Evaluation of the OECD 314B Activated Sludge Die-Away Test for Assessing the Biodegradation of Pharmaceuticals

Abstract

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.

In Silico Assessment of Chemical Biodegradability

“…These biodegradation data have not been used in previous publications of the QSBR model development. The other was the BIOWIN data set, including 884 compounds tested using MITI-I protocol, also known as OECD test guideline 301C. , For the modeling purpose, substances were scored +1 or −1 based on the BOD values in either 28-day tests (for the OECD version of MITI-I) or 14-day tests (the original MITI-I protocol, only some substances applicable): if BOD ≥ 60% of maximum theoretical oxygen demand, the substance was scored +1 and labeled as RB; otherwise, the substance was scored −1 and labeled as NRB. The detailed description about the scoring criteria can be found in the literature. , …”

“…In a blind test, 27 novel compounds were predicted by the above-mentioned combinational classification models and further assayed by the OECD test guideline 301C. , OECD test guideline 301C is a standard screening test for chemicals for ready biodegradability in aerobic aqueous medium. The detailed description about OECD test guideline 301C can be found as follows:…”

Evolution of the sewage treatment plant model SimpleTreat: Use of realistic biodegradability tests in probabilistic model simulations

“…The OECD 314B test was designed to simulate low test material concentration, high biomass concentration, nongrowth, first‐order kinetics conditions, representative of activated sludge treatments, in a simple batch test system (Ericson ). The test can generate a realistic biodegradation rate, but this method has not been evaluated for use in SimpleTreat, possibly because few data have been generated because the standard guidance was issued by the OECD in 2008.…”

“…In activated sludge, suspended solids mostly consist of biomass and therefore it is reasonable to derive a bulk rate applicable to the sludge/water suspension. The most convenient method is the activated sludge die‐away batch test (OECD 314B, OECD ), which was recently recommended for the biodegradability assessment of pharmaceuticals (Ericson ). The OECD 314B is an aerated, closed system run at low test material concentration and high biomass concentration for 28 days, providing conditions for nongrowth kinetics typical of activated sludge.…”

From laboratory to environmental conditions: a new approach for chemical’s biodegradability assessment

“…Simulation tests (e.g., OECD 314 (OECD 2008)) are designed to evaluate the long-term chemical behavior in the environment. However, these tests are expensive, technically sophisticated, and time-consuming (e.g., use of several different tests and the use of 14 C-labeled chemicals) (Nyholm et al 1992;Ericson 2010), limiting the tests' use to a very small number of substances. There is, therefore, a gap between ease of use and biodegradability assessment, hence the necessity for the community of environmental stakeholders to strike a balance to assess biodegradation between Ready Biodegradation Tests and simulation.…”