Endotoxin testing milestone reached with European Pharmacopoeia’s animal shift

Pyrogen testing in Europe is moving into a new era after the removal of the rabbit pyrogen test (general chapter 2.6.8. Pyrogens) from European Pharmacopoeia (Ph. Eur.) texts at the turn of the new year.

From 1 January 2026, pharmaceutical manufacturers will need to use advanced alternatives such as the monocyte-activation test or the bacterial endotoxins test (BET) instead of animal-based testing methods.

Use of either of the two newer approaches should be based on the specific risks of the substance or product containing non-endotoxin pyrogens, with individual method choices to be guided by risk assessment and suitability under Pyrogenicity (5.1.13).

The monocyte-activation test and BET both come with sustainability benefits, given that pharma manufacturers in the EU will no longer need to rely on animal-based testing methods that use limited natural resources like the horseshoe crab.

The Ph. Eur. has included recombinant Factor C (rFC) in Issue 13.1, making it one of the seven alternative methods chosen for BET (general chapter 2.6.14).

New technologies such as recombinant Cascade Reagents (rCR) are not yet included in the Ph. Eur., however the European Pharmacopoeia Commission (EPC) is promoting data generation for future consideration of its use.

A free joint symposium in February is being held by the EDQM and the European Partnership for Alternative Approaches to Animal Testing (EPAA) to support industry stakeholders. The session will discuss the roadmap and global approaches for this transition.

Alongside modernising its texts, Ph. Eur. continues to update and add new monographs and general chapters to its archive, including those focused on critical medicines. Last month the industry body published its first monoclonal antibody (mAb) medicinal product monograph with addition of the IgG1-antibody based TNF-alpha antagonist, Golimumab injection (3187). It will be enforced on 1 April.