Radiopharmaceutical
Production
Facility Equipment
STOP
Laboratory Equipment
•
•
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•
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Radiopharmaceutical production
laboratories must be equipped
with a range of production and
analytical instrumentation.
The major equipment will be the
cyclotron, the hot cells and all the
analytical equipment needed to
comply with GMP.
In all cases equipment should be
chosen to be able to meet GMP
requirements, but it is not
necessary to purchase more
expensive equipment which goes
far beyond these requirements.
Some critical pieces of equipment
may need back-ups in case of
equipment failure.
The cyclotron and targets are
covered in another section and will
not be covered here.
Contents
• Production Equipment
• QC Analytical Equipment
• General Laboratory Equipment
STOP
Production Equipment
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
•
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
The FDG production
equipment includes the hot
cells in which the synthesis
and dispensing modules will
be placed, the automated
FDG synthesis module, and
the laminar flow hoods where
the sterile preparations are
done.
The synthesis modules are
covered in another section.
Contents
• Hot cells
• Laminar flow hoods
• Dispensing Equipment
• Material Airlocks
STOP
Hot Cells
Radiopharmaceutical
Production
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
•
General Laboratory
•
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
The hot cell provides a shielded enclosure for handling highly
radioactive materials and can serve as an isolator providing
clean environment for the preparation of radiopharmaceuticals.
The number of hot cells and their size is determined by the
production capacity of the facility and the particular synthesizer
being used. The thickness of lead shielding is determined by
the quantity of FDG being processed; 75 mm of lead or
equivalent is typical, but the Radiation Safety Officer should be
consulted for an final determination..
For radiation safety reasons, the air pressure inside the hot
cells should be maintained well below the pressure of the room
where the hot cell is situated. Furthermore, the hot cells should
be equipped with an appropriate air handling system and
monitor (inlet and outlet air filters as a minimum).
Lead glass windows or TV monitors should be provided with the
hot cells. Production hot cells will generally not need
manipulators. Dispensing hot cells may need tongs or
manipulators depending upon the dispenser used.
Large Production Hot Cells
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
The hot cell provides space and handling facilities for
operations on highly radioactive materials. These can include
the synthesis of radiotracers, processing of irradiated targets,
radwaste processing and storage and other operations which
involve high levels of radioactivity.
Large Production Hot Cells
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
Manipulators can be
used for manual
synthesis when an
automated synthesis
unit is not available.
Smaller Hot Cells (Minicells)
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
•
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
•
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
It is common to have two
smaller hot cells in the FDG
production facility for housing
the synthesis modules (two
FDG synthesis modules are
recommended for redundancy)
and one additional dedicated
hot cell for dispensing of the
product.
Hot cells for the synthesis
modules should provide class C
environment.
A typical hot cell for housing two
synthesis units is shown on the
right.
Radiopharmaceutical
Production
Synthesis Unit in the Hot Cell
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
FDG Synthesizer installed in a small hot cell.
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
FDG Synthesis Unit in a Minicell
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Minicell next to laminar flow hood for QC testing
Room is GMP compliant
Sep-pak is shielded behind additional leaded glass window to
reduce radiation exposure during cleaning
Dual Mini-cells
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
•
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
•
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
Here are mini-cells
with a shielded laminar
flow ot cell next to it to
handle the quality
control testing.
There is a ionization
chamber in the floor of
the laminar flow hood
to enable dose
measurement
Only applicable in the
US
Laminar Flow Hoods
Radiopharmaceutical
Production
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
In addition to chemical fume hoods, there need to be separate
laminar flow hoods where the preparation of sterile materials,
testing of the product for pyrogens and dispensing of doses
may take place.
The most important part of a laminar flow hood is a high
efficiency bacteria-retentive filter. Room air is taken into the unit
and passed through a pre-filter to remove gross contaminants
(lint, dust etc). The air is then compressed and channeled up
behind and through the HEPA filter (High Efficiency Particulate
Air filter) in a laminar flow fashion--that is the purified air flows
out over the entire work surface in parallel lines at a uniform
velocity. The HEPA filter removes nearly all of the bacteria from
the air.
With poor technique it is easy to overcome the established
airflow velocity and introduce reverse currents that can reintroduce contaminants into the work area. Any equipment in
the laminar flow hood can also potentially disturb the laminar
flow.
