Monocyte activation test for pro-inflammatory and pyrogenic contaminants of parenteral drugs: test design and data analysis.
An optimised test designed for an in vitro monocyte activation test for pro-inflammatory and pyrogenic contaminants of parenteral drugs is described, together with ways to address the inherent variability of such assays in which cells are cultured using 96-well plates. The test preparation is cultured with peripheral blood mononuclear cells (PBMNC) and the contaminants in the test article stimulate the release from the cells of the endogenous pyrogenic cytokine interleukin-6 (IL-6). The test system is in use within the pharmaceutical industry and at a national control authority for detecting pro-inflammatory and pyrogenic contaminants, including 'rabbit-negative' and 'LAL-negative' non-endotoxin pyrogens. Products tested include small molecules, biologicals and vaccines. The PBMNC/IL-6 monocyte activation test has been approved by the US FDA as an 'end-product release test' and also is being used for in-process testing.
Gaines Das
Rose E
RE
National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, UK.
Brügger
Peter
P
Patel
Mehul
M
Mistry
Yogesh
Y
Poole
Stephen
S
D018929:Cell Culture Techniques / Q000379:methods; D003627:Data Interpretation, Statistical; D004340:Drug Contamination; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012107:Research Design
D004731:Endotoxins