What operating pressure to take during aseptic processing

Tony Rhodes, sales manager at Telstar's Technology Centre for Barrier Isolation System discusses what operating pressure manufacturers should choose during the aseptic processing of potent materials in isolators.

This is a question that is posed regularly and divides opinion on which approach is the correct one.

Individually there is no question what route should be taken and most would agree that an isolator designed purely to provide a grade A environment for an aseptic filling or manufacturing process must be designed as a positive pressure system, to maximise the protection of the product ‘within’ from external contaminants. From a containment stand point an isolator solely designed to protect the operator from hazardous API’s must be designed as a negative pressure system.

Increasingly however we are being faced with a combination of both scenarios, for example an aseptic filling process of high potent product and therefore we have a dilemma; do we opt for negative pressure to protect the operator first and run the risk of introducing particulate into a grade A environment or do we opt for a positive pressure system and run the risk of exposing the operator to potentially harmful particles.

Isolator Enclosures;- “Enclosures that are sealed to some standard of leak tightness, that contain within them a qualified controlled environment, at variance with the surrounding conditions.”

By definition an isolator enclosure leaks; how much it leaks is dependent upon a number of factors, not least the nature of the design, workmanship and build quality. So whether an isolator manufacturer would choose to provide a negative or positive pressure isolator in ‘our combined aseptic / potent scenario’ may well depend on their current designs as well as their past experience.

For many isolator manufacturers the standard approach is to provide a positive pressure isolator to protect the product but at the same time great emphasis should be placed on the design and build of the inherently weak points to ensure the operator is protected in equal measure, both during normal operation and in case of any unlikely breach condition.

In this context it is assumed all isolator enclosures would be designed and tested to a level of leak tightness to international standards ISO 14644-7 / ISO 10648-2 to either class 2 or class 3, dependent upon their size and geometry. In which case it is important that the weak points are designed correctly to ensure the leakage rate is maintained at all times, therefore many hours of research and development needs to expended on all these points to create reliable designs that produce positive results time and time again.

Coupled with the mechanical design should be intelligent control systems to regularly monitor conditions ensuring the system and its components are maintained to the highest standards. And should the unthinkable happen and there were a breach, for example a glove tear or seal burst, the control system would enter into an alarm condition, whereby the isolator operating system would revert to negative pressure and immediately induce inflow through the breach.

The response time from initial alarm to full negative breach condition, limits the potential exposure to the operator to an absolute minimal time period; typically 5 to 10 seconds is common dependent upon the size of the isolator enclosure, which could be considered an extremely low risk especially when extrapolated over an 8 hour long term or even a 15 minute short term exposure period.

Of course this is all theory and only extensive testing in controlled environments would either prove or disprove whether there really is a risk to the operator given this scenario. As already mentioned what approach a manufacturer adopts is based on their own experience, which is also true of Telstar’s approach to provide a positive pressure isolator for an aseptic / potent application based on its long history of providing aseptic and containment Isolators and based on its programme of R&D, but to back up this stance the company embarked on in-house trials to start testing this theory out.

In 2017/18 the company launched a programme of testing using a third party environmental monitoring company to monitor operator exposure whilst dispensing a placebo material in a single chamber 3 glove Isolator. The chosen isolator design was taken from its standard Pura range which is capable of being run in both positive and negative modes and was tested at different operating pressures. The isolator was first tested to class 3 leak tightness ISO 10648-2 as opposed to class 2, to obtain a worst case scenario and be more reflective of a larger filling line test level.

Test Results 

All the results given above are tasked based and are not time weighted averages. Excessive spillage was noted in some runs particularly on run 1 of the negative mode, however in real situations the same situation could occur, therefore it was felt that although the test was simplistic it provided a snapshot of what could arise in practice.

Conclusion

In this case the negative pressure mode returned the highest reading, however the mean exposure was very close, but slightly better in the case of the positive pressure mode. Given some runs had excessive spillage (mainly on run 1 negative) as stated above that may account for why the positive mode performed better in this trial, however it is acknowledged that the opposite effect could also occur.

Of course this is only the start of this process and more test data is needed, but already it can be concluded from these results that a well-designed, well-sealed enclosure will perform equally well from an operator protection perspective whether operating in a positive or negative regime.