Approaches to supply bioequivalent oral solid pharmaceutical formulations through the lifecycles of products: Four-media dissolution monitoring program in Japan

The continuous supply of pharmaceutical formulations therapeutically equivalent to the clinical batches used during development is important to ensure their safety and efficacy. The development of new generic drugs and the postapproval changes of the formulations (e.g., dosage form, dose strength, and composition) and manufacturing (e.g., facility and ingredient) require bioequivalence tests following the appropriate guidelines. Maintaining the formulation performance in the commercial production phase is often more challenging due to multiple manufacturing and stability factors affecting dissolution. A case of a product out of the bioequivalence range between batches in a post-marketed human study emphasized the risk. This minireview introduces multiple approaches to prevent significant bioinequivalence between batches and products through their life-cycles, focusing on a periodical dissolution-monitoring program using four media (acidic, intermediate, neutral, and water) in Japan. Setting the same procedure to monitor one of the complex critical quality attributes should efficiently reduce patient risk complementarily with appropriate specifications and GMP manufacturing.