Pharmaceuticals in the environment (PIE) continue to receive significant attention in the media and from regulatory agencies. The detection of low levels of active pharmaceutical ingredients (APIs) in the environment has led to highly publicized cases of impacts to fish and birds following exposure to PIE and growing concerns over antibiotic resistance and endocrine disruption. Gradient scientists are at the forefront of scientific developments in the PIE field. We have developed effective strategies to address a variety of PIE projects, including a tiered fate and effects data collection and assessment framework for potential environmental risks of existing and new APIs. We have provided comments on proposed regulations, developed best practices for wastewater and biosolids management, prepared environmental assessments to support regulatory filings in the US and Europe (including for antibiotics and endocrine-active APIs), published impactful reports in the scientific literature, and communicated PIE risks to the public and other stakeholders.
Bamgbose, IA; Mohar, I; Verslycke, T. 2020. “Are Existing Environmental Assessment Approaches Appropriate for Novel Drug Products?” Presented at the American College of Toxicology (ACT) 41st Annual Meeting, Austin, TX, November 12-19.
Marty, MS; Blankinship, A; Chambers, J; Constantine, L; Kloas, W; Kumar, A; Lagadic, L; Meador, J; Pickford, D; Schwarz, T; Verslycke, T. 2017. “Population-relevant endpoints in the evaluation of endocrine-active substances (EAS) for ecotoxicological hazard and risk assessment.” Integr. Environ. Assess. Manag. 13(2):317-330.
Williams, M; Backhaus, T; Bowe, C; Choi, K; Connors, K; Hickmann, S; Hunter, W; Kookana, R; Marfil-Vega, R; Verslycke, T. 2016. “Pharmaceuticals in the environment: An introduction to the ET&C special issue.” Environ. Toxicol. Chem. 35(4):763-766.
Verslycke, T; Mayfield, DB; Tabony, JA; Capdevielle, M; Slezak, B. 2016. “Human health risks of triclosan in land-applied biosolids.” Environ. Toxicol. Chem. 35(9):2358-2367.
Verslycke, T; Mastrocco, F; Lemay, JC. 2012. “A Concordance Assessment of Predicted No-Effect Concentration (PNEC) Aquatic Toxicity Data for Pharmaceuticals.” Presented at SETAC 6th World Congress, Berlin, Germany, May 20-24.
US FDA/European Medicines Agency Environmental Assessments
Gradient has conducted many environmental assessments with the US FDA and European Medicines Agency (EMA) to support drug approval for a wide range of active pharmaceutical ingredients, from those with relatively low toxicity to antimicrobials and endocrine-active compounds. We selected, designed, and oversaw additional environmental fate and toxicity testing to support the environmental assessments, and our environmental assessments have been accepted with limited agency comment.
Categorical Exclusion Requests
Gradient prepared requests to the US FDA for categorical exclusions from a full environmental assessment for several new drugs, based on known drug characteristics, disease prevalence information, and estimated environmental concentrations. Our requests were accepted with minimal agency comments.
Risk Assessment Framework
Gradient developed a protocol to evaluate environmental fate and human health and ecological effects from the manufacturing, use, and disposal of pharmaceuticals. Our client is using our approach to proactively establish best management practices, global regulatory compliance, and risk communication.
Risk-Based Remedial Strategy for a Pharmaceutical Manufacturing Plant
On behalf of a global pharmaceutical company, Gradient developed a risk-based closure strategy for a former pharmaceutical synthesis facility. Our strategy included identifying a subset of potentially risk-driving compounds and threshold concentrations protective of human and ecological receptors to form the basis of site cleanup. Our closure strategy was accepted by the state environmental agency.
Environmental Fate and Effects Database
Gradient reviewed pharmaceutical environmental fate and ecological effects data from proprietary, published, and governmental sources. We synthesized this data into a database for preparing ecological assessments and establishing risk-based wastewater discharge limits.
Critique of Proposed EU Pharmaceutical Environmental Assessment Requirements
Gradient provided two rounds of comments on the EU-proposed pharmaceutical environmental assessment requirements. We recommended a streamlined, scientifically sound, tiered fate and effects data collection and assessment program. Additionally, we provided comments on the most recent proposal to revise the existing EU guidance for environmental assessment of new human drugs.