The quantification of excipients and surfactants in final drug products (DP) poses significant challenges due to the limitations and inefficiencies of current off-line analytical techniques such as HPLC-CAD and LC-MS. This presentation demonstrates the potential of in-line and at-line Process Analytical Technology (PAT) solutions that leverage advanced spectroscopic methods and modeling techniques to facilitate rapid and accurate measurements of various excipient and surfactant components. In this work, we focus on a common formulation surfactant used in the stabilization of monoclonal antibody (mAb) drug products, and its interaction with polyethersulfone (PES), polyvinylidene fluoride (PVDF), and other membrane filters during final filtration operations. Using Raman spectroscopy, we characterized the non-specific binding of the surfactant to these membranes, a critical factor for ensuring the appropriate concentrations and distribution of surfactants in final drug product containers. Leveraging an FPLC (fast protein liquid chromatography) system for automated filtration and fractionation, in-line Raman spectra were generated along with corresponding offline reference samples to build robust calibration and validation sets for model development. This adaptable approach not only enhances the understanding of surfactant behavior but also supports the implementation of real-time monitoring during manufacturing processes, ultimately contributing to improved product quality and compliance with release criteria.
