Expiration Dating of Pharmaceutical Compounds in Relation to Analytical Variation,Degradation Rate,and Matrix Designs

Abstract

In order to establish a shelf life claim for the potency of pharmaceutical compounds drug stability studies are conducted by pharmaceutical companies. Frequently, the effects on stability of a variety of fixed factors are investigated, leading to large and expensive study designs. Consequently, the use of fractional factorial or matrix designs have received increasing attention from statisticians, with a view toward managing the size of such studies. Fixed factors of interest have been studied with respect to matrixing; however, matrixing on the choice of time points has not been thoroughly investigated. This paper studies the effect on the expiration dating of various matrix designs specifically on the choice of sampling time points, in relation to analytical variation and degradation rate. Some useful tables are also given comparing expiration dates from matrixing across sampling time points in relation to the analytical variation and degradation rate.