In pharmaceuticals it is increasingly important to ensure adequate mapping and monitoring, due to the expansion of the Code of Good Wholesaling Practice for Medicines.
If the highest temperature, highest RH (relative humidity), lowest temperature and lowest RH are in four different places, do we then need to monitor with four probes? And what if some of these locations are different under full vs empty load?
Do we then need even more probes for monitoring?
Most facilities measure the minimum and maximum values and note where they occur. This focus on the maximum and minimum values comes with the unspoken understanding that every other measurement at every other location would be between these two identified max/min values. Every measurement in the mapping is still important, as each one serves to demonstrate that a chamber has the ability to maintain the required uniformity. However,focus was placed on the maximum and the minimum, the legendary hot and cold spots, mainly as an artifact of analysis.
Are the hot spot and the cold spots actually important? Or is the focus on them only the result of the way to analyze mapping data with statistics? Why is it that the other 99.99% of the data that says the equipment is performing as expected are effectively ignored?
The hot and cold spots are of course important, but that’s only if they are out of specification, or close to the limits. But are they important when they are in specification? The analysis technique gives the focus on them, giving them greater weight than they may deserve.
To further explore this idea, available guidance shows no stipulation 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 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. Only in very few instances, where some monitoring probes are 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. One may 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, there is 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.
One pragmatic approach is: 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.
Now that the chamber is validated, one can rely on my monitoring sensor to tell when something is catastrophically wrong – door left open, compressor failed, power lost, etc. Validating the chamber ensures that not one part of it will be out-of-spec by 0.5C for 15 minutes. If the chamber barely passed validation and that it may not maintain temperature uniformity that is needed to monitor the hot/cold spots with multiple probes, then a new chamber is needed.
If the product is particularly expensive, or it is particularly sensitive to small temperature changes, that shifts the risk equation and an additional probe may be considered, or monitoring product temperature instead of air temperature, as a way to gain additional confidence in the environment. But for a “normal” product, especially a product in final packaging, more than one probe may be unnecessary.
Please contact us to find out more about Continuous Temperature and Humidity Monitoring Systems.
(Article courtesy of Vaisala)
