Chamber Mapping: Loaded, Unloaded, Percentage
This week, Paul Daniel goes into a bit more detail on empty mapping vs loaded mapping, and how to decide the percentage of loads during studies.Paul writes: USP 36 <1079> is very clear about this: "Temperature mapping should account for maximum and minimum loads to capture temperature variability resulting drug product temperature." Currently, empty mapping and loaded mapping is the best practice. From a qualification perspective, the empty mapping would occur in the Operational Qualification phase, and the loaded chamber would occur in the Performance Qualification phase. While this is "best practice" it does not mean that every facility does this.
Load Percentage: Consider Air Flow and Conduction
Appropriate percentage for loading is dependent on the type of chamber you are mapping. For instance, an ultra-low freezer performs best when full, because it doesn't rely on air flow to cool the product – it uses conduction. However, with a refrigerator, incubator, or stability chamber, air flow is the key method of temperature management. Unfortunately, most users over-fill such chambers and cause the heating/cooling of the unit to be less effective. The percentage used in a mapping study should be whatever load percentage is allowed by the Storage SOP for that particular product and chamber.
But... what if no specification is given?
We can use the NFx15-140 from 2002 from French Association for Standardization for the mapping of climatic chambers, which may be interpreted as including refrigerators, incubators, stability chambers, etc. (NOTE: This has been replaced by FD X15-140, published May 2013, "Mesure de l'humidité de l'air - Enceintes climatiques et thermostatiques - Caractérisation et vérification" which to date, is not yet translated.)
This guidance gives an indirect calculation for load percentage, instructing that stored materials should not be placed next to the walls, and provide the figure of 10% of the dimensions of the space. In a space that was 1m3 (1m x 1m x 1m), this would mean that no product should be within 10cm of the sides. If we follow this guidance we only have an effective storage area of 0.8mx0.8mx0.8m which equals… 0.51m3. This indicates that 50% is the maximum possible load.
In reality, if there isn't an internal specification for loading of the chamber, you may just need to select a load that is representative of normal use. Perhaps that data you collect while mapping may be used to support a load specification for the chamber in question?
Qualifying at Empty, Half and Full Storage
Some companies find good reasons to support mapping only empty chambers, as they think this represents the best overall challenge. If your system is expected (or known) to perform differently with different loads, then that would justify qualifying multiple loads. Whatever you choose, have a rationale for your choice that is supported by how the equipment is used. We welcome comments and questions in the comment fields below...