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Control of inorganic contaminants in pharmaceutical products traceable to the SI

High-accuracy monoelemental reference solutions for quality assurance in the pharmaceutical sector

PTB-News 2.2018
Especially interesting for

the pharmaceutical industry

chemical analysis

According to a European quality guideline, elemental contaminations in medicinal products have to be adequately controlled. Consequently, the “European Directorate for the Quality of Medicines and HealthCare” (EDQM), the Joint Research Center (JRC) Geel, the Federal Institute for Materials Research and Testing (BAM) and the PTB have prepared high-accuracy reference solutions for four particularly toxic elements: lead, cadmium, mercury, and arsenic. Since January 2018, these solutions have been commercially available at the EDQM.

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.


Anita Röthke
Department 3.1
Metrology in Chemistry
Phone: +49 531 592-3179
Opens window for sending emailanita.roethke(at)ptb.de

The European Guideline

EMA/CHMP/ICH/353369/2013: Opens external link in new windowhttp://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180284.pdf

Source of supply

Opens external link in new windowhttps://crs.edqm.eu/