European Pharmacopoeia 8th Edition: Supplement 8.8

A new supplement to the European Pharmacopeia has been issued. The points of interest are:

Revised texts - General Chapters

Chapter 2.2.3 Potentiometric determination of pH                                   

The main changes concern the choice of buffers used for the calibration of the pH meter which is now more flexible and does not start obligatorily with an initial calibration at pH 4.0. Furthermore, the chapter now allows the use of commercially available, certified reference materials as buffer solutions.

Chapter 2.2.46           Chromatographic separation techniques                           

Text modified to reflect current Ph. Eur. policy (system suitability, quantification).

Chapter 2.6.8 Pyrogens                                                                               

The text has been revised to include a reference to general chapter 2.6.30. Monocyte- activation test as a potential replacement of the test for pyrogens, therefore avoiding the use of live animals.

5.1.10  Guidelines for using the test for bacterial endotoxins              

This general chapter has undergone a general revision with the following scope.

A section has been added (section 2-4) to include aspects to be considered when establishing an endotoxin limit for a specific substance or product; also, the text has been revised to reflect the fact that an endotoxin limit is not always provided in a specific monograph.

Reference is made to general chapter 2.6.30. Monocyte-activation test as an alternative to the rabbit pyrogen test, and a recommendation is given to perform a risk assessment when using the bacterial endotoxin test as a pyrogenicity test, due to the potential for contamination by non-endotoxin pyrogens. In this respect, the previous section 11 concerning the replacement of the rabbit pyrogen test by a test for bacterial endotoxins has been substituted with a new text in agreement with a strategy to be applied for

testing of bacterial endotoxins or non-endotoxin pyrogens. A distinction is made between replacement methods already described in the Ph. Eur. and other alternative methods.

Reference is made to the use of alternative reagents to the Limulus amoebocyte lysate, such as recombinant factor C: this practice avoids the use of animal species.

A number of additional specific points have been included in the revision.

Method A is no longer declared as the reference method, and all methods A to F of general chapter 2.6.14. Bacterial endotoxins can be used. Where the method is stated in the monograph, the use of another method must be validated.

The expression ‘threshold endotoxin concentration’ has been replaced by the more appropriate expression ‘endotoxin limit concentration’ to harmonise with general chapter 2.6.30. Monocyte-activation test.

A new entry has been included in Table 5.1.10.-1 for formulations administered per square metre of body surface.

Chapter 5.3    Statistical analysis of results of biological assays and tests    

Equivalence testing: an explicit mention of ‘equivalence testing’ has been introduced in section 7.6.

Posted by Dr. Tim Sandle