A Biopharmetrics Approach for Drug Product Quality Control with Clinical Relevance.

To exemplify a systematic and quantitative approach (Biopharmetrics approach) for product quality control with clinical relevance, the study utilized multivariate models to connect raw material attributes of a product to its dissolution obtained in a DOE (design of experiment) and further extended the connection to the in vivo exposures (AUC and Cmax) of the product using an available IVIVC (in vitro/in vivo correlation). Thus, a model for the relationship between in vivo exposure and raw material attributes of the product was established. Based on the model, the exposure ratios between future batches (with various raw material attributes) and the pivotal clinical batches (with confirmed clinical efficacy and safety) were predicted resulting in a set of contour lines in a graphical representation. Among these contour lines, the lines for exposure ratios of 0.8 and 1.2 were defined as lower and upper limits. With the failure edges defined, clinically meaningful limits for the raw material quality control were specified. If the raw material attributes in the future production conform to the specifications, the manufacturing would lead to products bioequivalent to the clinical batches. From these exercises, Biopharmetrics, a subdiscipline of biopharmaceutics, was introduced and its definition, scope, and characteristics were discussed.