BEST PRACTICES ::QA/QC
Accelerated stability studies are based on the Arrhenius Equation, which de- scribes the mathematical relationship between the rate constant of a chemical reaction, the reaction temperature, and the activation energy for the molecule under study.4
Generally, for every 10-
degree rise in temperature (°C), the reaction rate doubles. Therefore, by increasing the temperature at which the product is stored, you can increase the reaction rate and degradation rate of a molecule or a product. For example, assuming an activation energy of 20 kcal/ mole/degree, storing a product at 35 °C for 30 days is approximately equivalent to storing the same product at 5 °C for 3 years, in terms of degradation rate.
Key considerations when design- ing accelerated stability studies In a recent article, some of the limita- tions of accelerated stability studies were highlighted.5
ity study when the product is stored under normal and unstressed storage conditions. This is especially true when the normal storage temperature of the product is at -10°C or lower, which means the product is frozen and is in a solid state, and accelerated stability studies are performed at higher tem- peratures (for example, 35°C), which means the product is now in the liquid state. For this reason, the prediction from the accelerated stability model may not be accurate and may result in overesti- mation or underestimation of shelf life. Some other factors that may result
Exposure of reagents
to raised temperatures during an accel- erated stability study may create condi- tions and chemical environments that produce degradation in the product. However, this degration may not be observed during a real time stabil-
in poor agreement between real time and accelerated stability studies are increased solubility and evaporation due to exposure of a reagent to higher temperatures, susceptibility of certain measurands to photodegradation more than thermal degradation, changes in re- sidual moisture in lyophilized reagents, increased or decreased proteolytic and enzymatic activities of liquid reagents due to exposure to raised temperatures, and changes in pH of the reagent due to escaping of dissolved gases and organic volatiles such as carbon dioxide, oxygen, and alcohols.
Conclusion Generally, accelerated stability studies predict stability and shelf life accurately, and there is reasonable and acceptable agreement between the actual shelf life from real time stability studies, which are performed over several years, and the estimated shelf life from accelerated stability studies, which are performed in a shorter period of time, typically over a few weeks. However, exposure of reagents to elevated temperatures during the acceler- ated stability study may create conditions and chemical environments that produce degradation in products that may not be typically observed during real time stability studies when the product is stored under normal and unstressed storage conditions. Product developers and labs should assess the applicability and suitability of the accelerated stability studies for their products by performing a few simple and fast experiments and consider the shortcomings of the accelerated stability studies prior to fully utilizing the model to estimate or establish product shelf life. For example, designing and executing pre-accelerated stability experiments, by storing key components of a reagent such as the liquid buffer system at the
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