In-line UV Spectrometry Monitoring in Cleaning Validation

Biopharmaceutical manufacturers rely heavily on non-specific at-line analytical testing to confirm cleanliness of equipment surfaces through final rinse water analysis, potentially leading to false positives and problematic on-line or off-line testing. Spectroscopy methods such as ultraviolet (UV) spectroscopy at 220 nm can be used for continuous, in-line monitoring of the cleaning process. The sensitivity of the method can be improved by adjusting the sanitary flow path length. Interference and enhancement testing was performed using a formulated alkaline and acid cleaner, and common biopharmaceutical process residues (such as monoclonal antibody (mAb) drug substances, insulin drug product, and bovine serum albumin (BSA) which displays a cumulative effect like in total organic carbon (TOC) analysis. The in-line monitoring capability of UV spectroscopy enables continuous monitoring of the entire cleaning cycle and applicability to Quality by Design (QbD), Process Analytical Technology (PAT), process digitalization, and sustainability goals of a Pharma 4.0 manufacturing facility.