1.0 1.2 1.0

MCY4440DFLP IA5766203 2.3 2.2 2.7 2.4 5.0

IA5766215 2.4 2.5 2.5 2.3 2.6

IA5766227 2.2 2.3 2.4 2.4 2.31 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C, maximum allowable limit values presented in Table 8.

Table 15Effects of in situ Steam Exposure at 140 °C on Filter Integrity for Fluorodyne II grade DFL FilterCartridges in Junior MCY-Style

Pall Filter Pall Cartridge Forward Flow1 (mL/min) test results Part Number Serial Number after following number of cycles at 140 °C

0 5 10 15 20

MCY1110DFLP IA4000007 0.6 0.5 0.5 0.6 0.7

IA4000019 0.7 0.6 0.6 0.5 0.5

IA4000023 0.5 0.5 0.4 0.5 0.5

IA1912067 0.7 0.5 0.7 0.8 0.8

IA1912081 0.5 0.5 0.6 0.6 1.7

IA1912089 0.5 0.6 0.6 0.7 0.6

MCY2220DFLP IA4267008 1.1 1.0 1.1 1.0 1.0

IA4267092 1.3 1.0 1.0 1.0 0.9

IA4267211 1.4 0.9 0.95 0.9 0.9

IA4267290 1.2 0.9 1.1 0.9 0.9

IA4267304 1.1 1.0 1.1 1.1 1.2

MCY4440DFLP IA1913090 2.6 3.1 2.5 2.7 2.7

IA1913077 2.7 2.7 2.3 2.5 2.5

IA1913105 3.0 2.8 2.7 2.5 2.41 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C, maximum allowable limit values presented in Table 8.

Table 16Effects of in situ Steam Exposure at 125 °C on Filter Integrity for Fluorodyne II grade DFL FilterCartridges in Junior Sealkleen Style, Part Number SLK7001DFLP


0 4 8 16 30 45 60

PILF2770014 1.32 1.45 1.25 1.40 1.45 1.25 1.25

PILF2770198 1.48 1.40 1.30 1.33 1.35 1.28 1.40

PILF2770159 1.41 1.25 1.40 1.30 1.30 1.50 1.55

PILF2770118 1.58 1.40 1.40 1.30 1.44 1.36 1.30

PILF2770147 1.45 1.35 1.40 1.33 1.30 1.20 1.251 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C, maximum allowable limit values presented in Table 8.

4.4 ConclusionsFluorodyne II grade DFL filter cartridges have been demonstrated to be capable of withstandingmultiple in situ steam cycles.

The data presented in this section of the guide support the following product claims for in situsteaming Fluorodyne II grade DFL filter cartridges and Novasip Filter Capsules:


24

Table 17Product Claims for in situ Steaming of Fluorodyne II grade DFL Filter Cartridges

Maximum RecommendedPall Fluorodyne II DFL Filter Style Steaming Cycle Steaming Conditions

High Area “AB Style” in situ steam cycles at 125 °C 30 x 1-hour cyclesFilter Cartridges in situ steam cycles at 140 °C 10 x 1-hour cycles

Junior Filter Cartridges – MCY Style, in situ steam cycles at 125 °C 30 x 1-hour cyclesand Novasip Filter Capsules in situ steam cycles at 140 °C 10 x 1-hour cycles

Junior Filter Cartridges – Sealkleenand SBF Styles in situ steam cycles at 125 °C 30 x 1-hour cycles

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

5. Resistance of Fluorodyne II grade DFL Filter Capsules to Autoclave Sterilization

5.1 IntroductionThe purpose of these tests was to determine the effects of repeated exposure to autoclavecycles on filter integrity, using standard Fluorodyne II grade DFL filter capsules from production.The tests were used to qualify autoclave exposure claims for Fluorodyne II grade DFL filtercapsules.

5.2 Summary of MethodsTypical Fluorodyne II grade DFL filter capsules were used for the tests. The filter samples wereexposed to 1-hour autoclave cycles at 125 °C. At intervals, between the autoclave cycles, thefilter integrity was checked using the Forward Flow integrity test.

