Pall Flowstar and AquaWIT Integrity Test Instruments Validation Guide

Brand: Pall

Model: Flowstar and AquaWIT Integrity Test Instruments

Type: Validation Guide

USTR 2184b

Validation Guide

Palltronic®Flowstar and

AquaWIT Integrity Test Instruments

Contents

1. Introduction, Design Philosophy and Description of the Tests .......................................5

1.1 Introduction....................................................................................................................5

1.2 The Design and Development Program..........................................................................5

1.2.1 Standards and Guidelines ....................................................................................5

1.2.2 Change Control ....................................................................................................6

1.3 Design Features of the Palltronic Flowstar and AquaWIT Instruments ............................6

1.3.1 Volume Dosing Measurement Method ..................................................................6

1.3.2 Variation between the Standard and High Flow Models ........................................6

1.3.3 Hydraulic Bridge System ......................................................................................7

2. Description of Critical Test Algorithms .............................................................................8

2.1 Self Test Sequence ........................................................................................................8

2.2 The Forward Flow Test ..................................................................................................8

2.2.1 Pressurization........................................................................................................9

2.2.2 Stabilization ..........................................................................................................9

2.2.3 Measurement Phase ............................................................................................9

2.2.4 Fixed Test Time ....................................................................................................9

2.2.5 Auto Test Time Mode............................................................................................9

2.2.6 Venting................................................................................................................11

2.3 The Water Intrusion Test ..............................................................................................11

2.4 The Fully Automated Water Intrusion Test using the Palltronic AquaWIT System..........11

2.4.1 Check on Water Temperature ............................................................................11

2.4.2 Filling of Filter System ........................................................................................11

2.4.3 Hydrostatic Pressure Measurement ....................................................................11

2.4.4 Pressurization, Stabilization and Measurement Phases ......................................12

2.4.5 Draining and Drying ............................................................................................12

2.5 The Bubble Point Test ..................................................................................................12

2.5.1 Pressurization and Stabilization ..........................................................................12

2.5.2 Measurement Phase ..........................................................................................12

2.6 The Flow Check Test....................................................................................................13

3. Accuracy and Reproducibility of Critical Test Functions...............................................13

3.1 Accuracy and Consistency of Set Pressures by the Palltronic Instrument ....................13

3.1.1 Purpose ..............................................................................................................13

3.1.2 Test Method........................................................................................................13

3.1.3 Results................................................................................................................14

3.1.4 Summary ............................................................................................................14

3.2 Conversion of Pressure Units ......................................................................................15

3.2.1 Purpose ..............................................................................................................15

3.2.2 Test Method........................................................................................................16

3.2.3 Test Results ........................................................................................................16

3.2.4 Summary ............................................................................................................16

3.3 Accuracy and Reproducibility of Forward Flow Measurements ....................................17

3.3.1 Purpose ..............................................................................................................17

3.3.2 Test Method........................................................................................................17

3.3.3 Results................................................................................................................18

3.3.4 Summary ............................................................................................................18

3.4 Accuracy of Forward Flow Measurements High Flow Range – Applicable to

High Flow Instruments Only ........................................................................................20

3.4.1 Purpose ..............................................................................................................20

3.4.2 Test Method........................................................................................................20

3.4.3 Results................................................................................................................20

3.4.4 Summary ............................................................................................................21

3.5 Accuracy of Water Intrusion Measurements by the Palltronic Flowstar Instrument ......21

3.5.1 Purpose ..............................................................................................................21

3.5.2 Test Method........................................................................................................21

3.5.3 Results................................................................................................................22

3.5.4 Summary ............................................................................................................23

3.6 Comparison of ‘Auto’ and ‘Fixed’ Test Times ..............................................................23

3.6.1 Purpose ..............................................................................................................23

3.6.2 Test Method........................................................................................................23

3.6.3 Results................................................................................................................24

3.6.4 Summary ............................................................................................................24

3.7 Accuracy and Reproducibility of Bubble Point Measurements......................................25

3.7.1 Purpose ..............................................................................................................25

3.7.2 Methods..............................................................................................................25

3.7.3 Results................................................................................................................26

3.7.4 Summary ............................................................................................................26

4. Qualification of the Palltronic AquaWIT System ............................................................28

4.1.Accuracy of Set Pressures by the Palltronic AquaWIT System ....................................28

4.1.1 Purpose ..............................................................................................................28

4.1.2 Test Method........................................................................................................28

4.1.3 Results................................................................................................................29

4.1.4 Summary ............................................................................................................29

4.2 Reproducibility of Palltronic AquaWIT Water Intrusion Test Flow Measurements ..........30

4.2.1 Purpose ..............................................................................................................30

4.2.2 Test Method........................................................................................................30

4.2.3 Results................................................................................................................31

4.2.4 Summary ............................................................................................................32

4.3 Influence of the Distance and Height of the Filter System on Flow Measurement

by the Palltronic AquaWIT System ..............................................................................32

