20/21 September 2022
In spite of careful precautions, temperature excursions from the declared storage temperatures happen again and again during transport of pharmaceutical products. To estimate the impact of such fluctuations on the product stability, the mean kinetic temperature (MKT) is calculated. The calculation formula (deriving from the Arrhenius equation) is based on the temperature fluctuations taken at different fluctuation times T1, T2 ... (DH = activation energy; R = general gas constant).
A while ago, the USP published a Stimuli Article in the Pharmacopoeial Forum on the correct use of the mean kinetic temperature. The reason for the creation of this article is the frequent misuse of MKT which misses its initial purpose, namely estimating the cumulative energy input into the product. The article gives as an example the calculation of MKT over a 52-week period where temperatures were recorded every 15 minutes. The individual excursions within the period aren't reflected but levelled in the MKT. According to the example's required storage temperature range of 20 - 25°, the 52-week MKT would be 23,98° and thus within the tolerance range. Now, looking at the 30-day MKT calculation, one can see that temperatures are temporarily far outside the authorised storage range. In the article's example, the MKT over a 30-day period was 28.98° and at one day even 30,7°. According to Monograph <659> Packaging and Storage Requirements (USP 41 p. 6384) a temperature range of 15 - 30° is allowed for products stored at room temperature with short-term excursions up to 40°, as long as they are less than 24 h in duration and the MKT is 25°. The MKT's peak value of 28.98° thus doesn't meet the requirements of monograph <659> and the product stability cannot be guaranteed any longer. The Stimuli Article's authors therefore recommend the calculation of the 30-day MKT for products which are stored a room temperature and have derived the 24-hour MKT for substances to be stored at cold temperature (2 - 8°) in an analogous example.
You can get to the complete Stimuli Article after successful registration in the Pharmacopoeial Forum.