VERMINDERUNG VON EMISSIONEN UND ENTFERNUNG VON MEDIKAMENTEN AN DER QUELLE (MITIGATION AND SOURCE TREATMENT OF PHARMACEUTICALS)

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1 VERMINDERUNG VON EMISSIONEN UND ENTFERNUNG VON MEDIKAMENTEN AN DER QUELLE (MITIGATION AND SOURCE TREATMENT OF PHARMACEUTICALS) Kai Bester, Helene Ek Henning, Thomas Møller 1

2 Which source matters? What mitigation options are there? What innovative treatment options can be used?

3 Which source matters?

4 Generally at source treatment: Is cheaper than central treatment However, it will only have effects on surface water concentrations IF single sources are the solely or predominantly responsible for the loadings in surface waters. Examples are: A company is sole user of a problematic compound in a catchment (PFOS) A company is the predominant source (50%) of Nonylphenol in a catchment

5 Pharmaceuticals in wastewater from hospitals Are hospitals a major source to pollution with pharmaceuticals? A constant increase in ambulant treatments at Aarhus University Hospital (AUH) indicate, that an increasingly amount of the pharmaceuticals are excreated from the patients own homes. Ambulant treatments at Aarhus University Hospital % increase in ambulant treatments at AUH from 2007 to 2015 Amount Year

6 How much is consumed at hospitals? 4% (kg) of the total consumed amount of pharmaceuticals in Denmark is consumed at hospitals Danish authorities are focusing on 4% of the number of drugs used at the hospitals (i.e. 40 compounds).

7 Mapping from Aarhus University Hospital Essential: Mapping is based on data from the Electronic Patient Journal (EPJ) Calculated environmental impact for Primary sector (home/ambulant) Secondary sector (hospitals) 6 pharmaceuticals alone are source to almost all (98%) of the calculated environmental impact Mycophenolic acid (71% alone), clarithromycine, sulfamethoxazole, sertraline, ciprofloxazine and capecitabine

8 Calculated environmental impact Environmental impact from ambulant treatment and hospital treatment vs total impact. (based on the 4% of the drugs consumed at hospitals, that the Danish authorities focus on) 2011: 78,4% 2015: 83,6% Percentages 100,0% 90,0% 80,0% 70,0% 60,0% 50,0% 40,0% 30,0% 20,0% 10,0% 0,0% Environmental impact from AUH distributed betw een am bulant and hospitalised patients Hospitalized Ambulant

9 Measured vs calculated concentrations at AUH Measured concentrations supports the calculated concentrations. Pharmaceutical inflow pilot WWTP at hospital Effluent pilot WWTP at hospital Calculated for hospital Effluent Municipal WWTP in DK µg/l µg/l µg/l µg/l Azithromycin 1,09 0,62 1,71 0,28 Carbamazepin 0,13 0,07 2,53 0,25 Ciprofloxacin 2,78 0,97 46,50 - Clarithromycin 1,60 0,33 13,78 0,13 Diclofenac 0,21 0,037 0,19 0,55 Ibuprofen 16,30 0,37 87,71 0,28 Propranolol 0,24 0,21 0,52 0,08 Sulfamethoxazole 1,83 0,79 135,51 0,13 Venlafaxine 2,70 1,40 2,23 0,41 Calculations are done for hospital wastewater based on in hospital usage (does not consider metabolisation) WWTP is an at source pilot treatment plant at (AUH Skejby) Green coloring indicate accordance between calculation and measuring

10 Conclusions from mapping pharmaceuticals in Aarhus There is a considerable risc that at source treatment will not result in less concentrations in surface waters. Results from mapping use of pharmaceuticals may vary depending on number and speciality of departments on the actual hospital. Removal of pharmaceuticals at the municipal WWTP will of course be more expensive than local treatment. But there are clear indications, that the environmental benefit from central treatment will have a significantly greater environmental effect. Hence central treatment may often be the right solution.

11 What mitigation options are there?

12 What mitigation options are there? The consumer uses less and/or less problematic compounds Unused pharmaceuticals are collected efficiently Human excreetions of patients are collected and disposed off appropriately

13 Educated decisions of patients and healthcare professionals Aim To raise awareness on environmental impacts of pharmaceuticals in the health care sector and to promote sustainable consumption of pharmaceuticals. To steer the use of pharmaceuticals from the environmentally hazardous APIs to the use of less hazardous APIs if the same effect on human health can be achieved. Example: Swedish environmental classification system.

