Appropriate collection and disposal of medicine-related waste has been identified as one of the main ways to decrease the emission of active pharmaceutical ingredients (APIs) into the environment. Improvement to the take-back and treatment of collected pharmaceutical waste may be considered lowhanging fruit when one is considering measures to reduce API emissions. However, comparable information that would enable estimating the potential impact of these efforts has not been available. Directive 2004/27/EC, related to medicinal products for human use, mandates that EU member states implement appropriate collection schemes for unused or expired human-use medicinal products. However, it does not provide any guidelines on practical implementation of these schemes. Several studies have pointed out significant differences among Member States in this regard. In March 2019, the European Commission published the European Union Strategic Approach to Pharmaceuticals in the Environment. The actions specified therein cover all stages of the pharmaceutical life cycle, from design and production to disposal and waste management. It emphasizes such elements as sharing good practices, co-operating at international level, and improving understanding of the risks. This report is aimed at filling knowledge gaps and proposing good practices for take-back and disposal of unused human and veterinary medicines and other pharmaceutical waste. The report is targeted to e.g. ministries, environment and medicines agencies, supervisory authorities, municipalities, hospitals, NGOs, pharmacists, doctors, and veterinarians. For the report, current national practices for take-back and disposal of unused medicines and other pharmaceutical waste in Denmark, Estonia, Finland, Germany, Latvia, Lithuania, Poland, Russia, and Sweden were evaluated. The pharmaceutical waste originating from households, hospitals and other health care institutions, the pharmaceutical industry, and veterinary use was considered. The proportion of citizens who return unused pharmaceuticals via designated collection points varies greatly between Baltic Sea countries, from about 10% to 70%, with 16–80% disposing of them of as mixed household waste and 3–30% flushing them down the drain. The most commonly cited reason for improper disposal of medicines on households’ part is lack of information about their environmental impacts and how to get rid of them in an environmentally sound manner. Separate collection of unused household pharmaceuticals does not exist in Russia, and the collection mechanism functions poorly in Latvia, Lithuania and Poland. Information on the take-back schemes for unused human medicines is more readily available than is corresponding information on veterinary medicines. We identified, all told, 21 good practices and recommendations for take-back and disposal of unused pharmaceuticals and other pharmaceutical waste and for promoting the rational use of pharmaceuticals in the Baltic Sea region. Nevertheless, implementing them at national level requires particular consideration due to differences in national legislation and other characteristics of the EU Baltic Sea countries and Russia. The good practices identified in this report answer the call issued in the EU strategic approach for an efficient risk-reduction strategy.

This report describes the contamination by pharmaceuticals and the environmental risks associated with their environmental levels in the Baltic Sea Region. Data were collected within the three-year project Clear Waters from Pharmaceuticals (CWPharma) funded by the EU’s Interreg Baltic Sea Region Programme. Sampling was performed in the river basin districts of Vantaanjoki in Finland, Pärnu in Estonia, Lielupe and Daugava in Latvia, Vistula in Poland, Warnow-Peene in Germany and Motala ström in Sweden. Analyses were performed on surface water, coastal water, sediment and soil that was fertilized with sewage sludge or manure. Analyses were also performed on emissions from municipal wastewater treatment plants, hospitals, pharmaceutical manufacturing facilities, landfills, and fish and livestock farms. In total, the study covered 13 365 data points from 226 samples as well as collection of human and veterinary consumption data of selected active pharmaceutical ingredients (APIs). Samples were screened for up to 80 APIs, representing antibiotics, antiepileptics, antihypertensives, asthma and allergy medications, gastrointestinal disease medications, hormones, metabolic disease medications, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics, other cardiovascular medicines, psychopharmaceuticals, veterinary medicines and caffeine. The measured APIs were selected based on analytical capacity, consumption rates, identified data gaps and potential environmental risks. Literature and databases were screened for ecotoxicological information. Acute toxicity tests were performed for two APIs, nebivolol and cetirizine, for which ecotoxicological data were lacking. Measured environmental concentrations were compared with predicted no-effect concentrations (PNEC) to assess environmental risks of the selected APIs.

