A Stability Chamber Problem

Stability programs are an essential part of life but represent a huge investment for any pharmaceutical company. We are completely dependent on our stability chambers to keep running year after year but in order to achieve this, it is important that we help them by providing regular performance monitoring and preventative maintenance programs. It is also important to learn from things that can go wrong but had not been anticipated and the following provides a real case example.

Testing and studies can be significantly impacted by various factors, but a common issue is inadequate preventative maintenance on the temperature and humidity chamber. Regular maintenance is crucial to avoid downtime and protect products and test results. – Jeremy Jackson, Service Manager, Parameter Generation & Control

This situation occurred in a reach-in chamber set up for accelerated study conditions (40℃/75%RH). The chamber contained a number of product studies and included a tablet product packaged in PVC/PVdC blisters that was undergoing a NDA registration study.

During one weekend, the chamber alarm was triggered which automatically signalled a Metrology Associate to attend urgently. The Associate found that the heating system had failed and the temperature had decreased to about 30℃. More seriously, the chamber was flooded with water and some of the blister packages of the tablet product were soaked and therefore invalid for this study.

The impacted chamber was evacuated. Those products that had not been impacted by the chamber flood were relocated to a different accelerated chamber and a Deviation Report (DR) was initiated.

It was clear that the root cause was due to break down of the chamber heater which was subsequently replaced and the chamber was requalified. But this then left us with the questions:

1. What was the cause of the chamber flood?
2. Why were some product samples damaged by flood water?

Relative humidities are very dependant on temperature as indicated in the Figure below:

The figure above demonstrates the relationship between temperature and mass of water that can be held by air over a temperature range of -20℃ to 50℃. The red curve indicates the mass of water required to saturate 1Kg of air (Dew Point or 100%RH) and the green curve represents the mass of water in 1Kg of air at 50%RH. The arrow on the right indicates the mass of water required to generate 75%RH at 40℃ in 1Kg of air (i.e. about 38g). If the heating system fails in a 40℃/75%RH chamber and the temperature decreases to 30℃, we get to a situation indicated by the arrow on the left which indicates that the approx. 38g per 1Kg of air is well above the Dew Point at 30℃ and we get a rainstorm inside the chamber.

Since stability chambers do carry that risk of flooding as just discussed, they are constructed with a drainage system on each of the shelves to avoid product damage. This was the case with this particular reach-in chamber so some further investigation was required to establish why we still encountered water damage to a number of product units. It turned out that this was due to mildew growth within the drainage system. The chamber condition of 40℃/75%RH provides a great environment for mildews and we found that this had created some blockages within the drainage system. The backed up water then led to the product damage that we encountered. Having now established a full root cause for this issue, we were able to set up an effective CAPA which was to enhance our chamber annual preventative maintenance (PM) program to include an action to conduct cleaning of the chamber drainage system to ensure that in the event of any flooding, the water would be effectively removed.

In some ways we were fortunate that this issue occurred in an accelerated stability chamber as samples are only held in this condition for 6 months. The real time storage condition for Zone IVb territories is 30℃/75%RH which would be susceptible to a very similar situation but samples are held in this condition for 2 to 3 years or more so the consequences could be far more serious.

Stability chambers are vital tools within any pharmaceutical company. We are all very dependent on them to keep performing within the ℃/%RH tolerances defined in ICH Guideline Q1A(R2) over several years and failures to do this can lead to extremely serious consequences. So in order to help this be achieved, regular requalification together with appropriate preventative maintenance is very strongly recommended.

Parameter Generation & Control is a renowned leader in temperature and humidity control solutions, boasting over 47 years of industry experience. We are dedicated to providing energy-efficient and cost-effective systems customized to meet the unique needs of each client. Our commitment to innovation and customer satisfaction has established Parameter as a standard-bearer in the industry.

See these links from PG&C for more chamber-related information!

• Stability Chambers & Products
• Climate Test Chambers
• Stability Chamber Validation Services
• Walk-In Stability Chambers