USTR 2838
Validation Guide
Supor®EX Grade ECV Filters
2
Table of Contents
1. Overview.......................................................................................................................................................4
1.1 Introduction ............................................................................................................................................4
1.2 Summary of Conclusions ........................................................................................................................5
2. Microbial Retention Validation Tests for AB Style Supor EX Grade ECV Cartridges...............................7
2.1 Introduction ............................................................................................................................................7
2.2 Summary of Methods ..............................................................................................................................8
2.3 Results ....................................................................................................................................................9
2.4 Conclusions ..........................................................................................................................................11
3. Microbial Validation Tests of Other Styles of Supor EX Grade ECV Filters............................................11
3.1 Introduction ..........................................................................................................................................11
3.2 Summary of Methods ............................................................................................................................11
3.3 Results ..................................................................................................................................................12
3.4 Conclusions ..........................................................................................................................................12
4. Endurance to In-Situ Steam Sterilization and Autoclaving .....................................................................13
4.1 Introduction ..........................................................................................................................................13
4.2 Summary of Methods ............................................................................................................................13
4.3 Results ..................................................................................................................................................14
4.4 Conclusions ..........................................................................................................................................16
5. Determination of Water Flow Characteristics ..........................................................................................17
5.1 Introduction ..........................................................................................................................................17
5.2 Summary of Methods ............................................................................................................................17
5.3 Results ..................................................................................................................................................17
5.4 Conclusions ..........................................................................................................................................17
6. Determination of Water Flow Characteristics for Other Styles of Supor EX Grade ECV Filters ...........18
6.1 Introduction ..........................................................................................................................................18
6.2 Summary of Methods ............................................................................................................................18
6.3 Results ..................................................................................................................................................18
6.4 Conclusions ..........................................................................................................................................19
7. Extractables Testing Using Water ............................................................................................................19
7.1 Introduction ..........................................................................................................................................19
7.2 Summary of Methods ............................................................................................................................19
7.3 Results of NVR and FTIR ......................................................................................................................21
7.4 Conclusions ..........................................................................................................................................23
8. Extractables Testing of Other Supor EX Grade ECV Filters Using Water...............................................23
8.1 Introduction ..........................................................................................................................................23
8.2 Summary of Methods ............................................................................................................................23
8.3 Results of NVR and FTIR ......................................................................................................................24
8.4 Conclusions ..........................................................................................................................................26
9. Biological Safety Tests on the Materials of Construction .......................................................................26
9.1 Introduction ..........................................................................................................................................26
9.2 Summary of Tests ..................................................................................................................................27
9.3 Results ..................................................................................................................................................28
9.4 Conclusions ..........................................................................................................................................28
www.pall.com/biopharm 3
4
1. Overview
1.1 Introduction
This guide contains validation data for 0.2 micron microbially rated Supor EX grade ECV filters
in sanitary “AB style” filter cartridge format and Supor EX grade ECV filters in Kleenpak™ Nova
capsule filter format.
Regulatory guidelines for the pharmaceutical industry comprise many well-defined and
established quality and safety standards for manufacturers to consider when qualifying
their processes (and components thereof) to ensure the output of reliable and reproducibly
manufactured finished goods.
Sterilizing grade filters incorporating advanced membrane filtration technology play an important
role as key components in these manufacturing processes. They are a significant contributor to
the successful accomplishment of stringent quality and safety objectives where in accordance
with Current Good Manufacturing Practices (cGMP), microbial and particulate contamination
of process fluids must be carefully negated.
Supor EX grade ECV filters have been designed as liquid sterilizing filters for use within the
pharmaceutical industry and can satisfy the safety and quality requirements of the end-user
across a range of fluids. These can include either those essential to the functioning of a unit
operation (buffers, growth media and bioreactor additives used in biological drug manufacturing)
or those containing active pharmaceutical ingredients in either intermediate or final delivery form
(topical, oral, or injectables).
The 254 mm (10 inch) sanitary AB style filter is manufactured using a patented laid-over pleat
construction. This pleat configuration maximizes membrane area in order to increase flow rates
and optimizes filter life.
The removal rating of Supor EX grade ECV filters of 0.2 micron is based on the proven retention
of Brevundimonas diminuta (ATCC 19146) under challenge conditions correlated to standard test
method ASTM 838-05. Supor EX grade ECV filters feature a novel construction, being comprised
of two layers of polyethersulfone (PES) membrane. The combination of the asymmetric upstream
membrane layer with the symmetric downstream membrane layer provides excellent flow and
throughput while enabling sterilizing grade bacterial removal performance.
As part of Pall’s commitment to delivering the highest quality sterilizing grade filters to the
pharmaceutical manufacturer, Supor EX grade ECV filters have been rigorously tested and
qualified by Pall’s R&D division to an appropriate performance specification. In addition,
Supor EX grade ECV filters are also systematically tested for quality during and after
production to confirm the maintenance of this specification from batch to batch.
This guide specifically documents the product qualification tests performed to establish Supor
EX grade ECV filter’s performance specification.
The purpose of the guide is to support the selection and qualification of Supor EX grade ECV
filters for a manufacturing process.
