Endotoxins Testing: Potential Change for WFI and Steam in the USP

In Pharmacopeial Forum (PF) 52(1), January 2026, the USP proposes to add an alternative endotoxins test: <86> Bacterial Endotoxins Test Using Recombinant Reagents, alongside the classical <85> Bacterial Endotoxins Test. If adopted, this could affect, among others, the monographs for Water for Injection, Sterile Water for Injection, Water for Hemodialysis, Pure Steam and other sterile waters. The endotoxins limit would remain unchanged.

Monograph <86> is based on animal-free, recombinant reagents and is already official in the USP. The proposed change would, for the first time, allow the specific application of <86> in USP water monographs. However, this requires product-specific verification by the user, including assessment of the supplier's primary validation data and internal suitability tests. For the selection of verification experiments, reference is made to <1226> Verification of Compendial Procedures. Regulatory authorities may request additional data, such as comparative studies between <86> and <85>.

The proposal is open for comment. If accepted, the use of <86> could be included in the relevant USP water monographs in 2027.

Pharmacopeial Forum (PF) is a free, bimonthly online publication in which the USP posts proposed revisions to the USP-NF for public comment (registration required).