Pall 0.2 µm-rated Filter Cartridges and Filter Capsules Validation Guide

Brand: Pall

Model: 0.2 µm-rated Filter Cartridges and Filter Capsules

Type: Validation Guide

USTR2611

Validation Guide

Pall 0.2 µm-rated Filter Cartridges and

Filter Capsules with Fluorodyne®II Grade

DFL Membrane

Table of Contents

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

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

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

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

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

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

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

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

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

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

Filter Cartridges ...........................................................................................................................................9

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

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

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

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

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

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

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

3.2 Summary of Methods ............................................................................................................................13

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

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

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

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

4.2 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

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 Prex 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) qualication of a corresponding Novasip

conguration 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 qualication of a

corresponding Kleenpak Nova conguration 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

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.

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

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

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

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

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

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

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

Page is loading ...

Pall 0.2 µm-rated Filter Cartridges and Filter Capsules Validation Guide

Brand: Pall

Model: 0.2 µm-rated Filter Cartridges and Filter Capsules

Type: Validation Guide

Download PDF

report

Pall 0.2 µm-rated Filter Cartridges and Filter Capsules Validation Guide

Pall 0.2 µm-rated Filter Cartridges and Filter Capsules Validation Guide

Related papers

Other documents