Pyrogenic response testing is a requirement for assessing the safety of products that have direct or indirect contact with blood circulation, lymphatic system and cerebrospinal fluid.
Lab4LIFE, a company of the COMPLIFE group, has recently accredited ISO 17025 the Monocyte Activation Test (MAT) method for the safety verification of injectable products.
This type of test is considered as a substitute for the in vivo test, for all medicinal substances and for MD constituted by substances and can detect the presence not only of bacterial endotoxins, but also the presence of material mediated pyrogens.
In the European Pharmacopoeia it is already recommended, where possible, to use the MAT method instead of the in vivo method. (Ref. EU Ph. 2.6.8) The choice must therefore fall on the in vitro method that our laboratories have already accredited.
[In vitro Method Reference Standard: EU PHARMA 01/2021:50110 + 07/2017:20630]
Monocyte Activation Test (MAT) – Pyrogens
WHAT IS IT ALL ABOUT?
The Monocyte Activation Test (MAT) allows detection of the full range of pyrogens, including endotoxins and non-endotoxin pyrogens (NEP), using human monocytic cells that reproduce the cytokine activation cascade, such as IL-6. Cytokines are then detected using an immunological method (ELISA TEST).
Until now, the only method to determine the presence of material mediated pyrogens, potentially very dangerous, was rabbit testing according to USP <151> or according to EU Ph. 2.6.8.
This test, in addition to being bloody, is not suitable for testing products that are not intended to be injected into the venous circulation, for example fillers for aesthetic medicine.
The Monocyte Activation method can instead be applied to all MDs made up of substances for which it is necessary to evaluate this endpoint (ISO 10993-11), but also to pharmaceutical products intended for injection.
WHAT ARE PYROGENS?
Adverse reactions to parenteral preparations were described as early as the late nineteenth century, often referred to as “injection fever”. The first agents that cause fever, the “pyrogens”, were identified in 1912 by Hort and Penfold, who were also the first to design a pyrogen test based on the injection of material into rabbits.
Pyrogenic agents may consist of endotoxins produced by Gram- bacteria that may contaminate parenteral products (medicines /medical devices). These agents are identified and quantified by LAL tests, but this method is not able to identify the material mediated pyrogens that are substances capable of stimulating a pro-inflammatory response of cytokines TNFα, IL-1β, IL-6, and INF-y.
Such substances may consist of contaminants of various kinds such as prostaglandins, heavy metals, nanomaterials, debris, etc. The characteristics that make a substance a pyrogen are not yet completely clear, for this reason it is a particularly insidious danger (more information see ISO/TR 21582:2021).
FOR INFORMATION ON THIS INNOVATIVE TEST METHOD AND TO TELL US ABOUT YOUR PROJECT CONTACT OUR TEAM.
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