The qualification test program for Supor EX grade ECV filters included:
• Microbial retention validation tests correlated to standard test method ASTM 838-05
• Endurance to in-situ steam sterilization and autoclaving under water wet conditions
• Determination of water flow characteristics
• Extractables testing using water
• Biological safety tests on filter components (after sterilization) – Compliance with United
Stated Pharmacopoeia (USP) Biological Reactivity Tests (in vivo) for Class VI-121 °C plastics
www.pall.com/biopharm 5
This guide may be combined with other documentation for Supor EX grade ECV filters,
namely the technical product datasheet and Pall’s pharmaceutical Certificate of Test for
a comprehensive package that substantiates the product specification and quality
control standards applied to Supor EX grade ECV filters.
Following an appropriate risk assessment and in reference to FDA’s Guidance for Industry:
Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice
(September 2004), Pall advises that, where necessary, Supor EX grade ECV filters are subject
to a process-specific test program that considers the end-user’s own operating conditions and
acceptance criteria.
Note: The units of pressure quoted in this document are “bar” and “pounds force
per square inch (psi)”. The following figures can be used to convert these units of
pressure to Pascals (Pa):
• 1 bar = 1 x 105Pa
• 1 psi = 6.89476 x 103Pa
1.2 Summary of Conclusions
Microbial Retention Validation Tests
Supor EX grade ECV filter cartridges in AB style were tested for bacterial retention of
Brevundimonas diminuta (ATCC 19146) using bacterial challenge tests correlated to ASTM
Standard Test Method F838-05, and in accordance with the FDA’s Guidance for Industry –
Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice
(September 2004).
The Forward Flow integrity test was shown to be a suitable non-destructive integrity test for
Supor EX grade ECV filter cartridges, and test parameters have been set as follows for 254 mm
(10 inch) filters (part number AB1UECV7PH4). These test parameters are also applicable to
254 mm (10 inch) capsule filters in Kleenpak Nova capsules, part number N*UECVP#G
(*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).
Table 1
Forward Flow Integrity Test Parameters for 254 mm (10 inch) Supor EX Grade ECV Filter Elements,
Part Numbers AB1UECV7PH4 and N*UECVP#G
* T (T-style) or P (In-line style), # Fitting code (1 = sanitary ange or 6 = Hose barb).
** During the test period the temperature of the lter assembly should not vary more than ± 1 °C (2 °F).
Test pressure 2760 mbar (40 psi)
Wetting liquid Water
Temperature 20 °C ± 5 °C (68 °F ± 9 °F)
Test gas Air
Maximum allowable Forward Flow limit** 21.0 mL/min
6
Endurance to In-Situ Steam Sterilization and Autoclaving
Supor EX grade ECV filter cartridges have been demonstrated to be capable of withstanding
multiple in-situ steam sterilization and autoclave cycles under various standard steaming
conditions. Tests performed demonstrate that the Supor EX grade ECV filter cartridges are
robust and capable of withstanding differential pressures up to 300 mbar (4.35 psi) in the
forward direction during steaming.
The data presented in this report support the following product claim for in-situ steaming and
autoclaving 254 mm (10 inch) Supor EX grade ECV filters in sanitary AB style cartridges:
The autoclave resistance of the Kleenpak Nova capsules has been investigated separately
and is documented in the Pall document USTR 2099 “Validation Guide for Pall ‘Kleenpak’
Nova Filter Capsules”. The product claim for autoclave resistance of Kleenpak Nova capsules
is three (3) autoclave cycles at 125 °C (257 °F). Kleenpak Nova capsules must not be subject
to in-situ steaming.
The following product claim for autoclaving is therefore applicable to 254 mm (10 inch) Supor
EX grade ECV filter cartridges in Kleenpak Nova G-grade capsules:
*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary ange or 6 = Hose barb).
The above claims are supported by data with a 100 % safety margin.
Determination of Water Flow Characteristics
Differential pressure measurements at set water flow rates have been determined. The typical
clean water flow rate for a 254 mm (10 inch) filter (part number AB1UECV7PH4) is 17 L/min at
a pressure drop of 100 mbar (1.45 psi) at 20 °C (68 °F). These data are also applicable to the
254 mm (10 inch) Supor EX grade ECV filters in Kleenpak Nova capsules and can thus be used
to assist users in sizing filter systems employing any 254 mm (10 inch) Supor EX grade ECV filters.
Extractables Testing using Water
The typical amount of non-volatile residue (NVR) extracted from Supor EX grade ECV filter
cartridges in sanitary AB1 style has been determined using water as the extraction fluid. For the
254 mm (10 inch) filter cartridges tested (part number AB1UECV7PH4) the aqueous extractables
values were 4.8-139.9 mg per cartridge in the first extraction without pre-flushing, and were
always much reduced in the second (consecutive) extraction (1.0-19.1 mg per cartridge),
demonstrating depletion of the extractables. The data justify the following product claim for
Supor EX grade ECV filter cartridges in AB1 style, part number AB1UECV7PH4: NVR < 150 mg.
The typical amount of non-volatile residue (NVR) extracted from Supor EX grade ECV filters of
other styles has also been determined using water as the extraction fluid. For the 254 mm
(10 inch) filters cartridges tested in Kleenpak Nova capsules after autoclaving (part number
NP6UECVP1G), the aqueous extractables values ranged from 48.5 to 118.9 mg. For the 254 mm
(10 inch) filter cartridges tested in Kleenpak Nova capsules after gamma sterilization with an
irradiation dose of 50 ± 5 kGy the aqueous extractables values ranged from 11.5 to 15.2 mg.
