Control of inorganic contaminants in pharmaceutical products traceable to the SI
High-accuracy monoelemental reference solutions for quality assurance in the pharmaceutical sector
In the context of expanding globalization, it is becoming increasingly important to adequately control elemental impurities in medicinal products in order to avoid hazards to patients caused by toxic substances in medicines. Therefore, the European Medicines Agency (EMA) has adopted the internationally harmonized quality guideline ICH Q3D (EMA/CHMP/ICH/353369/2013). Since June 2016, new medicines have had to be checked for elemental impurities using instrumental analytics; as of December 2017, the same requirement has applied to products that have already been authorized.
In the past, the simplest accepted proof of elemental contaminants in medicines was obtained by using an unspecific sulfidic precipitation followed by a comparison of the chromaticity with that of a reference. The ICH guideline has been rendered legally binding in the 38 countries where the European Pharmacopoeia (Ph. Eur.) applies by incorporating it into the Ph. Eur. Conducting a risk-assessmentbased quantification of contamination in a way that is traceable to the SI system is now required. This can be done, for instance, with analytical methods such as mass and optical emission spectrometry with inductively coupled plasma (ICPMS or ICP OES). Traceability to the SI units means that the methods described above are calibrated by means of reference solutions whose mass fraction of the elements to be determined is traceable to the SI.
In 2016 and 2017, reference solutions with four particularly toxic elements, namely lead, cadmium, mercury, and arsenic, were produced within the framework of this cooperation project. PTB and BAM are able to prepare and characterize elemental solutions at an exceptionally high accuracy level by drawing on the expertise they have acquired over two decades. When characterizing the mass fraction of lead in the solution by means of ICP OES, PTB was, for example, able to achieve measurement uncertainties one hundred times smaller than those usually obtained in routine measurements.
The partners have agreed on the continuation of their successful collaboration.
Contact
Anita Röthke
Department 3.1
Metrology in Chemistry
Phone: +49 531 592-3179
anita.roethke(at)ptb.de
The European Guideline
EMA/CHMP/ICH/353369/2013: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180284.pdf