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Advances in Radiotherapy
& Nuclear Medicine QC parameters in radiopharmaceuticals

Table 2. Pharmacopeial requirements for a comprehensive test procedure for sterility is present in pharmacopeias.
list of radiopharmaceuticals For bacterial contamination, the radiopharmaceutical
sample should be incubated for 14 days at 30 – 35° in a
No. Pharmacopeial requirements fluid thioglycolate medium. For fungal contamination,
1 Identification (Radioactive decay, measurement of t , and the radiopharmaceutical sample should be incubated for
½
determination of nature and energy of the radiation)
2 Measurement of radioactivity (radionuclidic purity, 14 days at 20 – 25° in a soybean casein digest medium. The
radiopharmaceutical is not sterile if bacterial, fungal, or
radiochemical purity, specific radioactivity, chemical purity, and
enantiomeric purity) yeast growth is observed in either medium used during the
3 Physiological distribution test. 26-29 The metabolic byproducts (endotoxin) produced
by these microbes, that is, bacterial, fungal, or yeast, can
4 Sterility
cause pyrogenicity.
5 Bacterial endotoxin test-pyrogen
6 pH 6.1.1. Challenge for sterility test
7 Storage and labeling Most radiopharmaceuticals are formulated and used
8 Filter integrity test within a week; thus, there needs to be more time to carry
9 Residual solvent measurement out the standard sterility testing procedures. Due to some
radionuclides’ half-life, the limited batch size, and the
radiation threat, sterility testing of radiopharmaceuticals
poses unique challenges. Since radiopharmaceutical has
an occasionally limited half-life, it must be delivered to
the individual immediately; therefore, it is impossible to
wait for the sterility test results. When the radionuclide
30
half-life is <5 min, the radiopharmaceutical preparation is
often administered to the patient on-site using a validated
production method. 9-13 At the same time, if the batch size of
a radiopharmaceutical preparation is restricted to one or a
few samples, sampling the batch for sterility testing may be
optional. In these circumstances, it is preferred to release
the product produced by a thoroughly approved process
Figure 1. Quality control parameters for radiopharmaceuticals parametrically. When aseptic manufacturing is used, the
sterility test must be executed to control the production
6.1. Sterility quality. 9-13 However, the sterility test is carried out
retrospectively, that is, after patient administration, which
Due to their nature of use, pharmaceuticals are required is the most significant difference between sterility testing
to be sterile and must routinely pass a sterility test. of regular pharmaceuticals and radiopharmaceuticals.
24
For parenteral administration, radiopharmaceutical The test must, however, begin as soon as feasible. If
30
preparations must be made using aseptic techniques to not started immediately, samples are kept in a storage
prevent microbial contamination and the associated risk environment that has been proven suitable for preventing
of infection. When introduced into a radiopharmaceutical, false adverse outcomes. 10,11 The concept of parametric
pathogens may survive the storage period and be injected release is duly addressed in IP 2022, BP 2023, EP 11.0,
in a viable state into the patient. Moreover, many patients USP 2022, and International Pharmacopoeia 11 edition
th
receiving radiopharmaceuticals may undergo cancer pharmacopeias concerning the release of short half-life
chemotherapy, which can compromise the immune system. radiopharmaceuticals. However, the JP 18 edition and CP
th
Testing for sterility is carried out to confirm that drugs are 2015 should be more active on this critical issue.
almost completely free of living microbes, such as fungi
and bacteria. This test must be carried out aseptically to 6.1.2. Significance of sterility testing time
9
prevent interference from external contaminants with the The traditional sterility test procedure requires 14 days
test samples during the experiment. For this, the test should to obtain the result. The results from these methods
ideally be performed in a sterile laminar air flow hood with cannot be used to prompt timely corrective action. The
qualified personnel. A dosage for a human should be used interval between the radiopharmaceutical manufacturing
as the minimum sample volume for the test. To identify and the sterility test must be as short as possible. For
bacterial and fungus contaminations, a quality control radiopharmaceuticals with a long half-life, this is

Volume 2 Issue 3 (2024) 8 doi: 10.36922/arnm.3619