Shelf life from temperature-accelerated studies

Shelf-Life Estimation from Temperature-Accelerated Studies... 

Because of the multiple degradation pathways that may take place at elevated temperature, protein stability monitoring data may not conform to the Arrhenius relationship, and the maximum temperature selected for accelerated stability studies must be carefully selected. Gu et al. [32] described the different mechanisms of inactivation of interleukin-1 (3 (IL-1 (3) in solution above and below 39°C. In this example, the multiple mechanisms precluded the prediction of formulation shelf life from accelerated temperature data. In contrast, by working at 40° C and lower, Perlman and Nguyen [33] were able to successfully extrapolate data from stability studies of tissue plasminogen activator down to 5°C. 

In temperature-accelerated studies, shelf life at a storage temperature 7 , is estimated from the shelf life at an elevated temperature T2, according to... 

In thermal stability studies, accelerated testing at elevated temperatures is used to minimize the time needed to assess the thermal stability of the substance/ product. From the Arrhenius plot, one can predict the shelf life of the product at a proposed storage temperature. 

For infrequently prepared products the analysis of some expired batches may also provide usefiil support for the shelf-hfe of a preparation. A more detailed product file should include data from a thorough stability study. Stability testing should ideally be performed prospectively, but it can also be performed concurrently by following the first batches produced, this can be particularly useful if accelerated storage at an elevated temperature is included in the study. The product shelf life can be increased during the study as more data becomes available. The design of a stability study is described in Sect. 22.5. 

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