2. Identifying and Managing Hazardous Pharmaceutical Waste MIRT Meeting May 15, 2002 Charlotte A. Smith, R. Ph., M.S. President 414-258-8359 csmith@ pharmecology.org 262-814-2635

3. §Founded Capital Returns, Inc. in 1991 §Pharmaceutical reverse distributor §Large quantity hazardous waste generator §Applied RCRA definitions item by item §Designated over 400,000 items §Pioneered seminars to the regulated industry §Sold Capital Returns, Inc. in 1997 §Affiliated as Chief Regulatory Advisor

4. §Development of Knowledge and Systems to Minimize the Destructive Impact of Pharmaceutical Waste on the Environment §To Insure Compliance with State and Federal Regulations in a Cost Effective Manner

5. Pharmaceuticals Entering the Waste Stream §Wastage of Raw Materials from Manufacturing Process §Wastage at the Distributor/ Pharmacy/Healthcare Facility §Wastage at the LTCF or other residential facility §Expired Pharmaceuticals §Wastage at the Consumer Level §Metabolites Entering Wastewater

6. How is Pharmaceutical Waste Generated at the Healthcare Facility? §IV Preparation §General Compounding §Spills/Breakage §Partially Used Vials/Syringes l If Contaminated, Biohazardous §Discontinued, Unused Preparations §Unused Repacks (Unit Dose) §Discontinued Indated Pharmaceuticals §Patients’ Personal Medications §Outdated Pharmaceuticals

7. Pharmaceutical Industry’s Unique Challenges §Substitution of less toxic chemicals usually not possible §Lack of application of EPA regulations to finished dosage forms §No readily retrievable source of information on specific products §Lack of knowledge of environmental regulations and the need to comply

8. RCRA Risk Management & Liability §Civil and criminal liability l Civil: State/USEPA enforcement l Criminal: FBI, Attorney General, Grand Jury §Corporate fines: $27,500 per violation/day §Personal liability: fines and/or imprisonment §No statute of limitations §Managers up through CEO

9. When is an Outdated Drug a Waste? §At the time and place the decision is made to discard it §Two EPA guidance letters to the industry: l Merck & Co., 1981 l BFI Pharmaceutical, 1991 §Enables shipping of potentially creditable outdates to a reverse distributor as product

10. History of Pharmaceutical Reverse Distribution §1987: Prescription Drug Marketing Act made returns processing by wholesalers & manufacturer reps more difficult §Late 1980’s, early 1990’s: Several entrepreneurs entered marketplace l Hospital oriented l Retail oriented l Manufacturer oriented

11. Demographics of DEA Registered Reverse Distributors: 38 Facilities in 20 States* §Illinois6 §Florida6 §Georgia5 §Tennessee 2 §Arizona2 §New Jersey2 §New York2 §North Carolina1 §Indiana1 §Iowa1 §Michigan1 §Missouri1 §Washington1 §Pennsylvania1 §Wisconsin1 §California1 §Delaware1 §Texas 1 §Ohio1 §Utah1 * 2000 DEA FOIA List of Registrants

12. Process Overview Industry Distribution/Reverse Distribution Model Manufacturers Wholesalers, Distributors Pharmacies, Institutions, other indirects Return 3 rd party processors Mfg. 3 rd party processors Incinerator

13. Reverse Distribution: Current Scenarios §Decision to discard is made at the pharmacy/wholesaler l By pharmacy/wholesaler personnel l By a contracted company l Pharmacy/wholesaler becomes the waste generator §Decision to discard is made at the reverse distributor l Reverse Distributor becomes the waste generator

14. Benefits of Reverse Distribution as an Industry §Development of core competency in receipt, handling, shipment of returnable items §Results in millions of dollars being returned to healthcare industry §Development of core competency in management of waste pharmaceuticals, RCRA and non-hazardous §Reduces likelihood of inappropriate disposal by healthcare industry

15. Case Study: Capital Returns, Inc. §20% to 30% of products received are non- returnable based on manufacturers’ policies and become waste at CRI §10% of non-returnable items are characterized as hazardous waste §2% to 3% of all returns received become hazardous waste

16. The Returns Industry Association §Association of pharmaceutical reverse distributors established in May, 1998 §Criteria includes a DEA registration to handle controlled substances in schedules II through V §RIA provides a unified voice for the industry,and a commitment to high quality standards and protection of the environment §Development of Guidelines for Minimum Regulatory Standards §Proposed development of Education & Certification Program

17. Federal and State Regulatory Agencies Governing Reverse Distribution EPA FDA DEA DOT OSHA State Env Protection State Board of Pharmacy DOH, Controlled Substance Board

