(438g) In silico Process Characterization of Drug Product Filling Operations: Predicting Quality Attributes from First Principles
AIChE Annual Meeting
2017
2017 Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Multivariate Modeling and Quality-by-Control Approaches for Pharmaceutical Processes
Tuesday, October 31, 2017 - 5:27pm to 5:49pm
As an alternative to empirical process characterization, we have developed a computational model which predicts process quality attributes â for instance flow rate, fill volume/weight, cavitation, droplet formation, and product concentration â from first principles of product dynamic properties, fluid dynamics, structural mechanics and control theory. Formulation of the model couples finite element and finite volume solutions to structural deformation and fluid dynamics in pinch valves, and leverages analytical solutions to ordinary differential and algebraic equations accounting for orifice and pipe flow as well as equipment control laws.
We present an application of the model to a Time/Pressure filling operation, including formulation, deployment as a software application, and development of a workflow for in-silico process characterization utilizing design space response studies, local sensitivity studies, and uncertainty analysis.