T4 Report evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test

Nina Hasiwa, Mardas Daneshian, Peter Bruegger, Stefan Fennrich, Astrid Hochadel, Sebastian Hoffmann, Felix E. Rivera-Mariani, Christoph Rockel, Stefanie Schindler, Ingo Spreitzer, Sandra Stoppelkamp, Kranthi Vysyaraju, Thomas Hartung

Research output: Contribution to journalArticlepeer-review

Abstract

Threats of pyrogenicity were discovered more than a century ago. Measures to determine the safety of parenterals and, more recently, medical devices and cell therapies for human use have been in place for 70 years. Currently, there are three testing possibilities available: the Rabbit Pyrogen Test, the Limulus Amebocyte Lysate test (Bacterial Endotoxin Test), and test systems using human whole blood or human monocytes, called Monocyte Activation Test (MAT). The MAT is based on the human fever reaction and thus most closely reflects the human situation. Unfortunately, regulations and testing guidelines are not fully harmonized, despite formal international validation. Furthermore, data showing that the MAT is capable of covering the totality of possible pyrogens relevant to humans were not included in the MAT validations of the last decade. For this review we collate evidence from published literature, unpublished data of our own, and results from the international validation study to show that there is overwhelming scientific evidence to conclude that the whole blood MAT reliably detects non-endotoxin pyrogens. Therefore, further validation exercises do not seem warranted.

Original languageEnglish (US)
Pages (from-to)169-208
Number of pages40
JournalALTEX
Volume30
Issue number2
DOIs
StatePublished - 2013

Keywords

  • Fungal immune stimuli
  • Gram-positive immune stimuli
  • Human whole blood
  • MAT
  • Non-endotoxin pyrogens

ASJC Scopus subject areas

  • Pharmacology
  • Medical Laboratory Technology

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