USTR2611
Validation Guide
Pall 0.2 µm-rated Filter Cartridges and
Filter Capsules with Fluorodyne®II Grade
DFL Membrane
2
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 (10in.) Fluorodyne II GradeDFL
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
3.2 Summary of Methods ............................................................................................................................13
3.3 Results ..................................................................................................................................................14
3.4 Conclusions ..........................................................................................................................................21
4. Resistance of 254 mm (10 in.) Fluorodyne II GradeDFL Filter Cartridges toin situ Steam ................21
4.1 Introduction............................................................................................................................................21
4.2 Summary of Methods ............................................................................................................................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
5.2 Summary of Methods ............................................................................................................................24
5.3 Results ..................................................................................................................................................24
5.4 Conclusions ..........................................................................................................................................26
6. Determination of Water Flow Characteristics ..........................................................................................27
6.1 Introduction............................................................................................................................................27
6.2 Summary of Methods ............................................................................................................................27
6.3 Results ..................................................................................................................................................27
6.4 Conclusions ..........................................................................................................................................32
7. Extractables Testing .................................................................................................................................33
7.1 Introduction............................................................................................................................................33
7.2 Summary of Methods ............................................................................................................................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 Summary of Methods ............................................................................................................................37
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
9.2 Summary of Methods ............................................................................................................................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
4
1. Overview
1.1 Introduction
This guide contains validation data applicable to 0.2 µm microbially rated Fluorodyne II grade
DFL filter cartridges and filter capsules. It consolidates data previously published in Pall
publications USTR1548 (Validation Guide for Pall 0.2 µm rated Fluorodyne II Membrane
Cartridges) 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 USTR
1666 (Validation Guide for Novasip™ Filters) and USTR2099 (Validation Guide for Pall Kleenpak
Nova Filter Capsules).
These filters have been designed as sterilizing-grade liquid filters. The removal rating of 0.2 µm
is based on challenges with Brevundimonas diminuta (ATCC 19146). The filter cartridges are
comprised of two layers of Pall polyvinylidene fluoride (PVDF) filter membrane with
polypropylene support and drainage materials. The core, cage and end caps of the filters are all
polypropylene, 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 supplied
pre-sterilized. Following manufacture, sterilization is achieved by gamma irradiation using a
minimum dose of 25 kGy (maximum dose 50 kGy). These conditions ensure a minimum Sterility
Assurance Level of 10-6. The sterilization process is validated and routinely controlled in
compliance with the following standards:
• ISO 11137-1:2006 ‘Sterilization of health care products - Radiation - Part 1 - Requirements
for 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 the
sterilization dose’.
• AAMI TIR 33:2005 ‘Sterilization of health care products- Radiation. Sustantiation of a selected
sterilization dose - Method VDmax.’.
Fluorodyne II grade DFL filter capsules with a ‘G’ designation in the part number may be
gamma 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 Fluorodyne
II 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 are
described in Pall publication USD2562 (Fluorodyne II Filters).
The units of pressure quoted in this document are bar or millibar (mbar) and pounds force per
square inch (psi). The following formulae can be used to convert these units of pressure to
Pascals (Pa):
1 bar = 1000 mbar = 1 x 105Pa
1 psi = 6.89476 x 103Pa = 0.069 bar = 69.85 mbar
www.pall.com/biopharm 5
Configurations of Fluorodyne II Grade DFL Filter Cartridges and Filter Capsules Supported by
this Validation Guide:
Part Number
Filter Type Style Prex Primary Use
Pleated membrane Junior Filter Cartridges SBF1DFL For sterile ltration of small volumes of uid,
lter cartridges, for (SBF Style) typically 2 L to 50 L
use in stainless steel
lter housings
Junior Filter Cartridges MCY1110DFL For sterile ltration of uids typically ranging from
(MCY Style) MCY2220DFL 20 L to 500 L in volume
MCY4440DFL
Sealkleen Filter SLK7001DFL
Cartridges SLK7002DFL
Standard (‘AB-Style’) AB05DFL For sterile ltration of uid, typically from 50 L to
Filter Cartridges AB1DFL > 1000 L in volume. Filter assemblies forming
AB2DFL AB-style lter cartridges are also available
AB3DFL encapsulated in polymeric lter housings,
AB4DFL as Kleenpak Nova lter capsules
Pleated membrane Mini Kleenpak KA02DFL For ltration of small volumes of uid, typically
lter elements in Capsules 2 L to 50 L, for use during research, process
polymeric capsule development or manufacturing
housing Kleenpak Capsules KA1DFL For ltration of uids from 10 L to 500 L in
KA2DFL process development and manufacturing
KA3DFL
KA4DFL
Novasip Capsules C05DFL For ltration of uids ranging from 10 L to 500 L.