Filter Part Number Steaming Conditions Maximum Steam Life Claim
AB1UECV7PH4 In-situ steam cycles at
125 °C (257 °F)
5 one-hour cycles
AB1UECV7PH4 In-situ steam cycles at
135 °C (275 °F)
1 one-hour cycle
AB1UECV7PH4 Autoclave cycles at
125 °C (257 °F)
5 one-hour cycle
Filter Part Number Steaming Conditions Maximum Steam Life Claim
N*UECVP#G Autoclave cycles at
125 °C (257 °F)
3 one-hour cycles
www.pall.com/biopharm 7
The data justify that the above product claim for 254 mm (10 inch) Supor EX grade ECV
filter cartridges in AB1 style, part number AB1UECV7PH4: NVR < 150 mg is also applied to
254 mm (10 inch) Supor EX filters in Kleenpak Nova capsules in G and S-grade.
The FTIR spectra of all extracts indicate the presence of compounds typical for these materials
of construction, i.e. the copolymer used to render the polyethersulfone membranes hydrophilic,
and oligomers associated with polypropylene. The latter were not detected in the extracts of
the Supor EX grade ECV filters in Kleenpak Nova capsules in S-grade (i.e. after gamma
sterilization) with the methods applied.
Actual service in pharmaceutical applications will impose different conditions, such as different
steaming conditions, exposure times, temperature, liquid type, etc. Evaluation under process
conditions is therefore also recommended.
Biological Safety Tests
All of the materials used in Supor EX grade ECV filters in AB style cartridges and in Kleenpak
Nova capsules meet the requirements of the United States Pharmacopoeia (USP) Biological
Reactivity Tests (in vivo) for Class VI-121 °C plastics. The tests included the Systemic Injection
test, the Intracutaneous test and the Implantation test.
Copies of the test reports are available by contacting Pall Corporation.
2. Microbial Retention Validation Tests for AB Style Supor EX Grade ECV Cartridges
2.1 Introduction
The FDA’s Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing –
Current Good Manufacturing Practice (September 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 micron 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 (ATCC 19146) were performed with Supor EX grade ECV 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 test was the integrity test
used during this study.
8
The Forward Flow Test
In the Forward Flow 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 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, see Figure 2.1.
Figure 2.1
The Automated Integrity Test
The aim of this study was to demonstrate the microbial removal efficiency of typical Supor
EX grade ECV filter cartridges in liquid challenge tests using Brevundimonas diminuta
(ATCC 19146) and to document the correlation of the integrity test parameters to the
microbial removal efficiency.
2.2 Summary of Methods
Supor EX grade ECV filter cartridges, part number AB1UECV7PH4 (membrane area 1.04 m2
[11.2 ft2]), were subjected to standard microbial challenge tests using an aqueous suspension
of Brevundimonas diminuta (ATCC 19146). Filter manufacturing and sampling considered
possible variation in the filter manufacturing conditions. The filter samples represent 4 different
sub-batches (A-D) with respect to the combination of different membrane rolls used in the
manufacture of these sub-batches.
Prior to the challenge tests the filter cartridges were installed in an appropriate housing,
flushed with deionized (DI) water at a flow rate of a minimum of 8 L/min for 10 minutes with
1 bar (14.5 psi) back pressure. A Forward Flow integrity test was performed using a Palltronic
Flowstar integrity test instrument with an air test pressure of 2760 mbar (40 psi). The filters
were autoclaved at 121 °C (250 °F) for 60 minutes. The filter assembly was aseptically
connected to the pre-sterilized challenge apparatus, as shown in Figure 2.2.
An aqueous suspension of Brevundimonas diminuta was passed through the filter to achieve a
challenge level of > 1 x 107colony forming units (CFU) per cm2of effective filtration area.
During the challenge test the entire filter effluent was passed through a 0.2 micron-rated
analysis disc on the downstream side of the test filter assembly. The filter disc was incubated
on agar and, following incubation, the disc was 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 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
integrity test instrument
TR= Total number of bacteria influent to the filter
Number of colonies recorded on the downstream analysis disc
When no colonies were detected downstream, the titer reduction was expressed as:
> Total number of bacteria influent to the filter (e.g. > 1 x 1010)
On completion of the challenge test the filter assemblies were autoclaved and then flushed
and Forward Flow integrity tested as described previously.
Figure 2.2
Microbial Challenge Apparatus
2.3 Results
The Forward Flow and Brevundimonas diminuta retention results are shown in Table 2.1.
The higher of the two Forward Flow values (pre- and post-challenge) is presented and the
data are arranged in order of increasing Forward Flow value.
All of the filter cartridges gave sterile effluent when challenged with > 1 x 107CFU per cm2
of filtration area using Brevundimonas diminuta.
www.pall.com/biopharm 9
Challenge
filter
Analysis
membrane filter
Drain
Pressure vessel
with bacterial
suspension
Regulated
air inlet
10
Table 2.1
Results of Forward Flow and B. diminuta Retention for Typical Supor EX Filter Cartridges,
Part Number AB1UECV7PH4
* Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C (68 °F ± 9 °F),
maximum allowable limit value 21.0 mL/min.