5.3 ResultsThe Forward Flow integrity test results are shown in Tables 18 and 19.

Table 18Effects of Autoclave Sterilization Exposure at 125 °C on Filter Integrity for Fluorodyne II gradeDFL Mini Kleenpak Filter Capsules, Part Number KA02DFLP2G

Serial Number Forward Flow1 test results after exposure to the following number of autoclave cycles:

0 1 2 3 4 5 6

ID3416006 0.28 0.30 0.29 0.34 0.21 0.30 0.27

ID3416016 0.30 0.32 0.42 0.38 0.27 0.33 0.33

ID3416034 0.29 0.31 0.27 0.35 0.25 0.28 0.24

ID3416035 0.29 0.31 0.26 0.33 0.30 0.30 0.28

ID3416051 0.29 0.31 0.31 0.34 0.24 0.32 0.26

ID3416065 0.51 0.30 0.27 0.34 0.27 0.30 0.32

ID3416075 0.27 0.32 0.35 0.38 0.27 0.32 0.30

ID4135141 0.08 0.22 0.14 0.23 0.28 0.21 0.27

ID4135144 0.06 0.28 0.27 0.27 0.29 0.24 0.17

ID4135162 0.12 0.27 0.27 0.26 0.32 0.24 0.20

ID4135166 0.05 0.22 0.25 0.24 0.25 0.26 0.30

Table 18 ContinuedEffects of Autoclave Sterilization Exposure at 125 °C on Filter Integrity for Fluorodyne II gradeDFL Mini Kleenpak Filter Capsules, Part Number KA02DFLP2G

Serial Number Forward Flow1 test results after exposure to the following number of autoclave cycles

0 1 2 3 4 5 6

ID4135167 0.05 0.32 0.32 0.27 0.30 0.28 0.31

ID4135171 0.03 0.25 0.25 0.23 0.30 0.25 0.22

ID4135197 0.06 0.23 0.27 0.21 0.29 0.26 0.31

ID4135200 0.02 0.25 0.25 0.27 0.28 0.22 0.23

ID4559025 0.05 0.17 0.10 0.23 0.34 0.33 0.26

ID4559069 0.07 0.26 0.11 0.25 0.29 0.30 0.26

ID4559083 0.06 0.28 0.10 0.27 0.33 0.34 0.26

ID4559085 0.07 0.25 0.22 0.14 0.31 0.35 0.36

ID4559134 0.06 0.12 0.10 0.24 0.30 0.32 0.26

ID4559138 0.08 0.14 0.13 0.27 0.33 0.35 0.33

ID4559159 0.08 0.13 0.11 0.28 0.33 0.33 0.29

ID4559175 0.09 0.22 0.10 0.20 0.36 0.28 0.311 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 ºC, maximum allowablelimit values presented in Table 8

Table 19Effects of Autoclave Sterilization Exposure at 125 °C on Filter Integrity for Fluorodyne II gradeDFL Kleenpak Filter Capsules

Pall Kleenpak Pall Capsule Capsule Serial Forward Flow1 (mL/min) test results after Part Number Number exposure to the following number of autoclave cycles

0 15 30 45 60

KA4DFLP1 IA6087003 4.4 4.4 4.3 4.1 4.0

IA6087045 5.0 4.7 3.6 3.5 3.7

IA6087048 4.5 4.3 3.9 4.0 4.6

IA6087080 4.7 4.6 4.7 4.5 4.5


Pall Kleenpak Pall CapsuleCapsule Part Serial Forward Flow1 (mL/min) test results after Number Number exposure to the following number of autoclave cycles

0 5 10 15 20

KA1DFLP1 IY7210017 0.5 0.5 0.5 0.5 0.5

IY7210045 0.5 0.7 0.5 0.5 0.5

IY7210065 0.5 0.5 0.5 0.5 0.6

IY7210035 0.5 0.6 0.6 0.6 0.5

IY7210058 0.7 0.6 0.6 0.5 0.51 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 ºC, maximum allowablelimit values presented in Table 8


26


Pall Kleenpak Pall CapsuleCapsule Part Serial Forward Flow1 (mL/min) test results after Number Number exposure to the following number of autoclave cycles