4.3.1 Purpose ..............................................................................................................32

4.3.2 Method ..............................................................................................................32

4.3.3 Results................................................................................................................33

4.3.4 Summary ............................................................................................................34

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5. Steam Trial Report............................................................................................................35

5.1 Purpose ......................................................................................................................35

5.2 Test Method ................................................................................................................35

5.3 Results ........................................................................................................................35

5.4 Summary ....................................................................................................................35

6. Software Validation ..........................................................................................................37

6.1 Qualification of the Palltronic Flowstar XC Instrument ..................................................38

Section 1 – Software Qualification of the Palltronic Flowstar XC Instrument ................38

Section 2 – Functional Qualification of the Palltronic Flowstar XC Instrument ..............39

6.2 Qualification of the Palltronic AquaWIT XC System ......................................................40

Section 1 – Software Qualification of the Palltronic AquaWIT XC System ....................40

Section 2 – Functional Qualification of the Palltronic AquaWIT XC system ..................41

Appendix A - Definitions ......................................................................................................41

1. Good Automated Manufacturing Practice (GAMP) Guidelines ......................................41

GAMP ..........................................................................................................................41

Appendix B - Qualification of the Calibration Procedure...................................................42

1. Purpose ......................................................................................................................42

2. Test Devices and References ......................................................................................42

2.1 Test Devices used for Qualification......................................................................42

2.2 References used during Qualification ..................................................................42

3. Test Method ................................................................................................................43

3.1 Forward Flow Test ..............................................................................................43

3.2 Water Intrusion Test ............................................................................................43

4. Test Results..................................................................................................................44

4.1 Forward Flow Test ..............................................................................................44

4.2 Water Intrusion Test ............................................................................................47

7. Summary...........................................................................................................................49

8. Document Revision Index................................................................................................49

1. Introduction, Design Philosophy and Description of the Tests

1.1 Introduction

This report contains validation data for the Palltronic Flowstar and Palltronic AquaWIT filter

integrity test systems. The report is designed to assist users of the device in meeting the

validation requirements of the various regulatory authorities within the pharmaceutical industry.

The validation program included tests to qualify the following functions:

• Accuracy and consistency of set pressures

• Accuracy and reproducibility of Forward Flow measurements

• Accuracy of Forward Flow measurements in the high flow range (high flow models)

• Accuracy of water intrusion measurements

• ‘Auto’ and ‘Fixed’ test time options

• Accuracy and reproducibility of bubble point measurements

• Accuracy of set pressures by the Palltronic AquaWIT system

• Reproducibility of Palltronic AquaWIT Water Intrusion Test measurements

• Influence of distance and height of the filter system on flow measurement for the

Palltronic AquaWIT system

• Qualification of the calibration procedure

The basic measurement function of the Palltronic AquaWIT system is the same as for the

Palltronic Flowstar instrument. The hydraulic bridge forms an incompressible link between the

filter and the measurement system.

The primary validation has therefore been performed on the Palltronic Flowstar instrument, as

this contains the main measurement function. Additional testing has been performed on the

Palltronic AquaWIT system to show that the hydraulic bridge has no influence on the water

intrusion measurement accuracy and reproducibility. These tests are described in Part 4.

The validation work in this guide was carried out on instruments with the part numbers FFS02,

FFS02H and AW02. However, because the hardware and software control used is the same for

the FFS02, FFS02H, FFS02AM, FFS02HAM, FFSXC, FFSXCH, FFSXCAM, FFSXCHAM,

FFSXCJ, FFSXCHJ, AW02, AW02XC and AW02XCH instruments this validation work is

applicable to all of them.

In addition to this Validation Guide, ask your Pall representative or distributor for the following

documents and services:

• IQ procedures and on-site services

• OQ procedures and on-site services

• PQ services

• On-site calibration and calibration documentation

• 21 CFR part 11 compliance guidance

• Design and Specification Documentation Package prepared to a GAMP format

• On-site operator training

1.2 The Design and Development Program

1.2.1 Standards and Guidelines

The Palltronic Flowstar and AquaWIT instruments have been developed in

accordance with Good Automated Manufacturing Practice (GAMP) guidelines.

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The Palltronic Flowstar and AquaWIT devices are manufactured under quality

management systems certified to ISO9001.

]The Palltronic Flowstar and AquaWIT systems are CE marked to indicate compliance

with relevant European Directives.

1.2.2 Change Control

Documented procedures exist for change control for both software and hardware

components. Each Palltronic Flowstar and AquaWIT system is identified by a unique

serial number allowing full manufacturing traceability. Full records are maintained for

each instrument manufactured.

1.3 Design Features of the Palltronic Flowstar and AquaWIT Instruments

1.3.1 Volume Dosing Measurement Method

The Palltronic Flowstar and AquaWIT integrity instruments measure flow on the

upstream side of the filter test assembly using a patented technique. This is based

on measurement of the amount of gas required to maintain a constant test pressure

on the filter.

