PharmEuropa - Revision of Chapter 2.6.30 Monocyte Activation Test

Recommendation

25-27 June 2024
Munich, Germany

European Microbiology Conference 2024

As early as the mid-1990s, Hartung and Wendel issued publications on the whole blood pyrogen test as a possibility for testing for pyrogens. Subsequently, various groups worked on establishing methods based on the activation of monocytes in practice and achieving applicability in routine. By 2010, the three MAT methods A (quantitative test), B (semi-quantitative test) and C ("reference lot comparison test") had crystallised.

At the end of 2009, the EMA Guideline "Replacement of rabbit pyrogen testing by an alternative test for plasma derived medicinal products" came into force, and in 2010 the MAT was introduced into the European Pharmacopoeia (Ph. Eur. 2.6.30) as an alternative to the rabbit test. In 2014, there was a revision of chapter 5.1.10. of the Ph. Eur. on testing for bacterial endotoxins and in 2017, there was a revision of MAT chapter 2.6.30.

Current development

However, even today the development of alternative methods continues and the corresponding monographs are also revised again and again. Accordingly, the EDQM has currently published a revision of Chapter 2.6.30 Monocyte Activation Test in Pharmeuropa 34.2 with a public deadline of 30 June 2022.

As an example, the previously differentiated methods A, B and C disappear. Methods A and B have been combined into a single semi-quantitative test called "Method 1". Method C is now referred to as "Method 2".

In addition, regarding concentrations and product dilutions, a new section has been added that provides recommendations on how to present endotoxin-equivalent concentrations in the MAT and explains how the use of per-sample or per-assay concentrations affect the reported sensitivity value of the assay.

The EDQM also notes that: "This revision is also part of a wider effort to remove the rabbit pyrogen test from the Ph. Eur. which will be announced in a forthcoming issue of Pharmeuropa:" (also see the EDQM newsroom report entitled European Pharmacopoeia to put an end to the rabbit pyrogen test). In this context, references to the rabbit pyrogen test have been removed from the introduction and from the guidelines.

Further details on the revision can be found, after registration, on the Pharmeuropa website.