New Annex 1 Requirements for Tunnel Qualification
MTL Projects Ltd have just completed another Tunnel Qualification in compliance with the new Annex 1 requirements to consider and challenge the air flow and differential pressure impacts on depyrogenation efficacy.
The findings from the studies and qualifications performed to date are very interesting and have demonstrated that the impact of these CPP's on depyrogenation efficacy can be significant.
With client permission we will be writing up the data into an article at some stage but for now, the highlights:-
Why Haven't we challenged this previously?
This new Annex 1 requirement is typically something that hasn't been challenged as part of most Tunnel commissioning / Qualification studies, however it is clearly a CPP that should have been considered and we now have evidence that it can make a difference in some instances. Annex 15 has been clear for the last 8 years that we need two understand CPP's their limits and challenge worst case, generally our understanding and control of CPP's has improved over that time with examples such as VHP systems where the control of CPP's has significantly improved our cycle performance, reliability and qualification. However Tunnel; air flow and differential pressure has not typically been included as a CPP for challenge in Tunnel qualification.
Some early problems:-
The starting point is to understand the CPP's related to air flow and differential pressures throughout the Tunnel, this has not always been straightforward.
We published a simple guidance paper earlier in the year to explain the approach we were taking to this new requirement (link here) this was useful but oversimplified the issue as there are many factors impacting these variables, not least that the differential pressures can vary throughout a run based upon gate positions as the glassware moves through the Tunnel.
The Impact of Tunnel Design and Control
Tunnel design and pressure/air flow control methodology has a huge impact on consistency of depyrogenation efficacy. Some general findings:-
Pressure Cascade Tunnels tend to be more impacted by changes.
Tunnels that have a gradual pressure cascade down the Tunnel from Grade A to Tunnel inlet/glassware washer are generally impacted more. Such a pressure cascade design results in the cooling zone being at a higher pressure than the depyrogenation zone and variability in control paramaters therefore have a greater impact with cold cooling zone air entering depyrogenation zone under worst case conditions and reducing depyrogenation efficacy. Worst case example; a Tunnel delivering a minimum Fd of 40 reliably delivered a minimum Fd of 32 when challenged at worst case conditions of air flow velocity and differential pressures. Although endotoxin challenges still delivered a greater than 3 log reduction, this is a 20% reduction in measured efficacy and demonstrates the impact these variables can have.
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'Sink" airlock Tunnels tend to be less impacted by changes.
Tunnels designed with a 'sink' air lock in the cooling zone, so that the cooling zone is a lower pressure than Grade A and also a lower pressure than the depyrogenation zone, tend to perform better. Challenging the limits of air flow and differential pressures has demonstrated worst case conditions where the depyrogenation zones still a higher pressure than.
Tunnels that do not directly control DP between depyrogenation and Cooling Zones are difficult to challenge reliably.
Some Tunnels measure and control the DP and Depyrogenation Zone either to each other or a fixed reference (e.g. background Grade C). This design appears to be more controllable, repeatable and easier to challenge. In some cases the cooling zone is a controlled DP to the Grade A Filling and the Depyrogenation zone is controlled DP to infer or background Grade C. When additional DP monitoring has been added as part of the investigation, this has shown a very inconsistent DP between the Depyrogenation Zone and Cooling Zone, particularly for RABS Grade A.
Tunnels with excellent control and monitoring.
Some very well engineered Tunnels have such good control and monitoring of velocities and differential pressures that an argument can be made that these CPP's are under constant control and monitoring such that the CPP's do not vary. Based on detailed analysis of :-
some Tunnels can argue that the CPP's are in control and do not vary. This bold statement must be backed up with excellent analysis data as described above and qualified instrumentation and critical alarms set appropriately.
For example on one site the data was reliably demonstrating control, the pressure cascade with positive from the depyrogenation zone (e.g. sink cooling zone) and the alarms on differential pressure were set +/- 2 Pa from set point. Based upon this analysis no further physical challenge of worst case limits was required
Conclusions
cGMP for the commissioning, cycle development and qualification of Depyrogenation Tunnels will develop, driven by this new Annex 1 requirement. However, studies and qualification work performed by our engineers this year have concluded that this is a worthwhile development. The CPP's of air flow and differential pressure can have a significant impact on depyrogenation efficacy.
Thanks for sharing Nick.