Health risk assessment of elemental impurities in an oral drug product


A contract manufacturer of pharmaceuticals required an assessment of elemental impurities in a multi-component oral drug product, in line with the ICH Q3 Guideline on Elemental Impurities (EMA, 2016; ICH, 2014).


A pharmaceutical contract manufacturer.

Project goals

Bibra was asked to evaluate the toxicological risks posed to patients by the presence of metal impurities, at the estimated ‘worst-case’ maximum doses, by comparison with the Permitted Daily Exposures’ (PDEs) recommended in the ICH Q3 Guideline.


The client provided documentation for each of the components of the drug product, giving information on the levels of each of the seven metals deemed relevant for an oral exposure by the ICH Q3 Guideline. Such documentation was either an analytical report on the component, giving a measured level or a Limit of Detection (LoD) figure, or a statement of absence from the component manufacturer. Bibra calculated the potential maximum exposure of the patient to each metal from each component using these data together with the manufacturing formula for the drug treatment and the drug treatment regimen. A comparison of the total exposure to each metal was made with the relevant oral PDE.

Project outcome

A health risk assessment report was provided to the client, giving details of the calculations performed, and a very large margin of safety was evident for each of the seven metal impurities. It was concluded that there would be no significant toxicological risk from exposure to the elemental impurities from the intended treatment with the drug product.

Bibra project team

Anne Edwards
Pete Watts


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