Initial Exploration on the Application of the MoCMC Approach for Determining In Vitro Product Comparability.

purposeTo provide an initial assessment of the Matrix of Chemistry, Manufacturing and Control (MoCMC) approach for evaluating product physicochemical (Q3) similarity as part of the bioequivalence assessment of products containing non-systemically absorbed drugs. METHODOLOGY: Each Q3 parameter was expressed as the radius of a polygon using a mathematical formula that converted each specified reference Q3 parameter mean to a value of "5". That formula was applied to the corresponding individual test and reference product Q3 parameters, and the areas of the resulting treatment polygons were determined. The ratio of product area/outer area [Matrix Comparability Index (MCI)] was calculated where each side of the outer polygon had a radius of "10". When generated across multiple lots per treatment, the MCI values were statistically compared. Both actual (from our previously published investigation) and hypothetical MCI values were used to characterize the performance of the MoCMC across a range of situations.

resultsThe influence of any individual Q3 parameter decreased as the number of radii increased. The ability to identify statistically significant product differences decreased as variability of either test or reference MCI values increased. Nevertheless, by combining statistical analysis with a comparison of the spread of test and reference MCI values, the MoCMC identified product differences previously not detected by in vitro dissolution profiles alone.

conclusionsThe MoCMC can serve as a tool for comparing products containing non-systemically absorbed drugs. However, statistical refinements are needed when applying this approach to an evaluation of product bioequivalence. The latter is under development.