Current Issue - Article Summary
Back to table of contents 2/13Evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test
Download article (4 KB)Nina Hasiwa1,2, Mardas Daneshian1, Peter Bruegger4, Stefan Fennrich5, Astrid Hochadel2, Sebastian Hoffmann6, Felix E. Rivera-Mariani3, Christoph Rockel7, Stefanie Schindler8, Ingo Spreitzer9, Sandra Stoppelkamp5, Kranthi Vysyaraju3, and Thomas Hartung1,3
1 CAAT-Europe, University of Konstanz, Konstanz, Germany;
2 AtaX-Advice, Konstanz, Germany;
3 Johns Hopkins University, Bloomberg School of Public Health, CAAT, Baltimore, USA;
4 Novartis, Basel, Switzerland;
5 Department of Thoracic, Cardiac and Vascular Surgery, Tübingen University Hospital, Tübingen, Germany;
6 seh consulting + services, Paderborn, Germany;
7 Enzler Hygiene AG, Center for Hygiene, Pratteln, Switzerland;
8 Animalfree Research, Zürich, Switzerland;
9 Paul-Ehrlich Institut (PEI), Langen, Germany
Summary
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 For this review we collate evidence from published literature, unpublished data of our own, and results from the international validation study to show that there is overwhelming scientific evidence to conclude that the whole blood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.
ALTEX 30(2), 169 – 208 |
