1. 1 An Evaluation of Unused Medicine Disposal Options On Wastewater Treatment Plant Influents Douglas S. Finan – GlaxoSmithKline Matthew D. Garamone - Pfizer Inc. James Jahnke - Schering-Plough Corporation Fourth Annual Unused Drug Return Conference October 31 – November 1, 2007 Portland, Maine

2. 2 Some Background on PIE n 1999, USGS National Reconnaissance of Emerging Contaminants  sampled a network of 139 streams across 30 states for the presence of pharmaceuticals  nonprescription drugs were found with the greatest frequency, followed by antibiotics, reproductive hormones, and other prescriptions drugs  concentrations were very low (i.e., part per trillion level) Lots of Press Many interested stakeholders

3. 3 Some Background on PhRMA - The research based pharmaceutical industry is working to understand PIE n PhRMA is committed to applying the same level of scientific rigor to PIE that we apply in other areas of our business n We have developed working groups around PIE subjects n Fate and Transport n Human Health n Environmental Risk Assessment n Hormones n Unused Medicines n Treatment n Communications

4. 4 Some Background on Unused Medicine Disposal n In the past patients were told that drain disposal was the safest way to dispose of unused medicines. n Publications on PIE identified unused medicine disposal as a driver for detection of pharmaceutical compounds in surface waters n Several cities & towns have sponsored unused medicines take- back events n Some states such as Maine and California have introduced legislation designed to encourage the development of pharmaceutical take-back programs n In 2007 ONDCP/EPA/FDA issue Federal Guidelines on the Proper Disposal of Prescription Drugs n In 2007 a bill was introduced in the US Congress directing EPA to study pharmaceutical take back programs

5. 5 PRINCIPAL PATHWAYS FOR PHARMACEUTICALS INTO THE ENVIRONMENT WWTP Landfill Incineration What is the Impact of Unused Medicine Disposal on WWTPs?

6. 6 Objectives n Determine the impact on WWTP influent concentrations if active pharmaceutical ingredients (API) if: n all patient unused medicine was flushed n all patient unused medicine was placed in household trash n all patient unused medicine was taken back for incineration. n Compare estimated API influent concentrations currently with those anticipated if take back programs were widely available and implemented. n Identify next steps and additional data that are needed to answer the question: What is the best way to dispose of unused medicine?

7. 7 OBJECTIVE 1 Determine the impact on WWTP influent concentrations if active pharmaceutical ingredients (API) if: n all patient unused medicine was flushed n all patient unused medicine was placed in household trash n all patient unused medicine was taken back for incineration.

8. 8 First, How Much Medicine Given to Patients Goes Unused? n No definitive answer yet n What do we know - from peer reviewed literature n LTCF 6.7% unused based on financial data n LTCF 13.1% unused based on financial data n General public 2.3% unused based on financial data n General Public 3% unused based on unit counts n For our analysis, it was assumed that 10% of medicine purchased by the patient is unused.

9. 9 Next, What Compounds Should be Studied n What have been detected (USGS etc.) n What data are available n Other studies n Identified twenty-four APIs representing a range of prescription drugs in terms of sales and physical-chemical properties AcetaminophenDiltiazemIbuprofenRanitidine Albuterol SulfateDoxycyclineLincomycinSulfamethoxazole CimetidineEnalaprilatMetforminSulfathiazole CiprofloxacinErythromycin-H2ONorfloxacinTetracycline CodeineFluoxetineOxytetracyclineTrimethoprim DigoxinGemfibrozilParoxetine metabolite Warfarin

10. 10 n Estimating influent mass for each API from Patient Use n Annual Sales Data converted to Kgs of API (Tischler, L. In Press) n % of sales that goes unused (assumed 10%) n Loss by human metabolism (Tischler, L. In Press) n Influent Amount (Kg) = Sales*(0.90)*(1-Metabolism%) n Estimating influent concentration for each API n U.S. FDA method for estimating aquatic conc. (FDA, 1998) Uses Kg/yr of API Annual liters of wastewater entering WWTPs = 4.431x10 13 (FDA, 1998) Influent Conc. μ g/l= Estimating WWTP Influent Concentrations From Patient Use API (kg/yr) 4.431x10 13 (l/yr) * 1x10 9 (μg/kg)

11. 11 Estimated API Concentrations From Patient Use (also influent concentration if all unused medicine is taken back for incineration)

