Changes in Testing for Nitrate and Endotoxins in pharmaceutical Waters in the European Pharmacopoeia

In the Ph.Eur. Supplement 11.4, the EDQM announces the deletion of the test for nitrate in Water For Injection (WFI) and Purified Water (PW) if the test for conductivity meets the pharmacopoeial requirement for WFI. In addition, a change in the test for endotoxins is pending. The changes affect both the monograph for Water for Injection (0169) and the monograph for Purified Water (008).

The nitrate test can be omitted (PW & WFI)  in future if the conductivity requirements for WFI are met. This change is the long-awaited harmonisation with the US Pharmacopoeia USP, in which the nitrate test was dropped years ago.

In future, the use of recombinant factor C (rFC) will be permitted for testing for endotoxins. This is a logical step after the new general chapter 2.6.32 already became effective in January 2021, which describes a bacterial endotoxin test (BET) that can be used as an alternative to the classical Limulus amebocyte lysate (LAL)-based methods for quantifying endotoxins from Gram-negative bacteria. Unlike LAL, rFC is a synthetic reagent that is not based on lysate from horseshoe crabs, which are considered endangered in some parts of the world.

The amendments were adopted by the Ph. Eur. Commission as early as March 2023. They will be published in Supplement 11.4 of Ph. Eur. (October 2023). The amendments will come into force on 1 April 2024.