Novel Methods Developed in Bioequivalence Assays: Patent Review

Abstract

This study examines advancements in bioequivalence (BE) assessment methods, with a focus on in vitro-in vivo correlation (IVIVC) and dissolution testing technologies. A systematic patent search was conducted via Espacenet, following PRISMA criteria and the study objectives, revealing 216 relevant patents, of which 28 were selected based on their contributions to novel BE methodologies. Analysis indicates a rapid increase in patent filings from 2021 to 2022, with a significant concentration of contributions from China. Key innovations include enhancements in dissolution testing apparatus, application of physiologically based pharmacokinetic (PBPK) modeling for IVIVC, and advanced statistical approaches for BE assessment. In dissolution testing, ƒ1 and ƒ2 factors remain essential metrics for assessing similarity, especially in solid oral dosage forms. These innovations enhance the efficiency (streamline) of BE evaluations, optimizing the biowaiver process and minimizing the need for extensive clinical trials while ensuring greater precision and reliability. The dissolution test, particularly when combined with PBPK models, allows for predictive evaluation of formulation changes and population-specific responses, fostering efficiency in drug development. Overall, these novel BE assessment approaches provide a framework for regulatory compliance, cost-effective production, and assurance of therapeutic equivalence in generic formulations. While they may not always be implemented in practice, they contribute significantly to innovation in the field, driving advancements in bioequivalence evaluation. This review highlights the evolving landscape of BE and IVIVC methodologies and underscores the importance of incorporating innovative testing approaches to advance pharmaceutical science and regulatory practices.

Graphical Abstract