The measurement principle is one of ‘volume dosing’. The measurement module

consists of high-precision pressure transducers and internal chambers of precisely

defined volume. The system is controlled by purpose-designed software.

Figure 1

Illustration of the Volume Dosing Measurement System inside the Palltronic Flowstar

and AquaWIT Instruments

One transducer (P1) measures the pressurization of one of the volume chambers.

The other (P2) measures the filter test pressure.

As gas or liquid passes through the test filter, constant pressure is maintained on the

upstream side by discharging the pressurized gas held in one of the volume

chambers. The volume chamber used depends on the flow rate across the filter

membrane. The precise quantity of gas discharged is known and by counting the

number of discharges over time, the precise flow rate is measured.

Volume dosing has been shown to be a reliable, robust and stable flow measurement

method that has been successfully used in Palltronic instruments for over ten years.

1.3.2 Variation between the Standard and High Flow Models

In order to increase the flow measurement range of the Palltronic Flowstar and

AquaWIT instruments a third volume chamber has been incorporated into the high

Volume 1

Volume 2

Filter

P2P1

flow models (Pall part numbers FFS02H, FFS02HAM, FFSXCH, FFSXCHAM,

FFSXCHJ, AW02H and AW02XCH). See Figure 2.

Figure 2

Schematic of the Volume Dosing Measurement System inside the Palltronic High Flow

Flowstar and AquaWIT Instruments

1.3.3 Hydraulic Bridge System

The Palltronic AquaWIT integrity test system is made up of a Palltronic Flowstar

integrity test instrument and a base unit. The base unit enables the Water Intrusion

Test function of the Palltronic Flowstar instrument to be extended to include

automatic filling of the filter housing before the test and draining after the test.

The gas flow measurement does not extend directly to the filter housing as it typically

would when using the Palltronic Flowstar instrument alone, but to the measurement

chamber inside the Palltronic AquaWIT system (see Figure 3).

Figure 3

Schematic of the Palltronic AquaWIT System Test Set-up for a Fully Automated Water

Intrusion Test

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Volume 1

Volume 2

Volume 3

Filter

P2P1

Measurement Chamber

Filter System

Palltronic

Flowstar

Instrument

The hydraulic bridge system eliminates all air from the upstream filter system and

tubing. Flow measurement is then performed in a more controlled location within the

Palltronic AquaWIT system. Stable results can be obtained even when the

environmental temperature is changing.

The hydraulic bridge system and automated operation of three external process

valves by the Palltronic AquaWIT system also mean that testing vent filters in

positions with difficult access is simple and quick.

2. Description of Critical Test Algorithms

2.1 Self Test Sequence

The Palltronic Flowstar self-test sequence is automatically performed each time the unit is

switched on. The purpose of these tests is to provide the user with assurance that the

software, electronic, mechanical and pneumatic components are operating correctly. The test is

performed during the 600 second warm-up period, designed to allow the unit to reach thermal

equilibrium before each use.

The following tests are performed during the self-test:

• Check on last calibration date

• Check on last back-up date

• EPROM checksum test

• Internal communication check

• Inlet pressure check

• Check on pressure transducers

• Valve check

• Pressure regulator check

• Internal leak test

• Compact Flash test

2.2 The Forward Flow Test

The Forward Flow test quantitatively measures the diffusive gas flow (typically air or nitrogen)

through all the wetted pores, and the bulk gas flow through larger non-wetted pores, when a

predetermined gas pressure is applied to a wetted filter. The Palltronic Flowstar test system

measures Forward Flow by measuring the gas flow required to maintain constant pressure on

the upstream side of a filter assembly containing a wetted filter. The upstream flow of gas is

converted to a flow at standard temperature and pressure that equates to a downstream flow

measurement.

If the gas flow though the filter membrane is equal to or less than the pass limit input by the

operator then the filter passes the test. If the gas flow exceeds the pass limit then the filter fails

the test.

The Forward Flow test conducted by the Palltronic Flowstar system is performed in four stages

as shown in Figure 4.

Figure 4

The Four Stages of the Automated Forward Flow Test

2.2.1 Pressurization

A zero check is performed immediately prior to pressurization. This check ensures

that the test pressure is accurately set relative to the actual atmospheric pressure in

the environment in which the test is to be performed. Compressed gas is then

directed through the Palltronic Flowstar instrument and into the filter assembly being

tested. When pressure in the filter assembly reaches the assigned test pressure, the

stabilization phase automatically starts.

2.2.2 Stabilization

During the stabilization phase the Palltronic Flowstar system monitors the upstream

pressure and feeds exactly the same amount of compressed gas into the filter

assembly as that leaving the upstream volume across the wetted membrane. During

this phase of the test a bar chart is displayed which shows the upstream pressure

that is continuously being measured. The instrument automatically switches to the

measurement phase of the test when the upstream pressure can be properly

maintained by the system.

