Palltronic® Flowstar and AquaWIT Integrity Test Instruments

USTR 2184bValidation Guide

Palltronic® Flowstar and AquaWIT Integrity Test Instruments

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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

www.pall.com/biopharm 3

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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 IntroductionThis report contains validation data for the Palltronic Flowstar and Palltronic AquaWIT filterintegrity test systems. The report is designed to assist users of the device in meeting thevalidation 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 thePalltronic Flowstar instrument. The hydraulic bridge forms an incompressible link between thefilter and the measurement system.

The primary validation has therefore been performed on the Palltronic Flowstar instrument, asthis contains the main measurement function. Additional testing has been performed on thePalltronic AquaWIT system to show that the hydraulic bridge has no influence on the waterintrusion 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 forthe FFS02, FFS02H, FFS02AM, FFS02HAM, FFSXC, FFSXCH, FFSXCAM, FFSXCHAM,FFSXCJ, FFSXCHJ, AW02, AW02XC and AW02XCH instruments this validation work isapplicable to all of them.

In addition to this Validation Guide, ask your Pall representative or distributor for the followingdocuments 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 GuidelinesThe Palltronic Flowstar and AquaWIT instruments have been developed inaccordance with Good Automated Manufacturing Practice (GAMP) guidelines.


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The Palltronic Flowstar and AquaWIT devices are manufactured under qualitymanagement systems certified to ISO9001.

]The Palltronic Flowstar and AquaWIT systems are CE marked to indicate compliancewith relevant European Directives.

1.2.2 Change ControlDocumented procedures exist for change control for both software and hardwarecomponents. Each Palltronic Flowstar and AquaWIT system is identified by a uniqueserial number allowing full manufacturing traceability. Full records are maintained foreach instrument manufactured.

1.3 Design Features of the Palltronic Flowstar and AquaWIT Instruments

1.3.1 Volume Dosing Measurement MethodThe Palltronic Flowstar and AquaWIT integrity instruments measure flow on theupstream side of the filter test assembly using a patented technique. This is basedon measurement of the amount of gas required to maintain a constant test pressureon the filter.

The measurement principle is one of ‘volume dosing’. The measurement moduleconsists of high-precision pressure transducers and internal chambers of preciselydefined volume. The system is controlled by purpose-designed software.

Figure 1Illustration of the Volume Dosing Measurement System inside the Palltronic Flowstarand 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 theupstream side by discharging the pressurized gas held in one of the volumechambers. The volume chamber used depends on the flow rate across the filtermembrane. The precise quantity of gas discharged is known and by counting thenumber of discharges over time, the precise flow rate is measured.

Volume dosing has been shown to be a reliable, robust and stable flow measurementmethod that has been successfully used in Palltronic instruments for over ten years.

1.3.2 Variation between the Standard and High Flow ModelsIn order to increase the flow measurement range of the Palltronic Flowstar andAquaWIT instruments a third volume chamber has been incorporated into the high

Volume 1

Volume 2Filter

P2P1

flow models (Pall part numbers FFS02H, FFS02HAM, FFSXCH, FFSXCHAM,FFSXCHJ, AW02H and AW02XCH). See Figure 2.

Figure 2Schematic of the Volume Dosing Measurement System inside the Palltronic High FlowFlowstar and AquaWIT Instruments

1.3.3 Hydraulic Bridge SystemThe Palltronic AquaWIT integrity test system is made up of a Palltronic Flowstarintegrity test instrument and a base unit. The base unit enables the Water IntrusionTest function of the Palltronic Flowstar instrument to be extended to includeautomatic 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 typicallywould when using the Palltronic Flowstar instrument alone, but to the measurementchamber inside the Palltronic AquaWIT system (see Figure 3).

Figure 3Schematic of the Palltronic AquaWIT System Test Set-up for a Fully Automated WaterIntrusion Test


Volume 1

Volume 2

Volume 3Filter

P2P1

Measurement Chamber

Filter System

PalltronicFlowstarInstrument

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The hydraulic bridge system eliminates all air from the upstream filter system andtubing. Flow measurement is then performed in a more controlled location within thePalltronic AquaWIT system. Stable results can be obtained even when theenvironmental temperature is changing.

The hydraulic bridge system and automated operation of three external processvalves by the Palltronic AquaWIT system also mean that testing vent filters inpositions with difficult access is simple and quick.

2. Description of Critical Test Algorithms

2.1 Self Test SequenceThe Palltronic Flowstar self-test sequence is automatically performed each time the unit isswitched on. The purpose of these tests is to provide the user with assurance that thesoftware, electronic, mechanical and pneumatic components are operating correctly. The test isperformed during the 600 second warm-up period, designed to allow the unit to reach thermalequilibrium 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 TestThe 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 apredetermined gas pressure is applied to a wetted filter. The Palltronic Flowstar test systemmeasures Forward Flow by measuring the gas flow required to maintain constant pressure onthe upstream side of a filter assembly containing a wetted filter. The upstream flow of gas isconverted to a flow at standard temperature and pressure that equates to a downstream flowmeasurement.

If the gas flow though the filter membrane is equal to or less than the pass limit input by theoperator then the filter passes the test. If the gas flow exceeds the pass limit then the filter failsthe test.

The Forward Flow test conducted by the Palltronic Flowstar system is performed in four stagesas shown in Figure 4.

Figure 4The Four Stages of the Automated Forward Flow Test

2.2.1 PressurizationA zero check is performed immediately prior to pressurization. This check ensuresthat the test pressure is accurately set relative to the actual atmospheric pressure inthe environment in which the test is to be performed. Compressed gas is thendirected through the Palltronic Flowstar instrument and into the filter assembly beingtested. When pressure in the filter assembly reaches the assigned test pressure, thestabilization phase automatically starts.

2.2.2 StabilizationDuring the stabilization phase the Palltronic Flowstar system monitors the upstreampressure and feeds exactly the same amount of compressed gas into the filterassembly as that leaving the upstream volume across the wetted membrane. Duringthis phase of the test a bar chart is displayed which shows the upstream pressurethat is continuously being measured. The instrument automatically switches to themeasurement phase of the test when the upstream pressure can be properlymaintained by the system.

2.2.3 Measurement PhaseDuring the measurement phase of the test, flow through the filter is continuouslymeasured and monitored. Flow is determined by measuring the exact volume of gasrequired to keep a constant pressure on the upstream side of the filter assembly.Changes in flow are sensed and evaluated. During the measurement phase theupstream pressure, flow rate and time elapsed are represented in bar charts on thedisplay. A real time graph showing time elapsed and flow rate can also be displayedduring the measurement phase of the test.

The duration of the test is determined by the test time mode selected by theoperator. The instrument uses either ‘Fixed’ or ‘Auto’ test mode.

2.2.4 Fixed Test TimeWhen 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 flowvalue 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 WaterIntrusion Test performed under stable environmental conditions. Higher flow rates aretypically observed at the start of the measurement phase. This higher flow is primarilydue to the small temperature increase that takes place as a result of gascompression at the start of the test. As the system stabilizes, the flow graduallydecreases to a stable and constant rate.

2.2.5 Auto Test Time ModeWhen the ‘Auto’ test time mode is selected the Palltronic Flowstar instrumentautomatically ends the test when certain criteria have been met. During themeasurement phase the instrument measures the actual flow rate and the rollingaverage value over a 150 second interval.


Pressurization Stabilization Testing(measurement)

VentingPressure inmeasurementchamber

Time

10

If, at the start of the measurement phase, the measured flow value is under the passlimit then a 120 second countdown is performed. If at any time the measured valuegoes over the pass limit then the timer is reset. After 120 seconds the test willautomatically end and the average result will be reported providing that the flow isstable 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 andcriterion (1) is increased to 80% of the pass limit. After this time if the ‘Auto’ criteriahave again not been met the test time is extended for a further 30 seconds. Aftereach additional 30 second interval, criterion (1) is gradually increased until theaverage value is 95% of the pass limit.

The algorithms used during the ‘Auto’ test ensure that test times are minimized whentesting stable filter systems that have flow values well below the pass limit (seeFigure 5). For filter systems where the flow rate fluctuates or where the measuredvalue is close to the pass limit the test times are automatically extended to ensure asafe and accurate result as shown in Figures 6 and 7.

