The Use of Mean Kinetic Temperature to Aid Evaluation of Temperature Excursions: Proper and Improper

The extent of physicochemical degradation of drug products depends on factors such as product stability, how a product is stored, and how it is packaged. A major consequence of drug product degradation is that the product can fail to maintain its critical quality attributes. Temperature is likely to vary during the life of the product which can impact its degradation rate and stability profile.

Temperature excursions happen, although organizations expend a lot of effort to avoid them. Describing the magnitude of an excursion event as simply a high- or low-temperature event is meaningless without the factor of time. A typical unplanned excursion has a fluctuation in temperature over a period of time as opposed to a static temperature change. If the temperature at which the excursion occurred was static over time, it would be a lot easier to evaluate its impact on product stability.

Mean kinetic temperature (MKT) can be used to evaluate temperature excursions for storage (or transportation) of controlled room temperature (CRT) and controlled cold temperature (CCT) pharmaceutical products. Mean kinetic temperature is a simplified way of expressing the overall effect of temperature fluctuations on finished drug products. MKT integrates the time-temperature history and takes into account the fact that long temperature excursions at slightly elevated temperatures can be just as, or more, impactful than short temperature excursions at elevated temperatures. Thus, MKT is a way to summarize the time-history of a product’s temperature exposure with a single “effective” or “virtual” temperature.

The MKT is widely used in the pharmaceutical industry and should not be used to compensate for poor temperature control of storage (or transportation) facilities. It should be applied in situations where control is good but where occasional excursions may be encountered.

Over the years MKT has been misunderstood and misused and thus the seminar will focus on the proper and improper application of MKT to evaluate temperature excursion of finished drug products as they are stored and transported. During the webinar, the efforts to revise and develop several USP standards will be discussed along with two articles on the topic:

• USP General Chapters

• USP Stimuli Articles