White Paper: Monitoring Trihalomethanes In Pharmaceutical Water Using A Direct Conductometric TOC Analyzer

By Terry Stange, Ph.D., Vice President Research and Development, Hach Ultra Analytics

With thousands of units installed worldwide in pharmaceutical manufacturing plants, Hach Ultra's ANATEL Total Organic Carbon (TOC) analyzers have become the industry standard for monitoring Purified Water (PW) and Water for Injection (WFI) systems. ANATEL TOC analyzers are designed specifically for use in PW and WFI applications where accuracy and stability are critical parameters for daily process monitoring of water distribution systems. The need for accuracy and stability drove Hach Ultra's decision to use direct conductometric (DC) technology, self-calibrating conductivity circuits, and dynamic endpoint detection to measure on-line TOC. While Hach Ultra pioneered the application of membrane conductivity (MC) for TOC measurement in the mid-80's, this technology was abandoned for use in on-line PW and WFI applications due to the inherent instability of membrane-based TOC analyzers. MC-based analyzers suffer from continuous drift and instability owing to the constant change in CO2 transfer rates across the membrane in real-world, on-line applications. Variations in pH, temperature, membrane fouling, rouging, and dissolved gases (e.g. chlorine) all contribute to variations in CO2 transfer rates. These variations require frequent calibration of MC-based TOC analyzers compared to DC-based analyzers, which are much simpler to operate and maintain. DC TOC analyzers are based on the assumption that the only conductive species generated during UV oxidation is CO2 – an assumption rarely violated in today's advanced PW and WFI systems. When water conditions depart from normal ultra-pure water (UPW) levels (events also known as "excursions"), DC TOC analyzers like the ANATEL A643a and ANATEL PAT700 can alert facilities engineers to subtle water chemistry changes that are otherwise ignored by MC-based TOC analyzers.

This paper discusses the response of the ANATEL TOC analyzer to hypothetical trihalomethane (THM) excursions in an UPW system. The unique sensitivity of DC analyzers to the halogen ions created during oxidation of THMs can alert UPW engineers to potential excursions that might harm the water system components or even violate the EPA's requirements for total THMs in water used to manufacture pharmaceutical products. When incoming source water or UPW meets EPA requirements for THM levels, ANATEL TOC analyzers will never report a false positive TOC value. In the rare occurrence of THM excursions, the ANATEL analyzer becomes more than just a TOC analyzer – it also becomes a THM event monitor.