Versatile real-time and wireless systems for measurements in various types of pharmaceutical applications
The validation procedure encompasses many aspects with the process vessel and product both needing detailed study. In both cases it is important to find the cold spot at which the slowest heat transfer will be applied. Three phases of tests should be considered:
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Safety – Ensuring that microbial stability has been achieved |
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Optimization – Reducing process times to increase production |
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Process Validation – Providing documentation to demonstrate |
There are many factors that can have an impact on the efficiency of a thermal process. In the development of processes for sterilization of pharmaceuticals, one of the main considerations is the acquisition of accurate time/temperature profiles. The main reasons for this are:
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Temperature Distribution - Temperature mapping within a fully loaded process vessel to investigate performance against a control program and identify the cold spot. |
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Cold Point Determination - Multiple measurements are made within a product container to find the slowest heating point within the product. This will be product and packaging dependent. |
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Heat Penetration - Replicate measurements with temperature measurement devices located at the position identified within the cold point tests. |
All of the phases above are focused on identifying the worst case conditions to which the product would be exposed. The lowest temperatures and slowest heat transfer would lead to the lowest microbial reduction. It is crucial that the temperature measurement devices have high accuracy and reliability. A systematic or experimental error of 1°C in a temperature measurement system at the sterilization reference temperature of 121.1°C would lead to a corresponding error of 26% in the calculated Fo sterility value.
It is important that the correct equipment is applied for a given validation. We have developed a large selection of probes, sensors, packing glands, and tools which are available for correct mounting in various styles and designs of containers. The range of fittings available is being continually expanded and improved with the following parameters taken into consideration:
• Correct Positioning of the Measuring Device
It is very important that the packing gland and probe are correctly positioned in the "cold spot". If this is not obtained it can result in "false" measurements, risking high Fo-values.
• Elimination of Steam and Water Ingression
It is pertinent that the packing gland and the probe are mounted so that the integrity of the container is maintained. Properly mounting the gland will also ensure that water/steam ingression cannot occur, which would lead to false data and high Fo-values.
• Minimizing Risks of Heat Conduction
It is recommended that the probe and gland are mounted from the side of the container with the longest distance to the "cold spot" so that heat conduction from the water/steam is avoided. Even if the probe/gland is as small as possible and made of materials with the lowest conductivity there will always be a risk of heat conduction.
• Minimizing the Probe Assembly Inside the Container
It is very important that the probe and fixture are as small as possible so that the impact on the internal environment (product) of the container, including the headspace, is minimized.
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