Figure 5Representation of ‘Auto’ and ‘Fixed’ Test Times when Testing a Filter Assembly underStable Environmental Conditions

Figure 6Representation of ‘Auto’ and ‘Fixed’ Test Times when Testing a Filter Assembly underInitially Fluctuating Environmental Conditions

Flow(mL/min)

Pass limit

Test end point usingAuto test mode

Test end point usingFixed test mode

Time (seconds)

Flow(mL/min)

Pass limit



Time (seconds)

Figure 7Representation of ‘Auto’ and ‘Fixed’ Test Times when Testing a Filter Assembly with aFlow Rate Close to the Pass Limit

2.2.6 VentingOn completion of the test the instrument automatically vents the test system in twophases. The remote vent valve initially vents the compressed gas in the upstreamside of the filter assembly and then the compressed gas in the manifold of thePalltronic Flowstar instrument is vented through the vent connection on the side ofthe unit.

2.3 The Water Intrusion TestThe Water Intrusion Test quantitatively measures the flow of water through a hydrophobicmembrane 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 flowof 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 Flowtest. The results are expressed as actual flow on the upstream side of the filter whereas theForward Flow reports results that have been converted to a downstream gas flow understandard temperature and pressure.

2.4 The Fully Automated Water Intrusion Test using the Palltronic AquaWIT SystemThe 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 TemperatureThe 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 valuesare issued for a water temperature between 18 and 22 °C and water temperatures less than18 °C may cause a false pass result.

The water temperature in the main water tank is checked before the test and displayed on thescreen. If the water temperature is below 18 °C, the option to abort the test is given.

2.4.2 Filling of Filter SystemThe filter housing and associated tubing is automatically filled with water on theupstream side of the filter.

2.4.3 Hydrostatic Pressure MeasurementWhere the filter is positioned above the Palltronic AquaWIT system, the hydraulicbridge transmits the hydrostatic pressure to the measurement chamber. Therefore, toensure that the test pressure at the filter is correct, the system automaticallymeasures the hydrostatic pressure and adjusts the pressure in the measurementchamber to compensate.


Flow(mL/min)

Pass limit



Time (seconds)

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(Note: “Hydraulic bridge” refers to the piping or tubing between the measurementinstrument and the filter under test when it and the filter assembly are completelyfilled with water. “Hydrostatic pressure” refers to the pressure exerted by the weightof water in a vertical pipe.)

2.4.4 Pressurization, Stabilization and Measurement PhasesA 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 ismeasured in the measurement chamber of the Palltronic AquaWIT system.

2.4.5 Draining and DryingOn completion of the Water Intrusion Test the Palltronic AquaWIT system drains thefilter housing and blows air across the filter membrane to minimize excess water inthe assembly.

2.5 The Bubble Point TestA Bubble Point test is performed by incrementally increasing the pressure on the upstream sideof a filter assembly containing a wetted filter. The Bubble Point value is the upstream pressureat which liquid is forced from the largest pores of the membrane. During a visual Bubble Pointtest a tube is connected to the outlet of the filter assembly and the other end is submerged in acontainer filled with liquid. The Bubble Point is identified when vigorous bubbling is observedissuing from the downstream tube.

The Bubble Point test conducted by the Palltronic AquaWIT system is performed in four stagesas shown in Figure 8.

Figure 8Four Automated Stages of the Bubble Point Test

2.5.1 Pressurization and StabilizationCompressed gas is directed through the Palltronic AquaWIT system and into the filterassembly being tested until a pressure of 700 mbar (10.2 psig) is reached. Theinstrument stabilizes the pressure for 30 seconds and then monitors the upstream pressure for a period of 60 seconds inorder to determine if there are any large leaks in the system.

2.5.2 Measurement PhaseDuring the measurement phase of the test the pressure in the upstream volume ofthe filter system is increased in increments of reducing size until the upstreampressure is 500 mbar (7.3 psig) below the Bubble Point pressure entered by theoperator. Between each pressure increment the inlet supply pressure is closed andpressure decay is measured over a short interval. The upstream pressure is thenincreased in 50 mbar (0.73 psi) increments and between each step the pressuredecay is measured over a 5 second interval.

The Bubble Point is identified when two sequential pressure decay values areobtained that are significantly greater than the preceding values. The Bubble Pointvalue reported is the pressure at which the first of the significantly higher pressuredecay values was obtained.

Upstreampressure

Time

StabilizationLeak Test

Testing(measurement)

VentingPressurization

2.6 The Flow Check TestThe Flow Check test uses the Forward Flow test algorithm to measure the flow of gas througha calibrated capillary (Palltronic Flow Check instrument). The test result is compared to theexpected flow through the capillary and reported as a percentage. The test has been designedto 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 PurposeThe Palltronic Flowstar instrument measures Forward Flow and water intrusion bymeasuring the flow required to maintain constant pressure in the upstream side ofthe test assembly. The aim of this series of tests was to qualify the accuracy andconsistency of upstream pressures set by the Palltronic Flowstar instrument duringForward Flow and Water Intrusion Tests.

3.1.2 Test MethodA calibrated pressure reference device (Druck Limited, part number DPI 601, serialnumber 162967/73-03) was installed between the filter assembly under test and thePalltronic 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 9Diagram of Test Set-up for Measuring Accuracy and Consistency of Set Pressures

Forward Flow and Water Intrusion integrity tests were performed using a number ofdifferent 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 duringthe test phase the pressure displayed on the upstream indicator was measured every30 seconds.


Wetted filter(in housing)

Outlet open toatmosphericpressureUpstream

isolated

Calibrated pressure reference device upstream of

filter assembly

Regulatedcompressedgas supply

Palltronic Flowstar integrity test instrument

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Table 1Filters and Test Parameters used for the Tests

Pall Filter Partand Serial Numbers Type of Test Wetting Liquid Set Air Test Pressure

KA1V002PV1 Forward Flow Isopropanol in water 830 mbarIA8757268 (60/40 v/v) (12.0 psi)

KA2NLP1 Forward Flow Water 1720 mbarIB0995007 (24.9 psi)

KA3PFRP1 Water Intrusion Not applicable 2500 mbarIA3982116 (36.3 psi)

C3DFLP1 Forward Flow Water 2760 mbarIB70351019 (40.0 psi)

KA2NDP1 Forward Flow Water 3440 mbarIA9521005 (49.9 psi)

KA3PFRP1 Water Intrusion Not applicable 3500 mbarIA3982116 (50.8 psi)

C3DV50P1 Forward Flow Water 5875 mbarPB515100 (85.2 psi)

3.1.3 ResultsDuring each test the upstream pressure was measured using the reference calibratedpressure reference device at intervals during the test phase. These measured valueswere compared with the previously programmed set test pressures. The setpressures 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 instrumentwas determined by comparing the maximum difference between the measuredvalues and the set test pressure for each test. The maximum difference observedbetween 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 bycalculating the difference between the maximum and minimum measured valuesduring each test. The upstream pressure was always maintained within a range of2 mbar (0.029 psi) during the test phase.

3.1.4 Summary

Table 2Summary 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 3Upstream Test Pressures measured using a Reference Device compared toProgrammed Set Pressures

Time in 830 1720 2500 2760 3440 3500 5875Seconds 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 PurposeThe validation and qualification work on the Palltronic Flowstar instrument wascompleted using millibar (mbar) as the unit to measure pressure. The aim of this testis to demonstrate that the Palltronic Flowstar instrument converts pressure units topsi, kp/cm2 and kPa with accuracy and precision.


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3.2.2 Test MethodForward Flow integrity tests were performed on a wetted integral filter cartridge withan accurate calibrated pressure reference device (Mano Cali, KellerDruckmesstecknik, serial number 6584) installed upstream of the filter assembly asshown in Figure 10.

Tests were performed with the system programmed to show units of pressure in psi,kp/cm2 and kPa. The upstream pressure on the filter assembly was compared to thepressure programmed into the Palltronic Flowstar instrument (serial number05020326) for the Forward Flow test.

