Demystifying MKT for Drug Product Storage
The United States Pharmacopeia (USP) chapter 1079 defines Mean Kinetic Temperature (MKT) as “the single calculated temperature at which the total amount of degradation over a particular period is equal to the sum of the individual degradations that would occur at various temperatures” So there you go, clear as mud, as my mom used to say. To make it even more clear for the non-science major, this equation is provided.
MKT is so misunderstood that USP is publishing chapter 1079.2 in December 2020 to explain it in clearer language. No wonder many people do not understand what MKT is or why it is useful!
Let me see if I can help. MKT is a way to summarize the history of a product’s temperature exposure with a single “virtual” temperature. If that virtual temperature (i.e. MKT) is within the limits of the acceptable temperature range, then the conclusion can be made that your product degradation is within the acceptable limits that you validated.
The FDA expects drug manufacturers, hospitals, and pharmacies to store their drug products (USP 1079 does not apply to drug substances) at the temperature range that has been validated through stability studies. The reason for this is that higher temperatures, the drug could degrade or become less effective or less safe.
Temperatures that are defined in the USP General Notices section are:
Any temperature not exceeding 8°C (46°F). A refrigerator is a cold place in which the temperature is maintained thermostatically between 2°C and 8°C (36°C to 46°C).
Any temperature between 8°C and 15°C (46°F to 59°F). An article that requires cool storage may be stored in a refrigerator, unless otherwise specified by the individual USP monograph.
The temperature prevailing in the workplace.
Controlled Room Temperature
A temperature maintained thermostatically that encompasses the usual and customary working environment of 20°C to 25°C (68°F to 77°F) that allows for brief deviations between 15°C and 30°C (59°F to 86°F) that are experienced in pharmacies, hospitals, and warehouses.
Any temperature between 30°C and 40°C (86°F to 104°F).
So the question becomes, if you have a drug product that should be stored at Controlled Room Temperature (CRT), and you have a power outage (or some other event) that causes the temperature to go higher than 25 deg C (or higher than 8 deg C for Controlled Cold Storage) for a brief time, what is the impact to that product? Is it still good? USP 659 uses 24 hours as the maximum excursion time for both CRT and Controlled Cold Temperature (CCT), but what if your temperature exceeds the excursion limits? MKT to the rescue!
MKT is a mathematical calculation that allows you to calculate a single temperature at which the total amount of product degradation over a particular period that is equal to the sum of degradations over various temperatures. That is a bit confusing, so let’s think about it in a different way.
You are monitoring your CRT warehouse, and all is well for a week and then you have an HVAC unit break down and the temperature rises to 42 deg C for 2 hours until you get it fixed. Since the USP says that only excursions up to 40 deg C are acceptable, you need to figure out the impact of the 42 deg excursion.
The USP talks about taking temperature readings every 15 minutes so let us say that is what you are doing. How do you evaluate whether the degradation to your product at 42 deg C for 2 hours is acceptable? You calculate MKT over the course of 30 days (24 hours for CCT) up to and including the excursion times and temperatures. If the MKT is below the CRT limit (i.e. 25 deg C for CRT or 8 deg C for CCT), then you can assume that the accumulated degradation is acceptable because it is still within the limits of CRT (20-25 deg C). Simple right?
There are many types of temperature monitoring software that will record temperatures over time and calculate MKT either continuously or on demand. So there is no need to figure out the equation for yourself or try to enter it into your Excel spreadsheet unless you want to revisit your college years.
One last thing I would like to emphasize, and this comes directly from the USP as well. It says “MKT may not be used to justify a storage or transportation system that has repeated excursions. Such a system is not in control and needs to be corrected.”