Pharmaceutical Manufacturing Handbook: Production and

90 RADIOPHARMACEUTICAL MANUFACTURING
be fast and effective. Still, some radiopharmaceuticals with very short half - lives may
have to be distributed and used after assessment of batch documentation even
though all quality control tests have not been completed. It is acceptable, though,
for these products to be released in a two - stage process, before and after full analytical
testing. In this case there should be a written procedure detailing all production
and quality control data that should be considered before the batch is dispatched.
A procedure should also describe the measures to be taken by the QP if unsatisfactory
test results are obtained after dispatch (GMP, Annex 3).
The quality control tests fall in two categories: biological tests and physiochemical
tests. The biological tests establish the sterility and apyrogenicity, while the
physiochemical tests include radionuclidic, chemical, and radiochemical purity tests
along with determination of pH, osmotic pressure, and physical state of the sample
(for colloids).
For lyophilized preparation kits containing reducing agents, such as 99m Tc kits, a
test for moisture content can be necessary. Residual water in the freeze - dried pellet
may lead to oxidation of the reducing agent.
Radionuclidic Purity Radionuclidic purity is defi ned as the fraction of the total
radioactivity in the form of the desired radionuclide present in a radiopharmaceutical.
Radionuclide impurities may arise from impurities in the target material or from
fi ssion of heavy elements in the reactor [2] . In radionuclide generator systems, the
appearance of the parent nuclide in the daughter nuclide product is a radionuclidic
impurity. In a 99 Mo/ 99m Tc generator, 99 Mo may be found in the 99m Tc eluate due to
breakthrough of 99 Mo on the aluminum column. The presence of these extraneous
radionuclides increases the radiation dose to the patient and may also obscure the
scintigraphic image.
Radionuclidic purity is determined by measuring the characteristic radiations
emitted by individual radionuclides. Gamma emitters are distinguished from another
by identifi cation of their γ energies on the spectra obtained from a NaI crystal or a
Ge (germanium) detector. This method is called γ spectroscopy.
Pure β emitters are not as easy to check as the γ emitters. However, they may be
checked for purity with a β spectrometer or a liquid scintillation counter.
Radiochemical Purity The radiochemical purity (RCP) of a radiopharmaceutical
is the fraction of the total radioactivity in the desired chemical form in the radiopharmaceutical.
Radiochemical impurities arise from decomposition due to the
action of solvent, change in temperature or pH, light, presence of oxidizing or reducing
agents, and radiolysis [2] . Examples of radiochemical purity are free 99m Tc -
pertechenetate and hydrolyzed 99m Tc in labeled 99m Tc radiopharmaceuticals. The
presence of radiochemical impurities in a radiopharmaceutical results in poor -
quality images due to the high background from the surrounding tissues and blood.
It also gives the patient unnecessary radiation doses.
A number of analytical methods are used to detect and determine the radiochemical
impurities in a given radiopharmaceutical. Most commonly used are
methods like paper (PC), thin - layer (TLC), and gel chromatography, paper and gel
electrophoresis, HPLC, and precipitation. A common principle for the different
methods is that they can chemically separate the different radiolabeled components
in the radiopharmaceutical. It may sometimes be necessary to perform more than