Elevated levels of active pharmaceutical ingredients (API) have been detected in the Baltic Sea for many years. These APIs are often discharged from hospitals, households, pharmaceutical manufacturing plants, and animal farms, among other sources. As APIs are not completely degraded in municipal wastewater treatment plants (WWTP), they are then transported to the Baltic Sea. Although research on the effects of APIs in the Baltic Sea has been ongoing, the consequences of API discharges on the environment, in terms of potentially risky ecological effects, have not yet been fully evaluated. The European Union’s Interreg Baltic Sea Region programme funded the Clear Waters from Pharmaceuticals (CWPharma) project, which quantified API loading into the Baltic Sea from six river basin districts. Seven Baltic Sea Region (BSR) countries were involved as CWPharma partners (Denmark, Estonia, Finland, Germany, Latvia, Poland and Sweden). Surface water, soil, and sediment samples were collected from coastal, rural, and agricultural locations and analysed for up to 80 APIs. By comparing the API concentrations detected in rivers with predicted no-effect levels (PNEC), the environmental risk of individual APIs was quantified. A GIS-based model was developed which allowed illustration and assessment of API loads into the Baltic Sea coming from the project partner countries, as well as evaluation of the impacts of various emission reduction scenarios. Different types of emission reduction measures were proposed. Reductions of API emission from WWTPs through the application of advanced wastewater treatment (AWT) technologies were experimentally validated at full- and pilot-scale. AWT technologies tested in CWPharma included full-scale ozonation and various post-treatment technologies, such as moving bed bioreactors, constructed wetlands, deep bed filters using sand/anthracite, and granular activated carbon. Additionally, 21 recommendations for other reduction measures focused on improving collection and disposal of unused pharmaceuticals and pharmaceutical waste, targeting various groups and emitters, were also developed. By simulating the variety of API reduction methods within the API loading model, the most effective measures for reducing API emissions could be determined. Similarly, both the costs and global warming potential of upgrading various classes of WWTPs with AWT in the form of ozonation or activated carbon were calculated for each CWPharma project partner country. This report summarizes the most important recommendations elicited from the CWPharma project.

This report aims to identify good practices for environmental permitting of pharmaceutical plants in some Baltic Sea (BS) countries and spread them to other countries where they are lacking or inefficient. The objective is to enhance permitting of pharmaceutical plants within current legislation framework to obtain information on their active pharmaceutical ingredient (API) emissions to municipal WWTPs (MWWTPs) and environment, resulting in improved information on pharmaceutical emissions, and aiding with direct mitigation measures when necessary. The pharmaceutical industry is highly globalized, interconnected and heterogeneous both spatially and temporally. The pharmaceutical industry includes API-production and the production of pharmaceutical products. Emissions from these activities may vary significantly. Also, as many activities are patch processes, emissions of specific substances are likely to happen only sporadically. The pharmaceutical industry may also include (re)packaging and other activities. The UNESCO & HELCOM Status Report on Pharmaceuticals (2017) [1] contains some information on pharmaceutical production in Estonia, Finland and Sweden, but no information on permitting practices of pharmaceutical plants. Thus, this report fills in identified information gaps related to the production of pharmaceuticals, e.g. by HELCOM. The working method evaluates the current national practices for environmental permitting for pharmaceutical plants in all seven countries represented in the project CWPharma (Denmark, Estonia, Finland, Germany, Latvia, Poland and Sweden) with the aim of collecting some information also from Russia. In the Baltic Sea region (BSR), wide recommendations on good practices for environmental permitting of pharmaceutical plants are proposed to initiate the process that clarifies the role of the pharmaceutical industry as a possible source of APIs and to estimate the need for measures that control the pharmaceutical industry’s emissions. Additionally, the aim is to evaluate the industrial wastewater contracts between municipal wastewater treatment plants (MWWTPs) and pharmaceutical plants in each BS country, even if this task is more difficult than the task related to environmental permitting of pharmaceutical plants. These documents are not publicly available, and thus the information on contracts proved difficult to obtain. The BSR wide recommendations are aimed at formulating good practices for industrial wastewater contracts between MWWTPs and pharmaceutical plants. The activities of this report pose very high transnational relevance in the Baltic Sea region (i.e. transnational spreading of good practices), because the recommendations are based on the current good practices in BSR countries and improvements made for them. Furthermore, the objective is that the recommendations will be utilised and implemented in all Baltic Sea countries. The information presented in this report will be used to identify priority measures at a national level to reduce pharmaceutical emissions. The results will also increase knowledge among target groups under the CWPharma project (pharmaceutical industry, operators of MWWTPs, permitting and supervisory authorities) and other relevant stakeholders through national stakeholder meetings and reports.