Pall Cartridge
Serial Number Sub-Batch
Forward Flow*
(mL/min) Sterile Effluent Titer Reduction
IR1311237 D 14.7 yes >1.10 x 1012
IR1311054 A 15.0 yes >2.97 x 1011
IR1311162 C 15.0 yes >4.99 x 1011
IR1311004 A 15.1 yes >3.00 x 1011
IR1311001 A 15.2 yes >1.78 x 1011
IR1311049 A 15.2 yes >2.13 x 1011
IR1311113 B 15.2 yes >2.17 x 1011
IR1311194 D 15.3 yes >2.97 x 1011
IR1311219 D 15.3 yes >4.12 x 1011
IR1311055 A 15.4 yes >1.37 x 1011
IR1311193 D 15.5 yes >1.18 x 1012
IR1311075 B 15.6 yes >2.20 x 1011
IR1311157 C 15.7 yes >1.50 x 1012
IR1311149 C 15.8 yes >1.96 x 1011
IR1311230 D 15.8 yes >1.43 x 1012
IR1311090 B 15.9 yes >5.32 x 1011
IR1311104 B 15.9 yes >2.10 x 1012
IR1311069 B 16.1 yes >2.17 x 1011
IR1311034 A 16.2 yes >9.25 x 1011
IR1311165 C 16.2 yes >2.33 x 1011
IR1311229 D 16.3 yes >2.79 x 1011
IR1311179 C 16.4 yes >2.40 x 1011
IR1311248 D 16.7 yes >2.47 x 1011
IR1311029 A 16.8 yes >2.38 x 1011
IR1311028 A 16.9 yes >1.98 x 1012
IR1311107 B 17.0 yes >9.91 x 1011
IR1311066 B 17.2 yes >2.64 x 1011
IR1311150 C 18.0 yes >1.93 x 1012
IR1311118 B 18.3 yes >2.40 x 1011
IR1311168 C 18.6 yes >1.83 x 1011
IR1311128 C 24.6 yes >2.27 x 1011
IR1311208 D 98.3 yes >2.75 x 1011
2.4 Conclusions
Supor EX grade ECV filter cartridges (part number AB1UECV7PH4) were found to provide
sterile effluent when subjected to aqueous microbial challenge tests using Brevundimonas
diminuta at a challenge level of > 1 x 107CFU/cm2.
Forward Flow integrity test parameters have been defined for Supor EX grade ECV filter
cartridges based on the above results of the microbial challenge tests and additional
considerations and parameters. Data showing that filters with a Forward Flow value
>21.0 mL/min were still bacterially retentive demonstrate an adequate safety margin for
the established limit value. Capability of the Forward Flow test to distinguish non-retentive
filters has been demonstrated in other Filter Validation Guides.
Table 2
Forward Flow Integrity Test Parameters for Supor EX Grade ECV Filter Cartridges,
Part Number AB1UECV7PH4*
* See Section 2.2 for test procedure.
** During the test period the temperature of the lter assembly should not vary more than ± 1°C (2 °F).
3. Microbial Validation Tests of Other Styles of Supor EX Grade ECV Filters
3.1 Introduction
Based on the integrity test parameters set for AB style Supor EX grade ECV filters
(see Table 2.1), Forward Flow test parameters were set for other filter styles incorporating
Supor EX grade ECV filter medium. The purpose of this series of tests was to perform
Forward Flow and bacteria challenge tests on these other filter styles to demonstrate
that filters passing the Forward Flow test provided sterile filtrate during challenge tests.
3.2 Summary of Methods
Forward Flow test parameters were set for other filter styles incorporating Supor EX grade ECV
filter medium are shown in Table 3.1:
Table 3.1
Forward Flow Test Parameters for Other Styles of Supor EX Grade ECV Filters
Forward Flow values at 20 °C ± 5 °C (68 °F ± 9 °F).
During the test period the temperature of the lter assembly should not vary more than ± 1 °C (2 °F).
*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary ange or 6 = Hose barb).
In order to validate the performance and to confirm the integrity test limit values, relevant
samples of these filter styles from three different production batches were subjected to
Forward Flow and liquid bacterial challenge tests using Brevundimonas diminuta according
to the procedures described previously in Section 2: Microbial Validation Tests for AB Style
Supor EX Grade ECV cartridges.
www.pall.com/biopharm 11
Test pressure 2760 mbar (40 psi)
Wetting liquid Water
Temperature 20 °C ± 5 °C (68 °F ± 9 °F)
Test gas Air
Maximum allowable Forward Flow limit** 21.0 mL/min
Part Number Wetting Liquid Air Test Pressure
Maximum Allowable
FF (mL/min) Test Limit
N*6UECVP#G Water 2760 mbar (40 psi) 21.0
N*6UECVP#S Water 2760 mbar (40 psi) 21.0
12
N*6ECVP#G Kleenpak Nova capsules are sterilizable by autoclaving and incorporate filter
cartridges directly comparable to AB1UECV7PH4 filter cartridges. Filters of this type are
therefore fully covered by the bacterial challenge testing of AB1UECV7PH4 filter cartridges,
which were also autoclaved prior to bacterial challenge testing. S-Grade Kleenpak Nova
capsules (part number N*6ECVP#S) are sterilized by gamma irradiation (max. dose: 50 kGy).
Representative sample of N*6ECVP#S filters were therefore sterilized by gamma irradiation
at a target dose of 50 kGy (variation of irradiation process: ± 5 kGy) and submitted to
bacterial challenge testing to verify their bacteria retention capabilities.
