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Water Intrusion Test

Integrity Testing

Test description

Conventional integrity testing of

membrane filters using the

bub-ble point, diffusion or pressure

hold tests requires that the filter

membrane be completely wetted

with a suitable wetting agent

Hydrophobic filter elements can

be tested by this method only if

the surface tension of the

wetting agent is less than the

critical surface tension of the

filter material being used

Other-wise, complete wetting does not

take place

This is why different organic

solvents like ethanol or solvent |

water mixtures are used as

prac-tical wetting media This aspect is

especially detrimental when the

system is used as a “sterile air

filter" for venting tanks,

bio-reactors and fermenters

Integrity testing of filters for

liq-uids is usually performed in situ

However, the in situ integrity

testing of hydrophobic gas

filters is only possible to a limited

degree due to safety reasons (e.g.,

explosion protection when

test-ing with organic solvents) and to

keep the product from solvent

contamination Besides these

complicated individual tests must

be followed by a drying phase

before any filter elements can

be installed

Additionally the filter sealing in

the housing still has to be tested

in situ Since the filters should be

retested immediately aher in-line

steam sterilization, tests with a

solvent | water mixture are

impractical for the user

Moreover, the drying procedure

must be validated since solvent

residues can contaminate the

product if drying has been

insufficient

The Water Intrusion Test (WIT)

was developed to overcome all of

these disadvantages The WIT can

be used to run routine integrity

tests simply, easily and reliably

Definition Water Intrusion Test (WIT).

The Water Intrusion Test (WIT)

is an in-situ integrity test for hydrophobic filters The WIT measures the decay rate of

a pressure level imposed upon

a hydrophobic membrane enveloped in water.

Theoretical principles.

Among other things, a pressure gradient that is dependent on pore size is necessary to over-come negative capillary forces (cohesive forces) This pressure is generally called the "Water Penetration Point" (WPP), the pressure at which water is pressed through a hydrophobic membrane The WPP is depend-ent on the hydrophobicity of the filter material and the pore size and is comparable to the bubble point

The relationship can be illustrated as follows:

Dmax= Diameter of the largest

pore

σ = Surface tension of the

liquid in dynes/cm (water 72)

θ = Angle of contact

(greater than 90° in hydrophobic filters)

∆ p = Available upstream

differential pressure (bar | psi)

k = Correction factor

(required since membrane filter pores are not cylindrical capillaries)

Introduction

4 · σ · cos θ

Intrusion (ml/10 min)

Test Pressure (bar)

350 300 250 200 150 100 50 0

Water Intrusion

Water Penetration

Water Intrusion Characteristics at Different Test Pressures

Pore Size: 0.2 µm, Height: 10’’, Temperature: 20°C

Principle of Water Intrusion Test

The Water Intrusion Test (WIT)

was developed as an integrity

testing method to test

hydropho-bic sterilizing grade filters These

filters are often used as inlet air

and off-gas filters for fermenters

bioreactors and for venting

sterilizers, freeze dryers

auto-claves and tanks

The WIT is employed in both the

qualification of filter elements

and as an inplace test procedure

The WIT - like the mercury

intrusion test - is based on the

capillary depression of non

wetting liquids on the outer

surface of the membrane To

withstand these capillary forces,

a certain pressure gradient,

which is dependent on the pore

size among other factors, is

necessary The test run is in a

similar manner to the Diffusion

Test, although there is a major

difference In the Diffusion Test,

the diffusive gas flow through a

wetted membrane is measured

However, during the WIT a

hydrophobic filter installed in a

filter housing is flooded with

water on the upstream side

The pressure drop detected by an

automatic integrity tester

indi-rectly measures the volume of

water intruding into the

mem-brane matrix At first the test

system has to be flooded with

water, pressurised at the defined

test pressure and then stabilised

for a defined time After the

stabilisation time

is complete, the

water intrusion

will be measured

Origin of the pressure drop.

The pressure drop has two main reasons:

1 The upstream volume is in fact increasing due to remaining compaction processes Since this compaction is an asymp-totic process, it is never absolutely completed There-fore, a certain time has to be determined after which most

of the compaction is already done That is the main reason for the stabilization time of

10 Minutes

2 Water molecules actually get transported through the mem-brane In case of an integer membrane, this process is mainly due to evaporation of water molecules through the pore structure If the mem-brane is punctured, water is mainly flowing through the punctured hole

Water vanishes from the up-stream side The effect is, that the upstream volume is increasing (keep in mind that water is not subject to compaction) This amount of water (∆V) can be determined using the fundamen-tal law of Boyle and Mariott (p1· V1= p2· V2)

Principle of WIT testing

compressed air |gas







p1

p2

V1 · ∆p (p1- ∆p)

