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

Founded Capital Returns, Inc. in 1991Pharmaceutical reverse distributorLarge quantity hazardous waste generatorApplied RCRA definitions item by itemDesignated over 400,000 itemsPioneered seminars to the regulated industrySold Capital Returns, Inc. in 1997Affiliated as Chief Regulatory Advisor

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

Pharmaceuticals Enteringthe Waste Stream

Wastage of Raw Materials from Manufacturing Process

Wastage at the Distributor/ Pharmacy/Healthcare Facility

Wastage at the LTCF or other residential facilityExpired PharmaceuticalsWastage at the Consumer LevelMetabolites Entering Wastewater

How is Pharmaceutical Waste Generated at the Healthcare Facility?

IV PreparationGeneral CompoundingSpills/BreakagePartially Used Vials/Syringes

If Contaminated, BiohazardousDiscontinued, Unused PreparationsUnused Repacks (Unit Dose)Discontinued Indated PharmaceuticalsPatients’ Personal MedicationsOutdated Pharmaceuticals

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

RCRA Risk Management & Liability

Civil and criminal liability Civil: State/USEPA enforcement Criminal: FBI, Attorney General, Grand Jury

Corporate fines: $27,500 per violation/dayPersonal liability: fines and/or

imprisonmentNo statute of limitations Managers up through CEO

When is an Outdated Drug a Waste?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: Merck & Co., 1981 BFI Pharmaceutical, 1991

Enables shipping of potentially creditable outdates to a reverse distributor as product

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 Hospital oriented Retail oriented Manufacturer oriented

Demographics of DEA Registered Reverse Distributors: 38 Facilities

in 20 States* Illinois 6 Florida 6 Georgia 5 Tennessee 2 Arizona 2 New Jersey 2 New York 2 North Carolina 1 Indiana 1 Iowa 1

Michigan 1 Missouri 1 Washington 1 Pennsylvania 1 Wisconsin 1 California 1 Delaware 1 Texas 1 Ohio 1 Utah 1

* 2000 DEA FOIA List of Registrants

Process OverviewIndustry Distribution/Reverse Distribution Model

ManufacturersWholesalers, Distributors

Pharmacies, Institutions,

other indirects

Return3rd party

processors

Mfg.3rd party

processors

Incinerator

Reverse Distribution: Current Scenarios

Decision to discard is made at the pharmacy/wholesaler By pharmacy/wholesaler personnel By a contracted company Pharmacy/wholesaler becomes the waste

generatorDecision to discard is made at the reverse

distributor Reverse Distributor becomes the waste

generator

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

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

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

Federal and State Regulatory Agencies Governing

Reverse Distribution

EPA FDADEA

DOT OSHA

State EnvProtection

State Board of Pharmacy

DOH,Controlled Substance

Board

David Jenkins Executive Director

703-787-8574 RIA@hdmanet.org

www.returnsindustry.com

RIA Contact Information

Which Discarded Drugs Become Hazardous Waste?P-listed chemicals

Sole active ingredientU-listed chemicals

Sole active ingredientCharacteristic of hazardous waste

Ignitability Toxicity Corrosivity Reactivity

P-Listed Chemicals

Acutely hazardousLD50 < 50mg/kgSole active ingredientNo concentration thresholdCause entire formulation to be hazardous Weight of container/solvent included>1 kg/month (2.2 lbs) = Large Quantity

Generator

Examples of P-Listed Pharmaceutical Waste

Arsenic P012Epinephrine P042Nicotine P075Nitroglycerin P081Physostigmine P204Physostigmine Salicylate P188Warfarin >0.3% P001

U-Listed Waste

May be U-listed due to toxicity, ignitability, corrosivity, reactivity

Pharmaceuticals U-listed primarily due to toxicity

Sole active ingredientOver 100 kg/month (220 lbs) = Small

Quantity Generator

Examples of U-listed Pharmaceutical Waste

Chloral Hydrate(CIV) U034

Chlorambucil U035

Cyclophosphamide

U058

Daunomycin U059

Melphalan

U150

Mitomycin C U010

Streptozotocin U206

Lindane U129

Saccharin U202

Selenium Sulfide U205

Warfarin<0.3% U248

Chemotherapy WasteSeven chemotherapy agents are U-listedWaste protocols for “Chemo Waste”

Empty vials, syringes, IV’s 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

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 oxidizerHazardous Waste Number: D001

Examples of Ignitable Discarded Pharmaceuticals

Rubbing AlcoholParegoric (CIII)Cleocin T Topical SolutionRetin A GelListerine MouthwashErythromycin Topical SolutionSilver Nitrate (oxidizer) Collodion Based Preparations

Characteristic of Corrosivity

An aqueous solution having a pH < or = 2 or > or = to 12.5

Examples: Primarily compounding chemicals Glacial Acetic Acid Sodium Hydroxide

Hazardous waste number: D002

Characteristic of Toxicity

Approximately 40 chemicals which meet specific leaching concentrations

Examples of potential toxic pharmaceuticals:Arsenic m-CresolBarium Mercury (thimerosal)Cadmium phenylmercuric acetate)Chloroform Selenium Chromium SilverLindane

Evaluation of Thimerosal Toxicityper Merck Index, Twelfth Edition:

Thimerosal (C9H9HgNaO2S) mol. wt. 404.82

C 26.70%H 2.24%Hg 49.55%Na 5.68%O 7.90%S 7.92%

1:1000 Solution:Thimerosal may be used as a preservative in aconcentration of 1:1000, which means, by definition, 1gram in 1000ml of solution.Since thimerosal is 49.55% mercury (see above):1g thimerosal x 49.55% = 0.4955g mercury.