3.3 Results
The Forward Flow and Brevundimonas diminuta retention results for Supor EX grade ECV
filters tested are shown in Table 3.2. The Forward Flow value of the filter type NP6UECVP1S
presented is the result of the Forward Flow test out-of-box prior to challenge, after the filter
capsules have been flushed with DI water at a flow rate of minimum 4 L/min for 10 min with
a 2 bar (29 psi) back pressure.
All of the filter cartridges gave sterile effluent when challenged with > 1 x 107CFU per cm2of
filtration area using Brevundimonas diminuta.
Table 3.2
Results of Forward Flow and B. diminuta Retention for Typical Pre-Sterilized (Irradiated) Supor
EX Grade Filters in Kleenpak Nova Capsules
* Forward Flow values at 2760 mbar (40 psi) air test pressure, wet with water, at 20 °C ± 5 °C (68 °F ± 9 °F).
3.4 Conclusions
Supor EX grade ECV filters incorporated in Kleenpak Nova capsules and sterilized by gamma-
irradiation were found to provide sterile effluent when subjected to aqueous microbial challenge
tests using Brevundimonas diminuta at a challenge level of > 1 x 107CFU/cm2. The results
confirm that the Forward Flow limit value for 254 mm (10 inch) Supor EX grade ECV filters in
sanitary AB-style (21.0 mL/min) is also applicable to 254 mm (10 inch) Supor EX grade ECV
filters incorporated in Kleenpak Nova capsules (part number N*6UECVP#S).
Part Number
Irradiation Dose
(kGy)
Pall Filter
Serial Number
Forward Flow*
(mL/min) Sterile Effluent Titer Reduction
NP6UECVP1S 48.3 – 49.9 IR4931 69588 15.6 yes >2.29 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69590 14.2 yes >3.34 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69592 15.4 yes >2.0 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69593 15.9 yes >1.76 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69596 15.1 yes >2.53 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69599 17.1 yes >1.94 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69602 15.6 yes >1.95 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69598 15.3 yes >2.11 x 1011
NP6UECVP1S 48.3 – 49.9 IR4931 69622 15.3 yes >2.65 x 1011
NP6UECVP1S 48.3 – 49.9 IR4932 69612 16.8 yes >2.45 x 1011
NP6UECVP1S 48.3 – 49.9 IR4932 69616 15.5 yes >2.33 x 1011
NP6UECVP1S 48.3 – 49.9 IR4932 69619 15.7 yes >3.00 x 1011
NP6UECVP1S 48.3 – 49.9 IR4932 69621 15.6 yes >3.25 x 1011
NP6UECVP1S 48.3 – 49.9 IR4932 69623 15.8 yes >2.27 x 1011
NP6UECVP1S 48.3 – 49.9 IR4932 69624 16.4 yes >3.62 x 1011
NP6UECVP1S 48.3 – 49.9 IR4932 69627 15.6 yes >2.69 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 005 11.8 yes >3.65 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 036 14.7 yes >2.48 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 042 17.0 yes >2.94 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 079 14.6 yes >3.82 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 114 15.7 yes >2.37 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 118 14.7 yes >2.24 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 128 17.1 yes >3.12 x 1011
NP6UECVP1S 47.3 – 47.6 IS0534 132 14.7 yes >2.27 x 1011
4. Endurance to In-Situ Steam Sterilization and Autoclaving
4.1 Introduction
The purpose of these tests was to determine the effects of repeated exposure to in-situ steam
cycles and autoclaving on filter integrity and water wettability using Supor EX grade ECV filter
cartridges. The tests were used to qualify the steam exposure claims for Supor EX grade ECV
filter cartridges.
4.2 Summary of Methods
In-Situ Steaming at 125 °C (257 °F) Under Water Wet Steaming Conditions
Supor EX grade ECV filters part number AB1UECV7PH4 were used for the tests.
Filter manufacturing and sampling considered possible variation in the filter
manufacturing conditions.
Twenty four (24) filter cartridges were flushed with DI water for 10 minutes and then Forward
Flow integrity tested using an air test pressure of 2760 mbar (40 psi). The wet filter cartridges
were then subjected to a one-hour in-situ steam cycle at 125 °C (257 °F).
During the initial stages of the steam cycles, the wet filter membrane caused the differential
pressure to increase across the filter cartridge as steam was introduced. The steam inlet valve
was controlled so that the differential pressure across the wetted filter cartridge did not exceed
300 mbar (4.35 psi).
Immediately after each one-hour steam cycle had finished, dry compressed air was flushed
across the upstream side of the filter cartridge surface for 30 minutes in order to replace the
steam and cool the assembly. The cartridges were then flushed with water prior to Forward
Flow integrity testing between steaming cycles and also prior to starting the next steam cycle.
This test sequence was repeated until each filter cartridge had been exposed to 10 one-hour
steam cycles. The filters were Forward Flow integrity tested after steam cycle 1, cycle 2,
cycle 3, cycle 4, cycle 5, cycle 8, and cycle 10.
In-situ Steaming at 135 °C (275 °F) Under Water Wet Steaming Conditions
Supor EX grade ECV filters part number AB1UECV7PH4 were used for the tests.
Filter manufacturing and sampling considered possible variation in the filter
manufacturing conditions.
