Calculating acceptability thresholds for cross-contamination — or for cleaning agents — is not rocket science. In practice, it simply comes down to applying the right mathematical formula based on the context.
Even though these formulas sometimes have their limitations, several parameters can be adjusted to arrive at a more "comfortable" criterion, meaning a higher one — while still remaining consistent with real-world conditions.
Before trying to inflate the criterion value, it is worth taking a step back. A good criterion is above all an achievable one. For example, if a limit has been set at 5 µg/cm² but that value is too low to be measured reliably or simply reached under real conditions, then yes, it may well be worth aiming for 7 µg/cm².
Concrete example using the HBEL-based calculation formula
- ARL = Acceptance Residue Limit
- PDE = Permitted Daily Exposure of product A
- MBS = Minimum Batch Size of product B
- LDD = Largest Daily Dose of product B
- Surface = shared surface area between products A and B
Here, the PDE and LDD values are product-specific: they cannot really be changed. On the other hand, the minimum batch size (MBS) and the shared surface area depend directly on the operational configuration of production activities. And that is precisely where action can be taken.
Two simple levers to boost your ARL
1. Increase the minimum batch size (MBS)
Not always straightforward, as it can disrupt your operational and economic constraints. But even a small upward adjustment can make a significant difference to the final criterion.
2. Optimize the shared equipment train surface area
This is often the simplest lever to activate. But first it is important to be clear on what "shared surface area" actually means.
Shared surface area: think smarter
The shared surface area is that of the equipment used for both product A and product B. In the early stages of determining the acceptance criterion, the total equipment surface area is generally taken into account. But does the total equipment surface area actually come into contact with the product? Not always.
Take an example: vessel domes. They are not in direct contact with the product. They can therefore be excluded from the surface area calculation. And just like that, 5% of surface area is gained.
It is possible to go even further: calculate the product-contact surface area based on the actual volume in the vessel. Everything above the liquid level then becomes an indirect contact zone. And that can make a real difference.
This does not mean that these surfaces should not be cleaned or validated! They still form part of cleaning validation. But for the purpose of calculating the acceptance criterion, the focus is on the shared equipment train surface area that is in direct contact with the products.
And in practice, how do you do this simply?
Hally-pharma integrates all the features needed to streamline the optimization of the shared equipment train surface area. It makes it possible to precisely model direct and indirect contact zones, document these choices, and automate acceptance criteria calculations based on your configurations. In short: everything needed to save time, secure your data and calculations, without resorting to complex and ill-adapted Excel files.
Conclusion
Instead of accepting an overly strict criterion, it is often possible to optimize it intelligently, without compromising on safety. A good criterion is a realistic one, consistent with your environment, and demonstrably so. And sometimes, it simply takes a closer look at how you use your equipment to find meaningful room for improvement.