ALTEX :: Alternatives to Animal Experiments

2001, VOLUME 2

Replacement of the Pyrogen-Test as Batch Control Test for the Biological Substances Aprotinin and Urokinase

Karl-Heinz Diehl

Aventis Pharma Deutschland GmbH, D-Marburg

SUMMARY

In the Pharmeuropa Vol. 10, No. 4, December 1998, the European Pharmacopoeia Commission published an appeal to replace the pyrogen test by the limulus test for a total of 10 biological substances. These substances included the active ingredients aprotinin and urokinase, contained in our sales products Antagosan® and Actosolv®. After successful validation of the limulus test, we calculated endotoxin limit concentrations for these and submitted these to the European Department for Quality of Medicines (EDQM). We expect -- not least on the basis of the data submitted by ourselves -- that the pyrogen test will be replaced in future as a quality control test by the limulus test in testing aprotinin and urokinase compounds for the presence of pyrogenic substances. This leads to a reduction in the number of rabbits used as opposed to the current pyrogen test for testing the stated compounds.

Keywords: 3R, replacement, Aprotinin, Urokinase, pyrogen test, limulus test, validation