Overview of stability study designs.
Stability requirements for the worldwide registration of pharmaceutical products have changed dramatically in the past few years. A series of guidelines on the design, conduct, and data analysis of stability studies of pharmaceuticals have been published by the International Conference on Harmonization (ICH); however, the statistical discussion on study design is limited. In this paper, stability designs including full, bracketing, and matrixing designs will be exemplified. The statistical aspects of these stability designs will be discussed in relation to the recent ICH guidelines. The statistical and regulatory considerations on the selection of stability design will also be presented. The stability study should be well designed so the shelf life of the drug product can be estimated with a high degree of accuracy and precision. Several commonly used criteria for design comparison will be presented. Finally, a case study is presented to illustrate the potential problems of an overreduced design from the statistical and regulatory perspectives.
Lin
Tsae-Yun Daphne
TY
Office of Biostatistics, Center for Drug Evaluation and Research, FDA, Rockville, Maryland 20850, USA. Lind@cder.fda.gov
Chen
Chi Wan
CW
D002626:Chemistry, Pharmaceutical / Q000592:standards*; D004355:Drug Stability; D004356:Drug Storage / Q000592:standards / Q000706:statistics & numerical data; D017408:Guidelines as Topic; D015233:Models, Statistical; D012107:Research Design / Q000592:standards*; D013997:Time Factors