Abstract

Metal Impurities in Pharmaceutical Products / Aspects of USP, Ph. Eur., EMA and ICH

The United States Pharmacopeia (USP) published their General Chapters <232> and <233>, which have official status from February 2013 on, and in which limits and analytical methods are discussed that are to be applied on all monographs from May 2014 on. The chapters aim on the replacement of the out-of-date wet chemistry method of sulphide precipitation, as it is still valid in USP, but also in the European Pharmacopoeia (Ph. Eur.) and the Japanese Pharmcopoeia (JP), for drug substances and excipients. Already by the end of 2008 the European Medicines Agency (EMA) issued their „Guideline on the Specification Limits for Residues of Metal Catalysts or Metal Reagents“, which is relevant for market approval in the European region. This guideline will be adopted by Ph. Eur. as General Text 5.20. in supplement 7.7. The same supplement sees the introduction of the new chapter 2.4.20. (Metal Catalysts or Metal Reagents). In this article, both documents will be compared to the new USP chapters. The ICH, on the other hand, is still in a preparation phase to a draft of its guideline „Q3D: Impurities – Guideline for Metal Impurities“.

The following article outlines the particular initiatives, which in parts were already in place before the USP initiative started. A comparison of EMA and USP documents is also provided. Furthermore, it becomes clear that the progress in analytical technology and toxicological assessment – as previously for organic impurities and residual solvents – leads to even safer medicines, but also provides challenges for the pharmaceutical companies when it comes to analytical efforts.

Dr. Christian Zeine studierte Chemie an der Westfälischen Wilhelms-Universität Münster, wo er auch 1998 promoviert wurde. Nach Projektarbeiten an der Universität folgten ab 1999 Tätigkeiten bei Herstellern von Medizinprodukten und In-vitro-Diagnostika, u. a. bei B. Braun Melsungen. Seit 2002 arbeitet Dr. Zeine im Produktmanagement für pharmazeutische Referenzmaterialien bei LGC Standards in Wesel. LGC Standards ist ein führendes Unternehmen im Bereich von Referenzmaterialien für verschiedenste analytische Einsatzgebiete und Teil der international tätigen LGC-Gruppe.