Tuesday, 22 July 2014

European Pharmacopeia update: 8.3

European Pharmacopoeia 8th Edition - Review of Supplement 8.3

Below is a list of monographs and general chapters that are new, or that have been revised, corrected or deleted for the 8th Edition (supplement 8.3) of the European Pharmacopeia.

General Chapters

2.2.29  Liquid Chromatography                                                                 

The chapter has been revised to include a reference to LC systems using short columns and reduced particle-size stationary phases, such as sub-2 ┬Ám particles, and mobile phases at high pressure but avoiding reference to trading names such as e.g. UPLC, RRLC, etc.

2.4.22  Composition of fatty acids by gas chromatography                     

Content of oleic acid: sentence added to clarify that content of oleic acid is sum of oleic acid (18:1 n-9) and cis-vaccinic acid (18:1 n-7)

2.7.5    Assay of Heparin                                                                  

The clotting assay in sheep plasma has been replaced by a more specific chromogenic assay for anti-factor IIa activity following an international collaborative study (Gray E., Hogwood J., Rigsby P. et al. An international collaborative study to value assign the 6th international standard for unfractionated heparin and the US pharmacopeial heparin reference standard for assay lot F. Ref: WHO/BS/09.2124. WHO Expert Committee on Biological Standardization; 2009).

The revised chapter also comprises an assay for anti-factor Xa activity, which is used to establish the ratio of anti-factor Xa to anti-factor IIa activity, used as an identification criterion in the unfractionated heparin monographs (heparin sodium (0333), heparin calcium (0332)). As part of this revision, heparin sodium BRP was recalibrated for use with these new methods.

3.2.1    Glass containers for pharmaceutical use                                       

Production: section introduced to address the risk related to potential delamination of glass containers, by raising awareness of the glass manufacturers and users of the glass containers in the pharmaceutical industry to the factors contributing to the phenomenon

Harmonisation with ISO 4802-1 and 4802-2: adjustments made to avoid ambiguities with ISO, including an additional volume specification for containers of 2-3 mL in Table 3.2.1.-3 and Table 3.2.1.-7

Hydrolytic resistance of glass grains: alternative grinding device introduced to include state-of-the-art equipment that increases reproducibility of sample preparation.


Acetic acid, glacial (0590)                                                                
Reducing substances: test revised to replace potassium dichromate (proscribed under REACH regulation).

Ethanol (96 per cent) (1317)                                                

Volatile impurities: formula for calculation of the content of acetaldehyde and acetal has been corrected.

Heparin sodium (0333)                                                        

Definition. The scope has been restricted to heparin material of porcine origin since some of the latest requirements do not apply to materials of other origins and that heparin medicinal products currently on the European market are all of porcine origin. Further to the replacement of the clotting assay by 2 chromogenic assays for anti-factor IIa activity and anti-factor Xa activity in general chapter 2.7.5. Assay of heparin, potency is now measured by the assay of anti-factor IIa activity.

Production. A statement was introduced during the last revision, which requires testing for identity of the source species and the absence of material from other likely cross-contaminant species. Further indications have been added that reflect current widely spread practices.

Identification: a requirement for the ratio of anti-factor Xa activity to anti-factor IIa activity has been introduced; a ratio of 1 is typical of unfractionated heparin.

Sodium: range modified in line with current batch data

Sucrose (0204)                                                                      

This monograph has been revised to indicate its status within the context of International Harmonisation, a collaboration between the Japanese Pharmacopoeia, the United States Pharmacopeia and the European Pharmacopoeia. A footnote has been included in the text to refer to chapter 5.8. Pharmacopoeial harmonisation.

 Posted by Tim Sandle