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Harmonised Guideline For Elemental Impurities

At the end of last year the ICH published the harmonised Guideline For Elemental Impurities.

This guideline sets out the PDEs (Permitted Daily Exposures) of elements that can occur as impurities in medicines. These impurities can enter the medicine through various routes (interactions with process equipment or with primary packaging, as impurities in one of the components or as the remains of a catalyst that was used in the chemical production process). The scope of the guideline is all new drug products, with a number of exceptions, such as gene and cell therapy, tissue, blood and blood derivatives, radiopharmaceuticals, etc. Important: Existing medicines fall within the scope from 36 months after publication, i.e. by the end of 2017! The elements are divided into three different classes. Class 1 contains the highly toxic substances As, Cd, Hg and Pb. An evaluation via risk analysis is required for all possible sources in the production of the medicine for these substances. The outcome of the risk assessment can result in the medicine needing to be tested for the presence of these substances. Class 2 elements are toxic, depending on the method of administration. Class 2A elements (Co, Ni, V) also have a relatively high probability of occurring, and also require a risk analysis. It will mainly be this Class 2A, and in particular the new addition of Nickel to it, that will cause concern for the industry.

The conduct of the risk analysis and the control of these impurities are clearly described in this guideline. (chapter 5 ff.) Appendix 2 (p. 25) contains the table with the PDEs for all elements, and also a table with the resulting permitted concentrations in both oral, injectable and inhalable medicines. Earlier in the guideline it was, however, noted that in some cases overruns are permitted, among other things for live-saving medicines and medicines that can only be administered for a short period. Appendix 3 contains the individual safety assessments for each element.

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