Online Monitoring of TOC Contaminations in Cleanin-Place Processes for Optimized Process Control, Increased Process Efficiency and Quality

Abstract

A Process Analytical Technology (PAT) compliant unit (acronym PATOV) was designed for online monitoring of Clean-in-Place (CIP) processes used in the pharmaceutical and food industry. The PATOV unit tends to significantly optimize CIP processes by online monitoring Total Organic Carbon (TOC) equivalent contaminations in the CIP off-stream to increase the efficiency and the quality of the cleaning process. The data will be used for an online control of the process to ensure optimal cleaning in minimized time. This will certainly allow for extensive savings of energy, water, and cleaning agents. Commercially available TOC analyzers qualified for the purpose require several minutes to provide a reliable TOC result. By implementing a mid-IR laser absorption technology, more precise a sensor based on an External Cavity-Quantum Cascade Laser (EC-QCL), the necessary information can be gained within seconds. An experimental CIP pilot plant was installed to reproduce CIP procedures by cleaning a vessel of a typical size used in pharmaceutical production processes. A continuous sample flow is gathered from the CIP offstream and fed into the PATOV unit which is placed close to the CIP pilot plant. The contamination of the CIP process water can be measured with a time resolution down to one second. The retention time of contaminations from the CIP pilot plant to the PATOV unit was minimized to <10 s by the design of an optimized sampling system. Currently, the TOC can be detected within the short timelines mentioned for single contaminants down to a concentration of e.g. 20 ppm for glycerol. Provided that the detection of lower concentrations and the calibration for other model contaminants, such as xanthan and proteins can be achieved, the PATOV unit has a high potential to improve the efficiency and the quality of CIP processes in the pharmaceutical and food industry.