What’s the Importance of Mean Kinetic Temperature in Monitoring Pharmaceuticals?
A single temperature excursion in the cold chain doesn’t translate to a spoiled product. Loss of product stability is a result of not one, but several temperature excursions. It’s not the occurrence of an excursion that dictates the result. Rather it is the frequency and severity of the event.
For instance, a vaccine in storage changes temperature, from 4°C to 10°C (36°F – 39°F) for the whole duration of its transport. The product is still fit as the excursion only happened once. But if the temperature increased to 20°C several times the quality of the product would be in question.
It’s easy to determine at what degree the product changes in temperature or at what time or how often. But it’s not so easy to determine if the cargo is still fit for purpose. There is a way to do this, and it has something to do with the Mean Kinetic Temperature.
What is Mean Kinetic Temperature?
Mean Kinetic Temperature (MKT) is a calculation used in stability studies of pharmaceutical products. Stability tests can measure the acceptable temperature range of new and old products. The result defines the products’ normal storage conditions and displayed on product labels.
In simple terms, MKT is the value that indicates the effect of temperature variations over a period of time. In other words, that single temperature is the equivalent of all temperature changes. The stability of the product at this temperature depends on if it is within the acceptable temperature range.
It is important to note that MKT is different from other means such as simple numerical average or arithmetic mean. To compute for the MKT, the formula gives greater weight to higher temperatures. This is because higher temperatures pose more risk to pharmaceutical products.
This weighting of higher temperatures recognizes the accelerated rate of thermal degradation present at higher temperatures.
Several guidelines like the European Union Guidance on Good Distribution Practices, FDA Code of Federal Regulations, and United States Pharmacopeia (USP), and International Conference on Harmonization (ICH) and the Technical Requirements for Registration of Pharmaceuticals for Human, Use urge companies to store products in “conditions that will maintain their stability, integrity, and effectiveness, and ensure that the drug samples are free of contamination, deterioration, and adulteration.” This could not be possible without the help of MKT.
How to Calculate the Mean Kinetic Temperature?
The International Conference on Harmonization stability testing guidelines define MKT as:
A single derived temperature that, if maintained over a defined periods of time, affords the same thermal challenge to a drug substance or a drug product as would be experienced over a range of both higher and lower temperatures for an equivalent defined period.
Through this exact definition, we know that Mean Kinetic Temperature means:
● Single temperature
● Calculated from a range of temperatures
● Representing the same thermal challenges
● Over the same time period
The MKT formula involves some complex math:
● ΔH = activation energy (typically from 60 to 100 kJ/mol for solids and liquids)
● R = universal gas constant (8.314472 J/mol-K)
● T1 – Tn = the temperature data points measured
● TK = Result in degrees Kelvin
● n = the number of sample periods over which data is collected
To compute for the celsius, subtract 273.15°K from the resulting temperature in Kelvin (TK – 273.15°K).
Before calculating the MKT, here are some of the most important things to consider:
● Make sure that the temperature intervals are equal and regular. This means no reading should be missed.
● Measure fluctuations during different legs like loading or unloading, where excursions are more likely to occur.
● Temperature excursions that had happened should still be investigated even if the MKT result is a safe temperature. The investigation can help catch a problem before it becomes real.
How to Measure MKT in real-time?
The easiest way to measure temperatures for the MKT is through the use of data loggers. Some cheap and basic data loggers don’t provide real-time data. An effective MKT result should come from real-time data. Advanced data loggers come with real-time data reporting and analytics. In this way, the management will know the temperature during transit and alerts sent when excursions occur.
Here’s how to know the real-time temperature and solve the MKT formula using real-time data:
- Make use of data loggers that can read temperatures and send data to an analytics platform in real-time. Even without a connection, the devices should buffer readings for transmission. The wireless temperature sensors from companies like Pharma-Mon can achieve this.
- Use cloud services. Localized logging and analytics analyzed post-mortem and rarely actionable. It’s better to stream temperature data to a cloud or online storage platform to access the analytics.
- Use the right analytical approach. MKT results can differ depending on the perspective of the management. Data models can help them guide their reactions to the MKT results:
● Regular MKT – This model only uses the formula as a standard test to determine the condition of the products. This can only be calculated if all readings at a regular interval are available.
● Optimistic MKT – Method of viewing temperature excursions as only deviant rather than disastrous. This model is used on semi-perishable products and inexpensive cargos. Her minor temperature spikes don’t equate damaged items.
● Pessimistic MKT – In contrast with optimistic MKT, this method approaches temperature excursions as emergency situations. Used to evaluate the condition of sensitive and expensive cargo such as pharma products where excursions can spoil products.
● Predictive MKT — This is the most reliable method as it depends on the reason behind the temperature excursions. The management will gauge the impact of the excursions on the future outcome of the cold chain products.
The advent of MKT has made monitoring of temperature-sensitive products a little bit easier. This has led to less spoilage and more high quality and stable products.
Although MKT is a game-changer, using it doesn’t entail a perfect cold chain. Temperature excursions will still happen from time to time and exposed products will still go unnoticed.
It serves as a reminder that monitoring solutions mustn’t be complacent. The awareness and capability to act on temperature excursions as they happen and know the reason behind the events is still irreplaceable. MKT can be a helpful accessory, an effective piece of information to an already efficient monitoring solution.