All production phases where the possibility of contact between sterilized material and classified areas with degree 100,000
. Various sterilized material protected by wrappings is transferred to the autoclave. Because the area of the isolators is
classified degree 100,000 the wrapping may potentially be contaminated. Biodecontamination of the surface of the wrappings
inside the isolators necessitates that all material inside the isolators and all surfaces are appropriated. The sterilized
stoppers are transferred by the isolator to the loading hopper made of stainless steel endowed with a a/ valve that protects
the stoppers and in general the content of the hopper from the area with degree 100,000 and allows the stoppering phase in
the capping section of the filling line.
Management of environmental impact
When manufacturing high-potency drugs, managing the environmental impact of the process (i.e., refluent, industrial waste,
liquids, gas, and air) is important. Critical points in managing environmental impact are:
- Collecting and treating the water used to wash the components that come in contact with the product, and the external surfaces
of the final containers (i.e., vials) that may be potentially contaminated by the product and the freeze-dryer
- Treating circulating air in rooms and chambers. potentially contaminated (isolators).
The principal precautions that should be made to manage these risks are outlined below.
Collecting and treating the used water.
Water from washing processes that may be polluted are channeled and collected in a single system. The waters, gathered in
a storage tank, are submitted to a concentration process through distillation (see Figure 2). The distilled water has to be
tested and validated by high-performance liquid chromatography for the absence of active principles. The water is sent to
the sewer system while the concentrate is subject to the elimination of special waste. The concentration of refluent can be
substituted or supported with a chemical demolition process of the active principle through the use of oxidizing or denaturizing
Figure 2: The concentration of a refluent—scheme of the system. (ALL FIGURES AND IMAGES ARE COURTESY OF THE AUTHOR.)
Treating circulating air.
Depending on the phase of the manufacturing process, the surroundings of isolators may be in depression (i.e., when the
drug is a powder, but not yet sterile, and is highly dangerous because of its aerosol dispersion) or in overpressure (i.e.,
when the aseptic processing becomes the most critical element).
The air that is poured into the isolators of degree 100 is subject to absolute filtering. The air taken by isolators is partly
expelled in the environment and partly recycled with an input of fresh air from the ambient environment. The amount of air
subject to recirculation is treated by filtration using high-efficiency particulate air (HEPA) filters, HEPA filter efficiency
classification H13 (i.e., recovery), and afterward by a H13 filter (expulsion). In these isolators, the product can be present
only in liquid form and only because of accidental reversal or vials that are not well closed. Therefore, the aerosol contamination
is near to zero.
In case of isolator compounding, the exhaust air is treated by a H14 filter (i.e., HEPA filter efficiency classification H14).
The retaken one is a totally recycled previous filtration by a H14 filter with the use of a further intermediate H13 filter.