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

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

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 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 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 Comparison n Sewer Disposal – Average = 0.9 μg/l n Landfill Disposal – Average = μg/l n Take Back – No Change Max = 12.8 μg/l Min = μg/l Max = 0.01 μg/l Min = < 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 Comparison Chart

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

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 Current State - Average 10% Influent Contribution From Unused

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

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

23 Comparison of Chart

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 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 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 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 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 SUMMARY & QUESTIONS

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

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32 References n What happens to expired medications? A survey of community medication disposal, Kuspis DA, Krenzelok EP, Veterinary and human toxicology, 2/1/1996, 38(1), 1 n Patient Practices and Beliefs Concerning Disposal of Medications, Seehusen DA, Edwards J, Journal of the American Board of Family Medicine, 11/1/2006, Vol. 19 No. 6, 2 n Medication destruction and waste measurement and management in long-term care facilities, Paone RP, Vogenberg FR, Caporello E, Rutkowski J, Parent R, Fachetti F, The Consultant Pharmacist, 1/1/1996, Vol. 11, 3 n The Disposition of Unused Medications in Nursing Facilities Study, Unpublished report prepared for the Ohio Department of Job & Family n The Cost of Medication Waste, Bolvin M, Canada Pharm Journal, 5/1/1997,, 5 n The economic impact of Wasted Prescription Medication in an outpatient Population of Older Adults, Morgan TM, The Journal of Family Practice, 9/1/2001, Vol. 50 No. 9, 6 n Household Disposal of Pharmaceuticals as a Pathway for Aquatic Contamination in the United Kingdom, Bound JP, Voulvoulis N, Environmental Health Perspectives - available at 8/9/2005, n Reasons why medicines are returned to Swedish pharmacies unused, Ekedhal ABE, Pharm World Science (2006) - DOI /s , 1/13/2007, Vol. n Washington Citizens for Resource Conservation - a Soundstats Report, Unpublished, 1/1/2006,, 9 n An investigation of returned medicines in primary care, Langley CA, Marriott JF, Mackridge A, Daniszewsi R,, Pharm World Sci (2005), 1/1/2005, Vol. 27, 10 n Drugs up in smoke: a study of caseated drugs in Sweden, Isacson D, Olofsson C, Pharm World Sci 1999, 1/1/1999, Vol. 21(2), 11 n Report on San Francisco Bay Area's Safe Medicine Disposal Days, Unpublished available at -, n Three Years' Experience with a Medidump Program Operating from a Suburban Community Hospital, Stuchbery P, Australian Journal Of Hospital Pharmacy 1988, 1/1/1988, Vol. 18 No. 4, 13 n Guidance for Industry: Environmental Assessment of Human Drug and Biologics Applications, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), July 1998, Available at: n Potential Contribution of Unused Medicines to Environmental Concentrations of Pharmaceuticals, Tischler, L., September 2007, In Press n Municipal Solid Waste in the United States 2005 Facts and Figures, US EPA, October 2006, EPA-530-F