0 5 10 15 20

KA2DFLP6 ID0342015 1.26 1.31 1.47 Not Not determined determined

ID0342028 1.32 1.06 0.99 Not Not determined determined





KA3DFLP1 IA4029032 2.4 2.3 2.4 2.5 2.5

IA4029048 1.5 2.3 2.2 2.3 2.2

IA4029001 2.8 2.3 2.5 2.2 2.3

IA4029022 2.0 2.3 2.2 2.1 2.0

IA4029014 1.9 1.7 1.9 2.2 2.2

KA3DFLP6 IA3451012 2.5 2.0 2.1 2.2 2.1

IA3451016 2.8 2.1 2.0 2.2 2.0

IA3451026 2.2 2.1 2.2 2.1 2.1

IA3451028 2.6 2.4 2.2 2.0 2.2

IA3451044 2.5 2.3 2.3 2.3 2.2

KA4DFLP6G IB8101004 6.0 5.3 6.7 5.5 5.2

IB8101006 5.8 5.4 6.6 5.0 4.9

IB8101010 2.6 5.6 5.8 4.8 5.2

IB8101023 4.6 5.2 6.8 5.0 5.2

IB8101048 4.7 5.1 6.7 4.8 5.2

IB8101088 2.5 5.3 6.0 5.0 5.11 Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 ºC, maximum allowablelimit values presented in Table 8

5.4 ConclusionsFluorodyne II grade DFL filter capsules have been demonstrated to be capable of withstandingmultiple autoclave sterilization cycles.

The data presented in this section support the following product claims for autoclavesterilization of Fluorodyne II grade DFL filter capsules.

Table 21Product Claims for Autoclave Sterilization of Fluorodyne II grade DFL Filter Capsules

Maximum Recommended Pall Filter Part Number Autoclave Temperature Autoclave Conditions1

KA02DFLP*G Autoclaving at 125 °C 3 x 1-hour cycles

KA*DFLP* Autoclaving at 125 °C 30 x 1-hour cycles

KA*DFLP* Autoclaving at 140 °C 10 x 1-hour cycles1 The above information is supported by data with a safety margin.

6. Determination of Water Flow Characteristics

6.1 IntroductionThe purpose of these tests was to determine the typical differential pressures acrossFluorodyne II grade DFL filter cartridges and filter capsules at set water flow rates. Refer to Pall publication USD 2562 for detailed part numbering information.

6.2 Summary of MethodsThe tests were performed on standard production filter cartridges and capsules.

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.

Further flow measurements for AB style filter cartridges were taken with the test assembly withno filter cartridge or capsule installed, so that the piping/housing losses could be measured andthen subtracted from the filter assembly results.

The results were corrected for a standard temperature of 20 °C.

6.3 ResultsThe water flow characteristics for typical Fluorodyne II grade DFL filter cartridges and capsulesare presented in Figures 3 – 12. To calculate the expected water flow rate for fluids other thanwater, multiply the differential pressure by the fluid viscosity (cP).

Figure 3Water Flow/Differential Pressure Characteristics of the Fluorodyne II grade DFL Filter Cartridge,Part Number AB1DFL7PH4 – Typical Liquid Flow vs Differential Pressure


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28

Figure 4Water Flow/Differential Pressure Characteristics of Fluorodyne II grade DFL T-style KleenpakNova Filter Capsules – Typical Liquid Flow vs Differential Pressure

Figure 5Water Flow/Differential Pressure Characteristics of Fluorodyne II grade DFL In-line KleenpakNova Filter Capsules – Typical Liquid Flow vs Differential Pressure

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P1/P9/P19 DFL P6/P16 DFL

Figure 6Water Flow/Differential Pressure Characteristics of Fluorodyne II grade DFL Junior Filter Cartridges – Sealkleen Style Typical Liquid Flow vs Differential Pressure

Figure 7Water Flow/Differential Pressure Characteristics of Fluorodyne II grade DFL Junior Filter Cartridges – SBF and MCY Styles – Typical Liquid Flow vs Differential Pressure


