Everything You Need to Know About Mean Kinetic Temperature (MKT)

There is a lot of mystery about the Mean Kinetic Temperature, its uses, and how we should interpret the value.

Introduction

Mean Kinetic Temperature (MKT) is a vital concept in the field of environmental monitoring, particularly in industries such as pharmaceuticals, biotechnology, and food storage, where maintaining the stability and efficacy of temperature-sensitive products is crucial. MKT provides a more accurate representation of the thermal stress experienced by a product over time compared to simple arithmetic means. This article explores the importance of MKT, its calculation, and the implications of temperature variations.

Mean Kinetic Temperature (MKT) Explained Like You're 5

Imagine you have a bowl of ice cream. If you leave it in the sun for just a little while, it starts to melt quickly, even if it was in the freezer all night. This is because the heat from the sun is more powerful at melting the ice cream than the cold from the freezer was at keeping it frozen.

In Pharma

In the world of medicines, we use something called Mean Kinetic Temperature (MKT) to figure out how much "heat" or stress a product has been through over time, like your ice cream melting in the sun.

What is Mean Kinetic Temperature?

MKT is a calculated value that expresses the cumulative effect of temperature fluctuations over a specified period. It is used to predict the shelf life of perishable goods and the stability of sensitive products. Unlike the arithmetic mean temperature, MKT gives greater weight to higher temperatures, which can accelerate degradation processes.

Calculation of Mean Kinetic Temperature

The formula by J.D. Haynes, published in the Journal of Pharmaceutical Sciences in 1971, provides a mathematical approach to calculate the “Virtual Temperature” or today's MKT. The formula takes into account the exponential nature of chemical degradation, which is accelerated at higher temperatures.

The formula for MKT is derived from the Arrhenius equation, which describes the temperature dependence of reaction rates. The calculation involves the following steps:

See calculation example here ==> Mean Kinetic Temperature Calculator

Limitations of MKT

Lack of Time Consideration:

• Explanation: MKT does not explicitly account for the duration of exposure to different temperatures. It treats each temperature data point as a static value, without considering how long the product was exposed to each temperature.
• Impact: Short-term temperature spikes and prolonged exposures are weighted equally, which can lead to an underestimation or overestimation of thermal stress.

Uniform Weighting of Data Points:

• Explanation: MKT averages the exponential effects of temperature on degradation rates but does not differentiate between prolonged exposure to moderate temperatures and brief exposure to extreme temperatures.
• Impact: This can result in a single MKT value that might not accurately reflect the real-world conditions impacting product stability.

Can Mean Kinetic Temperature (MKT) Be Used to Assess the Impact of Cold Temperatures?

The Challenge of Cold Temperatures Cold temperatures can also affect the stability and efficacy of pharmaceutical products. Exposure to temperatures that are too low can cause:

• Crystallization: Certain drug formulations may crystallize at low temperatures, affecting their bioavailability and efficacy.
• Phase Separation: In emulsions, cold temperatures can cause phase separation, leading to product instability.
• Protein Denaturation: For biologics, freezing or near-freezing conditions can lead to protein denaturation, rendering the product ineffective.

Six Basic Recommendations for Using Mean Kinetic Temperature (MKT)

1. Do Not Use MKT to Compensate for Temperature Excursions

MKT should never be used to justify or ignore temperature deviations. All temperature excursions must be investigated and resolved.

2. Ensure Adequate Sampling

For accurate MKT calculations, ensure you have a sufficient number of time/temperature samples. The more data points included, the better the calculation.

3. Avoid Using MKT in Uncontrolled Temperature Areas

MKT should not be used in environments where temperature control is inconsistent. Reliable MKT calculations require stable temperature conditions.

4. Use MKT for Products Stored below 25°C

Apply MKT only if the product’s storage temperature specified on the label does not exceed 25°C. MKT is most effective for controlled room temperature storage.