2.2.3 Measurement Phase

During the measurement phase of the test, flow through the filter is continuously

measured and monitored. Flow is determined by measuring the exact volume of gas

required to keep a constant pressure on the upstream side of the filter assembly.

Changes in flow are sensed and evaluated. During the measurement phase the

upstream pressure, flow rate and time elapsed are represented in bar charts on the

display. A real time graph showing time elapsed and flow rate can also be displayed

during the measurement phase of the test.

The duration of the test is determined by the test time mode selected by the

operator. The instrument uses either ‘Fixed’ or ‘Auto’ test mode.

2.2.4 Fixed Test Time

When the ‘Fixed’ test time mode is selected the measurement phase lasts for a pre-

determined time entered by the operator. The result reported is the average flow

value determined over the last 150 seconds of the measurement phase.

Figure 5 shows a typical graph of flow versus time during a Forward Flow or Water

Intrusion Test performed under stable environmental conditions. Higher flow rates are

typically observed at the start of the measurement phase. This higher flow is primarily

due to the small temperature increase that takes place as a result of gas

compression at the start of the test. As the system stabilizes, the flow gradually

decreases to a stable and constant rate.

2.2.5 Auto Test Time Mode

When the ‘Auto’ test time mode is selected the Palltronic Flowstar instrument

automatically ends the test when certain criteria have been met. During the

measurement phase the instrument measures the actual flow rate and the rolling

average value over a 150 second interval.

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Pressurization Stabilization Testing

(measurement)

Venting

Pressure in

measurement

chamber

Time

If, at the start of the measurement phase, the measured flow value is under the pass

limit then a 120 second countdown is performed. If at any time the measured value

goes over the pass limit then the timer is reset. After 120 seconds the test will

automatically end and the average result will be reported providing that the flow is

stable and well below the pass limit, as determined using the following criteria:

1. The average value is under 75% of the pass limit

2. The variation coefficient of continuous measurements is within an acceptable range

If these criteria are not met then the test continues for a further 30 seconds and

criterion (1) is increased to 80% of the pass limit. After this time if the ‘Auto’ criteria

have again not been met the test time is extended for a further 30 seconds. After

each additional 30 second interval, criterion (1) is gradually increased until the

average value is 95% of the pass limit.

The algorithms used during the ‘Auto’ test ensure that test times are minimized when

testing stable filter systems that have flow values well below the pass limit (see

Figure 5). For filter systems where the flow rate fluctuates or where the measured

value is close to the pass limit the test times are automatically extended to ensure a

safe and accurate result as shown in Figures 6 and 7.

Figure 5

Representation of ‘Auto’ and ‘Fixed’ Test Times when Testing a Filter Assembly under

Stable Environmental Conditions

Figure 6

Representation of ‘Auto’ and ‘Fixed’ Test Times when Testing a Filter Assembly under

Initially Fluctuating Environmental Conditions

Flow

(mL/min) Pass limit

Test end point using

Auto test mode

Test end point using

Fixed test mode

Time (seconds)

Flow

(mL/min) Pass limit

Test end point using

Auto test mode

Test end point using

Fixed test mode

Time (seconds)

Figure 7

Representation of ‘Auto’ and ‘Fixed’ Test Times when Testing a Filter Assembly with a

Flow Rate Close to the Pass Limit

2.2.6 Venting

On completion of the test the instrument automatically vents the test system in two

phases. The remote vent valve initially vents the compressed gas in the upstream

side of the filter assembly and then the compressed gas in the manifold of the

Palltronic Flowstar instrument is vented through the vent connection on the side of

the unit.

2.3 The Water Intrusion Test

The Water Intrusion Test quantitatively measures the flow of water through a hydrophobic

membrane when a predetermined gas pressure is applied to a water-filled filter assembly.

The Palltronic Flowstar Flowstar instrument determines water flow by measuring the exact flow

of compressed gas on the upstream side required to maintain constant upstream pressure.

This compressed gas flow equates to the water flow through the filter.

The test protocol used for the Water Intrusion Test is identical to that used for the Forward Flow

test. The results are expressed as actual flow on the upstream side of the filter whereas the

Forward Flow reports results that have been converted to a downstream gas flow under

standard temperature and pressure.

2.4 The Fully Automated Water Intrusion Test using the Palltronic AquaWIT System

The Palltronic AquaWIT system can be used to perform a fully automated Water Intrusion

Test on a filter system. In addition to the test protocol described above the following steps

take place.

2.4.1 Check on Water Temperature

The Water Intrusion flow rate across a filter membrane is dependent on water temperature.

A higher water temperature will give higher flow rates. Standard Pall Water Intrusion Test values

are issued for a water temperature between 18 and 22 °C and water temperatures less than

18 °C may cause a false pass result.

