USP Revises the Pharmaceutical Water Monographs

In September 2026, the USP published numerous revisions to the water monographs on the USP-NF website. The monographs affected are <1231> Water for Pharmaceutical Purposes, Water for Injection, Bacteriostatic Water for Injection, Sterile Water for Inhalation, Sterile Water for Injection, Sterile Water for Irrigation and Pure Steam. The new monographs will become official on 1 April 2027.

Although the list is long, the actual changes are limited in scope. The main change is the inclusion of an additional option for endotoxin testing. This was already proposed in PF 52(1) in January 2026 and now permits the use of Bacterial Endotoxins Test Using Recombinant Reagents <86> as an alternative to the conventional LAL test under <85>. The endotoxin limit remains unchanged.

The changes to the overarching monograph <1231> Water for Pharmaceutical Purposes are mainly editorial, but content from FAQs published by the USP on its website in recent years has also been incorporated. Although these FAQs are not an official part of the monographs, they serve as a practical supplement to reach industry and other stakeholders quickly and efficiently. The additions cover, among other things, sampling for chemical impurities compared with microorganisms, the handling of additives and potential risks such as nitrosamines. The aim is to provide users with better support in assessing and monitoring pharmaceutical waters.

With regard to chemical assessments, the text in <1231> has been expanded to provide greater clarity on testing and sampling. For example, it explicitly states that the Stage 1 test in USP <645> "Water Conductivity", although designed for online use, can also be performed offline. However, caution is required when performing a Stage 1 test offline: the ingress of CO2 can distort conductivity readings, making the resulting data unsuitable for trend analysis. The online Stage 1 test under <645> is therefore recommended, particularly for conductivity trending.

For sterile waters, e.g. Sterile Water for Injection, the new explanations in <1231> also provide insight into how the limits in USP chapters <643> "Total Organic Carbon" and <645> "Water Conductivity" are established. While the chemical limits for sterile waters are higher than the corresponding limits for bulk water, the rationale for these higher limits is now explained in greater detail.

The monographs are available on the USP website.