Development validation and applications of the monocyte activation test for pyrogens based on human whole blood

Stefanie Schindler, Sonja Von Aulock, Mardas Daneshian, Thomas Hartung

Research output: Contribution to journalArticle

Abstract

Microorganisms such as Gram-negative or Gram-positive bacteria, viruses and fungi contain components that activate the innate immune system. These components, called pyrogens (Greek: pyros=fire), can occur independently of viable microorganisms and are a major safety concern in parenterally administered drugs, since they can cause severe reactions such as fever, organ failure, and shock in the recipient. So far these drugs have been tested by injecting them intravenously into rabbits and measuring their fever reaction or, alternatively, by the Limulus Amoebocyte Lysate (LAL) test, employing the coagulation of the hemolymph lysate of Limulus polyphemus. Both tests have inherent limitations. A new in vitro monocyte activation test (MAT) based on human whole blood, capable of measuring all pyrogens relevant to the human patient, introduced in this journal in 1995, was validated and recently accepted by European Pharmacopoeia and US FDA. This review describes its principle, development, validation and the wide spectrum of applications, such as for testing of medical devices, blood products, toxic or immunomodulatory drugs, dialysis liquids, lipidic parenterals, and air quality. This alternative method promises to replace the rabbit pyrogen test fully and to overcome several limitations of the LAL assay.

Original languageEnglish (US)
Pages (from-to)265-277
Number of pages13
JournalAltex
Volume26
Issue number4
StatePublished - 2009

Fingerprint

Pyrogens
Horseshoe Crabs
Monocytes
Fever
Pharmaceutical Preparations
Rabbits
Pharmacopoeias
Hemolymph
Poisons
Gram-Positive Bacteria
Dialysis
Immune System
Shock
Fungi
Air
Viruses
Safety
Equipment and Supplies
endotoxin binding proteins

Keywords

  • Alternatives to animals
  • Interleukin-1β
  • Monocyte activation test
  • Validation study

ASJC Scopus subject areas

  • Medical Laboratory Technology
  • Pharmacology
  • Medicine(all)

Cite this

Development validation and applications of the monocyte activation test for pyrogens based on human whole blood. / Schindler, Stefanie; Von Aulock, Sonja; Daneshian, Mardas; Hartung, Thomas.

In: Altex, Vol. 26, No. 4, 2009, p. 265-277.

Research output: Contribution to journalArticle

Schindler, Stefanie ; Von Aulock, Sonja ; Daneshian, Mardas ; Hartung, Thomas. / Development validation and applications of the monocyte activation test for pyrogens based on human whole blood. In: Altex. 2009 ; Vol. 26, No. 4. pp. 265-277.
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