The water temperature in the main water tank is checked before the test and displayed on the

screen. If the water temperature is below 18 °C, the option to abort the test is given.

2.4.2 Filling of Filter System

The filter housing and associated tubing is automatically filled with water on the

upstream side of the filter.

2.4.3 Hydrostatic Pressure Measurement

Where the filter is positioned above the Palltronic AquaWIT system, the hydraulic

bridge transmits the hydrostatic pressure to the measurement chamber. Therefore, to

ensure that the test pressure at the filter is correct, the system automatically

measures the hydrostatic pressure and adjusts the pressure in the measurement

chamber to compensate.

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Flow

(mL/min) Pass limit

Test end point using

Auto test mode

Test end point using

Fixed test mode

Time (seconds)

(Note: “Hydraulic bridge” refers to the piping or tubing between the measurement

instrument and the filter under test when it and the filter assembly are completely

filled with water. “Hydrostatic pressure” refers to the pressure exerted by the weight

of water in a vertical pipe.)

2.4.4 Pressurization, Stabilization and Measurement Phases

A standard Water Intrusion Test as described in Section 2.3 is then performed.

Instead of measuring water flow in the upstream side of the filter housing, flow is

measured in the measurement chamber of the Palltronic AquaWIT system.

2.4.5 Draining and Drying

On completion of the Water Intrusion Test the Palltronic AquaWIT system drains the

filter housing and blows air across the filter membrane to minimize excess water in

the assembly.

2.5 The Bubble Point Test

A Bubble Point test is performed by incrementally increasing the pressure on the upstream side

of a filter assembly containing a wetted filter. The Bubble Point value is the upstream pressure

at which liquid is forced from the largest pores of the membrane. During a visual Bubble Point

test a tube is connected to the outlet of the filter assembly and the other end is submerged in a

container filled with liquid. The Bubble Point is identified when vigorous bubbling is observed

issuing from the downstream tube.

The Bubble Point test conducted by the Palltronic AquaWIT system is performed in four stages

as shown in Figure 8.

Figure 8

Four Automated Stages of the Bubble Point Test

2.5.1 Pressurization and Stabilization

Compressed gas is directed through the Palltronic AquaWIT system and into the filter

assembly being tested until a pressure of 700 mbar (10.2 psig) is reached. The

instrument stabilizes the pressure for

30 seconds and then monitors the upstream pressure for a period of 60 seconds in

order to determine if there are any large leaks in the system.

2.5.2 Measurement Phase

During the measurement phase of the test the pressure in the upstream volume of

the filter system is increased in increments of reducing size until the upstream

pressure is 500 mbar (7.3 psig) below the Bubble Point pressure entered by the

operator. Between each pressure increment the inlet supply pressure is closed and

pressure decay is measured over a short interval. The upstream pressure is then

increased in 50 mbar (0.73 psi) increments and between each step the pressure

decay is measured over a 5 second interval.

The Bubble Point is identified when two sequential pressure decay values are

obtained that are significantly greater than the preceding values. The Bubble Point

value reported is the pressure at which the first of the significantly higher pressure

decay values was obtained.

Upstream

pressure

Time

Stabilization

Leak Test

Testing

(measurement)

VentingPressurization

2.6 The Flow Check Test

The Flow Check test uses the Forward Flow test algorithm to measure the flow of gas through

a calibrated capillary (Palltronic Flow Check instrument). The test result is compared to the

expected flow through the capillary and reported as a percentage. The test has been designed

to check that the Palltronic Flowstar instrument is measuring flow correctly.

3. Accuracy and Reproducibility of Critical Test Functions

3.1 Accuracy and Consistency of Set Pressures by the Palltronic Instrument

3.1.1 Purpose

The Palltronic Flowstar instrument measures Forward Flow and water intrusion by

measuring the flow required to maintain constant pressure in the upstream side of

the test assembly. The aim of this series of tests was to qualify the accuracy and

consistency of upstream pressures set by the Palltronic Flowstar instrument during

Forward Flow and Water Intrusion Tests.

3.1.2 Test Method

A calibrated pressure reference device (Druck Limited, part number DPI 601, serial

number 162967/73-03) was installed between the filter assembly under test and the

Palltronic Flowstar instrument (serial number 11011926), as shown in Figure 9.

The calibrated pressure reference device had previously been calibrated to be within

± 0.025 % of the applied pressure.

Figure 9

Diagram of Test Set-up for Measuring Accuracy and Consistency of Set Pressures

Forward Flow and Water Intrusion integrity tests were performed using a number of

different filter assemblies in order to cover a range of pressure settings (Table 1).

The integrity tests were performed using a fixed test time of 600 seconds and during

the test phase the pressure displayed on the upstream indicator was measured every

30 seconds.

