1. INTRODUCTION
In order to handle radioactivity, special facilities are required to shield the radiation emitted and
to prevent contamination of the environment by the radioactive materials released during handling and
processing. In production laboratories the processed activities are high and therefore the requirements
for shielded facilities with well controlled ventilation and remote handling devices are greater. Several
versions of shielded hot cells and remote handling devices have been developed and used over the
years in major radioisotope production centres. The evolution of different designs has reflected the
growing emphasis on optimization of protection and safety. As radioisotopes are increasingly being
used in various fields, the demand for larger quantities has risen and more complex handling facilities
are in need in the isotope production laboratories.
Some of the recent developments in the use of radioisotopes in medical field have also
significantly impacted on the evolution of handling facilities. Application of pharmaceutical good
manufacturing practice (GMP) requirements for air quality and processing conditions in the handling
facilities of radioactive pharmaceuticals has led to significant improvements in the construction of
isolator-like hot cells and clean rooms with HEPA filtered ventilation and air conditioning (HVAC)
systems. Clean grade A (Class 100) air quality isolator-like hot cells compliant with GMP
requirements for handling radiopharmaceuticals are now available commercially. Nevertheless, the
application of clean room requirements in radioisotope laboratories in general and hot cells in
particular is technically not an easy task. The technical problems have not been completely overcome
and need on-going efforts.
Furthermore, GMP requirements exclusively designed to conditions for producing radioactive
pharmaceuticals should be elaborated and distributed to facilitate the design, construction and
operation of such facilities. GMP guidelines are guidelines for radioactive pharmaceuticals, by
describing their specific character and refer to the production of sterile pharmaceutical products.
Due to the beneficial nuclear and chemical character of
99m
Tc radionuclide as well as its easy
availability from the
99
Mo-
99m
Tc generator, it is the ‘workhorse’ of the nuclear medicine and is widely
used in nuclear medicine centres for diagnostic purposes. The manufacture of
99
Mo-
99m
Tc generators
ranges from small scale batch techniques through semi-automatic dispensing systems to fully
automatic production lines. Their manufacture and quality control are also made under aseptic
conditions to comply with GMP requirements.
The last decade has seen an increased use of positron emission tomography (PET) in regular
diagnostic imaging and PET radiopharmaceuticals, (particularly
18
F-FDG in the hospitals). The 511
KeV, high-energy radiation needs thicker shielding and more sophisticated handling devices. In view
of the short half-lives, the emphasis is also increasingly on the process and handling as per GMP than
final QC. The clean area concept is more often applied to isolator-like hot cells for PET
radiopharmaceuticals. The need for rapid, remote and reliable synthesis of PET radiopharmaceuticals
has also been responsible for the introduction of microprocessor controlled synthesis modules. This
experience has also led to the development of similar microprocessor controlled synthesis systems for
other radioactive pharmaceuticals.
Miniature size radioactive sealed sources of
192
Ir,
125
I and
103
Pd have found widespread
applications in brachytherapy of cancer. The production of such sealed sources together with that of
the conventional sealed sources (
192
Ir and
60
Co) also require remote precision welding using laser or
arc and microprocessor controlled positioning devices.
Several radioisotope production centres have developed innovative devices and systems for
remote handling of various important operations in hot cells such as target handling, capping and
decapping, dispensing and autoclaving. Often these developments have resulted in significant
reduction of radiation dose and increased the GMP compliance.
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