Troubleshooting

Report
Radiopharmaceutical
Production
FDG Production Problems
Troubleshooting
STOP
Table of Contents
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
No Fluorine-18 transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released from the resin column
No trapping of tetraacetate on C-18 column
Final product not delivered into vial
Product purity is low due to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure and recovery
Pyrogen test failure
Ionization chamber failure
STOP
[18O]H2O Delivery
Radiopharmaceutical
Production
Source of Problem Symptom or
problem
description
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Transfer
Potential Solution(s)
No delivery of irradiated Check for delivery path,
water from the target
maybe it was
after irradiation
delivered into a
different hot cell?
Check for clogged
transfer frit at the
target
Transfer lines itself can
be clogged after
using them for a few
weeks/month
[18O]H2O Delivery
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source Problem
Potential Solution(s)
of
Symptom
problem or
description
Transfer
No delivery
of irradiated
water from
the target
after
irradiation
He bottle for transfer is empty (you
would be surprised how often this
happened in the beginning)
X
Check that the water target was
actually loaded with O-18 water
[18O]H2O Delivery
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of
problem
Problem Symptom or
description
Potential Solution(s)
Transfer
Only parts of the
irradiated water are
delivered
Check for leaks in the
transfer line
Check for the target filler
system, especially after a
few years of heavy use
they need high
maintenance
Check to see if the water
broke up during transfer
(significant residual
activity in the transfer
line). If so depressurize
the line and slowly
pressurize again
No 18F- Trapping
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of Problem Symptom or
problem description
Potential Solution(s)
Trapping
of 18F
Forgot to condition the
ion exchange
cartridge before
installation
No trapping of the
[18F]fluoride on the
ion exchange
cartridge in the
module
In the last months/past
year the quality of
the cartridges are
questionable, so
even correctly
conditioned
cartridges failed
18FRadiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Release
Source Problem Symptom Potential Solution(s)
of
or description
problem
Release
of 18F
No transfer of the
Forget to install eluant vial
[18F]fluoride from
at the module (it is a
the ion exchange
little bit out of the way
cartridge into the
and tends to be
reactor
forgotten)
Pinch valves at the eluant
block tend to fail after a
few weeks of use
without maintenance
Eluant leaks out
The concentration of the
carbonate solution is
incorrect or has lost
strength over time
Tetraacetate Separation
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of
problem
Problem Symptom or Potential Solution(s)
description
Trapping of Low trapping efficiency
tetraacetate of the un-hydrolysed
labeled acetylated
compound (2[18F]fluoro-1,3,4,6tetra-O-acetyl-Dglucose) on the
reverse phase
cartridge from
WATERS.
In the last months/past
year the quality of the
reverse phase cartridge
(Sep-Pak Plus C18)
from WATERS are
questionable
Incorrect acetonitrile to
water ratio when
applied to seppak
STOP
No FDG Delivery
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of Problem Symptom or
problem description
Potential Solution(s)
Final
Product
Delivery
Forgot to install the
sterile filter at the final
product vial
Final Product does not
arrive in the multiinjection vial
If the product is
transferred from the
production hot cell into
the dispensing hot cell
the wrong transfer line
is hooked up to the
final product vial in the
dispensing cell
STOP
No FDG Delivery
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of Problem Symptom or
problem description
Potential Solution(s)
Final
Product
Delivery
Vent needle is inserted
too deep into the
product vial, so FDG
solution can spray out
Final Product does not
arrive in the multiinjection vial
of the vent
Final purification
cartridges not
conditioned or installed
properly
STOP
FDG Purity Problems
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of Problem Symptom or
problem description
Potential Solution(s)
Product
purity
Acid concentration was
too low
Product is not
completely hydrolyzed
Vessel was not up to
temperature during
hydrolysis step
Mechanical Problems
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of
problem
Problem Symptom
or description
Mechanical Slow transfer of
Problems
reagents
Loss of vacuum
Potential Solution(s)
Replace frits, back
flush valves, look for
crimped lines
Change
damaged/broken lines
Software Problems
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Source of Problem Symptom or
problem description
Potential Solution(s)
Software
Problems
Valve did not open
during the run
Set appropriate
conditions
(temperature. Pressure)
and open the valve
manually
Reactor heater did not
respond
Set appropriate
temperature and turn
on heater manually
Human Errors
Radiopharmaceutical
Production
Source of Problem Symptom or
problem description
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Human
error
Potential Solution(s)
System not pressurized Open valve on the He
cylinder
Run failed due to
precursor not being
transferred into reactor
Observe the video
monitor at critical times
Run failed due to wrong Be alert when doing
position of F-18 trap
synthesis
and purification column
Forgot to dissolve
triflate, used only
acetonitrile
Follow the procedures
exactly as written
Sterile Filtration Failure
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Syringe Filter Integrity Test
• Conduct the integrity test for the filter used to filter the
final product into the MIV. If the test fails, indicating that
filter is not intact at the time of testing, the product can be
re-filtered into a new set sterile MIV, and delivered to the
PET.