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Figure 8Water Flow/Differential Pressure Characteristics of Fluorodyne II grade DFL Novasip Filter Capsules – Typical Liquid Flow vs. Differential Pressure

Figure 9Water Flow/Differential Pressure Characteristics of the Fluorodyne II grade DFL Mini Kleenpak filter capsule part configuration KA02DFLP – Typical Liquid Flow vs. Differential Pressur

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Figure 10Water Flow/Differential Pressure Characteristics of the Fluorodyne II grade DFL Kleenpak filter capsule part configuration KA1DFL – Typical Liquid Flow vs Differential Pressure



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6.4 ConclusionsDifferential pressure measurements at set water flow rates have been determined for typicalFluorodyne II grade DFL filters cartridges and capsules. The data presented can be used to size filtration systems employing Fluorodyne II grade DFL filter membrane.

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7. Extractables Testing

7.1 IntroductionThe aim of this series of tests was to quantify and characterize the material that can beextracted from Fluorodyne II grade DFL filter cartridges and filter capsules.

7.2 Summary of MethodsStandard production filters were used for the tests.

7.2.1 Preparation of Filter SamplesPrior to the extraction test, the filter samples were autoclaved in order to maximizethe quantity of any extractable material present. The filter cartridges were wrapped inaluminum foil, while the inlet and the outlet ports of the capsules were covered withaluminum foil with the vent and drain valves open. The filters were then autoclavedfor one hour at 125 °C ± 5 °C, using a slow exhaust cycle. Visible droplets of waterremaining on the filter elements were allowed to evaporate at room temperaturebefore the extraction was performed.

7.2.2 Extraction Procedure for Filter CartridgesDynamic extraction tests were performed in a known volume of extracting liquid atambient temperature. The test filters were immersed in the extraction fluid in a cleanmeasuring cylinder, as shown in Figure 13. For four (4) hours the filter was gentlymoved up and down. This movement created flow through the filter membrane as aresult of the pressure head that was created each time the element was partially liftedout of the liquid.

Following the extraction period, a measured volume of the extraction liquid wasevaporated to dryness and the non-volatile residue (NVR) were determinedgravimetrically. A correction was made to the NVR value to account for the totalextraction volume used.

The extractables were also analyzed by Fourier Transform Infra Red Spectroscopy (FTIR).

Figure 14Filter Extraction Apparatus for Filter Cartridges


Motor witheccentric rotor

Filter cartridgein measuringcylinder filled withextraction fluid

Stainless steelweight

34

7.2.3 Extraction Procedure for Filter CapsulesFor the filter capsules a known volume of extraction liquid was re-circulated througheach filter for four (4) hours at ambient temperature as shown in Figure 15.

Following the extraction period, a measured volume of the extraction liquid wasevaporated to dryness and the non-volatile residue (NVR) were determinedgravimetrically. A correction was made to the NVR value to account for the totalextraction volume used.

The extractables were also analyzed by Fourier Transform Infra Red Spectroscopy (FTIR).

Figure 15Filter Extraction Apparatus for Filter Cartridges

7.3 ResultsTable 22 shows the levels of extractables obtained from the Fluorodyne II grade DFL filtercartridges and filter capsules that were tested.

Table 22Non-volatile Extractables Obtained Using Fluorodyne II grade DFL Filter Cartridges and FilterCapsules after Autoclaving at 125 °C ± 5 °C (4 Hours Extraction Time at Ambient Temperature)

Pall Filter Pall Cartridge Non-Volatile Residue Part Number Extraction Fluid Serial Number per Cartridge (mg)

AB1DFL7P DI water IW9440049 < 0.1 mg1

IW9440076 2 mg

IW6080043 2 mg

IW6080106 < 0.1 mg

IW9820082 3 mg

IW9440011 2 mg

IW9440052 1 mg

Ethanol IW9440037 121 mg

IW9440047 140 mg

AB1DFL7P(irradiated at 36 kGy) DI water ID1090392 < 0.1 mg

ID1090246 < 0.1 mg

ID1090254 2 mg

Kleenpak CapsuleFilter withFluorodyne IIMembrane

Pump

Water

Table 22 ContinuedNon-volatile Extractables Obtained Using Fluorodyne II grade DFL Filter Cartridges after Auto-claving at 125 °C ± 5 °C (4 Hours Extraction Time at Ambient Temperature)