Figure 10Diagram of Test Set-up for Checking Conversion of Pressure Units

3.2.3 Test ResultsDuring each test the upstream pressure was measured using the reference calibratedpressure reference device during the test phase. These measured values werecompared with the previously programmed set test pressures.

The pressure readings displayed on the upstream calibrated pressure referencedevice, were all within ± 0.2% of the expected pressures.

3.2.4 Summary


Conversion of Pressure Units Test pressures were converted by the Palltronic Flowstar instrument to an accuracy of 0.2%.

Table 5Upstream Test Pressures measured using a Reference Device compared toProgrammed Set Pressures in psi, kp/cm2 and kPa

PressureProgrammed Expected Value Displayed on Deviation DeviationTest Pressure (mbar) Reference (mbar) (mbar) (%)

40 psi 2757 2761 4 0.14

3 kp/cm2 2941 2947 6 0.20

276 kPa 2760 2763 3 0.11

Wetted filter(in housing)

Outlet open toatmosphere

Upstream isolated


filter assembly


Palltronic Flowstarintegrity test instrument

3.3 Accuracy and Reproducibility of Forward Flow Measurements

3.3.1 PurposeThe aim of these tests was to qualify the accuracy and reproducibility of the flowmeasurement system of the Palltronic Flowstar instrument using calibrated capillaries.This method was chosen because capillaries provide highly reproducible flow rateswhen a pre-determined gas pressure is applied.

3.3.2 Test MethodForward Flow tests were conducted using a Palltronic Flowstar integrity instrumenton three different capillary units. In order to ensure stable flow conditions, eachcapillary was connected to a fixed volume empty chamber that was connectedimmediately upstream of the capillary. The capillary units had previously beencalibrated so they were known to provide an expected and reproducible flow ratewhen 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 aPalltronic Flowstar instrument as shown in Figure 11. The Palltronic Flowstar unit wasprogrammed 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 thereproducibility of Forward Flow measurements. The influence of upstream volumewas also investigated by performing some tests with additional upstream volumeconnected to the capillary unit.

Figure 11Diagram of Test Set-up for Measuring Accuracy and Reproducibility of Forward Flow measurements


EmptyChamber



Capillary

Capillary Tube

18

For each series of tests the percentage difference between the average measuredflow values and the expected flow was calculated. The coefficient of variation forrepeat measurements was also calculated. The calculations were performed usingthe following formulae:

% Difference =Average measured value - Expected value

x 100Expected value

% Coefficient =

Standard deviationx 100

of variation Average measured value

3.3.3 ResultsThe Forward Flow values measured through the capillary units using a PalltronicFlowstar instrument are shown in Table 7. Forward Flow tests were performed on fivecapillary 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 thecapillary. Upstream volumes of 60 mL, 260 mL, 2500 mL and 15,000 mL weretested.

The Forward Flow results reported by the Palltronic Flowstar instrument are widelyindependent of upstream volume. When the flow/upstream ratio was less than 0.7and above 0.001 the value reported by the Palltronic Flowstar instrument differedfrom the expected value by between 0.03% and 2%.

The flow to upstream volume ratio for a standard Pall filter system is typically withinthe range 0.006 and 0.3.

Test to test variability as determined by the variation coefficient for thesemeasurements was found to be less than 1%.

3.3.4 Summary


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 variationcoefficients 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.

((

))


Table 7Comparison of Forward Flow Values measured by the Palltronic Flowstar Instrumentwith 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 3.08Upstream 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 – –



Expected Flow/ 0.01 0.02 0.19 0.38 0.71Upstream 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 0.27Expected Flow (%)

Variation Coefficient (%) 1.42 0.28 0.25 0.44 0.27





2.59 7.96 51.0 98.6 185.3

2.49 7.91 50.6 98.8 185.9


Difference Measured/ 4.40 1.98 0.66 1.30 0.60Expected Flow (%)






3.46 8.38 50.5 96.8 184.1

2.81 9.19 50.9 96.8 185.0

Table 7 ContinuedComparison of Forward Flow Values measured by the Palltronic Flowstar Instrumentwith Previously Calibrated Values



Difference Measured/ 38.40 13.79 0.20 -0.03 0.05Expected Flow (%)


* ‘Flow Too High’ error message

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

3.4.1 PurposeThe aim of these tests is to qualify the accuracy and reproducibility of the PalltronicHigh Flow Flowstar instrument for the extended flow range (200 – 2,000 mL/min).

3.4.2 Test MethodForward Flow tests were conducted using a Palltronic High Flow Flowstar integrityinstrument (serial number 3699926) as described in Section 3.3. The capillary unitswere 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 valveas shown in Figure 12.

Figure 12Diagram of Test Set-up for Measuring Accuracy of Forward Flow Measurements inthe High Flow Range

The influence of upstream volume was also investigated by performing some testswith additional upstream volume between the Palltronic High Flow Flowstarinstrument and the needle valve.

The percentage difference between the expected flow value and the measured flowvalue was calculated using the following formula:

% Difference =Measured value - Expected value

x 100Expected value

3.4.3 ResultsThe Forward Flow values measured using the Palltronic High Flow Flowstarinstrument are shown in Table 9. Forward Flow measurements were performed onexpected flows between 300 mL/min and 2,000 mL/min.

( )

20

NeedleValve

Pressure supply

Palltronic High Flow Flowstar Instrument

MolblocCalibration

SystemVariableVolume

The Forward Flow results reported by the Palltronic High Flow Flowstar instrument inthe high flow range were found to be within 3% of the expected flow rates.

3.4.4 Summary


Accuracy of Forward Flow Forward Flow measurements obtained using a Measurements (High Flow Range) Palltronic High Flow Flowstar instrument were

found to be accurate to within 3% of expected flow values for the high flow range.

Influence of Upstream Volume Accuracy of Forward Flow measurements (High Flow Range) demonstrate that the Palltronic High Flow Flowstar

Forward Flow test is suitable for testing a wide range of filter assemblies without the requirement to control or measure upstream volumes.

Table 9Comparison of Forward Flow Values measured by the Palltronic High Flow FlowstarInstrument and a Reference Device


Expected flow (mL/min) 302.9 302.1 1157 1159 2097 2123

Measured flow (mL/min) 309.7 309.7 1132 1131 2039 2061

Difference measured/ 2.2 2.5 -2.2 -2.5 -2.8 -3expected flow (%)



Measured flow (mL/min) 310.4 310 1238 1231 2038 2025

Difference measured/ 1 0.9 -0.3 -0.6 -2.0 -2.6expected flow (%)

Upstream Volume 20000 mL


Measured flow (mL/min) 313.5 312.9 1019 1016 2095 2087

Difference measured/ 1.8 1.7 0.9 0.7 0 -0.5expected flow (%)

3.5 Accuracy of Water Intrusion Measurements by the Palltronic Flowstar Instrument

3.5.1 PurposeThe aim of this series of tests was to qualify the accuracy of water intrusionmeasurements using a test system that had been designed to produce small waterflows typical of those measured during Water Intrusion Tests through hydrophobicfilter cartridges.

3.5.2 Test MethodThe test system was comprised of a vessel partly filled with water with a needle valve(Swagelok™ part number SS-4MG) fitted to the downstream outlet. The testassembly was connected to the outlet of a Palltronic Flowstar instrument (serialnumber 02010125) as shown in Figure 13.


22

Figure 13Diagram of Test Set-up for Measuring Accuracy of Water Intrusion Measurements

The Palltronic Flowstar instrument was programmed to perform Water Intrusion Testsusing an air test pressure of 2500 mbar (36.3 psi) and a fixed test time of 600seconds. Prior to the start of each test the needle valve was adjusted to provide asmall and stable flow of water.

During the Water Intrusion Tests performed by the Palltronic Flowstar instrument, theflow of water was simultaneously measured by collecting the water issuing from theneedle valve in a small container placed on a calibrated electronic balance (Mettler-ToledoTM PG 203S, serial number 1117281654). The balance was linked to a PC and the data recorded by the balance was recorded automatically every5 seconds. The weight of water collected over a three-minute interval during the lastfour minutes of the test performed by the Palltronic Flowstar instrument was used asa reference measurement of water flow.

