Download Wholesaler Taskforce

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
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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
 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 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
How is Pharmaceutical Waste
Generated at the Healthcare Facility?
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IV Preparation
General Compounding
Spills/Breakage
Partially Used Vials/Syringes
 If Contaminated, Biohazardous
Discontinued, Unused Preparations
Unused Repacks (Unit Dose)
Discontinued Indated Pharmaceuticals
Patients’ Personal Medications
Outdated Pharmaceuticals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
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Civil: State/USEPA enforcement
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
When is an Outdated Drug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:
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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
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Hospital oriented
Retail oriented
Manufacturer oriented
Demographics of DEA Registered
Reverse Distributors: 38 Facilities
in 20 States*
 Illinois
6
 Michigan
 Florida
6
 Missouri
 Georgia
5
 Washington
 Tennessee
2
 Pennsylvania
 Arizona
2
 Wisconsin
 New Jersey
2
 California
 New York
2
 Delaware
 North Carolina 1
 Texas
 Indiana
1
 Ohio
 Iowa
1
 Utah
* 2000 DEA FOIA List of Registrants
1
1
1
1
1
1
1
1
1
1
Process Overview
Industry Distribution/Reverse Distribution Model
Wholesalers,
Distributors
Manufacturers
Mfg.
3rd party
processors
Pharmacies,
Institutions,
other indirects
Return
3rd party
processors
Incinerator
Reverse Distribution:
Current Scenarios
 Decision to discard is made at the
pharmacy/wholesaler
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By pharmacy/wholesaler personnel
By a contracted company
Pharmacy/wholesaler becomes the waste
generator
 Decision to discard is made at the reverse
distributor
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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 nonreturnable 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
DEA
EPA
FDA
OSHA
DOT
DOH,
Controlled
Substance
Board
State Env
Protection
State Board
of Pharmacy
RIA Contact Information
David Jenkins
Executive Director
703-787-8574
[email protected]
www.returnsindustry.com
Which Discarded Drugs
Become Hazardous Waste?
 P-listed chemicals
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Sole active ingredient
 U-listed chemicals
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Sole active ingredient
 Characteristic of hazardous waste
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Ignitability
Toxicity
Corrosivity
Reactivity
P-Listed Chemicals
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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
Examples of P-Listed
Pharmaceutical Waste
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Arsenic
Epinephrine
Nicotine
Nitroglycerin
Physostigmine
Physostigmine Salicylate
Warfarin >0.3%
P012
P042
P075
P081
P204
P188
P001
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
Examples of U-listed
Pharmaceutical Waste
 Chloral Hydrate(CIV)
U034
 Streptozotocin
U206
 Chlorambucil
U035
 Lindane
U129
 Cyclophosphamide
U058
 Saccharin
U202
 Daunomycin
U059
 Selenium Sulfide U205
 Melphalan
U150
 Warfarin<0.3%
 Mitomycin C
U010
U248
Chemotherapy Waste
 Seven chemotherapy agents are U-listed
 Waste protocols for “Chemo Waste”
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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 oxidizer
 Hazardous Waste Number: D001
Examples of Ignitable
Discarded Pharmaceuticals
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Rubbing Alcohol
Paregoric (CIII)
Cleocin T Topical Solution
Retin A Gel
Listerine Mouthwash
Erythromycin Topical Solution
Silver 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
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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-Cresol
 Barium
Mercury (thimerosal)
 Cadmium
phenylmercuric acetate)
 Chloroform
Selenium
 Chromium
Silver
 Lindane
Evaluation of Thimerosal Toxicity
per Merck Index, Twelfth Edition:
Thimerosal (C9H9HgNaO2S) mol. wt. 404.82
C
H
Hg
Na
O
S
26.70%
2.24%
49.55%
5.68%
7.90%
7.92%
1:1000 Solution:
Thimerosal may be used as a preservative in a
concentration of 1:1000, which means, by definition, 1
gram 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
Responses
 Epinephrine Residue in Syringe not P042
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Hotline December 1994
 Discarded Nitroglycerine Pills are P081
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Hotline September 1993; Modified Aug 14, 2001?
 Disposal of CESQG hazardous waste
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Hotline August 1999
 Anti-Neoplastic Agents
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January 30, 1986
April 25, 1988
Washington State
State-only Dangerous Waste
 Services
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National and Regional Seminars to Raise
Awareness
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Confidential On-Site Reviews of Current
Practices, Possible Areas of Concern
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Implementation Assistance in Developing
Compliant Systems
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Web-based PharmEcology Wizard
The PharmEcology™ Wizard
 Web-based database enabling search by product
for waste management recommendations
 Search 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 Wizard
Prototype
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
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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 CDRom
 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 newborn
 Estradiols, testosterone, progesterone
 Lindane
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
Location of 139 Stream Sampling
Sites: USGS, 1999 - 2000
Drug Residues In Ambient Water:
Initial Surveillance in New Mexico*
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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, lipidregulators, 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 database
 Estrogen mimics, blockage of
testosterone, disruption of
thyroid hormones
 www.ourstolenfuture .org
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
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Low sperm counts
Infertility
Genital deformities
Hormonally triggered human cancers
Neurological disorders in children
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Hyperactivity
Attention deficit
 Developmental & reproductive
problems in wildlife
Early Warnings
 Copenhagen, Denmark: 1992
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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 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
Identification of Endocrine
Related Pharmaceuticals
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Estrogens
Progesterones
Testosterones
Corticosteroids
Glucosteroids
Thyroid
Identification of Pharmaceuticals
as Endocrine Disruptors*
 Chloroform: Reproductive
 Ketoconazole: Reproductive
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Nizoral®
 Lindane: Estrogen/Androgen
 Malathion: Thyroid
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Ovide®
 Permethrin: Androgen mimic
Elimite®, Acticin®, Nix®
*http://www.ourstolenfuture.org/Basics/chemlist.htm
* Generations at Risk: Reproductive Health and the
Environment
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Identification of Pharmaceuticals
as Endocrine Disruptors*
 Nonylphenol: Estrogen
 Resorcinol: Thyroid
 Arsenic: Glucocortocoid
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Trisenox®, Atrivex®
 Mercury: Reproductive/Thyroid
Thimerosal, Mersol®, Aeroaid®
*http://www.ourstolenfuture.org/Basics/chemli
st.htm
Generations at Risk: Reproductive Health and
the Environment
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