Evaluation of the OECD 314B activated sludge die-away test for assessing the biodegradation of pharmaceuticals

The European Medicines Agency guideline for the environmental risk assessment of medicinal products provides a step-by-step phased approach to evaluate the potential risks of new medicines to the environment. Phase I ("prescreen") estimates the initial exposure of the new medicine in the environment. Phase II A ("screen") estimates the fate and effects in the environment. The fate screen determines the inherent properties of the new medicinal active ingredient to sorb to sludge, soil, and sediment matrices and its potential to degrade in a sewage treatment plant and in the subsequent water-sediment compartment. Current ERA Guidance (2006) recommends the OECD 301B Ready Biodegradation Test for Phase II Tier A testing without a clear recommendation for Phase II Tier B testing when further refinement may be needed. With the recent approval of the OECD 314B method for activated sludge, there is now an alternative test method that may be better suited for Phase II Tier A testing and to the data needs of the ERA. As a batch test, it fits the needs of a Tier A screen. It is not designed to simulate the operational steps of a sewage treatment plant, such as the OECD 303 tests, and yet provides the following without considerable costs or resources of OECD 303: (1) useful kinetic information in a test that reflects the conditions of the sewage-treatment environment, i.e., realistic biomass solids concentrations and low level test material concentrations to simulate first-order (nongrowth) kinetics, (2) mass balance analysis for CO(2) evolution and for residues found in mixed liquor, (3) use of an abiotic control to assess losses other than those attributed to biotic biodegradation, and (4) biotransformation profile of degradants. This paper presents the results of OECD 301B with that of OECD 314B for activated sludge biodegradation for five Pfizer drug substances. The use of this new method as an alternative to OECD 301B would strengthen the fate testing screen in Phase II Tier A of the EMEA ERA. It would provide a characterization of a substance's potential for biotransformation and mineralization during sewage treatment and provide a means for revising predicted environmental concentration of surface water for amount removed during sewage treatment.