Two series of tests were performed. In the first series of tests the upstream volume ofair in the system was adjusted to 100 ± 15 mL and in the second series of tests theupstream volume of air was increased to 300 ± 25 mL.

3.5.3 ResultsThe results are shown in Table 11. The needle valve in the test system was adjustedso that the Palltronic Flowstar instrument was tested at a number of different waterflow rates ranging from 0.08 mL/min to 1.45 mL/min.

The accuracy of the results obtained using the Palltronic Flowstar instrument wasdetermined by comparing the results with those obtained using the referencemeasurement of water flow. The maximum deviation between the results obtainedwith the Palltronic Flowstar instrument and the reference measurement was less thanor equal to ± 0.009 mL/min.

The influence of upstream volume was determined by performing two series of tests,one series where the upstream volume was approximately 100 mL and anotherseries where the upstream volume was approximately 300 mL. The accuracy of theresults obtained was not influenced by the change in upstream volumedemonstrating that Water Intrusion Tests performed by the Palltronic Flowstarinstrument are independent of system volumes.

Air

Water

Needle Valve

Balance



3.5.4 Summary


Accuracy of Water Intrusion Water intrusion measurements obtained using Measurements a Palltronic Flowstar instrument were demonstrated

to be accurate to within ± 0.009 mL/min compared to a reference measurement of flow.

Influence of Upstream Volume Water intrusion measurements determined by the Palltronic Flowstar intrument were demonstrated to be independent of system volumes. These data demonstrate that the Palltronic Flowstar Water Intrusion Test is suitable for testing a wide range of filter assemblies without the requirement to control or measure upstream volumes.

Table 11Comparison of Water Intrusion Values measured by the Palltronic Flowstar Instrumentwith a Reference Water Flow Measurement

Upstream Gas Volume 100 ± 15 mL Upstream Gas Volume 300 ± 25 mL

A-Palltronic A-PalltronicFlowstar B-Reference Deviation Flowstar B-ReferenceResults Measurement (B-A) Results Measurement Deviation(mL/min) (mL/min) (mL/min) (mL/min) (B-A)

1.45 1.441 -0.009 1.34 1.342 +0.002

0.96 0.964 -0.004 0.95 0.956 +0.006

0.94 0.945 +0.005 0.72 0.729 +0.009

0.56 0.564 +0.004 0.71 0.715 +0.005

0.47 0.466 -0.004 0.59 0.599 +0.009

0.40 0.395 -0.005 0.38 0.378 -0.002

0.26 0.264 +0.004 0.36 0.364 +0.004

0.21 0.211 +0.001 0.29 0.298 +0.008

0.11 0.112 +0.002 0.08 0.078 -0.002

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

3.6.1 PurposeThe Palltronic Flowstar instrument has ‘Auto’ and ‘Fixed’ test time options forForward Flow and Water Intrusion Tests. For the ‘Fixed’ test mode, the measurementphase of the test lasts for the programmed test time input by the operator. In the‘Auto’ test mode, the measurement phase automatically ends when the measuredflow characteristics satisfy the internal algorithms for determining stable flow.

The purpose of this series of tests was to compare Forward Flow and Water Intrusionresults when ‘Auto’ and ‘Fixed’ test times were used.

3.6.2 Test MethodAppropriate Novasip™ and Kleenpak™ filter assemblies were selected for performingForward Flow and Water Intrusion Tests (part number C3DFLP1 and KA3PFRP1respectively). The Forward Flow and Water Intrusion Tests were performed using aPalltronic Flowstar instrument (serial number 04012126) according to the normalrecommended procedures. The filter assemblies were protected from temperaturechanges in the surrounding environment during the tests in order to ensure stableflow conditions.


24

Repeat integrity tests were performed using the ‘Fixed’ and ‘Auto’ test modes.During the tests performed with the fixed test time, a test time of 600 seconds wasused. Further tests were then performed using the ‘Auto’ test mode where theentered pass limit for the test was reduced so that it was closer to the measuredflow. In each of the tests performed the stabilization and test times were measuredusing an electronic timer. On completion of the tests, the graphical display on thePalltronic Flowstar unit was observed to check if the flow rate was stable over thelast 90 seconds of the test.

3.6.3 ResultsThe stabilization, test times and reported flow results are shown in Table 13.

During the tests with the ‘Fixed’ test times the overall test times ranged between780 to 795 seconds for the Forward Flow tests, and 814 to 886 seconds for theWater Intrusion Tests. In all of these tests the graphical display of the results on thePalltronic Flowstar instrument indicated that the flow rate had been stable andconstant over the last 150 seconds of the tests.

Under the same test conditions, when the ‘Auto’ test mode was used, the overalltest times were significantly reduced, down to 369 to 383 seconds for the ForwardFlow tests and 428 to 495 seconds for the Water Intrusion tests. During these teststhe ‘Auto’ test mode allowed almost a 50% reduction in the overall test times.

In all of these tests a ‘pass’ result was obtained because the measured flow rateswere well below the entered pass limit. During the tests performed with the ‘Auto’test mode the reported flow rates were slightly higher than the results obtained withthe ‘Fixed’ test time because in these tests the flow had not completely stabilized toa constant value.

In order to determine the safety of the ‘Auto’ test mode when the measured flow wasclose to the entered pass limit, tests were performed where the flow pass limit waslowered so that it was just above the results reported during the earlier tests. Duringthese tests the overall test times were extended to between 434 to 463 seconds forthe Forward Flow tests and 498 to 522 seconds for the Water Intrusion results. As the measured flows were closer to the pass limit the tests lasted longer before the‘Auto’ test time criteria were satisfied. Again all of the results were passes and thereported flow rates were again slightly higher than the results obtained during theoriginal ‘Fixed’ test time tests as the flow rates had not completely stabilized to aconstant value.

3.6.4 Summary


Use of ‘Auto’ Test Time Mode Use of the ‘Auto’ test time mode reduced overall Forward Flow and Water Intrusion Test times by almost 50% compared to standard test times using the ‘Fixed’ test time mode.

Safety of the ‘Auto’ Test Mode During tests performed where the measured flow value was close to the pass limit, the test times automatically extended to ensure that safe results were obtained.

Table 13Comparison of ‘Auto’ and ‘Fixed’ Test Times measured by the Palltronic Flowstar Instrument

Forward Flow TestsPart number of filter used: C3DFLP1, air test pressure 2760 mbar (40.0 psi), wetting liquid water

Maximum Test Stabilization Test Total TestFlow Value Time Time Time Time ResultEntered Mode (Seconds) (Seconds) (Seconds) (mL/min)

3.4 mL/min Fixed 180 600 780 2.04

195 600 795 2.12

181 600 781 2.08

3.4 mL/min Auto 203 179 382 2.30

178 191 369 2.14

184 199 383 2.19

2.4 mL/min Auto 113 350 463 2.12

194 240 434 2.11

130 327 457 2.13

Water Intrusion TestsPart number of filter used: KA3PFRP1, air test pressure 2500 mbar (36.3 psi)

Maximum Test Stabilization Test Total TestFlow Value Time Time Time Time ResultEntered Mode (Seconds) (Seconds) (Seconds) (mL/min)

0.1 mL/min Fixed 260 600 860 0.04

214 600 814 0.04

286 600 886 0.05

0.1 mL/min Auto 359 136 495 0.05

341 120 461 0.06

294 134 428 0.05

0.07 mL/min Auto 346 169 515 0.06

339 183 522 0.06

338 160 498 0.06

3.7 Accuracy and Reproducibility of Bubble Point Measurements

3.7.1 PurposeThe aim of this series of tests was to demonstrate that the Bubble Point valuesdetermined by the Palltronic Flowstar instrument are comparable to the Bubble Pointobserved visually downstream at the same time as the automatic test is performed.Repeated measurements were also taken in order to qualify the reproducibility of thePalltronic Flowstar Bubble Point test.

3.7.2 MethodsBubble Point measurements were performed using a Palltronic Flowstar instrument(serial number 04012126) on three filter assemblies, including a 47 mm membranedisc and a high area pleated filter cartridge (part numbers FTKNFZ, KA2NLP1 andKA4DFLP1).