C3DFL Can be sterilized by in-line steaming (SIP).
CL1DFL Novasip lters comprise a steam resistant
(MCY1110) polymeric lter capsule containing Junior MCY
CL2DFL style lter cartridge elements (element size
(MCY2220) shown in brackets). Data for Junior MCY style
CL3DFL lters in this guide can be used to support the
(MCY4440) qualication of a corresponding Novasip
conguration and may be used in conjunction
with data in Pall publication USTR1666
(Validation Guide for Novasip Filters)
Kleenpak Nova NP5LDFL For ltration of liquids in medium to large scale
Capsules (AB05) GMP production environments (typically for
NP6DFL (AB1) ltration of 50 L to > 1000s L)
NP7DFL (AB2) Kleenpak Nova lters comprise a polymeric
NP8DFL (AB3) capsule containing lter assemblies used in
NT6DFL (AB1) AB- style lter elements (AB element size shown
NT7DFL (AB2) in brackets). Data for AB-style lters in this guide
NT8DFL (AB3) can be used to support the qualication of a
corresponding Kleenpak Nova conguration and
may 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 number
system for the above formats of Fluorodyne II grade DFL lters are detailed in Pall publication USD2562 (Fluorodyne
II 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 Tests
Fluorodyne II grade DFL filter cartridges and filter capsules were tested for bacterial
retention of Brevundimonas diminuta (ATCC 19146) using bacterial challenge tests
per modified ASTM F838-05 Standard Test Method, and in accordance with the U.S.
FDA’s Guidance for Industry — Sterile Drug Products Produced By Aseptic
Processing (September 2004).
The Forward Flow integrity test was shown to be a suitable non-destructive integrity
test 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 filter
cartridges and Kleenpak Nova filter capsules as indicated in Table 1.
Table 1
Forward Flow Integrity Test Parameters for 254 mm (10 in.) Filter elements used in
Fluorodyne II grade DFL Filter Cartridges, Part Number AB1DFL7PH4 and Kleenpak
Nova 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 limit112 mL/min
1During 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 styles
incorporating Fluorodyne II grade DFL filter membrane, as shown in Table 2.
Typical filters from production were subjected to Forward Flow integrity testing and
bacterial challenge tests, demonstrating that the filters that pass the Forward Flow
integrity test also provide a sterile effluent.
