In-line Process Analytical Technology based on qualitative near-infrared spectroscopy modeling - An innovative approach for the pharmaceutical quality control

Due to the increasing competition in the pharmaceutical industry the cost effectiveness of manufacturing becomes more and more important. Process Analytical Technologies (PAT) are endeavored to increase the process understanding and thereby reduce the risk of producing poor quality. Furthermore, an integrated quality control shortens the process times being one of the main cost drivers. Accordingly it was attempted to replace the Karl Fischer titration of individual sealed vials of an established lyophilization process by a high-speed in-line near-infrared inspection of entire batches. Since a simple classification result is sufficient to test against a certain acceptance limit, a quantitative water determination was replaced by an innovative qualitative chemometric calibration. This reliable method was robust and fast but reduced the validation effort remarkably; however a threshold challenge was introduced as a new criterion.