Environmental risk assessment for excipients from galenical pharmaceutical production in wastewater and receiving water

- First formal environmental risk assessment for pharmaceutical excipients.
- Based on material balances of single galenical productions at two sites.
- PEC/PNEC risk ratios for wastewater treatment plants and the receiving water.
- No risk identified for wastewater treatment or receiving water (River Rhine).

Many different excipients are used in galenical pharmaceutical production, in addition to the active pharmaceutical ingredients. Excipients are little investigated regarding their environmental fate and impact, even though some of them are used in appreciable quantities. For 35 excipients used in galenical production at Roche Basle and Roche Kaiseraugst, both in Switzerland, in the years 2013 and 2014, the environmentally relevant properties were collated. A predicted environmental concentration (PEC) was calculated for the wastewater treatment plants (WWTPs) and the receiving water, the River Rhine for both sites, based on maximum daily losses of the single excipients to wastewater, derived by mass balance, and the site-specific dilution factor. Predicted no effect concentrations (PNECs) were derived for the WWTPs and the River Rhine. PECs and PNECs were compared for the WWTPs and the receiving water, in an environmental risk assessment. Additionally, to simulate a worst case scenario, certain galenical productions where given excipients are used in the highest amounts were assumed to take place in parallel on the same day, resulting in theoretical maximum excipient losses to wastewater. All PEC/PNEC risk characterisation ratios for the excipients currently used by Roche in Switzerland are well below 1 throughout. Together with the fact that based on biodegradability data many excipients will be removed in the WWTP, this indicates that the excipients currently used do not present a risk to the environment.