Pall Filter Pall Cartridge Non-Volatile Residue Part Number Extraction Fluid Serial Number per cartridge (mg)

AB1DFL7P(irradiated at 50 kGy) DI water ID0859370 1 mg

ID1090224 2 mg

ID1090247 2 mg

SLK7001DFLP DI water IW4530165 < 0.1 mg

IW4530013 4 mg

SBF1DFLP DI water IA1914068 < 0.1 mg

IA1914028 < 0.1 mg

KA02DFLP DI waterNon-irradiated samples ID4559088 < 0.1 mg

ID4559172 0.5 mg

ID4559119 < 0.1 mg

DI water. Samples irradiated at 50 kGy ID4559169 4.8 mg

ID4559041 4.7 mg

ID4559148 4.9 mg

KA2DFLP2S DI water. Samples irradiated at 27.1 – 32.0 kGy IB8364093 1 mg

IB8364148 < 0.1 mg

IB8364194 < 0.1 mg

DI water. Samples irradiated at 50 kGy IB8364032 1 mg

IB8364214 < 0.1 mg

IB8364336 1 mg

KA3DFLP1 DI water IA7707042 1 mg

IA7707062 < 0.1 mg

KA4DFLP6G DI water. Samples irradiated at 26.3 – 30.4 kGy IC0522173 2 mg

IC0522005 2 mg

IC0522023 1 mg1 0.1 mg is the minimum detection limit for the test measurement equipment used

A typical infrared spectrum of an ethanol extract from a Fluorodyne II grade DFL filter cartridge(part number AB1DLF7PH4) is shown in Figure 14.

The FTIR spectrum of the ethanol extracts from Fluorodyne II grade DFL filter cartridgesindicates the presence of extractables typical of polypropylene resins (stearate salts or esters, aphenolic antioxidant and small amounts of polypropylene oligomers) of the acrylate copolymerused to render the membrane hydrophilic, and from a polyester material that is used to supportthe filter membrane during manufacture, which is not incorporated into finished product.


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Figure 16Typical Infrared Spectrum of the Aqueous Extractables from Fluorodyne II grade DFL Filter Cartridge, part number AB1DFL7PH4

7.4 ConclusionsThe data presented in this section support the following product claims for autoclavesterilization of Fluorodyne II grade DFL filter capsules:

Table 23Product Claims for Aqueous Extractables for Fluorodyne II grade DFL Filter Cartridges and Filter Capsules

Pall Filter Part Number Typical Extractables in Water at 20 °CAfter 4 Hours Extraction

AB1DFL7PH4 < 5 mg

Junior MCY and Sealkleen Styles < 5 mg

Mini Kleenpak G option < 1 mg

All other Kleenpak styles < 5 mg

Actual service will impose different conditions, such as different steaming conditions, exposuretimes, temperature and liquid types. Evaluation under process conditions is therefore alsorecommended.

8. Biological Reactivity Tests on the Materials of Construction

8.1 IntroductionThe aim of this study was to evaluate the biological suitability of the materials of construction ofFluorodyne II grade DFL cartridges and capsules. The materials of construction of the filters aredetailed in Table 24.

Wave Numbers

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9590858075706560555045403530252015105

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Table 24Materials of Construction

Membranes Hydrophilic polyvinylidene fluoride (PVDF) membrane

Membrane support and drainage layers Polypropylene

Core, cage and endcaps Polypropylene

O-rings Silicone elastomer for ‘H4’ option

Capsule Housing for Kleenpak capsules Polypropylene

8.2 Summary of MethodsThe tests were performed in accordance with the Biological Reactivity Tests in vivo for ClassVI- 121 Plastics as described in the current United States Pharmacopoeia (USP) Chapter <88>.