Twenty four (24) filter cartridges were flushed with DI water for 10 minutes and then Forward
Flow integrity tested using an air test pressure of 2760 mbar (40 psi). The wet filter cartridges
were then subjected to a one-hour in-situ steam cycle at 135 °C (275 °F).
During the initial stages of the steam cycles, the wet filter membrane caused the differential
pressure to increase across the filter cartridge as steam was introduced. The steam inlet valve
was controlled so that the differential pressure across the wetted filter cartridge did not exceed
300 mbar (4.35 psi).
Immediately after each one-hour steam cycle had finished, dry compressed air was flushed
across the upstream side of the filter cartridge surface for 30 minutes in order to replace the
steam and cool the assembly. The cartridges were then flushed with water prior to Forward
Flow integrity testing between steaming cycles and also prior to starting the next steam cycle.
This test sequence was repeated until each filter cartridge had been exposed to 3 one-hour
steam cycles. The filters were Forward Flow integrity tested after steam cycle 1, cycle 2,
and cycle 3.
www.pall.com/biopharm 13
14
Autoclaving at 125 °C (257 °F) Under Water Wet Autoclave Conditions
Supor EX grade ECV filters part number AB1UECV7PH4 were used for the tests.
Filter manufacturing and sampling considered possible variation in the filter
manufacturing conditions.
Twelve (12) filter cartridges were flushed with DI water for 10 minutes and then Forward Flow
integrity tested using an air test pressure of 2760 mbar (40 psi). The wet filter cartridges were
then subjected to five (5) autoclave cycles at 125 °C (257 °F) (slow exhaust). After the autoclave
has cooled down to ambient temperature, the filter cartridge was removed from the autoclave,
flushed with DI water for 10 minutes and then Forward Flow integrity tested using an air test
pressure of 2760 mbar (40 psi). This test sequence was repeated so that each filter cartridge
had been exposed to 10 autoclave cycles.
4.3 Results
In-situ Steaming at 125 °C (257 °F) Under Water Wet Steaming Conditions
The Forward Flow integrity test results for Supor EX grade ECV filter cartridges (part number
AB1UECV7PH4) before and after exposure to one-hour in-situ steam cycles are shown in
Table 4.1. All of the filter cartridges retained integrity following exposure to ten (10) one-hour
cycles at 125 °C (275 °F).
Table 4.1
Effects of Wet In-Situ Steam Exposure at 125 °C (257 °F) on Filter Integrity for Supor EX Grade
ECV AB1UECV7PH4 Filter Cartridges
* Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C (68 °F ± 9 °F),
maximum allowable limit value 21.0 mL/min.
Forward Flow* (mL/min) test results before and after exposure
to 10 in-situ steam cycles at 125 °C (257 °F):
Pall Cartridge
Serial Number
FF (mL/min)
pre steaming
FF (mL/min)
post steaming
IP5325001 15.1 12.2
IP5325002 15.8 14.4
IP5325014 16.7 13.8
IP5325019 14.4 13.4
IP5325031 14.9 13.2
IP5325035 13.9 16.8
IP5325039 14.0 14.8
IP5325048 15.8 13.3
IP5325060 14.8 11.8
IP5325067 15.4 13.0
IP5325073 15.2 12.1
IP5325090 15.1 12.0
IP5325112 16.1 18.9
IP5325124 15.9 15.7
IP5325134 Not Tested 14.6
IP5325137 16.6 12.6
IP5325146 18.5 16.4
IP5325153 15.0 13.3
IP5325154 15.2 13.2
IP5325167 16.1 13.3
IP5325173 15.2 13.1
IP5325178 16.2 14.2
IP5325183 17.4 15.6
IP5325187 16.2 14.4
In-situ Steaming at 135 °C (275 °F) Under Water Wet Steaming Conditions
The Forward Flow integrity test results for Supor EX grade ECV filter cartridges (part number
AB1UECV7PH4) before and after exposure to one-hour in-situ steam cycles are shown in
Table 4.2. All of the filter cartridges retained integrity following exposure to three (3) one-hour
cycles at 135 °C (275 °F).
Table 4.2
Effects of Wet In-Situ Steam Exposure at 135 °C (275 °F) on Filter Integrity for Supor EX Grade
ECV AB1UECV7PH4 Filter Cartridges
* Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C (68 °F ± 9 °F),
maximum allowable limit value 21.0 mL/min.
www.pall.com/biopharm 15
Pall Cartridge
Serial Number
Forward Flow* (mL/min) test results before and after exposure
to 3 in-situ steam cycles at 135 °C (275 °F):
FF (mL/min)
pre steaming
FF (mL/min)
post steaming
IR1311007 17.5 12.4
IR1311008 15.8 12.0
IR1311009 12.3 9.29
IR1311012 16.7 12.1
IR1311032 16.1 12.2
IR1311035 15.3 12.6
IR1311056 17.0 12.7
IR1311070 16.9 12.3
IR1311087 16.9 14.7
IR1311094 16.6 12.1
IR1311106 16.9 13.8
IR1311116 16.4 15.1
IR1311119 16.6 15.1
IR1311131 16.3 12.8
IR1311140 17.6 13.6
IR1311167 14.3 13.6
IR1311180 17.1 14.3
IR1311185 15.6 11.1
IR1311186 17.3 14.5
IR1311196 15.7 12.5
IR1311203 16.1 12.7
IR1311222 15.4 13.4
IR1311225 17.0 13.4
IR1311234 15.7 12.1
16
Autoclaving at 125 °C (257 °F) Under Water Wet Autoclave Conditions
The Forward Flow integrity test results for Supor EX grade ECV filter cartridges (part number
AB1UECV7PH4) before and after exposure to one-hour autoclave cycles are shown in
Table 4.3. All of the filter cartridges retained integrity following exposure to ten (10) one-hour
cycles at 125 °C (257 °F).
