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Ph. Eur. Revises Bacterial Endotoxin Chapter - Adds Recombinant Factor C as an Alternative Method

The European Directorate for the Quality of Medicines & HealthCare  (EDQM) has recently proposed a significant revision to European Pharmacopoeia Chapter 5.1.10, Guidelines for Using the Test for Bacterial Endotoxins.

The proposed revision includes the use of alternative reagents to the Limulus amoebocyte lysate (LAL), such as recombinant factor C: this practice avoids the use of endangered animal species and can be considered in the context of the use of an alternative method as described in the General Notices.

The proposed revision includes the following additions:
  • Replacement of the rabbit pyrogen test required in a pharmacopoeial monograph by an amoebocyte lysate test, or by other methods such as the monocyte-activation test or a test using recombinant factor C as a replacement for the amoebocyte lysate, constitutes the use of an alternative method of analysis and hence requires demonstration that the method is appropriate for the given substance or product and gives a result consistent with that obtained with the prescribed method as described in the General Notices.
  • Replacement of a rabbit pyrogen test or a bacterial endotoxin test prescribed in a monograph by a test using recombinant factor C or any other reagent as a replacement of the amoebocyte lysate is to be regarded as the use of an alternative method in the replacement of a pharmacopoeial test, as described in the General Notices.
  • The test and assays described are the official methods upon which the standards of the Pharmacopoeia are based. With the agreement of the competent authority, alternative methods of analysis may be used for control purposes, provided that the methods used enable an unequivocal decision to be made as to whether compliance with the standards of the monographs would be achieved if the official methods were used. In the event of doubt or dispute, the methods of analysis of the Pharmacopoeia are alone authoritative.
The deadline to submit comments on the proposed revision is December 31, 2014.

The revision is found in Pharmeuropa, Issue 26.4. The online version can be accessed at Access to the online version requires registration, but this is a free service.


  1. Dear Michael,

    maybe it will be of interest, that representatives of the European Authorities and members of the expert groups will present the current developments at the Endotoxin and Pyrogen Testing Conference during the PharmaLab Congress on 10 and 20 November 2014 in Neuss/Düsseldorf, Germany. More details can be found at

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