Transcript Procedure

Radiopharmaceutical Production
Filter integrity test
STOP
Filter Integrity Test
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The filter integrity test is one of the
most important tests that are
carried out on the final product.
A satisfactory result from this test
gives assurance that the final
product is sterile and therefore
acceptable for human use.
Contents
• Acceptance Criteria
• Discussion
• Procedure
• Example SOP
Filter integrity test
Radiopharmaceutical
Production
QC Tests
Filter Integrity Test
Contents
Acceptance Criteria
Discussion
Procedure
Example SOP
STOP
Acceptance Criteria: The membrane filter integrity test is not
mentined in the International Pharmacopeia. However, it is a
requirement of GMP guidelines on aseptic processing using
final sterilizing filtration. It is highly recommended that this test
is performed prior to release of the product.
Filter integrity test
Radiopharmaceutical
Production
QC Tests
Filter Integrity Test
Contents
Acceptance Criteria
Discussion
Procedure
Example SOP
Discussion: Although this test is not required by the
International Pharmacopeia, the fact that the sterility test results
will not be available when the radiopharmaceutical is injected,
assessment of the filter integrity using bubble point or pressureretaining test represents an appropriate indication of the
performance of the aseptic processing and sterility of the
product. Therefore, it is highly recommended that the filter
integrity test be performed after dispensing and prior to release
of the FDG product batch.
It must be emphasized that the filter integrity test does not
replace the required sterility test.
STOP
Filter integrity test
Radiopharmaceutical
Production
QC Tests
Filter Integrity Test
Contents
Acceptance Criteria
Discussion
Procedure
Example SOP
STOP
Procedure: Connect to a three way valve a 50-60 cc syringe, a
pressure gauge (reading >60 psi), and the filter being tested. (If
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
dipped in a beaker filled with water. As pressure is applied by
pushing the plunger, record the pressure reading when
continuous stream of bubbles is formed in water. Nominal
pressure reading for an intact filter is >45 psi.
Example Procedure
Radiopharmaceutical
Production
Vented filter procedure
Filter Wetting: The filter must have been thoroughly wetted
prior to testing. Using it for final product filtration wets it
adequately. The vent should be closed with mineral oil
QC Tests
Filter Integrity Test
Contents
Acceptance Criteria
Discussion
Mounting the Filter: Mount the filter in the Bubble Point
testing apparatus. There is a female Luer fitting on top of
the bubbling chamber (Picker vial with water in it) and a male
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.
STOP
Example Procedure
Radiopharmaceutical
Production
Unvented filter Procedure
Filter Wetting: Wet the filter with the appropriate fluid,
typically water for hydrophilic membranes or an
alcohol/water mixture for hydrophobic membranes.
QC Tests
Filter Integrity Test
Pressurize the system to about 80% of the expected bubble
point pressure which is stated in the manufacturer’s
literature.
Contents
Acceptance Criteria
Discussion
Slowly increase the pressure until rapid continuous bubbling
is observed at the outlet.
Procedure
Example SOP
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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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