Current work presents Sanofi’s approach to manufacturability evaluation using material sparing approach for flow (~0.5cc) and tablettability (~25cc) assessment. Our methodology leverages bond number-based predictive model to evaluate processing risks in powder flowability and mixing rules to evaluate powder tablettability. By establishing cross-functional teams integrating drug substance, crystallization, and drug product development expertise, we incorporate particle engineering directly into formulation design. The predictive models analyze critical material attributes including particle size distribution, true density, and surface energy to assess manufacturing risks before committing to pilot-scale production. We are expanding this framework to investigate solid state properties, specifically the impact of percent crystallinity on formulation performance and the risk of process-induced solid form transformations during manufacturing. This characterization approach will comprehensively evaluate formulations developed at early stages for manufacturability in dry granulation and direct compression routes.
In this workflow the predictive model along with material sparing techniques are used as a process characterization tool represents a shift in pharmaceutical development, allowing earlier decision-making, reduced drug substance consumption, and more efficient transition to continuous manufacturing platforms—ultimately accelerating drug development timelines while maintaining quality standards.
Author Disclosure: All authors are Sanofi employees and may hold shares and/or stock options in the company.