We recently received a question about placing temperature and humidity probes for monitoring stability chambers, based on where the hot and cold spots are found.
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I'm a Senior Validation Engineer at a global medical company specializing in eye care products. I learn a lot from Vaisala's webinars, so thank you!
I have a question about stability chambers…We have many stability chambers that have both temperature and RH specs, typically ±2° C and ±5%RH. We do empty-chamber mapping as part of OQ and full-load mapping as part of PQ. My question is this: If the highest temperature, highest RH, lowest temperature and lowest RH are in four different places, do we then need to monitor with four probes?
Then (even worse) what if some of these locations are different under full vs empty load? Do we then need even more probes for monitoring? If yes, we could conceivably end up with eight probes for monitoring. A couple of our chambers have only two monitoring probes in place, so our concern is that they don't account for the highest and lowest parameters. Any help you can provide is appreciated!
I'm very pleased to hear you have found our webinars useful! We hope you make use of our archived webinars.
Your question is a common one. Unfortunately, the scenario you have described is not well addressed in guidance documents. My hope and expectation is that we will start to see more formal answers for this question.
Before I answer, I want to acknowledge that the ways we typically analyze our mapping data creates a monitoring perspective that I consider to be an artifact of mapping, and not necessarily representative of our goals in monitoring.
To ensure I'm not being vague… let me try to explain further. We analyze our mapping data as efficiently as possible, finding the maximum and minimum values during the mapping, and noting where they occurred. This focus on the maximum and minimum values comes with the unspoken understanding that every other measurement at every other location would therefore be between these two identified max/min values. Every measurement in the mapping is still important, as each one serves to demonstrate that our chamber has the ability to maintain the required uniformity. However, we focus on the maximum and the minimum, the legendary hot and cold spots, mainly as an artifact of our analysis.
The question that I want to ask is: Are the hot spot and the cold spots actually important? Or is our focus on them only the result of the way we analyze mapping data with statistics? Why is it that we are effectively ignoring the other 99.99% of the data that says the equipment is performing as expected?
Of the hot and cold spots are important, but that's only if they are out of specification, or close to the limits. But are they important when they are in spec? I simply think that our analysis technique makes us focus on them, giving them greater weight than they may deserve.
To further explore this idea, I searched through the available guidance. I found no guidance that stipulates anything like this: "After mapping, place a monitoring probe at the hot spot and another at the cold spot." What the majority of guidance says is something linguistically similar, but categorically different.
Guidance tends to say something more like this: "After mapping, place monitoring probes in a way that takes into account the results of your mapping, including any hot and cold spots."
The words used barely differ, but the difference is big.
Further, looking at 20 years of pharmaceutical experience, almost every controlled environment I have seen has the monitoring probe in a location that makes logistical sense – protected enough so the probe isn't damaged, and on a wall or column to ensure it can be mounted to prevent movement. In very few instances I have seen monitoring probes placed at the actual hot or cold spot, which is often within the storage area to be used. Placing a monitoring sensor in the working spaces causes some problems: the probe either gets damaged, moved, or hidden in product which dampens its ability to respond to changes in air temperature.
Most people compromise by choosing a sensible monitoring location on the wall of the chamber, but calculate offsets to virtually monitor the hot and cold spot. This sounds like a sound approach on the surface, but this approach presents challenges. You end up with the logistical nightmare of managing a multitude of specialized offset alarms, and the math to determine the measurement process uncertainty is beyond the training of most non-metrologists.
So, we have an interesting conundrum. Guidance appears to tell us the hot and cold spots are important. In practice, almost no one monitors their exact hot and cold spots. And those that attempt to do so run into serious logistical issues.
My approach has always tended to be pragmatic. Map the chamber. If it passes the mapping, (empty, loaded etc.) then it is validated. The chamber will continue to be validated so long as the set-point is maintained, so long as PMs are regularly performed, so long as annual calibrations are performed. Then I make sure the probe, usually a single probe (unless the space exceeds 20 cubic meters) is in a safe, sensible location, representative of product storage, out of direct airflow from the heating/cooling system, and where the impact of door openings can be sensed, but without causing nuisance alarms.
Because the chamber is validated, I can rely on my monitoring sensor to tell me when something is catastrophically wrong – door left open, compressor failed, power lost, etc. Because I validated the chamber I am not worried that one part of it will be out-of-spec by 0.5C for 15 minutes. If my chamber barely passed validation and I am so worried that it will not maintain temperature uniformity that I feel the need to monitor the hot/cold spots with multiple probes, then I probably need a new chamber.
In some sense, a multitude of monitoring probes starts to look like trying to test quality into the product, which is known to be an inefficient way to ensure quality. The more practical approach is to design a process that inherently ensures quality. In this case, it might simply be tighter limits during validation, or purchasing a higher performance chamber that can maintain a tighter temperature and %RH uniformity. If you need a multitude of probes, it might be a sign that you need to improve the quality inherent in your process.
If your product is particularly expensive, or it is particularly sensitive to small temperature changes, that shifts the risk equation and you might consider an additional probe, or monitoring product temperature instead of air temperature, as a way to gain additional confidence in your environment. But for a "normal" product, especially a product in final packaging, more than one probe may be unnecessary.
Thank you again for asking; your question is both timely and relevant because the need for adequate mapping and monitoring has increased due to the expansion Good Distribution Practices.
Sr. Regulatory Compliance Expert / Validation Program ManagerPaul Daniel