title: A comparison of the analysis of covariance (ANCOVA) and range-based approaches for assessing batch-to-batch variability of the stability of pharmaceutical products.
abstract: Stability data were generated by the Monte Carlo method, and batch-to-batch variability was evaluated by analysis of differences in slope and intercept according to the analysis of covariance (ANCOVA) approach recommended in the FDA Guidance. Using the same generated data, batch-to-batch variability was also evaluated by assessing the equivalence of shelf lives estimated for individual batches based on the range (Range-based approach) in order to compare the ability of the two approaches to detect stability differences among batches. The results of the study indicated that the Range-based approach can detect a 30% difference in the slope of degradation curves among batches with a similar beta error as the ANCOVA approach, provided that degradation data are obtained with assay errors below 0.5. The range-based approach appears to be useful as an alternative method to ANCOVA, if it is modified such that the variance of estimates is taken into account.
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyop, Japan. yoshioka@nihs.go.jp
authors.forename: Sumie
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Yukio
authors.initials: Y
authors.lastname: Aso
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kojima
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Cappuccino
mesh_terms: D000704:Analysis of Variance; D003627:Data Interpretation, Statistical; D004345:Drug Industry; D004355:Drug Stability; D009010:Monte Carlo Method; D014481:United States; D014486:United States Food and Drug Administration