Proposed non-animal derived reagent Chapter published

Chapter <86> Bacterial Endotoxins Test Using Recombinant Reagents, proposed by the USP Microbiology Expert Committee, is now published as a General Announcement. This is in advance of the official open comment period, according to USP. Comments are welcome from 1 November 2023 to 31 January 2024.

The new standard was proposed by the committee earlier in 2023. This was based on the its evaluation of whether animal-free reagents could be used in addition to current methods for endotoxin testing utilising animal-derived reagents.

This new chapter includes methods for using several reagents, including recombinant Factor C (rFC) and recombinant cascade reagents (rCR). It offers information for manufacturers of new and established biopharmaceuticals on ways to incorporate them into their quality testing.

Information included in the proposed Chapter <86> Bacterial Endotoxins Test Using Recombinant Reagents

• The user’s responsibility for reviewing a supplier’s primary validation package
• Product suitability verification for use in testing products or materials (referencing <1226> Verification of Compendial Procedures)
• The possibility that regulatory authorities may require supplemental data prior to acceptance.

According to USP, <86> Bacterial Endotoxins Test Using Recombinant Reagents will be published in Pharmacopeial Forum 49(6) [Nov.–Dec. 2023]. This revision proposal will include methods for recombinant Factor C (rFC) and recombinant cascade reagents (rCR).

In a recent publication in the Pharmacopeial Forum 45(5) [Sep.-Oct. 2019], the USP Microbiology Expert Committee proposed the inclusion of recombinant factors for endotoxin testing in chapter <85> Bacterial Endotoxins Test.

The USP’s committee went onto cancel this proposal, based on public comments. A separate informational chapter was developed to expand on the use, validation, and comparability of endotoxin tests based on recombinantly derived substances.

The proposed informational chapter <1085.1> Use of Recombinant Reagents in the Bacterial Endotoxins Test – Photometric and Fluorometric Methods Using Recombinantly Derived Reagents was published in the Pharmacopeial Forum 46(5) [Sep.-Oct. 2020]. It was cancelled by the USP Microbiology Expert Committee, again based on comments that were received.

Determining accurate estimation of true endotoxin concentration