Mean Kinetic Temperature (MKT): Calculation, Benefits, and Limitations

During the storage and transportation of medicinal products, temporary temperature deviations may occur despite careful planning and technical measures – for example, due to environmental factors, delays, or unforeseen events. To better assess the impact of such temperature fluctuations on product stability, the so-called Mean Kinetic Temperature (MKT) can be used. It provides a mathematical approach to evaluating the thermal stress to which a product is exposed over a defined period of time.

Definition

The ICH Guideline Q1A(R2) “Stability Testing of New Drug Substances and Products” defines MKT as follows:

Mean kinetic temperature: A single derived temperature that, if maintained over a defined period of time, affords the same thermal challenge to a drug substance or drug product as would be experienced over a range of both higher and lower temperatures for an equivalent defined period. The mean kinetic temperature is higher than the arithmetic mean temperature and takes into account the Arrhenius equation.

In simple terms, the MKT is a calculated temperature that reflects the same impact on a product’s stability as the actual, fluctuating temperature profile. In the calculation, higher temperatures weigh more heavily than lower ones – in line with the Arrhenius equation, which states that chemical reactions accelerate exponentially with increasing temperature.

Formula and Calculation

MKT is calculated using a logarithmic function that includes individual temperature values (in Kelvin), the universal gas constant, and an assumed activation energy. In practice, this calculation is typically carried out using specialized software.

A single short-term temperature spike can significantly increase the MKT – even if the arithmetic mean remains within the acceptable range. This makes MKT a sensitive indicator of thermal exposure.

MKT does not replace Compliance with specified Temperature Limits

Despite its practical usefulness, MKT does not replace the obligation to adhere to the labeled storage and transport temperatures – neither from a regulatory nor a quality perspective.

Regulatory authorities often take a critical view of using MKT to retrospectively justify temperature deviations. For example, the Questions and Answers document on operating a pharmaceutical wholesale business ("Frage- und Antwortpapier zum Betreiben
eines Großhandels mit Arzneimitteln), published by the German ZLG (Central Authority of the Federal States for Health Protection regarding Medicinal Products and Medical Devices), states:

“MKT does not account for effects that can lead to irreversible quality defects, even with short-term exceedance of certain temperature limits identified during stability studies as part of the marketing authorization process. Possible crack formation in glass ampoules or vials at temperatures around the freezing point would also remain undetected. Moreover, calculating the MKT requires knowledge of the complete temperature history of all previous transport steps. These data are usually not available, so a meaningful calculation cannot be performed. Compliance with the labeled storage or transport temperature remains essential (see also questions on transport and storage temperatures).” (Translation by the editorial team)

Conclusion

MKT can be a useful supplementary tool within a risk-based temperature management approach – especially for interpreting temperature logger data during transport. However, it must not be misunderstood as a general justification for temperature deviations. Adherence to the defined storage conditions remains essential to safeguard product quality and ensure patient safety.