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Accelerated Stability Assessment Program (ASAP): Improved Protocol and Data Analysis for Accelerated Shelf-Life Estimation of Solid Dosage Forms

Kenneth C. Waterman1, Anthony J. Carella2, Michael J. Gumkowski1, Bruce C. MacDonald1, Michael C. Roy1, and Sheri L. Shamblin1. (1) Pharmaceutical Sciences, Pfizer Inc, Eastern Point Road, Groton, CT 06340, (2) Non-Clinical Statistics, Pfizer Inc, Eastern Point Road, Groton, CT 06340

A more rapid and more accurate accelerated aging protocol (ASAP)is used to determine the shelf-life of drugs in solid dosage forms based on different drug development phases, from excipient compatibility through post-approval changes. Reliable estimates for temperature and relative humidity effects on chemical stability are provided using the combination of an isoconversion paradigm and a humidity-corrected Arrhenius equation. Imprecision is incorporated into a Monte-Carlo simulation to propagate the variation inherent in the experiment. In early development phases, greater imprecision in predictions is tolerated to allow faster screening with reduced sampling. As programs progress, early development data are used to design appropriate test conditions for late stage stability programs. Parameters generated from the protocol also allow package selection without explicit screening. ASAP is being used to define the critical degradation products for developing analytical methods, to select the appropriate packaging configuration, and to understand the stability impact of changes in the API or drug product manufacturing processes.