Changes to the 'Water Monographs' in the European Pharmacopoeia

Changes to the water monographs have been published in the European Pharmacopoeia (Ph. Eur. 12.3). The chapters concerned are Water for Injections (0169), Water, Purified (0008), and 2.2.44. Total organic carbon in water for pharmaceutical use.

Water for injections (0169)

The main change in Chapter 0169 is the replacement of the test for oxidisable substances by the total organic carbon (TOC) test in the section Sterilised Water for Injections (SWFI). The TOC test is considered state of the art and represents an important step towards international harmonisation, in particular with the USP.

In addition, adjustments have been made to the physical-chemical tests for water for injections in bulk. For the TOC test, explicit reference is now made to Method A in accordance with Chapter 2.2.44; the limit value has been revised from 0.5 mg/L to 0.50 mg/L, aligning it with the concentration of the standards used in the general chapter. In the conductivity test, a metrological clarification has been made in the section on system calibration: the permissible deviation refers to the expected conductivity value of the respective reference solution and not to the measured value. 

Water, Purified (0008)

The monograph Water, Purified (0008) has been adjusted in the course of the revision of the general chapter 2.2.44 Total Organic Carbon in Water for Pharmaceutical Use. The changes also affect purified water in bulk. For the TOC test, reference is now also made to Method A in Chapter 2.2.44; as with WFI, the limit value is specified as 0.50 mg/L instead of 0.5 mg/L. As with 0169, the description of the conductivity test is being amended: in future, the accuracy of the measurement will be based on the expected conductivity value of the reference solution. These changes primarily intend to clarify and harmonise the text without introducing any new content requirements. 

2.2.44 Total Organic Carbon in Water for Pharmaceutical Use

The general section 2.2.44 has been extended. Method B, which applies to sterilised water for injections (SWFI), has been added. This completely replaces the previous test for oxidisable substances for SWFI with the TOC test. This change is relevant from a regulatory perspective, as it clearly aligns with USP requirements.

It should be noted that Method B specifies container-dependent TOC limits: different acceptance criteria apply depending on the container size, with a total of three limits defined.

In addition, the reagents sucrose R and 1,4-benzoquinone R used to date will be replaced by chemical reference substances (CRSs). This change is primarily intended to simplify the process and enable the use of USP reference standards; however, it has a significantly lower practical impact compared to the introduction of Method B.

The revised monographs will come into force on 1 July 2026.