TY - JOUR
T1 - International validation of novel pyrogen tests based on human monocytoid cells
AU - Hoffmann, Sebastian
AU - Peterbauer, Anja
AU - Schindler, Stefanie
AU - Fennrich, Stefan
AU - Poole, Stephen
AU - Mistry, Yogesh
AU - Montag-Lessing, Thomas
AU - Spreitzer, Ingo
AU - Löschner, Bettina
AU - Van Aalderen, Mirjam
AU - Bos, Rogier
AU - Gommer, Martin
AU - Nibbeling, Ria
AU - Werner-Felmayer, Gabriele
AU - Loitzl, Petra
AU - Jungi, Thomas
AU - Brcic, Marija
AU - Brügger, Peter
AU - Frey, Esther
AU - Bowe, Gerard
AU - Casado, Juan
AU - Coecke, Sandra
AU - De Lange, Jan
AU - Mogster, Bente
AU - Næss, Lisbeth M.
AU - Aaberge, Ingeborg S.
AU - Wendel, Albrecht
AU - Hartung, Thomas
N1 - Funding Information:
We thank U. Lüderitz-Püchel from the Paul Ehrlich Institute, Langen, Germany, for providing rabbit pyrogen test data. This work was supported by the European Union [QLRT-1999-00811].
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
KW - Alternatives to animals
KW - Cell culture
KW - Cytokines
KW - Monocytes
KW - Pyrogens
KW - Validation study
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U2 - 10.1016/j.jim.2005.01.010
DO - 10.1016/j.jim.2005.01.010
M3 - Article
C2 - 15847806
AN - SCOPUS:20244375715
SN - 0022-1759
VL - 298
SP - 161
EP - 173
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
IS - 1-2
ER -