Zur Verminderung von Spurenstoffeinträgen in Oberflächengewässer wurden bereits einige Kläranlagen in Deutschland und der Schweiz um eine weitergehende Reinigungsstufe (Ozon oder Aktivkohle) erweitert. Zur Erzielung einer gleichbleibenden Spurenstoffelimination und einer gleichzeitigen Vermeidung von Fehldosierungen (Kosten, Rohstoffeinsatz) werden verlässliche Messverfahren und robuste MSR-Konzepte (Mess-, Regel- und Steuerung) benötigt. Im Rahmen des Projekts „MeReZon" (Schnelle und zuverlässige Messtechnik und Steuer-/Regelkonzepte für eine weitergehende Abwasserreinigung) wurde an einer Pilot-Ozonanlage zur Behandlung von gereinigtem Abwasser untersucht, unter welchen Randbedingungen eine verlässliche Onlinemessung möglich ist. Dabei wurde u.a. die Leistungsfähigkeit eines neu entwickelten Ultraschallreinigungsmoduls zur Vermeidung einer Messwertdrift durch Fouling untersucht und mit den Sonden bzw. Reinigungsmodulen anderer Hersteller in verschiedenen Konfigurationen verglichen. Dabei wurden deutliche Unterschiede festgestellt. Darauf aufbauend wurde das bestehende MSR-Konzept der Ozonanlage optimiert und ein alternierender Messbetrieb, d.h. abwechselnde Beschickung einer Messsonde mit Zu- bzw. Ablauf der Ozonung, implementiert. Die Ergebnisse zeigen, dass mit dem optimierten MSR-Konzept eine stabile Abnahme des SAK254 (<U+0394>SAK254) erzielt werden kann, welche mit der Spurenstoffelimination korreliert. Die erfolgreiche Umsetzung des alternierenden Messbetriebs ermöglicht die Ermittlung der SAK254 Abnahme mit nur einer Messsonde, was prinzipiell Vorteile bei einer Regelung der Ozondosis auf ein stabiles <U+0394>SAK254 mit sich bringt. Zudem konnte gezeigt werden, dass die Onlinemessung der Fluoreszenz eine praktikable Alternative zum <U+0394>SAK254 darstellt, da diese ebenfalls eine Änderung des Ozonbedarfs integral erfassen kann und mit der Spurenstoffelimination korreliert. Die gewonnenen Ergebnisse bieten Messgeräteherstellern wertvolle Anhaltspunkte wie sie ihre Onlinesonden und Reinigungsmodule weiter optimieren können. Das entwickelte MSR-Konzept bzw. der alternierende Messbetrieb kann von Betreibern von Ozonanlagen auf kommunalen Kläranlagen zur Optimierung bestehender oder zukünftiger Anlagen genutzt werden.