www.pall.com/biopharm 7
Table 2
Forward Flow Integrity Test Parameters for Other Styles of Fluorodyne II grade DFL
Filter Cartridges and Capsules
Pall Filter Maximum Allowable
Part Number1Wetting Liquid2Air Test Pressure Forward Flow Limit3
KA02DFLP* Water 2760 mbar (40 psi) 0.5 mL/min
KA1DFLP* Water 2760 mbar (40 psi) 1.0 mL/min
KA2DFLP* Water 2760 mbar (40 psi) 2.0 mL/min
KA3DFLP* Water 2760 mbar (40 psi) 3.4 mL/min
KA4DFLP* Water 2760 mbar (40 psi) 7.4 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
C(L)3DFLP* Water 2760 mbar (40 psi) 3.4 mL/min
SBF1DFLP Water 2760 mbar (40 psi) 1.0 mL/min
MCY1110DFL Water 2760 mbar (40 psi) 0.8 mL/min
MCY2220DFL Water 2760 mbar (40 psi) 1.6 mL/min
MCY4440DFLP Water 2760 mbar (40 psi) 3.4 mL/min
SLK7001DFLP Water 2760 mbar (40 psi) 2.0 mL/min
SLK7002DFLP Water 2760 mbar (40 psi) 4.0 mL/min
AB05DFL2P Water 2760 mbar (40 psi) 6.0 mL/min
1* denotes “blank”, S or G option- see Pall website for detailed part numbering information
2Temperature: 20 °C ± 5 °C
3During 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 Conditions
Fluorodyne II grade DFL filter cartridges and Novasip filter capsules have demonstrated
the ability to withstand multiple in situ steam and autoclave cycles, and other
Fluorodyne II grade DFL filter capsules have demonstrated the ability to withstand
multiple autoclave cycles. Kleenpak Nova, Kleenpak and Mini Kleenpak capsules with
Fluorodyne 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 3
Product Claims for in situ Steaming of Fluorodyne II grade DFL Filter Cartridges
and Novasip Filter Capsules
Fluorodyne II grade Maximum Recommended
DFL Filter Styles Steaming Conditions Steam Life Claim1
“AB Style” Filter Cartridges in situ steam cycles at 125 °C 30 x 1 hour cycles
in 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 cycles
MCY Style and Novasip Filter in situ steam cycles at 140 °C 10 x 1 hour cycles
Capsules
Junior Filter Cartridges – in situ steam cycles at 125 °C 30 x 1 hour cycles
Sealkleen and SBF Styles
1The above claims are supported by data that incorporates a safety margin.
Table 4
Product Claims for Autoclave Sterilization of Fluorodyne II grade DFL Mini Kleenpak,
Kleenpak, and Kleenpak Nova Filter Capsules
Maximum Recommended
Pall 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 cycles
1The above claim is supported by data that incorporates a safety margin.
1.2.3 Determination of Water Flow Characteristics
Differential pressure measurements at set water flow rates have been determined for
typical Fluorodyne II grade DFL filters cartridges and capsules. These data can be
used to assist users in sizing filter systems employing Fluorodyne II grade DFL filter
cartridges 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 grade
DFL filter cartridges and capsules have been determined using water as the
extraction fluid.
The data presented in this guide support the following product claims for aqueous
extractables for Fluorodyne II grade DFL filter cartridges and capsules as shown in
Table 5.
Table 5
Product Claims for Aqueous Extractables from Fluorodyne II grade DFL Filter
Cartridges and Filter Capsules
Typical Extractables in Water at 20 °C
Pall 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 mg
and 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 Tests
All of the materials used in Fluorodyne II grade DFL filter cartridges and capsules
meet the requirements of the Biological Reactivity Tests (in vivo), listed in the current
revision of the United States Pharmacopeia (USP) chapter <88> for Class VI-121 °C
plastics. The tests included the Systemic Injection test, the Intracutaneous test and
the Implantation test.
1.2.6 Evaluation of Shelf Life (Pre-sterilized Capsules)
The data presented in this report demonstrate that pre-sterilized Fluorodyne II grade
DFL filter capsules retain their strength and expected performance after storage for
up 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 in
Fluorodyne II grade DFL Filter Cartridges and Kleenpak Nova filter capsules
2.1 Introduction
The 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 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 micrometer rated filters because of its small
size (0.3 µm mean diameter).”
In accordance with the requirements of this guideline, liquid challenge tests using
Brevundimonas diminuta were performed with Fluorodyne II grade DFL filter cartridges using
a minimum of 1 x 107colony forming units (CFU)/cm2of effective filtration area.
