Definition of medicine shelf-life based on the assessment of the total risk of false conformity decisions due to measurement uncertainty – A multiparameter approach

Abstract

The ICH quality guidelines define how drug stability study should be accomplished in order to obtain a safe shelf life. To assess the risks of decision making one must consider the measurement uncertainty information. The stability study must consider the conformity assessment of all parameters (content, degradation product, among others), but the ICH approach does not consider the use of uncertainty information and considers the evaluation of only the most critical parameter to define the shelf life time. In this way, the current approach does not make it possible to assess the total consumer's risk, which can lead to the risk of obtaining a longer shelf life than the drug supports. The present study proposes to consider the uncertainty information in the definition of the shelf life, simultaneously considering all the parameters tested in the stability study. A MS-Excel spreadsheet was developed and made available as supplementary material (Stability_4Risk) for risk values calculation and shelf life definition, considering a stability study data and simultaneous parameters evaluation. The measurement uncertainty information, regression model types, metrological correlation of measured results, specification limits and the simultaneous parameters evaluation impacted on the risks and, consequently, on the definition of the shelf life. Thus, it was possible to establish a new approach for the definition of a safe shelf life, based on total consumer's risk, considering the measurement uncertainty and the simultaneous parameters evaluation, which guarantees the quality, efficacy and safety of medicines until its shelf life.