A length of clear plastic tubing was connected to the downstream side of the filterassembly and inserted into a beaker containing water. A calibrated pressurereference device (Druck Limited, part number DPI601, serial number 162967/73-03)was also installed on the upstream side of the filter assembly, as shown in Figure 14.


26

As the automatic test was performed, the pressure at which a steady stream ofbubbles was observed coming out of the tubing was recorded using the externalcalibrated pressure reference device. This pressure was compared to the BubblePoint value reported by the Palltronic Flowstar instrument.

Figure 14Diagram of Test Set-up for Performing Bubble Point Tests

3.7.3 ResultsThe results showing a comparison of the results obtained with the Palltronic Flowstarinstrument with the visual observations of the Bubble Point values are shown inTables 15 to 17.

The automated and visual Bubble Point determinations were found to be highlycomparable. A total of thirty bubble point tests were performed and the deviationsobserved between the automated and visual tests ranged from 0 to 86 mbar(1.2 psi).

The Bubble Point tests performed by the Palltronic Flowstar instrument were found to be extremely reproducible. The test to test variability, as determined by thecoefficient of variation, was found to be 0.67, 1.03 and 1.62 in the three series oftests performed.

3.7.4 Summary


Comparison of Bubble Point Results with Palltronic Flowstar Bubble Point tests were Visual Observations of Bubble Point comparable to visual observations of Bubble Point

for three different test filter systems, the maximum deviation between the two types of measurement was 86 mbar (1.2 psi).

Bubble Point Reproducibility The Bubble Point results reported by the Palltronic Flowstar instrument were found to be highly reproducible, the coefficient of variation was less than 1.7 in the three series of tests performed.

Water-filled downstreambeaker for observationof visual bubble point

Upstream isolated


filter assembly



Table 15Comparison of Bubble Point Values measured by the Palltronic Flowstar Instrumentwith a Visual Determination of Bubble Point (Filter Part Number FTKNFZ)

A - Bubble Point Values reported by Palltronic B - Visual Observation of Flowstar Instrument Bubble Point Deviation (B-A)

(mbar) (psi) (mbar) (psi) (mbar) (psi)

3450 50.0 3505 50.8 55 0.8

3500 50.8 3530 51.2 30 0.4

3500 50.8 3570 51.8 70 1.0

3500 50.8 3570 51.8 70 1.0

3500 50.8 3580 51.9 80 1.1

3500 50.8 3580 51.9 80 1.1

3500 50.8 3530 51.2 30 0.4

3500 50.8 3580 51.9 80 1.1

3500 50.8 3586 52.0 86 1.2

3550 51.5 3580 51.9 30 0.4

For repeat Palltronic Flowstar instrument Bubble Point values: % Coefficient of variation = 0.67

Table 16Comparison of Bubble Point Values measured by the Palltronic Flowstar Instrument with a Visual Determination of Bubble Point (Filter Part Number KA2NLP1, Serial Number IB0996007)



2300 33.4 2360 34.2 60 0.8

2300 33.4 2340 34.0 40 0.6

2300 33.4 2358 34.2 58 0.8

2350 34.1 2380 34.5 30 0.4

2350 34.1 2380 34.5 30 0.4

2350 34.1 2390 34.7 40 0.6

2350 34.1 2390 34.7 40 0.6

2350 34.1 2410 34.9 60 0.8

2350 34.1 2400 34.8 50 0.7

2350 34.1 2400 34.8 50 0.7



28

Table 17Comparison of Bubble Point Values measured by the Palltronic Flowstar Instrument with a Visual Determination of Bubble Point (Filter Part Number KA4DFLP1, Serial Number IA9106016)



3300 47.9 3350 48.6 50 0.7

3350 48.6 3375 48.9 25 0.3

3350 48.6 3380 49.0 30 0.4

3400 49.3 3450 50.0 50 0.7

3400 49.3 3400 49.3 0 0

3400 49.3 3450 50.0 50 0.7

3400 49.3 3400 49.3 0 0

3400 49.3 3450 50.0 50 0.7

3450 50.0 3480 50.5 30 0.5

3500 50.8 3440 49.9 -60 -0.9


4. Qualification of the Palltronic AquaWIT System

The basic measurement function of the Palltronic AquaWIT system is the same as for the PalltronicFlowstar instrument. The hydraulic bridge forms an incompressible link between the filter and themeasurement system.

The primary validation has therefore been performed on the Palltronic Flowstar instrument, as thiscontains the main measurement function. Additional testing has been performed on the PalltronicAquaWIT system to show that the hydraulic bridge has no influence on the water intrusionmeasurement accuracy and reproducibility. These tests are described in following section.

4.1. Accuracy of Set Pressures by the Palltronic AquaWIT System

4.1.1 PurposeThe Palltronic AquaWIT system fills the filter system with water on the upstream sideof the filter. If the filter system is at a different height to the measurement chamberthere will be a hydrostatic pressure on the measurement chamber. This is measuredby the Palltronic AquaWIT system which automatically adjusts the pressure in themeasurement chamber to ensure that the pressure on the filter is the test pressure.

The aim of this series of tests was to qualify the accuracy and consistency ofupstream pressures set by the Palltronic AquaWIT system at the filter assembly.

4.1.2 Test MethodA calibrated pressure reference device (Mano Cali, Keller Druckmesstechnik, serialnumber 6583) was installed at the filter assembly.

Water Intrusion Tests were performed using a Palltronic AquaWIT system (serialnumber 01010028 / 08060226) with the filter assembly at 50 cm (1.6 feet), 150 cm(4.9 feet) and 250 cm (8.2 feet) above the measurement chamber. The integrity testswere performed using a fixed test time of 600 seconds and repeated 3 times foreach filter height.

Figure 15Diagram of Test Set-up for Measuring Accuracy of Filter Test Pressures Set by thePalltronic AquaWIT System

4.1.3 ResultsDuring each test the upstream pressure was measured using the calibrated pressurereference device. The measured values were compared with the previouslyprogrammed set test pressure of 2500 mbar (36.3 psi). The difference observedbetween the programmed and measured pressures was found to range from23 mbar to -32 mbar (0.33 psi to -0.46 psi).

4.1.4 Summary


Pressure Control and Accuracy Test pressures set by the Palltronic AquaWIT system for Water Intrusion Tests were accurate to within 1.28% of the programmed set pressure for filter heights between 50 cm (1.6 feet) and 250 cm (8.2 feet).

Table 19Influence of Height of the Filter System on the Test Pressure

Height: 50 cm (1.6 feet)

Test Pressure Set Test Pressure Actual Deviation Deviation (%)

2500 mbar (36.3 psi) 2519 mbar (36.5 psi) 19 mbar (0.2 psi) 0.76




A

C

B

V13

V1V2 V3

V5

V8

V4

V6

V7

V9

PalltronicFlowstarInstrument

FILTER

ReferenceManometer

P

Table 19 ContinuedInfluence of Height of the Filter System on the Test Pressure

Height 150 cm (4.9 feet)


2500 mbar (36.3 psi) 2486 mbar (36.1 psi) -14 mbar (-0.2 psi) -0.56



Height 250 cm (8.2 feet)





It is possible to test filters which are more than 250 cm (8.2 feet) above the testsystem. For these installations we recommend an installation specific performancequalification. Contact your local Pall office or distributor for more information.

4.2 Reproducibility of Palltronic AquaWIT Water Intrusion Test Flow Measurements

4.2.1 PurposeThe aim of this series of tests was to show the reproducibility of the Water IntrusionTest measurements made using the Palltronic AquaWIT system.

4.2.2 Test MethodWater Intrusion Tests were performed using a Palltronic AquaWIT system (serialnumber 01010028/08060226). In order to remove the influence of the filter on thetest result measurement, no filter was connected to the test system. Connections Aand B were directly connected with pneumatic tubing. A calibrated capillary(Palltronic Flow Check instrument FC01) was connected between the test instrumentand the test system to simulate a flow across a filter. This method was chosenbecause capillaries provide highly reproducible flow rates when a pre-determined gaspressure is applied. The Palltronic Flow Check instrument had previously beencalibrated so it was known to provide an expected and reproducible flow rate when apressure of 2000 mbar (29.0 psi) was applied to it.

