Total organic carbon test (TOC) to replace test for oxidisable substances in sterile water for injection?

The experts of the European Pharmacopoeia (Ph. Eur.) are considering replacing the test for oxidisable substances by the test for total organic carbon (TOC) in the Tests section of the “Sterilised water for injections” part of the monograph on Water for injections (0169). This change has been discussed with other pharmacopoeias (United States Pharmacopeia – USP, Japanese Pharmacopoeia – JP) and is already implemented in one of them.

The USP is working on harmonising the monograph for sterile WFI with Ph. Eur. and JP, focusing on the test point TOC. The USP already replaced the test for oxidisable substances for sterilised WFI with a TOC test some years ago, but not with a limit of 500 ppb. The USP limit varies, starting at 8 ppm (ppm) and increasing depending on the volume of the container. This is because containers and the installation process can add TOC. Larger containers have lower TOC limits. Small dosage forms (e.g. water for reconstitution of an injection) have a higher TOC limit.

The experts of the Ph. Eur. would like to gather information from manufacturers, before the official consultation phase, to make sure that the method and acceptance criteria envisaged in the discussions with partner pharmacopoeias would be appropriate and feasible for European manufacturers of sterilised water in containers. The survey consisting of 12 questions on the conversion of the test for oxidisable substances to TOC for sterilised water in containers can be found on the EDQM website.