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Wetted filter

(in housing)

Outlet open to

atmospheric

pressure

Upstream

isolated

Calibrated pressure reference

device upstream of

filter assembly

Regulated

compressed

gas supply

Palltronic Flowstar

integrity test instrument

Table 1

Filters and Test Parameters used for the Tests

Pall Filter Part

and Serial Numbers Type of Test Wetting Liquid Set Air Test Pressure

KA1V002PV1 Forward Flow Isopropanol in water 830 mbar

IA8757268 (60/40 v/v) (12.0 psi)

KA2NLP1 Forward Flow Water 1720 mbar

IB0995007 (24.9 psi)

KA3PFRP1 Water Intrusion Not applicable 2500 mbar

IA3982116 (36.3 psi)

C3DFLP1 Forward Flow Water 2760 mbar

IB70351019 (40.0 psi)

KA2NDP1 Forward Flow Water 3440 mbar

IA9521005 (49.9 psi)

KA3PFRP1 Water Intrusion Not applicable 3500 mbar

IA3982116 (50.8 psi)

C3DV50P1 Forward Flow Water 5875 mbar

PB515100 (85.2 psi)

3.1.3 Results

During each test the upstream pressure was measured using the reference calibrated

pressure reference device at intervals during the test phase. These measured values

were compared with the previously programmed set test pressures. The set

pressures used during the tests ranged from between 830 mbar to 5875 mbar

(12.0 psi to 85.2 psi). The results are shown in Table 3.

The accuracy of the upstream pressures set by the Palltronic Flowstar instrument

was determined by comparing the maximum difference between the measured

values and the set test pressure for each test. The maximum difference observed

between the programmed and measured pressures was found to range from -

1 mbar to +14 mbar (-0.015 psi to +0.203 psi).

The consistency of the upstream pressure during each test was determined by

calculating the difference between the maximum and minimum measured values

during each test. The upstream pressure was always maintained within a range of

2 mbar (0.029 psi) during the test phase.

3.1.4 Summary

Table 2

Summary of Tests

Pressure Control and Accuracy Test pressures set by the Palltronic Flowstar

instrument for Forward Flow and Water Intrusion

Tests were accurate to within 0.72% of the

programmed set pressure.

Consistency of Upstream Pressure Upstream pressures were found to remain stable

within a range of 2 mbar (0.029 psi) during the test

phase of Forward Flow and Water Intrusion Tests.

Table 3

Upstream Test Pressures measured using a Reference Device compared to

Programmed Set Pressures

Time in 830 1720 2500 2760 3440 3500 5875

Seconds mbar mbar mbar mbar mbar mbar mbar

(12.0 psi) (24.9 psi) (36.3 psi) (40.0 psi) (49.9 psi) (50.8 psi) (85.2 psi)

30 836 1724 2499 2765 3446 3500 5888

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

60 836 1723 2499 2766 3446 3499 5888

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

90 836 1723 2499 2766 3446 3500 5887

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

120 836 1723 2499 2766 3446 3500 5888

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

150 836 1723 2499 2765 3446 3500 5888

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

180 836 1723 2499 2765 3446 3500 5889

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

210 836 1723 2499 2765 3446 3500 5888

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

240 836 1722 2499 2765 3446 3499 5888

(12.1) (25.0) (36.2) (40.1) (50.3) (50.8) (85.4)

270 836 1723 2500 2765 3446 3500 5888

(12.1) (25.0) (36.3) (40.1) (50.3) (50.8) (85.4)

300 836 1723 2500 2765 3445 3500 5886

(12.1) (25.0) (36.3) (40.1) (50.3) (50.8) (85.4)

Accuracy of Pressure Control

Maximum Difference between Measured Values and the Set Test Pressure:

mbar +6 +4 -1 +6 +6 -1 +14

(psi) (+0.087) (+0.058) (-0.015) (+0.087) (+0.087) (-0.015) (+0.203)

Maximum Difference as a percentage of Set Test Pressure:

0.72% 0.23% 0.04% 0.21% 0.17% 0.03% 0.24%

Consistency Of Pressure Control

Difference between Maximum and Minimum Measured Values:

0 mbar 2 mbar 1 mbar 1 mbar 1 mbar 1 mbar 2 mbar

(0 psi) (0.029 psi) (0.015 psi) (0.015 psi) (0.015 psi) (0.015 psi) (0.029 psi)

Note: Measurements were made in mbar, conversions to psi are for information only.

3.2 Conversion of Pressure Units

3.2.1 Purpose

The validation and qualification work on the Palltronic Flowstar instrument was

completed using millibar (mbar) as the unit to measure pressure. The aim of this test

is to demonstrate that the Palltronic Flowstar instrument converts pressure units to

psi, kp/cm2and kPa with accuracy and precision.

www.pall.com/biopharm 15

3.2.2 Test Method

Forward Flow integrity tests were performed on a wetted integral filter cartridge with

an accurate calibrated pressure reference device (Mano Cali, Keller

Druckmesstecknik, serial number 6584) installed upstream of the filter assembly as

shown in Figure 10.

