Testing the quality of pharmaceutical grade water is not only important for drug product quality and safety, but it is strictly enforced by regulatory bodies around the world such as the United States Pharmacopeia (USP). USP <643> was revised effective May 2021 to require packaged sterile water to have container volume-dependent TOC limits and system suitability concentrations. TOC is an important quality attribute that contributes to understanding water quality before use in critical applications.
TOC Limits for Pharmaceutical Water - What Changed?
Previously, sterile water had a standardized limit and system suitability concentration of 8 ppm. This concentration was applied regardless of container size. With the 2021 changes to USP <643>, the limit of TOC changed from a defined value of 8.0 mg/L C (8 ppm) to a variable limit determined by container volume. This testing procedure changed from a pass/fail limit test to a staged testing procedure.
Why Were the Changes Implemented?
If Bulk Water Meets TOC Conductivity Requirements, Why Would It Have to Be Tested After Packaging? When water is packaged, there is risk of organic impurities leaching from the packaging to the water. Different container size brackets help address the surface area-to-volume ratio differences. For example, low volume containers falling in the <5mL container bracket have higher surface area-to-volume than that of larger containers, leading to increased opportunity for leaching of organic impurities. Although bulk waters may have met acceptance criteria of USP <643>, this does not represent water quality following manufacturing of packaged water.
Is the Methodology or Technology Required Different?
The methodology for analyzing total organic carbon has not changed. All technologies must be able to discriminate between CO2 generated from oxidation and inorganic carbon that can be present in water samples prior to analysis.
Are New Standards Needed?
Are There New System Suitability Requirements for Sterile Water TOC Analysis? USP revisions for sterile packaged water require system suitability and acceptance criteria to be contingent on container volumes. Benzoquinone and Sucrose are still the required compounds; however, the concentrations have changed to reflect container volume size. With these changes, it is important to examine technology and procedures to make sure TOC testing is up to regulatory expectations. The Sievers M9 can fully support these changes with analytical range, accuracy, precision, and data integrity. Furthermore, Sievers has outlined the recommended protocol configurations to easily help users with analysis. More details are provided in this article here.