The European Directorate for the Quality of Medicines (“EDQM”) has published draft revisions to its Guidelines for Using the Test for Bacterial Endotoxins. Bacterial endotoxins are contaminants from gram-negative bacteria and are the most common cause of pyrogenicity in pharmaceutical products. The EDQM Guidelines explain the justifications for the requirements in the test for bacterial endotoxins. They also provide guidance on reading and interpreting test results.

The revisions are intended to clarify the existing Guidelines and bring these in line with current knowledge. In particular, the following revisions have been introduced to the Guidelines:

  • A new section has been included on bacterial endotoxins. The amplification includes issues to be considered when establishing an endotoxin limit for a specific substance or product;
  • A recommendation that a monocyte-activation test or test for bacterial endotoxins is preferred to the rabbit pyrogen test. This revision is intended to avoid the use of live animals and reflects the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes;
  • A recommendation that a risk assessment be performed when using the bacterial endotoxin test as a pyrogenicity test. This is due to the potential for contamination by non-endotoxin pyrogens.

The draft Guidelines have been published on EDQM’s online publication, Pharmeuropa, and are available here. The draft revisions are open for comments from manufacturers, industry associations and other interested parties until 31 December 2014. Details on how to comment are available here.