Mean-Kinetic-Temperature

Mean Kinetic Temperature (MKT) and Temperature Excursions


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To get free Excel sheet for MKT calculation, refer end section of the article.

What is Mean Kinetic Temperature (MKT)?

  • An isothermal storage temperature produces similar effect as non-isothermal temperature of storage temperature deviation.
  • It exhibits the cumulative effect of thermal stress that is experience by a drug product.
  • Mean kinetic temperature (MKT) also called as “virtual” temperature.

The use of Mean Kinetic Temperature (MKT) is considered an acceptable practice for storage and can be use to justify an impact excursions during transit (see <659> Packaging and storage requirement, USP 42).

Temperature monitoring devices to monitor temperature during transportations and in the warehouse

To monitor the temperature of the storage area in warehouses, shipment during transportation of cold chain materials and products, digital data loggers are used.

Nowadays, various types of data loggers are available in the market, having a more comprehensive range of temperature, excellent accuracy, and data available in different formats such as PDF, Spreadsheet, etc. When data are available in Data available in spreadsheet format, it can be helpful for various types of data analysis such as calculation of Mean Kinetic Temperature.

A variety of data loggers are available in the market, such as multi-use, single-use, logger with GPS tracking, etc. Following are few examples of suitable data loggers available on Amazon that you can check out and purchase depending on your need.


Tempnote T32 Multi-use Temperature Data Logger for Temperature Monitoring in Transit, PDF and CSV Reports

  • Economical Reusable Temperature Data Logger for Cold Chain Monitoring
  • Tempnote T32 is integrated with USB, auto-generates secured PDF report.
  • No software required to access data file


Enviro Slim And Compact Design Sudl-518 Temperature Single Use Data Logger

  • Auto Generated Secured Pdf Report
  • Calibration Certificate
  • Measurement Range -22°F to 158°F (-30°C to 70°C) and Accuracy ±0.5℃(-20℃ to +40℃)

Controlled room temperature and its connection to Mean Kinetic Temperature (MKT)

  • Mean kinetic temperature should not to exceed 25° C
  • Temperature excursions are allowed in hospitals, storage facilities, pharmacies, and during shipments. The allowed excursion is between 15° C and 30° C (59° and 86° F). However, MKT should not more than 25° C
  • Some excursions also allowed up to 40° C. However, it should not be more than 24 hours
  • Excursion more than 40°C may be permitted only in case scientific data are available such as stability study, excursion studies etc.

Stability testing and its connection to Mean Kinetic Temperature (MKT)

Similar expectation as above is described in the ICH Q1A (R2), Stability testing of New Drug Substances and Products. Version dated 6 February 2003.

Definition of Mean kinetic temperature (MKT)

Mean-Kinetic-Temperature

Key points to remember

The MKT will always be more than the arithmetic mean value of temperature.

It considers the Arrhenius equation.

The formula of J. D. Haynes (J. Pharm. Sci., 60:927-929, 1971) is used when MKT needs to be established for a fixed duration.

Arrhenius equation describes the temperature dependence of simple chemical reaction rates at ambient temperatures. As per this, the rate of reaction mostly doubles with every 10 ° C raise in temperature.

Mean Kinetic Temperature (MKT)as per USP

Mean-Kinetic-Temperature as per USP

Mean Kinetic Temperature (MKT) calculation equation

The Mean Kinetic Temperature (MKT) calculation equation is derived from the Arrhenius equation). Refer following equation.

Mean-Kinetic-Temperature definition

View of Medicines and Healthcare products Regulatory Agency (MHRA) on Mean kinetic temperature (MKT)

MKT caution

Use of MKT as per Good storage and distribution practices for drug products, USP 42

  • It acceptable practice to justify excursions for short period of time and during transit, not applicable for long term storage
  • It can be used for the product with first order kinetics over the temperature range experienced.

MKT caution

To calculate Mean Kinetic Temperature (MKT), USP recommends following duration with respective conditions during the excursions:

Temperature condition Data to be considered
Controlled Room Temperature (CRT) 30 days
Controlled Cold Temperature (CCT) 24 hours data

The following three requirements must be met in order to meet the USP CCT permissible excursion allowance:

(1) the excursion may not exceed 15° (59° F);

(2) the excursion time may not exceed 24 h;

(3) the 24-h MKT must not exceed 8° (46 °F).

Criteria for use of MKT for controlled room temperature (CRT) and controlled cold temperature (CCT) excursions

Criteria for allowance to use MKT to evaluate temperature excursions that may occur during storage or transit shall be based on the following guidance.

  Storage Range Acceptable Excursion Range Maximum Temperature MKT (NMT) Time Period of Calculation
CRT 20°- 25° 15°- 30° 40° 25° 30 days
CCT 2°- 8° 8° – 15° 15° 24 h

Reference: Stimuli Article published by the USP in the Pharmacopoeial Forum

For Controlled Room Temperature:

Mean Kinetic Temperature (MKT) calculation can be done a continuing basis. Another approach is to calculate it when there is a temperature excursion. In the approach last 30 days data from (and including) the high excursion temperature should be used. Similarly, for Controlled Cold Temperature, 24 hours data is expected.

As per regulatory expectations, all excursions required to be investigated and evaluated. The drug product manufacturer required to evaluate excursions outside of the USP allowance criteria. The data needs to compare against stability data in order to make a final drug product disposition. Multiple excursions while transit and storage must be investigated by the manufacturer and in such situation. MKT calculation cannot be used. Multiple excursions indicate that the system is out of control and need maintenance and rectification.

Conclusion

This article highlights the various guidance and literature where importance of Mean Kinetic Temperature (MKT) is described/ The article also provide information that in which scenarios Mean Kinetic Temperature (MKT) can be used to justify short-term storage or transportation excursions.

Mean Kinetic Temperature (MKT) value shows an overall impact because temperature variations on the drug products during storage or transit. Mean Kinetic Temperature (MKT) is not meant to provide justification poor temperature control of storage or transportation facilities; however, it should be applied to justify sort-term excursions and where facility controls are adequate.

Use and caution for using MKT

  1. As per guidance
    • MKT can be used for only Cool temperature and Room Temperature.
    • At less temperature, the reaction rates is clow (freeze/ thaw) hence, it does not follow Arrhenius rule.
  2. Only some guidance, such as USP and MHRA supports MKT but it is not supported by German authority.
  3. Don’t use MKT to justify temperature excursions because of poor facility control.
  4. Use as many as data points (time and temperature).
  5. Investigation is must for all temperature excursions during storage and transit. Use of MKT is additional tool as per applicability and allowance mentioned in above article.

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