A model-based strategy for the selection of the critical process parameters in integrated continuous pharmaceutical manufacturing [Extended abstract]

<p>The implementation of Quality-by-Design (QbD) for integrated multistage continuous pharmaceutical processes is hampered by several challenges such as the inherent large sets of interactive or correlated process parameters, which may impact the critical quality attributes (CQA) of the drug products. A novel approach is proposed to help select the minimum set of critical process parameters (CPP) leading to more design spaces that minimize risks and deliver built-in quality assurance for drug safety and efficacy. To help rank the process parameters and identify a cut-off threshold for the CPP, two methods are proposed and compared. The first method is based on the global estimability analysis (GEA) and the second on the analytical hierarchy process (AHP). The approach is validated using a plant-wide model of a multistep integrated reaction, crystallization, and wash-filtration continuous manufacturing of ibuprofen.</p>