Traditional isolator design. Note the restricted reach of the operator.
Isolators are sealed boxes. Access is by glove port. There are no doors to give access directly to the interior. Airlock arrangements exist to get materials and components used during operations into them.
So the inside provides an environment where products can be made without the potential contamination from people and the external environment. Usually the exterior environment does not have to be kept at such a high standard compared to situations where the there is no enclosure.
However the gloves are a weakpoint in the containment since they can leak. The reach via a glove into the interior of the isolator is severely restricted. This makes isolators difficult to use and really restricts the dimensions and their layout.
Air In or Air Out?
In pharmaceutical manufacturing they are usually used for making sterile products. To ensure that the interior is kept clean they are usually kept at a positive pressure. Almost invariably they are sterilised using VHP. [Vapour Phase Hydrogen Peroxide]
They can also be used as a containment device when handling potent or toxic materials. However in this situation it would be logical to keep teh isolator at negative pressure. Thus any leakage or failure of the ‘box’ means that the product inside does not leak out but this neagtive pressure means that the product is at risk of could be contaminated by the external environment.
So where the product must be kept clean and it is also potent and should be kept contained there is a conflict as to whether the interior is kept at a positive or negative pressure. This is a fundamental conflict that cannot be solved with single skin isolators with glove ports.
Double wall isolators & Robotics
For the European Space Agency STC worked with SEA to develop an isolator that allowed separation of the interior and external environments and allowed for any leakage. The isolators were designed to house Martian samples (bought back from the mars lander expedition). These samples had to be kept separate from the earth’s environment first so there could be no potential for any Martian organism escaping to the earths ecology, but at the same time the the Martian samples have to be kept away from any earth organisms that could spoil the scientific work [examination of the Mars samples for signs of life..].
In principle the isolator is a sealed double wall box with internal robotics to perform the internal manipulations. The absence of gloves removes a major weakness and potential leakage path. The space between the double skins is filled with clean air and kept at pressure. So any leakage in or out allow the escape of clean air and the interior and exterior environments are kept separate.
In a more practical development it was realised that the e wall could be reduced to a single skin and the double wall was only needed where the wall materials are jointed, say where glass joins stainless steel.
AqVida, a German start up specialising in oncology products, in their new facility have developed a production facility that uses isolators with the handling inside done with robotics, reducing the need for glove ports.
Summary Pro and Con
- Isolators are great for protecting teh product from contamination since people are on the outside of an enclosure and the process on the inside.
- Sanitisation using VHP is very simple and reproducible.
- Surrounding environments can be of lesser quality which reduces the complexity of the layouts, energy use and overall space requirements
- It is difficult to adjust the equipment on the inside since access is difficult.
- Since the walls are rigid and the reach of a person through a glove port the dimensions and layout is very limited
- They are not easily adapted to meet unforeseen or future needs.