30

Figure 16Diagram of Test Set-up for Measuring Reproducibility of Water Intrusion TestMeasurements with the Palltronic AquaWIT System

The test was set up as shown in Figure 16 and the Water Intrusion Test program wasstarted from the Palltronic AquaWIT menu of the test instrument.

Six tests were carried out during which the tubing between connections A and B wasfilled with water and the measurement automatically carried out. After themeasurement was completed the system was emptied following the PalltronicAquaWIT Water Intrusion Test protocol.

4.2.3 ResultsThe Water Intrusion values measured using the Palltronic AquaWIT system are shownin Table 21.

The maximum deviation of the measurement from the average flow value was± 0.005 mL/min. The results show high reproducibility of flow measurement.


A

C

B

V13

V1

V2 V3

V5

V8

V4

V6

V7

V9

PalltronicFlowstar

Instrument

FC01

32

4.2.4 Summary


Reproducibility of Water Intrusion The maximum deviation of the measurementmeasurements by the Palltronic AquaWIT from the average flow values was system

± 0.005 mL/min. The results show highreproducibility of flow measurement.

Table 21Reproducibility of Flow Measurement of the Palltronic AquaWIT System

Test Instrument Flow Measurement (mL/min) Deviation from Average Value (mL/min)

0.84 +0.005

0.84 +0.005

0.83 -0.005

0.83 -0.005

0.83 -0.005

0.84 +0.005

The average value of the measurement was 0.835 mL/min

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

4.3.1 PurposeThe aim of these tests was to show filter height and distance from the PalltronicAquaWIT system have no influence on the Water Intrusion Test measurement.

4.3.2 MethodThe test set-up is shown inFigure 17.

Figure 17 Diagram of Test Set-up to show Height and Distance of Palltronic AquaWIT Systemfrom the Filter have no influence on Flow Measurement

A Pall Emflon® PFR filter, part number AB1PFR7PVH4, serial number IE4280174,was connected to the Palltronic AquaWIT system (serial number 01010028/08060226) as shown in Figure 17. The filter was tested at distances of 2 m (6.6 feet),5 m (16.4 feet) and 10 m (32.8 feet) from the Palltronic AquaWIT system. A finalmeasurement with the filter at 2.5 m (8.2 feet) above the test instrument and adistance of 10 m (32.8 feet) was also made.

The filter was tested 3 times at each distance using the standard automated WaterIntrusion Test function in the Palltronic AquaWIT Main Menu screen.

The reference value for the flow across the filter was defined as the average valuewith 2 m (6.6 feet) of tubing.

4.3.3 ResultsThe reference value for the measurement at 2 m (6.6 feet) distance between thePalltronic AquaWIT unit and the filter system was found to be 0.163 mL/min asshown in Table 23.

The results from each test were compared to the reference value. These results areshown in Tables 24 and 25.

It is possible to test filters which are more than 2.5m (8.2 feet) above the test systemor greater than 10 m (32.8 feet) distance. For these installations we recommend aninstallation specific performance qualification. Contact your local Pall office ordistributor for more information.


A

C

B

V13

V1V2 V3

V5

V8

V4

V6

V7

V9

PalltronicFlowstar

Instrument

FILTER

34

4.3.4 Summary


Influence of filter height and distance on Water Intrusion measurements were all within Water Intrusion measurements by the ±0.013 mL/min of the reference value.

These Palltronic AquaWIT system results show that heights up to 2.5 m (8.2 feet) and a distance of 10 m (32.8 feet) between the filter system and the Palltronic AquaWIT unit has no significant effect on the flow measured by the Palltronic AquaWIT instrument.

Table 23Test Results for the Reference Value (2 m [6.6 feet] Distance between Test Systemand Filter)

Tubing Length 2 m (6.6 feet)

Test Result (mL/min) Reference (Average) Value (mL/min)

0.16 –

0.17 –

0.16 –

– 0.163

Table 24Measurement at 5 m (16.4 feet) and 10 m (32.8 feet) distance between Test Systemand Filter


Test Result (mL/min) Deviation from Reference (mL/min)

0.17 +0.007

0.16 -0.003

0.15 -0.013



0.17 +0.007

0.17 +0.007

0.16 -0.003

Table 25Qualification of the Palltronic AquaWIT Test System with a Tubing Length of 10 m(32.8 feet) and a Height Difference of 2.5 m (8.2 feet)

Tubing Length 10 m (32.8 feet) and 2.5 m (8.2 feet) Height Difference


0.16 -0.003

0.15 -0.013

0.15 -0.013

5. Steam Trial Report

5.1 PurposeThe Palltronic AquaWIT system includes the capability to sanitize the water contact parts of thepipework with steam. During the steam phase the temperature in the main water tank iselevated to 121 °C for a period of twenty minutes. The purpose of the thermal mapping was to determine the efficiency of the steam phase by determining the steam distribution and temperature.

5.2 Test MethodThermocouples were placed in the Palltronic AquaWIT system (serial number 01010028/08060226) at points indicated in Figure 18. Once the Palltronic AquaWIT system steam phasewas started, data from the thermocouples was recorded using a Kaye Validator® 2000 systemSerial Number: 0011027. The temperature data was displayed using line Temperature/Timecharts with which the results of steam efficiency and distribution were analyzed. A full length(20 minute) test was performed to analyze the system’s performance.

The steam supply pressure was set to 1.3 barg (18.9 psi). The Kaye Datalogger tooktemperature readings at 30 second intervals.

5.3 ResultsDuring the test (T > 121 °C timer set to 1200 seconds) the steam stability was monitored bythe Palltronic AquaWIT internal temperature sensor. The temperature reading showing thetemperature was maintained between 121 °C and 122 °C.

The warm up period of the steam phase was short, lasting only two to three minutes before thesteam timer commenced its count down. All thermocouple test points heated at a similar rate,aside from the steam inlet point, which reached temperature before the others. During thesteaming phase, all test points located in the system reached 121 °C. This included the fillingtank B1, the chamber B2, the measurement chamber B3 and all water wetted pipework.

Once at temperature the steam was stable, fluctuating by a maximum of 1 °C . The results ofthe steam trials show the unit is suitable for the steaming process.

5.4 Summary


Palltronic AquaWIT system steam trial The Palltronic AquaWIT system is suitable for steaming.


36

Figure 18Diagram of Test Set-up for Performing Steaming Trial

D

A

V

C

E

F

G

B

Control Box

V2

V5

14 ltr

3 ltr

V7

V6

V13

V3V4

V9

V14

V1

TP1

TP2

AIR INFF OUT V10

V11V12V8 V16

Palltronic FlowstarInstrument

B114.5 ltr

OUTIN

VENT

L1

P1

T1

L2

L3

B3 0.4 ltr

B2 0.3 ltr

STEAM

TP3

TP5

TP7

TP10

TP4

TP6

TP8

TP9

Figure 19Temperature/Time 20 Minute Test

6. Software Validation

In addition to the tests described in this report and which validate the measurement functions of thePalltronic Flowstar XC and AquaWIT XC systems, the other functions of the Palltronic Flowstar XC andAquaWIT XC systems were tested to complete the software validation. The tests performed are listedbelow. These tests are performed for each software version prior to release.


