Replacing the rabbit pyrogen test with a test for endotoxin

Some readers have asked about the replacement of the rabbit pyrogen test with a test for bacterial endotoxin (such as LAL). Within Europe, this is outlined in the European Pharmacopeia. In chapter “Substances for pharmaceutical use (2034)”, it reads:

“Pyrogens (2.6.8). If the test for pyrogens is justified rather than the test for bacterial endotoxins and if a pyrogen-free grade is offered, the substance for pharmaceutical use complies with the test for pyrogens. The limit and test method are stated in the individual monograph or approved by the competent authority. Based on appropriate test validation for bacterial endotoxins and pyrogens, the test for bacterial endotoxins may replace the test for pyrogens.”

Evidently a case must be made and discussion held with the appropriate regulatory agency. Nonetheless, the signal from the EQDM is clear: a justification can be made to replace the pyrogen test with a test for endotoxin.

Posted by Tim Sandle