Pyrogen Testing by Monocytes Activation Test

What is the Monocyte Activation Test?

The Monocyte Activation Test (MAT) is a human blood cell-based in-vitro assay designed to test parenteral drugs, biologics, and medical devices for all classifications of pyrogens.

How does the Monocyte Activation Test work?

• The parenteral is incubated in human blood peripheral monocytes
• The monocytes immune system is activated
• Quantification of cytokine concentration
• Endotoxin equivalent calculation

Where does the Monocyte Activation Test apply according to Ph.Eur.?

• While for 100 years the Rabbit Pyrogen Test has been the gold standard for pyrogen testing, regulatory bodies like the European Pharmacopeia (Ph. Eur.) are now mandating the transition towards in-vitro alternatives – specifically recommending the Monocyte Activation Test where possible and after product specific validation (Ph. Eur. Chapter 2.6.8.).
• For products employing Bacterial Endotoxin Testing (BET) as a release assay, the Ph. Eur. Chapter 5.1.10 stipulates that the risk of non-endotoxin pyrogenic substances must be assessed and ruled out while the product's production process is being established, or upon batch release once it has been established by way of a Monocyte Activation Test.

Applications of the Monocyte Activation Test

• Replace Rabbit Pyrogen Test (RPT) with Ph. Eur.'s in-vitro replacement.
• Test medical devices by direct incubation where Baceterial Endotoxin Test (BET) or Rabbit Pyrogen Test (RPT) fail.
• Overcome low endotoxin recovery (LER) effects.
• Test products with lowest Contaminant Level Concentrations (CLCs) thanks to the implemented MAT method with 0.004 EU/mL LoD.

Implementation of alternative methods

• CellMade^TM Laboratories selects alternative methods from trusted suppliers.
• The implementation process of a novel compendial method within our laboratory is performed according European Pharmacopoeia 10th edition, 10.6, General Notices, Section 1.1.2 Compliance with the Ph. Eur., January 2022. The method verification report(s) and data are available under the Resources Centre of this website.

Proficiency tests

• CellMade^TM Laboratories regularly participates in international proficiency tests organized by recognized companies and institutions.
• The results of the proficiency test(s) are available under the Resources Centre of this website.

Below table summarizes the available testing services using MAT.