126 125 124 123 122 121 120 50 40 30

TP2TP3

TP4TP5TP6

TP7TP8TP9

TP10TP1

Temperature Deg C Temperature Deg C

Tim

e in

Min

utes

Tim

e in

Min

utes

47

45

43

41

39

37

35

33

31

29

27

25

23

21

19

17

15

13

11

9

7

5

3

1

47

45

43

41

39

37

35

33

31

29

27

25

23

21

19

17

15

13

11

9

7

5

3

1

38

6.1 Qualification of the Palltronic Flowstar XC Instrument

Section 1 – Software Qualification of the Palltronic Flowstar XC Instrument1 Data entry, handling and printing

1.1 Manual entry

1.1.1 Check on correspondence between the data entered and the data printed onthe output (FF test option)

1.1.2 Check on correspondence between the data entered and the data printed onthe output (WIT option)

1.1.3 Check on correspondence between the data entered and the data printed onthe output (BP test option)

1.1.4 Check on correspondence between the data entered and the data printed onthe output (FF + BP test option)

1.1.5 Check on correspondence between the data entered and the data printed onthe output (FC test option)

1.1.6 Check on correspondence between the data entered and the data printed onthe output when reprinting stored test results

1.2 Usage of pre-configured test data (Test Programs)

1.2.1 Check on correspondence between the data entered in the test programfunction and the data printed on the output (FF test option)

1.2.2 Check on correspondence between the data entered in the test programfunction and the data printed on the output (WIT option)

1.2.3 Check on correspondence between the data entered in the test programfunction and the data printed on the output (BP test option)

1.2.4 Check on correspondence between the data entered in the test programfunction and the data printed on the output (FF + BP test option)

1.3 Check on password function

1.3.1 Password challenge on System and Test Program functions

1.3.2 Password change

1.4 Check on time and date change

1.4.1 Time and date change

1.5 Check on ‘User Rights’ function

1.5.1 Check on the correct function of the user management

1.5.2 Check on the change of name for User 1

1.5.3 Check on the possibility to create two users with the same user name

1.5.4 Check if the usage of the same PIN for two users is not allowed

1.5.5 Check on the PIN/Password change function

1.5.6 Check on the correct function of the access control

1.5.7 Check if Level 2 access is required to create/edit test Programs

1.5.8 Check on the correct printout using the Electronic signature function

1.5.9 Check if notes entered in the notes field of the signature screen are printed and stored

1.6 Check on Differential of Electronically Signed and Unsigned Records

1.6.1 Check if the device differentiates between signed and unsigned test programs

1.6.2 Check if the device differentiates between signed and unsigned test result

1.6.3 Check if the device stores a test result as unsigned if the signature is notperformed in the correct way

1.7 Check on Password Management features

1.7.1 Check on the password ageing function

1.7.2 Check on the password length feature

1.7.3 Check on user lock out after entering repeatedly wrong passwords

1.7.4 Check on System lock out after entering repeatedly wrong PINs

1.8 Check on Self Test Sequence with ‘User Rights’ on

1.8.1 Check on self test function with ‘User Rights’ on

1.9 Check on Audit Trail Planning

1.9.1 Check on printing the system audit trail

1.9.2 Check on printing the test program audit trail

1.9.3 Check on printing the user audit trail

Section 2 – Functional Qualification of the Palltronic Flowstar XC Instrument2 Functional Qualification

2.1 General System

2.1.1 Verification of serial number and software version

2.1.2 Check on “line pressure too low” error message

2.1.3 Check on “cancel self test” message

2.1.4 Verification of correct operation of Palltronic Flowstar XC self test

2.2 Test Pressure Setting

2.2.1 Check on set test pressures (FF test option)

2.2.2 Check on set test pressures (WIT option)

2.2.3 Check on set test pressures (FC test option)

2.2.4 Check on correct conversion to other units (psi, kg/cm2, kPa)

2.2.5 Check on correct usage of a test program defined in a different pressure unitthan the system configuration

2.2.6 Power off test

2.3 Forward Flow

2.3.1 Check “within limits” and “outside limits” analysis is accurate

2.3.2 Check on “flow too low” error message

2.3.3 Check on “flow too high” error message

2.3.4 Check on “flow measurement unstable” error message

2.3.5 Check on “manual abort” message

2.3.6 Check on Auto test time function


40

2.4 Water Intrusion

2.4.1 Check “within limits” and “outside limits” analysis is accurate




2.4.5 Check on “manual abort” message

2.4.6 Check on Auto test time function

2.5 Bubble Point

2.5.1 Check that the “within limits” and “outside limits” analysis of results is accurate

2.5.2 Check on function of the leak test

2.5.3 Check on manual abort function

2.6 Forward Flow and Bubble Point

2.6.1 Check on automatic operation of FF + BP function

2.7 Flow Check

2.7.1 Check on the correct operation of the Flow Check function


6.2 Qualification of the Palltronic AquaWIT XC System

Section 1 – Software Qualification of the Palltronic AquaWIT XC System1 Data entry, handling and printing

1.1 Manual Entry

1.1.1 Check on correspondence between the data entered and the data printed onthe output (WIT option)

1.1.2 Check on correspondence between the data entered and the data printed onthe output (Parameter entry

1.2 Use of pre-configured test data (Test Programs)

1.2.1 Check on correspondence between the data entered in the test programmefunction and the data printed on output (WIT option)

1.3 Check on correct data transfer using the Transfer Program

1.3.1 Password challenge using the transfer program

1.3.2 Check on the correct transfer of test programs from the Palltronic AquaWIT XCsystem to a PC

1.3.3 Check on the correct transfer of test programs from a PC to the PalltronicAquaWIT XC system

1.4 Check on password function

1.4.1 Password challenge on Parameter Input, Test Program and Service functions

1.5 Check on “User Rights” feature

1.5.1 Check on “User Rights” function

1.5.2 Check on the correct level access of the “User Rights” feature

Section 2 – Functional Qualification of the Palltronic AquaWIT XC system2 Functional Qualification

2.1 General system

2.1.1 Verification of serial number

2.1.2 Verification of correct software version installed

2.2 Test pressure setting

2.2.1 Check on set test pressures including correction for hydrostatic pressure (WIT option)

2.2.2 Power off test

2.2.3 Check on correct conversion to other units (PSI, kg/cm2, kPa)

2.3 Water Intrusion Test

2.3.1 Check that the “within limits” and “outside limits” analysis is correct





2.3.6 Check on temperature warning

2.3.7 Check on correct function of sensor L1

2.3.8 Check on valve sequence for the external valves (V10, V11, V12)

2.4 Water discard function

2.4.1 Check on water discard function

2.5 Steaming

2.5.1 Check on operation of the steaming function

2.5.2 Check on correct detection of low temperature during steaming

2.5.3 Check on systems reaction to insufficient steam supply

2.6 Cleaning and rinsing

2.6.1 Check on cleaning and rinsing step functions

2.7 Drying of the system

2.7.1 Check on drying function

2.8 Filter cooling

2.8.1 Check on filter cooling function

Installation and Operational qualification protocols are available from Pall.

Appendix A - Definitions

1. Good Automated Manufacturing Practice (GAMP) Guidelines

GAMPThe Good Automated Manufacturing Practice (GAMP) Guide for Validation of AutomatedSystems is the most widely used, internationally accepted guideline for validation of computersystems. The GAMP guide is produced by International Society for Pharmaceutical Engineering(ISPE) and the GAMP forum. More information on GAMP and copies of the guide can be foundat www.ISPE.org.


42

The GAMP guide recommends that comprehensive documentation is produced duringdevelopment of a computer system. Various documentation packages are available from Pallincluding the following documents:

• Functional Specification

• Hardware Design Specification

• Software Design Specification

• Hardware Acceptance Test Specification

• System Acceptance Test Specification

• Installation and Operational Qualification protocols

Appendix B - Qualification of the Calibration Procedure

1. Purpose The current calibration method of the Palltronic Flowstar instruments is based on the technical requirements and, beside the calibration of the pressure transducers, includes thecalibration against flow references in the range of 5 – 10 mL/min and 30 – 60 mL/min. The calibration points are selected based on the technical requirements of the measuringprinciples of the device.

The calibration of test devices is, especially at the low flow end, difficult due to limited sourcesfor transfer standards for the complete flow range.

The aim of the investigation is to demonstrate that this calibration method of the PalltronicFlowstar instrument is valid for the complete flow range of the device.

2. Test Devices and References

2.1 Test Devices used for Qualification

Table 27Devices used for Qualification

Test Device Serial Number Calibration Date

Palltronic Flowstar FFS02 08030526 26th April 2001

Palltronic Flowstar FFS02 20059626 8th June 2001

Palltronic Flowstar FFS02H 05020326 20th September 2001

2.2 References used during Qualification

References for the Gas Flow Measurements (Forward Flow Test)The gas flow of the capillaries used was estimated with a Molbox/Molbloc reference system

Table 28Instruments used for Qualification

Instrument Type Serial Number

Molbox RFM-M 169

Molbloc 1E1-VCR-V-Q 2126

Molbloc 2E2-VCR-V-Q 1817

Reference Instrument for the Water Flow Measurements (WIT)


Table 28 ContinuedInstruments used for Qualification

Instrument Type Serial Number

Mettler Balance PG 203 S 1117281654

3. Test MethodAll tests were performed at room temperature (19 °C – 23 °C)

3.1 Forward Flow TestThe Forward Flow tests were conducted at six capillaries with different flow valuesusing three Palltronic Flowstar integrity instruments which had been calibrated on thedates shown.