During the last decades, it has become evident that some active pharmaceutical ingredients (API) have harmful environmental impacts on aquatic ecosystems. Therefore, there is a need to decrease the amount of pharmaceutical residues that end up in the environment. Information gaps related to increased awareness of the environmental impacts of pharmaceuticals in the health care sector and the promotion of sustainable consumption of pharmaceuticals have been identified in the Status Report on Pharmaceuticals in the aquatic environment of the Baltic Sea Region (BSR) published by UNESCO and HELCOM in 2017. The aim of the current report is to fill in some of the identified knowledge gaps identified in the HELCOM report, specifically increasing awareness about the environmental impacts of pharmaceuticals. In Sweden, there are good practices for healthcare professionals about how to consider the environmental impacts of medications already at the prescription phase, as well as guidelines for how to make the environmental information available and accessible to healthcare professionals and the public. The Swedish practices are described and evaluated, and the measures that can be implemented in the other BSR countries are formulated as recommendations. Eight recommendations were formulated through dialogues with stakeholders in Sweden. The recommendations are divided into four main areas i.e. education, databases and guidelines, dissemination of information to public, and collaboration among stakeholders. Some recommendations might be implemented without any large challenges or financial costs while other recommendations require large changes such as economic investments and changes in legislation. This report also contains information about existing practices in other countries in the Baltic Sea region (BSR), provided by the project partners in the CWPharma project. The countries in the BSR are currently at different levels when it comes to management of pharmaceuticals and their residues in the environment. Public awareness of the environmental impacts of pharmaceuticals differs, as do the systems for returning leftover medications. Basic education for health care personnel regarding the environmental consequences of different medications and pharmaceutical compounds exists in most of the BSR countries but the scope and content differs. One recommendation in the report is that environmental impacts of APIs should be compiled in a national, or ideally an EU level, database. As a first step, the Baltic Sea countries could investigate the possibility to establish national interfaces to the Swedish databases “Pharmaceutical and environment” (Janusinfo) or FASS. Although the data in “Pharmaceutical and environment” and FASS are not complete, they are existing platforms which provide valuable information and gather criteria important for classification. In Sweden, there are several channels for the dissemination of information about the environmental consequences of pharmaceuticals with the aim to raise public awareness regarding this subject. Examples of actions to be considered by other countries are information campaigns driven by pharmacies for returning unused and left over medications (Germany and Finland have similar campaigns), and distribution of leaflets with information about the environmental impacts of pharmaceuticals, which have proven to be efficient in raising awareness among pharmacists, doctors and the public. The collaboration of different stakeholders is one of the foremost reasons for the progress that has been made regarding pharmaceuticals in the environment in Sweden. The Swedish Medical Production Agency has set up a Knowledge Centre for Pharmaceuticals in the Environment, providing a platform for different actors to discuss environmental issues connected to pharmaceuticals. Among these actors there is a sense of a shared environmental vision with common goals. Hence, one recommendation for the BSR countries is to investigate the possibilities of establishing similar national knowledge centers within medicine agencies, or to use existing networks as a starting point to also involve other environmental issues related to pharmaceuticals and to find new collaboration possibilities. Finally, collaboration between the EU countries is crucial to successfully implement environmental aspects in the lifecycle of the pharmaceuticals.

The overall aim of the CWPharma project is to reduce the load of active pharmaceutical ingredients (APIs) going into the aquatic environment and especially the Baltic Sea. Municipal wastewater treatment plants (WWTPs) are relevant point sources of APIs, as they treat the wastewater from public households, hospitals and industry of the connected catchment area. However, conventional "state-of-the-art" WWTPs can only remove some APIs, which are either easily biodegradable and/or absorbable to activated sludge, whereas other APIs can pass the WWTP with minor to no reduction. Therefore, reduction of a broad range of APIs can only be achieved by using targeted advanced treatment techniques such as ozonation or powdered and granular activated carbon, respectively, which have already been applied on full-scale for API removal in wastewater treatment in Germany and Switzerland and proven their practical and economical suitability. At the usual applied ozone doses, ozonation of secondary effluent does not mineralize (convert an organic substance into inorganic matter) but transforms organic compounds into smaller and (usually) more biodegradable compounds. Secondary effluent is a complex water matrix consisting of hundreds of different organic substances, and it is not feasible to determine all possible transformation products and oxidation by-products, which might be created by the ozonation process. Thus, utilities and water authorities sometimes struggle with the uncertainties of the ozonation process as they perceive difficulties to judge whether oxidation of the organic matrix is beneficial or if it is creating more problems. As chemical analysis of the water only provides quantitative data for known APIs and transformation products for which chemical standards are available, effect-based ecotoxicological test systems can be used to assess the integrated actual toxicity of the whole water matrix. Based on previous research compiled by Völker et al. (2019), ozonation has a positive impact on several toxicological endpoints. But there are also indications that ozonation can create negative effects for a few toxicological endpoints that can be reduced by a suitable post-treatment. However, only little knowledge is available regarding suitable post-treatments and which ecotoxicological test systems are appropriate to evaluate their impact. In addition, post-treatment options might also have beneficial impacts on water quality parameters, APIs and transformation products. Thus, this report will evaluate different aspects regarding the impact of ozonation and its posttreatment options on (i) water quality parameters, (ii) APIs and transformation products (TPs) and (iii) ecotoxicological effects. The evaluation was conducted at three WWTPs in Linköping (SE), Kalundborg (DK) and Berlin (DE) and different post-treatment options such as moving bed bioreactors (MBBR), deep-bed filters, and a constructed wetland.

