Estimating Drug Shelf-life with Unknown Lot-to-lot Variability

This article addresses the problem of estimating the shelf-life of a drug through a standard stability study that is routinely performed in the pharmaceutical industry. Based upon a dataset of the degradation of the drug efficacy over time, the objective is to estimate at what time point the drug efficacy falls below a minimally acceptable level. In this article, attention is directed toward the different roles played by lot-to-lot variability and measurement error in the performances of various estimation methodologies. The standard estimation method, as proposed by the United States Food and Drug Administration, for example, in accordance with current international guidelines, is compared with some new approaches. Simulation results are presented, which illustrate the advantages and disadvantages of the different estimation methodologies, and some recommendations and suggestions are made for shelf-life estimations.