18. David Jenkins Executive Director 703-787-8574 RIA@hdmanet.org www.returnsindustry.com RIA Contact Information

19. Which Discarded Drugs Become Hazardous Waste? §P-listed chemicals l Sole active ingredient §U-listed chemicals l Sole active ingredient §Characteristic of hazardous waste l Ignitability l Toxicity l Corrosivity l Reactivity

20. P-Listed Chemicals §Acutely hazardous §LD50 < 50mg/kg §Sole active ingredient §No concentration threshold §Cause entire formulation to be hazardous §Weight of container/solvent included §>1 kg/month (2.2 lbs) = Large Quantity Generator

21. Examples of P-Listed Pharmaceutical Waste §ArsenicP012 §Epinephrine P042 §NicotineP075 §NitroglycerinP081 §Physostigmine P204 §Physostigmine SalicylateP188 §Warfarin >0.3%P001

22. U-Listed Waste §May be U-listed due to toxicity, ignitability, corrosivity, reactivity §Pharmaceuticals U-listed primarily due to toxicity §Sole active ingredient §Over 100 kg/month (220 lbs) = Small Quantity Generator

23. Examples of U-listed Pharmaceutical Waste §Chloral Hydrate(CIV)U034 §ChlorambucilU035 §CyclophosphamideU058 §DaunomycinU059 §MelphalanU150 §Mitomycin C U010 §StreptozotocinU206 §LindaneU129 §SaccharinU202 §Selenium SulfideU205 §Warfarin<0.3%U248

24. Chemotherapy Waste §Seven chemotherapy agents are U-listed §Waste protocols for “Chemo Waste” l Empty vials, syringes, IV’s l Treated as infectious medical waste through autoclaving and landfilling or low temperature incineration §If not empty, should be placed into Hazardous Waste container §“Empty” means all contents removed that can be removed through normal means

25. Characteristic of Ignitability §Aqueous Solution containing 24% alcohol or more by volume & flash point<140° F. §A Liquid having a flash point <140° F. §An ignitable compressed gas (certain aerosols) §An oxidizer §Hazardous Waste Number: D001

26. Examples of Ignitable Discarded Pharmaceuticals §Rubbing Alcohol §Paregoric (CIII) §Cleocin T Topical Solution §Retin A Gel §Listerine Mouthwash §Erythromycin Topical Solution §Silver Nitrate (oxidizer) §Collodion Based Preparations

27. Characteristic of Corrosivity §An aqueous solution having a pH or = to 12.5 §Examples: Primarily compounding chemicals l Glacial Acetic Acid l Sodium Hydroxide §Hazardous waste number: D002

28. Characteristic of Toxicity §Approximately 40 chemicals which meet specific leaching concentrations §Examples of potential toxic pharmaceuticals: §Arsenicm-Cresol §Barium Mercury (thimerosal) §Cadmiumphenylmercuric acetate) §ChloroformSelenium §ChromiumSilver §Lindane

30. Characteristic of Reactivity §Meet eight separate criteria identifying certain explosive and water reactive wastes §Nitroglycerin formulations are considered exempt as of August 14, 2001 under FR: May 16, 2001. States must still adopt. §Hazardous Waste Number: D003

31. Applicable USEPA Interpretative Letters & Hotline Responses §Epinephrine Residue in Syringe not P042 l Hotline December 1994 §Discarded Nitroglycerine Pills are P081 l Hotline September 1993; Modified Aug 14, 2001? §Disposal of CESQG hazardous waste l Hotline August 1999 §Anti-Neoplastic Agents l January 30, 1986 l April 25, 1988

32. Washington State State-only Dangerous Waste

33. §Services l National and Regional Seminars to Raise Awareness l Confidential On-Site Reviews of Current Practices, Possible Areas of Concern l Implementation Assistance in Developing Compliant Systems l Web-based PharmEcology Wizard

34. The PharmEcology™ Wizard §Web-based database enabling search by product for waste management recommendations §Search by NDC, product or generic name, active ingredient l Recommendations citing federal regulations and recommended waste streams l State regulation alerts if more stringent than federal l Risk Management alerts based on professional knowledge (e.g. chemotherapy agents not regulated at the state or federal level)

35. The PharmEcology Wizard Prototype

37. 2-2576-5

39. Readi-Cat

43. Future Considerations §Identify which hazardous wastes as defined present a real threat at levels normally seen in pharmaceuticals §Establish a relationship between professional pharmacy organizations and USEPA, state environmental regulatory agencies §Work towards exemptions from and expansion of RCRA where appropriate §Work towards consistent standards of enforcement

44. Resources §www. ourstolenfuture.org §www. lindane.org/world/environment/water §www. h2e-online.org §“Safely Managing Hazardous Materials and Hazardous Waste,” ASHP Clinical Midyear, 2001, Handouts on CD- Rom §RCRA On-Line www.epa.gov/rcraonline §RCRA Hot Line 1-800-424-9346 §Improper Discard of Toxic Drugs Hurts Environment, Leads to Fines, AJHP, Vol 58, #17 September 1, 2001 pp 1576-1578.

