Radiopharmaceutical Production

Filter integrity test

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 Filter Integrity Test
• The filter integrity test is one of the Contents
most important tests that are • Acceptance Criteria
carried out on the final product. • Discussion
• A satisfactory result from this test • Procedure
gives assurance that the final
product is sterile and therefore • Example SOP
acceptable for human use.
 Filter integrity test
Radiopharmaceutical
Production

Acceptance Criteria: The membrane filter integrity test is not

QC Tests
mentined in the International Pharmacopeia. However, it is a
Filter Integrity Test requirement of GMP guidelines on aseptic processing using
final sterilizing filtration. It is highly recommended that this test
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is performed prior to release of the product.
Acceptance Criteria
Discussion
Procedure
Example SOP

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 Filter integrity test
Radiopharmaceutical
Production

Discussion: Although this test is not required by the

QC Tests
International Pharmacopeia, the fact that the sterility test results
Filter Integrity Test will not be available when the radiopharmaceutical is injected,
assessment of the filter integrity using bubble point or pressure-
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retaining test represents an appropriate indication of the
Acceptance Criteria
performance of the aseptic processing and sterility of the
Discussion
product. Therefore, it is highly recommended that the filter
Procedure
integrity test be performed after dispensing and prior to release
Example SOP
of the FDG product batch.

It must be emphasized that the filter integrity test does not

replace the required sterility test.

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 Filter integrity test
Radiopharmaceutical
Production

Procedure: Connect to a three way valve a 50-60 cc syringe, a

QC Tests
pressure gauge (reading >60 psi), and the filter being tested. (If
Filter Integrity Test using a vented filter, block the vent hole with a drop of oil). At
end of the filter, attach an extension tube, other end of which is
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dipped in a beaker filled with water. As pressure is applied by
Acceptance Criteria
pushing the plunger, record the pressure reading when
Discussion
continuous stream of bubbles is formed in water. Nominal
Procedure
pressure reading for an intact filter is >45 psi.
Example SOP

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 Example Procedure
Radiopharmaceutical
Production
Vented filter procedure
Filter Wetting: The filter must have been thoroughly wetted
QC Tests prior to testing. Using it for final product filtration wets it
adequately. The vent should be closed with mineral oil
Filter Integrity Test

Mounting the Filter: Mount the filter in the Bubble Point

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testing apparatus. There is a female Luer fitting on top of
Acceptance Criteria the bubbling chamber (Picker vial with water in it) and a male
Discussion Luer fitting on a 1/8" line for the gas supply.
Procedure
Example SOP Initial Pressure Test: Turn V2 to "Test" and then turn V1 to
"Low." This will apply a pressure of 35 psig to the filter.
Observe that there is not a stream of bubbles exiting the
filter. A single bubble or two is quite acceptable as the gas
pressure forces the filter to deform slightly.

Find the Bubble Point: Turn V1 to "High" to slowly increase

the pressure to the rated bubble point of the filter. Note the
pressure at which the filter begins to pass a steady stream of
bubbles. Record the bubble point pressure in the batch
record. Technically the filter passed the manufacturer
specifications when it held ≥32 psig.
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 Example Procedure
Radiopharmaceutical
Production Unvented filter Procedure
Filter Wetting: Wet the filter with the appropriate fluid,
typically water for hydrophilic membranes or an
QC Tests alcohol/water mixture for hydrophobic membranes.
Filter Integrity Test
Pressurize the system to about 80% of the expected bubble
point pressure which is stated in the manufacturer’s
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literature.
Acceptance Criteria
Discussion
Slowly increase the pressure until rapid continuous bubbling
Procedure is observed at the outlet.
Example SOP

A bubble point value lower than the specification is an

indication of one of the following:
– fluid with different surface tension than the
recommended test fluid
– integral filter, but wrong pore size
– high temperature
– incompletely wetted membrane
– non-integral membrane or seal

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