Part 2 - Q&A from our controlled temperature chamber validation webinar

In this video blog, Vaisala's Paul Daniel and Nathan Roman of Genesis AEC continue to answer questions on how to validate temperature-controlled chambers.  To learn about Vaisala solutions for monitoring, mapping and measuring GxP environments, please contact us. To learn about services offered by Genesis AEC, visit their website. 

Q&A video blog #1 

Q&A video blog #3

Question: What are the recommended intervals for remapping freezers/warehouses?

Paul: Per the new revision of the ISPE Controlled Temperature Chamber Good Practice Guide,  this is something that you determine yourself based on the performance, history, and criticality of the chamber. The ISPE's guide now allows you to not remap in some situations... Personally, I have always defaulted to every three years. However, if the chamber is used for expensive materials or critical processes, then consider remapping more often. One example here is a stability chamber; if the chamber is used for inexpensive or low-risk items, then I would re-map every 5 years. An example here would be a refrigerator holding lab reagents. For a warehouse, if you do need to re-map, I would do that in both summer and winter seasons.

Question: Do you find that companies complete annual temperature and relative humidity mapping studies in chambers to verify the performance following annual maintenance/calibration of the equipment? And, are the these completed with a standard 24-hour study with the in-situ load?

Nathan: Good question. Maintenance and calibration activities are typically on a 6- or 12-month interval, but mapping is not typically performed at the same frequency. However, I have seen yearly temperature mapping done in a GLP laboratory, but that was all based on their level of risk, and they did couple the validation activity with the calibration interval. Twenty-four-hour mapping was completed and the chambers were mapped in-situ. Unless of course the maintenance protocol required a defrost, in which the unit would need to be emptied. Typical industry re-mapping frequency is 3-5 years for CTC’s. However, there are no hard fast regulations applicable for this. New guidance suggests that controlled temperature chambers should be periodically assessed to determine the need for revalidation or remapping.

The control systems, equipment, monitoring, and procedures for the units should be a part of the periodic review to ensure the unit still operates in a qualified manner. Also, the frequency of the requalification or remapping is suggested now to be determined on the results of a risk assessment or when significant modifications are made to the unit. As for the item to consider during risk assessment: what is your level of risk of failure to maintain uniform temperature? The storage of high value/critical products or temp sensitive products may warrant more frequent requalification. Industry practice varies but should always be performed in alignment with your risk assessment and rationale for your determined frequency documented.

Question: Is temperature mapping always part of OQ for a storage warehouse for pharmaceutical products? For example, for the storage of medications that require a "cool dry place". If yes, then how do you handle the fact that mapping should be done in summer and in winter?

Paul: Yes, temperature mapping should be part of the Operational Qualification of any storage location for pharmaceuticals. You will need to find a numerical definition of “cool dry place”. U.S. Pharmacopeia (USP) <659> "Packaging and Storage Requirements" defines “Cool” as: Any temperature between 8° and 15° (46° and 59 °F). European Pharmacopoeia gives the same range for "Cold or Cool." The USP defines dry as not exceeding 40%RH at 20C, or equivalent water vapor pressure at other temperatures. The need to store something at any defined temperature, “Cool and dry” or otherwise, doesn’t change the fact that you must map in winter and summer in a warehouse. In the summer, you will be challenging your cooling system, and in the winter, you will be challenging your heating system. At least in the northern hemisphere. The fact that two different systems are in use is WHY we need to map at both times of the year.

Question: I am a validation consultant and my last client asked me to use the ISO 14644-1 guide which states the particle count sampling locations and use it as the sensor location for temperature and humidity mapping of a bulk product storage area. Is that justified? Is it a new industry standard?

Paul: As far as I know, there is no overlap or relationship between best practice for particle monitoring locations and best practice temperature mapping locations. There certainly is no rule that says you can’t place mapping sensors at these particle locations as well as the locations you would normally map at. However, if the customer is asking you to map ONLY at the particle measuring locations, and nowhere else, I would not do it. Regardless of the best locations for particle monitoring, you must place your temperature/humidity mapping sensors in locations that represent the entire area that needs to be temperature and humidity controlled.

Nathan: There is no new industry standard that specifies this scenario. Please refer to the ISPE Good Practice Guide: Cold Chain Management or the ISPE Good Practice Guide on Controlled Temperature Chambers, Commissioning and Qualification, Mapping and Monitoring because these guides provide describe practices for placing Temperature & RH sensors. You’ll need to place sensors in a uniform pattern in all three dimensions of the space. You’ll need to also consider the potential storage locations, distance between probes, vulnerable areas that may be in direct path of air or a heat source and add additional sensors where you suspect cool or warm areas exist, as well as near the control sensors and monitoring sensors.