By adopting this approach, hydrogen peroxide, in its vapour phase, would be recognized as a sterilizing agent, which could not only decontaminate the internal enclosure of the isolator but also sterilize the materials which would be enclosed.

Notwithstanding these evident advantages, regulatory authorities have not supported the use of VPHP sterilization process yet. Their concerns are mainly founded on the “fragility” of the process itself, taking into account the difficulty to achieve VPHP penetration in all parts of items to be sterilized and still the presence of high degree of risk in managing a VPHP sterilization procedure for critical items.

In the last few years, the limitations in using VPHP as a sterilizing agent have been overcome with the development of sterilizers where suitable operating conditions are applied for a batch sterilization process, at low temperature.

The basic VPHP sterilization cycle consists of three fundamental stages: vacuum generation, H2O2 injection and aeration. The whole process takes approximately 2 hours, including aeration time (removal of H2O2). After the aeration is complete, the sterilized items are removed.

These different configurations allow to design a sterilization process which can be applied to either heat-resistant or heat-sensitive products and materials, before their introduction in an isolator, depending on the use of a standard steam sterilization, a dry heat sterilization or a low temperature VPHP sterilization process.

This configuration includes a double magnetic-driven door, allowing to load the items into the sterilizer and to unload the sterilized items directly into the isolator, by the presence of a tight connection between the two pieces of equipment.

The peculiarity of this configuration is its flexibility, as it can easily be adapted to specific process needs. In fact, the sterilizer can be one of the following options: steam sterilizer, air/steam sterilizer, dry heat sterilizer, VPHP sterilizer or a piece of equipment that combines washer/steam sterilizer or washer/VPHP sterilizer.

According the choice of the sterilizer, this configuration can be applied, for instance, to the following operations, which are requested for aseptic processing of various items:

• washing and steam sterilization of heat-resistant parts of the aseptic line, which are to be used in the isolator, where the filling process is carried out,
• de-pyrogenation of containers, which are to be used within the isolator,

• VPHP sterilization of heat-sensitive parts of the aseptic line, which are to be used for the filling process in the isolator.

It is, in particular, to be observed that the direct connection of a VPHP sterilizer with the isolator allows to apply a sterilization process to all items which can’t be reliably decontaminated and sterilized within the isolator, due to the uncertain penetration of VPHP when used at atmospheric pressure.

This configuration includes a double magnetic-driven door connecting the unloading side of the isolator with the sterilizer. This would allow to directly unload items from the isolator into a sterilizer, by the presence of a tight connection between the two pieces of equipment.

Even in this case, a flexibility of application of this configuration is maintained, taking into account that the sterilizer can be a steam sterilizer, an air/steam sterilizer or a VPHP sterilizer.

As an example, when the isolator is connected to a VPHP sterilizer, this solution allows the terminal sterilization of sealed packages containing products which are heat-resistant or heat-sensitive, after their aseptic processing inside the isolator.

This configuration includes a single or a double magnetic-driven door, connecting the sterilizer with an alternative loading/unloading side of the isolator.

This configuration has been conceived considering any need to move items from the isolator into a sterilizer and back into the isolator when the sterilization process is finished.

According to the aseptic process needs, the sterilizer can be, as in the previous configurations, a steam sterilizer, an air/steam sterilizer, a dry heat sterilizer, a VPHP sterilizer or a piece of equipment that combines washer/steam sterilizer or washer/VPHP sterilizer.

The particular application of this configuration is for moving ancillary items, which are used in processing (e.g. in a filling line installed inside the isolator) directly from the isolator chamber into a sterilizer, without the need of taking them out from the isolator in the clean-room. This direct connection allows to get back the items into the same isolator as soon as they have been sterilized.

The main advantage of this configuration stays in the reduced request of space in the clean-room, an optimization of process operations, always keeping low the risk of contamination, by using the direct connection between the sterilizer and the isolator through a magnetic- driven door.