The flow values of the capillary units at 2000 mbar (29.0 psi) differential pressurewere estimated using a Molbox™ (Type Molbox™ RFM-M, serial number169)/Molbloc™ (Type 1E1-VCR-V-Q, serial number 2196 and type 2E2-VCR-V-Q,Serial number 1817) gas flow calibration system (DH Instruments, Phoenix, AZ, USA).

In order to perform the tests a capillary unit was connected to the outlet of aPalltronic Flowstar instrument as shown in Figure 20. The Palltronic Flowstarinstrument was programmed to perform Forward Flow tests using an air pressure of2000 mbar (29.0 psi) with a fixed test time of 600 seconds.

Figure 20Diagram of Test Set-up for the Forward Flow Measurements

3.2 Water Intrusion TestWater Intrusion tests were conducted at six different expected flow values using threePalltronic Flowstar integrity instruments which had been calibrated on the datesshown.

The test system was comprised of a vessel partly filled with water with a needle valve(Swagelok™ part number SS-4MG) fitted to the downstream outlet. The testassembly was connected to the outlet of a Palltronic Flowstar instrument as shown inFigure 21.

EmptyChamber



Capillary

Capillary Tube

44

Figure 21Diagram of Test Set-up for the Water Intrusion Measurements

The Palltronic Flowstar instrument was programmed to perform Water Intrusion Testsusing an air test pressure of 2500 mbar (36.3 psi) and a fixed test time of 600seconds. Prior to the start of each test the needle valve was adjusted to provide asmall and stable flow of water.

During the Water Intrusion tests performed by the Palltronic Flowstar instrument, theflow of water was simultaneously measured by collecting the water issuing from theneedle valve in a small container placed on a calibrated electronic balance (Mettler™PG 203S, serial number 1117281654). The balance was linked to a PC and the datarecorded by the balance was recorded automatically every 5 seconds. From thesedata the weight increase per minute (= water flow in mL/min) was calculated. Theweight increase over a three-minute interval at the end of the test performed by thePalltronic Flowstar instrument was used as a reference measurement of water flow.

4. Test Results

4.1 Forward Flow TestThe Forward Flow values measured using three Palltronic Flowstar instruments areshown in Figures 22 to 24. Forward Flow tests were performed on capillariesbetween 1.26 mL/min and 184.5 mL/min at 2000 mbar (29.0 psi). The alloweddeviation was ± 3% as acceptance criteria.

Air

Water

Needle Valve

Balance



Figure 22Comparison of Forward Flow Values measured by the Palltronic Flowstar Instrumentswith Reference Values (Test Device 1)

Table 29Test Device 1

Serial Number: 08030526

Calibration Date: 26th April 2001

Test Date: 14th December 2001

Expected Flow Measured Flow(mL/min) (mL/min) Deviation (mL/min) Deviation (%)

1.26 1.27 0.01 0.8

2.5 2.47 -0.03 -1.2

7.76 7.85 0.09 1.2

50.4 49.8 -0.6 -1.2

97.5 96.7 -0.8 -0.8

184.5 180.6 -3.9 -2.1



Mea

sure

d F

low

(mL/

min

)

Expected Flow (mL/min)

0 50 100 150 200

200

180

160

140

120

100

80

60

40

20

0

Mea

sure

d F

low

(mL/

min

)


0 50 100 150 200

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120

100

80

60

40

20

0

46



Calibration Date: 8th June 2001



1.26 1.27 0.01 0.8

2.5 2.46 -0.04 -1.6

7.76 7.80 0.04 0.5

50.4 51.2 0.8 1.6

97.5 99.1 1.6 1.7

184.5 186.7 2.2 1.2




Calibration Date: 20th September 2001



1.26 1.24 -0.02 -1.6

2.5 2.47 -0.03 -1.3

7.76 7.81 0.05 0.6

50.4 50.6 0.2 0.4

97.5 98.9 1.4 1.4

184.5 186.6 2.1 1.1

The acceptance criteria were achieved.

Mea

sure

d F

low

(mL/

min

)


0 50 100 150 200

200

180

160

140

120

100

80

60

40

20

0

4.2 Water Intrusion TestThe Water Intrusion values measured using three Palltronic Flowstar instruments areshown in Figures 25 to 26. Water Intrusion Tests were performed in the flow range0.04 mL/min to 1.06 mL/min. the allowed deviation was ±0.02 mL/min asacceptance criteria.

Figure 25Comparison of Water Intrusion Values measured by the Palltronic Flowstar Instrumentwith Reference Water Flow Measurement (Test Device 1)



Calibration Date: 20th September 2001

Test Date: 7th February 2002

Expected Flow (mL/min) Measured Flow (mL/min) Deviation (mL/min)

0.05 0.06 0.01

0.08 0.08 0

0.13 0.14 0.01

0.33 0.34 0.01

0.53 0.54 0.01

0.72 0.73 0.01

1.01 1.01 0


Mea

sure

d F

low

(mL/

min

)


0 0.2 0.4 0.6 0.8 1.0 1.2

1.2

1.0

0.8

0.6

0.4

0.2

0.0

48




Calibration Date: 26th April 2001



0.03 0.04 0.01

0.11 0.12 0.01

0.40 0.40 0

0.70 0.72 0.02

1.04 1.06 0.02


Mea

sure

d F

low

(mL/

min

)


0 0.2 0.4 0.6 0.8 1.0 1.2

1.2

1.0

0.8

0.6

0.4

0.2

0.0

Mea

sure

d F

low

(mL/

min

)


0 0.2 0.4 0.6 0.8 1.0 1.2

1.2

1.0

0.8

0.6

0.4

0.2

0.0

Europe+41 (0)26 350 53 00 phone+41 (0)26 350 53 53 [email protected] E-mail

United States800.717.7255 toll free (USA)516.484.5400 phone516.801.9548 [email protected] E-mail

International OfficesPall Corporation has offices and plants throughout the world in locations such as: Argentina, Australia, Austria,Belgium, Brazil, Canada, China, France, Germany, India, Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico,the Netherlands, New Zealand, Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden,Switzerland, Taiwan, Thailand, the United Kingdom, the United States, and Venezuela. Distributors in all major industrial areas of the world.

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

© 2010, Pall Corporation. Pall, , Palltronic, Novasip, Emflon and Kleenpak are trademarks of PallCorporation. ® indicates a trademark registered in the USA. Filtration. Separation. Solution.SM is a servicemark of Pall Corporation. uSwagelok is a trademark of Swagelok Company. Mettler-Toledo is a registeredtrademark of Mettler-Toledo Ltd. Validator is a registered trademark of Kaye Inc. Molbloc and Molbox aretrademarks of DH Industries Inc. GAMP is a trademark of ISPE.

05/10, PDF, UK GN09.3731 USTR 2184b

Visit us on the Web at www.pall.com/biopharmE-mail us at [email protected]



Calibration Date: 8th June 2001



0.05 0.05 0

0.12 0.12 0

0.41 0.42 0.01

0.67 0.69 0.02

1.00 1.01 0.01

The acceptance criteria were achieved.

7. Summary


Validity of the calibration method for the flow The standard calibration method is valid for the complete flow rangerange of the Palltronic Flowstar instrument and especially for the low flow range (< 1 mL/min) which cannot be

included in standard calibration procedures.

8. Document Revision Index

Issue Date Item Change Page

b 13 August 2009 All Formula typographical error amended – now divided 18/20by expected flow

The Average Measured Flow value has been rounded 19/20to two decimal points

Millibar to psi conversion in Table 19 amended – 30affecting ‘Test pressure actual’ (247 mbar at 8.2 ft)

Palltronic® Flowstar and AquaWIT Integrity Test Instruments

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