Environmental risk assessment for ancillary substances in biotechnological production of pharmaceuticals

An increasing number of pharmaceutical active substances are produced through biotechnological processes. For sustained and safe growth of the host organisms as well as optimal expression, purification, and formulation of the product, biotechnological manufacturing processes need optimal and robust environmental conditions, which are attained through the use of buffers, chelators, and antibiotics, beside nutrients. These ancillary substances are drained with the wastewater to a wastewater treatment plant (WWTP) and are released after treatment with the effluent to receiving waters. The potential risks of such substances to WWTPs and surface waters were investigated. Three common buffers (morpholinoethane sulfonic acid [MES], morpholinopropanesulfonic acid [MOPS], 1,4-piperazine (diethanesulfonic acid) [PIPES]), one chelator (ethylenediaminetetraacetic acid [EDTA]), and one antibiotic (gentamycin) were searched in the literature for environmental data or tested for biodegradability and inhibition of activated sludge as well as acute toxicity to algae, daphnids, and fish. Amounts of the ancillary substances used in the European biotechnological production plants of F. Hoffmann-La Roche Ltd in Basle (Switzerland) and Penzberg (Germany), and actual wastewater fluxes through the respective WWTP, as well as realistic dilution factors for the local receiving water, were documented. Based on this information, site-specific predicted environmental concentrations (PECs) for the WWTPs and surface waters in Basle and Penzberg were extrapolated. These PECs were compared with predicted no effect concentrations (PNECs) for the WWTP and surface waters, derived from sludge inhibition and ecotoxicity results, respectively. For all five ancillary substances investigated, all PEC/PNEC risk characterization ratios are <1, indicating no significant risk to the WWTPs or the receiving waters at both sites.