45. Resources §www. pharmecology.org Go to link to article “Bad Medicine” January 2001 §Your Risks in Handling Outdated and Unusable Drugs: A Guide to JCAHO and Regulatory Standards. Capital Returns, Inc., 1998 Call 1-800-950-5479 §A Guide on Hazardous Waste Management for Florida’s Pharmacies, www. floridacenter.org. §Guidelines for Reverse Distributors: Minimum Federal Regulatory Standards, www.returnsindustry.com

46. Appendix Endocrine Disruptors: Emerging Contaminants

47. Cause for Concern? §Endocrine Disruptors: chemicals that interfere with the normal function of the endocrine system §Mimic hormone, trigger identical response, block a hormone §Do not follow the normal dose/response curve §Active at much lower doses, especially in the fetus and newborn §Estradiols, testosterone, progesterone §Lindane

48. USGS Water Quality Study* §First nationwide reconnaissance of occurrence of pharmaceuticals, hormones, other organic wastewater contaminants §139 streams in 30 states, analyzed for 95 different OWCs §82 of the 95 detected in at least one sample §One or more OWCs found in 80% of stream samples §13% of sites had more than 20 OWCs *http://toxics.usgs.gov/pubs/OFR-02-94/index.html

49. Location of 139 Stream Sampling Sites: USGS, 1999 - 2000

50. Drug Residues In Ambient Water: Initial Surveillance in New Mexico* §NM Environment Department §Scientific Laboratory Division §Drug detection limits into low ppt (10 ng/L) §Test included Darvon, Dilantin, Prozac other antidepressants, prednisone, estrogens, caffeine, tamoxifen §8 sites positive, 16 negative §Next study will include antibiotics, lipid- regulators, and cardiovascular pharmaceuticals * http://www.nmenv.state.nm.us/gwb/drugs.html

51. New Mexico Drug Residue Sampling Red = Positive

52. California has tested for lindane, reported contamination levels, banned use on humans for lice and scabies* *www.lindane.org/world/environment/ water/national.htm

53. Our Stolen Future: How Endocrine Disruptors May Be Threatening Our Lives and Survival §Seven years synthesizing research on endocrine-disrupting chemicals §Extensive database §Estrogen mimics, blockage of testosterone, disruption of thyroid hormones §www.ourstolenfuture.org

54. Generations at Risk: Reproductive Health and the Environment §Ted Schettler, MD. Gina Solomon, MD, Maria Valenti, Annette Huddle §Reproductive Physiology and Toxicology §Reproductive and Developmental Effects of Selected Substances and Human Exposure §A Guide to Investigating Environmental Threats

55. §Low sperm counts §Infertility §Genital deformities §Hormonally triggered human cancers §Neurological disorders in children l Hyperactivity l Attention deficit §Developmental & reproductive problems in wildlife

56. Early Warnings §Copenhagen, Denmark: 1992 l Review of 61studies by Niels Skakkeback, University of Copenhagen l Average human male sperm counts dropped by almost 50% between 1939 and 1990 l Incidence of testicular cancer jumped l Undescended testicles and shortened urinary tracts rising among young boys

57. Early Warnings DES (Diethylstilbestrol) §Used in the 1950’s - early 1970’s to prevent miscarriages - potent estrogenic §Resulted in daughters of mothers given DES developing clear-cell cancer of the vagina, other reproductive effects §Sons not studied well, but indications of reproductive abnormalities, testicular cancer

58. Early Warnings §Steady 1% a year increase in breast cancer rates since WWII §Exposure during prenatal period critical §51 synthetic chemicals now identified as hormone disruptors; at least half are persistant and resist natural decomposition §Mother’s breast milk is contaminated

59. Identification of Endocrine Related Pharmaceuticals §Estrogens §Progesterones §Testosterones §Corticosteroids §Glucosteroids §Thyroid

60. Identification of Pharmaceuticals as Endocrine Disruptors* §Chloroform: Reproductive §Ketoconazole: Reproductive l Nizoral® §Lindane: Estrogen/Androgen §Malathion: Thyroid l Ovide® §Permethrin: Androgen mimic l Elimite®, Acticin®, Nix® *http://www.ourstolenfuture.org/Basics/chemlist.htm * Generations at Risk: Reproductive Health and the Environment

61. Identification of Pharmaceuticals as Endocrine Disruptors* §Nonylphenol: Estrogen §Resorcinol: Thyroid §Arsenic: Glucocortocoid l Trisenox®, Atrivex® §Mercury: Reproductive/Thyroid l Thimerosal, Mersol®, Aeroaid® *http://www.ourstolenfuture.org/Basics/chemli st.htm Generations at Risk: Reproductive Health and the Environment