Laminar Flow Hoods
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
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Provide clean air to the working
area.
Provide a constant flow of air out
of the work area to prevent room
air from entering.
The air flowing out from the hood
suspends and removes
contaminants introduced into the
work area by personnel.
• The environmental control of air is of concern because room
air may be highly contaminated. Example: Sneezing produces
100,000 - 200,000 aerosol droplets which can then attach to
dust particles. These contaminated particles may be present in
the air for weeks. (Have you ever viewed the air around you
when you open the curtains on a sunny day?)...
• Laminar hoods should remain on 24 hours a day. If turned
off for any reason, it should be on for at least 30 minutes and
thoroughly cleaned before reusing.
Laminar Flow Hoods
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
Laminar flow hood
ready for first
cleaning
Number one rule:
always think of the
patient.
A well thought out
training program for
aseptic technique
should focus on
safety and accuracy.
Periodic retraining is
advisable.
Array of syringes, needles
and filters ready for
assembly in the hood.
Radiopharmaceutical
Production
Equipment
Aseptic FDG production
10 % NaCl
W.F.I.
Contents
Production Equipment
STERILE
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
0.3 M
NaOH
STERILE
EtOH
STERILE
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
Syringes, filters, needles,
vials, etc…
STOP
STERILE
Radiopharmaceutical
Production
Dispensing Units
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
•
•
•
STOP
Once the
radiopharmaceutical is
prepared, it must be
dispensed.
The dose may be prepared
as a multi-injection vial
which allows several doses
to be drawn from a single
container, or it may be
dispensed into syringes to
be used as a single unit
dose
Commercial dispensers are
available for both these
operations
The type of enclosure for
these operations is a matter
for local regulations
A simple hand dispenser is
shown at right
Jong O Park et al ARI 2005
Dispensing Units
Radiopharmaceutical
Production
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
At right is a commercial
dispensing unit which will
prepare unit doses of FDG or
any other radiopharmaceutical
The unit is contained in a hot
cell and is controlled by a PC
on the outside of the hot cell
Below: Dispenser for vials
Radiopharmaceutical
Production
Dispensing Units
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
Below is the interior of the
dispensing unit shown in
the last slide.
Syringe in holder
ready for
packaging and
shipping
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
Syringes being
filled through
sterilizing filter
Material Airlocks
Radiopharmaceutical
Production
Equipment
•
Integral to the working of a
cleanroom is the passage of
material in and out of the clean
environment. A pass-through
must provide a tight seal
between clean and non-clean
areas and allow enough space
for the passage of materials.
•
Pass-throughs can be made in
various sizes and fit in
modular walls, drywall, block
or other partitions. Options
include shelves, stainless steel
construction, mechanical or
electrical interlocks, full vision
doors or solid doors with
windows. The can also be
customized to include gas
purge systems, water tanks,
and other specialty
requirements.
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
QC Analytical Equipment
Radiopharmaceutical
Production
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
•
•
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
•
STOP
The Quality Control laboratory
will have two primary
functions: to qualify the FDG
bulk radiopharmaceutical; and
to qualify raw materials and
supplies used in production of
FDG.
The QC lab should be
equipped with the typical
analytical instrumentation,
plus some specific equipment
allowing performance of these
tests
The tests which are required
to release a
radiopharmaceutical such as
FDG are outlined in the QC
section and the instruments
needed to carry out these test
are listed at right
The correlation diagram
between the required test and
the instrument are diagramed
in the following slide.
Contents
• Overview: QC of [18F]FDG
• High Pressure Liquid
Chromatography
• Radio-Thin Layer
Chomatography
• Gas Chromatograph
• pH Measurement
• Osmolality
• Gamma Spectrometer
• Dose Calibrator
• Membrane Filter Testing
• Endotoxin testing
QC of [18F]FDG
Radiopharmaceutical
Production
Equipment
Contents
Identity
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
radionuclide
Dose Calibrator
Chemical (molecule)
Radio-TLC
Dose calibrator
g-spectrometer
Radionuclidic
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
Purity
Chemical
Radiochemical
HPLC-UV
TLC
GC
HPLC-g
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
Radio-TLC
pH-paper
pH
Injectability
Osmolality (isotonic?)
