Pharmaceutical Manufacturing Handbook: Production and

68 RADIOPHARMACEUTICAL MANUFACTURING
1.3.3
MANUFACTURING ASPECTS
1.3.3.1 Design of Manufacturing Sites
The manufacturing of radiopharmaceuticals is potentially hazardous. Both small -
and large - scale production must take place on premises designed, constructed, and
maintained to suit the operations to be carried out. Radiation protection regulations
stipulate that radionuclides must only be used in specially designed and approved
“ radioisotope laboratories. ” National regulations with regard to the design and classifi
cation of radioisotope laboratories must be fulfi lled. Such laboratories are normally
classifi ed according to the amount of the various radionuclides to be handled
at any time and the radiotoxicity grading given to each radionuclide. When planning
the layout of the laboratory, it is recommended to allocate separate working areas
or contained units for the various procedures to avoid possible cross - contamination
of radionuclides [4, 5] . Premises must be designed with two important aspects in
mind:
The product should not be contaminated by the operator.
The operator and the environment should be protected from contamination by
the radioactive product.
This is the basic principle of good radiopharmaceutical practice (GRPP).
One of the most important factors in planning a radioisotope laboratory is the
design of the ventilation system. Laboratories with medium and high grading must
be designed with the purpose of protecting the personnel from inhaling radioactive
gases or particles. The system should be designed to provide lower pressure at the
actual working area compared to the surrounding environment. Furthermore, the
system should have an appropriate number of air changes per hour and the replacement
air should be fi ltered. Air extracted from the area where radioactive products
are handled, though, should not be recirculated. Exhaust air to the environment
should be monitored for radioactivity, and it may be necessary to install active
charcoal fi lters to absorb radioactive gases and small particles [4] .
Aseptic production of radiopharmaceuticals, that is, when the products cannot
be terminally sterilized, will increase the requirements for the design and construction
of the premises. Contained workstations and clean - room technology will be
applied to a much higher degree. The general requirements for the design of such
premises are the same as for nonradioactive pharmaceuticals, including entry of staff
and the introduction of materials through air locks. The main difference is found in
the planning and design of the ventilation system. Laboratories for aseptic work
normally have a positive pressure relative to the surrounding areas. On the other
hand, in laboratories for work with radioactivity, it is good practice to have a negative
pressure to avoid the spread of radioactive material. In order to meet both
pharmaceutical and radiation protection requirements, it is necessary to balance
carefully the air pressures in the clean rooms, the air locks, and the surrounding
areas. From a pharmaceutical point of view a negative pressure in the area designated
for aseptic work can only be accepted in special cases. There are various ways
to meet the required balance between these apparently contradictory principles.
A frequently chosen solution is to use sealed production units or contained work-