The testing procedures described in the USP include:

• Injection of extracts of plastic materials

• Implantation of the solid material into animal tissue

The four (4) extracting media listed in the USP simulate parenteral solutions 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 USP states that extracts may be prepared at one of three standard conditions: 50 °C for72 hours, 70 °C for 24 hours, or 121 °C for 1 hour. The most stringent condition not resulting inphysical changes in the plastic is recommended, therefore the filter materials were extracted at121 °C for one hour.

8.2.1 Acute Systemic Injection TestsAn Acute Systemic Injection Test was performed to evaluate the potential of a singleinjection of an extract to produce systemic toxicity. The Sodium Chloride Injectionand 1 in 20 Solution of Alcohol in Sodium Chloride Injection were injectedintravenously. The vegetable oil extract and Polyethylene Glycol 400 extract wereinjected intraperitoneally.

8.2.2 Intracutaneous Tests An Intracutaneous Test was performed to evaluate the potential of a single injectionof an extract to produce tissue irritation. All four (4) of the extracts listed above wereused for these tests.

8.2.3 Implantation TestsImplantation tests were also performed, in order to subject the materials ofconstruction to the most stringent conditions included in the USP. Each of thematerials of the Fluorodyne II grade DFL cartridges and capsules was implantedseparately.

8.3 ResultsNo biological response was observed in any of the tests performed and therefore the materialsused in Fluorodyne II grade DFL cartridges and capsules passed all of the tests specified.

8.4 Conclusions The materials used in Fluorodyne II grade DFL cartridges and capsules met the requirements of the USP Biological Reactivity Tests (in vivo) for Class VI-121 °C plastics.


38

The tests included the Systemic Injection test, the Intracutaneous test and the Implantation test.

Copies of the reports are available on request.

9. Evaluation of Shelf Life

9.1 IntroductionThe purpose of these tests was to determine the shelf-life of pre-sterilized Fluorodyne II gradeDFL filter capsules following gamma irradiation.

9.2 Summary of MethodsTypical pre-sterilized Kleenpak Fluorodyne II filter capsules from production were stored in theiroriginal packaging at room temperature for a set time and then subjected to a range of tests inorder to confirm that the performance of the product had not degraded over time.

The tests performed on samples of the stored product were as follows:

• Integrity of packaging

• Forward Flow integrity testing

• Liquid bacterial challenge testing using Brevundimonas diminuta (ATCC 19146)

• Burst pressure testing

Typical pre-sterilized Kleenpak Fluorodyne II filter capsules are supplied double-bagged, withthe inner bag sealed under vacuum. The packaging of the stored product was inspected priorto other tests being performed. During the visual inspection, the outer bag was checkedfollowed by a check on the integrity of the vacuum of the inner bag.

The other tests performed on stored product were conducted as described previously.

9.3 Results

9.3.1 Integrity of PackagingThe packaging of pre-sterilized Kleenpak Fluorodyne II filter capsules was found to be integralon product that had been stored for up to 36 months.

9.3.2 Forward Flow Integrity Test and Bacterial Challenge TestThe Forward Flow integrity test and bacterial challenge test results are shown inTable 25. Following gamma irradiation with a dose of up to 36.8 kGy, filter capsulesretained integrity and passed the bacterial challenge test after 36 months storage.Capsules that had been gamma irradiated with a dose of up to 50 kGy were testedafter 5 and 6 months storage and again the samples passed both the Forward Flowintegrity test and bacterial challenge test.

Table 25Forward Flow Integrity Test and Bacterial Challenge Test Results after Storage

Filter Filter Forward Part Serial Irradiation Storage Flow Sterile Titer Number Number Dose Time (mL/min)1 Effluent Reduction

KA02DFLP2S ID9543002 35.0 – 3 months 0.17 yes > 9.8 x 109

36.8 kGy

ID9543042 35.0 – 3 months 0.21 yes > 9.0 x 109

36.8 kGy

ID9543054 35.0 – 3 months 0.23 yes > 5.3 x 109

36.8 kGy

Table 25 ContinuedForward Flow Integrity Test and Bacterial Challenge Test Results after Storage


