Options for a Strategic Approach to Pharmaceuticals in the Environment

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Options for a Strategic Approach to Pharmaceuticals in the Environment Options for a strategic approach to pharmaceuticals in the environment Task 1 Report Revised version September 2016 Since 26 June 2013 the legal entity BIO Intelligence Service is a 100% owned subsidiary of Société Fiduciaire Internationale d’Audit which is owned by Deloitte. Document information CLIENT European Commission – DG ENV REPORT TITLE Task 1 report – Revised version PROJECT NAME Options for a strategic approach to pharmaceuticals in the environment DATE September 2016 PROJECT TEAM Deloitte, INERIS, Klaus Kümmerer, LSE, Milieu Ltd AUTHORS Ms Sarah Lockwood, Deloitte Ms Nada Saïdi, Deloitte Ms Valerie Ann Morgan, Deloitte REVIEWERS Ms Katherine Salès, Deloitte Ms Florence Didier-Noaro, Deloitte Mr Sébastien Soleille, Deloitte Mr Klaus Kümmerer Mr Tony Zamparutti, Milieu Ltd. Ms Yoline Kuipers, Milieu Ltd. Ms Sandrine Andres, INERIS DISCLAIMER The information and views set out in this report are those of the author(s) and do not necessarily reflect the official opinion of the Commission. The Commission does not guarantee the accuracy of the data included in this study. Neither the Commission nor any person acting on the Commission’s behalf may be held responsible for the use which may be made of the information contained therein. 2 Options for a strategic approach to pharmaceuticals in the environment – Task 1 Report Contents 1. INTRODUCTION ________________________________________________________ 7 1.1. Background to the study _________________________________________________ 7 1.2. Objectives of the study and of this report ___________________________________ 8 1.3. Objectives of this report _________________________________________________ 8 2. SETTING THE SCENE: THE PRODUCTION AND CONSUMPTION OF PHARMACEUTICALS IN THE EU ___________________________________________________________ 11 2.1. The EU pharmaceutical industry in figures _________________________________ 12 2.2. Trends in marketing authorisations _______________________________________ 13 2.3. Trends in pharmaceuticals consumption __________________________________ 14 3. PHARMACEUTICAL EMISSIONS THROUGHOUT THEIR LIFE CYCLE __________________ 19 3.1. Manufacturing ________________________________________________________ 20 3.2. Consumption _________________________________________________________ 21 3.2.1. Sources of emissions from human consumption ______________________ 21 3.2.2. Sources of emissions from animal consumption ______________________ 22 3.3. Waste management ____________________________________________________ 23 3.3.1. Solid waste _____________________________________________________ 23 3.3.2. Effluents of wastewater treatment ___________________________________ 24 3.3.3. Contamination of soil due to contact with waste _______________________ 25 4. OCCURRENCE OF PHARMACEUTICALS IN THE ENVIRONMENT ______________________ 28 4.1. Occurrence and concentrations of pharmaceuticals in the environment _________ 29 4.2. Occurrence and concentrations of transformation products___________________ 35 4.3. Factors influencing the types and concentrations of pharmaceuticals in the environment __________________________________________________________ 36 5. RISK TO ECOSYSTEMS _________________________________________________ 37 5.1. Environmental risk assessments (ERA) ____________________________________ 37 5.2. State of knowledge on environmental concentrations and ecotoxicity used in the ERA _________________________________________________________________ 39 5.2.1. State of knowledge on environmental concentrations used in the ERA ________ 39 5.2.2. State of knowledge about ecotoxicity data for the ERA ____________________ 41 5.3. Illustration of suspected risks ___________________________________________ 45 5.4. Illustration of observed impacts __________________________________________ 49 5.5. Focus on endocrine disruption, as a growing threat to the biota _______________ 49 6. PHARMACEUTICALS MIGHT POSE HUMAN HEALTH RISKS VIA INDIRECT EXPOSURE ______ 52 6.1. Risks to humans via drinking and other routes of exposure ___________________ 53 6.2. Human exposure to endocrine disruptors compounds (EDC) __________________ 57 6.3. The issue of emergence of anti-microbial resistance (AMR) in the environment and its health implications ______________________________________________ 57 CONCLUSIONS 65 3 Options for a strategic approach to pharmaceuticals in the environment – Task 1 Report List of abbreviations ABR Antibiotic Resistant Bacteria AMR Anti-Microbial Resistance AOP Adverse Outcome Pathway API Active Pharmaceutical Ingredient ATC Anatomical Therapeutic Chemical (Classification System) CHMP Committee for Medicinal Products for Human use CMR Carcinogenic, Mutagenic