=

∆ V

∆t

Vn · ∆p (p1– ∆p) · ∆t

∆ V = V2- V1 = V1· - 1 =

with:

p1: Absolute pressure at the beginning of the pressure drop measurement [mbar]

p2: Absolute pressure at the end of the pressure drop measurement [mbar]

∆p: = p1- p2

V1: Upstream Volume at the beginning of the measurement [ml] (= Vn)

V2: Upstream Volume at the end of the measurement [ml]

The increase in Volume per time is defined as:

This value is defined – as one easily understands – as the “Water Flow Value” This value is basically linked to the Water Intrusion Value by a simple mathematical correlation:

The Water Intrusion is a value that has been defined in analogy to the diffusion For small pressure drops (< 5% of the absolute test pressure), the following equation holds:

with:

Vn: Upstream Volume [ml]

∆p: Pressure Drop [mbar]

1000 mbar: Reference Pressure

∆t: measurement duration [min]

Physically, air molecules pass through the wetted membrane If one collects all these molecules, they will fill a certain volume at 1000 mbar reference pressure at the ambient temperature as reference temperature This volume pre time is the Diffusion value

The Water Intrusion is calculated using the same formula:

If one imagines the volume ∆V that has been added to the upstream Volume due to the Water Flow to be filled with gas, it would use a different volume at an ambient pressure of 1000 mbar Again, the required volume at 1000 mbar (∆V10OO) can be calculated with Boyle Mariott's law to be:

∆V

∆t

Vn · ∆p (p1- ∆p) · ∆t WIT = · p1 - ∆p = · =

1000 mbar

(p1 - ∆p)

1000 mbar

Vn · ∆p

1000 mbar · ∆t

Diff = Vn · ∆p

1000 mbar · ∆t

WIT = Vn · ∆p

1000 mbar · ∆t

∆ V1000 = ∆ V · (p1 - ∆p)

1000 mbar







Test parameters

Practical aspects Water

Intrusion Test.

• Allows inplace testing after

sterilization

• Avoids using wetting agents,

e.g IPA/Water

- Therefore no contamination

- No removal problems

No alcohol residue or

down-stream contamination

• The hydrophobicity of the

filter stays hydrophobic during

the test

• High sensitivity of the test

• The hydrophobicity of the filter

is evaluated by the test

• The time is reduced, especially

at multiple systems, which

reduces the shut down periods

• Directly correlated to the ASTM

Bacteria Challenge Test

System set-up.

The WIT can be used in a variety

of air filtration applications that require minimal engineering changes, however, some times systems may have to be reconfig-ured This is where the Sartorius Technical Support team comes to your assistance

The diagram to the right shows

an example of a manual WIT sys-tem The basic construction does not differ significantly from that used for the diffusion test In principle, WIT systems can be designed as manual, semi-auto-matic and fully autosemi-auto-matic units

to suit the applications, e.g., sterile venting systems for auto-claves, Iyophilizers, fermenters and tanks

Basic requirements for the test are:

1 The surface tensions of the water used must be > 72 dynes/cm

2 Minimized temperature differ-ence between the water and the inlet air ± 1k

3 Temperature fluctuations must

be avoided during the test

4 Filter element must be com-pletely hydrophobic

5 Adequate effective filter area, i.e., > 0.1 m2

6 The integrity tester must have sufficient accuracy, e.g., Sartocheck®unit

Operating sequence:

1 Completely fill the upstream side of the filter housing with water

2 Close all upstream valves

3 Connect the integrity tester, e.g., Sartocheck 3 unit

4 Start the test: The unit per-forms the WIT automatically

5 The test is completed and the results are printed out

6 Empty the filter housing through an appropriate drain

or condensate valve

7 Briefly vent dry using pressu-rized air with the inlet and drain valves open

8 Start operating the system

Maximum permissible intrusion rates

False failures and

trouble-shooting.

If the filter cartridge does not

pass the test, it might be that

partial hydrophilization of the

membrane has occurred In this

case, the filter must be

steam-sterilized for at least 30 min at

121°C or 134°C and then

repeat-edly blown dry with hot air

Other false failures might be

attributable to water surface

tension and temperature

fluctua-tions All of these factors will

invariably cause elevated water

intrusion values (false failures)

Experience has shown that these

increased values indicate

“marginal“ failures and do not

lead to high water flow rates or

extreme pressure drops An

isopropanol|water test will

deter-mine whether one of these

causes is the problem or whether

the filter cartridge is out of

specification Fault free filters

will pass the solvent test because

this test cannot detect any

hydrophilization or reduced

sur-face tension of the water used

for the initial WIT

After the WIT, the filter

cartridges need to reach their

original air flow rate as quickly

as possible In other words, they

must not become blocked with

water, e.g., residual water in the

fleeces The time that the filter

cartridge needs to achieve 100%

of the original flow rate is called

the “blow-down" time

Test pressure.