KA02DFLP2S ID9543011 35.0 – 3 months 0.25 yes > 5.1 x 109

36.8 kGy

ID9543046 35.0 – 3 months 0.25 yes > 1.1 x 109

36.8 kGy

ID9280038 29.8 – 6 months 0.22 yes > 8.4 x 109

31.9 kGy

ID9280022 29.8 – 6 months 0.24 yes > 7.0 x 109

31.9 kGy

ID9280042 29.8 – 6 months 0.25 yes > 7.7 x 109

31.9 kGy

ID9280009 29.8 – 6 months 0.26 yes > 6.4 x 109

31.9 kGy

ID9280006 29.8 – 6 months 0.28 yes > 6.2 x 109

31.9 kGy

ID9543023 35.0 – 12 months 0.2 yes > 6.9 x 109

36.8 kGy

ID9543052 35.0 – 12 months 0.2 yes > 5.8 x 109

36.8 kGy

ID9543007 35.0 – 12 months 0.28 yes > 5.4 x 109

36.8 kGy

ID9543022 35.0 – 36 months 0.28 yes > 1.0 x 1010

36.8 kGy

ID9543016 35.0 – 36 months 0.31 yes > 8.4 x 109

36.8 kGy

ID9543034 35.0 – 36 months 0.42 yes > 1.0 x 1010

36.8 kGy

KA2DFLP2S IC0045052 27.1 – 12 months 1.0 yes > 7.8 x 1010

32.0 kGy

IC0045054 27.1 – 12 months 1.2 yes > 2.5 x 1010

32.0 kGy

IC0045056 27.1 – 12 months 0.8 yes > 3.8 x 1010

32.0 kGy

IC0045019 27.1 – 24 months 0.9 yes > 5.8 x 1010

32.0 kGy

IC0045043 27.1 – 24 months 0.8 yes > 6.6 x 1010

32.0 kGy

IC0045044 27.1 – 24 months 0.7 yes > 6.0 x 1010

32.0 kGy

IC0045013 27.1 – 36 months 0.7 yes > 2.7 x 1010

32.0 kGy

IC0045034 27.1 – 36 months 0.7 yes > 2.1 x 1010

32.0 kGy


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Table 25 ContinuedForward Flow Integrity Test and Bacterial Challenge Test Results after Storage


KA4DFLP6G IB8101107 49.8 – 5 months 4.0 yes > 6.8 x 1010

50.0 kGy

IB8101101 49.8 – 5 months 4.5 yes > 8.8 x 1010

50.0 kGy

IB8101049 49.8 – 5 months 4.3 yes > 8.9 x 1010

50.0 kGy

IC0522146 52.6 – 6 months 4.4 yes > 9.4 x 1010

57.7 kGy

IC0522021 52.6 – 6 months 3.7 yes > 8.0 x 1010

57.7 kGy

IC0522186 52.6 – 6 months 4.6 yes > 7.1 x 1010

57.7 kGy1 Air test pressure 2760 mbar (40 psi), wetting liquid water

9.3.3 Burst Pressure TestingThe burst pressure test results are shown in Table 26. Filter capsules were testedthat had been stored for up to 36 months, following gamma irradiation with dosesbetween of 25 – 35 kGy. In all cases, the burst pressure exceeded 13.1 bar/190 psi.This burst pressure is over twice the maximum recommended operating pressure of5.2 bar (75.4 psi).

Table 26Filter Capsule Burst Pressures After Storage

Filter Filter Part Number Serial Number Irradiation Dose Storage Time Burst Pressure

KA2DFLP2S IB8364083 27.1 – 32.0 kGy 12 months 15.2 bar/220 psi

IB8364210 27.1 – 32.0 kGy 12 months 15.2 bar/220 psi

IB8364261 27.1 – 32.0 kGy 12 months 15.2 bar/220 psi

IC0045019 27.1 – 32.0 kGy 24 months 24.8 bar/360 psi





KA3DFLP6S PILF4170026 27.9 – 34.5 kGy 18 months 13.1 bar/190 psi

PILF4170034 27.9 – 34.5 kGy 18 months 13.1 bar/190 psi


PILF3930058 26.9 – 38.7 kGy 20 months 24.1 bar 350 psi




9.4 ConclusionsThe data presented in this report demonstrate that Fluorodyne II grade DFL filter capsules retaintheir strength and expected performance after storage for up to 36 months, following irradiationat doses ranging between 25 – 35 kGy.