and Reprotoxic CVMP Committee for Medicinal Products for Veterinary use DDD Defined Daily Dose DDE Dichlorodiphenyldichloroethylene DID DDD per 1,000 inhabitants per day E2 17 beta-estradiol EE2 17 alpha-ethinylestradiol EEA European Economic Area EC50 Half maximal Effective Concentration ECDC European Centre for Disease Prevention and Control EDC Endocrine-disrupting chemical EMA European Medicines Agency EPAR European Public Assessment Report EPR Extended Producer Responsibility ERA Environmental Risk Assessment EU European Union FDA United States Food and Drug Administration FDW Finished Drinking Water IED Industrial Emissions Directive (2010/75/EU) IMI Innovative Medicines Initiative LC50 Half maximal Lethal Concentration 4 Options for a strategic approach to pharmaceuticals in the environment – Task 1 Report LC/MS Liquid Chromatography / Mass Spectrometry LOAEL Lowest-observed-adverse-effect level MA Market Authorisation MEC Measured Environmental Concentration MoA Mode of Action MUMS Minor Use Minor Species MRL Maximum Residue Limit MS Member State NOAEL No-observed-adverse-effect level NSAID Nonsteroidal Anti-inflammatory Drug OTC Over The Counter PAR Public Assessment Report (national) PBT Persistence, Bioaccumulation and Toxicity PCU Population Correction Unit PEC Predicted Environmental Concentration PNEC Predicted No Effect Concentration QSAR Quantitative structure–activity relationship R&D Research & Development REACH Regulation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (1907/2006) RMM Risk Mitigation Measure UF Uncertainty Factor VICH Veterinary International Conference on Harmonization WFD Water Framework Directive (2000/60/EC) WHO World Health Organization WWE Waste Water effluents WWI Waste Water Influents WWTP Waste Water Treatment Plant 5 Options for a strategic approach to pharmaceuticals in the environment – Task 1 Report 1. Introduction This introductory chapter presents the background to and the objectives of the study on Options for a strategic approach to pharmaceuticals in the environment, of which this report constitutes the first deliverable. 1.1.Background to the study Health care as practised in the European Union (EU) heavily relies on the consumption of pharmaceuticals, as reflected by the continuous growth of the European market for medicines for human and veterinary use. The EU is even considered the second biggest consumer in the world after the United States of America. While the benefits of a responsible use of these substances for human health and veterinary care are recognised, there is, however, increasing concern over the potential adverse effects of these substances on the environment and on human health via the environment. It is now widely acknowledged that pharmaceuticals and their residues – including Active Pharmaceutical Ingredients (API), metabolites and transformation products – are emitted into the environment at different stages of their life cycle, from their production to their use to their disposal. A large body of literature1 reports the presence of pharmaceuticals in environmental compartments (e.g. surface and ground water, soils, biota) in different parts of the world, including the EU Member States. They are generally detected at low concentrations (e.g. in the range of sub ng/L to µg/L in the aquatic environment). The level and frequency of exposure of biota (e.g. plants, animals, bacteria) and humans to these substances and their residues is a key component of the risk they pose to human health and the environment, along with their inherent hazard level. Actual exposure can be particularly complex to determine, because of the multiplicity of sources of emissions and contamination pathways (diffuse contamination, point source pollution from sewage networks or landfill leachates) as well as transformation and transfer processes in different environmental compartments. Another challenge lies in assessing the potential effects on the environment and human health of chronic exposure to low doses of mixtures of pharmaceuticals. In the EU, the issue of pharmaceuticals in the environment is to some extent addressed in the chemicals (including pharmaceuticals), industrial emissions, water, waste and food legislation. Most do not include specific provisions for pharmaceuticals, but can be applicable to the issue. The present study is part of the effort to develop the EU strategic approach for pharmaceuticals mentioned in Directive 2013/39/EU,2 which is likely to take the form of a Commission Communication. This approach must allow coordinating and balancing efforts across Member States and categories of stakeholders towards: better knowledge of the issue (e.g. through fostering research and adequate monitoring and reporting activities); more sustainable production, consumption and disposal patterns;
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