Additional Sterile MIV
• If there is another identical sterile setup available from a
later run, this may be used after changing the label to
indicate the correct delivery number.
• Otherwise, a new sterile setup must be prepared using
the standard sterile setup technique. The product must
be drawn up from the original MIV using a sterile needle
and syringe, and filtered as usual into the new MIV.
• The new filter must be integrity tested before delivery can
be made.
Pyrogen test failure
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
Positive Pyrogen Tests
• If the sample showed positive results for pyrogen on the
20 minute PTS test at maximum allowable dilution, this is
a serious matter and NO deliveries can be made for
humans until the problem is resolved.
• If a radiotracer has failed to pass the two consecutive
tests, then a sample must be sent to AppTec
(Commercial Testing Company) for pyrogen testing.
Responsible Physician Notification
• In all cases, the responsible physician should be
informed, so appropriate notations can be made in the
subject’s file.
Capintec Failure
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
High Background
• If background activity exceeds normal background limits,
then check for radioactivity in the hood and remove or
shield appropriately. Re-check background.
Contaminated Capintec
• If no radioactivity is found in the area then check for
contamination of the chamber liners and/or dipper.
Replace if contaminated and re-check background.
Capintec Problems
• If normal background cannot be established with either
procedure above then the chamber must be re-calibrated,
repaired or replaced.
Noisy response
• A noisy response is defined as abnormal fluctuations in
displayed numbers with or without radioactivity. Check that
the proper isotope selection button is depressed. Depress
the button then release and repeat several times to confirm
position. Check cable connections from chamber to
display. Repeat daily check if noise is eliminated to assure
proper operation.
Capintec Failure
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
• No Capintec response
• If no numbers are displayed then check power
connections, circuit breaker and main power switch on
display unit. A circuit breaker may be reset only one time
to restore power. If numbers appear, but do not change
after a known change in radiation levels, then confirm
radioactivity levels with another device (e.g. frisker) and
re-check cables and isotope selection button.
• Malfunction during Synthesis
• Most often the problems above will be detected during
the daily performance check when there is time to carry
out corrective actions and re-check instrument
performance. If there is a malfunction during synthesis
and the corrective actions listed above are not possible
then:
– Alternate Ion Chamber- If the final product assay chamber
malfunctions then the radioactivity of the product may be
measured in another calibrated chamber in the laboratory.
Confirm that the chamber has been properly calibrated
before use and document in the batch record.
Summary
Radiopharmaceutical
Production
No Fluorine-18
transferred to synthesizer
Partial transfer of F-18
Fluorine-18 not released
from the resin column
No trapping of
tetraacetate on C-18
column
Final product not
delivered into vial
Product purity is low due
to unhydrolyzed
tetraacetate
Mechanical problems
Software problems
Human errors
Sterile filtration failure
and recovery
Pyrogen test failure
Ionization chamber
failure
STOP
• There are several problems which can occur during the
production and delivery of the fluoride
• There are other problems that may occur during the
production
• Some of these problems can be anticipated and
corrective actions taken if the corrective actions are
planned and documented in advance.
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