12. 12 n Drain Disposal = Annual mass of API from patient use plus mass of the 10% of sales that goes unused and total flow to WWTPs. n Take Back Programs = patient use concentrations since it is assumed that all take back would be incinerated. n Household Trash – annual mass of API from patient use plus amount of medicines in landfill leachate for 10% unused (Tischler, L. In Press) and total flow to WWTPs. n Tischler’s Method Estimate concentration of API in landfill leachate Estimate leachate volume (assume all leachate sent to WWTPs) Estimate mass of API in leachate Assumed all medicine unpackaged & immediately available for leaching Fate in landfill incorporates three loss mechanisms n Partitioning to solids (based on Kp) n Anaerobic degradation n Hydrolysis Comparing Influent Concentrations of Disposal Methods

13. 13 Estimated API Concentrations From Patient Use and 100% Sewer Disposal of Unused Medicine In this scenario, on average, 21% of influent load is due to unused medicine disposal to the sewer. 79% of influent load is due to patients taking medicines

14. 14 Estimated API Concentrations From Patient Use and 100% Household Trash Landfill Disposal of Unused Medicine On average, 0.9% Influent Load is due to unused medicine disposal to landfill. 99.1% of influent load is due to patients taking medicines

15. 15 Comparison n Sewer Disposal – Average = 0.9 μg/l n Landfill Disposal – Average = 0.001 μg/l n Take Back – No Change Max = 12.8 μg/l Min = 0.005 μg/l Max = 0.01 μg/l Min = <0.0000001 μg/l n Influent Concentration Changes in μg/l From Unused Disposal Max = 74% Min = 10% Max = 11% Min = 0.0% n Sewer Disposal – Average = 21% n Landfill Disposal – Average = 0.9% n Take Back – 0.0% n % Influent Load From Unused

16. 16 Comparison Chart

17. 17 OBJECTIVE 2 Compare estimated API influent concentrations currently with those anticipated if take back programs were widely available and implemented.

18. 18 What Do Patients Currently Do With Their Unused Medicine n Household Trash = 45% to 55% n Drain Disposal = 20% to 35% n Take Back or Household Hazardous Waste = 1% to 8% n Other: n Give it to other people n Store it n Always take it all n We will use the upper bound n 15% of household trash in the US is incinerated

19. 19 Current State - Average 10% Influent Contribution From Unused

20. 20 What Kind of Participation Can We Expect In Take Back Programs n US unused medicine take back pilots - 1% n European unused medicine take back programs – 50% n Canada – 20% n Other US take back or mail back programs n Dry Cell Batteries – 3% n Car Batteries – 90% n Electronic Equip – 15% n Plastic Shopping Bags – 3% n Household Hazardous Waste – 3% n Curbside Recycling – 80% n We use 20% participation for a US program and assume that the rest is disposed of in the trash

21. 21 Future State with Mature Take Back - Average 0.7% Influent Contribution From Unused

22. 22 Comparison Of Present and Potential Future States n Average Estimated Influent Difference Between Take Back and Household Trash Disposal is: n Concentration - 0.2 parts per trillion n Percent of Influent Load From Unused 0.15% * 15% of household trash is incinerated *

23. 23 Comparison of Chart

24. 24 OBJECTIVE 3 Identify next steps and additional data that are needed to answer the question: What is the best way to dispose of unused medicine?

25. 25 Some Data Gaps n Amount of Unused Medicine n Long Term Care Facilities may help answer this question n Coroner's offices may also have some data n Better data collection during pilots n Confirmation of landfill leachate estimations n Actual sampling of leachate n Take Back Participation n Work with pilots to understand participation rates

26. 26 Evaluation of Other Environmental Drivers Needed n Carbon Footprint and Climate Change n Air Emissions n Repackaging n Groundwater Contamination n Considering a Lifecycle Assessment of Take Back and Trash Disposal

27. 27 We Need to Understand the Drug Abuse & Poisoning Issue Where Does It Occur? Landfill Incineration Take Back Household Trash Mail Back Household Hazardous Waste

28. 28 We Need to Understand Why Medicine Goes Unused n From Patient Surveys n Adverse Effects n Condition Resolved n Excess supplies n Medication expired n Medication or dosage changed n Non-adherence - Perceived Ineffective n Patient left (hospitalized, transferred, died) n Over Prescribing n Insurance Company Practices

29. 29 SUMMARY & QUESTIONS

30. 30 Summary n Even with current disposal practices, drain disposal of unused medicines is very unlikely to contribute more than 10% of the APIs found in WWTP influents. n Either household trash disposal or take back programs can reduce the unused medicine contribution of APIs in WWTP influent to < 1% n Drain disposal of unused medicine should be discouraged n It is likely that there would be little effect (less than a 1 part per trillion) on WWTP API influent concentrations as a result of implementing unused medicine take back programs compared to household trash disposal. n More information is needed before the “best way to dispose of unused medicine” can be determined n the other environmental impacts of landfill and incineration disposal of unused medicines n where in the unused medicine physical flow drug abuse and poisoning occur

31. 31

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