Tests were performed with the system programmed to show units of pressure in psi,

kp/cm2and kPa. The upstream pressure on the filter assembly was compared to the

pressure programmed into the Palltronic Flowstar instrument (serial number

05020326) for the Forward Flow test.

Figure 10

Diagram of Test Set-up for Checking Conversion of Pressure Units

3.2.3 Test Results

During each test the upstream pressure was measured using the reference calibrated

pressure reference device during the test phase. These measured values were

compared with the previously programmed set test pressures.

The pressure readings displayed on the upstream calibrated pressure reference

device, were all within ± 0.2% of the expected pressures.

3.2.4 Summary

Table 4

Summary of Tests

Conversion of Pressure Units Test pressures were converted by the Palltronic

Flowstar instrument to an accuracy of 0.2%.

Table 5

Upstream Test Pressures measured using a Reference Device compared to

Programmed Set Pressures in psi, kp/cm2and kPa

Pressure

Programmed Expected Value Displayed on Deviation Deviation

Test Pressure (mbar) Reference (mbar) (mbar) (%)

40 psi 2757 2761 4 0.14

3 kp/cm22941 2947 6 0.20

276 kPa 2760 2763 3 0.11

Wetted filter

(in housing)

Outlet open to

atmosphere

Upstream

isolated

Calibrated pressure reference

device upstream of

filter assembly

Regulated

compressed

gas supply

Palltronic Flowstar

integrity test instrument

3.3 Accuracy and Reproducibility of Forward Flow Measurements

3.3.1 Purpose

The aim of these tests was to qualify the accuracy and reproducibility of the flow

measurement system of the Palltronic Flowstar instrument using calibrated capillaries.

This method was chosen because capillaries provide highly reproducible flow rates

when a pre-determined gas pressure is applied.

3.3.2 Test Method

Forward Flow tests were conducted using a Palltronic Flowstar integrity instrument

on three different capillary units. In order to ensure stable flow conditions, each

capillary was connected to a fixed volume empty chamber that was connected

immediately upstream of the capillary. The capillary units had previously been

calibrated so they were known to provide an expected and reproducible flow rate

when a pressure of 2000 mbar (29.0 psi) was applied to them.

In order to perform the tests a capillary unit was connected to the outlet of a

Palltronic Flowstar instrument as shown in Figure 11. The Palltronic Flowstar unit was

programmed to perform Forward Flow tests using an air test pressure of 2000 mbar

(29.0 psi) with a fixed test time of 600 seconds.

Repeat measurements were performed on each capillary unit in order to qualify the

reproducibility of Forward Flow measurements. The influence of upstream volume

was also investigated by performing some tests with additional upstream volume

connected to the capillary unit.

Figure 11

Diagram of Test Set-up for Measuring Accuracy and Reproducibility of

Forward Flow measurements

www.pall.com/biopharm 17

Empty

Chamber

Regulated

compressed

gas supply

Palltronic Flowstar

integrity test instrument

Capillary

Capillary Tube

For each series of tests the percentage difference between the average measured

flow values and the expected flow was calculated. The coefficient of variation for

repeat measurements was also calculated. The calculations were performed using

the following formulae:

% Difference = Average measured value - Expected value x 100

Expected value

% Coefficient =Standard deviation x 100

of variation Average measured value

3.3.3 Results

The Forward Flow values measured through the capillary units using a Palltronic

Flowstar instrument are shown in Table 7. Forward Flow tests were performed on five

capillary units which provided expected flows of 2.50 mL/min, 7.76 mL/min,

50.4 mL/min, 97.5 mL/min and 184.5 mL/min.

Each capillary unit was tested with different volumes between the instrument and the

capillary. Upstream volumes of 60 mL, 260 mL, 2500 mL and 15,000 mL were

tested.

The Forward Flow results reported by the Palltronic Flowstar instrument are widely

independent of upstream volume. When the flow/upstream ratio was less than 0.7

and above 0.001 the value reported by the Palltronic Flowstar instrument differed

from the expected value by between 0.03% and 2%.

The flow to upstream volume ratio for a standard Pall filter system is typically within

the range 0.006 and 0.3.

Test to test variability as determined by the variation coefficient for these

measurements was found to be less than 1%.

3.3.4 Summary

Table 6

Summary of Tests

Accuracy of Forward Flow Measurements Forward Flow measurements obtained using a

Palltronic Flowstar instrument were found to be

accurate to within 2% of expected flow values.

Reproducibility of Forward Flow Test to test variability as determined by the

Measurements coefficient of variation was less than 1%.

Influence of Upstream Volume Accuracy and reproducibility of Forward Flow

measurements as given above were found for a

wide range of upstream volumes. Only if the ratio

between flow and upstream volume is above 0.7

and below 0.002 are the accuracy and the variation

coefficients significantly affected. These data

demonstrate that the Palltronic Flowstar Forward

Flow test is suitable for testing a wide range of filter

assemblies without the requirement to control or

measure upstream volumes.