10. Validation of Sterilization by Gamma Irradiation of Pall Pre-sterilized Filter Capsules

10.1 Principles of Gamma IrradiationGamma irradiation is the application of electromagnetic radiation (i.e. gamma rays), emittedfrom radionucleotides Cobalt-60 and Caesium-130 isotopes. Gamma rays are not retained by most materials and are able to penetrate through most components. Microorganisms areinactivated by breaks in their nucleic acids resulting from this ionizing irradiation. Gammairradiation dose is measured in kilogray (kGy) units, which quantify the deposited energy of radiation.

The gamma irradiation process uses well-defined operating parameters to ensure accuratedosing. For a given density of material the only variable determining the amount of radiation theproduct and microorganisms receives is the time the material spends within the radiation field.Products are not exposed to heat, humidity, pressure or vacuum.

10.2 Validation

Gamma irradiation sterilization validation is comprised of two parts, dose setting / auditing anddose mapping as detailed in ISO 11137 Parts 1 and 2 Sterilization of health care products –Radiation. Pall conducts validation and routine control of the sterilization process of ‘S’ variantfilter capsules as per the requirements of these standards.

10.3 Dose Establishment and Dose Auditing

A sterilization dose is selected and substantiated for the product based on a determination of bioburden and the actual resistance of microorganisms contained on the product through the performance of a dose verification study. The dose verification study establishes theirradiation dose which will achieve a Sterility Assurance Level (SAL) of 10-6. Products aregrouped into ‘families’ for dose verification taking into account product related variables thataffect bioburden. These variables include the nature and source of raw materials, components,product design, manufacturing process, manufacturing equipment, manufacturing environmentand manufacturing location. A representative product from the family is chosen forperformance of the verification study and results are interpreted as per ISO 11137-2Sterilization of health care products – Radiation –Part 2 Establishing the sterilization dose. Dose audits are performed at set intervals in order to assure that the chosen dose continues to be effective for achieving the desired SAL of 10-6. Dose auditing involves selecting therequired number of product samples from routine production, determining the bioburden ofeach product sample as per the established procedure and performing a confirmatoryverification dose experiment. Results of the verification dose experiment are interpreted as per the requirements of ISO 11137-1 Sterilization of health care products – Radiation –Part 1Requirements for development, validation, and routine control of a sterilization process formedical devices and ISO 11137-2 Sterilization of health care products – Radiation – Part 2Establishing the sterilization dose.

10.4 Dose MappingDose mapping follows the requirements of ISO 11137-1 ‘Sterilization of health care products –Radiation – Requirements for development, validation and routine control of a sterilizationprocess for medical devices’.

The objective is to determine the dose distribution of dose mapping cartons of product. The absorbed radiation dose is measured by dosimeters placed throughout the product unit andread after sending the product through the irradiator. The cartons are processed around thecontinuous plant at a speed designed to achieve greater than the specified minimum dose. After irradiation, all dosimeters are recovered, read, and the absorbed doses calculated.


The results are presented as a pictorial representation of the product and dosimeter positions,and as a tabulated summary of absorbed dose. From this data, the maximum and minimumdose range likely to be encountered can be established, as well as the acceptable maximumand minimum routine dosimeter readings to stay within the process specifications.

Dose mapping is performed for each pre-sterilized Pall product.

10.5 Dosimeter Release

Each irradiation load contains a dosimeter, which is placed in a specific position in the load. Theload is released based on the dose reading from the dosimeter. Certification is received from thesterilization contractor for each load. Certificates detail the dose achieved.

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 distributor nearest you, visit www.pall.com/contact.

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

© 2015, Pall Corporation. Pall, , and Fluorodyne are trademarks of Pall Corporation. ® indicates atrademark registered in the USA and TM indicates a common law trademark. Filtration.Separation.Solution.is a service mark of Pall Corporation.

5/15, PDF, GN14.5995 USTR2611

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