Pharmaceutical Manufacturing Handbook: Production and

MANUFACTURING ASPECTS 69
stations supplied with unidirectional airfl ow (UDAF) and with a lower pressure
compared to the aseptic laboratory. The laboratory itself may then have positive
pressure in relation to the surrounding premises.
Waste management is an important aspect when planning a radiopharmaceutical
manufacturing site. The key factor is to reduce the amount of radioactive waste to
a minimum. There should be a system for dividing the waste according to physical
half - life and radiotoxicity, both for solid and liquid waste. As an example, waste
containing α emitters is normally kept separately, when possible. National legislation
will vary considerably and infl uence the requirement that must be set for handling
of radioactive waste material.
1.3.3.2 Design of Production Processes
The design of a radiopharmaceutical production process depends very much upon
the kind of radiopharmaceutical to be made. Although most radiopharmaceuticals
are intended for parenteral use, also oral radiopharmaceuticals in different forms
are widely used. One must emphasize different factors when planning for production
of parenteral radiopharmaceuticals compared to oral radiopharmaceuticals.
Still, a common factor is the involvement of radioactive materials, and the radiation
protection of the personnel must always be an integral part of the design.
The production of a radiopharmaceutical will normally take place within a contained
box unit, consisting of either plastic walls or a combination of plastic and
stainless steel. The latter is more optimal for clean - room work. The box units may
be shielded by lead, either as large lead panels or as lead brick walls (see Figure 1 ).
Depending on the kind of radionuclides used and the amount of radioactivity
handled in the box, the walls are typically 5 – 15 cm in thickness. Shielded production
units like these are often called “ hotcells. ”
When the box is used for productions of radiopharmaceuticals incorporating α -
or β - emitting radionuclides, closed box units without any lead coating may be suffi -
cient. When handling radionuclides with mixed emitting properties, a possibility is
to concentrate the shielding to critical parts of the process. This can be done by use
of local shielding inside the production unit. However, for aseptic production, one
must keep in mind a potential disturbance of the airfl ow inside the box.
FIGURE 1 Shielding of box units (hot cells) with lead bricks. ( Photo courtesy of Institute
for Energy Technology .)