Temperature mean kinetic

Mean Kinetic Temperature — 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. 

When establishing the mean kinetic temperature for a defined period, the formula of J. D. Haynes (J. Pharm. Sci. 60 927-929, 1971) can be used. 

Pharmacists are expected to maintain the repackaging facility where the dosage forms are stored and repackaged at temperatures such that the mean kinetic temperature (MKT) (see Pharmaceutical Stability (1150) for further discussion on MKT) is not greater than 25° C. If plastic materials are used for repackaging, the USP requires that these materials should afford better protection than PVC in other words, a Class A-type package is advocated. 

In subsequent years, a number of guidance documents related to stability of pharmaceutical products have been issued. The guidance documents are based on the concept of climatic zones (1). There are four zones based on Mean Kinetic Temperature and Mean Annual Relative Humidity (RH) Zone I (temperate climate), e.g., Canada and Northern European, Zone 11 (subtropical), e.g., the United States and Southern Europe, Zone III (hot and dry), e.g.. Egypt and Zone IV (hot and humid), e.g., Brazil. The United States, Europe, and Japan are all in Zones I and II so the ICH guidelines are applicable for these zones. 

Before the ICH was formed, agreement on the appropriate storage conditions for stability studies was always controversial. The regulatory agencies in different countries did not always agree with each other. For example, the definition of room temperature or controlled room temperature was different globally. Currently, the world is divided into four climatic zones based on the mean kinetic temperature. The definition of room temperature in the four zones is given in Table 5 as is the relative humidity. Some of the countries that fall into these zones are also shown. 

The choice of test conditions defined in this guideline is based on an analysis of the effects of climatic conditions in the three areas of the EC, Japan and the USA. The mean kinetic temperature in any region of the world can be derived from climatic data (Grimm, W. Drugs Made in Germany 28, 196-202,1985 and 29, 39-47, 1986). 

Brief exposure to temperatures up to 40°C/104°F may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F). However, such exposure should be minimized. 

Controlled Room Temperature [USP] — Temperature maintained thermostatically that encompasses the usual and customary working environment of 20°-25°C (68°-77°F) and that results in a mean kinetic temperature calculated to be not more than 25°C and allows for excursions between 15° and 30°C (59°-86°F) that are experienced in pharmacies, hospitals, and warehouses. 

Mean Kinetic Temperature [ICH Q1A] — Isothermal temperature that corresponds to the kinetic effects of a time-temperature distribution. 

Mean Kinetic Temperature The single test temperature for a drug product corresponding to the effects on chemical reaction kinetics of a given temperature-time distribution. A mean kinetic temperature is calculated for each of the four world climatic zones according to the formula developed by Haynes (2). It is normally higher than the arithmetic mean temperature. 

In a stability study, the effect on the product in question of variations in temperature, time, humidity, light intensity and partial vapor pressure are investigated. The effective or mean kinetic temperature therefore reflects the actual situation better than the measured mean temperature a product kept for 1 month at 20°C and 1 month at 40eC will differ from one kept for 2 months at 30°C. 

To fully understand the decision of ICH storage conditions as well to better design the stability program, the stability professional needs to understand mean kinetic temperature a discussion of mean kinetic temperature is provided in Section 3.6. 

In addition, the warehouse conditions where bulk samples are stored must be monitored and mean kinetic temperature calculated. 

A major step forward toward the definition of adequate stability testing conditions based on good science was made by introducing the Mean Kinetic Temperature... 

An additional parameter, which is including the reaction rate constants in the evaluation of the impact of heat on pharmaceutical products, is the Mean Kinetic Temperature (MKT). The MKT was calculated by applying an equation derived by Haynes [11] based on the Arrhenius equation. At first, the activation energy Ea (assumed to be 83.144 kJ/mol) is divided by the universal gas constant R, the result is then divided by the temperature at each time point and place per day measured in degrees... 

Then the mean kinetic temperature per day for each month (MKTd) is achieved by calculating the negative natural logarithm of the above result, converted into degrees Celsius, using the following equation ... 

MKT = Mean Kinetic Temperature, calculated as described above. 

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