Harmonisation of Bacterial Endotoxin Testing - ICH guideline Q4B Annex 14
In May 2013, the "ICH Guideline Q4B Annex 14 to note for evaluation and recommendation of pharmacopoeial texts for use in the ICH regions on bacterial endotoxins tests – general chapter" will become effective.
This document is based on the following pharmacopoeial references:
European Pharmacopoeia (Ph. Eur.) 2.6.14: Supplement 6.6 (official January 1, 2010), Bacterial Endotoxins (reference 01/2010:20614).
Japanese Pharmacopoeia (JP): General Test 4.01 Bacterial Endotoxins Test as it appears in the JP Sixteenth Edition (March 24, 2011, The Ministry of Health, Labour and Welfare Ministerial Notification No.65).
United States Pharmacopeia (USP): General chapter <85> Bacterial Endotoxins Test, USP 33 Reissue (published April 2010 and official October 1, 2010).
The guideline includes that the 3 described analytical procedures can be used interchangeably in the ICH regions, but are subject to the following conditions:
Any of the three techniques can be used for the test. In the event of doubt or dispute, the gel-clot limit test should be used to make the final decision on compliance for the product being tested.
The USP, JP, and Ph.Eur. reference standards are considered interchangeable as they have been suitably calibrated against the WHO (World Health Organization) International Standard for Endotoxin.
In the section Photometric quantitative techniques, Preparatory testing, Test for interfering factors, the user should perform the test on solutions A, B, C, and D on at least 2 replicates using the optimal conditions as recommended by the lysate manufacturer.
With the incorporation of this annex into the regulatory process in ICH Step 5 in an ICH region, it can be applied there. The respective date may differ in the regions.