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Jun 4, 2014

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Multivariate Testing of the Similarity of Dissolution Curves (EU2018 104)

Level: Beginner
Piet Hoogkamer, Principal Analytical Scientist, Abbott Healthcare Products

Dissolution testing of pharmaceutical products is important, as it is a surrogate measure of in-vivo dissolution. In-vivo dissolution may affect the bio-availability, which may affect pharmacokinetics (blood levels) and, as a result, safety and efficacy. In case a change is proposed with respect to the formulation, manufacturing process or manufacturing site, “equivalence” needs to be demonstrated to obtain a bio-waiver. Similarity of curves may be tested using the mathematical f2 metric, where a value between 50 and 100 suggests similarity. The f2 metric will be explained in detail. However, in case the variability is too high (between tested units, within a time point), a multivariate distance-based statistic needs to be used instead. Some options will be shown for model-dependent and model-independent approaches. Use of JMP, both with standard functionality and with a dedicated script, will be illustrated for the Mahalanobis distance.