Structure-Function Relationships in Lyophilized Biologics for Stability Prediction

This will be the 2nd presentation in a 2hr session called: Emerging challenges in Developing Biologics: Charting the Course from Discovery to Clinical Applications. Haichen Nie Ph.D. (community chair for excipients) who organized this session will be the moderator for this session.

brief description: Lyophilized biologics offer the promise of enhanced stability and extended shelf life, critical aspects for the delivery and effectiveness of therapeutic proteins. However, predicting stability for these freeze-dried preparations remains a formidable challenge. A central concern is the intricate molecular architecture of biologics, where even subtle structural changes, often undetectable by conventional analytical methods, can profoundly affect stability. The impact of different excipients, such as bulking agents, cryoprotectants, lyoprotectants, and buffering agents, introduces another layer of complexity. These excipients, vital for the lyophilization process and product reconstitution, can have diverse, sometimes unpredictable, effects on biologic stability. A pivotal factor, often overlooked, is the role of residual water post-lyophilization. Its interaction with biology is intricate and varies among different molecules, making universal predictions elusive. Advanced, high-resolution analytical techniques are urgently needed to bridge this knowledge gap, enabling the detection of nuanced structural changes and their implications for stability. This presentation will focus on the application of advanced analytical techniques for predicting the stability of biologics formulations in the solid state, including methods to non-destructively determine water content in vials containing lyophilized and other solid-state biologics. As the field advances to meet the rising demand for biologics, understanding the interplay of structure, function, and stability in lyophilized preparations will be paramount for ensuring both drug efficacy and patient safety.