Part 3 – Final Q&A on controlled temperature chamber validation

In this third and final video blog, Paul Daniel and Nathan Roman answer more questions, this time focusing on loaded chamber mapping with empty boxes, percentage of space in loaded chamber mapping, and power outage tests. 

You can find previous video blogs: 

• Part 1 Controlled Temperature Chamber Q&A
• Part 2 Controlled Temperature Chamber Q&A

Question: Is a loaded mapping test with empty boxes an accurate method of mapping?

Paul: I think this strategy provides the maximum challenge and is also a lot easier to do than filling the boxes with placebo products. But our goal is not to provide the maximum challenge, it is to provide an appropriate or reasonable challenge. And since there will likely never be a time that the chamber is filled with empty boxes, this may not be a representative test. I would go ahead and do this, being careful not to overload the unit, and see what happens. If the study fails, be prepared to repeat it with boxes that are full of product, as this is a much more likely real scenario, that will be easier to pass, though harder to perform.

Nathan: Loaded chamber testing is conducted to provide verification that the system performs per its intended use when operated under routine challenged conditions and that the unit meets the pre-approved criteria. For the loaded study I would use material that best represents the contents of what is expected to be stored. If using empty boxes represents the material of contents, then use this as a test load. If freezer cold packs best represents the stored material, then load the unit with a specified number of freezer cold packs. But whatever you choose, be sure to document your approach into your protocol, ideally beforehand.

Question: what percentage of the shelf space should be occupied for full load scenario in an incubator or refrigerator and what type of material should be used for loading?

Paul: The best source for full load limits is the chamber manufacturer. But you might not be able to get this information from them. We can infer some information from the ISPE CTC guide. The sensors at the sides and corner are not placed in the absolute corner, but rather at the edge of what is called the “working area”. In the French norm, which the ISPE placements are based on, this distance is defined as 10% of the unit’s dimensions. So, a CTC of exactly 1 cubic meter of volume, and a perfect square one meter on a side, would only have a “working area” of 80cm x 80cm x 80cm. If you do the math, that is about 51% of the total volume if we allow space on the sides for air flow. You may be able to get this information from the owner of the incubator/refrigerator – sometimes they will include load limits in their SOPs. And of course, depending on the type of unit, air flow might not matter at all. For Instance, an ultralow freezer relies on conduction, not convection (airflow) to keep a space cool, so you can usually pack these units fully. The challenge with these units is not to pack them so full that you can’t find what you are looking for. But for a rule of thumb, on a typical refrigerator or incubator, I would not go over 50% for a full load.

Question: What are acceptable acceptance criteria for power outage test?

Nathan: From my perspective, temperature mapping is a way to validate and document that a temperature-controlled space is suitable for its intended purpose. And so, it is my experience that power outage testing or power failure testing is performed to determine the time it takes for the temperature to exceed temperature specifications in case the power is lost. If power is lost, would you like to know how long the temperature in your CTC remains within limits? To provide this information, we must close the doors and switch off the power and temperature map. The purpose of this test is to find out how long the materials are safe inside the space once power fails. This study in the IOQ is typically for information only, so there is no real requirement to include it into your Mapping Qualification.

However, the test data can be used to evaluate the potential impact of temperature excursions occurring during routine use. It can also help you to write an SOP (Standard Operating Protocol) for the actions to be taken in case of a power failure. As for acceptable criteria, the equipment should power down successfully and when power is restored the equipment recovers from the power loss and returns within process range (required operating parameters). In addition, verify that the operating set point and alarm set points remain as programmed when power is restored to the system.

Paul: This is why I don’t like power outage tests, and I don’t consider them to be validation. Acceptance criteria need to come from somewhere. We can’t just make them up. And if you don’t have acceptance criteria, it isn’t validation. So where would we get this acceptance criteria? The vendor of the CTC isn’t going to give it to us. Usually, these studies just say to perform the test and see how long the temps stay in specification, and then this data is kept on file to evaluate future situations where the power is lost. There may be situations where a validation department has put in a policy that they want to see temps stay good for 15 minutes with the power off. That is really the only place I can think of where you will get acceptance criterion for a power failure test. That’s because these tests are about gathering information, not about meeting acceptance criteria. That’s why I don’t like calling them validation. But if you are going to do these tests The best time to do them is during a temperature mapping.