What is Mean Kinetic Temperature (MKT): Mean Kinetic Temperature (MKT) is a concept
used in various industries, especially in pharmaceuticals, food processing, and
storage, to assess the cumulative effect of temperature fluctuations on product
stability over a defined period.
Temperature is a crucial factor affecting the stability
and quality of many products. In industries such as pharmaceuticals, food
processing, and storage, maintaining product efficacy and safety is of most importance. Temperature-sensitive products can degrade or spoil if exposed to
extreme temperatures or significant temperature variations over time.
Therefore, it becomes crucial to develop a comprehensive approach to quantify
and understand the thermal stress experienced by these products during their
lifecycle.
The Mean Kinetic Temperature provides a means of
calculating an equivalent constant temperature that would cause the same
cumulative effect as the actual temperature profile over a specific period. By
considering the effect of temperature on the rate of chemical reactions, the
MKT offers a more accurate representation of the overall thermal stress
experienced by a product. This concept has gained significant recognition and
application in industries dealing with perishable or temperature-sensitive
goods.
In simple word we can say the Mean Kinetic Temperature is
calculated for understanding the effects of variations in temperature for
temperature-sensitive goods during storage and transportation.
Here I am going to explain about the usage of Mean
Kinetic Temperature by giving a very easy example and hope everybody can easily
understand.
Suppose there is a medicine which is prescribed by
manufacturer to store between 2°C to 8°C. This medicine is transported by a
temperature maintaining van for about 12 hours and the vehicle maintaining the
temperature between 2°C to 8°C. A data logger kept inside the boxes to record
the temperature. After completion of transportation, downloaded the data and
found for some time temperature goes out side the 8°C and some time is goes
outside the 2°C. As the medicine is recommended to store between 2°C to 8°C
then there will be doubts as this medicine is now suitable or not. Hence in
that case we calculate the Mean Kinetic Temperature and check if MKT value is
within 2°C to 8°C then respective medicine can be used without any doubts
otherwise need to evaluate about impact of temperature excursion on medicine.
The Arrhenius Equation and Its Significance: To
comprehend the concept of MKT better, it is essential to explore into the
Arrhenius equation, which forms the foundation for its calculation. The
Arrhenius equation relates the rate of a chemical reaction to temperature. It
is given by:
k =
Ae(-Ea / RT)
Where:
k is the rate constant of the reaction,
A is the pre-exponential factor (frequency factor) that
represents the rate of reaction at an infinite temperature,
e is the base of the natural
logarithm (Euler’s number) i.e. exponential.
Ea is the activation energy, which is the energy barrier
that molecules must overcome for the reaction to occur,
R is the universal gas constant (8.314 J/(mol*K)), and
T is the temperature in Kelvin (K).
The Arrhenius equation indicates that the rate constant
(k) of a reaction is exponentially related to the reciprocal of the temperature
(1/T). As temperature increases, the reaction rate also increases. The concept
of activation energy (Ea) highlights the sensitivity of reaction rates to
temperature changes. Higher activation energies imply that the reaction is more
sensitive to temperature variations.
The MKT Calculation: The
MKT is calculated by considering discrete temperature data points collected at
regular intervals over a defined period. These data points can be hourly,
daily, or any other suitable time interval based on the context.
As per ICH guideline Q1A (R2) the definition of MKT is as
“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.
To calculate the Mean Kinetic Temperature, first equation
was given by J. D. Haynes with the
help of Arrhenius equation.
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Where in Tk = Mean Kinetic temperature in
kelvin.
ΔH = Heat of activation / activation energy
i.e. 83.144 kilojoules· mole-1 (unless more accurate information is available
from experimental studies)
R = universal gas constant, 8.3144 x 10-3 kj.mole-1.
K-1
n = total number of storage temperatures
recorded during the observation period
T 1 = value for the temperature recorded
during the first time period
T2 = value for the temperature recorded
during the second time period
T = value for the temperature recorded during the nth
time period
To calculate the MKT, number of software is commercially available
who are automatically provides the MKT value. Otherwise we can calculate by
using simple excel sheet by applying the above formula in excel. Refer below
image:-
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In above excel, there is 15 time point recorded of
temperature and the by applying the formula the MKT value observed as 24.8°C.
It is clear as the MKT value is slightly higher the direct average value of all
temperature readings.
The Significance of MKT: Mean
Kinetic Temperature is an essential concept for several reasons:
Accurate Representation: The
MKT offers a more realistic representation of the overall thermal stress
experienced by a product compared to conventional temperature averages. Using
simple averages can overlook the impact of temperature fluctuations on product
stability.
Predictive Analysis: MKT
helps in predicting product stability and quality based on the cumulative
thermal exposure. This allows manufacturers to estimate the shelf life of
products under different temperature conditions.
Regulatory Compliance: Many
industries, especially pharmaceuticals and food, must adhere to strict
regulatory guidelines concerning storage and transportation temperature limits.
MKT provides a valuable tool for assessing compliance with these regulations.
Quality Control: MKT
aids in implementing robust quality control measures. By monitoring MKT,
manufacturers can identify potential issues with temperature-sensitive products
and take corrective actions to maintain product integrity.
Supply Chain Management: For
industries with complex supply chains, monitoring MKT can help in identifying
temperature excursions during transportation and storage, thereby ensuring that
products are delivered in the desired condition to consumers.
Risk Assessment: MKT
facilitates risk assessment by quantifying the impact of temperature variations
on product stability. This information can be used to develop risk mitigation
strategies and make informed decisions about product handling.
Product Development: MKT
plays a crucial role in the development of new products. By assessing how
different formulations or packaging materials respond to temperature variations,
manufacturers can optimize product stability and improve overall quality.
Limitations and Considerations: While
Mean Kinetic Temperature is a valuable tool for assessing thermal stress, it
has some limitations and considerations:
Simplifying Assumptions: The
MKT calculation assumes that the reaction follows the Arrhenius kinetics model,
which may not be valid for all products or reactions.
Constant Activation Energy: The
Arrhenius equation assumes a constant activation energy for the reaction, which
might not always hold true in practice.
Time Interval Selection: The
choice of time intervals for temperature data collection can significantly
influence the MKT result. The selection should be based on the specific
application and context.
Non-Isothermal Conditions: MKT
assumes that the temperature variations are isothermal (constant) during each
time interval. However, real-world temperature profiles might be more complex,
requiring more advanced models to account for non-isothermal conditions.
Overall we can say the Mean Kinetic Temperature is a
valuable concept that finds extensive application in various industries dealing
with temperature-sensitive products. By considering the cumulative effect of
temperature variations, MKT offers a more accurate representation of the
thermal stress experienced by products during storage, transportation, and
processing. It plays a vital role in quality control, regulatory compliance,
risk assessment, and product development. However, careful consideration of the
limitations and context-specific factors is essential while utilizing MKT for
specific applications.
Abhishek Singh is the author of Pharma technical support. He is pharmaceutical professionals, having experience of more than 12 years in Quality.