Osmometer
Biological Purity
STOP
Endotoxin
Sterility
LAL-test
Radiopharmaceutical
Production
QC laboratory for FDG
It is possible to measure 15 QC parameters with
5 QC instruments in 30 min
Equipment
Contents
pH
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
TLC
HPLC
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
GC
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
Printer
High Pressure Liquid
Chromatograph
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
•
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
•
General Laboratory
•
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
The HPLC can be used both to
separate the final product from the
starting material and to measure
radiochemical purity in quality
control testing.
It may also be used to test the
radiochemical purity although here
validation studies are required to
ensure that there is quantitative
recovery of the sample.
Regardless of the use, both semipreparative and analytical columns
may be used in daily operations.
The semi-prep columns can be
used to purify product or starting
material while the analytical
columns will be used for QC.
Radiopharmaceutical
Production
Thin Layer Radiochromatograph
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
•
Thin layer chromatography (TLC) is
used for both, determining the
radiochemical identity and
radiochemical purity of the final FDG
product. A radioactivity scanner is
required for quantitative
measurement of the radioactivity
distribution corresponding to the
individual spots on TLC. The TLC
plate can be either plastic or glass
and is developed in the usual
process in a developing tank.
The TLC scanner can be either a gas
proportional counter, phosphor or
scintillation counter mounted so that
the entire plate is scanned.
It can also be used for doing routine
separations for development of new
radiotracers or improvements in
synthetic procedures.
Gas Chromatograph
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
•
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
Identification and quantitation of
the residual solvents
(acetonitrile, and perhaps
ethanol and ether) in the final
product may need to be
performed prior to release of the
FDG.
The test is performed with a gas
chromatograph equipped with a
flame ionization detector (FID)
and an appropriate column
(packed column or capillary
column).
An integrator with software to
identify and quantitate the
residual solvents is a useful
feature and is generally supplied
with the equipment.
Radiopharmaceutical
Production
GC and TLC
Equipment
Contents
•
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
TLC scan results for FDG
STOP
Placement of GC and TLC in
typical Quality Control
Laboratory
Solvent analysis and
radiochemcial purity
pH Measurement
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
•
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
•
The measurement of pH is one on
the requirements for release of the
final product. The pH may be
measured either with a pH meter
or with pH paper.
The latter method is preferred due
to need for a smaller test sample.
It is, however, necessary that the
pH paper is validated for its
suitability.
A pH meter may also be required
for other purposes in the lab.
Osmolality
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
A radiopharmaceutical
preparation should ideally be
isotonic (250-350 mOsm/kg is
considered isotonic). In most
cases, the product may be
released without performing
this test.
An Osmometer is used for
measurement of osmolality of
the radiopharmaceutical
solution. The equipment is
calibrated with known
standard prior to use.
Radiopharmaceutical
Production
Gamma Spectrometer
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
•
To determine radionuclidic purity, a
gamma spectrometer is required.
This will allow the determination of
small amounts of a radionuclidic
impurity in the final product.
This can be carried out either
before the release of the product, or
as is more often the case with
shorter lived radionuclides, this test
is carried out at validation and if
changes are made to the cyclotron
target.
A very simple gamma spectrometer
is shown on the right
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
High purity germanium detector (HPGE)
STOP
Dose Calibrator
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
A dose calibrator is required for
measurement of the radioactivity
(radioassay) in the product vials
to be dispatched to PET facilities.
Dose calibrators are available
from several commercial
companies
Membrane Filter Testing
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
•
[18F]FDG
Overview: QC of
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
At majority of facilities, FDG is not
sterilized with steam, but rather
manufactured in aseptic
conditions with final product being
filtered through a membrane filter.
Assessment of the membrane
filter integrity is the indirect
measure of sterility, which can be
assessed through a relatively
simple test measuring the point at
which the filter allows nitrogen gas
to pass through.
There are automated systems as
well as manual systems available
for carrying out this test.
Endotoxin Testing
Radiopharmaceutical
Production
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
The bacterial endotoxin test
(BET) is based on the
formation of a gel clot by
LAL reagent in the presence
of endotoxins. The formation
of the gel may be inspected
manually or with use of a
device known as endotoxin
test reader.
