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International validation of novel pyrogen tests based on human monocytoid cells

2005; Elsevier BV; Volume: 298; Issue: 1-2 Linguagem: Inglês

10.1016/j.jim.2005.01.010

1872-7905

Sebastian Hoffmann, Anja Peterbauer, Stefanie Schindler, Stefan Fennrich, Stephen Poole, Yogesh Mistry, Thomas Montag-Lessing, Ingo Spreitzer, Bettina Löschner, M. van Aalderen, Rogier Bos, Martin Gommer, Ria Nibbeling, Gabriele Werner‐Felmayer, Petra Loitzl, Thomas W. Jungi, Marija Brcic, Peter Brügger, Esther Frey, Gerard Bowe, Juan Casado, Sandra Coecke, Jan de Lange, Bente Mogster, Lisbeth Meyer Næss, Ingeborg S. Aaberge, Albrecht Wendel, Thomas Härtung,

Viral Infections and Outbreaks Research

It is a requirement that parenteral medicines be tested for pyrogens (fever causing agents) using one of two animal-based tests: the rabbit pyrogen test and the bacterial endotoxin test. Understanding the human fever reaction has led to novel non-animal alternative tests based on in vitro activation of human monocytoid cells in response to pyrogens. Using 13 prototypic drugs, clean or contaminated with pyrogens, we have validated blindly six novel pyrogen tests in ten laboratories. Compared with the rabbit test, the new tests have a lower limit of detection and are more accurate as well as cost and time efficient. In contrast to the bacterial endotoxin test, all tests are able to detect Gram-positive pyrogens. The validation process showed that at least four of the tests meet quality criteria for pyrogen detection. These validated in vitro pyrogen tests overcome several shortcomings of animal-based pyrogen tests. Our data suggest that animal testing could be completely replaced by these evidence-based pyrogen tests and highlight their potential to further improve drug safety.