EFFECT OF THE UNCERTAINTY OF THE STABILITY DATA ON THE SHELF LIFE ESTIMATION OF PHARMACEUTICAL PRODUCTS

Abstract

The estimated shelf life of a drug product is highly influenced by the variability of the measured data. The fluctuation of the stability data is composed of the manufacturing process variation (batch-to-batch and within batch variability) and of the uncertainty of the analytical method (reproducibility and repeatability). The aim of the paper is to show a calculation method by which all of the variance components can be estimated before commencing the stability study. The effect of the uncertainty on the estimated shelf life is also considered: the expected variance of a single stability time point and the width of the 95\% one-sided confidence limit after 2 storage years are calculated. For the computation the results of the content uniformity test and the validation (specifically the precision study) of the analytical method are used. The applied mathematical method is the analysis of variance. The advantage of the concept is that if the magnitude of the uncertainty is known in advance, one may consider whether the present manufacturing process and analytical method is suitable for the stability study.