Risk assessment of a Pharmaceutical leachable


A pharmaceutical company.


Bibra was asked to evaluate the risks of adverse health effects occurring in patients exposed to a leachable in a pharmaceutical intended for subcutaneous injection. As part of this analysis, it was requested that we identify the most relevant TTC threshold for the compound, and classify it in accordance with the current (as of January 2016) ICH guidance on mutagenic impurities in pharmaceuticals.

Project goals

To identify toxicity data relevant to the leachable, and to assess the risks posed to patients who may potentially be exposed to this compound over a lifetime. We also aimed to conclude on the most relevant ICH class (with respect to mutagenic and carcinogenic potential) and TTC threshold value.


Literature searches failed to identify any laboratory data on the leachable itself, but a Toxtree analysis identified structural alerts for genotoxicity. Information on other structurally-related chemicals was considered as part of a read-across approach.

Project outcome

Based on read-across information, and using expert judgement, it was considered that the leachable is not likely to be genotoxic in vivo, despite its structural alerts, and that the TTC threshold for Cramer Class 1 compounds (1800 µg/day) is appropriate. Under ICH guidance, the leachable should be treated as a non-mutagenic impurity. No adverse health effects were expected in patients.

Project Team

Beth O’Connell

James Hopkins



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