5. Do Not Use MKT for Below-Freezing Products

MKT should not be used for products that need to be stored below freezing temperatures. The Arrhenius equation, which underlies MKT, does not adequately account for phase

6. Investigate All Temperature Excursions

Regardless of whether you use MKT, every temperature excursion must be investigated to ensure product quality and compliance with regulatory standards.

At the end of the day, MKT is an estimation and not definitive scientific data upon which firm conclusions can be drawn. However, it is a useful piece of information when combined with other data when it's time to evaluate an excursion.

Conclusion

Mean Kinetic Temperature (MKT) is a valuable tool for assessing the cumulative thermal impact on pharmaceutical products during storage and distribution. However, it must be used appropriately, with a thorough understanding of its limitations and requirements. The six key recommendations provided ensure that MKT is applied correctly, avoiding misuse and ensuring the stability and efficacy of products. Proper application of MKT, combined with thorough investigation of all temperature excursions, helps maintain product quality and compliance with regulatory standards.

How ATEK Can Help

Implementing a robust real-time monitoring system is crucial for maintaining consistent temperature control and accurately tracking environmental conditions. ATEK's continuous monitoring solutions provide precise and reliable data, ensuring that all temperature excursions are promptly identified and addressed. With ATEK's advanced monitoring capabilities, you can:

• Ensure Comprehensive Temperature Control: Real-time alerts and continuous data collection help maintain stable storage conditions, preventing deviations that could compromise product quality.
• Improve Regulatory Compliance: Automated monitoring and detailed reporting support compliance with regulatory requirements, including those related to MKT.
• Enhance Product Safety and Efficacy: By maintaining optimal storage conditions, ATEK helps ensure the safety and efficacy of your pharmaceutical products throughout their lifecycle.

For more information on how ATEK can support your temperature monitoring needs, visit ATEK's website or contact us at [email protected].

Sources

• European Medicines Agency, Committee for Human Medicinal Products (CHMP), “Guideline on Declaration of Storage Conditions: A) In the product information of Medicinal Products B) For Active Substances”
• European Compliance Academy (ECA), GMP News 07.05.2014: “GDP Question: When to use Mean Kinetic Temperature Calculation (MKT)?”
• European Compliance Academy (ECA), GMP News 22.04.2015: “GDP: Is temperature control required for each Transport?”
• FDA: Guidance for Industry Q1A(R2) Stability Testing of New Drug Substances and Products
• ICH Harmonized Tripartite Guideline, Stability Testing of New Drug Substances and Products Q1A(R2)
• ICH Q1F, Explanatory Note on the Withdrawal of ICH Q1F on the ICH Website
• J. Pharm. Sci., 60:927-929, 1971. John D. Haynes. “Worldwide Virtual Temperatures for Product Stability Testing”
• The Pharmaceutical Journal
• USP 43 Chapter <1160> Pharmaceutical Calculations in Pharmacy Practice
• USP 43 Chapter <1079> Risks and Mitigation Strategies for the Storage and Transportation of Finished Drug Products
• WHO Technical Report Series No. 953, 2009, Annex 2, Appendix 1 “Long-term stability testing conditions as identified by WHO Member States”
• WHO Technical Report Series, No. 953, 2009, Annex 2, Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products
• “Drug Stability Testing – Classification of Countries According to Climatic Zone” published in Drugs Made in Germany, by Dietz, R., Feilner, K., Gerst, F., Grimm, W.
• European Medicines Agency (EMA), "Guideline on Good Distribution Practice of Medicinal Products for Human Use"
• International Society for Pharmaceutical Engineering (ISPE), "Good Practice Guide: Cold Chain Management"
• Health Canada, "Good Manufacturing Practices (GMP) Guidelines – 2009 Edition, Version 2 (GUI-0001)"
• Pharmaceuticals and Medical Devices Agency (PMDA) Japan, "Guidelines for Good Distribution Practice (GDP) of Medical Products"

Hakim Rouab

[email protected]

ATEK's website