The overall aim of the "Clear Waters from Pharmaceuticals" (CWPharma) project is to provide guidance on how to reduce the load of active pharmaceutical ingredients (APIs) entering the aquatic environment and especially the Baltic Sea. Even though different methods for reducing the amount of APIs entering the wastewater exist and, thus, "end-of-pipe" measures are also necessary. API usage cannot be completely avoided. Municipal wastewater treatment plants (WWTPs) are relevant point sources of APIs as they treat the wastewater from public households, hospitals, and industry of the connected catchment area. However, conventional "state-of-the-art" WWTPs can only remove APIs that are either easily biodegradable and/or absorbable to activated sludge, whereas others can pass the treatment process with no or only minor reductions. Therefore, reduction of a broad range of APIs can only be achieved by using targeted advanced wastewater treatment (AWT) techniques, such as ozonation or application of powdered and granular activated carbon. All of these technologies for API removal are already used at full-scale WWTPs and have proven their practical and economical suitability. This guideline is meant to provide an overview on how to plan, start, and operate AWT technologies for API elimination. The recommendations are based on the experiences and results from the CWPharma project, but also on the available knowledge from Germany and Switzerland, which is collected and distributed by competence centres such as the German Micropollutants Competence Centre Baden-Württemberg (KomS) Verfahrenstechnik Mikroverunreiniungen and the Swiss Plattform as well as by expert groups from the related water associations. Membrane separation via dense membrane such as nanofiltration (NF) or reverse osmosis (RO) was not considered in this guideline, as both technologies produce a brine with high API concentrations. At coastal WWTPs, this brine might be discharged directly to the sea in order to protect fresh water ecosystems, but this would not reduce the API load to the Baltic Sea. Thus, the brine also requires treatment, which makes this approach less economical in comparison to the other established API removal technologies.

Upgrading wastewater treatment plants (WWTPs) with advanced technologies is one key strategy to reduce micropollutant emissions. Given the complex chemical composition of wastewater, toxicity removal is an integral parameter to assess the performance of WWTPs. Thus, the goal of this systematic review is to evaluate how effectively ozonation and activated carbon remove in vitro and in vivo toxicity. Out of 2464 publications, we extracted 46 relevant studies conducted at 22 pilot or full-scale WWTPs. We performed a quantitative and qualitative evaluation of in vitro (100 assays) and in vivo data (20 species), respectively. Data is more abundant on ozonation (573 data points) than on an activated carbon treatment (162 data points), and certain in vitro end points (especially estrogenicity) and in vivo models (e.g., daphnids) dominate. The literature shows that while a conventional treatment effectively reduces toxicity, residual effects in the effluents may represent a risk to the receiving ecosystem on the basis of effect-based trigger values. In general, an upgrade to ozonation or activated carbon treatment will significantly increase toxicity removal with similar performance. Nevertheless, ozonation generates toxic transformation products that can be removed by a post-treatment. By assessing the growing body of effect-based studies, we identify sensitive and underrepresented end points and species and provide guidance for future research.

In the recent years, an increasing number of organic micropollutants (OMPs) such as pharmaceuticals, industrial chemicals etc. have been detected within the water cycle. Conventional municipal wastewater treatment plants (WWTPs) are an important entry path of OMPs into the surface waters, as they can only partly eliminate OMPs. Thus, advanced wastewater treatment options such as activated carbon and/or ozonation can be used to reduce the amount of OMPs entering the receiving waters. Especially for the operation of an ozonation plant, aspects such as monitoring of the OMP elimination as well as an adaption of the ozone dose to a varying water quality are of great importance. Practical experiences in the last years have shown that the reduction of UVA254 (delta UVA254) by the ozonation can be used for the regulation of the ozone dose [1] and to monitor the ozonation process as it is recommended by the Swiss Water Association (VSA) in addition to a periodic measurement of the OMP elimination [2]. As an alternative to UVA254, usage of fluorescence online sensors have been also in discussion as its decrease due to the ozonation process also shows a good correlation with the OMP elimination [3]. Currently, fluorescence online measurements are used for detecting algae blooms in lakes or oil in water. However, practical experiences of the operation of fluorescence online sensors at ozonation plants used for OMP elimination are limited. Within this presentation results of the operation of a fluorescence online measurement at an ozonation pilot plant will be shown and compared to the operation of a UVA254 online measurement regarding sensitivity, impact of the water matrix, fouling effects as well as maintenance efforts.