Evaluation of Statistical Methods for BAtch-pooling and Design in Shelf-life Estimation

According to U.S. Food and Drug Administration (FDA) guidelines, the purpose of a stability study is to establish, based on testing a minimum of three batches of the drug substance or product, a retest period or shelf life and label storage instructions applicable to all future batches manufactured and packaged under similar circumstances. However, to test every batch under all possible combinations of time, strength, storage conditions, and packaging methods on a long-term testing schedule can be expensive and time consuming. As an alternative, a reduced design may be considered as an efficient method for reducing the number of testings needed to obtain the necessary information. In this thesis, we discuss the statistical aspects of stability study designs in relation to the recent guidelines. In addition, several commonly used criteria for design comparison are presented.
Based on Tsong’s mean value method, we propose a procedure to test the hypothesis for pooling factors. Finally, a simulation study was conducted to empirically compare the performance of the two methods in terms of size and power in estimating the shelf life of the drug product. Simulation results show that our simultaneous pairwise C.I.s method is superior to Tsong’s method.