Development of an In Vitro Release Test to Characterize Onivyde® Using Bio-Beads SM-2 Resin

The development of generic versions of Onivyde® (irinotecan liposome injection) requires a reliable and discriminative in vitro release test (IVRT) to ensure product quality and support regulatory approval. Conventional dialysis-based IVRT often is limited in maintaining sink conditions and is affected by membrane-related variability and batch inconsistency. To overcome these challenges, we developed an IVRT using Bio-Beads SM-2 Resin (BioBeads), which rapidly adsorb released free irinotecan via hydrophobic interactions. Key parameters, including BioBeads concentration, agitation speed and angle, temperature, and formulation concentration, were systematically optimized. Identified optimized conditions were 50 mg/mL BioBeads, vertical rotation at 10 rpm, 25°C, and an Onivyde® concentration of 45 µg/mL. Under these conditions, the method achieved > 90% drug release within 24 h with minimal liposomal disruption. Among all parameters, mechanical agitation had the greatest impact on release kinetics by promoting liposomal destabilization and cholesterol depletion. Using the similarity factor (f2) as a quantitative criterion, the method demonstrated high reproducibility and effectively distinguished between non-stressed and stressed formulations. Compared to dialysis-based approaches, this method more effectively maintains sink conditions, eliminates membrane-related diffusion limitations, and simplifies sample handling by avoiding separation steps. Overall, the BioBeads-based IVRT offers a practical, robust, and sensitive platform for accelerated release testing and quality control of liposomal irinotecan, with strong potential for use in generic drug development and regulatory evaluation.