Health risk assessment of two impurities in a pharmaceutical


A pharmaceutical company


A pharmaceutical product based on a generic API contained two impurities at concentrations (end of shelf life) slightly higher than the ICH/EMA Quality Thresholds.

Project Goals

Bibra was asked to evaluate whether the higher levels of these impurities would be toxicologically acceptable to patients and, if so, to generate scientific justifications to support this conclusion.


Little or no substance-specific toxicity information was available on the impurities themselves, but bibra identified good closely-related analogues that had been subjected to testing and Expert Group review. The human health risk assessment was based on a combination of this read-across information, predictions from Toxtree and OECD Toolbox, and the TTC concept. Threshold and non-threshold toxicity endpoints were assessed.

Project Outcome

Based on the above approaches, bibra was able to derive tolerable oral intake figures for both impurities. The estimated exposures fell below the derived tolerable intake values, demonstrating that the impurities would be tolerable at the concentrations in the client’s pharmaceutical product. The impurities were thus considered to be qualified at these higher concentrations.

Project Leader

Pete Watts


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