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|Title:||Pyrogen Testing of Lipidic Parenterals with a nNovel in Vitro Test- Application of the IPT based on Cryopreserved Human Whole Blood|
|Authors:||SCHINDLER Stefanie; ROSENBERG U; SCHLOTE D.; PANSE K.; KEMPE A.; FENNRICH Stefan; HARTUNG THOMAS|
|Citation:||Pharmeuropa Scientific Notes no. 1 p. 1-7|
|Publisher:||European Directorate for the Quality of Medicines & HealthCare|
|JRC Publication N°:||JRC36759|
|Type:||Articles in Journals|
|Abstract:||The European Pharmacopoeia has made the testing of small volume parenterals (<15) obligatory since 2004. This concerns many formulations, e.g. vitamins, steroids and hormones, many of which are applied intramuscularly using a lipidic carrier. Lipopolysaccharides, the best established endotoxins from Gram-negative bacteria, bind strongly to lipophilic substrances, which mask them in Limulus amebocyte lysae assays. End-product testing, therefore, can only be carried out in rabbit pyrogen tests. This will lead to a pronounced increase in animal experiments if no alternative procedures become available. We have described a novel in vitro pyrogen test (IPT) based on human whole blood, which has recently been validated in a collaborative study including the European Pharmacopoeia. Here, the utility of the IPT for lipophilic substances and lipid-containing end-products was assessed. For a variety of lipids commonly added to formulations of injectable endproducts, namely peanut oil, sesame oil, miglyol and paraffin, a protocol which allows interference-free testing was established applying the pharmacopoeial criterion of 50 to 200% retrieval of an LPS spike. Furthermore, end-product testing for three sample formulations was possible. In all, a method could be established which allows the determination of given or calculated ELC (endotoxin limit concentrations) according to Pharmacopoeia. It is concluded that monocytes do react to lipid-bound LPS, indicating that immune responses to contaminated endproducts must be anticipated, and that the IPT is suitable for endproduct control of these formulations.|
|JRC Institute:||Institute for Health and Consumer Protection|
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