(168c) Partial-Least-Squares Based Analysis to Manage Risks Identified for a Fluid Bed Wet Granulation Operation

An important step at the outset of any pharmaceutical process development is the process risk assessment that identifies the process variables carrying a higher risk towards the product quality attributes. Throughout the development phase, data is gathered to mitigate the risks. For this purpose, it is important to obtain a holistic understanding of the process while evaluating the importance of each variable (considered in the risk assessment) towards influencing the product quality.

This work presents a case study on a risk driven development of a fluid bed wet granulation operation followed by compression for making the tablets (drug product). The parallel mechanisms of fluidization, granulation and drying are coupled and dependent on one another that makes fluid bed wet granulation a complex process. In this study, multivariate perturbations via changing material properties and operating conditions were explored. A partial-least-squares model developed from the experimental data was used to evaluate the failure modes on the tablet critical quality attributes for more insight into what variable combinations could result in such situations. Finally, the conclusions from the partial-least-squares model were used to eliminate/manage some of the identified risks.