So: 1g thimerosal = 0.4955g Hg =1000ml 1000ml

495.5mg Hg = 495.5mg Hg . 1000ml 1 liter

The regulatory limit for mercury is 0.2mg . 1 liter

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

Applicable USEPA Interpretative Letters & Hotline

ResponsesEpinephrine Residue in Syringe not P042

Hotline December 1994

Discarded Nitroglycerine Pills are P081 Hotline September 1993; Modified Aug 14, 2001?

Disposal of CESQG hazardous waste Hotline August 1999

Anti-Neoplastic Agents January 30, 1986 April 25, 1988

Washington State

State-only Dangerous Waste

Services National and Regional Seminars to Raise

Awareness Confidential On-Site Reviews of Current

Practices, Possible Areas of Concern Implementation Assistance in Developing

Compliant Systems Web-based PharmEcology Wizard

The PharmEcology™ WizardWeb-based database enabling search by product for waste

management recommendationsSearch by NDC, product or generic name, active ingredient

Recommendations citing federal regulations and recommended waste streams

State regulation alerts if more stringent than federal Risk Management alerts based on professional

knowledge (e.g. chemotherapy agents not regulated at the state or federal level)

The PharmEcology WizardPrototype

2-2576-5

Readi-Cat

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

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.

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

Appendix

Endocrine Disruptors:

Emerging Contaminants

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 newbornEstradiols, testosterone, progesteroneLindane

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 sampleOne or more OWCs found in 80% of stream

samples13% of sites had more than 20 OWCs*http://toxics.usgs.gov/pubs/OFR-02-94/index.html

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

Drug Residues In Ambient Water: Initial Surveillance in New Mexico*

NM Environment DepartmentScientific Laboratory DivisionDrug detection limits into low ppt (10 ng/L)Test included Darvon, Dilantin, Prozac other

antidepressants, prednisone, estrogens, caffeine, tamoxifen

8 sites positive, 16 negativeNext study will include antibiotics, lipid-regulators,

and cardiovascular pharmaceuticals* http://www.nmenv.state.nm.us/gwb/drugs.html

New Mexico Drug Residue Sampling

Red = Positive

California has tested for lindane, reported contamination levels, banned

use on humans for lice and scabies*

*www.lindane.org/world/environment/ water/national.htm

Our Stolen Future:How Endocrine Disruptors May

Be Threatening Our Lives and Survival

Seven years synthesizing research on endocrine-disrupting chemicals

Extensive databaseEstrogen mimics, blockage of

testosterone, disruption of thyroid hormones

www.ourstolenfuture .org

Generations at Risk: Reproductive Health and the

EnvironmentTed Schettler, MD. Gina Solomon, MD,

Maria Valenti, Annette HuddleReproductive Physiology and

ToxicologyReproductive and Developmental Effects

of Selected Substances and Human Exposure

A Guide to Investigating Environmental Threats

Low sperm counts InfertilityGenital deformitiesHormonally triggered human cancersNeurological disorders in children

Hyperactivity Attention deficit

Developmental & reproductive problems in wildlife

Early Warnings

Copenhagen, Denmark: 1992 Review of 61studies by Niels Skakkeback,

University of Copenhagen Average human male sperm counts dropped by

almost 50% between 1939 and 1990 Incidence of testicular cancer jumped Undescended testicles and shortened urinary

tracts rising among young boys

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

Early Warnings

Steady 1% a year increase in breast cancer

rates since WWIIExposure during prenatal period critical51 synthetic chemicals now identified as

hormone disruptors; at least half are persistant and resist natural decomposition

Mother’s breast milk is contaminated

Identification of Endocrine Related Pharmaceuticals

EstrogensProgesteronesTestosteronesCorticosteroidsGlucosteroidsThyroid

Identification of Pharmaceuticals as Endocrine Disruptors*

Chloroform: ReproductiveKetoconazole: Reproductive

Nizoral®Lindane: Estrogen/AndrogenMalathion: Thyroid

Ovide®Permethrin: Androgen mimic

Elimite®, Acticin®, Nix®*http://www.ourstolenfuture.org/Basics/chemlist.htm* Generations at Risk: Reproductive Health and the

Environment

Identification of Pharmaceuticals as Endocrine Disruptors*

Nonylphenol: EstrogenResorcinol: ThyroidArsenic: Glucocortocoid

Trisenox®, Atrivex®

Mercury: Reproductive/Thyroid Thimerosal, Mersol®, Aeroaid®

*http://www.ourstolenfuture.org/Basics/chemlist.htm

Generations at Risk: Reproductive Health and the Environment