The FDA guideline further states:
“After a filtration process is properly validated for a given product, process and filter, it is
important to ensure that identical filters (e.g. of identical polymer construction 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... Forward flow and bubble point tests,
when appropriately employed, are two integrity tests that can be used. A production filter’s
integrity test specification should be consistent with the data generated during bacterial
retention validation studies.”
The correlation between microbial retention and a non-destructive integrity test is an important
aspect of the validation of sterilizing-grade filters. The Forward Flow integrity test was the
integrity test used during this study.1
1Pall, David B., “Quality Control of Absolute Bacteria Removal Filters,” Bulletin of the Parenteral Drug Assoc., 1973.”
www.pall.com/biopharm 9
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2.1.1 The Forward Flow Integrity Test
In the Forward Flow integrity test, a filter is wetted with an appropriate test liquid and
a 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 can
be measured on the upstream side, using sensitive flow measurement equipment
such as the Palltronic®Flowstar filter integrity test instrument (Figure 1). This gas flow
is comprised of diffusion plus bulk flow through any unwetted pores.
Figure 1
The 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 using
Brevundimonas diminuta and to document the correlation of the integrity test
parameters to the microbial removal efficiency.
2.2 Summary of Methods
Typical Fluorodyne II grade DFL filter cartridges, part number AB1DFL7PH4, membrane area
0.55 m² (5.9 ft2), from a minimum of three separate manufacturing batches were subjected to
standard microbial challenge tests using an aqueous suspension of Brevundimonas diminuta.
Prior to the challenge tests the filters were installed in an appropriate housing, flushed with
deionized (DI) water at a flow rate of 8 L/min for 5 minutes, and then autoclaved at 121 °C for
60 minutes. A Forward Flow integrity test was then performed using an air test pressure of
2760 mbar (40 psi). The filter assembly was then aseptically connected to the pre-sterilized
challenge apparatus, as shown in Figure 2.
An aqueous suspension of Brevundimonas diminuta was passed through the filter cartridge to
achieve a challenge level of > 1 x 107CFU/cm2of effective filtration area.
During the challenge test the entire filter effluent was passed through a 0.2 µm-rated analysis
disc 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 not
bacteria had passed through the test filter during the challenge. The titer reduction (TR) for each
filter (Equation 1) was determined as follows:
Wetted filter
(in housing)
Outlet open to
atmospheric
pressure
Upstream
isolated
Calibrated pressure
indicator upstream of
filter assembly
Regulated
compressed
gas supply
Palltronic Flowstar instrument
integrity test
Equation 1
Titer Reduction
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 107)
On completion of the challenge test the filter assemblies were autoclaved and then flushed
and Forward Flow integrity tested as described previously.
Figure 2
Microbial Challenge Apparatus
2.3 Results
The Forward Flow and Brevundimonas diminuta retention results are shown in Table 6. The
higher 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 when
challenged with > 1 x 107CFU/cm2of filtration area using Brevundimonas diminuta.
Table 6
Results 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
www.pall.com/biopharm 11
Test
Filter
Analysis
Membrane Filter
Drain
Pressure Vessel
with Bacterial
Suspension
Regulated
Air Supply
12
Table 6 Continued
Results 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 103colonies
1Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C.
2.4 Conclusions
Based 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. Integrity
test parameters for Fluorodyne II grade DFL filter cartridges, part number AB1DFL7PH4, and
Kleenpak Nova filter capsules with the prefix NP6DFL or NT6DFL have been set as shown
in Table 7.
Table 7
Forward Flow Integrity Test Parameters for 254 mm (10 in.) Filter Elements used in Fluorodyne II
grade DFL filter cartridges part number AB1DFL7PH4 and Kleenpak Nova filter capsules, part
number 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 limit212 mL/min
1See Section 2.2 for test procedure.
2During 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 Introduction
Based on the integrity test parameters for 254 mm (10 in.) Fluorodyne II grade DFL filter
cartridges (Table 7), Forward Flow integrity test parameters were set for other filter styles
incorporating 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 from
production to demonstrate that filters passing the Forward Flow integrity test provided sterile
effluent during challenge tests.
