Exploring the Application of the MoCMC System for Determining In Vitro Product Comparability

Purpose To explore the utility of the Matrix of Chemistry, Manufacturing and Control (MoCMC) approach for evaluating product physicochemical (Q3) similarity as part of a product bioequivalence assessment. Methodology Each Q3 parameter was converted to a radius of a polygon using a mathematical equation that converted each reference Q3 parameter to a value of “5”. That equation was applied to the corresponding test product Q3 parameter and the areas of the treatment polygons determined. The ratio of the product area/outer area [Matrix Comparability Index (MCI)] was calculated using an outer polygon with each radius = “10”. When generated across multiple lots for each 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. Results MCI values successfully captured product Q3 differences, with the influence of any Q3 parameter decreasing as the number of radii increases. The ability to identify statistically significant product differences decreased as variability of either test or reference MCI values increased. By combining statistical analysis with a comparison of the spread of test and reference MCI values, the MoCMC provided a sensitive tool for assessing product comparability and identified product differences previously missed by comparing in vitro dissolution profiles alone Conclusions While the impetus for this research was to identify a tool for supporting the evaluation of product bioequivalence containing locally acting drugs, its strengths support its potential use across a wider scope of situations.