Table 4.3
Effects of Wet Autoclave Exposure at 125 °C (257 °F) on Filter Integrity for Supor EX Grade ECV
AB1UECV7PH4 Filter Cartridges for Integrity Testing
* Forward Flow values determined at 2760 mbar (40 psi) air test pressure, wet with water at 20 °C ± 5 °C (68 °F ± 9 °F),
maximum allowable limit value 21.0 mL/min.
4.4 Conclusions
Supor EX grade ECV filter cartridges have been demonstrated to be capable of withstanding
multiple in-situ steam and autoclave sterilization cycles, while water wet prior to steaming.
The filter cartridges will fully wet for integrity testing both before and after exposure to wet
in-situ steam cycles.
The data presented in this section support the following product claims for in-situ steaming and
autoclaving of 254 mm (10 inch) Supor EX grade ECV filter cartridges in AB style:
The data also support the autoclave resistance of Supor EX grade ECV filters in Kleenpak
Nova configuration (G-grade), as they incorporate 254 mm (10 inch) Supor EX grade ECV
filter cartridges.
The autoclave resistance of the Kleenpak Nova capsules has been investigated separately
and is documented in the Pall document USTR 2099 “Validation Guide for Pall ‘Kleenpak’
Nova Filter Capsules”. The product claim for autoclave resistance of Kleenpak Nova
capsules is three (3) autoclave cycles at 125 °C (257 °F).
Forward Flow* (mL/min) test results before and after exposure
to 10 autoclave cycles at 125 °C (257 °F):
Pall Cartridge
Serial Number
FF (mL/min)
pre autoclaving
FF (mL/min)
post autoclaving
IP5325015 15.3 11.5
IP5325027 14.4 12.4
IP5325029 13.9 12.5
IP5325058 14.0 12.3
IP5325070 13.7 10.2
IP5325087 13.2 10.1
IP5325158 15.7 13.7
IP5325161 15.0 14.1
IP5325169 14.5 12.0
IP5325174 14.0 12.6
IP5325189 16.8 12.4
IP5325195 15.6 14.3
Filter Part Number Steaming Conditions Maximum Steam Life Claim
AB1UECV7PH4 In-situ steam cycles at
125 °C (257 °F)
5 one-hour cycles
AB1UECV7PH4 In-situ steam cycles at
135 °C (275 °F)
1 one-hour cycle
AB1UECV7PH4 Autoclave cycles at
125 °C (257 °F)
5 one-hour cycle
The following product claim for autoclaving is therefore applicable to 254 mm (10 inch)
Supor EX grade ECV filter cartridges in Kleenpak Nova G-grade configuration:
*: T (T-style) or P (In-line style), # Fitting code (1 = sanitary ange or 6 = Hose barb).
The above claims are supported by data with a 100 % safety margin.
5. Determination of Water Flow Characteristics
5.1 Introduction
The aim of these tests was to determine the typical differential pressure across Supor EX grade
ECV filter cartridges at set water flow rates.
5.2 Summary of Methods
The tests were performed on twenty four (24) Supor EX grade ECV filter cartridges part number
AB1UECV7PH4. Filter manufacturing and sampling considered possible variation in the filter
manufacturing conditions. The filters represent four (4) different sub-batches with respect to
the combination of different membrane rolls used in the manufacture of these sub-batches.
Pre-filtered DI water was pumped through the filters in the normal flow (‘out to in’) direction.
Pressure readings from transducers on the upstream and downstream sides of the test
assembly were monitored to calculate the differential pressure at set water flow rates.
The results were corrected for a standard temperature of 20 °C (68 °F).
5.3 Results
Figure 5.1 shows the clean water flow rates of the twenty four (24) Supor EX grade ECV filter
cartridges, part number AB1UECV7PH4, that were tested.
Figure 5.1
Water Flow/Differential Pressure Values of Supor EX Grade ECV Filter Cartridges,
Part Number AB1UECV7PH4
5.4 Conclusions
Water flow rates at set differential pressures have been determined. The results support that
the typical clean water flow rate for a 254 mm (10 inch) Supor EX grade ECV filter cartridge
(part number AB1UECV7PH4) at 100 mbar (1.45 psi) pressure drop is 17 L/min at 20 °C
(68 °F). These data can be used to assist users in sizing filter systems employing Supor
EX grade ECV filter cartridges.
www.pall.com/biopharm 17
Filter Part Number Steaming Conditions Maximum Steam Life Claim
N*UECVP#G Autoclave cycles at
125 °C (257 °F)
3 one-hour cycles
Flow (L/min)
Differential pressure at 20 ˚C (mbar)
100
0
IP532500
IP532500
IP532501
IP532501
IP532503
IP532503
IP532503
IP532504
IP532506
IP532506
IP532507
IP532509
IP532511
IP532512
IP532513
IP532513
IP532514
IP532515
IP532515
IP532516
IP532517
IP532517
IP532518
IP532518
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
18
6. Determination of Water Flow Characteristics for Other Styles of Supor
EX Grade ECV Filters
6.1 Introduction
The aim of these tests was to determine the typical differential pressure across other styles of
Supor EX grade ECV filter cartridges at set water flow rates. Table 6.1 shows the additional
styles of Supor EX grade ECV filters that were tested.