14 The Swedish classification system Considering pharmaceuticals with similar effect on a disease may have different environmental impacts Pharmaceuticals are assessed with guidance of the Swedish authorities by the respective companies. Persistence, (PEC/PNEC) and Bioaccumulation are taken into account The results are publicly available under FASS.se The patients and healthcare professionals can decide on how to prioritise association for the research based pharmaceutical Industry in Sweden

15 Categorisation in FASS.SE Miljöinformationen för diklofenak är framtagen av företaget Novartis för Diklofenak Sandoz, Small risk Otriflu, Voltaren, Voltaren T Miljörisk: Användning av diklofenak har bedömts medföra försumbar risk för miljöpåverkan. Nedbrytning: Diklofenak bryts ned långsamt i miljön. Bioackumulering: Diklofenak har låg potential att bioackumuleras. PEC: 1,152 µg/l moderate risk degrading Slowly degrading Ibuprofen Miljörisk: Användning av ibuprofen har bedömts medföra medelhög risk för miljöpåverkan. Nedbrytning: Ibuprofen bryts ned i miljön. Bioackumulering: Ibuprofen har låg potential att bioackumuleras. PEC: 2.95 μg/l

16 Graphical information given by FASS.se

17 Background: Strong political pressure from the citizens via the ministry Harmonized approach (Pharmaceutical Industry, Stockholm City Council, Apoteket) + Swedish Environmental Research Institute (IVL) Good experience concerning detergents (washing powders) and cosmetics Acceptance for public awareness programmes (posters in subway/busses etc)

18 Environmental labelling at pharmacies Environmental labelling on non-prescription medicines was introduced in 2017 by Sweden's largest pharmacy chain. Aim is to guide customers to make a more sustainable choice. The labeling means that the supplier has a good and long-term environmental and sustainability work, contributing to a more sustainable drug production. Externally reviewed sustainability report according to GRI standard * Membership in PSCI. ** * Global Reporting Initiative is the most well-known international standard for sustainability reporting. ** Pharmaceutical Supply Chain Initiative is the global industry organisation that aims to share and spread the best expertise in environmental and sustainability issues in the supply chain. Environmental labelling; Choose with heart

19 Take-back and disposal of unused medicines Aim To reduce the disposal of unused medicines via solid waste or sewer/to enhance selective collections. CW Pharma Evaluates the current national practices for take-back system of unused medicines and how this waste is treated in collaboration with HELCOM. will give recommendations on good practices for efficient take-back schemes and disposal of unused medicines.

20 It is generally anticipated that the consumer will tune disposal strategies very much on how supportive the take back systems work: Are the pharmacies providing the service proactively? SE example: bonusses for brought back compounds Are the pharmacies non supportive but willing? Are the pharmacies communicating: You can as well put that into Your waste bin

21 Innovative treatment options (biofilm reactors)

22 Moving Bed Biofilm Reactor with carrier carriers of typically 20 mm Carrier Biofilm

23 Basis of the pilot staged aerobic MBBR Compound + Oxygen Biomass + CO 2 23

24 Staged aerobic MBBR Pump H0 ν i = 0.50 L h -1 Pump M1 M2 M3 21/26 compounds degraded >20% First order kinetics for most compounds Two phase kinetics for four compounds While M1 degrades faster, has M3 usually the more effective biomass Escola Casas et al., Wat Res., 2015 Diclofenac reaction rate K= K bio :

25 AARHUS UNIVERSITET Organic micropollutants - degradation Smart, energy friendly, but how? Competition with easy food Easy food/ BOD Micropollutant Micropollutant Essential co-degradation TITEL PÅ PRÆSENTATION NAVN NAVNESEN Easy food/ BOD 2. MAJ 2011

26 BOD/Cake Intermittant feeding -> Diclofenac Raw wastewater 3 Days 18 HRT Effluent wastewater 6 Days 36 HRT Tang et al., Bioresource Technology,

27 Removal of Diclofenac with MBBR under intermittant feeding Tang et al., Bioresource Technology, 2017

28 Metabolites in aerobic MBBR - Clindamycin - H H N O C H 3 CH 3 H H NH S O Cl OH OH OH H CH 3 Clindamycin H 3 C H H N O C H 3 CH 3 H H NH S O Cl O OH OH H CH 3 OH H H O NH C H 3 H H NH S O Cl OH OH OH H CH 3 H 3 C H 3 C Ooi et al. Wat Res, 2017 Clindamycin - sulfoxide Desmethyl-Clindamycin

29 Production kinetics of clindamycin metabolites in MBBRs Clindamycin sulfoxide N-desmethyl clindamycin Concentration (µg/l) Control Test sample Concentration (µg/l) Control Test sample Time (h) Time (h) Ooi et al. Wat Res, 2017

30 Hybrid technologies Ozonation Biofilm

31 Can those ozonation products be removed with biofilm reactors? El Taliawy et al., 2018 Ozonation of Erythromycin, Clarithromycin, Azithromycin

32 El Taliawy et al., 2018 Degradation of Clarithromycin N-oxide in MBBR (1 µg/l) Clarithromycin-N-oxide Clarithromycin-N-oxide (control)

33 El Taliawy et al., 2018 Degradation of Clarithromycin N-oxide in MBBR (elevated concentration 10 µg/l) Clarithromycin-N-oxide Clarithromycin-N-oxide (control)

34 Conclusions Treating point sources can be triggered by different means, but does not always result in decreasing surface water concentrations Mitigation can be promising but it needs a lot of communication and some political will Biofilm technology might have more potential in treating water than commonly thought 34