(

)

www.pall.com/biopharm 19

Table 7

Comparison of Forward Flow Values measured by the Palltronic Flowstar Instrument

with Previously Calibrated Values

Upstream Volume: 60 mL

Expected Flow (mL/min) 2.5 7.76 50.4 97.5 184.5

Expected Flow/ 0.04 0.13 0.84 1.63 3.08

Upstream Volume

Measured Flow (mL/min) 2.48 7.88 48.7 **

2.47 7.82 48.6 **

2.47 7.85 48.7 **

Average Measured Flow 2.47 7.85 48.67 ––

(mL/min)

Difference Measured/ -1.20 1.16 -3.43 ––

Expected Flow (%)

Variation Coefficient (%) 0.19 0.32 0.09 ––

Upstream Volume: 260 mL

Expected Flow (mL/min) 2.5 7.76 50.4 97.5 184.5

Expected Flow/ 0.01 0.02 0.19 0.38 0.71

Upstream volume

Measured Flow (mL/min) 2.49 7.74 49.9 97.7 184.4

2.56 7.79 49.6 97.7 185.0

2.57 7.78 49.8 96.8 185.6

Average Measured Flow 2.54 7.77 49.77 97.40 185.00

(mL/min)

Difference Measured/ 1.60 0.13 -1.25 -0.10 0.27

Expected Flow (%)

Variation Coefficient (%) 1.42 0.28 0.25 0.44 0.27

Upstream Volume: 2500 mL

Expected Flow (mL/min) 2.5 7.76 50.4 97.5 184.5

Expected Flow/ 0.001 0.003 0.02 0.04 0.07

Upstream Volume

Measured Flow (mL/min) 2.74 7.87 50.6 98.9 185.6

2.59 7.96 51.0 98.6 185.3

2.49 7.91 50.6 98.8 185.9

Average Measured Flow 2.61 7.91 50.73 98.77 185.60

(mL/min)

Difference Measured/ 4.40 1.98 0.66 1.30 0.60

Expected Flow (%)

Variation Coefficient (%) 4.11 0.47 0.37 0.13 0.13

Upstream Volume: 15000 mL

Expected Flow (mL/min) 2.5 7.76 50.4 97.5 184.5

Expected Flow/ 0.000 0.001 0.003 0.007 0.012

Upstream Volume

Measured Flow (mL/min) 4.11 8.91 50.1 98.8 184.7

3.46 8.38 50.5 96.8 184.1

2.81 9.19 50.9 96.8 185.0

Table 7 Continued

Comparison of Forward Flow Values measured by the Palltronic Flowstar Instrument

with Previously Calibrated Values

Upstream Volume: 15000 mL

Average Measured Flow 3.46 8.83 50.50 97.47 184.60

(mL/min)

Difference Measured/ 38.40 13.79 0.20 -0.03 0.05

Expected Flow (%)

Variation Coefficient (%) 21.23 4.33 0.65 0.97 0.20

* ‘Flow Too High’ error message

3.4 Accuracy of Forward Flow Measurements High Flow Range – Applicable to High Flow

Instruments Only

3.4.1 Purpose

The aim of these tests is to qualify the accuracy and reproducibility of the Palltronic

High Flow Flowstar instrument for the extended flow range (200 – 2,000 mL/min).

3.4.2 Test Method

Forward Flow tests were conducted using a Palltronic High Flow Flowstar integrity

instrument (serial number 3699926) as described in Section 3.3. The capillary units

were replaced by a Molbox™ (part number 400433, serial number 1453)/Molbloc™

(part number FAM006, serial number 131) gas flow calibration system

(DH nstruments, Phoenix, AZ, USA) and the flow was controlled by a needle valve

as shown in Figure 12.

Figure 12

Diagram of Test Set-up for Measuring Accuracy of Forward Flow Measurements in

the High Flow Range

The influence of upstream volume was also investigated by performing some tests

with additional upstream volume between the Palltronic High Flow Flowstar

instrument and the needle valve.

The percentage difference between the expected flow value and the measured flow

value was calculated using the following formula:

% Difference = Measured value - Expected value x 100

Expected value

3.4.3 Results

The Forward Flow values measured using the Palltronic High Flow Flowstar

instrument are shown in Table 9. Forward Flow measurements were performed on

expected flows between 300 mL/min and 2,000 mL/min.

()

Needle

Valve

Pressure supply

Palltronic High Flow

Flowstar Instrument

Molbloc

Calibration

System

Variable

Volume

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Pall Flowstar and AquaWIT Integrity Test Instruments Validation Guide

Brand: Pall

Model: Flowstar and AquaWIT Integrity Test Instruments

Type: Validation Guide

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Pall Flowstar and AquaWIT Integrity Test Instruments Validation Guide

Pall Flowstar and AquaWIT Integrity Test Instruments Validation Guide

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