The high air pressures needed to

force water penetration of the

PTFE membranes used in the

Sartofluor filter cartridges result

in very high test pressures used

for the various pore size ratings

This increases the tests reliability,

accuracy and precision

Pore Size Water WIT Test

Penetration Pressure

Pressure

bar psi bar psi

0.20 µm 4.5 65 2.5 36

0.45 µm 2.8 41 1.5 22

These variables are dependent on

the introduction of water with a

surface tension of > 72 dynes/cm

Stabilization and test time

The compressible upstream air volume above the water column and the actual water intrusion level are both low This illustrates the importance of maintaining sufficient stabilization and test times Enough time must be available for the water column to become saturated with air at the test pressure Similarly, the water must be distributed over the entire membrane area without the presence of air bubbles and the filter pleating must be fully compacted The following, values have been established for the stabilization and test times:

Stabilization time 1 13 min Stabilization time 2 10 min Test time 10 min

If these times are shortened the intrusion values may be too high due to insufficient distribution

of water across the membrane surface or faulty compacting of the membrane pleats

As in the diffusion test (and in all integrity tests), the maximum permissible water intrusion rates given by the filter manufacturer for the WIT must follow the ASTM bacteria challenge test methodology (HIMA Document

No 3, Vol 4, April 1982)

Factors influencing the Water Intrusion Test

Hydrophilizing active agents.

As already mentioned, the use of

WIT requires that the filter

elements be com pletely dry and

hydrophobic Surface active

agents like solvent vapors,

detergents or oils can lead to

partial membrane

hydrophiliza-tion and thus to false negative

results

Moreover, these agents might

also reduce the air flow rate if

parts of the membrane matrix are

blocked by these agents During

normal operations, strict

atten-tion must be paid to these factors

and appropriate counter

measu-res taken when necessary

If partial hydrophilization occurs

the filter cartridge must be

hand-led as described on previously

page

Difference in temperature.

False failures may occur if the temperature difference between the test air and the water is too great If the water temperature

is much lower than the air tem-perature, great drops in pressure and high intrusion rates can result If the water temperature is much higher, the pressure drops will be too low

This situation can be remedied by storing the water in a storage tank in the room where the test will be performed or by filling the housing with water adjusted to the right temperature

Low surface tension of the water.

This situation mostly arises when the tanks being used are not cleaned and rinsed thoroughly, old ion exchange resins are used for preparing the water, or the water temperature is too high (> 32°C|90° F) These parameters can be avoided by taking preven-tive measures or adapting the water temperature

Fluctuations in ambient temperature.

Such temperature fluctuations affect the pressure drop measured during the test The same applies to the diffusion and pressure drop test The possi-bilities for the test being affected are minimized because the area

of the housing that comes into contact with the test air is very small compared to that in the diffusion test

Moreover, the great heat capacity of water compensates for any fluctuations Integrity tests are normally performed

in airconditioned rooms This source of error is therefore encountered very rarely

Inlet volume.

Generally with large-volume systems, the precise volume can

be easily determined, whereas the measured pressure drop may merely amount to a few mbar The results may then border

on the accuracy limits of the integrity tester and false results could be obtained

Similarly, when dealing with very low net volumes, high pressure drops can occur, leading to inaccurate test results

The net inlet volume must there-fore be selected so that both parameters relevant for intrusion measurement – namely, volume and pressure drop – can be deter-mined as accurately as possible

Sartorius AG

Weender Landstrasse 94–108

37075 Goettingen, Germany

Phone +49.551.308.0

Fax +49.551.308.3289

www.sartorius.com

Sartorius Corporation

131 Heartland Boulevard,

Edgewood, New York 11717, USA

Phone +1.631.2544249

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Toll-Free +1.800.3687178

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KT199QN, Great Britain

Phone +44.1372.737159

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91127 Palaiseau, France

Phone +33.1.69192100

Fax +33.1.69200922

Sartorius S.p.A Via dell’Antella, 76 /A

50011 Antella (FI), Italy Phone +39.055.634041 Fax +39.055.6340526

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No 3 Hoya Building 8–17 Kamitakaido 1-chome Suginami-ku Tokyo 168-0074, Japan Phone +81.3.33295533 Fax +81.3.33295543

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28050 Madrid, Spain Phone +34.91.3586100 Fax +34.91.3588804

Specifications subject to change

without notice

Printed in Germany on paper that has been

bleached without any use of chlorine.

W/sart-153a · G

Publication No.: SP-4504-e04014