Design of a reliable control strategy for a continuous wet granulation manufacturing unit for Oral Solid Dosage Forms

Abstract

For my thesis, I had the opportunity to work in the Dry Forms Production department of UCB ("Union Chimique Belge", Belgian Chemical Union). During my stay, the company was building a new module centered around a Continuous Wet Granulation technology. The goal is to implement real-time release production of the drug. This means that the characteristics of the product have to be known in real-time. UCB plans to reach this goal step by step using a "Quality by Design" (QbD) approach for the process development. The objective of this control strategy is that the quality of the product should be built-in by understanding the product and the process which manufactures it. Also, the quality of the equipment used to manufacture the process should be ensured, both at the design stage and during production. First, the product’s "Target Product Profile" is defined. It is a list of the properties in the final product that ensure its quality. The link between the drug’s QA and a list of possible risks is then established iteratively. This list is first created based on theoretical knowledge and prior knowledge and then refined by making experiments. It will be used to choose how to monitor the Critical Process Parameters (CPP) and intermediate product Critical Quality Attributes (CQAs) which were deduced from the quality attributes. After the Critical Process Parameters are defined, the design space is modelled from the correlation between the CPPs and CQAs. This design space will have to be created directly from the continuous wet granulation production line and will be used as the initial control strategy. Also, the equipment should be designed to ensure that the quality of the product is maintained at any process step. Finally, the equipment and environment should be assessed and controlled to limit any possible quality risk to the product.