Table 6.1
Styles of Supor EX Grade ECV Filters Tested for Water Flow Characteristic
*S-Grade: Pre-sterilized by Gamma irradiation.
6.2 Summary of Methods
The tests were performed on twelve (12) Supor EX grade ECV filters from three (3) different
production batches of each filter style, part numbers NP6UECVP1G and NP6UECVP1S.
Pre-filtered DI water was pumped through the filters in the normal flow (‘out to in’) direction.
Pressure readings from transducers on the upstream and downstream sides of the test
assembly were monitored to calculate the differential pressure at set water flow rates.
The results were corrected for a standard temperature of 20 °C (68 °F).
6.3 Results
Figure 6.1 shows the clean water flow rates of the twelve (12) Supor EX grade ECV filters,
part number NP6UECVP1G that were tested. Figure 6.2 shows the clean water flow rates
of the twelve (12) Supor EX grade ECV filters, part number NP6UECVP1S (i.e. after gamma
sterilization), that were tested.
Figure 6.1
Water Flow/Differential Pressure Values of Kleenpak Nova Capsules with Supor EX Grade
ECV Filters, Part Number NP6UECVP1G
Part Number Test Condition
NP6UECVP1G Out-of-Box
NP6UECVP1S* Out-of-Box
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Flow (L/min)
Differential pressure at 20 ˚C (mbar)
0
100
IR49316958
IR49316958
IR49316958
IR49316958
IR49326960
IR49326961
IR49326960
IR49326960
IS05347186
IS05347186
IS05347186
IS05347186
Figure 6.2
Water Flow/Differential Pressure Values of Kleenpak Nova Capsules with Supor EX Grade
ECV Filters, Part Number NP6UECVP1S
6.4 Conclusions
Water flow rates at set differential pressures have been determined. The results support that
the typical clean water flow rate for a 254 mm (10 inch) Supor EX grade ECV filter cartridge
in AB style (part number AB1UECV7PH4) at 100 mbar (1.45 psi) pressure drop, which is
17 L/min at 20 °C (68 °F), is also applicable to the 254 mm (10 inch) Supor EX grade ECV
filters in Kleenpak Nova capsules in G and in S version, part numbers N*6UECV#PG and
N*6UECV#PS. These data can thus be used to assist users in sizing filter systems
employing 254 mm (10 inch) Supor EX grade ECV filters cartridges in any style.
(*T (T-style) or P (In-line style), # Fitting code (1 = sanitary flange or 6 = Hose barb).
7. Extractables Testing Using Water
7.1 Introduction
The aim of this series of tests was to quantify and characterize the material that can be
extracted from Supor EX grade ECV filter cartridges using water.
7.2 Summary of Methods
Forty four (44) Supor EX grade ECV filter cartridges in AB style (part number AB1UECV7PH4)
from five filter batches were used for the tests.
Preparation of Filter Samples
Prior to the extraction tests the Supor EX grade ECV filter samples were autoclaved in order to
maximize the quantity of any extractable material present. The filter cartridges were wrapped
in aluminum foil and autoclaved for one hour at 125 °C ± 5 °C (257 °F ± 9 °F), using a slow
exhaust cycle. Visible droplets of water remaining on the filter cartridges were allowed to
evaporate at room temperature before the extraction was performed.
Extraction Procedure for Filter Cartridges and Determination of Non-volatile
Residue (NVR)
Dynamic extraction tests were performed in a known volume of water at ambient temperature.
The test filters were immersed in the extraction fluid in a clean measuring cylinder, as shown in
Figure 7.1. For twenty four (24) hours the filter was gently moved up and down. This movement
created flow through the filter membrane as a result of the pressure head that was created
each time the element was partially lifted out of the liquid.
www.pall.com/biopharm 19
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Flow (L/min)
Differential pressure at 20 ˚C (mbar)
0
100
IR49316959
IR49316959
IR49316959
IR49316960
IR49326961
IR49326962
IR49326962
IR49326962
IS05347186
IS05347186
IS05347187
IS05347188
20
Some filter cartridges were submitted to a second (consecutive) dynamic extraction cycle
under the same extraction conditions as described above. Blank samples were determined
as appropriate for method and result controls.
Following the extraction period, a measured volume of the extraction liquid was evaporated to
dryness and the non-volatile residue (NVR) was determined gravimetrically. A correction was
made to the NVR value to account for the total extraction volume used.
Analysis by Fourier Transform Infra Red Spectroscopy (FTIR)
The dry NVR of some filter cartridges was analyzed by Fourier Transform Infra Red
Spectroscopy (FTIR) to provide information on the nature of its organic compounds.
The analysis included first and also second (consecutive) extracts.
Figure 7.1
Filter Extraction Apparatus
Motor with
eccentric roto
r
Filter cartridge
in measuring
cylinder filled with
extraction fluid
Stainless steel
weight
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