Page 30 - ARNM-2-3

Advances in Radiotherapy
& Nuclear Medicine QC parameters in radiopharmaceuticals

Table 3. Comparative status of endotoxin limit calculation based on radiopharmaceutical product administration
Administration form of IP 2022 9 BP EP 11.0 11 USP 2022 12 JP 18 International CP 2015 14
th
radiopharmaceutical products 2023 10 edition 15 Pharmacopoeia
11 ed.ition 13
th
Not administered intrathecal 175/V N/A N/A 175 EU/V N/A N/A N/A
where V is the maximum where V is
recommended dose in ml the maximum
recommended
dose in ml
Administered intrathecal 14/V N/A N/A 14 EU/V N/A N/A N/A
where V is the maximum
recommended dose in ml
Administered intravenous N/A K/M K/M where 175 EU/V K/M K/M where K is K/M
where K K is 2.5 IU where V is where K is 2.5 IU where
is 2.5/kg of endotoxin the maximum 2.5 IU K is 2.5
or 175/ per kg of recommended EU/kg/hr
person body mass dose in ml
Abbreviations: BP: British Pharmacopoeia; EP: European Pharmacopoeia; USP: US Pharmacopoeia; IP: Indian Pharmacopoeia; CP: Chinese
Pharmacopoeia; JP: Japanese Pharmacopoeia.

impossible to exclude the interfering factor(s). Due to the commencement of production of the finished product,
use of reducing agents and metal chelating agents in the the producers conduct these quality control checks.
formulation of many 99m Tc-radiopharmaceuticals, the LAL Sterility is a crucial quality factor for pharmaceutical
test may produce false negative or positive findings. Since preparations, among other biological quality control
the radionuclide in the preparation has a short half-life, it test parameters. For drugs that have been terminally
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can be challenging to conduct these tests before approving sterilized, parametric release typically replaces routine
the batch for use. 9-15 To conduct a rabbit pyrogen test, sterility testing. A robust quality assurance process is
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three healthy rabbits must first receive an intravenous necessary for parametric releases to generate a product
injection of the substance under test in a predetermined with the appropriate attributes and features. The
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volume, followed by a 3-h period of rectal temperature basis for parametric release is proof of successfully
monitoring. A positive test is recorded if an individual validating the manufacturing process in accordance with
rabbit’s temperature increases by ≥0.6° above baseline or established good manufacturing practices and sterilization
if the total temperature rises of all three rabbits surpasses protocols, as well as a review of the documentation on the
1.4°C. 40 additional process monitoring carried out throughout the
7. Status of radiopharmaceutical biological manufacturing process to support parametric release. 44,45
The use of parametric release, or release of a batch of
quality control standards in pharmacopoeia sterile items based on process data rather than submitting
The comparative status of radiopharmaceutical a sample of the items for sterility testing, may be carried
biological quality control standards present in different out if the appropriate regulatory body approves when
pharmacopeias of the world has been mentioned in a properly approved terminal sterilization procedure
Table 1, highlighting detailed information on the presence using steam, dry heat, or ionizing sterilization is applied.
or absence of biological test parameters in individual Aseptic assembly or filtration through a bacterial retentive
monographs. filter is utilized if terminal sterilization is not feasible for
parametric release. Regarding the requirement to test
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8. Discussion each consignment before release, an appropriate approach
Quality control is essential in all pharmaceutical is to conduct quality control tests on a single sample
production and formulation processes. The use of quality generator from each available supplier. In contrast, the
control processes guarantees that radiopharmaceutical remaining radiopharmaceuticals can be released based
formulations and preparations meet the requirements of on the outcomes of parametric tests. On the other hand,
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the pharmacopoeia for physicochemical and biological in the case of apyrogenicity of radiopharmaceuticals
tests to verify the effectiveness and safety of medicines. created using short-lived radioisotopes, endotoxin testing
It should be noted that biological tests are essential to after product release is permissible. Like all other drugs,
determine the material’s sterility and apyrogenicity. At the radiopharmaceuticals are governed by stringent endotoxin

Volume 2 Issue 3 (2024) 10 doi: 10.36922/arnm.3619