Chapter 13 - ASAP Application: Unstable Drug Candidate in Early Development

Abstract

ICH and WHO stability guidelines require minimum 6–12 months of stability data at recommended long-term and accelerated conditions to support the expiry dating for registration. This approach is problematic in early clinical development because of the lengthy duration of the stability studies. This is particularly true for a drug candidate that is considered very unstable, as in this case the stability of the candidate drug would be a critical issue and must be assessed routinely and quickly during early development. Recently, Accelerated Stability Assessment Program (ASAP) (Waterman et al., 2007) has been demonstrated to be a useful tool for prediction of drug chemical stability in a short period of time with reliable accuracy and precision. In this chapter, ASAP was applied to predict the stability of an unstable active pharmaceutical ingredient (API), which was eventually confirmed by long-term stability data, and to conduct comparative stability predictions of various prototype formulations to enable quick selection of stable formulations for early clinical studies. These quick predictions not only provided the insight into the possible retest period of the API, but also served as a quick decision-making tool during process and formulation development of the unstable candidate drug.