3.2 Summary of Methods
Forward Flow integrity test parameters were set for other filter styles incorporating Fluorodyne II
grade DFL filter media as shown in Table 8.
Table 8
Forward Flow Integrity Test Parameters for other styles of Fluorodyne II grade DFL Filter
Cartridges and Filter Capsules
Pall Filter Maximum Allowable
Part Number Wetting Liquid1Air 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
KA2DFLP Water 2760 mbar (40 psi) 2.0 mL/min
KA3DFLP Water 2760 mbar (40 psi) 3.4 mL/min
KA4DFLP Water 2760 mbar (40 psi) 7.4 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
C(L)3DFLP* Water 2760 mbar (40 psi) 3.4 mL/min
SBF1DFLP Water 2760 mbar (40 psi) 1.0 mL/min
MCY1110DFL Water 2760 mbar (40 psi) 0.8 mL/min
MCY2220DFL Water 2760 mbar (40 psi) 1.6 mL/min
MCY4440DFLP Water 2760 mbar (40 psi) 3.4 mL/min
SLK7001DFLP Water 2760 mbar (40 psi) 2.0 mL/min
SLK7002DFLP Water 2760 mbar (40 psi) 4.0 mL/min
AB05DFL2P Water 2760 mbar (40 psi) 6.0 mL/min
1Temperature: 20 °C ± 5 °C
2During the test period the temperature of the filter assembly should not vary more than +1 °C.
www.pall.com/biopharm 13
14
In order to validate the integrity test limit value, production samples of the respective filter styles
were subjected to Forward Flow integrity testing and liquid bacterial challenge testing using
Brevundimonas diminuta according to the principles of the procedures described in Section 2.
When testing pre-sterilized (irradiated) filter capsules, the samples were aseptically connected to
the bacterial challenge apparatus and no pre-challenge Forward Flow integrity test or autoclave
cycle was performed. A Forward Flow integrity test was conducted on completion of the
challenge test.
3.3 Results
The bacterial challenge and Forward Flow results for non-irradiated filter cartridges and
capsules (sterilized by autoclaving prior to bacterial challenge) are shown in Table 9. The
Forward Flow values that are presented are the higher of the pre- and post microbial challenge
measurements.
The bacterial challenge and Forward Flow results for pre-sterilized (irradiated) filter capsules are
shown in Table 10. The Forward Flow values that are presented are the post-microbial
challenge measurements.
All of the filters with Forward Flow values below the limit value provided a sterile effluent when
challenged. In some cases filters with Forward Flow values above the recommended limit value
also gave a sterile effluent when subjected to a liquid challenge test.
Table 9
Results 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 Continued
Results 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 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
www.pall.com/biopharm 15
16
Table 9 Continued
Results 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
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
Table 9 Continued
Results 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
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
SLK7001DFLP2IL4284012 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
www.pall.com/biopharm 17
18
Table 9 Continued
Results 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
SLK7001DFLP1IM0624060 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
SLK7002DFLP2IM8610033 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
AB05DFL2P2IL6286090 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
1Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C, maximum allowable limit
values presented in Table 8.
2Pre-challenge Forward Flow values are reported.
Table 10
Results of Forward Flow and Brevundimonas diminuta Retention for Typical Fluorodyne II grade
DFL Filter Capsules pre-sterilized by gamma irradiation at no greater than 50 kGy
Pall Filter Pall Filter Forward Flow1Sterile 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
www.pall.com/biopharm 19
20
Table 10 Continued
Results of Forward Flow and Brevundimonas diminuta Retention for Typical Fluorodyne II grade
DFL Filter Capsules pre-sterilized by gamma irradiation at no greater than 50 kGy
Pall Filter Pall Filter Forward Flow1Sterile Titer
Part Number Serial Number (mL/min) Effluent Reduction
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
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