Tecnologie per il monitoraggio in tempo reale dell'aggregazione di proteine nel processo di produzione di farmaci = Process Analytical Technologies for the real-time detection of protein aggregation during pharmaceutical manufacturing

The manufacturing of biopharmaceuticals can be challenging as of the preservation of the Active Pharmaceutical Ingredients (API). In fact, the various processing steps may cause different levels of denaturation and hence aggregation, resulting in massive loss of product. Currently, the aggregation phenomena are detected through off-line procedures which can take up to days and, thus, incompatible with the implementation of corrective actions on the manufacturing process to preserve the API integrity. In this thesis project, various Process Analytical Technologies (PAT) are compared for the online and inline detection of the protein aggregation during the manufacturing process. This analysis was carried out upon two model products, identified within the GSK portfolio. These model products were stressed by exposure to high temperatures or air/liquid interfaces, and an appropriate calibration curve was determined so as to obtain a quantitative estimation of the API aggregation. This curve was used to produce samples with known and controlled aggregation levels, which then will be used to test the various PATs object of investigation. Among the various PATs, the NIR spectroscopy resulted as the most accurate and reliable technology for the online estimation of the API aggregation.