The test with endotoxin test
reader is simpler and saves
great deal of time, which is
an important factor for quick
release of the FDG
radiopharmaceutical post
production. The device is
based upon turbidity or
kinetic measurement. The
test requires about 20
minutes and gives a more
easily readable test result
and assessment of the
endotoxin level.
Typical endotoxin test reader
is kit based
General Laboratory
Equipment
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
•
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
General laboratory equipment
may be required for a fully
functional manufacturing
facility. Not all equipment is
listed here, and the planners
need to envisage additional
requirements.
This equipment is identical to
that used in any normal
chemistry laboratory and
needs the same care in
selection and maintenance.
Contents
• Fume Hoods
• Balances
• Refrigerators and
Freezers
• Ovens and Incubators
• Melting Point Apparatus
Fume Hoods
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
•
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
For environmental and personal protection
from chemicals and volatile solvents, at
least one fume hood should be available in
the lab.
Fume hoods should have no air recirculation
and should be located as to minimize crossdrafts and turbulence. A face velocity of 0.5
- 0.6 m/sec (100-125 linear feet per minute)
of air is typically required, and should be
continuously monitored.
Typical safety measures, including fire
safety and prevention of small pieces from
being sucked up the exhaust, etc. should be
specified during selection of the equipment.
The development of new synthetic
procedures can also be carried out in these
hoods as long as the amount of radioactivity
is kept low and there is not a serious hazard
of airborne radioactivity.
Fume Hoods
Radiopharmaceutical
Production
Here are some general considerations for the choice of fume hoods
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment type
Consideration
Fume hood
Use the bypass style. Don’t use auxiliary air hoods.
Located to minimize cross-drafts and turbulence.
Face velocity of 0.5 - 0.6 m/sec.
Needs a continuous face velocity monitoring device.
No fire dampers should be placed in the exhaust ducts.
Debris screen to prevent small pieces from being
sucked up by the exhaust.
Single vertical sash.
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
Hood fire suppression system.
Visual or audible local alarm if regular alarm system
cannot be heard inside the room.
Base should be strong enough to hold any shielding.
Purchase of a shielded fume hood is an alternative.
STOP
Balances
Radiopharmaceutical
Production
•
Equipment
Contents
Production Equipment
•
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
Balances are used to weigh out precursors, to make calibration
standards and many other tasks in the laboratory
Balances are preferably in a separate room from production (in
the preparation room)
Separate balances for production and QC are required by GMP
guidelines.
Refrigerators and Freezers
Radiopharmaceutical
Production
Equipment
•
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
•
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
•
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
Many of the reagents used in chemical
synthesis are temperature sensitive
and therefore must be kept
refrigerated.
Other supplies such as the pyrogen
test kits are also temperature sensitive.
Refrigerators should be specified for
the required temperature range, and
also sufficiently large to accommodate
supplies necessary for the required
lead time for procurements.
Some supplies for synthesis (for
example mannose triflate) may require
storage at -20 ºC and if so a freezer
will be necessary.
A 24 hour continuous recording of the
temperature (with an alarm) will ensure
that the malfunction is detected quickly
and does not detrimentally affect the
stored material.
Ovens and Incubators
Radiopharmaceutical
Production
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
Ovens, incubators and sterilizers
are required only if the facility
plans to prepare sterile and
pyrogen free product components
(vials, stoppers, glassware), and
also plans to perform sterility
testing. Samples for testing
sterility are kept in an incubator at
37°C prior to test for the presence
of bacteria in the product.
Melting Point Apparatus
Radiopharmaceutical
Production
•
Equipment
Contents
Production Equipment
Hot cells
Laminar flow hoods
Dispensing Equipment
Material Airlocks
QC Analytical Equipment
Overview: QC of [18F]FDG
HPLC
Radio-TLC
GC
pH
Osmolality
Gamma Spectrometer
Dose Calibrator
Membrane Filter Testing
Endotoxin testing
General Laboratory
Equipment
Fume Hoods
Balances
Refrigerators and Freezers
Ovens and Incubators
Melting Point Apparatus
STOP
•
Assessment of the melting point could be used as an
identification test for reagents used in FDG manufacturing. A
melting point apparatus may be required for qualification of
these materials.
It is necessary that the equipment is calibrated with primary
standards with known melting points.
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